@article {pmid40473616,
year = {2025},
author = {Mazziotta, F and Martin, LE and Egan, DN and Bar, M and Kinsella, S and Paulson, KG and Voillet, V and Lahman, MC and Hunter, D and Schmitt, TM and Duerkopp, N and Yeung, CCS and Tang, TH and Gottardo, R and Asano, Y and Wilcox, EC and Lee, B and Zhang, T and Lopedote, P and Penter, L and Wu, CJ and Milano, F and Greenberg, PD and Chapuis, AG},
title = {A phase I/II trial of WT1-specific TCR gene therapy for patients with acute myeloid leukemia and active disease post-allogeneic hematopoietic cell transplantation: skewing towards NK-like phenotype impairs T cell function and persistence.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {5214},
pmid = {40473616},
issn = {2041-1723},
support = {n/a//Fred Hutchinson Cancer Research Center (Hutchinson Center)/ ; P01 CA018029/CA/NCI NIH HHS/United States ; 5K08CA169485//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; K08 CA169485/CA/NCI NIH HHS/United States ; n/a//Damon Runyon Cancer Research Foundation (Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation)/ ; T32 CA080416/CA/NCI NIH HHS/United States ; n/a//V Foundation for Cancer Research (V Foundation)/ ; n/a//Gabrielle's Angel Foundation for Cancer Research (Gabrielle's Angel Foundation)/ ; },
mesh = {Humans ; *Leukemia, Myeloid, Acute/therapy/immunology/genetics ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *WT1 Proteins/immunology/genetics ; Female ; Middle Aged ; Male ; Adult ; *Receptors, Antigen, T-Cell/genetics/immunology ; *Genetic Therapy/methods/adverse effects ; *Killer Cells, Natural/immunology ; Transplantation, Homologous ; CD8-Positive T-Lymphocytes/immunology ; Herpesvirus 4, Human/immunology ; Cytomegalovirus/immunology ; Aged ; T-Lymphocytes/immunology ; Young Adult ; Treatment Outcome ; },
abstract = {Relapsed and/or refractory acute myeloid leukemia (AML) post-allogeneic hematopoietic cell transplantation (HCT) is usually fatal. We previously reported that post-HCT immunotherapy with Epstein-Barr virus (EBV)-specific donor CD8[+] T cells engineered to express a Wilms Tumor Antigen 1-specific T-cell receptor (TTCR-C4) appeared to prevent relapse in high-risk patients. In this phase I/II clinical trial (NCT01640301), we evaluated safety (primary endpoint), persistence and efficacy (secondary endpoints) of EBV- or Cytomegalovirus (CMV)-specific TTCR-C4 in fifteen patients with active AML post-HCT. Infusions were well tolerated, with no dose-limiting toxicities or serious adverse events related to the product. However, TTCR-C4 cells did not clearly improve outcomes despite EBV-specific TTCR-C4 cells showing enhanced potential for prolonged persistence compared to CMV-specific TTCR-C4. Investigating the fate of persisting TTCR-C4, we identified a shift towards natural killer-like (NKL) terminal differentiation, distinct from solid tumor-associated canonical exhaustion programs. In one patient, treatment with azacitidine appeared to mitigate this NKL skewing, promoting TTCR-C4 persistence. These findings suggest that AML drives a distinct form of T-cell dysfunction, highlight the need for targeted approaches that preserve T-cell fitness, ultimately improving the efficacy of cellular therapies for AML.},
}

Humans
*Leukemia, Myeloid, Acute/therapy/immunology/genetics
*Hematopoietic Stem Cell Transplantation/adverse effects
*WT1 Proteins/immunology/genetics
Female
Middle Aged
Male
Adult
*Receptors, Antigen, T-Cell/genetics/immunology
*Genetic Therapy/methods/adverse effects
*Killer Cells, Natural/immunology
Transplantation, Homologous
CD8-Positive T-Lymphocytes/immunology
Herpesvirus 4, Human/immunology
Cytomegalovirus/immunology
Aged
T-Lymphocytes/immunology
Young Adult
Treatment Outcome

@article {pmid40473107,
year = {2025},
author = {Mascaux, C and Sen, T and Sanchez-Cespedes, M and Ortiz-Cuaran, S and Bossé, Y and Dammeijer, F and Cavic, M and Barr, MP and Arulananda, S and Armisen, R and Berger, AH and Bianchi, F and Carbone, DP and Cerciello, F and Lockwood, WW and Mitsudomi, T and Ohara, S and Politi, K and Qin, S and Roisman, LC and Samstein, R and Skoulidis, F and Tan, AC and Thomas, A and Zhang, J and Wynes, MW and John, T and Tsao, MS and , },
title = {Advances in lung cancer basic and translational research in 2025 - Overview and perspectives focusing on non-small cell lung cancer.},
journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtho.2025.05.024},
pmid = {40473107},
issn = {1556-1380},
abstract = {Basic and translational research in lung cancer is a rapidly evolving field with transformational impact in early detection, diagnosis, therapeutic development and personalization of care. Recent advances have greatly increased our understanding in the molecular genomics, proteomics, pathogenesis and cellular biology of this deadly malignancy. The International Association for the Study of Lung Cancer (IASLC) recently formed a Basic and Translational Science (BaTS) Committee to further enhance the scientific leadership of IASLC in thoracic cancer research. This review by members of the committee highlights the breadth of current research in NSCLC, with a focus on molecular risk factors and processes in tumorigenesis, heterogeneity, phenotypic plasticity, metabolic reprograming, immunobiology, the immune microenvironment and microbiome. This review also identifies future research areas that may lead to further improvement in survival outcomes and curative therapies especially for patients with advanced NSCLC.},
}

@article {pmid40472801,
year = {2025},
author = {Kurniansyah, N and Strausz, SJ and Chittoor, G and Gupta, S and Justice, AE and Hrytsenko, Y and Keenan, BT and Cade, BE and Spitzer, BW and Wang, H and Huffman, J and Moll, MR and Haring, B and Jung, SY and Raffield, LM and Kaplan, R and Rotter, JI and Rich, SS and Gharib, SA and Bartz, TM and Liu, PY and Chen, H and Fornage, M and Hou, L and Levy, D and Morrison, AC and Ochs-Balcom, HM and Psaty, BM and Wilson, PWF and Cho, K and Pack, AI and Ollila, HM and Redline, S and Gottlieb, DJ and Sofer, T and , and , and , },
title = {Polygenic scores for obstructive sleep apnoea reveal pathways contributing to cardiovascular disease.},
journal = {EBioMedicine},
volume = {117},
number = {},
pages = {105790},
doi = {10.1016/j.ebiom.2025.105790},
pmid = {40472801},
issn = {2352-3964},
abstract = {BACKGROUND: Obstructive sleep apnoea (OSA) is a common chronic condition, with obesity its strongest risk factor. Polygenic scores (PGSs) summarise the genetic liability to phenotype and can provide insights into relationships between phenotypes. Recently, large datasets that include genetic data and OSA status became available, providing an opportunity to utilise PGS approaches to study the genetic relationship between OSA and other phenotypes, while differentiating OSA-specific from obesity-specific genetic factors.

METHODS: Using race/ethnic diverse samples from over 1.2 million individuals from the Million Veteran Program, FinnGen, TOPMed, All of Us (AoU), Geisinger's MyCode, MGB Biobank, and the Human Phenotype Project, we developed and assessed PGSs for OSA, both without (BMIunadjOSA-PGS) and with adjustment for the genetic contributions of BMI (BMIadjOSA-PGS).

FINDINGS: Adjusted odds ratios (ORs) for OSA per 1 standard deviation of the PGSs ranged from 1.38 to 2.75. The associations of BMIadjOSA- and BMIunadjOSA-PGSs with CVD outcomes in AoU shared both common and distinct patterns. Only BMIunadjOSA-PGS was associated with type 2 diabetes, heart failure, and coronary artery disease, while both BMIadjOSA- and BMIunadjOSA-PGSs were associated with hypertension and stroke. Sex stratified analyses revealed that BMIadjOSA-PGS association with hypertension was driven by females (OR = 1.1, p-value = 0.002, OR = 1.01 p-value = 0.2 in males). OSA PGSs were also associated with body fat measures with some sex-specific associations.

INTERPRETATION: Distinct components of OSA genetic risk are related and independent of obesity. Sex-specific associations with body fat distribution measures may explain differing OSA risks and associations with cardiometabolic morbidities between sexes.

FUNDING: R01AG080598.},
}

@article {pmid40471097,
year = {2025},
author = {Jadvar, H and Rahbar, K and Ahmadzadehfar, H and Heidari, P and Esfahani, SA and Afshar-Oromieh, A and Iravani, A},
title = {Combination prostate-specific membrane antigen-targeted radiopharmaceutical therapy in metastatic prostate cancer.},
journal = {The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of...},
volume = {},
number = {},
pages = {},
doi = {10.23736/S1824-4785.25.03641-6},
pmid = {40471097},
issn = {1827-1936},
abstract = {Radiopharmaceutical therapy is emerging rapidly as an effective and safe pillar in cancer management. The regulatory approvals for [177]Lu-PSMA-617 radiopharmaceutical therapy in both the pre- and post-chemotherapy metastatic castration resistant prostate cancer clinical space have paved the way for the implementation of this life-prolonging therapy in clinical practice. However, the emergence of resistance to radiopharmaceutical therapy is inevitable, and therefore, combination therapies will be needed to synergize treatment efficacy without untoward collective toxicity. Biologically rational combination therapies across various phases of prostate cancer will lead to more optimal patient outcomes than what can be achieved with monotherapy. This article summarizes select clinical trials on prostate-specific membrane antigen-targeted radiopharmaceutical therapy in combination with other treatments that are either actively accruing or have provided preliminary results.},
}

@article {pmid40469905,
year = {2025},
author = {Fang, H and Eacker, SM and Wu, Y and Neufeld-Kaiser, W and Laurino, M and Keel, S and Horwitz, MS and Liu, YJ},
title = {Genetic and functional characterization of inherited complex chromosomal rearrangements in a family with multisystem anomalies.},
journal = {Genetics in medicine open},
volume = {3},
number = {},
pages = {103423},
pmid = {40469905},
issn = {2949-7744},
abstract = {PURPOSE: Complex chromosomal rearrangements (CCRs) are rare structural variants involving 3 or more chromosomal breakpoints. Most de novo-reported CCRs pose challenges for diagnosis and management. They often require karyotyping, fluorescence in situ hybridization, and chromosomal microarray analysis (CMA) for clinical diagnosis because of the limitations of each method. Here, we report an inherited, exceptionally complex CCR involving 4 chromosomes and 13 breakpoints in a family with multisystem anomalies.

METHODS: We evaluated the CCRs using karyotyping, fluorescence in situ hybridization, CMA, and 2 emerging genomic technologies: high-throughput chromosome conformation capture sequencing aka genomic proximity mapping and optical genome mapping. We also performed functional studies using transcriptome and methylome analyses.

RESULTS: The proband, who had intellectual disability and immune deficiency, shared CCRs with her unaffected mother involving chromosomes 1, 7, and 11 by karyotyping. However, CMA revealed a duplication and 3 deletions in the proband, in contrast to her mother's balanced genome. High-throughput chromosome conformation capture sequencing aka genomic proximity mapping and optical genome mapping detected the CCRs and copy-number alterations but also uncovered additional breakpoints at high resolution, including an insertion in 4p and 2 cryptic rearrangements at 7p. Transcriptome and methylome analyses identified likely biological pathways associated with the proband's phenotypes.

CONCLUSION: Combining cytogenetic and genomic methods provided comprehensive characterization and defined the breakpoints at high resolution in both proband and mother. This underscores the value of novel cytogenetic and genomic techniques in deciphering complex genome rearrangements and the significance of integrative genomic analysis and functional characterization in understanding clinical phenotypes.},
}

@article {pmid40469752,
year = {2025},
author = {Stone, D and Mietzsch, M and Ronzitti, G},
title = {Advancing AAV technology: From capsid design to scalable manufacturing.},
journal = {Molecular therapy. Methods & clinical development},
volume = {33},
number = {2},
pages = {101477},
pmid = {40469752},
issn = {2329-0501},
}

@article {pmid40469175,
year = {2025},
author = {Mugisha, NM and Pinder, LF and Menon, MP},
title = {Editorial: Cervical screening awareness week 2023: integrating cervical cancer screening and precancer treatments.},
journal = {Frontiers in oncology},
volume = {15},
number = {},
pages = {1614832},
pmid = {40469175},
issn = {2234-943X},
}

@article {pmid40469020,
year = {2025},
author = {Hamilton, EL and Guo, X and Dadabhai, S and Panchia, R and Ogendo, A and Reynolds, D and Chen, Y and Sandfort, TGM and , },
title = {Stigma and other correlates of self-esteem and depression in cisgender men and transfeminine persons with HIV who have sex with men in Kenya, Malawi, and South Africa (HPTN 075).},
journal = {AIDS care},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/09540121.2025.2488874},
pmid = {40469020},
issn = {1360-0451},
abstract = {ABSTRACTHIV-related stigma profoundly impacts individuals living with HIV, hindering self-esteem and access to treatment. Few studies, if any, have assessed the effects of stigma on depression and self-esteem among men who have sex with men (MSM) and transfeminine persons (TFP) with HIV in African settings. We explored factors, including various forms of stigma, contributing to low self-esteem and poor mental health among 71 MSM and TFP in Kenya, Malawi, and South Africa, using data from the HPTN (HIV Prevention Trials Network) 075 study. Lower self-esteem was associated with moderate to severe depression and was significantly lower among those who experienced HIV as a stigma. Moreover, participants who had encountered MSM-related stigma in healthcare settings were more likely to exhibit moderate to severe depression. Being employed was a protective factor against depression. These results suggest that interventions aimed at reducing MSM-related stigma in healthcare settings and enhancing self-esteem through employment opportunities for MSM and TFP living with HIV might contribute toward ending the HIV epidemic.},
}

@article {pmid40299576,
year = {2025},
author = {Kwek, SS and Yang, H and Li, T and Ilano, A and Chow, ED and Zhang, L and Chang, H and Luong, D and Lea, A and Clark, M and Starzinski, A and Shi, Y and McCarthy, E and Porten, S and Meng, MV and Ye, CJ and Fong, L and Oh, DY},
title = {Identification and regulation of circulating tumor-TCR-matched cytotoxic CD4+ lymphocytes by KLRG1 in bladder cancer.},
journal = {JCI insight},
volume = {10},
number = {11},
pages = {},
doi = {10.1172/jci.insight.177373},
pmid = {40299576},
issn = {2379-3708},
mesh = {Humans ; *Urinary Bladder Neoplasms/immunology/pathology/blood ; *Receptors, Immunologic/metabolism/immunology ; *Lectins, C-Type/metabolism/immunology ; *Receptors, Antigen, T-Cell/metabolism/immunology ; *CD4-Positive T-Lymphocytes/immunology ; Lymphocytes, Tumor-Infiltrating/immunology/metabolism ; *T-Lymphocytes, Cytotoxic/immunology ; Granzymes/metabolism ; Female ; Male ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; },
abstract = {While cytotoxic CD4+ tumor-infiltrating lymphocytes have anticancer activity in patients, whether these can be noninvasively monitored and how these are regulated remains obscure. By matching single cells with T cell receptors (TCRs) in tumor and blood of patients with bladder cancer, we identified distinct pools of tumor-matching cytotoxic CD4+ T cells in the periphery directly reflecting the predominant antigenic specificities of intratumoral CD4+ tumor-infiltrating lymphocytes. On one hand, the granzyme B-expressing (GZMB-expressing) cytotoxic CD4+ subset proliferated in blood in response to PD-1 blockade but was separately regulated by the killer cell lectin-like receptor G1 (KLRG1), which inhibited their killing by interacting with E-cadherin. Conversely, a clonally related, GZMK-expressing circulating CD4+ population demonstrated basal proliferation and a memory phenotype that may result from activation of GZMB+ cells, but was not directly mobilized by PD-1 blockade. As KLRG1 marked the majority of circulating tumor-TCR-matched cytotoxic CD4+ T cells, this work nominates KLRG1 as a means to isolate them from blood and provide a window into intratumoral CD4+ recognition, as well as a putative regulatory receptor to mobilize the cytolytic GZMB+ subset for therapeutic benefit. Our findings also underscore ontogenic relationships of GZMB- and GZMK-expressing populations and the distinct cues that regulate their activity.},
}

Humans
*Urinary Bladder Neoplasms/immunology/pathology/blood
*Receptors, Immunologic/metabolism/immunology
*Lectins, C-Type/metabolism/immunology
*Receptors, Antigen, T-Cell/metabolism/immunology
*CD4-Positive T-Lymphocytes/immunology
Lymphocytes, Tumor-Infiltrating/immunology/metabolism
*T-Lymphocytes, Cytotoxic/immunology
Granzymes/metabolism
Female
Male
Programmed Cell Death 1 Receptor/antagonists & inhibitors

@article {pmid40467920,
year = {2025},
author = {Mooney, SJ and Smith, CM and Spalt, EW and Piepmeier, L and Gassett, AJ and Gunning, G and Carlson, JA and Evenson, KR and Chambers, EC and Daviglus, M and Lovasi, GS and Gullón, PT and Hirsch, JA and Plascak, JJ and Rundle, AG and Fry, D and Bader, MDM and Kaufman, JD and Kaplan, R},
title = {Built Environment Change over Time Using Google Street View Assessments of Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Cities.},
journal = {Journal of urban health : bulletin of the New York Academy of Medicine},
volume = {},
number = {},
pages = {},
pmid = {40467920},
issn = {1468-2869},
support = {R01ES030994/ES/NIEHS NIH HHS/United States ; },
abstract = {Google Street View's historical imagery is a promising data source for measuring neighborhood conditions over time. However, images are not available for all years. To assess bias that may arise due to a mismatch between the year imagery is available and the year of researcher interest, we assessed prevalence of change in 20 commonly assessed built environment features between the oldest and newest available high-quality images (median difference 10.5 years, range from 2007 to 2023) on Street View at 2118 total locations in four US cities representing the Hispanic Community Health Study/Study of Latinos (New York City, Chicago, Miami, and San Diego). Seventeen (85%) of the features were the same in more than 90% of images; only litter differed in more than 20%. Patterns of change were consistent across all four cities and not notably different in tracts with higher or lower median household incomes. For built environment features reflecting sidewalk conditions and disinvestment in neighborhoods not selected for their known rapid change, auditing an image that does not temporally match the time of etiological interest is unlikely to be a major source of bias.},
}

@article {pmid40467365,
year = {2025},
author = {Bellmunt, J and Powles, T and Park, SH and Voog, E and Valderrama, BP and Gurney, H and Ullén, A and Loriot, Y and Sridhar, SS and Tsuchiya, N and Sternberg, CN and Aragon-Ching, JB and Petrylak, DP and Climent Duran, MA and Tyroller, K and Hoffman, J and Jacob, N and Grivas, P and Gupta, S},
title = {Avelumab First-line Maintenance for Advanced Urothelial Carcinoma: Long-term Outcomes from the JAVELIN Bladder 100 Trial in Patients with Nonvisceral or Lymph Node-only Disease.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2025.05.017},
pmid = {40467365},
issn = {1873-7560},
abstract = {In the JAVELIN Bladder 100 randomized phase 3 trial (N = 700), avelumab first-line maintenance plus best supportive care (BSC) significantly prolonged overall survival (OS; primary endpoint) and progression-free survival (PFS) versus BSC alone in patients with advanced urothelial carcinoma (aUC) without progression after first-line platinum-based chemotherapy (PBC). Here, we report exploratory analyses of subgroups with nonvisceral metastases at the start of PBC (including bone metastases) or lymph node-only disease at randomization. The median OS with avelumab versus control in patients with nonvisceral metastases (n = 318) was 31.4 versus 17.1 mo (hazard ratio [HR], 0.60 [95% confidence interval {CI},
0.45-0.79]), and in patients with lymph node-only disease (n = 102), it was 31.9 versus 22.7 mo (HR, 0.86 [95% CI, 0.51-1.47]). In patients with nonvisceral metastases, prolonged OS was observed with avelumab irrespective of the response to PBC or PBC regimen received. PFS analyses favored avelumab over control in all the subgroups. Incidences of avelumab-related adverse events were similar across the subgroups. Limitations include small sample sizes and the exploratory nature of analyses. Overall, exploratory analyses suggest that in first-line PBC-treated patients without progression, avelumab maintenance is effective and has a manageable toxicity profile in patients with aUC who have nonvisceral metastases or lymph node-only disease.},
}

@article {pmid40466030,
year = {2025},
author = {Liao, N and Li, C and Gradishar, WJ and Klimberg, VS and Roshal, JA and Yuan, T and Agarwala, SS and Valero, VK and Swain, SM and Margenthaler, JA and Rubio, IT and Hurvitz, SA and Geyer, CE and Lin, NU and Rugo, HS and Zhang, G and Liu, N and Balch, CM},
title = {Accuracy and Reproducibility of ChatGPT Responses to Breast Cancer Tumor Board Patients.},
journal = {JCO clinical cancer informatics},
volume = {9},
number = {},
pages = {e2500001},
doi = {10.1200/CCI-25-00001},
pmid = {40466030},
issn = {2473-4276},
mesh = {Humans ; *Breast Neoplasms/therapy/diagnosis ; Female ; Reproducibility of Results ; Middle Aged ; Generative Artificial Intelligence ; },
abstract = {PURPOSE: We assessed the accuracy and reproducibility of Chat Generative Pre-Trained Transformer's (ChatGPT) recommendations in response to breast cancer patients by comparing generated outputs with consensus expert opinions.

METHODS: 362 consecutive breast cancer patients sourced from a weekly international breast cancer webinar series were submitted to a tumor board of renowned experts. The same 362 clinical patients were also prompted to ChatGPT-4.0 three separate times to examine reproducibility.

RESULTS: Only 46% of ChatGPT-generated content was entirely concordant with the recommendations of breast cancer experts, and only 39% of ChatGPT's responses demonstrated inter-response similarity. ChatGPT's responses demonstrated higher concordance with CEN experts in earlier stages of breast cancer (0, I, II, III) compared to advanced (IV) patients (P = .019). There were less accurate responses from ChatGPT when responding to patients involving molecular markers and genetic testing (P = .025), and in patients involving antibody drug conjugates (P = .006). ChatGPT's responses were not necessarily incorrect but often omitted specific details about clinical management. When the same prompt was independently sent to CEN into the model on three occasions, each time by difference users, ChatGPT's responses exhibited variable content and formatting in 68% (246 out of 362) of patients and were entirely consistent with one another in only 32% of responses.

CONCLUSION: Since this promising clinical decision-making support tool is widely used currently by physicians worldwide, it is important for the user to understand its limitations as currently constructed when responding to multidisciplinary breast cancer patients, and for researchers in the field to continue improving its ability with contemporary, accurate and complete breast cancer information. As currently constructed, ChatGPT is not engineered to generate identical outputs to the same input and was less likely to correctly interpret and recommend treatments for complex breast cancer patients.},
}

Humans
*Breast Neoplasms/therapy/diagnosis
Female
Reproducibility of Results
Middle Aged
Generative Artificial Intelligence

@article {pmid40465842,
year = {2025},
author = {Mack, PC and Redman, MW and Tukachinsky, H and Kozono, DE and Minichiello, K and Dragnev, KH and Tolba, KA and Neal, JW and Madison, RW and Waqar, SN and Aggarwal, C and Hirsch, FR and Patel, JD and Herbst, RS and Chiang, AC and Reckamp, KL and Kelly, K and Borghaei, H and Gray, JE and Gandara, DR},
title = {Elevated ctDNA Tumor Fraction Is Associated with Improved Mutation Detection but Worse Overall Survival in Advanced Non-Small Cell Lung Cancer: a Lung-MAP Study.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-24-3658},
pmid = {40465842},
issn = {1557-3265},
abstract = {PURPOSE: Circulating tumor DNA (ctDNA) is a powerful diagnostic companion to tissue profiling. Tumor fraction (TF) is a global assessment of an individual's ctDNA burden. We evaluated the impact of plasma TF on mutation detection and clinical outcomes in patients with previously treated, advanced NSCLC on Lung-MAP.

EXPERIMENTAL DESIGN: Paired tumor tissue and plasma were collected prospectively from Lung-MAP patients. Plasma was collected within 30 days of a new biopsy with no intervening therapies. Tissue and ctDNA genomic profiling and ctDNA TF levels were assessed by Foundation Medicine. TF was primarily calculated from tumor aneuploidy, defaulting to fragmentomics and maximum somatic allele frequencies when aneuploidy was not detectable. The effect of TF on tissue-plasma mutation concordance, overall survival, and its relation to variant allele frequencies was assessed using linear regression, Lin's coefficient, and Cox modeling/log-rank testing.

RESULTS: 194 patients were eligible for analysis. TF≥1% was significantly associated with improved positive percent agreement (PPA) between ctDNA and tissue across multiple alteration types with the exception of copy number gains. For short variants, PPA improved from 51% when TF<1% to 95% when TF≥1%. TF showed a significant robust correlation with VAF for KRAS, STK11 and TP53 - the three most common mutations. TF<1% were significantly associated with improved patient overall survival compared to TF≥1% or TF≥10%.

CONCLUSIONS: TF provides an accurate, clinically useful assessment of ctDNA plasma levels from patients with refractory, advanced NSCLC. TF levels ≥ 1% are associated with significantly worse overall survival, but improved mutation detection in liquid biopsies.},
}

@article {pmid40465219,
year = {2025},
author = {Chalian, M and Park, C},
title = {Use of RADS in Musculoskeletal Imaging: Point-We've Done Enough Talking, Let's Dive In!.},
journal = {AJR. American journal of roentgenology},
volume = {},
number = {},
pages = {},
doi = {10.2214/AJR.25.33285},
pmid = {40465219},
issn = {1546-3141},
}

@article {pmid40464563,
year = {2025},
author = {Schiffer, JT and Mudd, JC and Antar, AAR and Spivak, AM and Reeves, DB},
title = {Applications and limitations of the passenger hypothesis for HIV reservoir persistence and cure.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0071425},
doi = {10.1128/jvi.00714-25},
pmid = {40464563},
issn = {1098-5514},
abstract = {Antiretroviral therapy (ART) suppresses HIV replication in people living with HIV (PWH), but a persistent population of reservoir cells prevents cure. Reservoir cells are mostly anatomically dispersed, latently infected CD4+ T cells harboring one copy of chromosomally integrated, replication-competent HIV proviral DNA. Despite their low frequency (0.01%-0.1%) among CD4+ T cells and the quiescence of most genetically intact proviruses, viremia usually recurs within weeks after ART cessation. When PWH are not on ART, the reservoir is sustained through viral infection and infected cell proliferation. During suppressive ART, HIV reservoir cells persist via mechanisms sustaining uninfected CD4+ T cells including antigen-responsive and homeostatic clonal proliferation, programmed cell death, and T cell subset differentiation. Rates of latently infected cell proliferation and death must exist in quasi-equilibrium to explain limited change in reservoir volume over decades of ART, and the rarity of cancers or lymphoproliferative disorders emerging from infected cells. Some reservoir cells are under additional selection forces during ART, illustrated by slightly higher clearance rates of genetically intact versus replication-defective HIV proviral DNA and by a gradual transition to a less transcriptionally active and more clonal reservoir. While a small but meaningful percentage of latently infected cells are negatively selected due to lytic viral replication or elimination by adaptive immune responses, most reservoir cell death occurs independently of harboring intact HIV DNA. Given that HIV is often a passenger in reservoir cells, CD4+ T cell proliferation, targeted death, and subset differentiation may be viable therapeutic targets for curative interventions.},
}

@article {pmid40463375,
year = {2025},
author = {Fredericks, MN and Kolodner, Z and Waalkes, A and Sawatzki, K and Hao, L and Long, DR and Penewit, K and Midkiff, CC and McCormick, CJ and Beraki, S and Edlefsen, PT and Barrow, J and Greninger, AL and Gale, M and Blair, RV and Salipante, SJ and Fuller, DH and O'Connor, MA},
title = {SIV/SARS-CoV-2 coinfection in rhesus macaques impacts viral shedding, host immunity, the microbiome, and viral evolution.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1587688},
pmid = {40463375},
issn = {1664-3224},
mesh = {Animals ; Macaca mulatta ; *Virus Shedding ; *COVID-19/immunology/virology ; *SARS-CoV-2/immunology/physiology/genetics ; *Simian Immunodeficiency Virus/immunology/physiology ; *Simian Acquired Immunodeficiency Syndrome/immunology/virology ; *Coinfection/immunology/virology ; Disease Models, Animal ; *Microbiota/immunology ; Antibodies, Viral/immunology/blood ; },
abstract = {People living with HIV (PLWH) have an increased risk of severe COVID-19, including prolonged viral shedding and emergence of mutations. To investigate the simian immunodeficiency virus (SIV) macaque model for HIV/SARS-CoV-2 coinfection, seven SIV+ rhesus macaques were co-infected with SARS-CoV-2. COVID-19 in all macaques was mild. SARS-CoV-2 replication persisted in the upper, but not the lower respiratory tract for 14 days post-infection. Animals showed impaired generation of anti-SARS-CoV-2 antibodies and T-cells. Animals also displayed transient changes in microbial communities in the upper airway and gastrointestinal tract. Evidence of SARS-CoV-2 evolution was observed in the upper respiratory tract. This study demonstrates that SIV/SARS-CoV-2 coinfection in rhesus macaques recapitulates aspects of COVID-19 in PLWH. We show that SIV impairs anti-SARS-CoV-2 immunity, potentially leading to prolonged viral shedding, altered pathogenesis, and viral evolution. This highlights the importance of HIV status in COVID-19 and supports the use of this model for HIV/SARS-CoV-2 coinfection.},
}

Animals
Macaca mulatta
*Virus Shedding
*COVID-19/immunology/virology
*SARS-CoV-2/immunology/physiology/genetics
*Simian Immunodeficiency Virus/immunology/physiology
*Simian Acquired Immunodeficiency Syndrome/immunology/virology
*Coinfection/immunology/virology
Disease Models, Animal
*Microbiota/immunology
Antibodies, Viral/immunology/blood

@article {pmid40462491,
year = {2025},
author = {Karuna, S and Laher, F and Dadabhai, S and Yu, PC and Grove, D and Orrell, C and Makhema, J and Hosseinipour, MC and Mathew, CA and Brumskine, W and Mgodi, N and Andrew, P and Gama, L and Karg, C and Broder, G and Baepanye, K and Lucas, J and Andrasik, M and Takuva, S and Villaran, M and Takalani, A and Tressler, R and Soto-Torres, L and Woodward Davis, AS and Dhai, A and Sanne, IM and Cohen, MS and Corey, L and Gray, G and deCamp, AC and Bar, KJ},
title = {Analytical treatment interruption among women with HIV in southern Africa who received VRC01 or placebo in the Antibody Mediated Prevention Study: ATI stakeholder engagement, implementation and early clinical data.},
journal = {Journal of the International AIDS Society},
volume = {28},
number = {6},
pages = {e26495},
pmid = {40462491},
issn = {1758-2652},
support = {UM1 AI068635/AI/NIAID NIH HHS/United States ; UM1AI068614//HVTN Leadership and Operations Center/ ; UM1AI068619//HPTN Leadership and Operations Center/ ; },
mesh = {Humans ; Female ; *HIV Infections/drug therapy/prevention & control/immunology ; Adult ; Africa, Southern/epidemiology ; *HIV Antibodies ; Viral Load ; *Anti-HIV Agents/administration & dosage/therapeutic use ; *Broadly Neutralizing Antibodies ; HIV-1/immunology ; *Antibodies, Monoclonal/therapeutic use/administration & dosage ; Middle Aged ; CD4 Lymphocyte Count ; Young Adult ; Treatment Interruption ; },
abstract = {INTRODUCTION: Antiretroviral therapy (ART) prevents and treats, but does not eradicate, HIV. Early ART initiation is associated with post-ART virologic control, particularly among African women, and anti-HIV-1 broadly neutralizing antibodies (bnAbs) may modulate immune responses to HIV. We evaluate whether early ART with or without anti-HIV-1 bnAb VRC01, present at HIV acquisition, is associated with later ART-free control in African women and we assess potential associations with observed control.

METHODS: Stakeholder engagement informed analytical treatment interruption (ATI) study design and implementation. Participants who received placebo or VRC01 and acquired HIV in the Antibody Mediated Prevention efficacy trial were assessed for ATI eligibility, including HIV acquisition within 8 weeks of receiving VRC01 or placebo, followed by early ART initiation and ≥1 year of viral suppression. Participation facilitators and barriers were assessed. From May 2021 to February 2024, participants enrolled, stopped ART and received frequent viral load and CD4+ T-cell count monitoring for safety and assessment of meeting ART reinitiation criteria.

RESULTS: Thirteen women enrolled from southern Africa. No ATI-related serious adverse events (AEs), HIV transmissions, pregnancies or ≥Grade 2 AEs were observed. Eight sexually transmitted infections were diagnosed in seven women during ATI. Two participants had tenofovir levels consistent with use during ATI; 2/11 (18%) who completed ATI without antiretroviral use exhibited ART-free control for ≥32 weeks. The median time to confirmed VL≥200 was 5.4 weeks (range 2.7-112). The most common ART reinitiation criterion met was virologic (n = 7). VRC01 receipt proximate to HIV acquisition was not associated with control. Controllers versus non-controllers did not differ by early post-acquisition viral load kinetics, acquired virus characteristics, or time from estimated acquisition to closest infusion or to ART initiation.

CONCLUSIONS: In a safe, well-tolerated ATI, 18% of 11 African women exhibited post-intervention control. Design and implementation lessons inform future ATIs in Africa. Analyses of peri-acquisition and post-ATI host and viral characteristics can inform the development of interventions for HIV cure, prevention and treatment.

CLINICAL TRIAL REGISTRATION: NCT04860323.},
}

Humans
Female
*HIV Infections/drug therapy/prevention & control/immunology
Adult
Africa, Southern/epidemiology
*HIV Antibodies
Viral Load
*Anti-HIV Agents/administration & dosage/therapeutic use
*Broadly Neutralizing Antibodies
HIV-1/immunology
*Antibodies, Monoclonal/therapeutic use/administration & dosage
Middle Aged
CD4 Lymphocyte Count
Young Adult
Treatment Interruption

@article {pmid40451460,
year = {2025},
author = {Kang, DW and Ficarra, S and Wilson, RL and Morgans, AK and Nguyen, PL and Rebbeck, TR and Einstein, DJ and Uno, H and Mossanen, M and Hill, DM and Gonzalo-Encabo, P and Norris, MK and Gardiner, J and Tjogas, D and Greer, J and Dieli-Conwright, CM},
title = {Exercise to enhance cardiovascular health among black men with prostate cancer with androgen deprivation therapy (the POWER trial): A study protocol.},
journal = {Contemporary clinical trials},
volume = {155},
number = {},
pages = {107973},
doi = {10.1016/j.cct.2025.107973},
pmid = {40451460},
issn = {1559-2030},
abstract = {BACKGROUND: Black men in the US are 1.8 and 2.2 times more likely to develop and die from prostate cancer (PCa) than non-Hispanic White men, respectively, and have the highest incidence globally. Furthermore, Black men undergoing androgen deprivation therapy (ADT) for PCa face a higher risk of cardiovascular disease (CVD) compared to men of other racial groups. Therefore, we have designed a randomized controlled trial (RCT) to investigate the impact of exercise on CVD risk factors among Black man undergoing ADT.

METHODS: The POWER trial is a dual-arm RCT designed to examine the effects of a 16-week, culturally tailored, remotely supervised cardiovascular and strength exercise program on Black men with PCa receiving ADT. Sixty-two patients will be randomized in a 1:1 allocation to either the exercise intervention or a waitlist control group. The patient population includes adult males who self-identify as Black, receiving ADT for at least four months prospectively at the time of recruitment. The primary outcome is the CVD risk assessed using the Framingham Risk Score. The secondary and exploratory outcomes include physical fitness and function, patient-reported outcomes, and clinical events at a one-year follow-up.

DISCUSSION: The POWER Trial evaluates a culturally tailored exercise program for Black men with PCa undergoing ADT, focusing on improving cardiovascular health. The findings of the study are expected to inform a larger phase clinical trial to examine long-term CVD-related clinical outcomes. Ultimately, our findings and subsequent trials would narrow the gap in health disparities among the communities of Black men with PCa.

TRIAL REGISTRATION: NCT05327465.},
}

@article {pmid40461885,
year = {2025},
author = {Flanagan, MR and van den Bruele, AMB and Downs-Canner, SM and Thomas, SM and Gallagher, KK and Jakub, JW and Tevis, SEA and Verdial, FC and Zhang, JQ and Elmore, LC and Mukhtar, RA and Brennan, M and Lillie, M and Gibson, TC and Verosky, A and Plichta, JK and Rosenberger, LH},
title = {ASO Visual Abstract: A Multi-institutional Analysis of Contralateral Axillary Metastases-Advanced Local-Regional Disease Divergent from Stage IV Breast Cancer.},
journal = {Annals of surgical oncology},
volume = {},
number = {},
pages = {},
doi = {10.1245/s10434-025-17563-8},
pmid = {40461885},
issn = {1534-4681},
}

@article {pmid40461383,
year = {2025},
author = {de Marinis, F and Kim, TM and Bonanno, L and Cheng, S and Kim, SW and Tiseo, M and Chu, Q and Proto, C and Sacher, A and Luo, YH and Novello, S and Hao, D and Baik, C and Bazhenova, L and Lee, JS and Cho, BC and Cadranel, J and Diep, TB and Metro, G and Narayanan, P and Yoneshima, Y and de Castro Carpeño, J and Baldotto, C and Nyhus, C and Yang, JC and Sequist, LV and Levy, B and Hartmaier, R and Igwegbe, I and Poole, L and Xu, W and Ahn, MJ},
title = {Savolitinib plus osimertinib in epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer with MET overexpression and/or amplification following disease progression on osimertinib: primary results from the phase II SAVANNAH study.},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.annonc.2025.04.003},
pmid = {40461383},
issn = {1569-8041},
abstract = {BACKGROUND: MET-based resistance following osimertinib treatment for epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC) is common. We report the primary analysis of the phase II SAVANNAH study (NCT03778229) evaluating savolitinib plus osimertinib in this setting.

PATIENTS AND METHODS: Patients had EGFR-mutated, advanced NSCLC with MET overexpression and/or amplification. MET cut-offs were initially MET immunohistochemistry (IHC)3+/≥50% (3+ intensity in ≥50% of tumor cells) and/or FISH5+ (≥5 MET gene copies or MET/chromosome 7 centromere ratio ≥2), and increased to MET IHC3+/≥90% and/or FISH10+ after a preliminary analysis. Patients received oral savolitinib [300 mg twice daily (b.i.d.) or once daily (o.d.), or 600 mg o.d.] plus osimertinib 80 mg o.d., or savolitinib 300 mg b.i.d. plus placebo. A primary endpoint was investigator-assessed objective response rate (ORR) in patients with progression on first-line osimertinib and MET IHC3+/≥90% and/or FISH10+ status receiving savolitinib 300 mg b.i.d. plus osimertinib (primary efficacy population). Safety was analyzed in all patients receiving savolitinib plus osimertinib.

RESULTS: Of the 365 patients treated, 341 received savolitinib plus osimertinib, with 80 of these included in the primary efficacy population. Investigator-assessed confirmed ORR in the primary efficacy population was 56.3% [95% confidence interval (CI) 44.7% to 67.3%]; the median duration of response (mDoR) was 7.1 months (95% CI 5.6-9.6 months); the median progression-free survival (PFS) was 7.4 months (95% CI 5.5-7.6 months). Blinded independent central review was consistent: confirmed ORR 55.0% (95% CI 43.5% to 66.2%); mDoR 9.9 months (95% CI 6.0-13.7 months); median PFS 7.5 months (95% CI 6.4-11.3 months). The most common any grade adverse events in patients receiving savolitinib plus osimertinib were peripheral edema (46.0%), nausea (40.5%), and diarrhea (23.2%).

CONCLUSIONS: Savolitinib 300 mg b.i.d. plus osimertinib demonstrated high, clinically meaningful and durable responses in patients with EGFR-mutated, advanced NSCLC with MET IHC3+/≥90% and/or FISH10+ status following progression on first-line osimertinib. The combination was well tolerated and may provide a new oral targeted treatment approach in this setting.},
}

@article {pmid40460679,
year = {2025},
author = {García-Estévez, L and Bardia, A and Rugo, HS and Carey, LA and Diéras, VC and Loibl, S and Piccart, M and Gianni, L and Kalinsky, K and O'Shaughnessy, J and Hurvitz, SA and Harting, E and Valdez, T and Phan, S and Lai, C and Cortés, J},
title = {The association of high body mass index with the safety and efficacy of sacituzumab govitecan in patients with metastatic triple-negative breast cancer from the ASCENT study.},
journal = {ESMO open},
volume = {10},
number = {6},
pages = {105294},
doi = {10.1016/j.esmoop.2025.105294},
pmid = {40460679},
issn = {2059-7029},
abstract = {BACKGROUND: Sacituzumab govitecan (SG) is a trophoblast cell-surface antigen 2-directed antibody-drug conjugate (ADC) approved in multiple countries for relapsed/refractory metastatic triple-negative breast cancer (mTNBC) based on results from the phase III ASCENT study. The incidence of obesity has grown to epidemic proportions in recent decades; it is unclear what impact this has on treatment outcomes, especially for ADCs like SG that have weight-based dosing. We report the association of body mass index (BMI) with efficacy and safety of SG versus chemotherapy among patients with mTNBC from the ASCENT study.

PATIENTS AND METHODS: This ad hoc subgroup analysis included patients from the intent-to-treat population of ASCENT who received SG at 10 mg/kg of body weight or chemotherapy. BMI, assessed at baseline, was classified as normal (18.5 to <25 kg/m[2]), overweight (25 to <30 kg/m[2]), and obese (≥30 kg/m[2]).

RESULTS: A total of 509 patients were included. Longer progression-free survival was observed with SG versus chemotherapy in patients from all BMI subgroups [normal: 4.2 versus 2.1 months, hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.34-0.67, P < 0.0001; overweight: 4.6 versus 1.5 months, HR 0.31, 95% CI 0.20-0.47, P < 0.0001; obese: 5.9 versus 2.6 months, HR 0.34, 95% CI 0.21-0.53, P < 0.0001]. SG also led to improved overall survival and objective response rates versus chemotherapy in all evaluated BMI subgroups. With SG treatment, the incidence of treatment-emergent adverse events of grade ≥3, and those leading to dose reductions and study drug interruptions, was higher in patients with overweight and obese BMI compared with normal BMI; however, the rates of treatment discontinuation remained low and similar across the subgroups.

CONCLUSIONS: To our knowledge, this is the first study evaluating the association of BMI with outcomes with ADCs. SG demonstrated improved efficacy versus chemotherapy and a manageable safety profile in all evaluated BMI subgroups from ASCENT.},
}

@article {pmid40460374,
year = {2025},
author = {Owens, K and Rahman, A and Bozic, I},
title = {Spatiotemporal dynamics of tumor-CAR T-cell interaction following local administration in solid cancers.},
journal = {PLoS computational biology},
volume = {21},
number = {6},
pages = {e1013117},
doi = {10.1371/journal.pcbi.1013117},
pmid = {40460374},
issn = {1553-7358},
abstract = {The success of chimeric antigen receptor (CAR) T-cell therapy in treating hematologic malignancies has generated widespread interest in translating this technology to solid cancers. However, issues like tumor infiltration, the immunosuppressive tumor microenvironment, and tumor heterogeneity limit its efficacy in the solid tumor setting. Recent experimental and clinical studies propose local administration directly into the tumor or at the tumor site to increase CAR T-cell infiltration and improve treatment outcomes. Characteristics of the types of solid tumors that may be the most receptive to this treatment approach remain unclear. In this work, we develop a simplified spatiotemporal model for CAR T-cell treatment of solid tumors, and use numerical simulations to compare the effect of introducing CAR T cells via intratumoral injection versus intracavitary administration in diverse cancer types. We demonstrate that the model can reproduce tumor and CAR T-cell data from small imaging studies of local administration of CAR T cells in mouse models. Our results suggest that locally administered CAR T cells will be most successful against slowly proliferating, highly diffusive tumors. In our simulations, assuming equal detectable tumor diameters at the time of treatment, low average tumor cell density is a better predictor of treatment success than total tumor burden or volume doubling time. These findings affirm the clinical observation that CAR T cells will not perform equally across different types of solid tumors, and suggest that measuring tumor density may be helpful when considering the feasibility of CAR T-cell therapy and planning dosages for a particular patient. We additionally find that local delivery of CAR T cells can result in deep tumor responses, provided that the initial CAR T-cell dose does not contain a significant fraction of exhausted cells.},
}

@article {pmid40458939,
year = {2025},
author = {Appelbaum, FR},
title = {Graft-versus-leukemia.},
journal = {Haematologica},
volume = {110},
number = {6},
pages = {1243-1244},
pmid = {40458939},
issn = {1592-8721},
}

@article {pmid40457567,
year = {2025},
author = {Marc, A and Schiffer, JT and Mentré, F and Perelson, AS and Guedj, J},
title = {Viral Dynamic Models During COVID-19: Are We Ready for the Next Pandemic?.},
journal = {CPT: pharmacometrics & systems pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1002/psp4.70055},
pmid = {40457567},
issn = {2163-8306},
abstract = {Mathematical models have been used for about 30 years to improve our understanding of virus-host interaction, in particular during chronic infections. During the COVID-19 pandemic, these models have been used to provide insights into the natural history of acute SARS-CoV-2 infection, optimize antiviral treatment strategies, understand factors associated with transmission, and optimize surveillance systems. The impact of modeling has been accelerated by the availability of unprecedented multidimensional immune data from animal and human systems, which enhanced partnerships between experimentalists and theorists and led to exciting new modeling and statistical developments. In this mini review, we examine the lessons learned from the COVID-19 pandemic and discuss the main insights provided by mathematical models of viral dynamics at the different stages of the outbreak. Although we focus on respiratory infection, we also consider the new areas for development in anticipation of future acute infections from new or reemerging pathogens.},
}

@article {pmid40456670,
year = {2025},
author = {Hoffman-Censits, J and Tsiatas, M and Chang, PM and Kim, M and Antonuzzo, L and Shin, SJ and Gakis, G and Blais, N and Kim, SH and Smith, A and Arranz Arija, JA and Su, YL and Zagouri, F and Maruzzo, M and Tournigand, C and Forget, F and Schneider, A and Tyroller, K and Jacob, N and Grivas, P and Valderrama, BP},
title = {Avelumab plus sacituzumab govitecan versus avelumab monotherapy as first-line maintenance treatment in patients with advanced urothelial carcinoma: JAVELIN Bladder Medley interim analysis.},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.annonc.2025.05.010},
pmid = {40456670},
issn = {1569-8041},
abstract = {BACKGROUND: Avelumab first-line maintenance is a recommended treatment option for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) without progression following platinum-based chemotherapy (PBC). The JAVELIN Bladder Medley phase II trial is investigating the efficacy and safety of maintenance treatment with avelumab combined with other antitumor agents versus avelumab monotherapy. We report an interim analysis of avelumab plus sacituzumab govitecan (SG) versus avelumab monotherapy.

PATIENTS AND METHODS: Patients with la/mUC without progression after first-line PBC were randomized 2 : 1 to receive avelumab (800 mg every 2 weeks) plus SG (10 mg/kg on days 1 and 8 of 21-day cycles) or avelumab monotherapy (800 mg every 2 weeks). Primary endpoints are investigator-assessed progression-free survival (PFS) and safety. For PFS and overall survival (OS), data in the avelumab monotherapy arm were extended per protocol using propensity score-weighted JAVELIN Bladder 100 data.

RESULTS: At data cut-off (16 September 2024), 38/74 patients (51.4%) in the avelumab plus SG arm and 10/37 patients (27.0%) in the avelumab monotherapy arm were still receiving study treatment. Median PFS with avelumab plus SG versus avelumab monotherapy was 11.17 versus 3.75 months, respectively [hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.31-0.76; prespecified efficacy boundary: HR ≤ 0.60]. OS data were immature; median OS was not reached versus 23.75 months, respectively (HR 0.79, 95% CI 0.42-1.50). In patients treated with avelumab plus SG or avelumab monotherapy, any-grade treatment-related adverse events (TRAEs) occurred in 97.3% versus 63.9% (grade ≥3 in 69.9% versus 0%), respectively.

CONCLUSION: In patients with la/mUC without progression after first-line PBC, PFS was prolonged with avelumab plus SG versus avelumab monotherapy as maintenance treatment. TRAEs were more frequent with the combination and were consistent with known safety profiles of SG and avelumab. Combining avelumab with anti-Trop-2 antibody-drug conjugates may be a promising strategy to improve patient outcomes in la/mUC.},
}

@article {pmid40456294,
year = {2025},
author = {Tsai, J and Grassberger, C and Nyflot, MJ and Thonglert, K and Zaki, P and Nguyen, MH and Schaub, SK and Apisarnthanarax, S and Bowen, SR},
title = {Functional liver imaging and dosimetry for risk stratification in patients with hepatocellular carcinoma undergoing radiotherapy: validation study.},
journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology},
volume = {},
number = {},
pages = {110963},
doi = {10.1016/j.radonc.2025.110963},
pmid = {40456294},
issn = {1879-0887},
abstract = {BACKGROUND: Functional liver imaging has potential to personalize management of Hepatocellular Carcinoma (HCC) by mitigating hepatotoxicity risk. We validated functional liver imaging and dosimetric parameters for risk-stratification in an expanded cohort of HCC patients.

METHODS: We reviewed 109 consecutive HCC patients who underwent Sulfur Colloid (SC)-SPECT/CT scans for radiation therapy (RT) planning and extracted previously reported functional liver imaging metrics. We generated elastic net multivariable Cox models with event-stratified and nested cross-validation folds to predict Overall Survival (OS) and increase in Child-Pugh score ≥ 2 (CP + 2). Test-fold patients were risk-stratified, and time-dependent model performance was characterized. ROC analysis generated prognostic cutoffs with confidence intervals to guide functional liver avoidance treatment planning.

RESULTS: Cross-validated model concordance was 0.70 (95 %CI: 0.67-0.73) for OS and 0.67 (95 %CI: 0.63-0.71) for CP + 2. Top-ranked OS predictors included tumor volume (HR = 1.56, 1.54-1.58), CP-score (HR = 1.36, 1.34-1.38), Liver-GTV V20 (HR = 1.310, 1.306-1.314), prior liver-directed therapy (HR = 0.83, 0.82-0.85), functional liver volume dosimetry (FLV-V20) (HR = 1.19, 1.14-1.23), and RT-year (HR = 0.89, 0.88-0.91). Top-ranked CP + 2 predictors were total liver function (TLF) (HR = 0.64, 0.63-0.66), Liver-GTV mean dose (HR = 1.40, 1.36-1.49), and CP-score (HR = 1.19, 1.16-1.23). Test-fold risk groups were defined for each endpoint (log-rank P < 0.001). OS model performance stabilized beyond 2 years; CP + 2 model stability peaked within 1 year. Optimal strata for 2-yr OS were FLV V20 < 25.8 % and Liver-GTV V20 < 25.4 %; 1-yr CP + 2 strata were TLF < 0.91 and Liver-GTV mean dose < 18.9 Gy.

CONCLUSION: Functional liver metrics on SC-SPECT/CT were validated alongside clinical and dosimetric factors within robust outcome models. Testing of personalized RT planning for HCC patients to preserve liver function is warranted in clinical trials.},
}

@article {pmid40455801,
year = {2024},
author = {Huang, Y and Prentice, RL},
title = {Biomarker-assisted reporting in nutritional epidemiology: addressing measurement error in exposure-disease associations.},
journal = {Biostatistics (Oxford, England)},
volume = {26},
number = {1},
pages = {},
pmid = {40455801},
issn = {1468-4357},
support = {R01 CA119171/CA/NCI NIH HHS/United States ; R01 CA277133/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Biomarkers/analysis ; Bias ; *Diet/statistics & numerical data ; Cardiovascular Diseases/epidemiology/etiology ; Female ; Proportional Hazards Models ; Self Report ; },
abstract = {In nutritional epidemiology, self-reported dietary data are commonly used to investigate diet-disease relationships. However, the resulting association estimates are often subject to biases due to random and systematic measurement errors. Regression calibration has emerged as a crucial method for addressing these biases by refining self-reported nutrient intake with objective biomarkers, which differ from the true values only by a random "noise" component. This paper presents methodological tools for analyzing nutritional epidemiology cohort studies involving time-to-event data when a biomarker subsample is available alongside dietary assessments. We introduce novel regression calibration methods to tackle two common challenges in this field. First, a widely used approach assumes that the log hazard ratio (HR) follows a linear function of dietary exposure. However, assessing whether this assumption holds-or if a more flexible model is needed to capture potential deviations from linearity-is often necessary. Second, another prevalent analytical strategy involves estimating HRs based on categorized dietary exposure variables. New methods are critically needed to minimize bias in defining category boundaries and estimating hazard ratios within exposure categories, both of which can be distorted by measurement error. We apply these methods to reassess the relationship between sodium and potassium intake and cardiovascular disease risk using data from the Women's Health Initiative.},
}

Humans
*Biomarkers/analysis
Bias
*Diet/statistics & numerical data
Cardiovascular Diseases/epidemiology/etiology
Female
Proportional Hazards Models
Self Report

@article {pmid40455622,
year = {2025},
author = {Shaukat, A and Burke, CA and Chan, AT and Grady, WM and Gupta, S and Katona, BW and Ladabaum, U and Liang, PS and Liu, JJ and Putcha, G and Robertson, DJ and Schoen, RE and Meng, Z and Piscitello, A and Sun, CK and Xu, C and Lin, CJ and Lee, LC and Baldo, L and Levin, TR and , },
title = {Clinical Validation of a Circulating Tumor DNA-Based Blood Test to Screen for Colorectal Cancer.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
pmid = {40455622},
issn = {1538-3598},
abstract = {IMPORTANCE: Colorectal cancer screening is widely recommended but underused. Blood-based screening offers the potential for higher adherence compared with endoscopy or stool-based testing but must first be clinically validated in a screening population.

OBJECTIVE: To evaluate the clinical performance of an investigational blood-based circulating tumor DNA test for colorectal cancer detection in an average-risk population using colonoscopy with histopathology as the reference method.

Prospective, multicenter, cross-sectional observational study enrolling participants between May 2020 and April 2022 who were asymptomatic adults aged 45 to 85 years, at average risk of colorectal cancer, and willing to undergo a standard-of-care screening colonoscopy. Participants, staff, and pathologists were blinded to blood test results, and laboratory testing was performed blinded to colonoscopy findings. The study was conducted at 201 centers across 49 US states and the United Arab Emirates. Site-based and mobile phlebotomy were used for blood collection.

EXPOSURES: Participants were required to complete a screening colonoscopy after blood collection.

MAIN OUTCOMES AND MEASURES: The primary end points were sensitivity for colorectal cancer, specificity for advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions), negative predictive value for advanced colorectal neoplasia, and positive predictive value for advanced colorectal neoplasia. The secondary end point was sensitivity for advanced precancerous lesions.

RESULTS: The median age of participants in the evaluable cohort (n = 27 010) was 57.0 years, and 55.8% were women. Sensitivity for colorectal cancer was 79.2% (57/72; 95% CI, 68.4%-86.9%) and specificity for advanced colorectal neoplasia was 91.5% (22 306/24 371; 95% CI, 91.2%-91.9%). The negative predictive value for advanced colorectal neoplasia was 90.8% (22 306/24 567; 95% CI, 90.7%-90.9%) and the positive predictive value for advanced colorectal neoplasia was 15.5% (378/2443; 95% CI, 14.2%-16.8%). All primary end points met prespecified acceptance criteria. The sensitivity for advanced precancerous lesions was 12.5% (321/2567; 95% CI, 11.3%-13.8%), which did not meet the prespecified acceptance criterion.

CONCLUSIONS AND RELEVANCE: In an average-risk colorectal cancer screening population, a blood-based test demonstrated acceptable accuracy for colorectal cancer detection, but detection of advanced precancerous lesions remains a challenge, and ongoing efforts are needed to improve test sensitivity.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04369053.},
}

@article {pmid40455131,
year = {2025},
author = {van den Bruele, AB and Rosenberger, LH and Downs-Canner, S and Flanagan, MR},
title = {ASO Author Reflections: Contralateral Axillary Lymph Node Metastasis of Breast Cancer: Time to Re-evaluate Conventional Thinking.},
journal = {Annals of surgical oncology},
volume = {},
number = {},
pages = {},
pmid = {40455131},
issn = {1534-4681},
}

@article {pmid40455079,
year = {2025},
author = {DiPeso, L and Pendyala, S and Huang, HZ and Fowler, DM and Hatch, EM},
title = {Image-based identification and isolation of micronucleated cells to dissect cellular consequences.},
journal = {eLife},
volume = {13},
number = {},
pages = {},
pmid = {40455079},
issn = {2050-084X},
support = {T32CA009657/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; RM1 HG010461/HG/NHGRI NIH HHS/United States ; R35GM124766/GM/NIGMS NIH HHS/United States ; R35 GM124766/GM/NIGMS NIH HHS/United States ; P30CA015704/CA/NCI NIH HHS/United States ; Scholars Program//Rita Allen Foundation/ ; T32 CA009657/CA/NCI NIH HHS/United States ; RM1HG010461/HG/NHGRI NIH HHS/United States ; },
mesh = {Humans ; *Micronuclei, Chromosome-Defective ; Transcriptome ; Cell Line ; *Cell Separation/methods ; Genomic Instability ; *Image Processing, Computer-Assisted/methods ; },
abstract = {Recent advances in isolating cells based on visual phenotypes have transformed our ability to identify the mechanisms and consequences of complex traits. Micronucleus (MN) formation is a frequent outcome of genome instability, triggers extensive changes in genome structure and signaling coincident with MN rupture, and is almost exclusively defined by visual analysis. Automated MN detection in microscopy images has proved challenging, limiting discovery of the mechanisms and consequences of MN. In this study we describe two new MN segmentation modules: a rapid model for classifying micronucleated cells and their rupture status (VCS MN), and a robust model for accurate MN segmentation (MNFinder) from a broad range of cell lines. As proof-of-concept, we define the transcriptome of non-transformed human cells with intact or ruptured MN after chromosome missegregation by combining VCS MN with photoactivation-based cell isolation and RNASeq. Surprisingly, we find that neither MN formation nor rupture triggers a strong unique transcriptional response. Instead, transcriptional changes appear correlated with small increases in aneuploidy in these cell classes. Our MN segmentation modules overcome a significant challenge with reproducible MN quantification, and, joined with visual cell sorting, enable the application of powerful functional genomics assays to a wide-range of questions in MN biology.},
}

Humans
*Micronuclei, Chromosome-Defective
Transcriptome
Cell Line
*Cell Separation/methods
Genomic Instability
*Image Processing, Computer-Assisted/methods

@article {pmid40454483,
year = {2025},
author = {Duan, Z and Shi, M and Kumaraswamy, A and Lin, D and Khokhani, D and Wang, Y and Zhang, C and Flores, D and Rodansky, E and Swaim, OA and Storck, WK and Beck, HN and Patel, RA and Sayar, E and Hanratty, BP and Xue, H and Dong, X and Maylin, ZR and Wan, R and Quigley, DA and Sjöström, M and Hu, YM and Zhao, F and Xia, Z and Cheng, S and Yu, X and Feng, FY and Zhang, L and Aggarwal, R and Small, EJ and Ravikumar, V and Rao, A and Bedi, K and Lee, JK and Morrissey, C and Coleman, I and Nelson, PS and Corey, E and Udager, AM and Rebernick, RJ and Cieslik, MP and Chinnaiyan, AM and Yates, JA and Haffner, MC and Wang, Y and Alumkal, JJ},
title = {PROX1 is an early driver of lineage plasticity in prostate cancer.},
journal = {The Journal of clinical investigation},
volume = {135},
number = {11},
pages = {},
pmid = {40454483},
issn = {1558-8238},
mesh = {Male ; *Prostatic Neoplasms/pathology/metabolism/genetics ; Prospero-Related Homeobox 1 Protein ; Humans ; *Tumor Suppressor Proteins/genetics/metabolism ; *Homeodomain Proteins/genetics/metabolism ; Animals ; Mice ; Cell Line, Tumor ; DNA Methylation ; *Gene Expression Regulation, Neoplastic ; *Cell Lineage ; *Cell Plasticity ; },
abstract = {Lineage plasticity is recognized as a critical determinant of lethality and resistance to AR pathway inhibitors in prostate cancer. Lineage plasticity is a continuum, ranging from AR activity-low tumors, AR-null tumors that do not express a neuroendocrine prostate cancer (NEPC) program (i.e., double-negative prostate cancer [DNPC]), and AR-null NEPC tumors. Factors upregulated early in lineage plasticity are not well-characterized. The clarification of such factors is essential to identify tumors undergoing lineage plasticity or at risk of this occurring. Our integrative analysis of metastatic prostate cancer patient tumors, patient-derived xenografts, and cell models determined that PROX1 is upregulated early in the lineage plasticity continuum and progressively increases as tumors lose AR activity. We determined DNA methylation is a key regulator of PROX1 expression. PROX1 suppression in DNPC and NEPC reduces cell survival and impacts apoptosis and differentiation, demonstrating PROX1's functional importance. PROX1 is not directly targetable with standard drug development approaches. However, affinity immunopurification demonstrated histone deacetylases (HDACs) are among the top PROX1-interacting proteins; HDAC inhibition depletes PROX1 and recapitulates PROX1 suppression in DNPC and NEPC. Altogether, our results suggest PROX1 promotes the emergence of lineage plasticity, and HDAC inhibition is a promising approach to treat tumors across the lineage plasticity continuum.},
}

Male
*Prostatic Neoplasms/pathology/metabolism/genetics
Prospero-Related Homeobox 1 Protein
Humans
*Tumor Suppressor Proteins/genetics/metabolism
*Homeodomain Proteins/genetics/metabolism
Animals
Mice
Cell Line, Tumor
DNA Methylation
*Gene Expression Regulation, Neoplastic
*Cell Lineage
*Cell Plasticity

@article {pmid40101143,
year = {2025},
author = {Xu, J and Sussman, JH and Yang, A and Yoshimura, S and Hu, J and Chen, C and Vincent, T and Bandyopadhyay, S and Li, EY and Lim, T and Elghawy, O and Barsouk, A and Karanfilovski, D and Wald, SL and Chen, GM and Wu, D and Newman, H and Li, A and Sun, Y and Chen, CH and Bernt, K and Wood, BL and Winter, SS and Dunsmore, KP and Raetz, E and Devidas, M and Pounds, S and Loh, M and Hunger, SP and Chiang, MY and Diorio, C and Di Giacomo, D and Pölönen, P and Mullighan, CG and Yang, JJ and Tan, K and Teachey, DT},
title = {STAT1-mediated interferon signatures are associated with preclinical JAK inhibitor sensitivity in T-ALL.},
journal = {Blood},
volume = {145},
number = {23},
pages = {2793-2798},
doi = {10.1182/blood.2025028566},
pmid = {40101143},
issn = {1528-0020},
support = {K12 CA076931/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *STAT1 Transcription Factor/genetics/metabolism ; *Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/genetics/metabolism/pathology ; *Janus Kinase Inhibitors/therapeutic use/pharmacology ; *Interferons/genetics/metabolism ; Male ; Drug Resistance, Neoplasm/genetics ; Female ; Child ; },
abstract = {We used single-cell genomics to characterize a patient with T-cell acute lymphoblastic leukemia treated in the Children's Oncology Group AALL0434 trial with poor clinical outcome despite favorable genomic features, identifying a STAT1-mediated interferon-related transcriptional signature and inflammatory microenvironment associated with sensitivity to small-molecule JAK inhibition.},
}

Humans
*STAT1 Transcription Factor/genetics/metabolism
*Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/genetics/metabolism/pathology
*Janus Kinase Inhibitors/therapeutic use/pharmacology
*Interferons/genetics/metabolism
Male
Drug Resistance, Neoplasm/genetics
Female
Child

@article {pmid40454419,
year = {2025},
author = {Stone, D and Takeuchi, R and Dulin, H and Loprieno, MA and Strongin, DE and Sathees, S and Cradick, TJ and Aubert, M and Roychoudhury, P and Gordon, J and Jerome, KR},
title = {Serum factors create species-specific barriers to hepatic gene transfer by lipid nanoparticles in liver-humanized mice.},
journal = {Molecular therapy. Methods & clinical development},
volume = {33},
number = {2},
pages = {101470},
pmid = {40454419},
issn = {2329-0501},
abstract = {Lipid nanoparticles (LNPs) can efficiently deliver nucleic acid therapeutics to a range of tissues, particularly hepatocytes to treat diseases of the liver. We initially investigated whether three LNPs with different ionizable lipids, previously validated in non-human primates (NHPs), could deliver functional GFP mRNA to human hepatocytes in chimeric NSG-PiZ and FRG mice. After intravenous delivery, GFP expression was observed throughout the livers but was restricted to mouse hepatocytes because the payload mRNA was not internalized by human hepatocytes. LNP transfection was also restricted to mouse hepatocytes in NSG-PiZ mice administered a different LNP containing the ionizable lipid SM-102. In vitro, primary human hepatocytes (PHHs) were transfected by LNPs containing lipids SM-102, LP01, or ALC0315 in the presence of normal mouse serum, but not chimeric NSG-PiZ serum. SM-102 LNP transfection of PHH was also inhibited by naive untransplanted NSG-PiZ serum. However, serum from NSG mice supported PHH transfection by SM-102 LNP. These results suggest that inhibitory factors in NSG-PiZ mouse serum are responsible for the lack of human hepatocyte transduction in chimeric mice. Finally, we found that LNPs displaying trivalent N-acetylgalactosamine (TriGalNAc), which targets them to the asialoglycoprotein receptor, can overcome species restriction, transfecting both mouse and human hepatocytes in chimeric NSG-PiZ mice.},
}

@article {pmid40453059,
year = {2024},
author = {DeZern, AE and Goll, JB and Jensen, TL and Nonavinkere Srivatsan, S and Gillis, NK and Abel, GA and Padron, E and Deeg, HJ and Al Baghdadi, T and Liu, JJ and Komrokji, RS and Gore, SD and Saber, W and Bejar, R and Walter, MJ and Lindsley, RC and Sherman, S and DiFronzo, N and Sekeres, MA},
title = {Correlation between peripheral blood and bone marrow mutations among patients with MDS from the National MDS Study.},
journal = {Blood neoplasia},
volume = {1},
number = {3},
pages = {100026},
pmid = {40453059},
issn = {2950-3280},
}

@article {pmid40451731,
year = {2025},
author = {Kmail, ZM and Shannon Dorcy, K and Laing, SS},
title = {Burnout Predictors Among Direct Clinical Services Health Care Professionals in Community Health Centers: A Cross-Sectional Study.},
journal = {American journal of health promotion : AJHP},
volume = {},
number = {},
pages = {8901171251348220},
doi = {10.1177/08901171251348220},
pmid = {40451731},
issn = {2168-6602},
abstract = {PurposeAssess burnout prevalence, identify the healthcare professionals experiencing burnout, and identify organizational predictors of burnout in community health centers (CHCs) nationwide.ApproachIn 2022 the Health Resources and Services Administration administered surveys to assess health center workforce well-being among the 1400+ community health centers that it oversees. Our team statistically evaluated the findings to isolate the factors likely to predict burnout among center healthcare professionals.SettingData completed by staff in 694 CHCs.ParticipantsRespondents were 52 568 healthcare professionals.MethodsChi-squared tests derived homogeneity in burnout among occupations; proportion tests evaluated differences in burnout indicators; and structural equation modeling with latent variables estimated direct and indirect effects of organizational burnout predictors and mediators.ResultsUp to 77% of direct clinical service professionals endorsed at least one symptom of burnout and reported higher burnout rates than management (P < .001). The most significant burnout predictors were engagement (-0.263***), work-life balance (0.281***), workload (0.174***) and professional growth (0.143***). For engagement, a perception of disconnection with the CHC predicted heightened burnout. Work-life balance, workload, and professional growth each had a positive effect on burnout, demonstrating that higher perceived work demands, greater work-life imbalance, and increased professional growth opportunities equated to higher burnout.ConclusionResults highlight the need to redesign healthcare delivery models to mitigate burnout, promote provider engagement and enhance workforce well-being.},
}

@article {pmid40451709,
year = {2025},
author = {St Laurent, MP and Psutka, SP},
title = {Reply to Chang-kun Mao, Chao-Yang, and Jun-ting Li's Letter to the Editor re: Marie-Pier St-Laurent, Bernard Bochner, James Catto, et al. Increasing Life Expectancy in Patients with Genitourinary Malignancies: Impact of Treatment Burden on Disease Management and Quality of Life. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2024.11.026.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2025.02.004},
pmid = {40451709},
issn = {1873-7560},
}

@article {pmid40450573,
year = {2025},
author = {Stein, MN and Vinceneux, A and Robbrecht, D and Doger, B and Autio, KA and Schweizer, MT and Calvo, E and Medina, L and Van Dongen, M and Deville, JL and Bernard-Tessier, A and Ghosh, D and Shotts, K and Shen, F and Jaiprasart, P and Chaudhary, R and Wu, S and Cartee, L and Schnepp, R and Gaut, D and Lauring, J and Wang, SC and Villalobos, VM and Baldini, C},
title = {Pasritamig, a First-in-Class, Bispecific T-Cell Engager Targeting Human Kallikrein 2, in Metastatic Castration-Resistant Prostate Cancer: A Phase 1 Study.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {101200JCO2500678},
doi = {10.1200/JCO-25-00678},
pmid = {40450573},
issn = {1527-7755},
abstract = {BACKGROUND: We report Phase 1 trial results for pasritamig, a first-in-class, T-cell engaging bispecific antibody targeting human kallikrein 2 (KLK2) expressed on the surface of prostate cancer (PC) cells.

METHODS: Participants had metastatic castration-resistant PC and ≥1 prior therapy. Pasritamig was escalated from 0.5 mg to 2000 mg for subcutaneous administration and from 150 mg to 900 mg for intravenous (IV) administration at dosing frequencies ranging from every week to every 6 weeks with different step-up dosing schedules. The primary objectives were to determine safety and the recommended Phase 2 dose (RP2D) of pasritamig. Secondary objectives included preliminary assessment of antitumor activity.

RESULTS: 174 participants received pasritamig, with a median of 4 prior lines of systemic therapy. Treatment-related adverse events (TRAEs) occurred in 144/174 (82.8%) participants, with 17/174 (9.8%) experiencing Grade ≥3 TRAEs. The RP2D was determined to be 3.5 mg (Day 1), 18 mg (Day 8), 300 mg (Day 15), then 300 mg IV every 6 weeks. In the RP2D safety population (N=45), infusion-related reactions (11/45, 24.4%), fatigue (7/45, 15.6%), cytokine release syndrome (CRS; 4/45, 8.9%, all Grade 1), and lipase increase (4/45, 8.9%) were the most frequent TRAEs; all were Grade 1 or 2. In the RP2D efficacy population (N=33), median radiographic progression-free survival was 7.85 (95% CI 2.89, not estimable) months, and 14/33 (42.4%) participants achieved a ≥50% decline in prostate-specific antigen.

CONCLUSIONS: Pasritamig demonstrated a favorable safety profile with very low rates of CRS and could be safely administered in an outpatient setting. Preliminary antitumor activity demonstrated proof of concept for KLK2 as a target in PC, warranting further development of pasritamig.},
}

@article {pmid40450382,
year = {2025},
author = {Cabahug, JPC and Cruzpero, RC and de Los Santos, LEF and Ford, EC and Yorke, AA},
title = {Radiotherapy medical physics in the Philippines: A contemporary overview.},
journal = {Journal of applied clinical medical physics},
volume = {},
number = {},
pages = {e70129},
doi = {10.1002/acm2.70129},
pmid = {40450382},
issn = {1526-9914},
support = {NCI 3UH3CA211310-04S1//NCI Diversity/ ; },
abstract = {PURPOSE: With cancer ranking as the third leading cause of death in the Philippines and a disparity in healthcare resources across regions, this research aimed to assess the state of radiotherapy medical physics in the country.

METHODOLOGY: The study utilized a comprehensive online survey with 94 structured questions answered by 19 clinics.

RESULTS: Most of the participants were within 1-3 years of training (41%), with a slight majority working in private hospitals (55%). linear accelerators (LINACs) were universally used with one Co-60 unit available, and High Dose Rate (HDR) brachytherapy was common. Intensity-Modulated Radiotherapy (IMRT) and 3D-Conformal Radiotherapy (3D-CRT) are practiced in all 19 clinics, with advanced techniques like Stereotactic Body Radiotherapy (SBRT), Stereotactic Radiosurgery (SRS), and Intraoperative Radiotherapy (IORT) limited to NCR, while modalities such as Volumetric Modulated Arc Therapy (VMAT) (21%) and 2D RT (68%) are more widely practiced. Imaging modalities included the wide adoption of Computed Tomography (CT), though only 64% of respondents had dedicated CT simulators in their clinics. Gynecologic and breast cancers were frequently treated, while bone marrow transplants (total body irradiation) were rare. For quality assurance (QA) devices, Solid Water Phantoms and Scanning Water Tanks (86%) were the most common devices for dosimetry and measurement. 82% reported performing patient-specific QA (PSQA), with EPID dosimetry being the most common (55%) PSQA device used. Quality management practices varied between Qualified Medical Physicists and Medical Physics Trainees, with most Qualified Medical Physicists performing routine checks. Treatment interruptions were mainly due to staffing and machine downtime, rather than power outages or natural disasters. Most clinics had their own systems (86%) to document safety incidents, but only a few reported incidents (32%) to the IAEA SAFRON program. Lastly, participants expressed a willingness to collaborate in research despite limited time.

CONCLUSION: This study provides an understanding of the current landscape of radiation therapy physics in the Philippines, highlighting the need to address workforce disparities, ensure equitable cancer treatment access, optimize dosimetric tools and QA devices, and prioritize resource allocation and research collaboration to advance radiation oncology practices.},
}

@article {pmid40448843,
year = {2025},
author = {Hasenstab, KA and Lu, J and Leong, LT and Bossard, E and Pylarinou-Sinclair, E and Devi, K and Cunha, GM},
title = {Relationship between spleen volume and diameter for assessment of response to treatment on CT in patients with hematologic malignancies enrolled in clinical trials.},
journal = {Abdominal radiology (New York)},
volume = {},
number = {},
pages = {},
pmid = {40448843},
issn = {2366-0058},
abstract = {PURPOSE: Investigate spleen diameter (d) and volume (v) relationship in patients with hematologic malignancies (HM) by determining volumetric thresholds that best correlate to established diameter thresholds for assessing response to treatment. Exploratorily, interrogate the impact of volumetric measurements in response categories and as a predictor of response.

METHODS: Secondary analysis of prospectively collected clinical trial data of 382 patients with HM. Spleen diameters were computed following Lugano criteria and volumes using deep learning segmentation. d and v relationship was estimated using power regression model, volumetric thresholds ([Formula: see text]) for treatment response estimated; threshold search to determine percentual change ([Formula: see text] and minimum volumetric increase ([Formula: see text]) that maximize agreement with Lugano criteria performed. Spleen diameter and volume predictive performance for clinical response investigated using random forest model.

RESULTS: [Formula: see text] describes the relationship between spleen diameter and volume. [Formula: see text] for splenomegaly was 546 cm³. [Formula: see text], [Formula: see text], and [Formula: see text] for assessing response resulting in highest agreement with Lugano criteria were 570 cm[3], 73%, and 170 cm[3], respectively. Predictive performance for response between diameter and volume were not significantly different (P=0.78).

CONCLUSION: This study provides empirical spleen volume threshold and percentual changes that best correlate with diameter thresholds, i.e., Lugano criteria, for assessment of response to treatment in patients with HM. In our dataset use of spleen volumetric thresholds versus diameter thresholds resulted in similar response assessment categories and did not signal differences in predictive values for response.},
}

@article {pmid40448577,
year = {2025},
author = {Shadman, M and Munir, T and Ma, S and Lasica, M and Tani, M and Robak, T and Flinn, IW and Brown, JR and Ghia, P and Ferrant, E and Tam, CS and Janowski, W and Jurczak, W and Xu, L and Tian, T and Lefebure, M and Agresti, S and Hirata, J and Tedeschi, A},
title = {Zanubrutinib and Venetoclax for Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With and Without Del(17p)/TP53 Mutation: SEQUOIA Arm D Results.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2500758},
doi = {10.1200/JCO-25-00758},
pmid = {40448577},
issn = {1527-7755},
abstract = {PURPOSE: Several chronic lymphocytic leukemia (CLL) studies have demonstrated promising efficacy with the combination of BCL2 and Bruton tyrosine kinase inhibitors; however, patients with CLL with del(17p) and/or TP53 mutation (TP53mut) comprised a small percentage of study populations or were excluded entirely. The purpose of the SEQUOIA Arm D cohort was to evaluate the combination of zanubrutinib + venetoclax in treatment-naïve (TN) patients with CLL/small lymphocytic lymphoma (SLL), in a large population of patients with TP53-aberrant disease.

PATIENTS AND METHODS: Arm D is a nonrandomized cohort of patients aged 65 years and older (or 18-64 years with comorbidities). Patients received zanubrutinib from cycle 1 and venetoclax from cycle 4 (ramp-up) to cycle 28, followed by continuous zanubrutinib monotherapy until progressive disease (PD), unacceptable toxicity, or meeting undetectable minimal residual disease (uMRD)-guided stopping criteria.

RESULTS: Between November 2019 and July 2022, 114 patients were enrolled: 66 (58%) with TP53-aberrant disease, 47 (41%) without TP53-aberrant disease, and 1 with missing TP53 results. At a median follow-up of 31.2 months, 85 patients (75%) remained on zanubrutinib monotherapy; 29 patients (25%) discontinued zanubrutinib because of adverse event, uMRD-guided stopping criteria, PD, or other. In the intention-to-treat population, 59% of patients achieved peripheral blood uMRD. The 24-month progression-free survival estimate was 92% (95% CI, 85% to 96%). The most common any-grade treatment-emergent AEs (TEAEs) were COVID-19 (54%), diarrhea (41%), contusion (32%), and nausea (30%). The most common grade ≥3 TEAEs were neutropenia (17%), hypertension (10%), diarrhea (6%), and decreased neutrophil count (6%).

CONCLUSION: Zanubrutinib + venetoclax demonstrated impressive efficacy and a favorable safety profile in patients with TN CLL/SLL, regardless of the presence of TP53-aberrant disease.},
}

@article {pmid40447729,
year = {2025},
author = {Sankaranarayanan, A and Khachaturov, G and Smythe, KS and Mittal, S},
title = {Quantitative benchmarking of nuclear segmentation algorithms in multiplexed immunofluorescence imaging for translational studies.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {836},
pmid = {40447729},
issn = {2399-3642},
mesh = {Humans ; *Cell Nucleus/metabolism ; Benchmarking ; *Algorithms ; *Fluorescent Antibody Technique/methods ; *Image Processing, Computer-Assisted/methods ; *Translational Research, Biomedical/methods ; },
abstract = {Multiplexed imaging techniques require identifying different cell types in the tissue. To utilize their potential for cellular and molecular analysis, high throughput and accurate analytical approaches are needed in parsing vast amounts of data, particularly in clinical settings. Nuclear segmentation errors propagate in all downstream steps of cell phenotyping and single-cell spatial analyses. Here, we benchmark and compare the nuclear segmentation tools commonly used in multiplexed immunofluorescence data by evaluating their performance across 7 tissue types encompassing ~20,000 labeled nuclei from human tissue samples. Pre-trained deep learning models outperform classical nuclear segmentation algorithms. Overall, Mesmer is recommended as it exhibits the highest nuclear segmentation accuracy with 0.67 F1-score at an IoU threshold of 0.5 on our composite dataset. Pre-trained StarDist model is recommended in case of limited computational resources, providing ~12x run time improvement with CPU compute and ~4x improvement with the GPU compute over Mesmer, but it struggles in dense nuclear regions.},
}

Humans
*Cell Nucleus/metabolism
Benchmarking
*Algorithms
*Fluorescent Antibody Technique/methods
*Image Processing, Computer-Assisted/methods
*Translational Research, Biomedical/methods

@article {pmid40447568,
year = {2025},
author = {Hazelwood, E and Canson, DM and Deslandes, B and Wang, X and Kho, PF and Legge, D and Constantinescu, AE and Lee, MA and Bishop, DT and Chan, AT and Gruber, SB and Hampe, J and Le Marchand, L and Woods, MO and Pai, RK and Schmit, SL and Figueiredo, JC and Zheng, W and Huyghe, JR and Murphy, N and Gunter, MJ and Richardson, TG and Whitehall, VLJ and Vincent, EE and Glubb, DM and O'Mara, TA},
title = {Multi-tissue expression and splicing data prioritise anatomical subsite- and sex-specific colorectal cancer susceptibility genes.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {5043},
pmid = {40447568},
issn = {2041-1723},
support = {MC_UU_00032/03//RCUK | Medical Research Council (MRC)/ ; C18281/A29019//Cancer Research UK (CRUK)/ ; P30 CA015704/CA/NCI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; U01 CA137088/CA/NCI NIH HHS/United States ; U24 CA074794/CA/NCI NIH HHS/United States ; APP1179170//Department of Health | National Health and Medical Research Council (NHMRC)/ ; U01 CA167551/CA/NCI NIH HHS/United States ; APP177524//Department of Health | National Health and Medical Research Council (NHMRC)/ ; C18281/A30905//Cancer Research UK (CRUK)/ ; T32 ES013678/ES/NIEHS NIH HHS/United States ; U01 CA122839/CA/NCI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; P01 CA196569/CA/NCI NIH HHS/United States ; HHSN268201200008I/HL/NHLBI NIH HHS/United States ; HHSN268201700006C/HL/NHLBI NIH HHS/United States ; U19 CA148107/CA/NCI NIH HHS/United States ; R01 CA059045/CA/NCI NIH HHS/United States ; R01 CA197350/CA/NCI NIH HHS/United States ; R01 CA076366/CA/NCI NIH HHS/United States ; U01 CA074794/CA/NCI NIH HHS/United States ; HHSN268201200008C/HL/NHLBI NIH HHS/United States ; R01 CA242218/CA/NCI NIH HHS/United States ; P30 CA014089/CA/NCI NIH HHS/United States ; 218495/Z/19/Z//Wellcome Trust (Wellcome)/ ; R01 CA081488/CA/NCI NIH HHS/United States ; R01 CA143237/CA/NCI NIH HHS/United States ; R01 CA201407/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Colorectal Neoplasms/genetics/pathology ; Female ; Male ; *Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study ; Gene Expression Regulation, Neoplastic ; Transcriptome ; Sex Factors ; Polymorphism, Single Nucleotide ; *RNA Splicing/genetics ; Semaphorins/genetics ; Gene Expression Profiling ; },
abstract = {Genome-wide association studies have suggested numerous colorectal cancer (CRC) susceptibility genes, but their causality and therapeutic potential remain unclear. To prioritise causal associations between gene expression/splicing and CRC risk (52,775 cases; 45,940 controls), we perform a transcriptome-wide association study (TWAS) across six tissues with Mendelian randomisation and colocalisation, integrating sex- and anatomical subsite-specific analyses. Here we reveal 37 genes with robust causal links to CRC risk, ten of which have not previously been reported by TWAS. Most likely causal genes with evidence of cancer cell dependency show elevated expression linked to risk, suggesting therapeutic potential. Notably, SEMA4D, encoding a protein targeted by an investigational CRC therapy, emerges as a key risk gene. We also identify a female-specific association with CRC risk for CCM2 expression and subsite-specific associations, including LAMC1 with rectal cancer risk. These findings offer valuable insights into CRC molecular mechanisms and support promising therapeutic avenues.},
}

Humans
*Colorectal Neoplasms/genetics/pathology
Female
Male
*Genetic Predisposition to Disease/genetics
Genome-Wide Association Study
Gene Expression Regulation, Neoplastic
Transcriptome
Sex Factors
Polymorphism, Single Nucleotide
*RNA Splicing/genetics
Semaphorins/genetics
Gene Expression Profiling

@article {pmid40447392,
year = {2025},
author = {Svatek, RS and Ankerst, DP and D' Amico, AV and Flaig, TW and Ford, LG and Goldkorn, A and Hernandez, J and Kumar, AP and Leach, RJ and Lerner, S and Liss, MA and McConkey, DJ and Minasian, L and Morilak, D and Mueller, EJ and Parekh, DJ and Platz, EA and Sudarshan, S and Unger, JM},
title = {A festschrift in honor of Ian M. Thompson Jr., MD.},
journal = {Urologic oncology},
volume = {43},
number = {7},
pages = {423-435},
doi = {10.1016/j.urolonc.2024.10.030},
pmid = {40447392},
issn = {1873-2496},
}

@article {pmid40445115,
year = {2025},
author = {Liang, M and Zhao, Y and Lin, DW and Cooperberg, M and Zheng, Y},
title = {Estimating optimally tailored active surveillance strategy under interval censoring.},
journal = {Biometrics},
volume = {81},
number = {2},
pages = {},
pmid = {40445115},
issn = {1541-0420},
support = {R01 CA236558/NH/NIH HHS/United States ; U24 CA086368/NH/NIH HHS/United States ; },
mesh = {Humans ; *Prostatic Neoplasms/pathology/diagnosis ; Male ; *Watchful Waiting/statistics & numerical data/methods ; Computer Simulation ; Disease Progression ; Biopsy/statistics & numerical data ; Cost-Benefit Analysis ; Models, Statistical ; Statistics, Nonparametric ; },
abstract = {Active surveillance (AS) using repeated biopsies to monitor disease progression has been a popular alternative to immediate surgical intervention in cancer care. However, a biopsy procedure is invasive and sometimes leads to severe side effects of infection and bleeding. To reduce the burden of repeated surveillance biopsies, biomarker-assistant decision rules are sought to replace the fix-for-all regimen with tailored biopsy intensity for individual patients. Constructing or evaluating such decision rules is challenging. The key AS outcome is often ascertained subject to interval censoring. Furthermore, patients will discontinue participation in the AS study once they receive a positive surveillance biopsy. Thus, patient dropout is affected by the outcomes of these biopsies. This work proposes a non-parametric kernel-based method to estimate a tailored AS strategy's true positive rates (TPRs) and true negative rates (TNRs), accounting for interval censoring and immediate dropouts. We develop a weighted classification framework based on these estimates to estimate the optimally tailored AS strategy and further incorporate the cost-benefit ratio for cost-effectiveness in medical decision-making. Theoretically, we provide a uniform generalization error bound of the derived AS strategy, accommodating all possible trade-offs between TPRs and TNRs. Simulation and application to a prostate cancer surveillance study show the superiority of the proposed method.},
}

Humans
*Prostatic Neoplasms/pathology/diagnosis
Male
*Watchful Waiting/statistics & numerical data/methods
Computer Simulation
Disease Progression
Biopsy/statistics & numerical data
Cost-Benefit Analysis
Models, Statistical
Statistics, Nonparametric

@article {pmid40444925,
year = {2025},
author = {Jacobs, JM and Traeger, L and Freese, M and Barata, A and Newcomb, R and Rabideau, D and Horick, N and DeFilipp, Z and Chen, YB and Gray, T and Pepper, J and Caruso, E and Amonoo, HL and Lee, SJ and Greer, JA and Temel, JS and El-Jawahri, A},
title = {BMT-CARE App: A Randomized Controlled Trial of a Psychosocial Digital Application for Caregivers of Patients Undergoing Hematopoietic Stem-Cell Transplantation.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2500713},
doi = {10.1200/JCO-25-00713},
pmid = {40444925},
issn = {1527-7755},
abstract = {PURPOSE: Family and friend caregivers of patients undergoing hematopoietic stem-cell transplantation (HSCT) struggle with immense caregiving burden, leading to substantial quality of life (QOL) impairments and psychological distress. Yet, interventions to address caregivers' needs are limited.

MATERIALS AND METHODS: We conducted a randomized controlled trial of a psychosocial digital application (BMT-CARE App) versus usual care for adult caregivers of patients with hematologic malignancies undergoing HSCT. The BMT-CARE App included five modules combining psychoeducation and evidence-based behavior change strategies. Participants completed self-report measures at baseline and day 60 post-HSCT. The primary end point was QOL at day 60 assessed by the CareGiver Oncology QOL (CarGOQOL) measure. We also assessed caregiving burden (Caregiver Reaction Assessment), anxiety and depression symptoms (Hospital Anxiety and Depression Scale), and post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist [PCL-5]). We used analysis of covariance adjusting for baseline scores to assess the effect of the intervention on study outcomes.

RESULTS: Between February 2023 and July 2024, we enrolled 125 of 174 approached caregivers (71.8%). Participants assigned to the BMT-CARE App used the app for a median of 146.9 minutes (range, 0-384.8). At day 60, BMT-CARE App caregivers reported clinically and significantly better QOL than those assigned to usual care (adjusted means = 76.3 v 69.9, P = .006). BMT-CARE App participants also reported significantly lower caregiving burden (11.2 v 12.3, P = .023), depression (3.8 v 5.6, P = .002), and PTSD symptoms (26.1 v 31.3, P = .012). The groups did not differ significantly in anxiety symptoms at day 60.

CONCLUSION: The BMT-CARE App led to significantly improved QOL, caregiving burden, depression, and PTSD symptoms among HSCT caregivers. This intervention should be tested in a multicenter study with a diverse HSCT caregiver population to determine generalizability and scalability.},
}

@article {pmid40443012,
year = {2025},
author = {Brixner, D and Richardson, T and Lockhart, CM and Ramsey, S and Fox, J and Pritchard, D and Mcleod, H and Bobolts, L and Bourbeau, B and Crum, E},
title = {Optimization of oncology biomarker testing in managed care: Best practices and consensus recommendations from an AMCP Market Insights program.},
journal = {Journal of managed care & specialty pharmacy},
volume = {31},
number = {6-a Suppl},
pages = {S1-S14},
pmid = {40443012},
issn = {2376-1032},
mesh = {Humans ; *Managed Care Programs/standards/organization & administration ; Consensus ; *Biomarkers, Tumor/analysis ; *Precision Medicine/methods/standards/economics ; Delphi Technique ; *Neoplasms/diagnosis/therapy ; *Medical Oncology/standards ; Practice Guidelines as Topic ; Cost-Benefit Analysis ; Surveys and Questionnaires ; },
abstract = {Precision medicine in oncology using actionable molecular biomarkers to guide treatment selection has been associated with favorable outcomes; however, many potentially eligible patients do not receive it. This Academy of Managed Care Pharmacy Market Insights program sought to characterize unmet needs in biomarker testing among managed care stakeholders, to develop best practice and consensus recommendations to support addressing these needs, and to gain insights on potential quality measures related to biomarker testing. The program used a modified Delphi process and included in-depth interviews with expert panelists, a national survey of managed care professionals, and a consensus survey of experts. Areas of unmet need in biomarker testing identified were education, guidelines and protocols, timeliness, process, and equity. Twenty-two best practices were suggested by managed care experts and other stakeholders; 9 of these best practices achieved consensus. These consensus recommendations addressed biomarker test ordering and test performance, treatment decisions based on biomarker testing, cost-effectiveness of biomarker testing, and health disparities in access to biomarker testing. Opportunities for education and improvements in infrastructure to implement these recommendations were identified. Further investigation is needed to develop quality measures; although, valuable insights were gained.},
}

Humans
*Managed Care Programs/standards/organization & administration
Consensus
*Biomarkers, Tumor/analysis
*Precision Medicine/methods/standards/economics
Delphi Technique
*Neoplasms/diagnosis/therapy
*Medical Oncology/standards
Practice Guidelines as Topic
Cost-Benefit Analysis
Surveys and Questionnaires

@article {pmid40442371,
year = {2025},
author = {Nugent, PJ and Park, H and Wladyka, CL and Yelland, JN and Sinha, S and Chen, KY and Bynum, C and Quarterman, G and Lee, SC and Hsieh, AC and Subramaniam, AR},
title = {Decoding post-transcriptional regulatory networks by RNA-linked CRISPR screening in human cells.},
journal = {Nature methods},
volume = {},
number = {},
pages = {},
pmid = {40442371},
issn = {1548-7105},
support = {GM119835//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; GM008268//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; CA230617//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; CA276308//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; GM135362//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 1846521//National Science Foundation (NSF)/ ; },
abstract = {RNAs undergo a complex choreography of metabolic processes that are regulated by thousands of RNA-associated proteins. Here we introduce ReLiC, a scalable and high-throughput RNA-linked CRISPR approach to measure the responses of diverse RNA metabolic processes to knockout of 2,092 human genes encoding all known RNA-associated proteins. ReLiC relies on an iterative strategy to integrate genes encoding Cas9, single-guide RNAs (sgRNAs) and barcoded reporter libraries into a defined genomic locus. Combining ReLiC with polysome fractionation reveals key regulators of ribosome occupancy, uncovering links between translation and proteostasis. Isoform-specific ReLiC captures differential regulation of intron retention and exon skipping by SF3B complex subunits. Chemogenomic ReLiC screens decipher translational regulators upstream of messenger RNA (mRNA) decay and identify a role for the ribosome collision sensor GCN1 during treatment with the anti-leukemic drug homoharringtonine. Our work demonstrates ReLiC as a powerful framework for discovering and dissecting post-transcriptional regulatory networks in human cells.},
}

@article {pmid40441807,
year = {2025},
author = {Seaton, KE and Paez, CA and Yu, C and Karuna, ST and Gamble, T and Miner, MD and Heptinstall, J and Zhang, L and Gao, F and Yacovone, M and Spiegel, H and Dumond, JB and Anderson, M and Piwowar-Manning, E and Dye, B and Tindale, I and Proulx-Burns, L and Trahey, M and Takuva, S and Takalani, A and Bailey, VC and Kalams, SA and Scott, H and Mkhize, NN and Weiner, JA and Ackerman, ME and McElrath, MJ and Pensiero, M and Barouch, DH and Montefiori, D and Tomaras, GD and Corey, L and Cohen, MS and Huang, Y and Mahomed, S and Siegel, M and Kelley, CF and , },
title = {Safety, pharmacokinetics, and neutralisation activity of PGDM1400LS, a V2 specific HIV-1 broadly neutralising antibody, infused intravenously or subcutaneously in people without HIV-1 in the USA (HVTN 140/HPTN 101 part A): a first-in-human, phase 1 randomised trial.},
journal = {The lancet. HIV},
volume = {12},
number = {6},
pages = {e405-e415},
doi = {10.1016/S2352-3018(25)00012-8},
pmid = {40441807},
issn = {2352-3018},
mesh = {Humans ; Adult ; Female ; Male ; Young Adult ; *HIV Antibodies/administration & dosage/adverse effects/immunology ; *HIV-1/immunology ; Middle Aged ; Adolescent ; *HIV Infections/prevention & control/immunology/drug therapy ; *Antibodies, Neutralizing/administration & dosage/adverse effects/immunology ; United States ; *Broadly Neutralizing Antibodies/administration & dosage/adverse effects ; Infusions, Intravenous ; *Antibodies, Monoclonal/administration & dosage/pharmacokinetics/adverse effects ; },
abstract = {BACKGROUND: PGDM1400LS is a human monoclonal antibody targeting the HIV envelope V2 apex with a lysine-serine modification intended to enhance serum and tissue half-lives and is being considered for use in combination monoclonal antibody trials. We sought to test whether PGDM1400LS was safe and had favourable serum concentration, pharmacokinetics, and neutralising ability in healthy adults.

METHODS: HVTN 140/HPTN 101 part A is an open-label, dose escalation, first-in-human phase 1 trial of PGDM1400LS given intravenously or subcutaneously to healthy adults aged 18-50 years without HIV-1. The study enrolled participants at four sites in the USA, across five groups, each receiving one dose of PGDM1400-LS intravenously (group 1: 5 mg/kg; group 2: 20 mg/kg; and group 4: 40 mg/kg) or subcutaneously (group 3: 20 mg/kg; and group 5: 40 mg/kg). Participants in group 1 were enrolled sequentially without random assignment. Participants in groups 2 and 3 were block randomised and enrolled simultaneously after group 1 safety review. Groups 4 and 5 followed the same process, contingent on groups 2 and 3 safety review. The primary endpoints were safety and tolerability of PGDM1400LS, serum concentration of PGDM1400LS, and serum neutralising activity after single administration of PGDM1400LS. Serum PGDM1400LS concentrations collected at seven timepoints (day 0, day 3, day 6, day 28, day 56, day 112, and day 168) were assessed via an anti-idiotype binding assay and characterised via non-compartmental pharmacokinetic analysis. Serum neutralisation activity (ID80) was assessed by a TZM-bl assay. The study is registered with ClinicalTrials.gov, NCT05184452.

FINDINGS: Between Nov 15, 2021, and March 4, 2022, 15 participants were enrolled into the five study groups (three participants per group) with 6 months of follow-up. Ten of 15 participants were female, 14 of 15 participants were non-Hispanic, and 11 of 15 participants were White, with a median age of 27 years (range 24-47). PGDM1400LS was safe and well tolerated, with mild to moderate solicited symptoms. Serum concentrations showed dose proportionality by administration route, with peak concentrations observed immediately after intravenous infusion (range 95·7-727·4 μg/mL) or on day 6 after subcutaneous infusion (205·6-547·1 μg/mL). The median elimination half-life was 55 days (range 48-59), representing a 2-to-3-times increase versus parental PDGM1400. Estimated subcutaneous (vs intravenous) bioavailability was 50-60%. ID80 titres showed agreement with concentration-predicted ID80 titres, indicating maintenance of neutralisation activity in vivo.

INTERPRETATION: PGDM1400LS is a promising candidate for combination monoclonal antibody efficacy trials going forward.

FUNDING: National Institute of Allergy and Infectious Diseases-National Institutes of Health.},
}

Humans
Adult
Female
Male
Young Adult
*HIV Antibodies/administration & dosage/adverse effects/immunology
*HIV-1/immunology
Middle Aged
Adolescent
*HIV Infections/prevention & control/immunology/drug therapy
*Antibodies, Neutralizing/administration & dosage/adverse effects/immunology
United States
*Broadly Neutralizing Antibodies/administration & dosage/adverse effects
Infusions, Intravenous
*Antibodies, Monoclonal/administration & dosage/pharmacokinetics/adverse effects

@article {pmid40440319,
year = {2025},
author = {Triplette, M and Omernik, B and Snidarich, M and Heffner, JL and Brooks, E and Crothers, K and Brown, MC and Murphy, NR and Louie, T},
title = {Tailored Patient Navigation to Support Lung Cancer Screening and Smoking Cessation in LGBTQ+ Individuals: A Pilot Study.},
journal = {Annals of the American Thoracic Society},
volume = {},
number = {},
pages = {},
doi = {10.1513/AnnalsATS.202502-215OC},
pmid = {40440319},
issn = {2325-6621},
abstract = {RATIONALE: Lung cancer is the leading cause of cancer death, with most cases attributable to cigarette smoking. People who identify as LGBTQ+ are more likely to smoke; however, there are limited interventions to support lung cancer prevention in this community. Through prior community-engaged work we developed a patient navigation intervention to support smoking cessation and lung cancer screening (LCS) for LGBTQ+ adults.

OBJECTIVE: To conduct a prospective pilot study of the patient navigation intervention to evaluate patient satisfaction, acceptability and knowledge change as well as LCS care completion and smoking cessation.

METHODS: We enrolled participants who currently smoked, identified as LGBTQ+ and were eligible for LCS into a patient navigation intervention and assessed outcomes over a 90-day period. We administered pre- and post-intervention surveys, tracked navigation and LCS activities in the electronic health record and verified tobacco cessation with exhaled carbon monoxide (CO) measurements. Primary outcomes included post-intervention Acceptability of Intervention Measure (AIM) scores, the Patient Satisfaction with Navigator Interpersonal Relationship (PSN-I) score, and knowledge change on two validated measures. Secondary outcomes included being appropriately up-to-date on LCS and smoking cessation, measured as reported >7 day floating abstinence and end-of-study CO-confirmed ≥30 day cessation.

RESULTS: Forty-one participants enrolled in the study and participated in the navigation program, with 34 completing post-intervention surveys at day 90. Acceptability (mean AIM score 4.5) and patient satisfaction (mean PSN-I score 40.8) were both high. Fifty-nine percent of individuals were appropriately up-to-date on LCS at day 90 compared to 22% at baseline. Of post-survey respondents, 41% reported a period of >7 day smoking abstinence during the study, with 18% reporting CO-confirmed abstinence of ≥30 days at study end.

CONCLUSIONS: Tailored patient navigation is a promising approach to enhance LCS uptake and smoking cessation in LCS-eligible LGBTQ+ individuals.

CLINICAL TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov NCT05304390. Primary Source of Funding. This work was funded through a grant from LUNGevity Foundation to Dr. Triplette.},
}

@article {pmid40440315,
year = {2025},
author = {Agrawal, P and Khechaduri, A and Salladay, KR and MacCamy, A and Ralph, DK and Riker, A and Stuart, AB and Siddaramaiah, LK and Shen, X and Matsen, FA and Montefiori, D and Stamatatos, L},
title = {Increased immunogen valency improves the maturation of vaccine-elicited HIV-1 VRC01-like antibodies.},
journal = {PLoS pathogens},
volume = {21},
number = {5},
pages = {e1013039},
doi = {10.1371/journal.ppat.1013039},
pmid = {40440315},
issn = {1553-7374},
abstract = {Antibodies belonging to the VRC01-class display broad and potent neutralizing activities and have been isolated from several people living with HIV (PLWH). A member of that class, monoclonal antibody VRC01, was shown to reduce HIV-acquisition in two phase 2b efficacy trials. VRC01-class antibodies are therefore expected to be one component of an effective HIV-1 vaccine elicited response. In contrast to the VRC01-class antibodies that are highly mutated, their unmutated forms do not engage HIV-1 envelope (Env) and do not display neutralizing activities. Hence, specifically modified Env-derived proteins have been designed to engage the unmutated forms of VRC01-class antibodies, and to activate the corresponding naïve B cells. Selected heterologous Env must then be used as boost immunogens to guide the proper maturation of these elicited VRC01-class antibodies. Here we examined whether and how the valency of the prime and boost immunogens influences VRC01-class antibody-maturation. Our findings indicate that, indeed the valency of the immunogen affects the maturation of elicited antibody responses by preferentially selecting VRC01-like antibodies that have accumulated somatic mutations present in broadly neutralizing VRC01-class antibodies isolated from PLWH. As a result, antibodies isolated from animals immunized with the higher valency immunogens display broader Env cross-binding properties and improved neutralizing potentials than those isolated from animals immunized with the lower valency immunogens. Our results are relevant to current and upcoming phase 1 clinical trials that evaluate the ability of novel immunogens aiming to elicit cross-reactive VRC01-class antibody responses.},
}

@article {pmid40440038,
year = {2025},
author = {Ding, Y and Naresh, KN},
title = {Primary myelofibrosis involving lymph nodes with the same mutational profile in bone marrow.},
journal = {Blood},
volume = {145},
number = {22},
pages = {2672},
doi = {10.1182/blood.2025028556},
pmid = {40440038},
issn = {1528-0020},
}

@article {pmid40439580,
year = {2025},
author = {Bondeelle, L and Cheng, GS and Bergeron, A},
title = {What's new in the management of pulmonary complications in allogeneic stem cell transplantation?.},
journal = {Expert review of respiratory medicine},
volume = {},
number = {},
pages = {},
doi = {10.1080/17476348.2025.2513519},
pmid = {40439580},
issn = {1747-6356},
abstract = {INTRODUCTION: As survival increases after allogeneic hematopoietic stem cell transplantation (allo-HCT), several organ complications have emerged, including those involving the lung, which require a multidisciplinary management approach. The constant evolution of allo-HCT procedures, advances in diagnostic tools for infections and pulmonary disease, as well as new treatment approaches, require frequent updating of knowledge in this field.

AREAS COVERED: We review the multiple infectious and noninfectious lung complications that occur both early and late after allo-HCT. This includes an updated description of these complications, risk factors, diagnostic approach and outcome. A literature search was performed using PubMed-indexed journals.

EXPERT OPINION: The diagnosis of pulmonary complications after allo-HCT remains challenging, further complicated by the frequent association of co-infections and/or links between infection and noninfectious complications. The development of metagenomic next-generation sequencing (mNGS) should enhance the diagnostic yield of bronchoalveolar lavage but its clinical relevance remains to be evaluated. A better understanding of the pathophysiology of the lung chronic graft-versus-host disease (GVHD) and improved phenotyping are essential for advancing its diagnostic and therapeutic management. This requires a revision of diagnostic criteria and the identification of new biomarkers of early disease.},
}

@article {pmid40438119,
year = {2025},
author = {Creighton, RL and Hughes, SM and Hladik, F and Gornalusse, GG},
title = {The intestinal interferon system and specialized enterocytes as putative drivers of HIV latency.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1589752},
pmid = {40438119},
issn = {1664-3224},
mesh = {Humans ; *Enterocytes/immunology/virology/metabolism ; *HIV Infections/immunology/virology/metabolism ; *Virus Latency/immunology ; *Interferons/metabolism/immunology ; *HIV-1/physiology/immunology ; CD4-Positive T-Lymphocytes/immunology/virology ; Animals ; Virus Activation ; Intestinal Mucosa/immunology/metabolism ; Signal Transduction ; },
abstract = {The barrier to HIV cure is the HIV reservoir, which is composed of latently infected CD4[+] T cells and myeloid cells that carry stably integrated and replication-competent provirus. The gastrointestinal tract (GIT) contains a substantial part of the HIV reservoir and its immunophysiology could be especially conducive for HIV persistence and reactivation. However, the exact cellular microenvironment and molecular mechanisms that govern the renewal of provirus-harboring cells and proviral reactivation in the GIT remain unclear. In this review, we outline the evidence supporting an overarching hypothesis that interferon activity driven by specialized enterocytes creates a microenvironment that fosters proliferation of latently infected CD4[+] T cells and sporadic HIV reactivation from these cells. First, we describe unique immunologic features of the gastrointestinal associated lymphoid tissue (GALT), specifically highlighting IFN activity in specialized enterocytes and potential interactions between these cells and neighboring HIV susceptible cells. Then, we will describe dysregulation of IFN signaling in HIV infection and how IFN dysregulation in the GALT may contribute to the persistence and reactivation of the latent HIV reservoir. Finally, we will speculate on the clinical implications of this hypothesis for HIV cure strategies and outline the next steps.},
}

Humans
*Enterocytes/immunology/virology/metabolism
*HIV Infections/immunology/virology/metabolism
*Virus Latency/immunology
*Interferons/metabolism/immunology
*HIV-1/physiology/immunology
CD4-Positive T-Lymphocytes/immunology/virology
Animals
Virus Activation
Intestinal Mucosa/immunology/metabolism
Signal Transduction

@article {pmid40438096,
year = {2025},
author = {Ackerley, CG and Edupuganti, S and Yu, C and Roxby, AC and Seaton, KE and Bekker, LG and Allen, M and DeRosa, SC and Yates, NL and Heptinstall, J and Mkhize, NN and Malahleha, M and Mngadi, K and Daniels, B and Innes, C and Furch, BD and Koutsoukos, M and Ferrari, G and Morris, L and Montefiori, DC and McElrath, MJ and Tomaras, GD and Laher, F and Moodie, Z},
title = {Retrospective analysis of sex-disaggregated immune responses to ALVAC-HIV and bivalent subtype C gp120/MF59 HIV vaccines.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1557009},
pmid = {40438096},
issn = {1664-3224},
mesh = {Humans ; *AIDS Vaccines/immunology/administration & dosage ; Male ; Female ; Adult ; Retrospective Studies ; *HIV Infections/immunology/prevention & control/virology ; *HIV Envelope Protein gp120/immunology ; HIV Antibodies/immunology/blood ; *HIV-1/immunology ; Young Adult ; Adolescent ; Antibodies, Neutralizing/immunology/blood ; Antibody-Dependent Cell Cytotoxicity ; Sex Factors ; Immunogenicity, Vaccine ; *Squalene/immunology/administration & dosage ; },
abstract = {INTRODUCTION: Generally, individuals assigned female at birth (AFAB) develop greater immunogenicity to various vaccines than individuals assigned male at birth (AMAB). Little is known about sex-disaggregated immunogenicity to HIV-1 vaccines. We disaggregated immune responses to an experimental HIV vaccine regimen.

METHODS: We retrospectively analyzed data from HVTN 100, a clinical trial conducted in South Africa during which 143 adults AMAB and 109 AFAB aged 18-40 years without HIV received ALVAC-HIV vCP2438 plus bivalent subtype C gp120/MF59 or placebo at 0, 1, 3, 6, and 12 months. Eligible data were from per-protocol vaccine recipients at month 6.5. We measured IgG binding antibodies, neutralizing antibodies, antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and CD4+ IFNγ and/or II-2 responses. We compared sex-based differences in response rates using Barnard's test and response magnitudes using Wilcoxon Rank Sum test. P-values were Holm-adjusted for multiple comparisons.

RESULTS: Of 185 vaccine recipients, 73 were AFAB and 112 were AMAB. Vaccine recipients AFAB had greater ADCC response rate (57.5% versus 29.5%; padj = 0.0003) and greater ADCC magnitude (area under the net % granzyme B activity vs log10 curve (AUC), 16.1 versus 11.2; padj = 0.05) to vaccine-matched antigen TV1.C gp120 compared to AMAB. Vaccine recipients AMAB had higher CD4+ T cell response rates to 2/3 vaccine-matched antigens at month 6.5 (ZM96.C gp120, [54.1% versus 36.8%; padj = 0.04]; 1086.C gp120, [44.1% versus 29.4%; padj = 0.05]) than AFAB. CD4+ T cell response magnitudes were similar by sex. IgG binding antibody response rate to B.CaseA V1V2 antigen (associated with reduced HIV acquisition risk in the RV144 trial) was 56.8% among AMAB vaccine recipients versus 38.9% among AFAB (padj = 0.08). There were no sex-based differences in neutralizing antibody or ADCP responses.

DISCUSSION: We identified sex-based differences in immune responses to an HIV vaccine regimen, but they varied by immunologic assay. While vaccine recipients AFAB demonstrated higher ADCC responses, AMAB exhibited higher CD4+ T cell response rates. Future analyses should investigate whether vaccine factors such as platform, dosing and adjuvants contribute to sex-based differences in immunogenicity of experimental HIV vaccines.},
}

Humans
*AIDS Vaccines/immunology/administration & dosage
Male
Female
Adult
Retrospective Studies
*HIV Infections/immunology/prevention & control/virology
*HIV Envelope Protein gp120/immunology
HIV Antibodies/immunology/blood
*HIV-1/immunology
Young Adult
Adolescent
Antibodies, Neutralizing/immunology/blood
Antibody-Dependent Cell Cytotoxicity
Sex Factors
Immunogenicity, Vaccine
*Squalene/immunology/administration & dosage

@article {pmid40435511,
year = {2025},
author = {Wudhikarn, K and Herr, MM and Chen, M and Martens, MJ and Baird, JH and Gowda, L and Rangarajan, HG and Abid, MB and Kharfan-Dabaja, MA and Williams, KM and Ganguly, S and Young, JH and Sharma, A and Fatobene, G and Jain, T and Kanakry, CG and Modi, D and Grover, NS and Salem, B and Batista, MV and Vergidis, P and Yin, DE and Beitinjaneh, AM and Kelkar, AH and Nishihori, T and Holter-Chakrabarty, J and Gergis, U and Smith, M and El Boghdadly, Z and Dandoy, CE and Murthy, HS and Huppler, AR and Perales, MA and Chemaly, RF and Hill, JA and Riches, M and Auletta, JJ},
title = {Infection after CD19 chimeric antigen receptor T cell therapy for large B cell lymphoma: Real-world analysis from CIBMTR.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025016141},
pmid = {40435511},
issn = {2473-9537},
abstract = {Infection is increasingly recognized as a significant cause of morbidity and mortality in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) receiving CD19 chimeric antigen receptor (CAR) T-cell therapy. The current study analyzed the natural history, risk factors, and outcomes of infection in 3350 R/R LBCL patients receiving commercial CD19 CAR T-cell (n=2804 axicabtagene ciloleucel, n=546 tisagenlecleucel) from December 2017 to June 2022. Infection developed in 834 (24.9%) patients within 100 days post-infusion, resulting in an infection density of 0.43 per 100 patient-days and a 100-day cumulative incidence of 22%. Bacterial, viral, and fungal infections were recorded in 527 (15.7%), 374 (11.2%), and 108 (3.2%) patients, respectively, with corresponding infection densities of 0.23, 0.15, and 0.04 per 100 patient-days. After a 24-month median follow-up, 1482 (44%) patients had died, with infection as the primary cause in 173 cases (12%). The 100-day infection-related mortality (IRM) was 1.6% (95% confidence interval, 1.2-2.0%). Patients with Karnofsky score ≤80, infection history pre-CAR-T, axicabtagene ciloleucel therapy, severe cytokine release syndrome (grade ≥3), and severe immune effector cell-associated neurotoxicity syndrome (grade ≥3) had increased infection risk. Infections within 100 days were an independent risk factor for inferior overall survival beyond day 100 after CD19 CAR T-cell therapy. In conclusion, study results show a significant incidence of infection and IRM in patients with R/R LBCL treated with CD19 CAR T-cell. Furthermore, results identify patients at heightened risk for infection, offering insights to guide potential interventions aimed at mitigating infection and improving patient outcomes after CAR T-cell therapy.},
}

@article {pmid40435447,
year = {2025},
author = {Nakasone, ES and Cohen, SA},
title = {Secondary Acute Myeloid Leukemia following Treatment for Metastatic Poorly Differentiated Pancreatic Neuroendocrine Carcinoma: A Cautionary Sequel to an Exceptional Response.},
journal = {Pancreas},
volume = {},
number = {},
pages = {},
doi = {10.1097/MPA.0000000000002520},
pmid = {40435447},
issn = {1536-4828},
}

@article {pmid40435434,
year = {2025},
author = {Daca-Álvarez, M and Brunori, A and Carbone, A and Carbonell, C and Tangen, CM and Unger, JM and Lucia, MS and Oliva, M and De Censi, A and Brenner, DR and Thompson, IM and Balaguer, F},
title = {Emerging Strategies for Drug-Based Cancer Risk Reduction.},
journal = {American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting},
volume = {45},
number = {3},
pages = {e473708},
doi = {10.1200/EDBK-25-473708},
pmid = {40435434},
issn = {1548-8756},
mesh = {Humans ; *Neoplasms/prevention & control/epidemiology/drug therapy/etiology ; Risk Factors ; Chemoprevention/methods ; Risk Reduction Behavior ; Female ; },
abstract = {Chemoprevention has emerged as a promising strategy to reduce cancer incidence by using pharmacologic agents that interrupt the carcinogenesis process. This review discusses emerging insights and recent advancements in chemoprevention, emphasizing novel approaches in several cancer types. Specifically, we examine breast cancer prevention, focusing on optimized endocrine therapy dosing to enhance adherence and minimize adverse effects while maintaining efficacy. Additionally, the potential of glucagon-like peptide-1 receptor agonists to mitigate obesity-related cancer risks is evaluated, highlighting their role in addressing an increasingly prevalent risk factor in the general population. The review further explores strategies targeting colorectal cancer (CRC), specifically in familial adenomatous polyposis, a hereditary CRC syndrome that exemplifies the complex interplay between chemoprevention, genetic risk, and patient management. In prostate cancer, we highlight the evidence supporting the use of 5-alpha reductase inhibitors, detailing their effectiveness in reducing cancer incidence as well as their safety profile. Across these areas, this review underscores the importance of precision medicine, advocating for personalized approaches that balance efficacy, safety, and quality-of-life considerations. Ultimately, advancing chemopreventive strategies through targeted research and clinical trials is essential for reducing cancer burden and improving patient outcomes.},
}

Humans
*Neoplasms/prevention & control/epidemiology/drug therapy/etiology
Risk Factors
Chemoprevention/methods
Risk Reduction Behavior
Female

@article {pmid40435263,
year = {2025},
author = {Marsh, NM and MacEwen, MJS and Chea, J and Kenerson, HL and Kwong, AA and Locke, TM and Miralles, FJ and Sapre, T and Gozali, N and Hart, ML and Bammler, TK and MacDonald, JW and Sullivan, LB and Atilla-Gokcumen, GE and Ong, SE and Scott, JD and Yeung, RS and Sancak, Y},
title = {Mitochondrial calcium signaling regulates branched-chain amino acid catabolism in fibrolamellar carcinoma.},
journal = {Science advances},
volume = {11},
number = {22},
pages = {eadu9512},
pmid = {40435263},
issn = {2375-2548},
mesh = {*Amino Acids, Branched-Chain/metabolism ; *Carcinoma, Hepatocellular/metabolism/genetics/pathology ; Humans ; *Liver Neoplasms/metabolism/pathology/genetics ; *Mitochondria/metabolism ; *Calcium Signaling ; Cell Line, Tumor ; Calcium Channels/metabolism/genetics ; Kruppel-Like Transcription Factors/metabolism/genetics ; Gene Expression Regulation, Neoplastic ; },
abstract = {Metabolic adaptations are essential for survival. The mitochondrial calcium uniporter plays a key role in coordinating metabolic homeostasis by regulating mitochondrial metabolic pathways and calcium signaling. However, a comprehensive analysis of uniporter-regulated mitochondrial pathways has remained unexplored. Here, we investigate consequences of uniporter loss and gain of function using uniporter knockout cells and fibrolamellar carcinoma (FLC), which we demonstrate to have elevated mitochondrial calcium levels. We find that branched-chain amino acid (BCAA) catabolism and the urea cycle are uniporter-regulated pathways. Reduced uniporter function boosts expression of BCAA catabolism genes and the urea cycle enzyme ornithine transcarbamylase. In contrast, high uniporter activity in FLC suppresses their expression. This suppression is mediated by the transcription factor KLF15, a master regulator of liver metabolism. Thus, the uniporter plays a central role in FLC-associated metabolic changes, including hyperammonemia. Our study identifies an important role for the uniporter in metabolic adaptation through transcriptional regulation of metabolism and elucidates its importance for BCAA and ammonia metabolism.},
}

*Amino Acids, Branched-Chain/metabolism
*Carcinoma, Hepatocellular/metabolism/genetics/pathology
Humans
*Liver Neoplasms/metabolism/pathology/genetics
*Mitochondria/metabolism
*Calcium Signaling
Cell Line, Tumor
Calcium Channels/metabolism/genetics
Kruppel-Like Transcription Factors/metabolism/genetics
Gene Expression Regulation, Neoplastic

@article {pmid40434773,
year = {2025},
author = {Andrews, LIB and Halloran, ME and Neuzil, KM and van der Laan, L and Huang, Y and Andriesen, J and Patel, M and Fisher, LH and Janes, H and Rouphael, N and Walsh, SR and Theodore, DA and Tieu, HV and Sobieszczyk, M and El Sahly, HM and Baden, LR and Falsey, AR and Campbell, TB and Kelley, CF and Healy, CM and Immergluck, L and Luft, B and Hirsch, I and de Bruyn, G and Truyers, C and Priddy, F and Sumner, KM and Flannery, B and Follmann, D and Gilbert, PB and , },
title = {Evaluating the Test-Negative Design for COVID-19 Vaccine Effectiveness Using Randomized Trial Data: A Secondary Cross-Protocol Analysis of 5 Randomized Clinical Trials.},
journal = {JAMA network open},
volume = {8},
number = {5},
pages = {e2512763},
pmid = {40434773},
issn = {2574-3805},
mesh = {Humans ; *COVID-19 Vaccines/therapeutic use ; *COVID-19/prevention & control/diagnosis ; *Vaccine Efficacy ; *Randomized Controlled Trials as Topic ; SARS-CoV-2/immunology ; Adult ; Female ; Male ; Middle Aged ; *Research Design ; },
abstract = {IMPORTANCE: The test-negative design (TND) has been widely used to assess postmarketing COVID-19 vaccine effectiveness but requires further evaluation for this application.

OBJECTIVE: To determine whether the TND reliably evaluates vaccine effectiveness against symptomatic COVID-19 using placebo-controlled vaccine efficacy randomized clinical trials (RCTs).

This secondary cross-protocol analysis constructed TND study datasets from study sites in 16 countries across 5 continents using the blinded phase cohorts of 5 harmonized phase 3 COVID-19 Prevention Network RCTs: COVE (Coronavirus Vaccine Efficacy and Safety), AZD1222, ENSEMBLE, PREVENT-19 (Prefusion Protein Subunit Vaccine Efficacy Novavax Trial COVID-19), and VAT00008. Participants included adults who received the intended number of doses, experienced COVID-19-like symptoms, and obtained SARS-CoV-2 testing. Start dates ranged from July 27, 2020, to October 19, 2021; data cutoff dates ranged from March 26, 2021, to March 15, 2022. Statistical analysis was performed from May 11, 2023, to February 25, 2025.

INTERVENTIONS: Participants received vaccines consisting of messenger RNA-1273 (COVE; 2 doses 28 days apart), ChAdOx1 nCoV-19 (AZD1222; 2 doses 28 days apart), Ad26.COV2.S (ENSEMBLE; 1 dose), NVX-CoV2373 (PREVENT-19; 2 doses 21 days apart), CoV2 preS dTM-AS03 (VAT00008; D614) (2 doses 21 days apart), or CoV2 preS dTM-AS03 (D614 plus B.1.351) (VAT00008; 2 doses 21 days apart) or placebo.

MAIN OUTCOMES AND MEASURES: Main outcomes were symptomatic COVID-19 according to each trial's primary efficacy definition and the Centers for Disease Control and Prevention definition. Vaccine effectiveness was estimated using targeted maximum likelihood estimation under a semiparametric logistic regression model and ordinary logistic regression. Noncase exchangeability, a core TND assumption for unbiased estimation, was also assessed by estimating vaccine efficacy against non-COVID-19 illness.

RESULTS: Among the 12 157 participants included in the analysis, mean (SD) age was 45 (15) years, 6414 were female (53%), 5858 were vaccinated (48%), 2835 experienced primary COVID-19 (23%), and 2992 experienced Centers for Disease Control and Prevention-defined COVID-19 (25%). TND vaccine effectiveness estimates were concordant with RCT vaccine efficacy estimates (concordance correlation coefficient, 0.86 [95% CI, 0.58-0.96] for both outcomes). The semiparametric method had 48% smaller variance estimates than ordinary logistic regression. Noncase exchangeability was generally supported with a median vaccine efficacy against non-COVID-19 illness of 7.7% (IQR, 2.7%-16.8%) across trial cohorts and most 95% CIs including 0.

CONCLUSIONS AND RELEVANCE: In this cross-protocol analysis, the TND provided reliable inferences on COVID-19 vaccine effectiveness in health care-seeking populations for multiple vaccines and symptom definitions when confounding and selection bias were absent. A machine-learning approach for robust confounding control in postmarketing TND studies was also introduced.},
}

Humans
*COVID-19 Vaccines/therapeutic use
*COVID-19/prevention & control/diagnosis
*Vaccine Efficacy
*Randomized Controlled Trials as Topic
SARS-CoV-2/immunology
Adult
Female
Male
Middle Aged
*Research Design

@article {pmid40427141,
year = {2025},
author = {Dahlberg, A and Stevenson, P and Bhatt, NS and Burroughs, L and Carpenter, PA and Summers, C and Tarlock, K and Thakar, MS and Milano, F and Deeg, HJ and Bleakley, M},
title = {Disease Burden at the Time of Transplantation Is a Primary Predictor of Outcomes in Pediatric MDS: A Single-Center Experience.},
journal = {Cancers},
volume = {17},
number = {10},
pages = {},
pmid = {40427141},
issn = {2072-6694},
abstract = {BACKGROUND: Hematopoietic cell transplantation (HCT) remains the only curative therapy for pediatric myelodysplastic syndrome (MDS) in all but rare cases. While HCT outcomes for pediatric MDS are similar across the largest registry and single-center trials, factors identified as contributing to inferior outcomes vary from study to study. We performed an analysis to provide more clarity on the prognostic implications of disease characteristics, including blast burden and cytogenetic abnormalities, in the current era.

METHODS: We conducted a retrospective analysis of 36 consecutive children (<18 years of age at HCT) who underwent allogeneic HCT for MDS between June 2000 and October 2019 at the Fred Hutchinson Cancer Center.

RESULTS: Overall survival (OS) was 77% (95% CI 64-92%) and relapse-free survival (RFS) was 71% (95% CI 57-88%) at 2 years post-HCT. Patients with <5% blasts by morphology in the bone marrow at the time of HCT showed superior 2-year OS at 87% (95% CI 74-100%) as compared to 54% (95% CI 32-93%) in patients with ≥5% blasts, consistent with an HR of 4.6 (CI 1.14-18.7, p = 0.03). The inferior outcomes in patients with ≥5% blasts were due to increased relapse incidence (HR 7.6, CI 1.5-39.3) with no difference in NRM or acute GVHD.

CONCLUSIONS: OS and RFS were comparable to what has been observed in other large, single-center studies (OS 77%, RFS 71% at 2 years) and compared favorably to outcomes from the largest multi-center retrospective analyses.},
}

@article {pmid40425844,
year = {2025},
author = {Kwan, EM and Ng, SWS and Tolmeijer, SH and Emmett, L and Sandhu, S and Buteau, JP and Iravani, A and Joshua, AM and Francis, RJ and Subhash, V and Lee, ST and Scott, AM and Martin, AJ and Stockler, MR and Donnellan, G and Annala, M and Herberts, C and Davis, ID and Hofman, MS and Azad, AA and Wyatt, AW and , },
title = {Lutetium-177-PSMA-617 or cabazitaxel in metastatic prostate cancer: circulating tumor DNA analysis of the randomized phase 2 TheraP trial.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {40425844},
issn = {1546-170X},
support = {PCF Challenge Award//Prostate Cancer Foundation (PCF)/ ; Young Investigator Award//Prostate Cancer Foundation (PCF)/ ; Young Investigator Award//Prostate Cancer Foundation (PCF)/ ; BC Trainee Award//Michael Smith Foundation for Health Research (MSFHR)/ ; NHMRC Investigator Fellowship #1177837//Department of Health | National Health and Medical Research Council (NHMRC)/ ; NHMRC Practitioner Fellowship APP1102604//Department of Health | National Health and Medical Research Council (NHMRC)/ ; },
abstract = {The prostate-specific membrane antigen (PSMA)-targeted radioligand [[177]Lu]Lu-PSMA-617 is a new standard treatment for metastatic castration-resistant prostate cancer (mCRPC), but predictive genomic biomarkers informing its rational use are unknown. We performed detailed dissection of prostate cancer driver genes across 290 serial plasma cell-free DNA samples from 180 molecular imaging-selected patients with mCRPC from the randomized TheraP trial of [[177]Lu]Lu-PSMA-617 (n = 97) versus cabazitaxel chemotherapy (n = 83). The primary endpoint was PSA50 biochemical response, with secondary endpoints of progression-free survival (PFS) and overall survival (OS). In this post-hoc biomarker analysis, a low pretreatment circulating tumor DNA (ctDNA) fraction predicted a superior biochemical response (100% versus 58%, P = 0.0067) and PFS (median 14.7 versus 6.0 months; hazard ratio 0.12, P = 2.5 × 10[-4]) on [[177]Lu]Lu-PSMA-617 independent of predictive PSMA-positron emission tomography imaging parameters, although this benefit did not extend to OS. Deleterious PTEN alterations were associated with worse PFS and OS on cabazitaxel, whereas ATM defects were observed in select patients with favorable [[177]Lu]Lu-PSMA-617 outcomes. Comparing pretreatment and progression ctDNA revealed population flux but no evidence that alterations in individual mCRPC genes (or FOLH1) are dominant causes of acquired [[177]Lu]Lu-PSMA-617 or cabazitaxel resistance. Our results nominate new candidate biomarkers for [[177]Lu]Lu-PSMA-617 selection and ultimately expand the mCRPC predictive biomarker repertoire. We anticipate our ctDNA fraction-aware analytical framework will aid future precision management strategies for [[177]Lu]Lu-PSMA-617 and other PSMA-targeted therapeutics. ClinicalTrials.gov identifier: NCT03392428 .},
}

@article {pmid40425554,
year = {2025},
author = {Borot, F and Humbert, O and Ehmsen, JT and Fields, E and Kohli, S and Radtke, S and Swing, K and Pande, D and Enstrom, MR and Laszlo, GS and Mayuranathan, T and Ali, AM and Weiss, MJ and Yen, JS and Newby, GA and Walter, RB and Liu, DR and Mukherjee, S and Kiem, HP},
title = {Multiplex base editing to protect from CD33 directed drugs for immune and gene therapy.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {4899},
pmid = {40425554},
issn = {2041-1723},
mesh = {Humans ; Animals ; *Gene Editing/methods ; *Sialic Acid Binding Ig-like Lectin 3/genetics/metabolism/immunology ; *Genetic Therapy/methods ; Hematopoietic Stem Cells/metabolism/drug effects ; Gemtuzumab/pharmacology ; *Immunotherapy/methods ; Polymorphism, Single Nucleotide ; CRISPR-Cas Systems ; Mice ; },
abstract = {The selection of genetically engineered immune or hematopoietic cells in vivo after gene editing remains a clinical problem and requires a method to spare on-target toxicity to normal cells. Here, we develop a base editing approach exploiting a naturally occurring CD33 single nucleotide polymorphism leading to removal of full-length CD33 surface expression on edited cells. CD33 editing in human and nonhuman primate hematopoietic stem and progenitor cells protects myeloid progeny from CD33-targeted therapeutics without affecting normal hematopoiesis in vivo, thus demonstrating potential for improved immunotherapies with reduced off-leukemia toxicity. For broader application to gene therapies, we demonstrate highly efficient (>70%) multiplexed adenine base editing of the CD33 and gamma globin genes, resulting in long-term persistence of dual gene-edited cells with HbF reactivation in nonhuman primates. Using the CD33 antibody-drug conjugate Gemtuzumab Ozogamicin, we show resistance of engrafted, multiplex edited human cells in vivo, and a 2-fold enrichment for edited cells in vitro. Together, our results highlight the potential of adenine base editors for improved immune and gene therapies.},
}

Humans
Animals
*Gene Editing/methods
*Sialic Acid Binding Ig-like Lectin 3/genetics/metabolism/immunology
*Genetic Therapy/methods
Hematopoietic Stem Cells/metabolism/drug effects
Gemtuzumab/pharmacology
*Immunotherapy/methods
Polymorphism, Single Nucleotide
CRISPR-Cas Systems
Mice

@article {pmid40425412,
year = {2025},
author = {Swaminathan, M and Holt, SK and Gore, JL and Nyame, YA and Wright, J and Shah, A and Sparks, JA and Makris, UE and Grivas, P and Suarez-Almazor, M and Psutka, S and Singh, N},
title = {Association Between Rheumatoid Arthritis, Frailty Status, and Mortality in Older Adults with Bladder Cancer.},
journal = {Clinical genitourinary cancer},
volume = {},
number = {},
pages = {102369},
doi = {10.1016/j.clgc.2025.102369},
pmid = {40425412},
issn = {1938-0682},
abstract = {BACKGROUND: To evaluate the associations between rheumatoid arthritis (RA) and all-cause (ACM) and cancer-Specific mortality (CSM) in older adults with bladder cancer and examine how frailty may affect these associations.

METHODS: Retrospective cohort study derived from the Surveillance Epidemiology and End Results (SEER) cancer registry and linked to Medicare claims data (SEER-Medicare). The cohort consisted of patients ≥ 65 years diagnosed with bladder cancer between 2004 and 2017. RA and frailty status were derived using validated administrative algorithms. ACM and CSM as derived from the SEER registry.

RESULTS: Frailty modified the relationship between RA and mortality outcomes (interaction P value for ACM: .002 and for CSM: .007). We observed that RA was associated with a higher risk of CSM (aHR 1.17, 95% CI, 1.01-1.35) and ACM (aHR 1.12, 95% CI, 1.05-1.20) in nonfrail patients. In frail patients with bladder cancer, RA was not independently associated with CSM (aHR 0.81, 95% CI, 0.62-1.06) or ACM (aHR 0.93, 95% CI, 0.83-1.05).

CONCLUSION: Frailty is associated with adverse health outcomes. As people are living longer, it is becoming increasingly prevalent among patients with chronic conditions such as RA. We observed that RA is associated with increased risk of ACM and CSM among nonfrail older adults with bladder cancer. The lack of an association between RA and mortality in frail patients with RA suggests that the effect of frailty on mortality may overpower the effect that RA may exert-this information can help prognosticate outcomes in patients with bladder cancer, RA, and frailty.},
}

@article {pmid40425247,
year = {2025},
author = {Tatunay, K and Cohen, S and Naylor, LV and Handford, CL and Jacobson, A and Shankaran, V and Oelschlager, B and Grady, WM and Sjoding, B and Lally, E and Facchini, L and Sun, Q and Laurino, MY and Pritchard, C and Konnick, EQ and Dubard-Gault, ME},
title = {Does paired genetic testing improve targeted therapy choices and screening recommendations for patients with upper gastrointestinal cancers and their families? A prospective cohort of 42 patients.},
journal = {BMJ open},
volume = {15},
number = {5},
pages = {e091745},
pmid = {40425247},
issn = {2044-6055},
mesh = {Humans ; Male ; Female ; *Genetic Testing/methods ; Prospective Studies ; Middle Aged ; Aged ; *Gastrointestinal Neoplasms/genetics/diagnosis/therapy ; *Esophageal Neoplasms/genetics/diagnosis/therapy ; *Early Detection of Cancer/methods ; Adult ; *Molecular Targeted Therapy ; *Stomach Neoplasms/genetics/diagnosis/therapy ; Genetic Predisposition to Disease ; },
abstract = {OBJECTIVES: Our study was designed to assess whether paired normal-tumour testing increased access to targeted therapy, clinical trials and influenced cancer screening recommendations given to patients and their families.

DESIGN: Prospective cohort study.

SETTING: Academic cancer centre in the Pacific Northwest region of the USA.

PARTICIPANTS: Patients newly diagnosed between 01 January 2021 and 31 December 2022 with cancers of the oesophagus, gastro-oesophageal junction and stomach (CEGEJS) were included. All other cancer diagnoses such as head and neck, duodenal and lower gastrointestinal tract cancers were excluded.

INTERVENTION: Paired germline and tumour genetic test within 90 days of new patient visit.

PRIMARY OUTCOME MEASURES: Number of targeted therapies received (or not) when eligible, follow-up treatment data and number of inherited predispositions to cancers identified. No secondary outcome measures.

RESULTS: Of 42 patients, 32 (76.2%) were eligible for at least one targeted therapy. 19 patients received immunotherapy, when 16 had a biomarker predicting immunotherapy benefit, and benefit of immunotherapy was unclear for 3. Another 11 did not have this biomarker, and 6 of them received immunotherapy. Six pathogenic variants were identified in four high-risk genes. By 01 January 2024, 18 patients (42.9%) had died of complications of cancer.

CONCLUSION: More than 75% of patients who received tumour testing were eligible for a targeted therapy regardless of their stage at diagnosis, emphasising the need to expand access to testing with staging workup to improve survival outcomes. Six families received personalised screening recommendations, thanks to this study.},
}

Humans
Male
Female
*Genetic Testing/methods
Prospective Studies
Middle Aged
Aged
*Gastrointestinal Neoplasms/genetics/diagnosis/therapy
*Esophageal Neoplasms/genetics/diagnosis/therapy
*Early Detection of Cancer/methods
Adult
*Molecular Targeted Therapy
*Stomach Neoplasms/genetics/diagnosis/therapy
Genetic Predisposition to Disease

@article {pmid40422973,
year = {2025},
author = {Zeller, M and Chang, J and Trevisan, G and Gauger, PC and Zhang, J},
title = {Nextclade data set for the ORF5-based lineage classification of PRRSV-1.},
journal = {Microbiology resource announcements},
volume = {},
number = {},
pages = {e0030325},
doi = {10.1128/mra.00303-25},
pmid = {40422973},
issn = {2576-098X},
abstract = {A Nextclade data set for PRRSV-1 ORF5 based on a global nomenclature for standardized lineage classification was developed. This tool enables rapid sequence analysis, visualization, and comparison with reference strains and vaccines. By providing accessibility, it facilitates broader adoption of PRRSV-1 classification frameworks for research and surveillance.},
}

@article {pmid40421959,
year = {2025},
author = {Spencer, KR and King, GG},
title = {MDM2 as a therapeutic target in advanced biliary tract cancers.},
journal = {The oncologist},
volume = {30},
number = {5},
pages = {},
pmid = {40421959},
issn = {1549-490X},
support = {//Boehringer Ingelheim Pharmaceuticals, Inc/ ; },
mesh = {Humans ; *Proto-Oncogene Proteins c-mdm2/genetics/antagonists & inhibitors/metabolism ; *Biliary Tract Neoplasms/drug therapy/pathology/genetics ; Molecular Targeted Therapy ; Tumor Suppressor Protein p53/genetics/metabolism ; },
abstract = {Biliary tract cancers (BTCs) are a heterogeneous group of tumors arising from cells in the bile ducts and gallbladder. The 5-year overall survival rate for all BTC stages combined is ~20%, and treatment options for patients with unresectable disease are limited, leaving an unmet clinical need. In recent years, significant efforts have been made to refine and implement targeted therapeutic approaches for patients with BTC. The adoption of early and comprehensive molecular profiling is crucial to identifying patients who may be candidates for effective targeted therapies. Characterization of the molecular landscape of BTCs led to the identification of murine double minute 2 homolog gene (MDM2) amplification across all BTC subtypes. The MDM2 protein is a critical negative regulator of p53 stabilization and activity that is an emerging actionable biomarker in BTCs. There are multiple therapeutic approaches that aim to target MDM2 activity, thereby restoring the intrinsic tumor suppressor function of p53 and halting oncogenesis. However, these have been limited by our evolving understanding of the role of MDM2 in BTC pathogenesis. Here, we offer a review of the current understanding of the role of MDM2 in BTC biology and its therapeutic implications.},
}

Humans
*Proto-Oncogene Proteins c-mdm2/genetics/antagonists & inhibitors/metabolism
*Biliary Tract Neoplasms/drug therapy/pathology/genetics
Molecular Targeted Therapy
Tumor Suppressor Protein p53/genetics/metabolism

@article {pmid40421022,
year = {2025},
author = {Paktinat, S and Gravett, MG and Tobey, C and Kirby, A and Horner, W and Shaffer, R and Fialkow, M and Nguyen, NP and Gornalusse, GG and Kalatehjari, M and Hughes, SM and Hladik, F and Vojtech, L},
title = {Extracellular vesicles from human semen induce unique tolerogenic phenotypes in vaginal dendritic cells and regulatory T lymphocytes.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1564002},
pmid = {40421022},
issn = {1664-3224},
mesh = {Humans ; *Dendritic Cells/immunology/metabolism ; Female ; *Semen/immunology/metabolism ; *T-Lymphocytes, Regulatory/immunology/metabolism ; *Extracellular Vesicles/immunology/metabolism ; *Immune Tolerance ; Cell Differentiation/immunology ; *Vagina/immunology/cytology ; Male ; Phenotype ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Cells, Cultured ; Pregnancy ; Coculture Techniques ; },
abstract = {INTRODUCTION: The regulation of immune responses to promote tolerance to the fetus is critical for successful pregnancy. An understudied aspect of this process is the initiation of regulation pre-conception via exposure to semen. Our study aimed to understand how semen impacts recipient dendritic cells (DCs) and their subsequent role in shaping CD4 T cell differentiation.

METHODS: Monocyte-derived DCs (MoDCs) were exposed to semen extracellular vesicles (SEV) or vesicle-depleted semen plasma (VDSP). Phenotypic and functional markers were analyzed using flow cytometry. We also exposed epithelial sheets from vaginal tissue to SEV and VDSP, and measured the number and marker expression of emigrating cells. Finally, we tested how SEV- or VDSP-exposed DCs altered CD4 T cell differentiation by co-culturing exposed MoDCs or tissue emigrated cells with autologous naïve CD4 T cells.

RESULTS: MoDCs exhibited a significant increase of CD141, CD1a, CD38, and ILT4 expression when exposed to SEV or VDSP. A unique feature of semen-treated MoDCs was expression of indoleamine 2,3-dioxygenase (IDO), a potent contributor to the induction of regulatory T cells (Tregs). SEV but not VDSP significantly increased the emigration of intraepithelial DCs. Additionally, SEV significantly enhanced the expression of multiple immunoregulatory markers in the emigrated DCs. After co-culture, we observed significantly more FOXP3+ Tregs expressing high levels of TIGIT in the groups that were initially exposed to SEV.

DISCUSSION: These findings indicate that exposure to SEV induces a tolerogenic program in DCs that can direct differentiation of a unique memory Treg subset, primed for expansion and presumably destined to support a successful pregnancy.},
}

Humans
*Dendritic Cells/immunology/metabolism
Female
*Semen/immunology/metabolism
*T-Lymphocytes, Regulatory/immunology/metabolism
*Extracellular Vesicles/immunology/metabolism
*Immune Tolerance
Cell Differentiation/immunology
*Vagina/immunology/cytology
Male
Phenotype
Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism
Cells, Cultured
Pregnancy
Coculture Techniques

@article {pmid40420384,
year = {2025},
author = {Hansen, SG and Schell, JB and Marshall, EE and Ojha, S and Feltham, S and Morrow, D and Hughes, CM and Gilbride, RM and Ford, JC and Cleveland-Rubeor, HC and McArdle, MR and Whitmer, T and Barber-Axthelm, A and Bochart, R and Smedley, J and Oswald, K and Fast, R and Shoemaker, R and Kosmider, E and Edlefsen, PT and Lifson, JD and Malouli, D and Früh, K and Picker, LJ},
title = {Glycoprotein L-deleted single-cycle rhesus cytomegalovirus vectors elicit MHC-E-restricted CD8+ T cells that protect against SIV.},
journal = {Journal of immunology (Baltimore, Md. : 1950)},
volume = {},
number = {},
pages = {},
doi = {10.1093/jimmun/vkaf104},
pmid = {40420384},
issn = {1550-6606},
support = {U19 AI128741/AI/NIAID NIH HHS/United States ; P01 AI174856/AI/NIAID NIH HHS/United States ; R01 AI059457/AI/NIAID NIH HHS/United States ; },
abstract = {Strain 68-1 rhesus CMV (RhCMV) vectors induce immune responses that mediate early, complete replication arrest of SIV infection in ∼60% of vaccinated rhesus macaques (RMs). This unique efficacy depends on the ability of these vectors to elicit effector memory (EM)-biased CD8+ T cells recognizing SIV peptides presented by MHC-E, rather than MHC-Ia. These efficacious responses still occurred when spread of the 68-1 vector was impaired by deletion of the viral anti-host intrinsic immunity factor phosphoprotein 71 (pp71), but efficacy was lost with a more stringent attenuation strategy based on destabilization of Rh108, the ortholog of the essential human CMV (HCMV) transcription factor UL79 that is required for late viral gene expression. Although unable to produce infectious progeny (ie single-cycle infection), Rh108-deficient vectors elicited durable, high frequency, EM-biased, SIV-specific CD8+ T-cell responses in RMs, but these responses were MHC-Ia-restricted and therefore non-efficacious. Here, we tested a different single-cycle attenuation strategy based on deletion (Δ) of the glycoprotein L (gL) that is essential for viral entry but allows for late gene expression and viral assembly. ΔgL 68-1 RhCMV/SIV vectors, grown on gL-complementing fibroblasts, were robustly immunogenic at doses above 105 PFU, generating high frequency, EM-biased, SIV-specific CD8+ T-cell responses that were also unconventionally restricted, including the MHC-E restriction associated with efficacy. Indeed, these single-cycle vectors manifested replication arrest efficacy in 70% of vaccinated RMs, further linking MHC-E restriction with efficacy, and demonstrating that 68-1 RhCMV/SIV efficacy does not require vector dissemination within the host.},
}

@article {pmid40419513,
year = {2025},
author = {Raychaudhuri, S and Gem, H and Chung, K and McLean, JS and Kerns, KA and Hullar, MAJ and Elmorr, E and Appelbaum, JB and Percival, MM and Walter, RB and Halpern, AB and Minot, SS and Kim, K and Zevin, AS and Rashidi, A},
title = {Distal gut colonization by oral bacteria during intensive chemotherapy: direct evidence from strain-level analysis of paired samples.},
journal = {NPJ biofilms and microbiomes},
volume = {11},
number = {1},
pages = {88},
pmid = {40419513},
issn = {2055-5008},
support = {T32HL007093/HL/NHLBI NIH HHS/United States ; n/a//American Academy of Oral Medicine Research Advancement Committee/ ; P30 CA015704/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; n/a//Kuni Foundation/ ; },
mesh = {Humans ; Feces/microbiology ; *Bacteria/classification/isolation & purification/genetics/drug effects ; *Mouth/microbiology ; Male ; Female ; Saliva/microbiology ; *Gastrointestinal Microbiome ; Middle Aged ; Adult ; Aged ; *Antineoplastic Agents/therapeutic use/adverse effects ; },
abstract = {Oral bacteria have been found in the colon in pathologies such as inflammatory bowel disease. To ascertain niche coalescence, 2 elements are essential: (i) paired oral/fecal samples and (ii) strain-level resolution. We profiled the microbiota in 283 samples from 39 patients undergoing intensive chemotherapy at baseline (saliva: 49, plaque: 51, stool: 43), week 2 (saliva: 18, plaque: 17, stool: 17), week 3 (saliva: 18, plaque: 21, stool: 21), and week 4 (saliva: 8, plaque: 10, stool: 10) of chemotherapy. Through strain-level analysis of paired samples, we demonstrate strong evidence for a breakdown of niche separation in most patients. The extent of overlap increased with time, particularly in patients with intestinal mucositis. Our findings provide definitive evidence for ectopic colonization of the distal gut by oral bacteria in a disease state, likely facilitated by intestinal mucositis. Microbiota contribution by the mouth to the colon may have consequences for the host.},
}

Humans
Feces/microbiology
*Bacteria/classification/isolation & purification/genetics/drug effects
*Mouth/microbiology
Male
Female
Saliva/microbiology
*Gastrointestinal Microbiome
Middle Aged
Adult
Aged
*Antineoplastic Agents/therapeutic use/adverse effects

@article {pmid40419509,
year = {2025},
author = {Dobersch, S and Yamamoto, N and Schutter, A and Cavender, SM and Robertson, TM and Kartha, N and Samraj, AN and Doron, B and Poole, LA and Wladyka, CL and Zhang, A and Jang, GH and Mahalingam, AH and Barreto, G and Raghavan, S and Narla, G and Notta, F and Eisenman, RN and Hsieh, AC and Kugel, S},
title = {HMGA2 and protein leucine methylation drive pancreatic cancer lineage plasticity.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {4866},
pmid = {40419509},
issn = {2041-1723},
support = {5R37CA241472-03//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 1R01CA255015-01//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R37 CA230617/CA/NCI NIH HHS/United States ; K08 CA260442/CA/NCI NIH HHS/United States ; R37 CA230617/CA/NCI NIH HHS/United States ; R01 CA276308/CA/NCI NIH HHS/United States ; 465590102//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; PF-24-1196662-01-RMC//American Cancer Society (American Cancer Society, Inc.)/ ; GM135362//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; },
mesh = {*HMGA2 Protein/metabolism/genetics ; *Pancreatic Neoplasms/metabolism/pathology/genetics ; Animals ; Humans ; *Carcinoma, Pancreatic Ductal/genetics/metabolism/pathology ; Mice ; RNA-Binding Proteins/metabolism/genetics ; Methylation ; Cell Line, Tumor ; Protein Phosphatase 2/metabolism/genetics ; Gene Expression Regulation, Neoplastic ; *Leucine/metabolism ; Proto-Oncogene Proteins p21(ras)/genetics/metabolism ; },
abstract = {Basal pancreatic ductal adenocarcinoma (PDAC) has the worst overall survival and is the only subtype that serves as an independent poor prognostic factor. We identify elevated levels of LIN28B and its downstream target, HMGA2, in basal PDAC. Notably, LIN28B significantly accelerates KRAS-driven PDAC progression in a mouse model. Here, we show that HMGA2 promotes basal PDAC pathogenesis by enhancing mRNA translation downstream of LIN28B. Mechanistically, HMGA2 suppresses leucine carboxyl methyltransferase 1 (LCMT1) at the chromatin level, reducing PP2A methylation and activity. This leads to increased phosphorylation of S6K and eIF4B, boosting mRNA translation. Additionally, HMGA2 downregulates B56α (PPP2R5A), disrupting functional PP2A holoenzyme assembly and further sustaining phosphorylated S6K levels. Impaired PP2A function mimics HMGA2's effects, reinforcing increased mRNA translation and basal lineage features. This work uncovers a critical link between the LIN28B/HMGA2 axis, protein synthesis, and PDAC lineage specificity via LCMT1-mediated PP2A methylation and B56α-PP2A disruption.},
}

*HMGA2 Protein/metabolism/genetics
*Pancreatic Neoplasms/metabolism/pathology/genetics
Animals
Humans
*Carcinoma, Pancreatic Ductal/genetics/metabolism/pathology
Mice
RNA-Binding Proteins/metabolism/genetics
Methylation
Cell Line, Tumor
Protein Phosphatase 2/metabolism/genetics
Gene Expression Regulation, Neoplastic
*Leucine/metabolism
Proto-Oncogene Proteins p21(ras)/genetics/metabolism

@article {pmid40419022,
year = {2025},
author = {Ahmed, S and Blosser, C and Israni, AK and Engels, EA},
title = {Reply to "Real-world registry evidence beware: Old-world risk analysis may not be applicable to new world belatacept utilization".},
journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajt.2025.05.027},
pmid = {40419022},
issn = {1600-6143},
}

@article {pmid40419020,
year = {2025},
author = {Mehta, RS and Schmidt, G and Williams, K and Patel, SA and Schetelig, J and Savani, B and Askar, M and Petersdorf, E and Ringden, O and Kanakry, CG and Kanakry, JA and Stefanski, H and Arrieta-Bolaños, E and Betts, B and Benjamin, C and Gadalla, S and Wang, T and Saultz, J and Spellman, S and Jurdi, NE and Bolon, YT and Lee, SJ},
title = {Choosing between HLA-Mismatched Unrelated and Haploidentical donors: Donor age considerations.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.05.019},
pmid = {40419020},
issn = {2666-6367},
abstract = {BACKGROUND: Haploidentical donors and HLA-mismatched unrelated donors (MMUDs) are increasingly utilized for hematopoietic cell transplantation (HCT), with post-transplantation cyclophosphamide (PTCy) emerging as an effective graft-versus-host disease (GVHD) prophylaxis strategy. Despite the growing use of these donor types, comparative data to guide donor selection remain limited. Donor age is a known predictor of HCT outcomes, yet its specific impact when choosing between haploidentical and MMUD donors with PTCy-based prophylaxis has not been thoroughly explored.

OBJECTIVES: This study aimed to evaluate the influence of donor age on HCT outcomes in patients receiving haploidentical or MMUD HCT with PTCy-based GVHD prophylaxis, hypothesizing that younger donors (<30 years) would be associated with improved outcomes compared to older donors (≥30 years) regardless of donor type.

STUDY DESIGN: We conducted a retrospective analysis of 7,116 patients with hematologic malignancies from the Center for International Blood and Marrow Transplant Research (CIBMTR) database, transplanted between 2013 and 2021. Donors were categorized into four groups: younger haploidentical (<30 years), older haploidentical (≥30 years), younger MMUD (<30 years), and older MMUD (≥30 years). The primary outcome was GVHD-free relapse-free survival (GRFS), defined as the absence of grade III-IV acute GVHD, chronic GVHD requiring systemic immunosuppressive therapy (IST), relapse, or death. Secondary outcomes included overall survival (OS), treatment-related mortality (TRM), relapse, grade III-IV acute GVHD, overall chronic GVHD, and chronic GVHD requiring IST. Comparisons were made between (a) younger MMUD vs. older haploidentical and (b) younger haploidentical vs. older MMUD groups using multivariable Cox proportional hazards models.

RESULTS: In multivariable analysis, the older MMUD group exhibited inferior GRFS (Hazard Ratio [HR] 1.20; 95% confidence interval [CI], 1.06-1.36; p=0.003), higher TRM (HR 1.49; 95% CI, 1.13-1.96; p=0.005), and increased grade III-IV acute GVHD (HR 2.88; 95% CI, 1.43-5.80; p=0.003) compared to the younger haploidentical group. The younger MMUD group had modest GRFS improvement over the older haploidentical group (HR 0.87; 95% CI, 0.78-0.98; p=0.02) and significantly reduced risks of grade II-IV acute GVHD (HR 0.67; 95% CI, 0.51-0.88; p=0.003) and chronic GVHD (HR 0.78; 95% CI, 0.65-0.94; p=0.009).

CONCLUSIONS: Younger donor age is associated with superior HCT outcomes, emphasizing the importance of prioritizing donors aged <30 years regardless of donor type when feasible.},
}

@article {pmid40415587,
year = {2025},
author = {Yang, Z and Rizopoulos, D and Heijnsdijk, EAM and Newcomb, LF and Erler, NS},
title = {Personalized Biopsy Schedules Using an Interval-Censored Cause-Specific Joint Model.},
journal = {Statistics in medicine},
volume = {44},
number = {10-12},
pages = {e70134},
pmid = {40415587},
issn = {1097-0258},
support = {CA253910/NH/NIH HHS/United States ; },
mesh = {Humans ; Biopsy/methods/statistics & numerical data ; *Prostatic Neoplasms/pathology/diagnosis ; Male ; Disease Progression ; *Precision Medicine/methods ; *Models, Statistical ; Computer Simulation ; Likelihood Functions ; Watchful Waiting ; },
abstract = {Active surveillance (AS), where biopsies are conducted to detect cancer progression, has been acknowledged as an efficient way to reduce the overtreatment of prostate cancer. Most AS cohorts use fixed biopsy schedules for all patients. However, the ideal test frequency remains unknown, and the routine use of such invasive tests burdens the patients. An emerging idea is to generate personalized biopsy schedules based on each patient's progression-specific risk. To achieve that, we propose the interval-censored cause-specific joint model (ICJM), which models the impact of longitudinal biomarkers on cancer progression while considering the competing event of early treatment initiation. The underlying likelihood function incorporates the interval-censoring of cancer progression, the competing risk of treatment, and the uncertainty about whether cancer progression occurred since the last biopsy in patients that are right-censored or experience the competing event. The model can produce patient-specific risk profiles up to a horizon time. If the risk exceeds a certain threshold, a biopsy is conducted. The optimal threshold can be chosen by balancing two indicators of the biopsy schedules: The expected number of biopsies and the expected delay in detection of cancer progression. A simulation study showed that our personalized schedules could considerably reduce the number of biopsies per patient by 41%-52% compared to the fixed schedules, though at the cost of a slightly longer detection delay.},
}

Humans
Biopsy/methods/statistics & numerical data
*Prostatic Neoplasms/pathology/diagnosis
Male
Disease Progression
*Precision Medicine/methods
*Models, Statistical
Computer Simulation
Likelihood Functions
Watchful Waiting

@article {pmid40414351,
year = {2025},
author = {Ahmed, SO and Fakih, RE and Kharfan-Dabaja, MA and Syed, F and Mufti, G and Chabannon, C and Rondelli, D and Mohty, M and Ahmari, AAA and Gauthier, J and Ruella, M and Perales, MA and Hashmi, S and Alfraih, F and Ghorashian, S and Alzahrani, M and Abba, Z and Koh, M and Pasquini, M and Ruggeri, A and Garderet, L and Albabtain, A and Weisdorf, D and Greinix, H and Samarkandi, H and Hamad, N and Atsuta, Y and Hamadani, M and Hari, P and Majhail, NS and Greco, R and Alzahrani, H and Sureda, A and Yakoub-Agha, I and Alahmari, AD and Niederwieser, D and Aljurf, M},
title = {Setting up a CAR-T Program: A Framework for Delivery from the Worldwide Network for Blood & Marrow Transplantation.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.05.012},
pmid = {40414351},
issn = {2666-6367},
abstract = {Chimeric antigen receptor therapy (CAR-T therapy) is a genetically engineered cellular therapy that is currently integrated into the management of hematological malignancies. Institutions treating patients with CAR-T therapy need to establish a framework of delivery that covers all the main components of the patient journey including intake of patients into the program from referring centers, patient selection according to established eligibility criteria, apheresis, logistics, bridging therapy, infusion and post-infusion care. A CAR-T therapy program, with its unique requirements, needs to be delivered by a multidisciplinary team (MDT). Prior to the establishment of the program, a well-structured business plan should be developed with a clear financial and/or reimbursement model. Consideration should be given to the overall capacity and staffing requirements. Standard operating procedures and guidelines are vital for ensuring that quality standards are clearly defined and adhered to. Institutions should develop a research plan for CAR-T that may incorporate not only industry sponsored trials but also in-house CAR-T manufacture of investigational CAR-T constructs. This report presents recommendations from a group of international experts highlighting the priorities and considerations when developing a new CAR-T program.},
}

@article {pmid40413188,
year = {2025},
author = {Zanti, M and O'Mahony, DG and Parsons, MT and Dorling, L and Dennis, J and Boddicker, NJ and Chen, W and Hu, C and Naven, M and Yiangou, K and Ahearn, TU and Ambrosone, CB and Andrulis, IL and Antoniou, AC and Auer, PL and Baynes, C and Bodelon, C and Bogdanova, NV and Bojesen, SE and Bolla, MK and Brantley, KD and Camp, NJ and Campbell, A and Castelao, JE and Cessna, MH and Chang-Claude, J and Chen, F and Chenevix-Trench, G and , and Conroy, DM and Czene, K and De Nicolo, A and Domchek, SM and Dörk, T and Dunning, AM and Eliassen, AH and Evans, DG and Fasching, PA and Figueroa, JD and Flyger, H and Gago-Dominguez, M and García-Closas, M and Glendon, G and González-Neira, A and Grassmann, F and Hadjisavvas, A and Haiman, CA and Hamann, U and Hart, SN and Hartman, MBA and Ho, WK and Hodge, JM and Hoppe, R and Howell, SJ and , and Jakubowska, A and Khusnutdinova, EK and Ko, YD and Kraft, P and Kristensen, VN and Lacey, JV and Li, J and Lim, GH and Lindström, S and Lophatananon, A and Luccarini, C and Mannermaa, A and Martinez, ME and Mavroudis, D and Milne, RL and Muir, K and Nathanson, KL and Nuñez-Torres, R and Obi, N and Olson, JE and Palmer, JR and Panayiotidis, MI and Patel, AV and Pharoah, PDP and Polley, EC and Rashid, MU and Ruddy, KJ and Saloustros, E and Sawyer, EJ and Schmidt, MK and Southey, MC and Tan, VK and Teo, SH and Teras, LR and Torres, D and Trentham-Dietz, A and Truong, T and Vachon, CM and Wang, Q and Weitzel, JN and Yadav, S and Yao, S and Zirpoli, GR and Cline, MS and Devilee, P and Tavtigian, SV and Goldgar, DE and Couch, FJ and Easton, DF and Spurdle, AB and Michailidou, K},
title = {Analysis of more than 400,000 women provides case-control evidence for BRCA1 and BRCA2 variant classification.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {4852},
pmid = {40413188},
issn = {2041-1723},
mesh = {Humans ; Female ; Case-Control Studies ; *BRCA2 Protein/genetics ; *Breast Neoplasms/genetics ; *BRCA1 Protein/genetics ; Genetic Predisposition to Disease ; Genetic Testing ; Germ-Line Mutation ; Middle Aged ; },
abstract = {Clinical genetic testing identifies variants causal for hereditary cancer, information that is used for risk assessment and clinical management. Unfortunately, some variants identified are of uncertain clinical significance (VUS), complicating patient management. Case-control data is one evidence type used to classify VUS. As an initiative of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Analytical Working Group we analyze germline sequencing data of BRCA1 and BRCA2 from 96,691 female breast cancer cases and 302,116 controls from three studies: the BRIDGES study of the Breast Cancer Association Consortium, the Cancer Risk Estimates Related to Susceptibility consortium, and the UK Biobank. We observe 11,207 BRCA1 and BRCA2 variants, with 6909 being coding, covering 23.4% of BRCA1 and BRCA2 VUS in ClinVar and 19.2% of ClinVar curated (likely) benign or pathogenic variants. Case-control likelihood ratio (ccLR) evidence is highly consistent with ClinVar assertions for (likely) benign or pathogenic variants; exhibiting 99.1% sensitivity and 95.3% specificity for BRCA1 and 93.3% sensitivity and 86.6% specificity for BRCA2. This approach provides case-control evidence for 787 unclassified variants; these include 579 with strong or moderate benign evidence and 10 with strong pathogenic evidence for which ccLR evidence is sufficient to alter clinical classification.},
}

Humans
Female
Case-Control Studies
*BRCA2 Protein/genetics
*Breast Neoplasms/genetics
*BRCA1 Protein/genetics
Genetic Predisposition to Disease
Genetic Testing
Germ-Line Mutation
Middle Aged

@article {pmid40413129,
year = {2025},
author = {Raychaudhuri, R and Cheng, HH and Gulati, R and Schweizer, MT and Lin, A and Yezefski, T and Khan, HM and Yu, EY and Hawley, JE and Nelson, PS and Pritchard, CC and Montgomery, B},
title = {Results from a Phase 2 Study of Induction Docetaxel and Carboplatin Followed by Maintenance Rucaparib in the Treatment of Patients with Metastatic Castration-resistant Prostate Cancer with DNA Homologous Recombination Repair Deficiency.},
journal = {European urology oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.euo.2025.04.026},
pmid = {40413129},
issn = {2588-9311},
abstract = {BACKGROUND AND OBJECTIVE: Our aim was to determine whether induction chemotherapy followed by PARP inhibitor (PARPi) maintenance improves outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC) harboring alterations in homologous recombination repair (HRR) genes in comparison to a historical control cohort treated with PARPi monotherapy.

METHODS: This single-arm, open-label, investigator-initiated phase 2 trial (NCT02985021) enrolled 18 patients with mCRPC with pathogenic alterations in HRR genes between 2018 and 2021 at a single center. Patients received four cycles of induction chemotherapy with docetaxel (60 mg/m[2]) and carboplatin (area under the curve 5) every 21 d, followed by maintenance rucaparib (600 mg twice daily) until progression or unacceptable toxicity. The primary outcome was radiographic progression-free survival (rPFS). Subsequent to study inception, multiple other studies reported alterations in genes of the BRCA complex (BRCA-C: BRCA1, BRCA2, PALB2) as most predictive of PARPi response; therefore, a post hoc analysis comparing patients with alterations in BRCA-C genes to a historical control cohort was performed.

KEY FINDINGS AND LIMITATIONS: After median follow-up of 40.3 mo (interquartile range 38.5-not reached [NR]), the median rPFS for all patients was 8.1 mo (95% confidence interval [CI] 6.5-31.2), similar to a historical control cohort treated with PARPi monotherapy. Among the 12 patients with BRCA-C alterations, median rPFS was 17.7 mo (95% CI 7.5-NR; p = 0.05). A key limitation is the single-arm design.

Induction platinum-based chemotherapy followed by maintenance PARPi therapy did not improve outcomes for patients with mCRPC broadly selected for HRR deficiency. However, results were promising in the more stringently selected group with BRCA-C gene alterations. Further studies comparing this approach to PARPi monotherapy are warranted.},
}

@article {pmid40412400,
year = {2025},
author = {Leng, T and Kessou, L and Heitner, J and Guédou, FA and Béhanzin, L and Olodo, M and Diabaté, S and Silhol, R and Dimitrov, D and Vickerman, P and Alary, M and Boily, MC and Mitchell, KM},
title = {Potential impact and cost-effectiveness of oral HIV pre-exposure prophylaxis for men who have sex with men in Cotonou, Benin: a mathematical modelling study.},
journal = {The Lancet. Global health},
volume = {13},
number = {6},
pages = {e1111-e1121},
doi = {10.1016/S2214-109X(25)00098-1},
pmid = {40412400},
issn = {2214-109X},
mesh = {Humans ; Male ; *Cost-Benefit Analysis ; *Pre-Exposure Prophylaxis/economics/methods ; *HIV Infections/prevention & control/epidemiology ; Benin/epidemiology ; *Homosexuality, Male/statistics & numerical data ; Adult ; Models, Theoretical ; *Anti-HIV Agents/economics/administration & dosage/therapeutic use ; Administration, Oral ; Young Adult ; Middle Aged ; Adolescent ; },
abstract = {BACKGROUND: Oral HIV pre-exposure prophylaxis (PrEP) can effectively reduce HIV incidence. A 2020-21 demonstration project assessed the feasibility and health outcomes of offering oral PrEP to men who have sex with men (MSM) in Cotonou, Benin. We evaluated the epidemiological impact and cost-effectiveness of this project and the potential scale-up of oral HIV PrEP for MSM in Cotonou.

METHODS: We calibrated an HIV transmission-dynamic model structured by age and risk within a Bayesian framework to MSM-specific HIV prevalence and treatment data, parameterised with project behavioural and cost (including PrEP drug, implementation, and HIV care costs) data. We estimated the impact and cost-effectiveness of the 2020-21 Cotonou demonstration project (PrEP coverage, 5-10% of all MSM who are not living with HIV in Grand Cotonou; and adherence, 13-21% taking at least four of seven required doses [ie, at least four doses per week for daily users and at least four of seven expected doses given reported sexual activity for on-demand users]) and of its potential scale-up over 5 years (from 2022 to 2027), reaching 30% coverage of MSM in Grand Cotonou and with demonstration project adherence levels. We additionally modelled ideal PrEP adherence (100% taking at least four of seven required doses). We estimated the percentage of cumulative new HIV infections averted among participating MSM over 1 year and among all MSM in Grand Cotonou and their female partners over 20 years, and cost-effectiveness as cost per disability-adjusted life-year (DALY) averted over 20 years. Costs and DALYs were discounted 3% annually.

FINDINGS: We found that the demonstration project averted an estimated 21·5% (95% uncertainty interval 16·6 to 26·2) of HIV infections among participants over 1 year. With ideal adherence, cases that would be averted increased to 95·2% (90·8 to 98·8). A 5-year PrEP scale-up could avert 3·2% (1·6 to 4·8) of HIV infections among all MSM and female partners over 20 years, at US$388 (36 to 2792) per DALY averted. With ideal adherence, this decreased to -$28 (-126 to 589) per DALY averted.

INTERPRETATION: Low adherence to PrEP restricted the impact of the demonstration project. At 30% coverage among MSM by 2027, PrEP scale-up would be cost-effective at a $1225 threshold with 86·6% probability, and it could be more cost-effective if high adherence could be reached without substantially increasing costs.

FUNDING: Canadian Institutes of Health Research and US National Institutes of Health.

TRANSLATION: For the French translation of the abstract see Supplementary Materials section.},
}

Humans
Male
*Cost-Benefit Analysis
*Pre-Exposure Prophylaxis/economics/methods
*HIV Infections/prevention & control/epidemiology
Benin/epidemiology
*Homosexuality, Male/statistics & numerical data
Adult
Models, Theoretical
*Anti-HIV Agents/economics/administration & dosage/therapeutic use
Administration, Oral
Young Adult
Middle Aged
Adolescent

@article {pmid40412394,
year = {2025},
author = {Bansi-Matharu, L and Moolla, H and Citron, DT and Stover, J and Pickles, M and Martin-Hughes, R and Boily, MC and Nyirenda, R and Mudimu, E and Ten Brink, D and Johnson, LF and Mugurungi, O and Cambiano, V and Dimitrov, D and Smith, J and Glaubius, R and Taramusi, I and Mpofu, A and Phillips, A and Bershteyn, A},
title = {Identifying gaps in the HIV treatment cascade in Africa: a model comparison study.},
journal = {The Lancet. Global health},
volume = {13},
number = {6},
pages = {e1006-e1019},
doi = {10.1016/S2214-109X(25)00121-4},
pmid = {40412394},
issn = {2214-109X},
mesh = {Humans ; *HIV Infections/epidemiology/drug therapy/transmission ; Female ; Male ; Adult ; Adolescent ; Young Adult ; Middle Aged ; Malawi/epidemiology ; Zimbabwe/epidemiology ; South Africa/epidemiology ; *Anti-HIV Agents/therapeutic use ; Africa/epidemiology ; Incidence ; Prevalence ; },
abstract = {BACKGROUND: Although HIV incidence has considerably decreased in eastern, central, and southern Africa, new HIV infections continue to be a major public health challenge in the region. We aimed to investigate where in the HIV treatment cascade new transmissions are occurring in Malawi, Zimbabwe, and South Africa (the three countries involved in the Modelling to Inform HIV Programmes in Sub-Saharan Africa project).

METHODS: In this model comparison study, we used six well described and independently calibrated HIV transmission dynamics models that have been used to inform HIV policy in Africa (Optima HIV, EMOD, Goals, Thembisa, PopART-IBM, and HIV Synthesis) to estimate and predict the proportion of annual new HIV transmissions attributable to people living with HIV who are undiagnosed, have been diagnosed but have not yet started antiretroviral therapy (ART), are receiving ART, and have interrupted ART in Malawi, Zimbabwe, and South Africa from 2010 to 2040 stratified by the age and sex of the individual acquiring HIV.

FINDINGS: Despite the different model structures and underlying assumptions, the six models were well aligned in relation to key HIV epidemic characteristics (including population estimates and HIV prevalence) in each of the three settings. There was, however, considerable variation in the predicted number of new infections, particularly in Malawi and Zimbabwe where this number ranged from fewer than 10 000 new infections to over 30 000 new infections in 2024. Most model results suggested that the mean age of HIV acquisition has been increasing since 2000, with men acquiring HIV at an older age than women in all three settings. All models attributed fewer than 5% of transmissions to individuals who had been diagnosed but had not yet started ART. In Malawi, the proportion of transmissions attributable to undiagnosed people with HIV in 2024 ranged from 33·3% to 75·3% across the models, and transmissions attributable to individuals who had experienced interrupted treatment ranged from 8·4% to 20·1%. In Zimbabwe, the proportion of transmissions attributable to undiagnosed individuals in 2024 ranged from 29·8% to 64·6% across the models and the proportion of transmissions attributable to individuals who had interrupted treatment ranged from 4·7% to 21·5%. In South Africa, 21·8-46·4% of transmissions in 2024 were attributable to undiagnosed individuals and 27·6-58·9% of transmissions were attributable to individuals who had interrupted treatment.

INTERPRETATION: Across the three study settings, a substantial proportion of new HIV transmissions were attributable to undiagnosed individuals and people who have received interrupted ART, reinforcing the importance of continuing HIV testing and ART re-engagement and retention interventions.

FUNDING: The Bill & Melinda Gates Foundation.},
}

Humans
*HIV Infections/epidemiology/drug therapy/transmission
Female
Male
Adult
Adolescent
Young Adult
Middle Aged
Malawi/epidemiology
Zimbabwe/epidemiology
South Africa/epidemiology
*Anti-HIV Agents/therapeutic use
Africa/epidemiology
Incidence
Prevalence

@article {pmid40411791,
year = {2025},
author = {Heffner, JL and Baker, K and Georgiou, K and Graham, AL and Kelly, MM and Konstantinou, P and Lamprou, E and Lele, C and Lok, KZ and Orzechowski, M and Ruiz, RA and Serfozo, E and Karekla, M},
title = {ACT on Vaping: Pilot Randomized Controlled Trial of a Novel Digital Health App with Text Messaging for Young Adult Vaping Cessation.},
journal = {Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco},
volume = {},
number = {},
pages = {},
doi = {10.1093/ntr/ntaf112},
pmid = {40411791},
issn = {1469-994X},
abstract = {BACKGROUND: There is no published evidence to support the efficacy of any digital vaping cessation program for young adults (YAs) at differing levels of readiness to quit. In this pilot randomized controlled trial, we evaluated the preliminary acceptability and efficacy of a program for vaping cessation based on acceptance and commitment therapy (ACT on Vaping), delivered via a smartphone app and text messaging.

METHODS: YAs age 18-30 (n=61) were randomized 1:1 to ACT on Vaping (n=31) or incentivized text message control (n=30). Outcome data were collected at 3 months post-randomization. Results were compared against a priori benchmarks for acceptability (satisfaction of ≥ 3.5 on 5-point scale) and efficacy relative to control (meeting at least one of three): ≥ 1-point difference in Contemplation Ladder change scores; ≥ 5 percentage difference in 24-hour quit attempts, ≥ 5 percentage difference in cotinine-confirmed 30-day point prevalence abstinence (PPA) from all non-therapeutic nicotine/tobacco.

RESULTS: Satisfaction with ACT on Vaping averaged 3.8, exceeding the acceptability benchmark. A higher proportion of participants in the ACT on Vaping arm reported a 24-hour quit attempt (87.5% vs. 75.9%), exceeding the efficacy benchmark. Both change in quit readiness (+0.96 in ACT on Vaping vs. +0.72 in control) and cotinine-confirmed 30-day PPA (4.2% in ACT on Vaping vs. 0% in control) were descriptively higher for ACT on Vaping but did not reach the benchmark level for efficacy.

CONCLUSIONS: ACT on Vaping had promising acceptability and preliminary efficacy. A fully-powered trial of ACT on Vaping is warranted to evaluate its efficacy.

IMPLICATIONS: Digital interventions are a promising yet under-researched approach for reaching and supporting young adults to quit vaping. This proof-of-concept pilot randomized controlled trial evaluated a novel mobile health application and associated text messaging program (ACT on Vaping) for young adult vaping cessation and found preliminary evidence for acceptability and efficacy relative to an incentivized text message control arm, warranting evaluation in a fully-powered trial as a next step.},
}

@article {pmid40410231,
year = {2025},
author = {Dhodapkar, KM and Castellino, S and Kapadia, S and Azeem, MI and Horvat, A and Lawrence, T and DeRyckere, D and Dhodapkar, MV},
title = {Immune-aging at diagnosis determines T-cell recovery in childhood leukemia survivors.},
journal = {npj aging},
volume = {11},
number = {1},
pages = {39},
pmid = {40410231},
issn = {2731-6068},
support = {R01 AR077926/AR/NIAMS NIH HHS/United States ; NIH CA238471/GF/NIH HHS/United States ; P30 CA138292/CA/NCI NIH HHS/United States ; R35CA197603/GF/NIH HHS/United States ; SCOR//Leukemia and Lymphoma Society/ ; R35 CA197603/CA/NCI NIH HHS/United States ; R01 CA238471/CA/NCI NIH HHS/United States ; },
abstract = {We show that T cells in survivors of childhood leukemia exhibit distinct profiles dominated by aging-associated changes and consistent with premature immune aging. Immune profiles during survivorship in biospecimens (n = 251) from uniformly-treated children with B-acute lymphoblastic leukemia recapitulate heterogeneity at diagnosis in individual patients and correlate with genetic-risk subtypes. These data suggest that pre-therapy immune aging may determine variance in immune status during survivorship.},
}

@article {pmid40409951,
year = {2025},
author = {Thomas, AB and Van Son, CR and Nelson, LA and Fergadiotis, G and Barbosa-Leiker, C},
title = {A Principle-Based Concept Analysis of Supported Conversation for Adults With Aphasia.},
journal = {Research and theory for nursing practice},
volume = {},
number = {},
pages = {},
doi = {10.1891/RTNP-2024-0094},
pmid = {40409951},
issn = {1541-6577},
abstract = {Background and Purpose: Supported Conversation for Adults with Aphasia (SCA[™]), an evidence-based framework to improve communicative access, is a unique concept to nursing with theoretical and technical components. Effective communication is essential in all patient interactions, and SCA™ could aid health care professionals in meeting the needs of people with aphasia. Methods: A principle-based concept analysis was conducted using a systematic and conceptually driven literature search. A review of literature from 1998 to 2024 contained in CINAHL, PubMed, and PsycINFO databases was performed on the concept of SCA[™] The concept was explored for (a) definitional clarity (epistemological principle), (b) relevance to nursing (pragmatic principle), (c) consistency in meaning (linguistic principle), and (d) differentiation from related concepts (logical principle). Results: The final dataset consisted of 49 articles. Findings revealed that (a) SCA[™] is composed of theoretical and technical components used to acknowledge and reveal the competence of a person with aphasia, but there is a vague use and a lack of definitional clarity; (b) the philosophical framework and techniques outlined by the concept are relevant and useful for nursing; (c) there is variability in the use, nomenclature, and conceptualization of SCA[™]; and (d) the concept is poorly differentiated from other similar concepts. Implications for Practice: Nurses working with people diagnosed with aphasia and other communication disorders should consider SCA[™] and its application in nursing practice. Findings from this concept analysis stress the importance of an interdisciplinary approach to future SCA[™] studies, as nursing can lend its distinct viewpoint to integrate SCA[™] techniques into practice.},
}

@article {pmid40409691,
year = {2025},
author = {Lee, SJ and Williams, KM and Sarantopoulos, S and Kitko, CL and Cutler, C and Pidala, J and Hill, GR and DeFilipp, Z and Greinix, HT and Wolff, D and Paczesny, S and Cuvelier, GDE and Schultz, KR and Pavletic, SZ},
title = {NIH Chronic Graft-versus-Host Disease Consensus Conference 2025 Update.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.05.016},
pmid = {40409691},
issn = {2666-6367},
abstract = {In 2020, the third NIH Consensus Development Project on Criteria for Chronic Graft-versus-Host Disease (GVHD) Clinical Trials was held with the goals of identifying gaps in understanding, prevention and treatment of chronic graft-versus-host disease (GVHD) and making actionable recommendations that would advance the field. An interim meeting was held in October 2024 to review progress on the 2020 recommendations. Each group was charged with reviewing their previous recommendations, assessing whether the field is on track to eventually achieve the goals, and considering whether recommendations should be modified in light of new data or insufficient progress. This manuscript summarizes the Working Groups' reports and helps define the research agenda for future studies in chronic GVHD. Overall, modest progress has been made on most initiatives. Some studies in progress will address key recommendations and results are eagerly anticipated.},
}

@article {pmid40409689,
year = {2025},
author = {Kampouri, E and Handley, G and Phan, TL and Lee, YJ and Shaw, R and Carpenter, PA and Dadwal, SS and Chemaly, RF and Papanicolaou, GA and Ogata, M and Boeckh, M and Zerr, DM and Hill, JA},
title = {American Society for Transplantation and Cellular Therapy Series #9: Management of HHV-6B After Hematopoietic Cell Transplantation and Chimeric Antigen Receptor (CAR)-T-Cell Therapy.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.05.001},
pmid = {40409689},
issn = {2666-6367},
abstract = {The Practice Guidelines Committee and the Transplant Infectious Disease Special Interest Group of the American Society for Transplantation and Cellular Therapy developed guidelines focusing on human herpes virus 6B (HHV-6B). A compendium-style approach was used to address a series of standalone frequently asked questions (FAQs), supported by tables and figures to spotlight key concepts. Adult and pediatric infectious disease and hematopoietic cell transplantation (HCT) content experts developed these FAQs, and finalized recommendations after consensus was reached. This ninth topic in the series focuses on the relevant risk factors, diagnostic considerations, prophylaxis, and treatment approaches relevant to HHV-6B infections after HCT and Chimeric Antigen Receptor (CAR)-T-Cell Therapy.},
}

@article {pmid40409326,
year = {2025},
author = {Wu, RL and Houser, KV and Gaudinski, MR and Widge, AT and Awan, SF and Carter, CA and Holman, LA and Saunders, J and Hendel, CS and Eshun, A and Whalen, WR and Wang, X and Arthur, A and Cunningham, JE and Beck, A and Casazza, JP and Yamshchikov, GV and Rothwell, RS and Strom, L and Dittakavi, T and Happe, M and Hickman, SP and Conan-Cibotti, M and Carlton, K and Zhang, L and Huang, Y and Capparelli, EV and Castro, M and Lin, BC and O'Connell, S and Flach, BS and Bailer, RT and Narpala, SR and Serebryannyy, L and McDermott, AB and Arnold, FJ and Gall, JG and Vazquez, S and Berkowitz, NM and Gordon, IJ and Chen, GL and Kwong, PD and Huang, J and Pierson, TC and Connors, M and Mascola, JR and Zhou, T and Doria-Rose, NA and Koup, RA and Dropulic, LK and , },
title = {Safety and pharmacokinetics of N6LS, a broadly neutralising monoclonal antibody for HIV: a phase 1, open-label, dose-escalation study in healthy adults.},
journal = {The lancet. HIV},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2352-3018(25)00041-4},
pmid = {40409326},
issn = {2352-3018},
abstract = {BACKGROUND: Broadly neutralising antibodies (bNAbs) have shown promise as both prevention and treatment strategies against HIV-1. The clinical effectiveness of bNAbs depends on enhancing their neutralisation breadth and extending their serum half-lives. In this study, we aimed to assess the safety, tolerability, pharmacokinetic profile, and neutralisation activity in serum of N6LS, a HIV-1 bNAb.

METHODS: In this first-in-human, dose-escalation, open-label, phase 1 trial, healthy adult participants (aged 18-50 years) who were HIV-1 negative were recruited to the National Institutes of Health Clinical Center (Bethesda, MD, USA). Three groups received one intravenous administration of N6LS at 5 mg/kg (n=3), 20 mg/kg (n=3), or 40 mg/kg (n=3); one group received one subcutaneous administration of 5 mg/kg N6LS (n=3); two groups received three administrations of either 5 mg/kg subcutaneous (n=5) or 20 mg/kg intravenous (n=5) N6LS every 12 weeks; and two groups received one subcutaneous administration of either 5 mg/kg (n=5) or 20 mg/kg (n=5) N6LS with ENHANZE drug product (EDP), recombinant human hyaluronidase PH20. The primary objectives were the safety and tolerability of N6LS with and without EDP. All participants who received N6LS were included in the primary safety analyses. This trial is registered at ClinicalTrials.gov, NCT03538626, and is complete.

FINDINGS: Between June 18, 2018, and April 11, 2022, we enrolled 33 healthy adults (19 female individuals and 14 male individuals). One participant did not receive N6LS and one participant was lost to follow-up after 8 weeks. N6LS had an encouraging safety profile similar to other HIV-1 bNAbs, with no serious adverse events. Local reactogenicity was observed after administration of N6LS, with the most common symptom being mild to moderate injection site pain or tenderness in subcutaneous groups, reported in six of eight participants. All ten participants who received N6LS with EDP had mild to severe injection site erythema, which, despite being graded as severe in size, was generally not noticed by participants or deemed bothersome, and resolved without intervention. Systemic reactogenicity was mild in all groups. N6LS had an overall mean serum half-life of 48·6 days and retained its broad and potent neutralisation characteristics in serum. EDP administration increased N6LS bioavailability. No functional anti-drug antibodies to N6LS were detected following administration.

INTERPRETATION: N6LS showed a promising safety and pharmacokinetics profile while retaining its potent neutralisation characteristics in serum, making it a promising candidate for inclusion in HIV-1 prevention and therapeutic combination strategies. The addition of EDP can enable safe subcutaneous administration of higher doses and larger volumes of N6LS, supporting additional methods for prophylactic and therapeutic bNAb administration.

FUNDING: US National Institute of Allergy and Infectious Diseases Intramural Research Program, National Institutes of Health.},
}

@article {pmid40408282,
year = {2025},
author = {Marsh, TL and Johnston, JM and Homan, C and Townshend-Bulson, LJ and Kim, NJ and VoPham, T and Li, X and He, Q and McMahon, BJ and Ioannou, GN and Feng, Z},
title = {HCC surveillance in hepatitis C: A longitudinal algorithm improves alpha-fetoprotein screening.},
journal = {Hepatology communications},
volume = {9},
number = {6},
pages = {},
doi = {10.1097/HC9.0000000000000719},
pmid = {40408282},
issn = {2471-254X},
mesh = {Humans ; *alpha-Fetoproteins/analysis/metabolism ; *Carcinoma, Hepatocellular/diagnosis/blood/virology ; *Algorithms ; *Liver Neoplasms/diagnosis/blood/virology ; Male ; Female ; Middle Aged ; *Hepatitis C/complications ; Bayes Theorem ; Sensitivity and Specificity ; Aged ; *Early Detection of Cancer/methods ; Alaska/epidemiology ; Liver Cirrhosis/blood ; Longitudinal Studies ; Adult ; *Hepatitis C, Chronic/complications/blood ; },
abstract = {BACKGROUND: Surveillance for HCC remains important after hepatitis C cure. Improved sensitivity of screening with alpha-fetoprotein (AFP) by using a parametric empirical Bayes (PEB) algorithm, which incorporates an individual patient's longitudinal AFP measurements, was previously demonstrated in a retrospective analysis of clinical trial data prior to widespread hepatitis C cure.

METHODS: We analyzed de-identified data extracted from the medical records of participants in the Alaska Hepatitis C Study, which aims to enroll all Alaska Native persons living in Alaska with a history of hepatitis C.We compared the performance characteristics of AFP as a screening test using the PEB method versus a fixed cutoff (FC) method in an observational setting, separately for HCC surveillance in active and cured hepatitis C.

RESULTS: The PEB and FC methods were applied to AFP levels from participants with F3/F4 fibrosis who had active hepatitis C (173 no HCC, 14 HCC) or after they achieved hepatitis C cure (162 no HCC, 12 HCC). Compared to a fixed 20 ng/mL cutoff, demonstrating 91.2% specificity in active hepatitis C, PEB increased sensitivity from 64.3% to 71.4%. After cure, a fixed 7.2 ng/mL cutoff demonstrated 91.2% specificity, and PEB increased sensitivity from 58.3% to 91.7%.

CONCLUSIONS: The PEB algorithm can increase sensitivity and lead to earlier detection of HCC among patients with F3/F4 fibrosis, both in active and even more so in cured hepatitis C. Lower AFP levels after cure indicate that for either PEB or FC methods, screening parameters, such as cutoffs for a target specificity, should be specified separately by hepatitis C treatment status for HCC surveillance.},
}

Humans
*alpha-Fetoproteins/analysis/metabolism
*Carcinoma, Hepatocellular/diagnosis/blood/virology
*Algorithms
*Liver Neoplasms/diagnosis/blood/virology
Male
Female
Middle Aged
*Hepatitis C/complications
Bayes Theorem
Sensitivity and Specificity
Aged
*Early Detection of Cancer/methods
Alaska/epidemiology
Liver Cirrhosis/blood
Longitudinal Studies
Adult
*Hepatitis C, Chronic/complications/blood

@article {pmid40407323,
year = {2025},
author = {Landazuri Vinueza, J and Salisbury, NJH and Dye, KN and Roman, A and Galloway, DA},
title = {Delta-catenin is required for cell proliferation in virus-positive Merkel cell carcinoma cell lines but not in human fibroblasts.},
journal = {mBio},
volume = {},
number = {},
pages = {e0083225},
doi = {10.1128/mbio.00832-25},
pmid = {40407323},
issn = {2150-7511},
abstract = {Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer often driven by the integration of Merkel cell polyomavirus (MCPyV) into the host genome and the persistent expression of its viral oncoproteins, small tumor (ST) antigen, and truncated large tumor (t-LT) antigen. While human fibroblasts support MCPyV replication, the cell of origin for MCC remains unknown. We hypothesized that MCPyV initially replicates in fibroblasts but, in rare cases, infects Merkel cell progenitors, contributing to MCC development. Using TurboID mass spectrometry, we identified δ-catenin as a novel ST interactor in fibroblasts. However, while ST binds δ-catenin in fibroblasts, this interaction is absent in virus-positive (VP)-MCC cell lines. Despite this, δ-catenin is essential for VP-MCC, but not for fibroblast cell proliferation. We found that fibroblasts predominantly express δ-catenin isoform 1, whereas VP-MCC cells mainly express isoform 3. Overexpression of isoform 1 in VP-MCC failed to restore ST binding. δ-Catenin promotes VP-MCC proliferation by regulating cell cycle gene expression through its interaction with Kaiso, a transcriptional repressor. Additionally, we found that lysine-specific histone demethylase 1 (LSD1, also known as KDM1A) regulates δ-catenin isoform 3 expression by modulating ESRP1, a δ-catenin splicing factor. Our findings reveal novel host factors involved in MCPyV infection and MCC tumorigenesis, suggesting that the host cell supporting viral replication and the MCC cell of origin may be distinct cell types.IMPORTANCEMerkel cell polyomavirus (MCPyV), the only known human oncogenic polyomavirus, is the primary cause of Merkel cell carcinoma (MCC), a rare and aggressive type of skin cancer. MCC is driven by two viral proteins: small T (ST) and large T (LT). While the virus can replicate in skin fibroblasts, it is still unknown which type of skin cell becomes cancerous. We found that ST binds to a host protein, δ-catenin in fibroblasts, potentially playing a role in the virus lifecycle, but this interaction is missing in the cancer cells. Our study provides evidence that the cells in which the virus replicates and causes cancer are different.},
}

@article {pmid40406922,
year = {2025},
author = {, and Rautalin, I and Volovici, V and Stark, BA and Johnson, CO and Kaprio, J and Korja, M and Krishnamurthi, RV and Nair, BS and Ranta, A and Rinkel, GJE and Vergouwen, MDI and Abate, YH and Abbastabar, H and Abd-Allah, F and Abdelkader, A and Abdi, P and Abdollahi, A and Abdullahi, A and Abiodun, OO and Aboagye, RG and Abouzid, M and Abtahi, D and Abu Rumeileh, S and Abualhasan, A and Abualruz, H and Abukhadijah, HJ and Abu-Zaid, A and Adamu, LH and Addo, IY and Adedoyin, RA and Adegboye, OA and Adra, S and Adzigbli, LA and Agyemang-Duah, W and Ahinkorah, BO and Ahmad, A and Ahmad, D and Ahmadzade, AM and Ahmed, A and Ahmed, H and Ahmed, SA and Aji, B and Akkaif, MA and Al-Ajlouni, Y and Al-Aly, Z and Albashtawy, M and Ali, MU and Alif, SM and Alimohamadi, Y and Aljunid, SM and Alomari, MA and Alrawashdeh, A and Alsabri, MA and Salman, RA and Altaf, A and Al-Tammemi, AB and Alvis-Guzman, N and Alwafi, H and Al-Wardat, M and Al-Worafi, YM and Aly, H and Alyahya, MSI and Alzoubi, KH and Amani, R and Amin, TT and Amindarolzarbi, A and Amusa, GA and Anderlini, D and Angappan, D and Anil, A and Anuoluwa, BS and Anwar, S and Anyasodor, AE and Apostol, GLC and Arabloo, J and Areda, D and Ärnlöv, J and Artamonov, AA and Artanti, KD and Arumugam, A and Aryan, Z and Asghari-Jafarabadi, M and Ashemo, MY and Ashraf, T and Athar, M and Athari, SS and Aujayeb, A and Awotidebe, AW and Azadnajafabad, S and Aziz, S and Azzam, AY and Babu, GR and Bagheri, N and Bahrami Taghanaki, P and Bahramian, S and Bai, R and Baig, AA and Bako, AT and Baltatu, OC and Bam, K and Banach, M and Bandyopadhyay, S and Banik, B and Bardhan, M and Barker-Collo, SL and Bärnighausen, TW and Barqawi, HJ and Barua, L and Bastan, MM and Basu, S and Bell, SL and Bensenor, IM and Berhie, AY and Beyene, KA and Bhagavathula, AS and Bhaskar, S and Bhat, AN and Bhat, V and Bhatti, GK and Bhatti, JS and Bijani, A and Bikbov, B and Birhan, MM and Birhanu, MM and Bitra, VR and Boloor, A and Borhany, H and Breitner, S and Brenner, H and Bugiardini, R and Bulamu, NB and Butt, ZA and Cabral, LS and Caetano Dos Santos, FL and Calina, D and Cámera, LA and Campos, LA and Campos-Nonato, I and Capodici, A and Carvalho, F and Castañeda-Orjuela, CA and Catapano, AL and Cegolon, L and Chadwick, J and Chakraborty, C and Chakraborty, PA and Chakraborty, S and Chandika, RM and Chanie, GS and Chattu, VK and Chaudhary, AA and Chi, G and Chichagi, F and Ching, PR and Chopra, H and Choudhari, SG and Chowdhury, EK and Chu, DT and Chung, SC and Columbus, A and Criqui, MH and da Silva, AG and Dabbagh Ohadi, MA and Dadras, O and Dai, X and Dalal, K and Dalli, LL and D'Amico, E and Dashti, M and Davletov, K and De la Cruz-Góngora, V and Debopadhaya, S and Delgado-Enciso, I and Derviševic, E and Devanbu, VGC and Dewan, SMR and Dhane, AS and Dibas, M and Do, TC and Do, THP and Dohare, S and Doheim, MF and Dokova, KG and Dongarwar, D and D'Oria, M and Doshi, OP and Doshi, RP and Dowou, RK and Dsouza, HL and Dutta, S and Dziedzic, AM and E'mar, AR and Edvardsson, D and Efendi, D and Efendi, F and El Nahas, N and Elgendy, IY and Elhadi, M and Eltaha, C and Eltahir, ME and Emeto, TI and Fabin, N and Fagbamigbe, AF and Fahim, A and Fakhradiyev, IR and Fares, J and Faris, PS and Fauk, NK and Fazylov, T and Fekadu, G and Ferreira, N and Fetensa, G and Fischer, F and Foschi, M and Fridayani, NKY and Gaipov, A and Gajjar, AA and Gandhi, AP and Ganesan, B and Garg, RK and Gebregergis, MW and Gebrehiwot, M and Gebremeskel, TG and Getie, M and Ghadimi, DJ and Ghadirian, F and Ghahramani, S and Ghasemzadeh, A and Ghazy, RM and Gholamalizadeh, M and Ghozy, S and Gil, AU and Gilani, JA and Gnedovskaya, EV and Goleij, P and Goulart, AC and Goulart, BNG and Guan, SY and Gupta, S and Habibzadeh, F and Hadei, M and Hadi, NR and Hamidi, S and Hanifi, N and Hankey, GJ and Harlianto, NI and Haro, JM and Hasan, F and Hasani, H and Hasnain, MS and Hassan Zadeh Tabatabaei, MS and Haubold, J and Havmoeller, RJ and Hay, SI and Hbid, Y and Heidari, G and Heidari, M and Hemmati, M and Hiraike, Y and Hoan, NQ and Holla, R and Hosseinzadeh, M and Hostiuc, S and Huang, J and Huynh, HH and Hwang, BF and Ibitoye, SE and Ikeda, N and Ikiroma, A and Ilaghi, M and Ilesanmi, OS and Ilic, IM and Ilic, MD and Islam, MR and Ismail, NE and Iso, H and Isola, G and Iwagami, M and Jacob, L and Jafarzadeh, A and Jain, A and Jairoun, AA and Jakovljevic, M and Jatau, AI and Jawaid, T and Jayapal, SK and Jonas, JB and Joseph, N and Jürisson, M and Kadashetti, V and Kalani, R and Kamal, VK and Kamireddy, A and Kanchan, T and Kandel, H and Karami, J and Karaye, IM and Karimi, Y and Karimi Behnagh, A and Kashoo, FZ and Kayode, GA and Kazemi, F and Kesse-Guyot, E and Khader, YS and Khaing, IK and Khan, F and Khan, MJ and Khatatbeh, H and Khatatbeh, MM and Khayat Kashani, HR and Kheirallah, KA and Khidri, FF and Khormali, M and Khosla, AA and Kim, K and Kim, YJ and Kisa, A and Kisa, S and Kivimäki, M and Kolahi, AA and Kompani, F and Korzh, O and Kostev, K and Kothari, N and Krishan, K and Krishna, V and Krishnamoorthy, V and Kuddus, M and Kulimbet, M and Kunutsor, SK and Kurniasari, MD and Kusuma, D and Kytö, V and La Vecchia, C and Lahariya, C and Lai, DTC and Lai, H and Laksono, T and Lallukka, T and Latief, K and Latifinaibin, K and Le, NHH and Le, TTT and Lee, M and Lee, SW and Lee, WC and Lee, YH and Lenzi, J and Leonardi, M and Li, MC and Li, X and Lim, SS and Lin, J and Liu, X and Lohner, V and Lorenzovici, L and Lotufo, PA and Lucchetti, G and Lusk, JB and Lutzky Saute, R and M Amin, HI and Malhotra, AK and Malhotra, K and Malik, AA and Malta, DC and Mansournia, MA and Mantovani, LG and Manu, E and Marateb, HR and Marino, M and Maroufi, SF and Martinez-Piedra, R and Martini, S and Martorell, M and Marzo, RR and Mathangasinghe, Y and Mathews, E and Maugeri, A and McPhail, SM and Mehmood, A and Mehndiratta, MM and Mehrabani-Zeinabad, K and Menezes, RG and Meo, SA and Meretoja, A and Mestrovic, T and Mettananda, CDK and Miazgowski, T and Micheletti Gomide Nogueira de Sá, AC and Minervini, G and Minh, LHN and Mirica, A and Mirrakhimov, EM and Mirza-Aghazadeh-Attari, M and Mishra, AK and Mithra, P and Mohamed, AZ and Mohamed, AI and Mohammad, AM and Mohammadi, S and Mohammadian-Hafshejani, A and Mohammed, S and Mokdad, AH and Molinaro, S and Momani, S and Moni, MA and Moodi Ghalibaf, A and Moradi, M and Moradi, Y and Moraga, P and Morawska, L and Msherghi, A and Munjal, K and Murray, CJL and Nagarajan, AJ and Naik, GR and Najdaghi, S and Nakhostin Ansari, N and Nargus, S and Davani, DN and Natto, ZS and Nauman, J and Nayak, VC and Nazri-Panjaki, A and Negoi, RI and Nematollahi, S and Newton, CRJ and Nguyen, DH and Nguyen, HTH and Nguyen, HQ and Nguyen, PT and Nguyen, VT and Niazi, RK and Nigatu, YT and Nikoobar, A and Nogueira de Sá, AT and Nomura, S and Noubiap, JJ and Nugen, F and Nzoputam, CI and Oancea, B and Oduro, MS and Ojo-Akosile, TR and Okati-Aliabad, H and Okeke, SR and Okekunle, AP and Olagunju, AT and Olaiya, MT and Oliveira, AB and Oliveira, GMM and Olorukooba, AA and Olufadewa, II and Ornello, R and Ortiz-Prado, E and Osuagwu, UL and Ouyahia, A and Owolabi, MO and Ozair, A and P A, MP and Padron-Monedero, A and Padubidri, JR and Panagiotakos, D and Panos, GD and Panos, LD and Pantazopoulos, I and Parikh, RR and Park, S and Patel, J and Patel, UK and Patoulias, D and Pedersini, P and Peprah, EK and Pereira, G and Perianayagam, A and Perico, N and Perna, S and Petermann-Rocha, FE and Philip, AK and Piradov, MA and Plotnikov, E and Polibin, RV and Postma, MJ and Pradhan, J and Prasad, M and Puvvula, J and Qasim, NH and Qian, G and Raggi, A and Rahim, F and Rahimi-Movaghar, V and Rahman, M and Rahman, MA and Rahmani, AM and Rahmanian, M and Rajaa, S and Rajabpour Sanati, A and Rajpoot, PL and Rajput, P and Ramadan, MM and Ramasamy, SK and Ramazanu, S and Rane, A and Rashedi, S and Rashidi, MM and Rathish, D and Rawaf, S and Razo, C and Reddy, MMRK and Redwan, E and Remuzzi, G and Rezaei, N and Rezaei, N and Rezaeian, M and Rocha, HAL and Rodriguez, JAB and Roever, L and Romoli, M and Romozzi, M and Ross, AG and Rout, HS and Roy, N and Roy, P and Saad, AMA and Saadatian, Z and Sabour, S and Sacco, S and Saddik, BA and Sadeghi, E and Saeed, U and Saheb Sharif-Askari, F and Sahebkar, A and Sahoo, PM and Sajib, MRUZ and Salaroli, LB and Saleh, MA and Samodra, YL and Samuel, VP and Samy, AM and Santric-Milicevic, MM and Saravanan, A and Sarkar, T and Sarode, GS and Sarode, SC and Sartorius, B and Satpathy, M and Schlaich, MP and Schneider, IJC and Schuermans, A and Selvaraj, S and Senthilkumaran, S and Sepanlou, SG and Sethi, Y and Seylani, A and Shaaban, AN and Shafie, M and Shahwan, MJ and Shaikh, MA and Shaikh, SZ and Shamim, MA and Shamsi, A and Shamsutdinova, A and Shanawaz, M and Shannawaz, M and Sharifan, A and Sharifi Rad, J and Sharma, V and Shashamo, BB and Shetty, M and Shetty, PK and Shigematsu, M and Shittu, A and Shiue, I and Shlobin, NA and Shorofi, SA and Siddig, EE and Singh, B and Singh, P and Singh, P and Singh, S and Sobia, F and Solanki, R and Solanki, S and Soraneh, S and Spartalis, M and Srinivasamurthy, SK and Stanaway, JD and Stanikzai, MH and Starodubova, AV and Sun, J and Sun, Z and Swain, CK and Szarpak, L and Tabaee Damavandi, P and Tabatabaei, SM and Tabatabaeizadeh, SA and Tabche, C and Taiba, J and Talaat, IM and Tamuzi, JL and Tan, KK and Temsah, MH and Teramoto, M and Thakur, R and Thankappan, KR and Thayakaran, R and Thirunavukkarasu, S and Ticoalu, JHV and Tiwari, K and Tonelli, M and Topor-Madry, R and Tovani-Palone, MR and Tran, AT and Tran, JT and Tran, TH and Tran Minh Duc, N and Truelsen, TC and Truyen, TTTT and Tsai, DH and Ullah, A and Unim, B and Unnikrishnan, B and Unsworth, CA and Usman, JS and Vahdati, S and Vaithinathan, AG and Valizadeh, R and Van den Eynde, J and Varghese, J and Vasankari, TJ and Venketasubramanian, N and Vervoort, D and Villafañe, JH and Vinayak, M and Vladimirov, SK and Wafa, HA and Waheed, Y and Wahood, W and Walde, MT and Wang, Y and Wickramasinghe, ND and Willeit, P and Wolde, AA and Wolfe, CDA and Wubie, YM and Xiao, H and Xu, S and Xu, X and Yamagishi, K and Yano, Y and Yarahmadi, A and Yaribeygi, H and Yaya, S and Ye, P and Yon, DK and Yonemoto, N and Yu, C and Zanghì, A and Zare, I and Zastrozhin, M and Zhang, C and Zhang, Y and Zhang, ZJ and Zhang, Z and Zhao, H and Zhou, SC and Zhumagaliuly, A and Zia, H and Zielinska, M and Zyoud, SH and Roth, GA and Feigin, VL},
title = {Global, Regional, and National Burden of Nontraumatic Subarachnoid Hemorrhage: The Global Burden of Disease Study 2021.},
journal = {JAMA neurology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaneurol.2025.1522},
pmid = {40406922},
issn = {2168-6157},
abstract = {IMPORTANCE: Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure.

OBJECTIVE: To estimate the worldwide burden of SAH.

Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021.

EXPOSURES: SAH and 14 modifiable risk factors.

MAIN OUTCOMES AND MEASURES: Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor-specific population attributable fractions (PAFs).

RESULTS: In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution.

CONCLUSIONS AND RELEVANCE: Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.},
}

@article {pmid40405591,
year = {2025},
author = {Feng, E and Feng, E and Berg, T and Nguyen, IS and Nguyen, LG and Chen, W and Zhang, M and Quigley, D and Sharifi, M and Li, H and Coleman, I and Nelson, PS and Sjöström, M and Zhao, SG},
title = {Identifying prognostic targets in metastatic prostate cancer beyond AR.},
journal = {FEBS open bio},
volume = {},
number = {},
pages = {},
doi = {10.1002/2211-5463.70059},
pmid = {40405591},
issn = {2211-5463},
support = {1DP2CA271832-01/GF/NIH HHS/United States ; P50CA097186/GF/NIH HHS/United States ; R50CA274336/GF/NIH HHS/United States ; PC190039//DoD/ ; PC210122//DoD/ ; PC200334//DoD/ ; PC230420//DoD/ ; //Institute for Prostate Cancer Research/ ; //Prostate Cancer Foundation/ ; //Swedish Cancer Society (Cancerfonden)/ ; //Swedish Prostate Cancer Foundation (Prostatacancerförbundet)/ ; //Hjelms Stiftelse för Medicinsk Forskning/ ; },
abstract = {Genome-wide screens using CRISPR/RNAi can identify new therapeutic vulnerabilities in prostate cancer. In this study, we combine DepMap functional screen data with a large gene expression database (N = 1012) and clinical outcomes to identify potentially druggable targets. Eight genes (CYC, CYP51A1, DHFR, EBP, KIF15, PPM1D, SQLE, and UMPS) demonstrated strong dependency in cell lines and were also associated with worse prognosis clinically, representing potential therapeutic targets in metastatic prostate cancer. Four of these (DHFR, EBP, KIF15, and PPM1D) demonstrated higher expression in neuroendocrine prostate cancer. Furthermore, all but one (KIF15) were not significantly decreased from pretreatment to posttreatment, suggesting that they may remain targetable postabiraterone therapy. All eight genes showed evidence of protein expression in prostate cancers or cell lines. These potentially druggable targets associated with prostate cancer cell line dependency and worse clinical outcomes have also demonstrated literature support as potential targets, supporting further research into their potential clinical relevance as therapeutic targets in prostate cancer.},
}

@article {pmid40404994,
year = {2025},
author = {Jones, DC and Elz, AE and Hadadianpour, A and Ryu, H and Glass, DR and Newell, EW},
title = {Cell simulation as cell segmentation.},
journal = {Nature methods},
volume = {},
number = {},
pages = {},
pmid = {40404994},
issn = {1548-7105},
support = {P01 CA225517/CA/NCI NIH HHS/United States ; U19AI128914//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01 CA264646/CA/NCI NIH HHS/United States ; P01 CA225517/CA/NCI NIH HHS/United States ; R01 CA264646/CA/NCI NIH HHS/United States ; },
abstract = {Single-cell spatial transcriptomics promises a highly detailed view of a cell's transcriptional state and microenvironment, yet inaccurate cell segmentation can render these data murky by misattributing large numbers of transcripts to nearby cells or conjuring nonexistent cells. We adopt methods from ab initio cell simulation, in a method called Proseg (probabilistic segmentation), to rapidly infer morphologically plausible cell boundaries. Benchmarking applied to datasets generated by three commercial platforms shows superior performance and computational efficiency of Proseg when compared to existing methods. We show that improved accuracy in cell segmentation aids greatly in detection of difficult-to-segment tumor-infiltrating immune cells such as neutrophils and T cells. Last, through improvements in our ability to delineate subsets of tumor-infiltrating T cells, we show that CXCL13-expressing CD8[+] T cells tend to be more closely associated with tumor cells than their CXCL13-negative counterparts in data generated from samples from patients with renal cell carcinoma.},
}

@article {pmid40404528,
year = {2025},
author = {Lee, W and Chung, JY and Baidoo, KE and Nambiar, D and Basuli, F and Coleman, I and Bakht, M and Li, C and Shin, J and Jeong, SU and Cho, YM and Beltran, H and Nelson, PS and Sowalsky, AG and Choyke, PL and Escorcia, FE},
title = {Glypican-3 as a Radiotheranostic Target for Neuroendocrine Prostate Cancer.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2025.05.007},
pmid = {40404528},
issn = {1873-7560},
}

@article {pmid40403387,
year = {2025},
author = {Mahalingam, D and Saeed, A and Powell, SF and Huerta, M and Sahai, V and Coveler, AL and Davis, EJ and Steeghs, N and Mulcahy, M and Raufi, AG and Cavalcante, L and Cervantes, A and Berlin, J and Weisskittel, T and Ugolkov, A and Mazar, AP and Mikrut, W and Smith, S and Giles, FJ and Carneiro, BA},
title = {Phase II study of elraglusib (9-ING-41), a GSK-3β inhibitor, in combination with gemcitabine plus nab-paclitaxel in previously untreated metastatic pancreatic cancer.},
journal = {ESMO open},
volume = {10},
number = {6},
pages = {105122},
doi = {10.1016/j.esmoop.2025.105122},
pmid = {40403387},
issn = {2059-7029},
abstract = {INTRODUCTION: The purpose of this study was to assess the efficacy and safety of elraglusib (9-ING-41), a GSK-3β inhibitor, in combination with gemcitabine/nab-paclitaxel (GnP) in previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC).

MATERIAL AND METHODS: In a nonrandomized, Simon's two-stage, phase II study, patients with mPDAC received elraglusib 15 mg/kg on days 1 and 4 each week and GnP on days 1, 8, and 15 in a 28-day cycle. The primary endpoint was disease control rate (DCR); secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-emergent adverse events (TEAEs).

RESULTS: A total of 42 patients, who were enrolled and treated, had a median age of 67 years and were 57.1% male. Overall, 38 patients received elraglusib at 15 mg/kg and 4 at 9.3 mg/kg with GnP. DCR was 35.7% [95% confidence interval (CI) 21.6% to 52.0%], and ORR was 26.2%. The median PFS and OS were 5.4 months (95% CI 4.4-9.2 months) and 11.9 months (95% CI 7.8-16.5 months), respectively. Most common TEAEs were visual impairment (83.3%), fatigue (69%), and nausea (66.7%). Grade ≥3 TEAEs occurred in 85.7% of patients and included neutropenia (52.4%), leukopenia (42.9%), and fatigue (21.4%). The dose of elraglusib was reduced to 9.3 mg/kg due to increased exacerbation of GnP-related toxicities and frequent dose interruptions and reductions of elraglusib.

CONCLUSIONS: Elraglusib/GnP showed preliminary clinical activity. In terms of safety, elraglusib resulted in a modest exacerbation of GnP-related toxicities, leading to a dose reduction of elraglusib to 9.3 mg/kg twice a week. Based on the initial efficacy and safety data, the study was amended to a randomized phase II study that will evaluate the 9.3 mg/kg dose.},
}

@article {pmid40402477,
year = {2025},
author = {Li, T and Su, YR and Lee, JM and O'Meara, ES and Miglioretti, DL and Kerlikowske, K and Henderson, L and Houssami, N},
title = {Tomosynthesis vs Digital Mammography Screening in Women with a Family History of Breast Cancer.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
pmid = {40402477},
issn = {2374-2445},
abstract = {IMPORTANCE: Evidence on screening outcomes with digital breast tomosynthesis (DBT) vs digital mammography (DM) in women with a family history of breast cancer is limited.

OBJECTIVE: To compare the performance of DBT and DM screening in women with a family history of breast cancer overall and subdivided by breast cancer family history category, breast density, age group, screening interval, and screening round, and to describe characteristics of cancers detected on screening vs interval cancers.

In this comparative cohort study at imaging facilities affiliated with the Breast Cancer Surveillance Consortium, adult women 18 years and older with a self-reported family history of breast cancer who underwent DBT or DM from 2011 to 2018 were included, with a 1-year follow-up for breast carcinoma. Data analysis was performed between November 2023 and August 2024.

EXPOSURES: DBT or DM.

MAIN OUTCOMES AND MEASURES: The main outcomes were absolute risk difference (ARD) between DBT and DM for recall rate, cancer detection rate, interval cancer rate, advanced cancer rate, biopsy rate, positive predictive values, sensitivity, and specificity, with inverse probability of treatment weighting.

RESULTS: A total of 208 945 women with a family history of breast cancer undergoing 502 357 screening examinations were included in the sample. Median (IQR) age was 58 (50-66) and 57 (49-66) years for the DBT and DM groups, respectively. Adjusted ARDs (DBT vs DM) were significant for recall rate (-1.51%; 95% CI, -2.42% to -0.59%) and specificity (1.56%; 95% CI, 0.65%-2.46%) in the overall cohort of 121 698 DBT and 380 561 DM examinations and among women with 1 first-degree relative (recall rate ARD, -1.72%; 95% CI, -2.70% to -0.74%; specificity ARD, 1.75%; 95% CI, 0.81%-2.69%). Among those with only second-degree relatives, the biopsy rate for DBT was significantly higher (ARD, 0.39%; 95% CI, 0.18%-0.61%). Significant ARDs were observed for the ductal carcinoma in situ detection rate (-0.71 per 1000 examinations; 95% CI, -1.03 to -0.38 per 1000 examinations) in women with almost entirely fatty breasts; recall rate (-1.90%; 95% CI, -2.88% to -0.92%) and specificity (1.93%; 95% CI, 0.97%-2.89%) in women with scattered fibroglandular densities. Significant ARDs were also observed for the positive predictive value for recall (1.75%; 95% CI, 0.84%-2.67%) in heterogeneously dense breasts, as well as the biopsy rate (0.48%; 95% CI, 0.16%-0.80%) and advanced cancer rate (-0.61 per 1000 examinations; 95% CI, -1.02 to -0.20 per 1000 examinations) in extremely dense breasts. DBT screening had a higher proportion than DM of screen-detected early-stage, invasive cancers with favorable prognostic characteristics.

CONCLUSIONS AND RELEVANCE: In this cohort study of women with a family history of breast cancer, DBT screening reduced recall rates and increased specificity compared to DM, particularly in women with 1 first-degree relative with breast cancer and those with scattered fibroglandular breast density, and reduced advanced cancer rates in women with extremely dense breasts.},
}

@article {pmid40402042,
year = {2025},
author = {Moosavi, D and Curtis, KR and Randolph, TW and Kahsai, OJ and Ammar, H and Lim, U and Cheng, I and Wilkens, LR and Le Marchand, L and Lampe, JW and Hullar, MAJ},
title = {Stability and Variability of the Human Fecal Microbiome Over Two Years in the Multiethnic Cohort Study: A Metagenomic Analysis.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-24-1770},
pmid = {40402042},
issn = {1538-7755},
abstract = {BACKGROUND: Understanding the longitudinal variability of the gut microbiome is essential for advancing microbiome-based measurements and designing robust sampling protocols in observational and intervention studies of cancer and other health outcomes. The aim of this study was to explore the temporal variability and stability of the fecal microbiome over a 2-year period, using intraclass correlation (ICC) analysis of metagenomic sequencing data.

METHODS: We studied 25 older adults from the Multiethnic Cohort Adiposity Phenotype Study (MEC-APS, 2013-2016). Stool samples were collected every six months over a two-year period (5 samples) and analyzed using metagenomic sequencing. The temporal stability was evaluated using ICCs across taxonomic levels, diversity, and functional genes and pathways.

RESULTS: The microbial community showed stability in alpha diversity and overall structure, with no significant changes across time points (Shannon diversity, p = 0.95). Taxonomic composition showed strong reliability over time, with median ICCs of 0.7 at the genus level and 0.75 at species level. Functional genes also demonstrated good stability (median ICC = 0.68). However, microbial pathways were more variable, with a fair median ICC of 0.49.

CONCLUSION: While the fecal microbiome was generally stable, some taxa and functions were more dynamic and responsive to external influences.

IMPACT: Findings highlight the need for reliable microbiome measurements and sampling strategies to reduce bias in studies of the microbiome and cancer.},
}

@article {pmid40381914,
year = {2025},
author = {Yeung, CCS and Narava, SK and Chang, TC and Saeed, M and Aicher, L and Beppu, LW and Majano, MS and Taylor, EM and Camalier, CE and Sandhuria, P and Sala-Torra, O and Li, J and Yee, LM and McShane, LM and Karlovich, C and Little, RF and Harris, L and Doroshow, JH and Williams, PM and Radich, JP and Jiwani, S},
title = {Analytical Performance of the NCI-myeloMATCH Assay: A Rapid Turnaround Genomic Profiling Assay for Myeloid Disorders.},
journal = {The Journal of molecular diagnostics : JMD},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jmoldx.2025.05.001},
pmid = {40381914},
issn = {1943-7811},
abstract = {myeloMATCH is a National Cancer Institute precision medicine clinical trial initiative to evaluate treatments for acute myeloid leukemia and myelodysplastic syndrome based on a patient's diagnostic presenting clinical and genetic profile. The National Cancer Institute myeloid assay version 2 (NMAv2) uses the Ion Torrent Genexus System, an automated platform with <48-hour turnaround from specimen receipt to reporting, to provide regulatory-compliant use for myeloMATCH across two independent clinical laboratories with harmonized workflows. Using marrow aspirate or peripheral blood clinical specimens, cell lines, and contrived reference materials, NMAv2 exhibited 99% sensitivity for 291 known mutations and 100% specificity. High reproducibility detecting all reportable variants was observed, with >98% mean positive percentage agreement and 100% negative percent agreement across six reproducibility assessments. Reproducibility experiments of companion diagnostic biomarkers (1 to 1.5× clinical limit of reporting) showed 100% positive percentage agreement and negative percent agreement. The limit of detection was 0.06% for hotspot single-nucleotide variants, 0.16% for non-hotspot single-nucleotide variants, 0.51% for hotspot insertion/deletions, approximately 1% for non-hotspot insertion/deletions, 0.23% for FLT3-internal tandem duplications, and ≤40 reads at 0.1% tumor content for fusions. Concordance of 99.39% was observed in orthogonal assays testing 76 blinded myeloid specimens in the sensitivity study, and 100% concordance was observed in testing 54 FLT3-internal tandem duplication specimens. The results show that NMAv2 has high specificity, sensitivity, accuracy, and reproducibility, and it can rapidly characterize genomic alterations in acute myeloid leukemia and myelodysplastic syndrome.},
}

@article {pmid40399683,
year = {2025},
author = {Rademaker, G and Hernandez, GA and Seo, Y and Dahal, S and Miller-Phillips, L and Li, AL and Peng, XL and Luan, C and Qiu, L and Liegeois, MA and Wang, B and Wen, KW and Kim, GE and Collisson, EA and Kruger, SF and Boeck, S and Ormanns, S and Guenther, M and Heinemann, V and Haas, M and Looney, MR and Yeh, JJ and Zoncu, R and Perera, RM},
title = {PCSK9 drives sterol-dependent metastatic organ choice in pancreatic cancer.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {40399683},
issn = {1476-4687},
abstract = {To grow at distant sites, metastatic cells must overcome major challenges posed by the unique cellular and metabolic composition of secondary organs[1]. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease that metastasizes to the liver and lungs. Despite evidence of metabolic reprogramming away from the primary site, the key drivers that dictate the ability of PDAC cells to colonize the liver or lungs and survive there remain undefined. Here we identified PCSK9 as predictive of liver versus lung colonization by integrating metastatic tropism data of human PDAC cell lines[2], in vivo metastasis modelling in mice and gene expression correlation analysis. PCSK9 negatively regulates low density lipoprotein (LDL)-cholesterol import and, accordingly, PCSK9-low PDAC cells preferentially colonize LDL-rich liver tissue. LDL-cholesterol taken up by liver-avid PCSK9-low cells supports activation of pro-growth mTORC1 activation at the lysosome, and through conversion into the signalling oxysterol, 24(S)-hydroxycholesterol, reprogrammes the microenvironment to release nutrients from neighbouring hepatocytes. Conversely, PCSK9-high, lung-avid PDAC cells rely on transcriptional upregulation of the distal cholesterol synthesis pathway to generate intermediates-7-dehydrocholesterol and 7-dehydrodesmosterol-with protective action against ferroptosis, a vulnerability in the oxygen-rich microenvironment of the lung. Increasing the amount of PCSK9 redirected liver-avid cells to the lung whereas ablating PCSK9 drove lung-avid cells to the liver, thereby establishing PCSK9 as necessary and sufficient for secondary organ site preference. Our studies reveal PCSK9-driven differential utilization of the distal cholesterol synthesis pathway as a key and potentially actionable driver of metastatic growth in PDAC.},
}

@article {pmid40399555,
year = {2025},
author = {Lammi, V and Nakanishi, T and Jones, SE and Andrews, SJ and Karjalainen, J and Cortés, B and O'Brien, HE and Ochoa-Guzman, A and Fulton-Howard, BE and Broberg, M and Haapaniemi, HH and Kanai, M and Pirinen, M and Schmidt, A and Mitchell, RE and Mousas, A and Mangino, M and Huerta-Chagoya, A and Sinnott-Armstrong, N and Cirulli, ET and Vaudel, M and Kwong, ASF and Maiti, AK and Marttila, MM and Posner, DC and Rodriguez, AA and Batini, C and Minnai, F and Dearman, AR and Warmerdam, CAR and Sequeros, CB and Winkler, TW and Jordan, DM and Rešcenko, R and Miano, L and Lane, JM and Chung, RK and Guillen-Guio, B and Leavy, OC and Carvajal-Silva, L and Aguilar-Valdés, K and Frangione, E and Guare, L and Vergasova, E and Marouli, E and Striano, P and Zainulabid, UA and Kumar, A and Ahmad, HF and Edahiro, R and Azekawa, S and , and , and , and , and , and , and , and , and , and Luoh, SW and Erikstrup, C and Pedersen, OBV and Lerner-Ellis, J and Colombo, A and Grzymski, JJ and Ishii, M and Okada, Y and Beckmann, ND and Kumari, M and Wagner, R and Heid, IM and John, C and Short, PJ and Magnus, P and Ansone, L and Valenti, LVC and Lee, SA and Wain, LV and Verdugo, RA and Banasik, K and Geller, F and Franke, LH and Rakitko, A and Duncan, EL and Renieri, A and Tsilidis, KK and de Cid, R and Niavarani, A and Abner, E and Tusié-Luna, T and Verma, SS and Smith, GD and Timpson, NJ and Madduri, RK and Cho, K and Daly, MJ and Ganna, A and Schulte, EC and Richards, JB and Ludwig, KU and Marks-Hultström, M and Zeberg, H and Ollila, HM},
title = {Genome-wide association study of long COVID.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {40399555},
issn = {1546-1718},
abstract = {Infections can lead to persistent symptoms and diseases such as shingles after varicella zoster or rheumatic fever after streptococcal infections. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can result in long coronavirus disease (COVID), typically manifesting as fatigue, pulmonary symptoms and cognitive dysfunction. The biological mechanisms behind long COVID remain unclear. We performed a genome-wide association study for long COVID including up to 6,450 long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We discovered an association of FOXP4 with long COVID, independent of its previously identified association with severe COVID-19. The signal was replicated in 9,500 long COVID cases and 798,835 population controls. Given the transcription factor FOXP4's role in lung physiology and pathology, our findings highlight the importance of lung function in the pathophysiology of long COVID.},
}

@article {pmid40398621,
year = {2025},
author = {R, SS and S, X and Temitope, O and Woo, AK and Othman, A and Yung-Tsi, B and Larisa, B and Jenni, B and Caitrin, B and Min, C and M, DS and Najla, EJ and Mehdi, H and Mary, H and H, HA and Samantha, J and Michelle, K and J, LS and Amy, M and M, PK and C, PM and Waleska, P and Rachel, P and Doug, R and Wael, S and E, SH and Patricia, S and Eileen, T and Alexis, V and Rebecca, V and J, AJ and E, SB and Mariam, AJ},
title = {Current Activity Trends and Outcomes in Hematopoietic Cell Transplantation and Cellular Therapy - A report from the CIBMTR.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.05.014},
pmid = {40398621},
issn = {2666-6367},
abstract = {The Center for International Blood and Marrow Transplant Research (CIBMTR) compiles annual summary slides describing trends in hematopoietic cell transplantation (HCT) and cellular therapy (CT) practice and outcomes. This year's report includes all patients receiving their first autologous and/or allogeneic HCT/CT in the United States between 2013 and 2023 or chimeric antigen receptor T-cell (CAR-T) from 2016 and 2023, reported to CIBMTR. Relative proportion of allogeneic and autologous HCT/CT was generated as percentage of total for donor type and for patient age, disease indication, graft-versus-host disease (GVHD) prophylaxis, and race and ethnicity. Causes of death were summarized using frequencies, and the Kaplan-Meier estimator was used for estimating overall survival. New for this year, disease risk stratification reflects European LeukemiaNet cytogenetic risk score for acute myeloid leukemia (AML) and the Revised International Prognostic Scoring System for myelodysplastic syndromes (MDS). Use of allogeneic HCT increased substantially in 2023, recovering from a decline in activity during the COVID-19 pandemic, with growth predominately in the 65-74 year-old age group. Overall, matched unrelated donors (MUD) continue as the most common allogeneic donor source (45%) followed by haploidentical related donors (Haplo) (21%), matched related donors (MRD) (18%), mismatched unrelated donors (MMUD) (12%) and cord blood (Cord) (3%). These trends hold in the adult patient population with a notable doubling of MMUD utilization since 2020 driven by the rapid shift to post-transplant cyclophosphamide based GVHD prophylaxis (PTCy) in this setting. In the pediatric setting, Haplo was the most common donor source surpassing MRD use in 2023 followed by MUD, Cord and MMUD. Autologous HCT continued to decline slightly while use of CAR-T therapy has rapidly increased since commercial approval in 2017 with lymphoma and multiple myeloma reaching 45% and 16%, respectively in 2023. Significant recent changes in GVHD prophylaxis in the adult allogeneic HCT setting have occurred. PTCy is most common in Haplo HCT with >90% since 2016. Among other donor sources, the most rapid adoption is in MMUD HCT at 82% in 2023. In MRD and MUD, PTCy use differs by conditioning intensity with RIC/NMA higher (58% and 64%, respectively), reflecting the standard of care established by BMT CTN 1703, compared to MAC (43% and 46%, respectively). In pediatrics, calcineurin inhibitor ± others remains the most common GVHD prevention strategy for MRD (88%) and MUD (68%). Although common in the pediatric Haplo HCT setting at 68% in 2023, use of PTCy is less common across other mismatched donor types where use of abatacept or ex-vivo T cell depletion/CD34 selection accounts for 28% and 17% in MMUD, respectively. Three-year overall survival continues to significantly improve among patients receiving allogeneic (62.1% vs 55.8%) and autologous (82.6% vs 79.6%) HCT when comparing HCT from 2017-2022 versus 2012-2016 (p<0.001), respectively. In both the adult and pediatric settings, primary cause of mortality after 100 days post-HCT remains primary disease in both allogeneic (47% and 45%, respectively) and autologous (60% and 79%, respectively). HCT/CT and CAR-T use continues to grow. Relapse remains the primary cause of death in the malignant setting supporting further efforts to mitigate risk.},
}

@article {pmid40398620,
year = {2025},
author = {Burleigh, K and Stratton, KG and Smith, JL and Jensen, MC and Turtle, CJ and Keenan, C and Annesley, C and Summers, C and Webb-Robertson, BJ and Hirayama, AV and Gardner, RA and Gustafson, HH},
title = {Low Peripheral Blood Counts and Elevated Proinflammatory Cytokines Signal a Poor CD19 CAR-T Response in ALL: Immune correlates of CAR-T response.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.05.003},
pmid = {40398620},
issn = {2666-6367},
abstract = {BACKGROUND: CD19 chimeric antigen receptor T-cell (CAR-T) therapy has significantly improved outcomes for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). However, approximately 20% of patients fail to achieve a complete remission (CR), and some develop severe, life-threatening toxicities. Understanding the biological mechanisms underlying both dysfunctional responses and severe toxicity is essential for optimizing patient management and improving therapeutic efficacy.

OBJECTIVES: This study aimed to (1) characterize cytokine profiles associated with dysfunctional responses and severe toxicity following CAR-T infusion, (2) examine the timing and trajectory of cytokine changes in relation to treatment outcomes and evaluate potential strategies for mitigating toxicity and treatment failure.

STUDY DESIGN: We conducted a comprehensive analysis of serum cytokine profiles in 86 adult and pediatric patients undergoing autologous CD19 CAR-T therapy for B-ALL. Patients were categorized into three groups: 1. Dysfunctional response- Patients who failed to achieve a minimal residual disease-negative complete remission (MRD- CR) by Day 63 or who experienced recurrence of CD19+ disease in the setting ongoing CAR T cell detection before Day 63. 2. Functional response with severe cytokine release syndrome (CRS) and/or Neurotoxicity (NTX)- Patients with best response of MRD- CR by Day 63 who experienced grade 3 or higher CRS or NTX. 3. Functional response without severe CRS or NTX- Patients with best response of MRD- CR by Day 63 who did not experience grade ≥ 3 CRS or neurotoxicity. Cytokine levels were measured during the first week post-infusion and correlated with treatment efficacy, toxicity outcomes, complete blood counts (CBCs), and CAR-T expansion dynamics. This analysis aimed to better understand how cytokine profiles relate to patient outcomes and immune responses in CAR-T therapy.

RESULTS: Patients with dysfunctional response exhibited decreased neutrophils, platelets and levels of granulocytic cytokines (suggestive of low bone marrow reserve) alongside elevated pro inflammatory cytokines by Day 1. Functional response with severe toxicity patients showed a progressive rise in proinflammatory cytokines, reaching similar levels to dysfunctional response patients by Day 7. We observed that high cytokines at both the Day 1 and Day 7 timepoints were associated with poor survival. These findings remained significant when adjusting for high disease burden, a known predictor of severe inflammatory toxicity and lack of response.

CONCLUSION: Early post-CAR-T infusion inflammation is associated with both dysfunctional response and severe toxicity-even after adjusting for disease burden. This suggests that inflammation, in addition to disease burden, plays a role in determining patient outcome. Therefore, strategies aimed at reducing the pro-inflammatory state prior to or early after CAR T cell infusion may improve outcomes for R/R B-ALL patients.},
}

@article {pmid40398416,
year = {2025},
author = {Aditham, AK and Radford, CE and Carr, CR and Jasti, N and King, NP and Bloom, JD},
title = {Deep mutational scanning of rabies glycoprotein defines mutational constraint and antibody-escape mutations.},
journal = {Cell host & microbe},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chom.2025.04.018},
pmid = {40398416},
issn = {1934-6069},
abstract = {Rabies virus causes nearly 60,000 human deaths annually. Antibodies that target the rabies glycoprotein (G) are being developed as post-exposure prophylactics, but mutations in G can render such antibodies ineffective. Here, we use pseudovirus deep mutational scanning to measure how all single-amino-acid mutations to G affect cell entry and neutralization by a panel of antibodies. These measurements identify sites critical for G function and define constrained regions that are attractive epitopes for clinical antibodies, including at the apex and base of the protein. We provide complete maps of escape mutations for eight monoclonal antibodies, including some in clinical use or development. Escape mutations for most antibodies are present in some natural rabies strains. Overall, this work provides comprehensive information on the functional and antigenic effects of G mutations that can inform development of stabilized vaccine antigens and antibodies that are resilient to rabies genetic variation.},
}

@article {pmid40397836,
year = {2025},
author = {Ramsey, SD and Sun, Q and Fedorenko, CR and Li, L and Panattoni, LE and Kreizenbeck, KL and Shankaran, V},
title = {Telehealth and Emergency Department Use Among Commercially Insured, Medicaid, and Medicare Patients Receiving Systemic Cancer Therapy in Washington State After COVID-19.},
journal = {JCO clinical cancer informatics},
volume = {9},
number = {},
pages = {e2400217},
doi = {10.1200/CCI-24-00217},
pmid = {40397836},
issn = {2473-4276},
mesh = {Humans ; *COVID-19/epidemiology/virology/prevention & control ; *Telemedicine/statistics & numerical data ; *Medicaid/statistics & numerical data ; *Medicare/statistics & numerical data ; Washington/epidemiology ; *Emergency Service, Hospital/statistics & numerical data ; Male ; Female ; *Neoplasms/therapy/epidemiology ; United States/epidemiology ; Aged ; Middle Aged ; SARS-CoV-2 ; Insurance, Health/statistics & numerical data ; Adult ; SEER Program ; },
abstract = {PURPOSE: In oncology, telehealth services were adopted as a means of mitigating the risk of COVID-19 transmission. We hypothesized that Medicaid enrollees would have less access to telehealth than commercially insured or Medicare enrollees during the pandemic, resulting in higher rates of emergency department (ED) visits during systemic cancer treatment.

METHODS: Linking Washington State SEER records with commercial, Medicaid, and Medicare records, we evaluated adults with new solid tumor malignancies who received initial systemic treatment before the COVID-19 pandemic (January 1, 2017-December 31, 2019) and after the pandemic (March 1, 2020-November 30, 2021). Poisson and logistic regressions were used to evaluate differences in the number of office visits, telehealth visits, and ED visits in the 3 months after starting systemic anticancer treatment between insurance groups before versus after the pandemic.

RESULTS: Among 2,936 commercial, 2,039 Medicaid, and 7,333 Medicare enrollees who met inclusion criteria, office-based visits fell substantially for all groups during the COVID-19 period. Medicare enrollees had fewer telehealth visits while Medicaid had more telehealth visits, compared with commercial enrollees. ED visits declined for all patients, but there were no differences between insurance groups.

CONCLUSION: In Washington State, COVID-19 resulted in a substantial decrease in office-based visits, with an accompanying increase in telehealth visits partially offsetting the difference in overall access to care. ED visit rates fell substantially, without differences between insurance groups.},
}

Humans
*COVID-19/epidemiology/virology/prevention & control
*Telemedicine/statistics & numerical data
*Medicaid/statistics & numerical data
*Medicare/statistics & numerical data
Washington/epidemiology
*Emergency Service, Hospital/statistics & numerical data
Male
Female
*Neoplasms/therapy/epidemiology
United States/epidemiology
Aged
Middle Aged
SARS-CoV-2
Insurance, Health/statistics & numerical data
Adult
SEER Program