@article {pmid41497599,
year = {2025},
author = {Trofimov, A and Montague, Z and Russell, ML and Ignacio, RB and Stevens-Ayers, T and Zamora, D and Mielcarek, M and Boeckh, MJ and Matsen, F and Nourmohammad, A},
title = {Genetic and environmental imprints on T cell receptor repertoires as predictors of graft-versus-host disease.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41497599},
issn = {2692-8205},
abstract = {Hematopoietic cell transplantation (HCT) as potentially curative treatment for patients with hematologic malignancies relies on T cells to mediate the potentially curative graft-versus-tumor (GVT) effect, which may be associated with graft-versus-host disease (GVHD), a potentially life-threatening complication. T cells recognize peptides presented by Human Leukocyte Antigen (HLA) molecules. It is commonly believed that matching HLA alleles between donors and recipients ensures similarity in their T cell receptor (TCR) repertoires, thereby reducing the risk of GVHD and graft rejection. However, TCR repertoires are shaped by multiple factors beyond HLA genetics, including sex, age, and immune history. The extent to which genetic variation and past infections influence TCR repertoire composition and GVHD risk remains unclear. Here, we show that while HLA haplotypes contribute to broad TCR repertoire differences, recent viral infections significantly impact TCR composition and influence GVHD risk. Analyzing 401 patients who were uniformly transplanted from healthy HLA-identical sibling HCT donors, we introduced HLA-TCR coherence, a metric that quantifies the extent to which an individual's TCR repertoire reflects their HLA haplotype. We find that higher TCR-HLA coherence is associated with greater HLA heterozygosity and an increased incidence of severe acute GVHD (grade 3-4) in transplant recipients. Furthermore, in silico identification of virus-associated TCRs (vaTCRs) using TCR sequencing and viral serology reveal specific vaTCRs predictive of either increased or decreased GVHD risk. These findings suggest that beyond HLA allele matching, donor-specific immune history and repertoire characteristics are critical determinants of GVHD risk. Thus, a more systematic integration of donor immune history may offer a complementary avenue for refining donor selection and potentially improving transplant outcomes.},
}

@article {pmid41497576,
year = {2025},
author = {Jones, JD and Valenzuela, Y and Pacheco, M and Nelson, L},
title = {Research Participation Among American Indian and Alaskan Native Individuals Living With Parkinson's Disease.},
journal = {Parkinson's disease},
volume = {2025},
number = {},
pages = {3207928},
pmid = {41497576},
issn = {2090-8083},
abstract = {BACKGROUND: There is a notable gap in racial and ethnic representation in Parkinson's disease (PD) research, particularly among American Indian and Alaska Native (AIAN) populations, despite a higher prevalence of PD in these groups. This study investigated research participation among AIAN individuals in terms of perceived access to research opportunities, willingness to participate, and potential concerns about participation.

METHODS: Data were obtained from the online Fox Insight (FI) study. A total sample of 4412 individuals who self-reported their race as White (n = 4363) or AIAN (n = 49) were selected. The Attitudes and Beliefs Regarding Research and Genetic Testing for PD survey was administered to assess participants' attitudes and knowledge about the research process, opportunities, and preferences.

RESULTS: A significantly smaller proportion of AIAN individuals (34.7%) reported concurrent or past participation in PD research compared with White non-AIAN participants (52.9%). Despite this lower participation rate and limited knowledge of research opportunities, a large majority of AIAN individuals (89.8%) expressed a willingness to participate in research. Additionally, both AIAN and White non-AIAN participants reported similar rates of concerns about research participation. Among AIAN individuals, the most common barriers were distance from research site, transportation, and time commitments.

CONCLUSION: These findings highlight that low research participation among AIAN individuals may be more associated with low engagement from the research community rather than unwillingness or relatively greater research concerns. Building stronger partnerships with tribal communities and involving community leaders to build trust may improve research representation among AIAN populations.},
}

@article {pmid41495267,
year = {2026},
author = {Werwath, KE and Lawn, RB and Salem, MT and Li, T and Mitchell, BL and Shen, H and Gordon, SD and Kung, B and Stafford, C and Vemuri, M and Ratanatharathorn, A and Meijsen, J and Shadyab, AH and Kooperberg, C and Koenen, KC and Crandall, CJ and Martin, NG and Duncan, LE},
title = {Trans-ancestry GWAS of hot flashes reveals potent treatment target and overlap with psychiatric disorders.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-025-01305-8},
pmid = {41495267},
issn = {2730-664X},
support = {MH125358//U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)/ ; },
abstract = {BACKGROUND: Most women experience hot flashes (hot flushes) during the menopause transition. Menopausal hot flashes typically persist for years, and for a sizeable minority of women, are substantially impairing. Genetic investigations can improve understanding of hot flash etiology.

METHODS: We conducted a trans-ancestry genome-wide association study (GWAS) of hot flashes (N = 149,560) among post-menopausal women age 35-88. The outcome variable was self-reported hot flashes in four samples (total n = 42,489) and menopausal hormone therapy as a proxy in one sample (n = 107,071). We estimated the heritability of hot flashes and genetic correlations with psychiatric phenotypes using linkage disequilibrium score regression.

RESULTS: In our trans-ancestry meta-analysis, the top locus lies on chromosome 4 in the neurokinin 3 receptor gene (TACR3, p = 7.2×10[-41]). We also identify another locus on chromosome 4 with top SNP rs13107507 (p = 3.5×10[-8]). Gene results implicate TACR3, GRID1, NUDT4, and PHF21B. SNP heritability is estimated to be 8% (h[2]liab = .08, h[2]SNP = .04, se = .02). Genetic correlations are statistically significant between hot flashes and PTSD (rg = 0.25, p = 0.01), schizophrenia (rg = 0.17, p = 0.02), depression (rg = 0.21, p = 0.01), and ADHD (rg = .22, p = 0.03).

CONCLUSIONS: These genomic findings are consistent with independent, robust basic science research which led to a recently developed treatment for hot flashes, namely, a neurokinin 3 receptor antagonist. This non-hormonal class of hot flash drugs blocks the receptor coded for by the top locus reported here (TACR3, the neurokinin 3 receptor gene). Hot flash GWAS results provide an example of how GWAS findings can point to potent treatment targets for complex brain phenotypes.},
}

@article {pmid41495079,
year = {2026},
author = {Yao, TH and Treekitkarnmongkol, W and Putluri, N and Sankaran, D and Nguyen, T and Balasenthil, S and Hurd, MW and Chen, M and Brand, RE and Lampe, PD and Kamal, AHM and Putluri, V and Hu, TY and Maitra, A and Koay, EJ and Killary, AM and Sen, S and Kundu, S},
title = {Machine learning-based multimodal biomarkers enable accurate diagnosis and early detection of pancreatic ductal adenocarcinoma.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {658},
pmid = {41495079},
issn = {2045-2322},
abstract = {While there has been some progress on discovering clinically validated biomarkers for early detection in pancreatic ductal adenocarcinoma (PDAC), several challenges remain. Most approaches rely on single-modality biomarkers with limited sensitivity and/or specificity. Using data from a multicenter study with an age-matched cohort (n = 203 with healthy controls n = 46, pancreatitis controls n = 36, and diagnosed cases n = 121), we developed a machine learning approach integrating 2,096 microRNAs, 125 metabolites, and CA19-9. Our method performs unsupervised selection of an optimal subset of biomarkers with maximal discriminatory power for diagnosis and early detection. In training data, the selected biomarker panel achieved [Formula: see text] area under the curve (AUC) and [Formula: see text] sensitivity when controlling specificity at [Formula: see text]. The classification results under the selected multimodal panel generalize well for validation samples. The panel outperforms recently proposed microRNA-based approaches and identifies key biomarkers (such as aminobutyric acid and homovanillic acid) with high classification importance. Decision tree–based cut-offs are derived to enhance clinical interpretability, revealing the association between the low aminobutyric acid level and non-cancer status. These results highlight the superior discriminative ability and interpretability of the proposed multimodal biomarker panel, offering a promising tool for PDAC diagnosis and early detection.},
}

@article {pmid41494888,
year = {2025},
author = {Kwendakwema, CN and Lan, KF and Kim, HN and Gopal, AK and Menon, MP},
title = {HIV, HBV, and HCV Testing in Newly Diagnosed Diffuse Large B-Cell Lymphoma: Experience From a Comprehensive Cancer Center.},
journal = {Clinical lymphoma, myeloma & leukemia},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.clml.2025.12.010},
pmid = {41494888},
issn = {2152-2669},
abstract = {PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype non-Hodgkin lymphoma. HIV, hepatitis B (HBV), and hepatitis C (HCV) infections are DLBCL risk factors. DLBCL remains a leading cause of cancer-related morbidity and mortality in those with HIV. DLBCL treatments can also increase the HBV reactivation risk and acute liver injury in HCV. We assessed HBV, HCV, and HIV screening rates in DLBCL patients receiving systemic therapy in a comprehensive cancer system.

MATERIALS AND METHODS: We analyzed newly diagnosed DLBCL patients receiving anti-CD20 therapies between January 2018 and December 2023. Patients were considered screened if they had viral testing or a prior diagnosis within 12 months before to 3 months after starting treatment. We used chi-squared and Fisher's exact tests to examine associations between patients who were and were not screened HBV, HCV, and HIV. We used univariate and multivariate logistic regression to identify the factors associated with screening.

RESULTS: A total of 535 patients with DLBCL were treated (median age 64, 42% female, 82% white). Among these patients, 410 (77%) had HBV testing or a known infection, 275 (51.4%) had HIV testing or a known infection, and 307 (53%) had HCV testing or a known infection. Younger people were more likely to be tested for HIV and HCV. There was no association between age and HBV testing.

CONCLUSION: Pre-treatment HIV, HBV, and HCV screening rates in newly diagnosed DLBCL patients remains suboptimal. Interventions to increase viral testing in this population could help reduce treatment-related morbidity and mortality.},
}

@article {pmid41494138,
year = {2026},
author = {Hicks, LK and Messersmith, HJ and Al Hadidi, S and Banerjee, R and Derman, BA and Kumar, S and Wildes, TM and Bal, S and Bhella, S and Chmielewski, C and Costello, C and Dabney, R and Hartley-Brown, M and Langerak, A and Lipe, B and Martin, T and McCurdy, A and Mian, H and Riva, E and Seth, R and Subramanian, L and Mikhael, J},
title = {Treatment of Multiple Myeloma: ASCO-Ontario Health (Cancer Care Ontario) Living Guideline.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2502587},
doi = {10.1200/JCO-25-02587},
pmid = {41494138},
issn = {1527-7755},
abstract = {PURPOSE: To provide updated guidance regarding the therapy for multiple myeloma.

METHODS: ASCO and Ontario Health (Cancer Care Ontario) convened a joint Expert Panel and conducted an updated systematic review of the literature.

RESULTS: The updated review identified a total of 161 relevant randomized trials.

UPDATED RECOMMENDATIONS: Daratumumab therapy may be offered to patients with high-risk smoldering myeloma. Quadruplet therapy with daratumumab or isatuximab, combined with bortezomib, lenalidomide, and dexamethasone, should be offered as initial therapy for transplant eligible patients. They should also be offered at least lenalidomide maintenance, with or without daratumumab, carfilzomib, and/or dexamethasone. Quadruplet therapy with daratumumab or isatuximab, combined with bortezomib, lenalidomide, and dexamethasone, should be offered as therapy for suitable transplant-ineligible patients. Patients with relapsed or refractory multiple myeloma should be offered triplet therapy or T-cell redirecting therapies according to a set of recommended principles.Additional information is available at www.asco.org/hematologic-malignancies-guidelines.},
}

@article {pmid41493894,
year = {2026},
author = {Ramírez, P and Lankowski, AJ and Gallardo-Cartagena, JA and Gonzales, P and Valencia, J and Lama, JR and León, M and Salvatierra, J and Sanchez, H and Cabello, R and Konda, KA and Sanchez, JL and , },
title = {Implementation of Daily Oral PrEP at HIV/AIDS Service Organizations in Lima, Peru: Early Findings From the PrEP PERU Demonstration Study.},
journal = {Journal of the International Association of Providers of AIDS Care},
volume = {25},
number = {},
pages = {23259582251411793},
pmid = {41493894},
issn = {2325-9582},
mesh = {Humans ; Peru/epidemiology ; *Pre-Exposure Prophylaxis/methods ; Male ; Adult ; *HIV Infections/prevention & control/epidemiology ; Prospective Studies ; Homosexuality, Male/statistics & numerical data ; Administration, Oral ; *Anti-HIV Agents/administration & dosage/therapeutic use ; *Tenofovir/administration & dosage/therapeutic use ; Medication Adherence ; COVID-19/epidemiology ; },
abstract = {BackgroundDespite global declines in HIV incidence, new infections continue to rise in Latin America. Oral tenofovir-based HIV pre-exposure prophylaxis (PrEP) is effective and can reduce incidence where implemented. PrEP PERU is a prospective cohort study evaluating daily oral PrEP delivery at HIV/AIDS service organizations (ASOs) in Peru.MethodsWe assessed 12-month PrEP retention and adherence among men who have sex with men (MSM) enrolled at 4 ASOs in Lima before the COVID-19 pandemic. The analysis included participants with ≥12 months of follow-up before the March 2020 lockdown. Follow-up visits occurred at weeks 4, 12, and quarterly thereafter. We used robust Poisson regression to evaluate associations between baseline characteristics and 2 outcomes: retention (attending ≥3 follow-up visits within 12 months) and optimal adherence (proportion of days covered ≥80%).ResultsAmong 264 MSM who initiated PrEP, median age was 31 years (IQR: 27-37). Retention at 12 months was 71%, and 55% achieved optimal adherence. Retention was associated with age ≥30 and bisexual identity in adjusted models. Optimal adherence was associated with being employed at baseline.ConclusionsPrEP delivery through ASOs in Lima is feasible and supports sustained engagement among MSM. Targeted strategies are needed to improve outcomes among younger individuals.},
}

Humans
Peru/epidemiology
*Pre-Exposure Prophylaxis/methods
Male
Adult
*HIV Infections/prevention & control/epidemiology
Prospective Studies
Homosexuality, Male/statistics & numerical data
Administration, Oral
*Anti-HIV Agents/administration & dosage/therapeutic use
*Tenofovir/administration & dosage/therapeutic use
Medication Adherence
COVID-19/epidemiology

@article {pmid41493843,
year = {2026},
author = {He, AR and Bouattour, M and Gupta, VG and Evesque, L and Zhen, DB and Park, JO and Sookprasert, A and Salvatierra, A and Vaccaro, G and Oh, SC and Ostoich, SA and Satoh, T and Kuzko, A and Żotkiewicz, M and Rokutanda, N and Oh, DY},
title = {Predictors of overall survival in advanced biliary tract cancer in the phase 3 TOPAZ-1 study.},
journal = {Hepatology communications},
volume = {10},
number = {1},
pages = {},
pmid = {41493843},
issn = {2471-254X},
}

@article {pmid41491041,
year = {2026},
author = {Ahmad, K and Wooten, M and Takushi, BN and Vidaurre, V and Chen, X and Henikoff, S},
title = {Cell-cycle-dependent repression of histone gene transcription by histone H4.},
journal = {Nature structural & molecular biology},
volume = {},
number = {},
pages = {},
pmid = {41491041},
issn = {1545-9985},
abstract = {In all eukaryotes, DNA replication is coupled to histone synthesis to coordinate chromatin packaging of the genome. Canonical histone genes coalesce in the nucleus into the histone locus body (HLB), where gene transcription and 3' mRNA processing occurs. Both histone gene transcription and mRNA stability are reduced when DNA replication is inhibited, implying that the HLB senses the rate of DNA synthesis. In Drosophila melanogaster, the S-phase-induced histone genes are tandemly repeated in an ~100 copy array, whereas, in humans, these histone genes are scattered. In both organisms, these genes coalesce into HLBs. Here, we use a transgenic histone gene reporter and RNA interference in Drosophila to identify canonical H4 histone as a unique repressor of histone synthesis during the G2 phase in germline cells. Using cytology and CUT&Tag chromatin profiling, we find that histone H4 uniquely occupies histone gene promoters in both Drosophila and human cells. Our results suggest that repression of histone genes by soluble histone H4 is a conserved mechanism that coordinates DNA replication with histone synthesis in proliferating cells.},
}

@article {pmid41489165,
year = {2026},
author = {Yang, Z and Rizopoulos, D and Newcomb, LF and Erler, NS},
title = {Time-Dependent Predictive Accuracy Metrics in the Context of Interval Censoring and Competing Risks.},
journal = {Biometrical journal. Biometrische Zeitschrift},
volume = {68},
number = {1},
pages = {e70108},
pmid = {41489165},
issn = {1521-4036},
support = {CA253910/NH/NIH HHS/United States ; },
mesh = {Humans ; *Biometry/methods ; Time Factors ; Male ; Prostatic Neoplasms ; Models, Statistical ; ROC Curve ; },
abstract = {Evaluating the performance of a prediction model is a common task in medical statistics. Standard accuracy metrics require the observation of the true outcomes. This is typically not possible in the setting with time-to-event outcomes due to censoring. Interval censoring, the presence of time-varying covariates, and competing risks present additional challenges in obtaining those accuracy metrics. In this study, we propose two methods to deal with interval censoring in a time-varying competing risk setting: a model-based approach and the inverse probability of censoring weighting (IPCW) approach, focusing on three key time-dependent metrics: area under the receiver-operating characteristic curve, Brier score, and expected predictive cross-entropy. The evaluation is conducted over a medically relevant time interval of interest, [ t , Δ t) $[t, \Delta t)$ . The model-based approach includes all subjects in the risk set, using their predicted risks to contribute to the accuracy metrics. In contrast, the IPCW approach only considers the subset of subjects who are known to be event-free or experience the event within the interval of interest. We performed a simulation study to compare the performance of the two approaches with regard to the three metrics. Furthermore, we demonstrated the three metrics using the two approaches on an example prostate cancer surveillance cohort. Risk predictions were generated from a joint model handling the interval-censored cancer progression and the competing event, early treatment, and repeatedly measured biomarkers.},
}

Humans
*Biometry/methods
Time Factors
Male
Prostatic Neoplasms
Models, Statistical
ROC Curve

@article {pmid41488889,
year = {2026},
author = {Jain, J and Pugh, K and Handa, S and Dvorak-Kornaus, KM and Zhao, Q and Walter, RB and Cook, R and Saultz, J and Swords, R and Li, J and Laszlo, GS and Grieselhuber, NR and Mims, AS and Larkin, KTM and Sahasrabudhe, K and Blachly, JS and Behbehani, GK and Eisfeld, AK and Long, M and Srisuwananukorn, A and Koenig, KL and Borate, U},
title = {Safety of gemtuzumab ozogamicin with cytarabine, daunorubicin, and midostaurin induction in FLT3-mutated AML.},
journal = {Blood neoplasia},
volume = {3},
number = {1},
pages = {100171},
pmid = {41488889},
issn = {2950-3280},
abstract = {This phase 1 study investigated the addition of gemtuzumab ozogamicin (GO) to intensive chemotherapy with cytarabine, daunorubicin, and midostaurin in 21 patients with newly diagnosed (ND) FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML). Four dose levels of GO were evaluated. The use of GO was tolerable, with all dose-limiting toxicities similar to those seen in standard-of-care treatment. After induction, the median time to platelet recovery was 26 days, and the median time to absolute neutrophil count (ANC) recovery was 27 days. The maximum tolerated dose was cytarabine 100 mg/m[2] on days 1 to 7, midostaurin 50 mg twice daily on days 8 to 21, daunorubicin 60 mg/m[2] on days 1 to 3, and GO 3 mg/m[2] on days 1 and 4. For the 18 patients who were evaluable for response after induction therapy, 16 patients (76%) achieved a composite complete response (complete remission [CR] + CR with incomplete hematologic recovery), and 2 (10%) had stable disease. Of the 14 patients who proceeded to consolidation, 5 discontinued the study for transplant, 1 for disease progression, and 1 for physician discretion. Seven patients completed consolidation therapy, all of whom achieved a CR. In total, 13 of the 21 patients (62%) received a hematopoietic stem cell transplant. Our results show that GO can safely be combined with intensive chemotherapy with midostaurin in ND, FLT3-mutated AML. This trial was registered at www.clinicaltrials.gov as #NCT03900949.},
}

@article {pmid41488033,
year = {2026},
author = {Courville, EL and Seifert, R and Sadigh, S and Chen, X and Calli, JL and Hasserjian, R and Siddon, AJ},
title = {Joining the National Resident Matching Program Fellowship Match: the hematopathology experience.},
journal = {Academic pathology},
volume = {13},
number = {1},
pages = {100230},
pmid = {41488033},
issn = {2374-2895},
abstract = {Hematopathology fellowships are a critical subspecialty within the field of pathology, and with a progressively earlier and earlier fellowship interview timeline, hematopathology decided to join the Pathology Fellowship Match in 2025. The pros and cons of participating in the National Resident Matching Program Match were evaluated, and ultimately it was decided to be undertaken. The National Resident Matching Program requires that 75% of programs and fellowship positions should be entered in order to sponsor the Match. The Society for Hematopathology Education Committee lead the process to recruit hematopathology fellowships into the Match, initiating a survey to assess initial interest, creating a listserv for program director questions, and maintaining a website with programs that ultimately decided to participate. The initial survey results showed that 79% of hematopathology program directors responded "yes" or "maybe" to whether they would participate in a formal Match. The Society for Hematopathology Education Committee then proceeded with a memorandum of understanding to show commitment to the Match. Multiple efforts to disseminate information followed, including informational webinars, social media outreach, and emails to program directors. Ultimately 83% of hematopathology fellowships participated in the 2025 Match, with 85% of positions filling, and 94.7% of hematopathology applicants matching. A follow-up program director survey showed that 98% of respondents planned to participate in the 2026 Match. This feedback solidifies that the Pathology Fellowship Match has shown mutual benefit for programs and applicants.},
}

@article {pmid41487700,
year = {2026},
author = {Ruiz, E and Gay, HA and Ixquiac, M and Velarde, A and Sun, B and García-Ramirez, J and Laugeman, E and Li, B and Michalski, J and de Falla, V and Hugo, G and Van Rheenen, J},
title = {Lessons Learned From an Epic Transformation of a Radiation Oncology Department in Guatemala: Keys to Success.},
journal = {Advances in radiation oncology},
volume = {11},
number = {1},
pages = {101928},
pmid = {41487700},
issn = {2452-1094},
abstract = {PURPOSE: We describe the radical modernization of a radiation oncology department in a developing country, Guatemala, from 2015 to the beginning of 2024. The Instituto de Cancerología y Hospital Dr. Bernardo del Valle S (INCAN) is the only public radiotherapy clinic serving patient referrals from the Ministry of Public Health and Social Assistance program.

METHODS AND MATERIALS: We describe the state of the radiation oncology department in 2015 versus 2024 while chronicling its gradual transformation. This multifaceted collaboration involved academic centers, government agencies, International Atomic Energy Agency (IAEA), industry, and nonprofits and continues to this day. We analyze the infrastructure, staff, radiotherapy equipment, physics equipment, patient careCo-60 decommissioning, and educational initiatives.

RESULTS: We graphically illustrate the impact of these changes in treatment delivery time, consults, follow-up visits, CT simulations, new patients treated in each linear accelerator, new patients treated with 2D, 3D, IMRT/VMAT, and superficial techniques, new patients treated with 2D LDR, 2D HDR, or 3D techniques, causes of linear accelerator downtime, and weekly patients on treatment. We provide a figure of the various sequential and parallel steps to modernize a radiation oncology department. We describe the complexities of radioisotope repatriation and safe disposal. We provide a comprehensive table of wisdom pearls regarding project governance, team, education, finances, culture, and language. We also discuss the impact of artificial intelligence in contouring.

CONCLUSION: The transformation of the INCAN radiation oncology department in Guatemala is a testimony to many's hard work, vision, and perseverance for the betterment of Guatemalan patients while facing incredible financial hardship. We hope that what we have learned in the past nine years will help others achieve even greater success in a shorter time.},
}

@article {pmid41479450,
year = {2025},
author = {Collienne, L and Matsen, FA},
title = {Tree rearrangement graphs admit paths of decreasing Robinson-Foulds distance.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {41479450},
issn = {2331-8422},
abstract = {Tree rearrangements such as Nearest Neighbor Interchange (NNI) and Subtree Prune and Regraft (SPR) are commonly used to explore phylogenetic treespace. Computing distances based on them, however, is often intractable, so the efficiently computable Robinson-Foulds (RF) distance is used in practice. We investigate how the RF distance behaves along paths in the NNI and SPR graphs, where trees are nodes, edges represent single rearrangements. We show that any two trees are connected by a path along which the RF distance to the target decreases monotonically in the NNI graph and strictly in the SPR graph; we also exhibit trees for which no strictly decreasing NNI path exists.},
}

@article {pmid41486674,
year = {2026},
author = {Kanetsky, PA and Almstrup, K and Cherlin, S and Cortessis, VK and Ferlin, A and Gietema, JA and González-Neira, A and Grotmol, T and Hamilton, RJ and Haugen, TB and Kiemeney, LA and Kim, J and Krausz, C and Lessel, D and Lothe, RA and Nead, KT and Nsengimana, J and Poynter, JN and Rajpert-DeMeyts, E and Richiardi, L and Schwartz, SM and Skotheim, RI and Stewart, DR and Turnbull, C and Wiklund, F and Zheng, T and Nathanson, KL and McGlynn, KA and , },
title = {The Testicular Cancer Consortium (TECAC): Filling Knowledge Gaps in the Genetic Etiology of Testicular Germ Cell Tumors.},
journal = {Andrology},
volume = {},
number = {},
pages = {e70168},
pmid = {41486674},
issn = {2047-2927},
support = {PC-35142/GF/NIH HHS/United States ; CAN2012/823//Swedish Cancer Society/ ; PK01-2007-0375//Norwegian Cancer Society/ ; PR-2006-0387//Norwegian Cancer Society/ ; III-FIS PI17/01822//Spanish Ministry of Health Instituto Carlos/ ; 101136622//European Union/ ; CN-67009/GF/NIH HHS/United States ; D15D18000410001//Italian Ministry for Education, University and Research/ ; CAN2019/0343//Swedish Cancer Society/ ; R01CA114478/GF/NIH HHS/United States ; 71081//Norwegian Cancer Society/ ; R01CA104786/GF/NIH HHS/United States ; 2010/808//Swedish Cancer Society/ ; S-12/07//Nordic Cancer Union/ ; C588/A19167//Cancer Research UK Programme/ ; HHSN26120130003C/GF/NIH HHS/United States ; U01 CA164947/CA/NCI NIH HHS/United States ; 2019/011633//Swedish Research Council/ ; 270870//Norwegian Cancer Society/ ; //Movember Foundation/ ; R01CA085914/GF/NIH HHS/United States ; U01CA164947/GF/NIH HHS/United States ; ZO1-CP-10144//National Cancer Institute, Intramural Research Program/ ; 2011/484//Swedish Cancer Society/ ; P30CA016520/GF/NIH HHS/United States ; 2008/708//Swedish Cancer Society/ ; 418975//Norwegian Cancer Society/ ; Dell'ElceFamilyFund//Princess Margaret Cancer Foundation/ ; 70113348//Deutsche Krebshilfe/ ; 223319//Norwegian Cancer Society/ ; },
abstract = {BACKGROUND: The Testicular Cancer Consortium (TECAC) was established in 2012 and is comprised of researchers from over 25 centers in Europe and North America. TECAC's overarching goal is to investigate the genetic susceptibility of testicular germ cell tumors (TGCT) to better understand their biology, impact prevention strategies, and inform treatment decisions.

OBJECTIVES: To provide an overview of TECAC genetic and phenotypic holdings.

MATERIALS AND METHODS: TECAC has composed by-laws describing the consortium structure and governance, codified the processes for manuscript development and data transfer, and developed guidance for the transfer of biological samples and access to data.

RESULTS: TECAC has assembled a vast amount of genetic information on males with TGCT-including SNP-array data on over 13,500 cases, whole-exome sequencing data on over 4500 cases, and low-pass whole-genome sequence data on over 2700 cases. Genetic information on males without TGCT (controls) is derived from studies designed to assess risk factors for TGCT and from publicly available resources. When available, corresponding phenotypic information is collected and harmonized. Fifteen publications have resulted from genetic and phenotypic information curated by TECAC.

DISCUSSION: The sharing of genetic and phenotypic data by TECAC centers to inform large studies of TGCT susceptibility has led to novel insights into the genetic architecture of this cancer, including the roles of genes involved in male germ cell development, sex determination, chromosomal segregation, and RNA transcription. These findings would not have been achievable by individual centers or smaller collaborative efforts.

CONCLUSION: We invite investigators from any discipline who have access to collections of germline DNA, somatic cell DNA, or genomic information on males with TGCT to consider joining TECAC to further strengthen our efforts to reduce the global burden of TGCT.},
}

@article {pmid41484087,
year = {2026},
author = {Kinsella, S and Evandy, CA and Cooper, K and Kirsche, E and Warren, M and deRoos, P and Cardinale, A and Iovino, L and Granadier, D and Smith, CW and Hopwo, K and Sullivan, LB and Velardi, E and Dudakov, JA},
title = {Damage-induced pyroptosis drives endogenous thymic regeneration by activating the purinergic receptor P2Y2.},
journal = {Cell death & disease},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41419-025-08345-x},
pmid = {41484087},
issn = {2041-4889},
support = {ASH Scholar//American Society of Hematology (ASH)/ ; R01-HL145276//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01-HL165673//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U01-AI70035//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
abstract = {T cell recovery is critical following damage, such as hematopoietic cell transplantation (HCT), with increased reconstitution associated with improved clinical outcomes. Endogenous thymic regeneration, a crucial process for restoring immune competence following cytoreductive therapies such as HCT conditioning, is often delayed, limiting T cell reconstitution. Fully understanding the molecular mechanisms driving regeneration is therefore crucial for uncovering therapeutic targets that can be exploited to enhance thymic function. Here, we identified that CD4+ CD8+ thymocytes rapidly and acutely undergo lytic cell death, specifically pyroptosis, following acute damage caused by ionizing radiation, and release damage-associated molecular patterns (DAMPS) into the thymic microenvironment, including ATP. Extracellular ATP stimulates the P2Y2 purinergic receptor on thymic epithelial cells (TECs)-a stromal cell crucial for supporting T cell development-resulting in the upregulation FOXN1, the master TEC transcription factor. Targeting the P2Y2 receptor with a P2Y2 agonist, UTPγS, promotes rapid regeneration of the TEC compartment in vivo following acute damage. These findings reveal a novel damage-sensing mechanism employed by the thymus where thymocytes adopt an alternative cell death mechanism which promotes thymic repair via P2Y2 signaling in TECs. This work identifies P2Y2 as a promising therapeutic target for enhancing thymus regeneration and improving immune recovery after HCT.},
}

@article {pmid41484084,
year = {2026},
author = {Zhang, S and Tang, TH and Kinsella, S and Mazziotta, F and Schweizer, MT and McAfee, MS and Munkhbat, A and Su, Y and Voillet, V and Martin, LE and Smith, CW and Asano, Y and Hailemariam, M and Bakhtiari, J and Lee, B and Yeung, C and Chen, H and Rizzi, AM and Chen, DG and Furiya, K and Horst, N and Zhang, T and Le, P and McKenna, K and Oda, SK and Rongvaux, A and Greenberg, PD and Schmitt, TM and Chapuis, AG},
title = {A CD8αβ co-receptor modified to contain an intracellular CD28 signaling tail enhances TCR-engineered T cell function independent of solid-tumor-associated co-stimulatory ligands.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-67446-5},
pmid = {41484084},
issn = {2041-1723},
support = {P01CA225517//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P01CA18029-41//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
abstract = {Adoptive transfer of T cells engineered with tumor-specific T cell receptors (TCRs) has shown limited efficacy in solid tumors, hindered by insufficient persistence, tumor trafficking, and dependence on tumor-associated co-stimulatory ligands. In a phase I trial (NCT04639245) for patients with metastatic MAGE-A1-expressing tumors and adequate organ function; one participant received treatment, which was well-tolerated. In this case and NSG murine models, infusion of CD4/CD8 T cells co-expressing a class-I MAGE-A1-specific TCR and CD8αβ, failed to control tumor progression. To enhance function downstream of TCR signaling, here we investigate the adaptability of TCR components to synthetic modification. Leveraging the obligate co-expression of CD8αβ required for class-I TCR function in CD4 T cells, we identify CD8β as a tractable site for engineering without loss of function. In vitro screening demonstrates incorporation of the CD28 intracellular tail, yielding a CD8/CD28 chimeric co-receptor, most effectively enhances cytokine production, T cell persistence, and tumor control in immunodeficient murine models while preserving stem-like transcriptional features compared to native CD8β. Further rational modification of the CD28 binding motifs improves tumor control in vivo with increased intratumoral accumulation and reduced exhaustion. This benefit also extends to PRAME and WT1-specific TCRs in vitro supporting generalizability.},
}

@article {pmid41482160,
year = {2025},
author = {Masurekar, AN and Burkett, KM and Rahgozar, A and Walter, RB and Othus, M and Abrol, K and Mortezaagha, P and Thyagu, S and Nampoothiri, RV and Kennah, M and Kekre, N and Giguere, P and Abduallah, Y and Atkins, H and Cieniak, C and Berardi, P and Ramsay, T and Mallick, R and Carrier, M and Bredeson, C and Allan, D},
title = {Defining the Limits of Pre-Transplant Risk Prediction in AML: Evidence from Machine Learning and Regression Models.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.12.996},
pmid = {41482160},
issn = {2666-6367},
abstract = {BACKGROUND: Allogeneic hematopoietic cell transplantation (allo-HCT) for acute myeloid leukemia (AML) is associated with considerable morbidity and mortality. Machine learning (ML) techniques are increasingly applied to predict outcomes in medicine.

OBJECTIVES: To evaluate the role of ML in predicting overall survival (OS) after allo-HCT for AML and compare ML with traditional Cox regression.

STUDY DESIGN: Using an internal cohort of 2,253 patients and 14 pre-allo-HCT variables, we developed three models: Cox regression with time-varying coefficients (Cox-TVC), Elastic-net Cox Regression (Cox-EN), and Random Survival Forest (RSF). Performance was evaluated using multiple metrics including C-index, net reclassification improvement (NRI) and decision curve analysis (DCA). Patients were stratified into tertiles of model predicted 24-month mortality. External validation was performed in 252 single-center patients with uniform measurable residual disease (MRD) assessment.

RESULTS: Model-derived risk scores strongly correlated (r=0.886-0.963). Across models, age ≥ 60 years, MRD positivity, and adapted European LeukemiaNet (aELN) adverse risk were the strongest predictors. Effects of age attenuated over time (HR for age ≥60: 2.59 [95% CI: 1.54-4.35] at 1 year, 1.92 [95% CI: 1.04-3.56] at 5 years). Compared with Hematopoietic Cell Transplant Comorbidity-Index (HCT-CI) and aELN, models improved risk stratification (NRI: 31-44%, p <0.001). Discrimination remained modest but was higher in external cohort compared with internal cohort (0.69-0.71 versus 0.60-0.61), likely reflecting uniform MRD assessment. At a 25% risk threshold for clinical decision-making, models identified approximately 1 additional high-risk patient per 100 versus HCT-CI, or aELN. At 2-years, 25-27% of patients categorized as low-risk had died, while 44.6-47.2% categorized as high-risk were alive.

CONCLUSIONS: ML approaches improved risk stratification over HCT-CI and aELN but performed comparably with Cox model. Individual outcome prediction using static pre-transplant models remained modest. Progress will require MRD standardization, richer data. and dynamic peri- and post-transplant modeling.},
}

@article {pmid41482012,
year = {2025},
author = {Dussault, N and Ma, J and Ivey, N and Bernal, T and Clifton, D and Jones, CA and Santivasi, WL},
title = {Caring through Complexity: Developing a Palliative Care Opioid and Stimulant Use Disorder Workflow.},
journal = {Journal of pain and symptom management},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jpainsymman.2025.12.017},
pmid = {41482012},
issn = {1873-6513},
abstract = {CONTEXT: Caring for individuals with serious illness and opioid or stimulant use disorder (OUD/STuD) is complex. Palliative care (PC) providers often lack addiction medicine training and report discomfort managing this population.

OBJECTIVES: This quality improvement project aimed to assess PC team comfort, provide targeted education, and create an institutional PC workflow around caring for individuals with OUD/STuD.

METHODS: This project was conducted within an academic health system's PC program. A pre-intervention survey assessed baseline comfort caring for individuals with OUD/StUD. The intervention included the development and dissemination of 1) an evidence-based, locally adapted workflow guiding opioid prescribing and clinic management protocols stratified by substance use risk and 2) educational sessions on buprenorphine for pain, substance use risk assessment, and safe opioid management. During implementation, the workflow was iteratively updated based on challenges identified in patient cases (i.e., diagnostic uncertainty, unexpected urine toxicology screens). A post-intervention survey assessed changes in provider comfort after implementation.

RESULTS: Of the 27 individuals who completed the pre-survey (response rate 73%), 66% felt uncomfortable overall caring for individuals with OUD/StUD; among prescribers, only 19% felt comfortable managing opioids for this population. The workflow was applied to ten patients (ages 38-76; all with cancer). In the post survey (n=23, response rate 62%), fewer respondents (35%) felt uncomfortable overall caring for individuals with OUD/StUD and a majority of prescribers (52%) felt comfortable managing opioids for this population.

CONCLUSION: Developing evidence-based, locally adapted workflows and educational sessions can improve PC provider comfort around caring for patients with OUD/StUD.},
}

@article {pmid41478442,
year = {2025},
author = {Kotini-Shah, P and Duran-Luciano, P and Kansal, M and Nasrollahi, F and Lee, UJ and Yuan, Y and Rangel, MO and Kaplan, R and Ponce, SG and Shah, SJ and Cai, J and Bilsker, MS and Pu, M and Hurwitz, BE and Rodriguez, CJ},
title = {Global Longitudinal Strain Reference Values in the Hispanic/Latino Population: Echocardiographic Study of Latinos (ECHO-SOL).},
journal = {The American journal of cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.amjcard.2025.12.014},
pmid = {41478442},
issn = {1879-1913},
abstract = {Global Longitudinal Strain (GLS) is a sensitive measure for detecting early cardiac dysfunction, but prone to variability by age, race/ethnicity, and sex. To date, GLS has not been described in Hispanics/Latinos, nor has GLS been associated with heart failure risk factors. Data from the Echocardiographic-Study of Latinos, a population-based study of Hispanics/Latinos in the United States, was used. A reference healthy sample was used to define the 95[th]-percentile lower limit of normal GLS value of -14.2% which was applied to the target population to describe the distribution of GLS across age, gender and Hispanic/Latino background groups. The proportion of normal/abnormal GLS and left ventricular ejection fraction (LVEF) are described; as well as the proportion of abnormal GLS across prevalent heart failure risk factors (hypertension, obesity, and diabetes). Survey statistics and weighted frequencies were used in all analyses. The study sample consisted of 1,818 adult participants (mean age 56.4 years; 42.6% female). The overall ECHO-SOL target population had a mean GLS of -17.6% with 12.1% having prevalent abnormal GLS. GLS was significantly worse in men than women and abnormal GLS was more prevalent among individuals of Cuban background than any other Hispanic/Latino background group. More than half (56.4%) of individuals with abnormal GLS had values within the normal LVEF range and there was worsening GLS values with increasing heart failure risk factor burden (p<0.01). In conclusion, our study establishes the first Hispanic/Latino-specific GLS reference values, emphasizing the importance of representative populations in the derivation of myocardial deformation thresholds. Abnormal GLS was prevalent among Hispanics/Latinos and increasing heart failure risk factor burden correlated with worsening GLS, reinforcing the role of risk factors in early cardiovascular risk assessment.},
}

@article {pmid41478324,
year = {2025},
author = {Ahmed, S and Kumar, A and Carpenter, P and Herrera, A and Kelly, K and Pinnix, C and Rutherford, S and Grover, N and Evens, A and Lynch, R and Kenkre, V and Merryman, R and Sauter, C and Nishihori, T and Moskowitz, A and Awan, F and Svoboda, J and Winter, J and Allen, P and Ermoian, R and Ansell, S and Aljuhaishi, T and Nieto, Y and Hamadani, M and Perales, MA},
title = {ASTCT Clinical Practice Recommendations for Transplantation in Classical Hodgkin Lymphoma.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.12.944},
pmid = {41478324},
issn = {2666-6367},
abstract = {Autologous hematopoietic cell transplantation (auto-HCT) remains the standard therapeutic approach for patients with chemotherapy-sensitive relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL). Over the past decade, the therapeutic landscape for cHL has evolved substantially with the introduction of novel agents, including antibody-drug conjugates and immune checkpoint inhibitors, which have demonstrated significant efficacy in the relapsed setting and are now incorporated into frontline treatment regimens. These advances have not only expanded the armamentarium available for disease management but have also led to improved long-term outcomes, raising important considerations regarding the optimal sequencing of therapies and the evolving role of transplantation in the modern treatment paradigm. Hematopoietic cell transplantation (HCT) remains a cornerstone in the management of cHL; however, consensus is lacking regarding the optimal timing of auto-HCT, the sequencing and integration of novel therapeutic agents, the potential role of maintenance therapy following auto-HCT, and the appropriate indications and timing for allogeneic (allo) HCT. Therefore, the American Society of Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines undertook a project to formulate consensus recommendations to address this unmet need. The RAND-modified Delphi method was used to generate 20 consensus statements with key recommendations as follows: (1) use of auto-HCT consolidation after salvage therapy in the first relapse setting, for patients with chemotherapy-sensitive R/R cHL in complete response; (2) preferred use of pre-HCT salvage therapy regimens with novel agents; (3) consultation for allo-HCT in eligible patients who have disease relapse after auto-HCT; (4) guidance regarding optimal stem cell donor source; (5) selection of conditioning regimen for both auto-HCT and allo-HCT; and (6) preferred graft versus host disease prophylaxis in the modern era. These clinical practice recommendations serve as a tool to guide clinical management of R/R cHL.},
}

@article {pmid41477868,
year = {2026},
author = {Lee, J and Jung, H and Kim, EG and Ahn, J and Haffner, MC and Nelson, PS and Kim, KP and Lee, JK and Yi, EC and Kim, KM},
title = {Phenotypic discovery and therapeutic evaluation of an ITGA3B1-targeting antibody-drug conjugate for bladder cancer.},
journal = {Science advances},
volume = {12},
number = {1},
pages = {eady0041},
pmid = {41477868},
issn = {2375-2548},
mesh = {*Urinary Bladder Neoplasms/drug therapy/metabolism/pathology ; Humans ; *Immunoconjugates/pharmacology/therapeutic use/chemistry ; Animals ; Cell Line, Tumor ; Mice ; Xenograft Model Antitumor Assays ; *Integrin alpha3beta1/antagonists & inhibitors/metabolism/immunology ; Oligopeptides/pharmacology/chemistry ; Proteomics ; Drug Discovery ; Phenotype ; Integrin alpha3 ; },
abstract = {Antibody-drug conjugates (ADCs) require antibodies with both high specificity and efficient internalization, features often overlooked by conventional discovery pipelines that rely on preselected antigens and recombinant proteins. Here, we describe an integrated phenotypic platform that combines target-unbiased live-cell biopanning with in situ chemical cross-linking and mass spectrometry to concurrently identify internalizing antibodies and their membrane-bound cognate antigens in a native cellular context. Using this approach, we identified 2E7, an antibody with rapid internalization and specificity for the integrin α3β1 (ITGA3B1) heterodimer. Integrated transcriptomic and proteomic analyses revealed pronounced overexpression of ITGA3B1 across multiple solid tumors, with particularly elevated levels in aggressive bladder cancer subtypes. A 2E7-MMAE (monomethyl auristatin E) ADC exhibited potent, dose-dependent antitumor activity in bladder cancer xenograft models, leading to tumor regression and prolonging survival. This study establishes a generalizable framework for function-first ADC discovery and nominates ITGA3B1 as a promising therapeutic target in bladder cancer.},
}

*Urinary Bladder Neoplasms/drug therapy/metabolism/pathology
Humans
*Immunoconjugates/pharmacology/therapeutic use/chemistry
Animals
Cell Line, Tumor
Mice
Xenograft Model Antitumor Assays
*Integrin alpha3beta1/antagonists & inhibitors/metabolism/immunology
Oligopeptides/pharmacology/chemistry
Proteomics
Drug Discovery
Phenotype
Integrin alpha3

@article {pmid41476111,
year = {2025},
author = {Van Buren, E and Zhang, Y and Li, X and Selvaraj, MS and Li, Z and Zhou, H and Palmer, ND and Arnett, DK and Blangero, J and Boerwinkle, E and Cade, BE and Carlson, JC and Carson, AP and Chen, YI and Curran, J and Duggirala, R and Fornage, M and Franceschini, N and Graff, M and Gu, C and Guo, X and He, J and Heard-Cosa, N and Hou, L and Hung, YJ and Kalyani, RR and Kardia, SLR and Kenny, E and Kooperberg, C and Kral, BG and Lange, L and Levy, D and Li, C and Liu, S and Lloyd-Jones, D and Loos, RJF and Manichaikul, AW and Martin, LW and Mathias, R and Minster, RL and Mitchell, BD and Mychaleckyj, JC and Naseri, T and North, K and O'Connell, J and Perry, JA and Peyser, PA and Psaty, BM and Raffield, LM and Vasan, RS and Redline, S and Reiner, AP and Rich, SS and Smith, JA and Spitzer, B and Tang, H and Taylor, KD and Tracy, R and Viali, S and Yanek, L and Zhao, W and , and Rotter, JI and Peloso, GM and Natarajan, P and Lin, X},
title = {cellSTAAR: incorporating single-cell-sequencing-based functional data to boost power in rare variant association testing of noncoding regions.},
journal = {Nature methods},
volume = {},
number = {},
pages = {},
pmid = {41476111},
issn = {1548-7105},
support = {R35-CA197449//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; U19-CA203654//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; U01-HG012064//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; U01-HG009088//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; R01HL173044//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92021F00229//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92021F00229//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; U01- HL072524//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL104135-04S1//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; U01-HL054472//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; U01-HL054473//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; U01-HL054495//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; U01-HL054509//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL055673-18S1//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; HHSN268201700001I/HL/NHLBI NIH HHS/United States ; HHSN268201700002I/HL/NHLBI NIH HHS/United States ; HHSN268201700005I/HL/NHLBI NIH HHS/United States ; HHSN268201700004I/HL/NHLBI NIH HHS/United States ; R01-HL153805//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R03- HL154284//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00001/HL/NHLBI NIH HHS/United States ; HHSN268201500003I/HL/NHLBI NIH HHS/United States ; N01-HC-95159//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00005/HL/NHLBI NIH HHS/United States ; N01-HC-95160//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00002/HL/NHLBI NIH HHS/United States ; N01-HC-95161//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00003/HL/NHLBI NIH HHS/United States ; N01-HC-95162//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00006/HL/NHLBI NIH HHS/United States ; N01-HC-95163//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00004/HL/NHLBI NIH HHS/United States ; N01-HC-95164//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00007/HL/NHLBI NIH HHS/United States ; N01-HC-95165//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; N01-HC-95166//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; N01-HC-95167//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; N01-HC-95168//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; N01-HC-95169//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071051//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071205//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01- HL071250//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071251//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071258//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071259//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; HHSN268201600018C/HL/NHLBI NIH HHS/United States ; HHSN268201600001C/HL/NHLBI NIH HHS/United States ; HHSN268201600002C/HL/NHLBI NIH HHS/United States ; HHSN268201600003C/HL/NHLBI NIH HHS/United States ; HHSN268201600004C/HL/NHLBI NIH HHS/United States ; HL105756//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 1R35-HL135818//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01- HL113338//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; HL046389//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00001/HL/NHLBI NIH HHS/United States ; HHSN268201500003I/HL/NHLBI NIH HHS/United States ; N01-HC-95159//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00003/HL/NHLBI NIH HHS/United States ; N01-HC-95162//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00006/HL/NHLBI NIH HHS/United States ; N01-HC-95163//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00004/HL/NHLBI NIH HHS/United States ; N01-HC-95164//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00007/HL/NHLBI NIH HHS/United States ; N01-HC-95165//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; N01-HC-95166//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; N01-HC-95167//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; N01-HC-95168//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; N01-HC-95169//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071051//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071205//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01- HL071250//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071251//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071258//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071259//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL142711//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL127564//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL142711//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL127564//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; UL1-TR-000040//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; UL1-TR-001079//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; UL1-TR-001420//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; UL1-TR001881//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; UL1-TR-000040//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; UL1-TR-001079//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; UL1-TR-001420//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; UL1-TR001881//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; DK063491//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; R01-DK117445//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; DK063491//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; UL1-RR033176//U.S. Department of Health & Human Services | NIH | National Center for Research Resources (NCRR)/ ; UL1-RR033176//U.S. Department of Health & Human Services | NIH | National Center for Research Resources (NCRR)/ ; R01-MD012765//U.S. Department of Health & Human Services | NIH | National Institute on Minority Health and Health Disparities (NIMHD)/ ; },
abstract = {Understanding how rare genetic variants influence complex traits remains a major challenge, particularly when these variants lie in noncoding regions of the genome. The effects of variants within candidate cis-regulatory elements (cCREs) often depend on the cell type, making interpretation difficult. Here we introduce cellSTAAR, which integrates whole-genome sequencing data with single-cell assay for transposase-accessible chromatin using sequencing data to capture variability in chromatin accessibility across cell types via the construction of cell-type-specific functional annotations and regulatory elements. To reflect the uncertainty in cCRE-gene linking, cellSTAAR uses a comprehensive strategy to link cCREs to their target genes. We applied cellSTAAR to data from the Trans-Omics for Precision Medicine consortium (n ≈ 60,000) and replicated our findings using the UK Biobank (n ≈ 190,000). Across four lipid traits, cellSTAAR improved the detection of biologically meaningful associations and enhanced biological interpretability. These results demonstrate the potential of cell-type-aware approaches to boost discovery in rare variant whole-genome sequencing association studies.},
}

@article {pmid41474700,
year = {2025},
author = {Kwendakwema, CN and Eastment, MC and Wanje, G and Richardson, BA and Mwaringa, E and Sherr, K and Mandaliya, KN and Barnabas, RV and Jaoko, W and McClelland, RS},
title = {Cross-sectional study evaluating organizational climate, change commitment, and change efficacy for predicting family planning clinics' success in increasing HIV counseling and testing in Mombasa, Kenya.},
journal = {PLOS global public health},
volume = {5},
number = {12},
pages = {e0005542},
pmid = {41474700},
issn = {2767-3375},
abstract = {Increasing HIV testing and counselling (HTC) is a first step to reducing HIV transmission. Implementing HTC in family planning (FP) clinics has been proposed to increase HIV testing coverage in at-risk populations. The Systems Analysis and Improvement Approach (SAIA) was used to improve HTC rates in FP clinics in Mombasa, Kenya. This hypothesis-generating exploratory analysis evaluated the associations between organizational climate characteristics, organizational readiness for implementing change, and successful implementation of HTC. Surveys were conducted with clinic managers and staff from FP clinics implementing SAIA to increase HTC. Likert-style questions were used to characterize organizational climate metrics and organizational readiness for implementing change (ORIC). Linear regression was performed to examine the association between organizational climate metrics, ORIC domains, and two FP client outcomes: 1) percentage of clients receiving pre-HIV test counseling, and 2) percentage of clients tested for HIV. Eleven clinic staff and 10 clinic managers completed the surveys. For clinic staff, higher innovation and flexibility scores were associated with higher change commitment (β = 0.20, CI 0.09-0.31, p = 0.001) and change efficacy (β = 0.17, CI 0.07-0.26, p = 0.002). Higher clinic manager scores for innovation and flexibility were associated with a higher change commitment (β = 0.44, CI 0.04-0.84, p = 0.03). Additionally, clinic managers' scores for management support (β = 0.25, CI 0.06-0.45, p = 0.01), commitment to facility (β = 0.78, CI 0.60-0.96, p = 0.001), and relative priority (β = 0.24, CI 0.08-0.39, p = 0.004) were positively associated with higher change commitment and change efficacy. In contrast, clinic managers' scores for tradition were negatively associated with change commitment (β = -0.38, CI -0.75-0.01, p = 0.05). Clinic staff perceptions of management support were positively associated with the proportion of clients counseled for HIV testing (β = 1.20, CI 0.08-2.32, p = 0.04). Support from leadership and innovation/flexibility are important predictors of change commitment and change efficacy. Strong management support may increase the likelihood of successful implementation of SAIA to improve HTC.},
}

@article {pmid41473276,
year = {2025},
author = {Nutt, WS and Kluesner, MG and Bingham, E and Gad, E and Miller, D and Zepeda, V and Snyder, AJ and Marsh, SA and Liudahl, SM and Hoffman, M and LeBlanc, L and Volfbeyn, ME and Garrison, SM and Sarvothama, M and Barry, KC and Headley, MB and Marcondes, M and Srivastava, S},
title = {NKTR-255, a polymer-conjugated IL-15, synergizes with CAR-T cell therapy to activate endogenous anti-tumor immunity and improve tumor control.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41473276},
issn = {2692-8205},
abstract = {CAR-T cells have yet to show widespread efficacy in solid tumors due in part to their poor persistence and loss of function in the tumor microenvironment. Further, heterogenous expression of most CAR target antigens in solid tumors can lead to escape of antigen-null tumors that resist CAR-T killing. Strategies to cooperatively boost both CAR-T and endogenous anti-tumor immunity could curb tumor escape and may be critical for achieving durable efficacy in cancer patients. NKTR-255 is a polymer-conjugated IL-15 with extended half-life that can boost endogenous T and NK cells, as well as CD19 CAR-T activity in B cell malignancies. However, whether NKTR-255 is sufficient to overcome CAR-T dysfunction in the suppressive solid tumor microenvironment, and how NKTR-255 and CAR-Ts together re-shape endogenous anti-tumor immunity, is not known. Using an autochthonous mouse model of ROR1[+] lung adenocarcinoma, we show that NKTR-255 significantly boosted accumulation, reduced exhaustion, and improved function of tumor-infiltrating CAR-T cells. Compared with NKTR-255 or CAR-T treatment alone, combination of NKTR-255 and CAR-T therapy synergistically increased tumor-infiltrating CD11b[+] cytotoxic NK cells, activated dendritic cells, and endogenous tumor-specific T cells that preserved a PD-1[+]Tcf1[+] stem-like phenotype. Consequently, NKTR-255 and CAR-T combination therapy induced complete elimination of ROR1[+] tumor and significantly improved survival, with enhanced tumor control dependent on activity of both CAR-Ts and endogenous T cells. Altogether, our data suggest that combining NKTR-255 with CAR-T therapy is a promising strategy to enhance both CAR-T and endogenous anti-tumor immunity to promote coordinated control of aggressive tumors.},
}

@article {pmid41472424,
year = {2025},
author = {Wallace, PK and Jellison, ER and Thornton, S and Kluepfel, K and Back, J and Beadnell, TC and Bebes, A and Behrends, J and Belkina, AC and Black, M and Bogdanoski, G and Bollati-Fogolín, M and Bonte, S and Van der Borght, K and Brinkman, RR and Brundage, K and Bushnell, T and Chiu, DT and Chow, N and Ciccolella, CO and Cochran, M and Czechowska, K and Dagla, K and Daniel, B and de la Cruz, G and Van Duyse, J and Font, LF and Fornas, Ò and Garcia-Garcia, S and Gardner, R and Van Gassen, S and Gimenes, D and Grenfell, R and Grider-Hayes, MJ and Grose, R and Hall, C and Hally, KE and Hameetman, M and Hogg, K and Houston, J and Irish, JM and Isterdael, GV and Jaimes, M and Janetzki, S and Kim, C and Koladiya, A and Lamote, J and Lannigan, J and Leconte, J and Litwin, V and Longhini, A and Loof, N and Lozano-Andrés, E and Lundsten, K and Mage, P and Mair, F and Martins, CG and McCausland, M and McGuire, HM and Meskas, J and Murphy, W and Nolan, J and Oliveira, B and Ordoñez-Rueda, D and Orlowski-Oliver, E and Petersen, CC and Poulton, NJ and Putri, G and Quadrini, KJ and Ramasz, B and Ruhrmund, D and Singh, VV and Small, SJ and Smith, NJ and Spidlen, J and Stegen, C and Tak, T and Thompson, S and Thomson, M and Vocelle, D and Walker, RV and Walsh, RE and Wang, L and Wang, YF and Weglarz, M and Winker, M and Wood, JCS and Woolard, S and Yeh, NY and Yuecel, R and Rajwa, B},
title = {Cyt-Geist: Current and Future Challenges in Cytometry: Reports of the CYTO 2025 Conference Workshops.},
journal = {Cytometry. Part A : the journal of the International Society for Analytical Cytology},
volume = {},
number = {},
pages = {},
doi = {10.1002/cytoa.70002},
pmid = {41472424},
issn = {1552-4930},
}

@article {pmid41470899,
year = {2025},
author = {Kadro, ZO and Rillamas-Sun, E and Langley, BO and Meisner, A and Contento, I and Koch, PA and Ogden Gaffney, A and Hershman, DL and Greenlee, H},
title = {Associations Between the Food Environment and Food Insecurity on Fruit, Vegetable, and Nutrient Intake, and Body Mass Index, Among Urban-Dwelling Latina Breast Cancer Survivors Participating in the &iexcl;Mi Vida Saludable! Trial.},
journal = {Nutrients},
volume = {17},
number = {24},
pages = {},
pmid = {41470899},
issn = {2072-6643},
support = {R01 CA186080/CA/NCI NIH HHS/United States ; R01 CA186080-02S1/CA/NCI NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; },
mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; *Body Mass Index ; *Breast Neoplasms ; *Cancer Survivors/statistics & numerical data ; *Diet ; *Food Insecurity ; Food Supply ; Fruit ; *Hispanic or Latino/statistics & numerical data ; Urban Population ; Vegetables ; },
abstract = {Background: Socioeconomic disparities may drive cancer inequities in Hispanic/Latino populations. We examined associations of perceived access to healthy foods (AHF) and food insecurity (FI) with diet and body mass index (BMI) changes in Latina breast cancer (BC) survivors. Methods: Latina BC survivors in a 12-month intervention trial aiming to increase fruit/vegetable intake and physical activity were analyzed. AHF was from a modified, validated neighborhood environment scale and dichotomized (low-medium vs. high). FI was defined as eating less and/or going hungry due to a lack of money. AHF and FI surveys were self-reported. Outcomes included dietary intake, diet quality, and BMI. Fruit/vegetable intake was log-transformed. Relationships between AHF and FI and changes in diet and BMI were evaluated using generalized estimating equations. Results: Of women with AHF data (n = 86), 58% reported low-medium access and 42% reported high access. Fruit/vegetable (FV) intake declined overall from baseline to 12 months, with greater reductions among low-medium AHF women (-32%, 95% CI: -51%, -7%) compared with high AHF women (-17%, 95% CI: -40%, +13%). Statistically significant 12-month decreases in total calories, carbohydrates, sugars, and fat occurred in low-medium AHF women but not high AHF women, and changes in total energy density, carbohydrates, sugars, and BMI at 12 months were statistically significantly different between women with low-medium AHF and women with high AHF, p ≤ 0.05. Among 157 women, 23% reported FI. Reductions in fruit/vegetable intake were larger in women with FI (-39%, 95% CI: -57%, -14%) than in women without FI (-10% reductions, 95% CI: -25%, +8%) and between-group differences were significant at both 6 and 12 months, p ≤ 0.05. Most diet measures decreased for both FI and non-FI women, with greater decreases among those with FI. Conclusions: Latina BC survivors with FI or perceived limited AHF experienced greater declines in indicators of healthy diets including FV intake. Future interventions should integrate strategies to measure AHF and FI to address disparate access to healthy food options.},
}

Adult
Aged
Female
Humans
Middle Aged
*Body Mass Index
*Breast Neoplasms
*Cancer Survivors/statistics & numerical data
*Diet
*Food Insecurity
Food Supply
Fruit
*Hispanic or Latino/statistics & numerical data
Urban Population
Vegetables

@article {pmid41469386,
year = {2025},
author = {Li, B and Lin, R and Ni, T and Yan, G and Burns, M and Li, JJ and Yao, Z},
title = {CellScope: high-performance cell atlas workflow with tree-structured representation.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-67890-3},
pmid = {41469386},
issn = {2041-1723},
support = {A-8001562-00-00//Ministry of Education - Singapore (MOE)/ ; A-0008520-00-00//Ministry of Education - Singapore (MOE)/ ; A-8002931-00-00//Ministry of Education - Singapore (MOE)/ ; },
abstract = {Single-cell sequencing enables comprehensive profiling of individual cells, revealing cellular heterogeneity and function with unprecedented resolution. However, current analysis frameworks lack the ability to simultaneously explore and visualize cellular hierarchies at multiple biological levels. To address these limitations, we present CellScope, a promising framework for constructing high-resolution cell atlases at multiple clustering levels. CellScope employs a two-stage manifold fitting process for gene selection and noise reduction, followed by agglomerative clustering, and integrates UMAP visualization with hierarchical clustering to intuitively represent cellular relationships simultaneously at multiple levels-such as cell lineage, cell type, and cell subtype levels. Compared to established pipelines such as Seurat and Scanpy, CellScope comprehensively improves clustering performance, visualization clarity, computational efficiency, and algorithm interpretability, while reducing dependence on hyperparameters across a multitude of single-cell datasets. Most importantly, it can reveal biological insights that other contemporary methods are unable to detect, thereby deepening our understanding of cellular heterogeneity and function, and potentially informing disease research.},
}

@article {pmid41468926,
year = {2025},
author = {Rangarajan, HG and Chellapandian, D and Atshan, R and Ahn, KW and Kumar, S and Knight, TE and Leung, W and Ganguly, S and Williams, KM and Shah, NN and Bhatt, NS and Lust, H and Prestidge, T and Brown, VI and Hayashi, RJ and Choe, M and Saad, A and Bidgoli, A and Thakar, MS and Wirk, B and MacMillan, ML and Lalefar, NR and Hematti, P and Schultz, KR and Phillips, CL and Mehta, PA and Qayed, M and Sharma, A and Broglie, L and Satwani, P},
title = {Impact of Extramedullary Disease at Diagnosis on Outcomes Post Allogeneic Hematopoietic Cell Transplant in Children and Young Adults with Acute Myeloid Leukemia: A CIBMTR Report.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.12.990},
pmid = {41468926},
issn = {2666-6367},
abstract = {BACKGROUND: Conflicting reports exist regarding the impact of extramedullary disease (EMD) at diagnosis upon outcomes after allogeneic hematopoietic cell transplantation (HCT) in children and young adults with acute myeloid leukemia (AML).

OBJECTIVES AND STUDY DESIGN: We retrospectively analyzed the effect of EMD at diagnosis on post-HCT outcomes in a large cohort of children and young adults (21 and younger) who had AML and received their first myeloablative allogeneic HCT for AML during 2008-2019 (N = 938; 52% males). Data were obtained from the Center for International Blood and Marrow Transplant Research database. Patients were grouped based on EMD at diagnosis as bone marrow (BM) involvement only (Group I; n = 630); BM + central nervous system (CNS) involvement (Group II; n = 212), and BM + other EMD ± CNS (Group III n = 96). All patients were in a morphologic complete remission (CR) with no evidence of EMD pre-HCT. Outcomes compared included 3-year progression-free survival (PFS), overall survival (OS), non-relapse mortality (NRM), and relapse incidence(RI).

RESULTS: Group III patients were younger at HCT (Group III median age 3, vs age 11 in Group I, and age 10 in Group II) and more often had high Pediatric Disease Risk Index scores (52% in Group III vs 22% in Group I and 25% in Group II). At a median follow-up of 70 months (range 3-155 months), the 1-year and 3-year PFS, NRM, RI, and OS were similar among all 3 groups on univariate analysis. On multivariable analysis, the presence of EMD was associated with decreased RI: Group II, with a hazard ratio (HR) of 0.70 (95% CI, 0.52-0.94; P = .020) and Group III with an HR of 0.70 (95% CI, 0.46-1.05; P = .086) compared to Group I. There was no difference in PFS (P = .21), NRM (P = .27), and OS (P = .82) among the groups.

CONCLUSION: In our study, in patients with AML who proceeded to HCT in CR, the presence of EMD at diagnosis was not associated with adverse outcomes or increased relapse risk.},
}

@article {pmid41143601,
year = {2026},
author = {Cliff, ERS and Pelaez, GD and Wan, F and Iyengar, V and Zhou, J and Chung, K and Abdel-Razeq, N and Allen, J and Major, A and Sharp, J and Epperla, N and Gould, P and Cherng, HJ and Houshyar, S and Wallace, DS and Lynch, RC and Kallam, A and Mei, MG and Merryman, RW and Fleyshman, M and Rhodes, JM and Kidwell, A and Fenske, TS and Malakhov, N and Mulvey, E and Watkins, MP and Alhaj Moustafa, M and Hilal, T and Nowakowski, GS and Wang, Y and Torka, P and Russler-Germain, DA},
title = {Cell-of-Origin Subtype Predicts Response to Polatuzumab Vedotin in Large B-cell Lymphoma.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {32},
number = {1},
pages = {159-168},
pmid = {41143601},
issn = {1557-3265},
support = {K12 CA167540/CA/NCI NIH HHS/United States ; T32 CA247815/CA/NCI NIH HHS/United States ; K12CA167540//National Cancer Institute (NCI)/ ; T32CA247815//National Cancer Institute (NCI)/ ; //Lymphoma Research Foundation (LRF)/ ; },
mesh = {Humans ; *Lymphoma, Large B-Cell, Diffuse/drug therapy/pathology/mortality ; Male ; Female ; Middle Aged ; Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; Adult ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage ; *Immunoconjugates/administration & dosage/therapeutic use ; Aged, 80 and over ; Prognosis ; Treatment Outcome ; Antibodies, Monoclonal ; },
abstract = {PURPOSE: Polatuzumab vedotin (polatuzumab) was approved for up-front treatment of diffuse large B-cell lymphoma in combination with chemoimmunotherapy (Pola-R-CHP) based on the POLARIX trial. However, when stratified by cell of origin (COO), polatuzumab seems to have greater efficacy in activated B-cell than germinal center B-cell (GCB) subtype disease. Most studies of polatuzumab used RNA expression to assess COO, whereas in routine clinical practice, the immunohistochemistry-based Hans algorithm is used.

EXPERIMENTAL DESIGN: To assess the impact of COO by immunohistochemistry on polatuzumab efficacy, we conducted a multicenter real-world study of adults with large B-cell lymphoma (LBCL) receiving polatuzumab from 2015 to 2024, split by receipt of polatuzumab in first-line versus relapsed/refractory settings. The primary endpoint was overall response rate (ORR) to polatuzumab-based treatment in GCB versus non-GCB relapsed/refractory LBCL.

RESULTS: Of 740 patients, 305 received polatuzumab in the first-line setting and 435 in the relapsed/refractory setting. In the relapsed/refractory cohort, the ORR in non-GCB versus GCB LBCL was 59.7% versus 36.3% [OR, 2.6; 95% confidence interval (CI), 1.77-3.84; P < 0.0001], with a complete response rate of 35.7% versus 17.7% (OR, 2.6; 95% CI, 1.66-4.02; P < 0.0001). Progression-free survival was longer for patients with non-GCB versus GCB COO (HR, 0.64; 95% CI, 0.5-0.83; P = 0.0006). In the first-line cohort, ORR, complete response rate, and progression-free survival were similar in non-GCB versus GCB LBCL, as hypothesized based on outcomes in the Pola-R-CHP arm of POLARIX, suggesting that the addition of polatuzumab overcomes the adverse risk of non-GCB COO in patients receiving R-CHOP.

CONCLUSIONS: Based on these data, COO classification by the Hans algorithm is a strong predictor of polatuzumab efficacy in LBCL, informing real-world treatment decisions.},
}

Humans
*Lymphoma, Large B-Cell, Diffuse/drug therapy/pathology/mortality
Male
Female
Middle Aged
Aged
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects
Adult
*Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage
*Immunoconjugates/administration & dosage/therapeutic use
Aged, 80 and over
Prognosis
Treatment Outcome
Antibodies, Monoclonal

@article {pmid41467901,
year = {2026},
author = {Hanson, F and Hickner, B and Fisher, C and Hein, H and Kukreja, K and Goss, J and Galvan, TN and Leung, DH and Banc-Husu, AM and Masand, P and Patel, K and Lopez-Terrada, D and Heczey, A and Vasudevan, S and Voeller, J},
title = {Case of Advanced Hepatocellular Carcinoma Treated With Transarterial Radioembolization and Subsequent Liver Transplantation in a 22-Month-old.},
journal = {Journal of pediatric hematology/oncology},
volume = {48},
number = {1},
pages = {e35-e40},
doi = {10.1097/MPH.0000000000003152},
pmid = {41467901},
issn = {1536-3678},
mesh = {Humans ; *Carcinoma, Hepatocellular/therapy/pathology ; *Liver Neoplasms/therapy/pathology ; *Liver Transplantation ; *Embolization, Therapeutic/methods ; Infant ; Male ; Yttrium Radioisotopes/therapeutic use ; },
abstract = {Hepatocellular carcinoma (HCC) is a rare malignancy in children, typically requiring chemotherapy, surgical resection, and/or transplant for treatment. Whether HCC arises as a novel tumor (de novo) or in the setting of chronic liver disease determines treatment strategy. We describe a case of a pediatric patient with unresectable HCC due to macrovascular invasion and tumor thrombus of the portal vein who received transarterial radioembolization (TARE) and underwent successful orthotopic liver transplantation outside of Milan criteria.},
}

Humans
*Carcinoma, Hepatocellular/therapy/pathology
*Liver Neoplasms/therapy/pathology
*Liver Transplantation
*Embolization, Therapeutic/methods
Infant
Male
Yttrium Radioisotopes/therapeutic use

@article {pmid41467111,
year = {2026},
author = {Mukhtar, RA and Flanagan, MR},
title = {Locoregional Considerations for Invasive Lobular Carcinoma.},
journal = {Current breast cancer reports},
volume = {18},
number = {1},
pages = {2},
pmid = {41467111},
issn = {1943-4588},
abstract = {PURPOSE OF REVIEW: This article summarizes recent literature on locoregional management of patients with invasive lobular carcinoma (ILC), including approaches to breast surgery, axillary management, and neoadjuvant therapy.

RECENT FINDINGS: Breast conservation therapy is safe in ILC, but has comparatively high rates of positive margins, which can be reduced by routine use of shave margins and oncoplastic surgery. Studies demonstrating the safety of de-escalation of axillary surgery have not included enough patients with ILC to draw strong conclusions; current guidelines do not support omission of sentinel node surgery in most patients with ILC. Neoadjuvant chemotherapy may improve breast conservation and increase nodal pathologic complete response in molecularly selected patients using genomic assays.

SUMMARY: The locoregional management of patients with ILC requires special considerations based on its unique features. ILC specific studies are needed to address knowledge gaps for patients diagnosed with this common tumor type.},
}

@article {pmid41466427,
year = {2025},
author = {Kareithi, T and Roche, SD and Meisner, A and Omollo, V and Ong'wen, PA and Harkey, K and Kiptinness, C and Otieno, P and Juma, L and Malen, RC and Anyona, MO and Curran, K and Banerjee, P and Gichuru, E and Asewe, M and Yu, K and Pintye, J and Mugambi, ML and Shah, PD and Sharma, M and Were, D and Ngure, K and Bukusi, EA and Ortblad, KF and , },
title = {Testing different models of pharmacy-based HIV pre- and post-exposure prophylaxis initiation and management in Kenya: protocol for a cluster-randomized controlled trial.},
journal = {Trials},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13063-025-09384-7},
pmid = {41466427},
issn = {1745-6215},
support = {INV-033052/GATES/Gates Foundation/United States ; R00 MH121166/MH/NIMH NIH HHS/United States ; },
abstract = {BACKGROUND: In Kenya, as in many African countries, private pharmacies are ubiquitous, frequently accessed, and underutilized for the delivery of HIV prevention services. Whether enabling private pharmacies to initiate and manage clients on HIV pre- and post-exposure prophylaxis (PrEP and PEP) leads to greater uptake and continuation than the current standard-pharmacy referral to clinic-based PrEP/PEP-is unknown. To address this gap and inform how private pharmacies might partner with the public sector, we are testing several models of pharmacy-delivered PrEP/PEP in comparison to the current standard.

METHODS: The Pharm PrEP cRCT is a 60-pharmacy, four-arm cluster-randomized controlled trial ongoing in Central and Western Kenya (first enrollment: 26 June 2023). Eligible pharmacies were licensed by the government, had a private room, and were willing to complete research activities (including a 3-day provider training). Study pharmacies were randomized 1:1:1:1 to (1) client-sustained delivery, in which clients pay pharmacies 250 KES (~$2 USD) per PrEP/PEP visit; (2) implementor-sustained delivery, in which clients pay nothing and implementors pay pharmacies 250 KES per PrEP/PEP visit; (3) implementor-sustained + counselor-supported delivery, in which clients pay nothing, delivery is supported by an HIV testing services (HTS) counselor, and implementors pay pharmacies 100 KES (~$1 USD) per PrEP/PEP visit; or 4) referral (control), in which clients pay nothing and implementors pay pharmacies 100 KES per referral to clinic-based PrEP/PEP. Pharmacies delivering PrEP/PEP receive supporting commodities free from government stock. Primary outcomes are PrEP initiation and continuation (any refilling) reported by clients 60 days post-enrollment; secondary outcomes include PEP initiation, PEP-to-PrEP transition, repeat PEP use, PrEP/PEP initiation, and PrEP/PEP continuation at 60 and 270 days post-enrollment. Primary analyses will compare each intervention arm to the control; secondary analyses will compare intervention arms to one another. We will additionally assess implementation outcomes (e.g., acceptability, feasibility, cost) from client and provider perspectives.

DISCUSSION: This trial will generate evidence on the potential benefits of leveraging private pharmacies for delivery of PrEP and PEP and the relative effectiveness of pharmacy delivery when subsidized by clients, implementors, and/or supported by HTS counselors. The findings may inform enabling policy and approaches for scale-up.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05842122. Registered on April 5, 2023.},
}

@article {pmid41461908,
year = {2025},
author = {, and Alberts, T and Albritton, CF and Alcazar, R and Aljabri, Z and Alvarez, M and Aradhey, A and Ayalew, M and Azizian, N and Balayah, Y and Ball, DD and Barragan, E and Beshoar, C and Best, L and Biggane, E and Biggane, J and Blick, J and Blosser, M and Brown, AK and Campbell, MC and Canizares, Z and Chanhuhwa, FN and Chen, Y and Chin, DR and Chowdhury, K and Collins, T and Compton, B and Da Silva, J and Davis, NR and DeCaro, N and Delgadillo, F and Deng, Y and Duncan, J and Egwu, AC and Ekalle, GD and Elnawam, N and Enke, R and Ewhe, N and Ferrel, MA and Fierst, J and Freymiller, G and Fuller, K and Fulton-Wright, L and Gaysinskaya, V and Gill, T and Gillespie, E and Gonzalez Moreno, P and Goodwin, S and Graham, N and Graham, ME and Graves, JL and Grob, E and Gutierrez, R and Hager, A and Hakim, ST and Harris, A and Hoffman, AM and Hoffmann, T and Horton, AM and Hughes, A and Humphries, EM and Ikechi-Konkwo, JS and Ishtiaq, A and Jackson, R and James, JR and James, K and Jamison, SA and Jimenez, A and Johnson, R and Kauffman, A and Kaur, H and Kc, K and Keeton, A and Kelly, OE and Kerr, J and Kucher, N and Kuehu, DL and Larson, WA and Lee, J and Lee, A and Leek, JT and Lemaic, D and Liburd, LE and Lopez, AF and Mahmanzar, M and Mamae, K and Manjikian, R and Marone, M and Marquez, K and Martinson, A and Mavruk Eskipehlivan, S and Medrano, A and Melendrez-Vallard, M and Meller, R and Méndez, LB and Mendez Gonzalez, MP and Mesquita, N and Miller, CM and Mohd-Ibrahim, I and Mortensen, P and Mosher, S and Muja, A and Nasrin, N and Nasu, M and Nguyen, MH and Nguyen, BT and Nishiguchi, M and O'Connor, LM and Okie, D and Olowookorun, T and Ostrovsky, A and Ozuna, K and Pandey, A and Patel, SB and Paul, G and Pawar, S and Pearson, A and Petrik, D and Platero, J and Pontino, C and Pratap, AP and Pratap, S and Qin, Y and Rai, SK and Ray, N and Repesh, E and Rhinehardt, K and Roche, B and Rodriguez, A and Roy, S and Roy, S and Sawa, A and Schatz, MC and Sen, SK and Serikawa, R and Smith, T and Smith, L and Sniezek, J and Stewart, RD and Suarez-Martinez, EB and Taganna, J and Tan, FJ and Tsotakos, N and Udolisa, N and Ulbricht, K and Veo, T and Vessio, J and Walker, L and Wang, O and Wang, Q and Wappel, R and Wesby, K and Whitford, M and Wild, N and Xie, X and Yang, H and York, S and Zirkle, L},
title = {Unearthing soil biodiversity through collaborative genomic research and education.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {41461908},
issn = {1546-1718},
support = {75N92023P00302//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 75N92022P00232//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U24HG013013//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 2000157//National Science Foundation (NSF)/ ; 1839895//National Science Foundation (NSF)/ ; 2011934//National Science Foundation (NSF)/ ; 2221924//National Science Foundation (NSF)/ ; 5T34GM151403//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; },
}

@article {pmid41461276,
year = {2025},
author = {Fan, YY and Salinas, ML and Mullens, DA and Davidson, LA and Goldsby, JS and Ivanov, IV and Jayaraman, A and Cai, JJ and Levy, L and Hullar, MA and Navarro, SL and Lampe, JW and Chapkin, RS},
title = {Pesco-vegetarian food components promote colonocyte ferroptosis in preclinical mouse models and a randomized crossover trial in healthy human adults.},
journal = {The Journal of nutrition},
volume = {},
number = {},
pages = {101287},
doi = {10.1016/j.tjnut.2025.101287},
pmid = {41461276},
issn = {1541-6100},
abstract = {BACKGROUND: Diet plays a critical role in colorectal cancer (CRC) prevention. Pesco-vegetarians, who consume both high fiber and fish containing n-3 polyunsaturated fatty acid (PUFA), have the lowest CRC risk. Ferroptosis is a form of regulated cell death characterized by the accumulation of lipid hydroperoxides that has emerged as a target for anti-cancer therapies.

OBJECTIVES: To assess the broad utility of diet modulation as a promising avenue to modulate ferroptosis in the colon.

METHODS: (i) Immortalized young adult mouse colonic epithelial cells (YAMC) were treated with control linoleic acid (LA) or docosahexaenoic acid (DHA) ± butyrate, followed by cell viability and lipid peroxidation measurements. (ii) Mice were fed diets containing fish oil and highly fermentable pectin (FP) vs. control corn oil and poorly fermentable cellulose (CC). Colons were isolated and used for bulk and single cell RNA-Seq analysis. (iii) A crossover pilot study was conducted by supplementing 30 healthy adults with soluble corn fiber (33 g/d) + fish oil (7.7 g/d n-3 PUFA) (SCF+FO) or maltodextrin + corn oil (MD+CO) for 30 d followed by a 60 d wash period and then 30 d of MD+CO or SCF+FO. Exfoliated colonocyte mRNA was isolated from stool and RNA-seq was performed for transcriptomic analysis.

RESULTS: In vitro treatment of DHA and butyrate reduced YAMC cell viability (P < 0.05), increased lipid peroxidation, a key biomarker of ferroptosis, compared to the counterpart group. In vivo FP-fed mice promoted lipid peroxidation in colonocytes relative to the control CC-fed mice (P < 0.05), and the induction of ferroptosis transcriptional networks exclusively in colonic epithelial cells. Furthermore, human subjects supplemented with SCF+FO exhibited an upregulation in intestinal ferroptosis related gene expression, as compared to similar doses of MD+CO.

CONCLUSIONS: Our findings demonstrate that dietary fish oil and fermentable fiber combination induces ferroptosis exclusively in colonocytes.

REGISTRATION: The human pilot study was registered at clinicaltrials.gov (NCT04211766).},
}

@article {pmid41446208,
year = {2025},
author = {Gómez-Garzón, C and Chen, Q and O'Brien, VP and Salama, NR},
title = {Metaplasia Enables Stomach Colonization by Fusobacterium animalis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41446208},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R00 CA263036/CA/NCI NIH HHS/United States ; R01 AI054423/AI/NIAID NIH HHS/United States ; R21 CA270512/CA/NCI NIH HHS/United States ; },
abstract = {Infection with Helicobacter pylori is the major risk factor for gastric cancer worldwide; yet the exact mechanisms behind this link remain unclear. H. pylori-associated tissue changes often disrupt the gastric microbiome, enabling secondary gastric colonization by oral bacteria. Among these secondary colonizers, Fusobacterium species have documented associations with several gastrointestinal cancers. We found that both F. animalis and F. nucleatum invade cultured human gastric adenocarcinoma cells, but F. animalis exhibited higher adherence and invasion, and hypoxic conditions promoted higher bacterial survival. Both adherence and invasion were inhibited by exogenous GalNAc, a glycan commonly observed in membrane glycoproteins of adenocarcinoma cells, and a target of the fusobacterial adhesin Fap2. Using a mouse model of gastric metaplasia, we found that F. animalis colonized gastric tissue only after metaplasia onset, growing in multispecies biofilms in the mucus layer, while F. nucleatum colonized neither healthy nor metaplastic gastric tissue. Metaplasia led to upregulation of Gal-GalNAc in the stomach, and reduced gastric acidity allowed higher F. animalis loads in this model. By contrast, inflammation and the presence of H. pylori did not significantly influence stomach colonization by F. animalis. Overall, our data support a model in which H. pylori-induced metaplasia makes the stomach susceptible to secondary infection by another cancer-associated microbe, F. animalis.},
}

@article {pmid41446058,
year = {2025},
author = {Schaefer-Babajew, D and Binet, L and Santos, GSS and Ruprecht, C and Deimel, LP and ElTanbouly, MA and Gharrassi, D and Uhe, C and Yao, KH and Hernandez, B and Agrawal, P and Gazumyan, A and Stamatatos, L and Hartweger, H and Nussenzweig, MC},
title = {Antibody Mediated Diversification of Primary and Secondary Immune Responses.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41446058},
issn = {2692-8205},
support = {P01 AI100148/AI/NIAID NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UM1 AI144462/AI/NIAID NIH HHS/United States ; UM1 AI191237/AI/NIAID NIH HHS/United States ; },
abstract = {Humoral immune responses are characterized by increasing antibody affinity and diversity over time. Increased affinity is mediated by a combination of immunoglobulin gene somatic mutation and iterative cycles of selection in germinal centers. Less is understood about how diversity increases in parallel with affinity. Here we examine the role of antibody feedback in diversifying immune responses in mice that produce B cells that are incapable of secreting antibodies. To this end, we produced two strains of mice, one that expresses only membrane and secreted forms of IgM, and a second that produces only the membrane bound form of IgM. Analysis of primary and secondary immune responses show that antibody feedback significantly diversifies both primary and secondary immune responses even when antibodies are present at levels that are 10-30 fold lower than physiologic. The data have significant implication for sequential vaccination approaches aimed at shepherding immunity to produce broadly neutralizing antibodies to highly diversified pathogens such as HIV-1 and Influenza.},
}

@article {pmid41332789,
year = {2025},
author = {Ruediger, CT and Styler, BS and Sawyer, EM and Spiri, S and King, G and Walsh, ME and Brar, GA and Jorgens, DM and Ünal, E},
title = {Tom70-mediated mitochondria-nuclear envelope contacts regulate nuclear pore complex inheritance during gametogenesis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41332789},
issn = {2692-8205},
support = {T32 GM132022/GM/NIGMS NIH HHS/United States ; R01 AG071869/AG/NIA NIH HHS/United States ; R35 GM134886/GM/NIGMS NIH HHS/United States ; T32 GM007127/GM/NIGMS NIH HHS/United States ; T32 GM007232/GM/NIGMS NIH HHS/United States ; R01 AG071801/AG/NIA NIH HHS/United States ; },
abstract = {Gametogenesis rejuvenates the cellular lineage and excludes senescence-associated factors from gametes. In Saccharomyces cerevisiae, this involves sequestration of nuclear constituents into the Gametogenesis-Uninherited Nuclear Compartment (GUNC), which is excluded from gametes. Here we identify the conserved mitochondrial import receptor Tom70 as a key regulator of GUNC-mediated exclusion. Loss of TOM70 disrupts the sequestration of nuclear pore complexes, but not senescence-associated aggregates and nucleolar components, into the GUNC. Tom70's role appears independent of its canonical function in mitochondrial import and instead reflects a meiosis-specific requirement for mitochondria-nuclear envelope tethering. During meiosis II, Tom70 concentrates around the GUNC, where it recruits the nuclear envelope tethering protein Cnm1. Loss of CNM1 partially phenocopies tom70∆, consistent with parallel tethering interactions. These findings uncover a previously unrecognized organelle contact-dependent pathway that remodels the nuclear envelope to support selective nuclear inheritance. More broadly, they highlight how organelle contacts integrate with nuclear quality control to safeguard gamete integrity.},
}

@article {pmid41461080,
year = {2025},
author = {Lucia, MS and Callis, S and Tangen, C and Almutairi, F and Chatzitolios, A and Kravtsov, O and Lenon, S and Manuchua, V and Simko, JP and Szecsei, CM and Yeh, YA and Zhang, L and Iczkowski, KA},
title = {Whole-Slide Telepathology Grading of Prostate Cancer in Biopsies Using ISUP Criteria: Inter- and Intra-Observer Concordance and Implications for Active Surveillance.},
journal = {The Journal of urology},
volume = {},
number = {},
pages = {101097JU0000000000004919},
doi = {10.1097/JU.0000000000004919},
pmid = {41461080},
issn = {1527-3792},
abstract = {INTRODUCTION: Subjectivity of prostate cancer (PCa) grading impacts biomarker investigations, assessments of imaging, and treatment decisions, especially for active surveillance. We conducted the first telepathology concordance study of PCa needle biopsy grading using contemporary International Society of Urologic Pathology guidelines.

METHODS: Whole slide images (n=120) of PCa biopsy cases across grade groups (GG), were examined by 11 urologic pathologists. Forty cases were blindly regraded, over-sampling cases with lower agreement on first review. Pathologists provided GG, percentage and type of pattern Gleason 4, and tumor length. Consensus for a case was defined as GG agreement by ≥7 pathologists. GG agreement among and within pathologists was measured using model-based weighted Kappa statistics (κw).

RESULTS: Consensus was achieved on 86/120 (72%) cases. Of 34 cases not achieving consensus, most were GG2 vs GG1 (41%) or GG2 vs GG3 (38%). The inter-rater κw was 0.34 (95% CI 0.28, 0.39) indicating fair agreement. Forty regraded cases had an intra-rater κw of 0.49 (95% CI 0.46, 0.53; moderate agreement). Sixty-four percent of the repeated grades agreed. Of the repeated ratings that did not agree, 39% involved GG1 vs GG2. Of the GG1 vs GG2 paired repeated ratings, 77% reported 1-10% pattern 4, and indicated common observation was "poorly-formed glands."

DISCUSSION: Inter- and intra-rater variability in GG is significant, particularly discerning GG1 from GG2 with ≤10% grade 4. These observations have profound implications for treatment decisions (surveillance vs definitive therapy) and studies of new biomarkers and imaging of prostate cancer.},
}

@article {pmid41460964,
year = {2025},
author = {Abramson, JS and Straus, DJ and Bartlett, NL and Burke, JM and Lynch, RC and Domingo-Domenech, E and Hess, BT and Schuster, SR and Linhares, Y and Gandhi, MD and Shah, HR and Jurczak, W and Re, A and Hahn, U and Prince, HM and Guo, W and Davis, G and Ho, L and Fanale, M and Yasenchak, CA and Lee, HJJ},
title = {Brentuximab Vedotin and Nivolumab in Combination With Chemotherapy for Nonbulky, Early-Stage Classical Hodgkin Lymphoma.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025030190},
pmid = {41460964},
issn = {1528-0020},
abstract = {Most patients with early-stage classical Hodgkin lymphoma (cHL) are treated with doxorubicin, bleomycin, vinblastine, and dacarbazine with or without radiation therapy, although studies are now evaluating the incorporation of novel agents paired with abbreviated chemotherapy. We present the efficacy and safety of brentuximab vedotin (BV) and nivolumab in combination with doxorubicin and dacarbazine (AN+AD) in patients with early-stage cHL. In this phase 2 study, patients with non-bulky (<10 cm) Ann Arbor stage I or II cHL received 4 cycles of AN+AD. The primary endpoint was complete response (CR) rate at end of treatment (EOT) by investigator. At the time of this analysis, 154 patients received ≥1 dose of AN+AD. The objective response rate at EOT was 96% (95% CI, 91.7-98.6), and the CR rate was 92% (95% CI, 86.0-95.4). In the favorable (n=56) and unfavorable (n=97) subgroups, CR rates were 95% (95% CI, 85.1-98.9) and 91% (95% CI, 83.1-95.7), respectively. The proportion of patients with duration of CR of at least 2 years was 96% (95% CI, 90.9-98.4). At a median follow-up of 27.9 months, the estimated 2-year PFS rate was 97% (95% CI, 92.0-98.8). Any-grade and grade ≥3 treatment-emergent adverse events occurred in 99% and 44% of patients, respectively; no events of febrile neutropenia were reported. Any-grade treatment-emergent immune-mediated adverse events occurred in 22% of patients. One disease-related death was reported after the safety reporting period. Results from this study support the use of BV and nivolumab in combination with limited chemotherapy in patients with non-bulky, early-stage cHL. ClinicalTrials.gov: NCT03646123.},
}

@article {pmid41460962,
year = {2025},
author = {Nguyen, C and Funes, J and Ghale, R and Duong, N and Victor, K and Gipson, B and Zhang, ZJ and Dai, A and Li, R and Armijo, GK and Huang, AS and Martinez, M and Chen, Y and Ghazarian, DM and Docampo, MD and Pathak, KV and Pirrotte, P and Markey, KA and Peled, JU and Paredes, J and Burgos da Silva, M and van den Brink, MRM},
title = {Enterococcus induces MHC-II expression by the intestinal epithelium during murine graft-versus-host disease.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024028248},
pmid = {41460962},
issn = {1528-0020},
abstract = {Intestinal Enterococcus domination has been associated with an increased risk of mortality by acute graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (allo-HCT), a curative-intent treatment for patients with hematologic malignancies. In this study, we investigate the interactions between Enterococcus and the intestinal epithelium as a mechanism to aggravate GVHD. We observed that endogenous intestinal Enterococcus outgrowth was associated with increased GVHD mortality and major histocompatibility complex class II (MHC-II) expression by intestinal epithelial cells (IECs) in the colon in an MHC-disparate mouse model of GVHD. Monocolonization of non-transplanted gnotobiotic mice with E. faecalis was sufficient to induce colonic MHC-II expression. Conversely, select species within the genus Enterococcus, as well as a consortium of four anaerobic commensal bacteria including Blautia producta, did not affect colonic MHC-II expression in gnotobiotic mice. In addition, E. faecalis colonization also induced inflammatory responses in CD4+ T cells and NK cells from the colonic lamina propria, the two main sources of interferon-gamma production that drives MHC-II expression in non-professional antigen-presenting cells. We further explored the potential therapeutic benefit of establishing colonization resistance against E. faecalis through administration of a lantibiotic-producing B. producta strain after allo-HCT. Colonization of transplanted mice with a consortium of commensal bacteria containing the lantibiotic-producing B. producta strain prevented intestinal Enterococcus domination post-transplant and improved GVHD survival. Our results demonstrate a potential mechanism by which Enterococcus aggravates GVHD through increased MHC-II expression in the intestinal epithelium. Targeting the Enterococcus-epithelium-MHC-II axis thus presents a therapeutic opportunity to prevent lethal GVHD.},
}

@article {pmid41279209,
year = {2025},
author = {Awany, D and Ariefdien, DT and Mendelsohn, SC and Rozot, V and Mulenga, H and Nyangu, S and Tameris, M and Moloantoa, T and Katona, A and Maruri, F and Noor, F and Panchia, R and Hlongwane, K and Stanley, K and van der Heijden, YF and Hadley, K and Gartland, AF and Innes, C and Brumskine, W and Dheda, K and Jaumdally, S and Perumal, T and Martinson, N and Leslie, A and Fourie, B and Hiemstra, A and Malherbe, ST and Walzl, G and Naidoo, K and Churchyard, G and Chegou, NN and Sterling, TR and Hatherill, M and Scriba, TJ},
title = {Inflammatory Biomarkers of Asymptomatic and Symptomatic Tuberculosis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279209},
issn = {2692-8205},
abstract = {A large proportion of individuals with tuberculosis (TB) are asymptomatic. The biological and inflammatory underpinnings of asymptomatic TB are unknown and may differ from symptomatic TB. We characterised blood transcriptomic and proteomic profiles in South African community screening vs. health facility-based triage cohorts. Asymptomatic TB shared core transcriptomic and proteomic features with symptomatic TB, including upregulation of innate, interferon and inflammatory pathways and downregulation of T and B cell pathways. Integration of transcriptomic and proteomic data from asymptomatic TB individuals identified two distinct sub-clusters characterized by higher or lower bacterial burden, blood IFN-γ responses, BMI, and chest radiographic abnormalities, suggesting different disease severity. We identified a new blood transcriptomic signature of asymptomatic TB. However, diagnostic performance of transcriptomic and proteomic markers was weaker for asymptomatic TB than symptomatic TB, suggesting that policy development for community-based, asymptomatic TB screening should not adopt biomarkers developed for symptomatic TB triage without further optimization.},
}

@article {pmid41460828,
year = {2025},
author = {Osuga, H and Chan, MC and Brower, K and Ray, LJ and Chowning, JT},
title = {Ten simple rules for running a virtual program to introduce computational biology at the high school level.},
journal = {PLoS computational biology},
volume = {21},
number = {12},
pages = {e1013830},
pmid = {41460828},
issn = {1553-7358},
}

@article {pmid41460282,
year = {2025},
author = {Woolf-King, SE and Dalton, MR and Firkey, M and Sheinfil, A and Bucci, V and Estrada, B and Ramos, J and Hahn, JA and Bricker, J and Gump, B and Bendinskas, KG and Maisto, SA},
title = {A Randomized Feasibility/Acceptability Trial of Acceptance and Commitment Therapy for People with HIV Who Drink at Unhealthy Levels.},
journal = {AIDS and behavior},
volume = {},
number = {},
pages = {},
pmid = {41460282},
issn = {1573-3254},
support = {R34AA026246/AA/NIAAA NIH HHS/United States ; R34AA026246-03S1/AA/NIAAA NIH HHS/United States ; },
abstract = {Unhealthy alcohol use is prevalent among people with HIV (PWH) and associated with significant health-related consequences. We describe here a randomized feasibility/acceptability trial of a brief, telephone-delivered transdiagnostic acceptance and commitment therapy (ACT) intervention for PWH who drink at unhealthy levels. This pilot trail was designed to match the procedures of a planned definitive RCT that will compare the ACT intervention to a brief alcohol intervention (BI). We randomly assigned PWH and unhealthy alcohol use 1:1 to either the ACT or the BI intervention and collected self-report and biomarker data post-treatment and again at 3-, 6-, and 12-months. The primary objectives of this pilot trial were to assess feasibility of recruitment, retention, and intervention delivery, and acceptability of intervention content. We also collected preliminary primary (alcohol use) and secondary (symptoms of anxiety, depression, and experiential avoidance) outcome data to examine general patterns of results at a purely descriptive level. In total, 192 participants were screened, 117 of whom were eligible, and 49 of whom were randomized to either the ACT (n = 24) or BI (n = 25) condition. Results provided evidence of feasibility and acceptability indicating that a definitive trial should proceed. Preliminary outcome data also suggested that ACT is a promising treatment for unhealthy alcohol use and co-morbid symptoms of depression, anxiety, and experiential avoidance. A definitive trial is currently underway and will determine the comparative efficacy of ACT versus BI for unhealthy alcohol use for PWH.},
}

@article {pmid41459934,
year = {2025},
author = {Reed, JC and Downs, C and McAllister, K and Mauer, C and McClurkan, CL and Wilson, D and Holzhauer, K and Dickerson, JA and Cannon, CA and Babu, TM and Golden, MR and Koelle, DM and Greninger, AL},
title = {Differentiating mpox infection and vaccination using a validated multiplex orthopoxvirus IgG serology assay.},
journal = {Journal of clinical microbiology},
volume = {},
number = {},
pages = {e0154825},
doi = {10.1128/jcm.01548-25},
pmid = {41459934},
issn = {1098-660X},
abstract = {UNLABELLED: The resurgence of monkeypox virus (MPXV) has increased demand for validated serological assays to assess exposure and immunity. Cross-reactivity among orthopoxviruses, stemming from high sequence conservation, complicates distinguishing antibody responses from natural MPXV infection versus vaccination or other orthopoxvirus exposures. We validated the Meso Scale Discovery (MSD) V-PLEX Orthopoxvirus Panel 1 (IgG) Kit, which quantifies antibody levels to five MPXV antigens and their vaccinia virus (VACV) orthologs, following Good Clinical Laboratory Practice guidelines. We assessed assay performance using serum from 26 individuals with prior mpox, 52 JYNNEOS vaccine recipients, and 179 unexposed controls. The assay reliably detected antibody responses in all exposed cohorts with peak levels observed 2 months post-vaccination. Antibody levels to specific antigens also correlated with Modified Vaccinia Ankara neutralization titer, particularly for MPXV B6R/VACV B5R, MPXV E8L/VACV D8L, and MPXV M1R/VACV L1. Receiver operating characteristic analysis showed that some individual antigens achieved high sensitivity and specificity for exposure detection (area under the curve [AUC] > 0.96 for VACV D8L, MPXV B6R, VACV B5R); however, individual antigens performed poorly in distinguishing infection from vaccination. In contrast, antibody level ratios between some MPXV and VACV orthologs effectively differentiated MPXV infection from vaccinia vaccination with high sensitivity and specificity (e.g., MPXV A35R/VACV A33R ortholog ratio, AUC = 0.97, sensitivity = 0.97, specificity = 0.96). Our findings validate the MSD assay for clinical research and serosurveillance to assess MPXV immunity and support the utility of ortholog pair ratio analysis as a strategy to discriminate vaccinated and infected individuals.

IMPORTANCE: Mpox continues to spread around the world, with recent data showing increasing incidence in the United States. While there are multiple Food and Drug Administration (FDA)-authorized real-time PCR tests for diagnostic use, there are no FDA-authorized serological tests and few laboratory-developed serological tests offered. We evaluated the Meso Scale Discovery V-PLEX Orthopoxvirus Panel 1 (IgG) Kit according to Good Clinical Laboratory Practice guidelines and found that the assay reliably detected antibody responses in monkeypox virus (MPXV)- and vaccinia virus (VACV)-exposed cohorts and could distinguish them from unexposed cohorts. Intriguingly, we found that antibody level ratios between certain MPXV and VACV orthologs could distinguish prior mpox infection from vaccinia vaccination. Overall, these data highlight the use of multi-antigen panels in challenging scenarios for serological testing, such as the cross-reactivity presented by orthopoxviruses.},
}

@article {pmid41446269,
year = {2025},
author = {Lin, C and Gheorghe, V and Chou, J and Alibai, S and Kim, S and Nazanin, EA and Xu, Y and Ma, X and Wilson, LL and Moser, RD and Kemp, CJ and Chen, J and Kopetz, S and Hart, T},
title = {Functional modules predict cancer-relevant genetic interactions in mammalian cells.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41446269},
issn = {2692-8205},
abstract = {Genetic interactions can reveal gene function and identify cancer-relevant synthetic lethals, but systematic mapping in human cells is constrained by inefficient reagents, vast combinatorial search space, and diversity of cell types. Here, we leverage principles from yeast genetic networks to identify human gene modules enriched for genetic interactions. Using our Cas12a-based In4mer combinatorial knockout platform, we screen all pairwise interactions within receptor tyrosine kinase and DNA damage response modules across eight diverse cancer cell lines. We identify hundreds of unreported synthetic lethals, including a dense network within the protein glycosylation machinery, and confirm that interactions in 2D cell culture are maintained in more physiologically relevant models. Our targeted modules show up to 16-fold enrichment of interaction density, providing a scalable strategy for systematic interaction mapping.},
}

@article {pmid41446115,
year = {2025},
author = {Soares, RF and Chang, CH and Koerich, LB and Malik, HS and Kuhn, GCS},
title = {Retention of a single Cenp-C gene in different syntenic locations in the montium group of Drosophila species.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41446115},
issn = {2692-8205},
abstract = {Chromosome segregation in eukaryotes requires the orchestrated interaction of chromosomes with microtubules, mediated by the kinetochore multiprotein complex that assembles on specific chromosomal regions known as centromeres. In most eukaryotes, two centromeric proteins, CenH3 and Cenp-C, are essential for centromere function. In Drosophila, the localization of CenH3 (referred to as Cid in Drosophila) depends on its chaperone CAL1 and Cenp-C. Previous studies have shown that both Cid and Cenp-C underwent a coincident gene duplication and likely functional specialization in the Drosophila subgenus. Independently, Cid duplications led to Cid1, Cid3, and Cid4 paralogs in the montium group (Sophophora subgenus), but it is unknown whether this group also underwent parallel duplications of Cenp-C. Here, we investigate this possibility by analyzing sequenced genomes of 23 montium group species. We identified Cenp-C genes in five distinct syntenic loci; we named these genes Cenp-C1b, Cenp-C1c, Cenp-C1d, Cenp-C1e and Cenp-C3. Despite their distinct synteny, most montium group species only encode a single Cenp-C; their phylogeny mirrors the species phylogeny, and they appear to have retained Cenp-C protein motifs indicative of function. A closer examination revealed that these Cenp-C genes resulted from gene translocations or alternate retention (duplication followed by loss of the ancestral copy); only one species, D. vulcana, retains two intact Cenp-C paralogs. Therefore, unlike the Drosophila genus, the co-retention of three Cid paralogs in the montium group has not resulted in a coincident Cenp-C paralog co-retention. Our work highlights differences in functional retention and likely specialization of the two most conserved centromeric proteins in eukaryotes.},
}

@article {pmid41459525,
year = {2025},
author = {Chapuis, AG and Orozco, JJ and Milano, F},
title = {Intrathecal rituximab for the treatment of Epstein-Barr virus-associated encephalitis.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1736017},
pmid = {41459525},
issn = {1664-3224},
mesh = {Humans ; *Rituximab/administration & dosage/therapeutic use ; *Epstein-Barr Virus Infections/drug therapy/virology/diagnosis/immunology ; Injections, Spinal ; *Herpesvirus 4, Human ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Encephalitis, Viral/drug therapy/diagnosis/virology/etiology ; Male ; Adult ; Treatment Outcome ; Female ; *Immunologic Factors/administration & dosage ; Middle Aged ; },
abstract = {Epstein-Barr virus (EBV)-associated encephalitis is seen in patients who have undergone allogeneic hematopoietic stem cell transplant and can be associated with significant morbidity and mortality. The mainstay of treatment has been antiviral therapy with nucleoside analogues and reduction of immunosuppression. Here, we describe an adult patient diagnosed with refractory EBV-associated encephalitis within 30 days post-allogeneic transplant successfully treated with intrathecal rituximab, which, to our knowledge, is the first case treated in this manner.},
}

Humans
*Rituximab/administration & dosage/therapeutic use
*Epstein-Barr Virus Infections/drug therapy/virology/diagnosis/immunology
Injections, Spinal
*Herpesvirus 4, Human
*Hematopoietic Stem Cell Transplantation/adverse effects
*Encephalitis, Viral/drug therapy/diagnosis/virology/etiology
Male
Adult
Treatment Outcome
Female
*Immunologic Factors/administration & dosage
Middle Aged

@article {pmid41452615,
year = {2025},
author = {Unger, JM and Fisch, MJ and Jones, SMW and Henry, NL and Hershman, DL},
title = {Baseline Fatigue and Severe Toxic Effects in Patients With Cancer Receiving Systemic Therapy.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
pmid = {41452615},
issn = {2374-2445},
abstract = {IMPORTANCE: Fatigue is a common symptom reported by patients with cancer, yet its role as a predictor of treatment-related toxic effects has not been well characterized. Understanding whether fatigue measured at treatment initiation may be associated with subsequent toxic effects could help guide individualized treatment planning and symptom monitoring.

OBJECTIVE: To evaluate the association between baseline patient-reported fatigue and the risk of adverse events (AEs) in cancer treatment trials.

This cohort study and pooled analysis assessed baseline fatigue data from 17 SWOG phase 2 and 3 trials conducted from 1990 to 2022. Patients were enrolled across multiple cancer types and treatment settings. Data analysis was performed from March 1, 2023, to October 17, 2025.

EXPOSURES: Baseline fatigue, classified on a 5-point Likert scale, analyzed as binary thresholds (eg,
MAIN OUTCOMES AND MEASURES: Adverse events were classified using the Common Terminology Criteria for Adverse Events (CTCAE), with multiple versions mapped to version 4. Symptomatic AEs followed the Patient-Reported Outcomes-CTCAE framework; laboratory-based or measurable toxic effects were considered objective (hematologic vs nonhematologic). Primary outcomes were grade 3 or higher (severe), grade 4 or higher (life-threatening), and grade 5 (fatal) AEs. Odds ratios (ORs) were estimated using generalized estimating equations. To account for confounding, the analysis was clustered by trial and adjusted for age, sex, race, and obesity.

RESULTS: Among 7086 patients (mean [SD] age, 62.1 [15.2] years; 2107 females [29.7%] and 4979 males [70.3%]) with prostate, lung, colorectal, lymphoma, breast, melanoma, ovarian, or pancreatic cancer, 103 738 AEs were reported. At baseline, 2771 participants (39.1%) reported some or more fatigue. Proportions with maximum AEs rated grade 3 or higher, grade 4 or higher, and grade 5 were 3128 participants (44.1%), 1001 (14.1%), and 62 (0.9%), respectively. Compared with those reporting no or minimal fatigue, patients with some fatigue or more had higher risks of severe or worse toxic effects (odds ratio [OR], 2.09; 95% CI, 1.58-2.78; P < .001), life-threatening or fatal toxic effects (OR, 1.96; 95% CI, 1.36-2.82; P < .001), and fatal toxic effects (OR, 2.35; 95% CI, 1.07-5.19; P = .03). A dose-response pattern was evident: patients reporting quite a lot or very much fatigue had an approximately 5-fold higher risk of fatal toxic effects (OR, 4.99; 95% CI, 1.84-13.51; P = .002). Findings were consistent across symptomatic, hematologic, and nonhematologic AE categories.

CONCLUSIONS AND RELEVANCE: This cohort study found that baseline patient-reported fatigue was associated with an increased risk of cancer treatment-related toxic effects. Fatigue assessments at treatment initiation may serve as an early clinical marker of risk for toxic effects and may help inform personalized treatment strategies and symptom monitoring.},
}

@article {pmid41451118,
year = {2025},
author = {McNeil, AJ and Parks, K and Pogharian, M and Cowen, EW and Lehman, J and Lee, SJ and Zhao, A and Pavletic, SZ and Saknite, I and Coco, J and Fabbri, D and Tkaczyk, ER and Dawant, BM},
title = {Improving U-Net Segmentation of Cutaneous Chronic Graft-Versus-Host Disease in Clinical Photographs with Semi-Supervised Training.},
journal = {Proceedings of SPIE--the International Society for Optical Engineering},
volume = {13407},
number = {},
pages = {},
pmid = {41451118},
issn = {0277-786X},
support = {IK2 CX001785/CX/CSRD VA/United States ; R01 HL169944/HL/NHLBI NIH HHS/United States ; TL1 TR002244/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; },
abstract = {Measuring skin involvement in chronic graft-versus-host disease (cGVHD) currently requires expert manual assessment, which is costly, time-consuming, and shows high interrater disagreement (>20% surface area). In our previous work, automated image analysis showed promise for measuring affected skin area under controlled photography conditions. Our aim is to improve the performance of these methods in standard clinical photographs without the need for costly expert annotations using a semi-supervised approach. A baseline U-Net model was trained in a fully supervised manner using 360 3D photographs from 36 cGVHD patients, with expert-marked ground truth contours of affected skin. The model was then iteratively retrained by incorporating an additional 5648 unlabeled photographs from 83 new patients using a semi-supervised method. Testing on clinical photographs of 20 held-out patients, the median surface area error improved from 19.2% (interquartile range 6.3 - 33.8) at baseline to 10.2% (4.5 - 22.6) after retraining. Semi-supervised training therefore provides an effective method for translating a pre-trained U-Net segmentation model to standard clinical photographs, without the need for additional expert annotations. Such models could help standardize cGVHD assessment and tracking, alleviating the need for costly expert evaluations and providing a reliable tool that would significantly enhance the current standard of manual assessment.},
}

@article {pmid41448908,
year = {2025},
author = {Mukui, I and Peacock, S and Donnell, D and Gati-Mirembe, B and Krows, M and Bukusi, EA and Imaan, L and Kotze, P and Gill, KM and Macdonald, P and Louw, C and Jaggernath, M and Marais, A and Peters, RPH and Delany-Moretlwe, S and Ward, A and du Preez, P and Kasaro, M and Gandhi, M and Heffron, R and Celum, C and , },
title = {High prevalence and incidence of curable sexually transmitted infections among young women using oral HIV pre-exposure prophylaxis in sub-Saharan Africa: results from the INSIGHT Cohort study.},
journal = {Sexually transmitted infections},
volume = {},
number = {},
pages = {},
doi = {10.1136/sextrans-2025-056625},
pmid = {41448908},
issn = {1472-3263},
abstract = {BACKGROUND: HIV pre-exposure prophylaxis (PrEP) programmes in Africa reach young women at risk of sexually transmitted infections (STIs). We evaluated curable STI prevalence, incidence and risk factors among women initiating PrEP.

METHODS: From August to December 2022, sexually active women aged 16-30 years from 15 South African sites, and one site each in Eswatini, Kenya, Malawi, Uganda and Zambia were enrolled into the INSIGHT cohort and offered oral emtricitabine/tenofovir PrEP with follow-up at 1, 3 and 6 months. At each visit, STI symptoms were assessed and treatment provided based on syndromic management or diagnostic testing. Diagnostic tests included nucleic acid amplification for Chlamydia trachomatis and Neisseria gonorrhoeae, the rapid OSOM for Trichomonas vaginalis at enrolment and month 6, and serological testing for syphilis at enrolment using rapid plasma reagin with confirmatory Treponema pallidum particle agglutination. Prevalence and incidence of each STI were calculated, and predictors assessed using multivariable regression.

RESULTS: Of 3087 participants offered daily oral PrEP with a median age of 23 (IQR 21-27), 3011 had STI results and 30.9% had one or more STIs, with 15.7% reporting symptoms. The prevalence of C. trachomatis, N. gonorrhoeae, T. vaginalis and syphilis was 20.8%, 6.8%, 6.0% and 4.4%, respectively. The incidence of one or more STIs (C. trachomatis, N. gonorrhoeae or T. vaginalis) was 49.3/100 person-years (95% CI 45.3 to 53.4) with 12.7% reporting symptoms. The incidence of C. trachomatis was 30.6/100 person-years (95% CI 27.5 to 33.7), N. gonorrhoeae 10.8/100 person-years (95% CI 9.0 to 12.6) and T. vaginalis 11.5/100 person-years (95% CI 9.7 to 13.4). An incident STI diagnosis was associated with low alcohol use (adjusted incidence rate ratio (aIRR) 1.3; 95% CI 1.0 to 1.6) and moderate alcohol use (aIRR 1.4; 95% CI 1.1 to 1.8), and having an STI diagnosed at enrolment (aIRR 1.8; 95% CI 1.5 to 2.1).

CONCLUSION: The high prevalence and incidence of STIs among African women initiating PrEP, most of whom did not report symptoms, highlights the need for aetiologic testing to detect STIs, guide treatment and reduce reproductive health sequelae and risk of transmission.

TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT05746065.},
}

@article {pmid41427323,
year = {2025},
author = {Raman, P and Khan, H and Young, JM and Tsukiyama, T and Malik, HS},
title = {Dynamic evolution of EZHIP, an inhibitor of the Polycomb Repressive Complex 2 in mammals.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41427323},
issn = {2692-8205},
abstract = {The Polycomb Repressive Complex 2 (PRC2) is an ancient, conserved chromatin-interacting complex that controls gene expression, facilitating differentiation and cellular identity during development. Its regulation is critical in most eukaryotes. EZHIP was recently characterized as a PRC2 inhibitor and 'oncohistone mimic' in mammals. Although Ezhip expression is typically restricted to the germline, its aberrant expression in pediatric brain tumors inhibits PRC2-mediated H3K27 methylation and drives disease progression. To gain a deeper understanding of its normal functions, we systematically examined Ezhip evolution across 70 mammals using comparative genomics, synteny analysis, and motif discovery. Bolstering previous work, we find that Ezhip originated and has been strictly retained on the X chromosome in placental mammals. In addition to the highly conserved H3K27M-like histone mimic motif, our motif analysis reveals seven previously unidentified EZHIP motifs, including a putative nuclear localization signal, and tandem repeats that are largely well-conserved in placental mammals, except in some lineages. We hypothesize that these motifs are also critical to EZHIP's functions, including in PRC2 interaction and inhibition. We show that Ezhip has evolved under strong diversifying selection in primates and underwent dynamic expansions and losses across species. Some paralogs, such as Ezhip2 in primates, also evolved under positive selection. Based on its evolutionary attributes and germ-cell expression, we propose that Ezhip arose and evolved rapidly due to inter-parental conflict over fetal development in utero in placental mammals. Our work provides a foundation for further investigations into EZHIP's essential, potentially multifaceted roles in mammalian reproduction and disease.},
}

@article {pmid41427272,
year = {2025},
author = {Vaz, J and Zhu, S and Useche, M and Shih, L and Marchiano, E and Beronja, S and Clurman, BE and Rodriguez, C and Barber, B and Chan, M and Gujral, TS},
title = {Subtype-Specific Dependencies and Drug Vulnerabilities Enable Precision Therapeutics in Head and Neck Cancer.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41427272},
issn = {2692-8205},
abstract = {Molecular heterogeneity in head and neck squamous cell carcinoma (HNSCC) is well recognized, yet existing subtype frameworks remain largely descriptive and have not translated into therapeutic decision-making. Here, we establish a mechanistic platform that converts transcriptomic diversity into drug-actionable tumor states. Integrating multi-cohort RNA-seq from 727 tumors across five independent datasets, genome-scale CRISPR dependency maps, and pharmacologic screening, we define distinct tumor survival circuits across HPV-negative HNSCC and nominate subtype-matched therapeutic strategies. These circuits encompass a proliferative axis (MYC, MET/FAK, inflammatory and translational programs), an epithelial-differentiated/adhesion program, an EMT-like state with stromal activation, and mitochondrial/oxidative metabolic states, each mapping to selective liabilities (e.g., mitotic/autophagy control, ERBB/PI3K and cadherin signaling, OXPHOS/mitochondrial translation, and G2/M-integrin-Notch pathways, respectively). We then develop a transcriptomic predictor of EGFR-inhibitor response using machine learning and validate it in prospectively collected, fresh patient-derived 3D microtumors. The resulting 13-gene signature identifies erlotinib-responsive tumors (R = 0.93) and maps biologically to an epithelial-differentiated state, outperforming EGFR expression alone. Our study establishes a subtype-to-dependency-to-therapy framework, enabling precision stratification and providing a clinically feasible path for prospective biomarker deployment.},
}

@article {pmid41448830,
year = {2025},
author = {Yamada, MM and Chandrasekhar, S and Gooley, TA and Chen, RE and Doolittle-Amieva, C and Ansstas, G and Bhatia, S and Hall, ET and Nghiem, PT and Park, SY and Chen, DY},
title = {Real-world outcomes of talimogene laherparepvec as salvage therapy for advanced melanoma.},
journal = {Journal for immunotherapy of cancer},
volume = {13},
number = {12},
pages = {},
pmid = {41448830},
issn = {2051-1426},
support = {P01 CA225517/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Melanoma/drug therapy/mortality/therapy/pathology ; Male ; Female ; Middle Aged ; Aged ; *Salvage Therapy/methods ; Adult ; *Oncolytic Virotherapy/methods ; Aged, 80 and over ; *Biological Products/therapeutic use/pharmacology ; Treatment Outcome ; Herpesvirus 1, Human ; *Skin Neoplasms/mortality ; Retrospective Studies ; },
abstract = {BACKGROUND: Talimogene laherparepvec (T-VEC) is an oncolytic herpes simplex virus therapy approved for treatment of unresectable and metastatic melanoma. However, real-world use often occurs in heavily pretreated patients, where evidence of effectiveness remains limited. This study evaluates treatment responses and clinical factors influencing T-VEC outcomes in patients with diverse treatment histories.

METHODS: We analyzed patients with metastatic melanoma treated with T-VEC between 2015 and 2024. Objective responses (OR), complete response (CR) and partial response were assessed using univariate and multivariate Cox regression models. Durability of responses, progression-free survival (PFS), and overall survival (OS) were evaluated using Kaplan-Meier estimates.

RESULTS: Among 121 patients, 105 (87%) patients received ≥1 prior lines of systemic therapy; 48 (40%) had a current or prior history of distant metastatic disease, and 42 (35%) had both injectable and non-injectable disease at the T-VEC initiation. Median PFS was 12.2 months (95% CI 6.2 to 20.9), and median OS was 35.5 months (95% CI 25.8 to 63.9). Of 113 evaluable patients, 76 (67%, 95% CI 58% to 76%) achieved an OR, including 39 (35%, 95% CI 26% to 44%) CR. The probability OR by 6 months was 56% (95% CI 46% to 65%). Of the 39 patients achieving CR, 37 (95%) remained alive and progression-free at last follow-up (median 19.1 months). In multivariate analysis, the adjusted HR (aHR) for OR in patients with non-injectable distant metastases at T-VEC initiation relative to those without was 0.43 (95% CI 0.23 to 0.78; p=0.006). The aHR for OR among those immunosuppressed compared with those not immunosuppressed was 0.18 (95% CI 0.04 to 0.69; p=0.013), indicating a reduced likelihood of response for patients who were immunosuppressed. Unadjusted HRs for achieving an OR after 1, 2, and ≥3 prior therapies (vs none) were 1.20 (95% CI 0.57 to 2.52; p=0.627), 1.21 (95% CI 0.52 to 2.80; p=0.653), and 0.77 (95% CI 0.35 to 1.68; p=0.507), respectively.

CONCLUSIONS: This study demonstrates T-VEC's potential efficacy in achieving meaningful disease control and response durability in patients with unresectable and/or metastatic melanoma, including those with diverse prior-treatment histories and comorbidities.},
}

Humans
*Melanoma/drug therapy/mortality/therapy/pathology
Male
Female
Middle Aged
Aged
*Salvage Therapy/methods
Adult
*Oncolytic Virotherapy/methods
Aged, 80 and over
*Biological Products/therapeutic use/pharmacology
Treatment Outcome
Herpesvirus 1, Human
*Skin Neoplasms/mortality
Retrospective Studies

@article {pmid41448829,
year = {2025},
author = {Balduzzi, A and Valsecchi, MG and Tran, TH and Zuna, J and Leoni, V and Cario, G and Fazio, G and Gandemer, V and Tasian, SK and van der Sluis, IM and Peccatori, N and Parasole, R and Monterisi, S and Loh, ML and Devidas, M and Hunger, SP and Kairalla, JA and De Lorenzo, P and Silverman, LB and Biondi, A},
title = {Philadelphia chromosome-positive acute lymphoblastic leukaemia in children and adolescents: A changing treatment landscape and a methodological challenge.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.70288},
pmid = {41448829},
issn = {1365-2141},
support = {//Ministero della Salute/ ; NW25-03-00276//Agentura Pro Zdravotnický Výzkum České Republiky/ ; U10CA180886/CA/NCI NIH HHS/United States ; U10CA180899/CA/NCI NIH HHS/United States ; 1U01CA232486/CA/NCI NIH HHS/United States ; 1U01CA243072/CA/NCI NIH HHS/United States ; 70112958//Deutsche Krebshilfe/ ; },
}

@article {pmid41447755,
year = {2025},
author = {Nair, MS and Scarborough, J and Reddy, CA and Bommireddy, AR and Brooks, E and Almassi, N and Weight, CJ and Campbell, S and Ornstein, MC and Nizam, A and Gilligan, T and Wee, C and Gupta, S and Scott, JG and Mastroianni, A and Tendulkar, R and Mian, OY},
title = {Trimodality Therapy for Bladder Cancer: A Single Institution Retrospective Analysis of Factors Associated With Outcomes for High-Risk Patients Undergoing Organ-Sparing Therapy.},
journal = {Clinical genitourinary cancer},
volume = {24},
number = {1},
pages = {102477},
doi = {10.1016/j.clgc.2025.102477},
pmid = {41447755},
issn = {1938-0682},
abstract = {PURPOSE: We sought to define patient and disease characteristics associated with outcomes after trimodality therapy (TMT) for high-risk nonmuscle invasive and muscle invasive bladder cancer (MIBC). A retrospective analysis of a large single institution cohort treated with bladder preservation therapy was performed to identify factors associated with survival.

METHODS AND MATERIALS: Patients with high-risk non-MIBC or MIBC who underwent definitive bladder sparing treatment between 2006 and 2022 were included. Variables for analysis included age, sex, Charlson Comorbidity Index (CCI), surgical candidacy, neoadjuvant/induction chemotherapy (NAC), tumor size, presence of hydronephrosis, carcinoma in-situ, and histologic subtype. Kaplan-Meier analysis was done to calculate rates of overall survival (OS) and disease-free survival (DFS), while cumulative incidence analysis was done to calculate rates of cancer specific mortality (CSM) and local recurrence. Cox proportional hazards regression was done to identify factors associated with OS and DFS. Competing risk regression was done to identify factors associated with CSM and local recurrence.

RESULTS: 226 patients were included in the cohort with a median follow up of 18.9 months (range 0.9-172.3). The median age was 79 years (range 49-98) and 79.2% were male. On univariate Cox proportional hazards regression, younger age, NAC, and cystectomy candidacy were associated with improved OS (P < .0001, HR = 1.05, 95% CI, 1.03-1.08; P = .04, HR = 0.62, 95% CI, 0.39-0.99; P < .0001, HR = 0.42, 95% CI, 0.27-0.65; respectively). On multivariable analysis, only younger age and cystectomy eligibility were associated with improved OS (P = .002, HR = 1.04, 95% CI, 1.02-1.07; P = .006, HR = 0.52, 95% CI, 0.33-0.83; respectively).

CONCLUSION: This study finds cystectomy eligibility to be associated with improved survival and underscores the importance of multi-disciplinary assessment in determining candidacy for organ preserving therapy in MIBC patients.},
}

@article {pmid41446897,
year = {2025},
author = {Zhai, G and Bar, M and Cowan, AJ and Rubinstein, S and Shi, Q and Zhang, N and Xie, E and Ma, W},
title = {AI for evidence-based treatment recommendation in oncology: a blinded evaluation of large language models and agentic workflows.},
journal = {Frontiers in artificial intelligence},
volume = {8},
number = {},
pages = {1683322},
pmid = {41446897},
issn = {2624-8212},
abstract = {BACKGROUND: Evidence-based medicine is crucial for clinical decision-making, yet studies suggest that a significant proportion of treatment decisions do not fully incorporate the latest evidence. Large Language Models (LLMs) show promise in bridging this gap, but their reliability for medical recommendations remains uncertain.

METHODS: We conducted an evaluation study comparing five LLMs' recommendations across 50 clinical scenarios related to multiple myeloma diagnosis, staging, treatment, and management, using a unified evidence cutoff of June 2024. The evaluation included three general-purpose LLMs (OpenAI o1-preview, Claude 3.5 Sonnet, Gemini 1.5 Pro), one retrieval-augmented generation (RAG) system (Myelo), and one agentic workflow-based system (HopeAI). General-purpose LLMs generated responses based solely on their internal knowledge, while the RAG system enhanced these capabilities by incorporating external knowledge retrieval. The agentic workflow system extended the RAG approach by implementing multi-step reasoning and coordinating with multiple tools and external systems for complex task execution. Three independent hematologist-oncologists evaluated the LLM-generated responses using standardized scoring criteria developed specifically for this study. Performance assessment encompassed five dimensions: accuracy, relevance, comprehensiveness, hallucination rate, and clinical use readiness.

RESULTS: HopeAI demonstrated superior performance across accuracy (82.0%), relevance (85.3%), and comprehensiveness (74.0%), compared to OpenAI o1-preview (64.7, 57.3, 36.0%), Claude 3.5 Sonnet (50.0, 51.3, 29.3%), Gemini 1.5 Pro (48.0, 46.0, 30.0%), and Myelo (58.7, 56, 32.7%). Hallucination rates were consistently low across all systems: HopeAI (5.3%), OpenAI o1-preview (3.3%), Claude 3.5 Sonnet (10.0%), Gemini 1.5 Pro (8.0%), and Myelo (5.3%). Clinical use readiness scores were relatively low for all systems: HopeAI (25.3%), OpenAI o1-preview (6.0%), Claude 3.5 Sonnet (2.7%), Gemini 1.5 Pro (4.0%), and Myelo (4.0%).

CONCLUSION: This study demonstrates that while current LLMs show promise in medical decision support, their recommendations require careful clinical supervision to ensure patient safety and optimal care. Further research is needed to improve their clinical use readiness before integration into oncology workflows. These findings provide valuable insights into the capabilities and limitations of LLMs in oncology, guiding future research and development efforts toward integrating AI into clinical workflows.},
}

@article {pmid41439761,
year = {2025},
author = {Hyams, B and Lowry, KP and Kerlikowske, K},
title = {Digital screening mammograms: current status and future prospects.},
journal = {Expert review of medical devices},
volume = {},
number = {},
pages = {},
doi = {10.1080/17434440.2025.2609759},
pmid = {41439761},
issn = {1745-2422},
abstract = {INTRODUCTION: Mammography has been a cornerstone of breast cancer screening for decades, demonstrating population-level reductions in breast cancer mortality. Limitations of mammography include reduced sensitivity in dense breast tissue, false-positive recalls and biopsies, and possible overdiagnosis. Emerging mammography technologies, including digital breast tomosynthesis (DBT), contrast-enhanced mammography (CEM), and artificial intelligence (AI) applications, seek to address these limitations and improve screening outcomes.

AREAS COVERED: In this review, we discuss endpoints for assessment of emerging mammography technologies, including cancer detection, interval cancer, and advanced cancer rates. We review clinical trial data for DBT, highlighting studies reporting interval and advanced cancer rates, and contrast performance in average-risk and high-risk populations. We review CEM as a new modality for supplemental screening in women with dense breasts. Lastly, we cover the rapidly expanding space of AI-supported mammography tools, including those for lesion detection, exam triage, breast density assessment, and risk prediction.

EXPERT OPINION: Emerging technologies in digital screening mammography have demonstrated improvements in surrogate endpoints like cancer detection, however, their effect on clinically meaningful outcomes such as interval cancer and advanced cancer reduction remains unproven. To ensure that innovations translate into tangible patient benefit, future research should prioritize clinically relevant endpoints and real-world evaluation.},
}

@article {pmid41439754,
year = {2025},
author = {Tantalo, LC and Chamakuri, KD and Greninger, AL and Lieberman, NAP and Giacani, L},
title = {Susceptibility to Penicillin G and Ceftriaxone in Three Clinical Treponema pallidum Isolates is not Altered by Amino Acid Polymorphisms in the Tp0705 Penicillin Binding Protein.},
journal = {Sexually transmitted diseases},
volume = {},
number = {},
pages = {},
doi = {10.1097/OLQ.0000000000002291},
pmid = {41439754},
issn = {1537-4521},
abstract = {We demonstrated no differences in susceptibility to penicillin G and ceftriaxone in three modern T. pallidum isolates (UW244B, UW249B, and UW330B), each carrying a variant of the penicillin-binding protein (PBP) Tp0705. This suggests that these polymorphisms should not be a reason for concern when β-lactams are prescribed for syphilis treatment.},
}

@article {pmid41436303,
year = {2025},
author = {Abe, T and Berger, AH},
title = {New insights in regulation of RAS isoforms revealed by protein structures.},
journal = {Trends in biochemical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tibs.2025.11.008},
pmid = {41436303},
issn = {0968-0004},
abstract = {Leucine zipper-like post translational regulator 1 (LZTR1) functions as a RAS degrader, but the molecular basis of LZTR1-RAS regulation has remained unclear. A recent report by Dharmaiah et al. presents crystal structures of the LZTR1 Kelch domain bound to RIT1, MRAS, or KRAS, providing the first atomic-level insights into LZTR1 substrate recognition.},
}

@article {pmid41435136,
year = {2025},
author = {Karasaki, S and Berberian, AG and Zewdie, HY and Cushing, LJ and VoPham, T},
title = {Geospatial Approaches for Environmental Justice: A Critical Review.},
journal = {Annual review of public health},
volume = {},
number = {},
pages = {},
doi = {10.1146/annurev-publhealth-090924-033158},
pmid = {41435136},
issn = {1545-2093},
abstract = {Environmental justice (EJ) research is an interdisciplinary field of study concerned with the unequal distribution of environmental burdens and benefits across different sociodemographic identities (e.g., race, class). While considerations of space and time with respect to environmental exposures and health outcomes have always been central to EJ, the state of the science on geospatial methods, measures, and technologies is rapidly advancing, as are their applications in research. We find that geospatial technologies have extended researchers' abilities to more precisely link the spatial extents of environmental exposures to when and where people live, work, and play. Geospatial data are also useful in analyzing systemic oppression and structural racism as root causes of environmental injustice via metrics of segregation and redlining. This review provides an overview of how geospatial methods and technologies are being applied to EJ research for (a) population identification, (b) exposure assessment, (c) outcome ascertainment, and (d) research translation.},
}

@article {pmid41433208,
year = {2025},
author = {Piliper, EA and Reed, J and Greninger, AL},
title = {Corrected and republished from: "Clinical validation of an RSV neutralization assay and analysis of cross-sectional sera associated with 2021-2023 RSV outbreaks to investigate the immunity debt hypothesis".},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0173925},
doi = {10.1128/spectrum.01739-25},
pmid = {41433208},
issn = {2165-0497},
abstract = {UNLABELLED: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections and hospitalization in infants and the elderly. Newly approved vaccines and the prophylactic antibody nirsevimab have heightened interest in RSV immunologic surveillance, necessitating the development of high-throughput assays assessing anti-RSV neutralizing activity. Quantitative viral neutralization remains the best correlate of protection for RSV infection and the gold standard for RSV immunological testing. Here, we developed a high-throughput RSV strain A2 focus-reduction neutralization test validated to CLIA/GCLP standards using both clinical specimens and commercially available reference sera. The assay is highly accurate, generating reference serum neutralizing titers within twofold of established assays, with an analytical measurement range between 8 and 1,798 international units (IU) per mL. Neutralizing activity measured by the assay strongly correlated with antibody titer determined via indirect ELISA (ρ = 1.0, P = 0.0014). Individuals recently having tested RT-qPCR positive for RSV had a 7.5-fold higher geometric mean neutralizing titer relative to RSV PCR negatives (P < 0.0001). The validated assay was then used to investigate the immunity debt hypothesis for resurgent RSV outbreaks in the 2022-2023 season, using adult clinical remnant sera sent for HSV-1/2 antibody testing. There was no difference in geometric mean anti-RSV neutralizing titers between sera sampled before and after the 2022-2023 RSV outbreak (P = 0.68). These data are consistent with limited changes in RSV neutralizing antibody levels in adults across the 2022-2023 RSV outbreak.

IMPORTANCE: Population surveillance studies of serum neutralizing activity against RSV are crucial for evaluating RSV vaccine efficacy and vulnerabilities to new strains. Here, we designed and validated a high-throughput assay for assessing anti-RSV neutralizing activity, standardized its measurements for comparison with other methodologies, and demonstrated its applicability to real-world samples. Our assay is precise, linear, and yields measurements consistent with other standardized assays, offering a methodology useful for large-scale studies of RSV immunity. We also find no significant difference in neutralizing titers among adults between taken before and after large RSV outbreaks associated with the latter stages of the COVID-19 public health emergency, underlining the need for a greater understanding of the dynamics of serological responses to RSV infection.},
}

@article {pmid41432664,
year = {2025},
author = {Duong, A and Bui, H and Fritzsche, D and Ruplin, A},
title = {Antiandrogen therapies: Management of drug interactions with anticoagulation.},
journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners},
volume = {},
number = {},
pages = {10781552251406879},
doi = {10.1177/10781552251406879},
pmid = {41432664},
issn = {1477-092X},
abstract = {BackgroundSecond-generation antiandrogens have significantly improved outcomes in patients with prostate cancer; however, their complex pharmacokinetic profiles can result in significant drug-drug interactions (DDIs) in patients with comorbid conditions which require chronic anticoagulation.ObjectiveThis review aims to describe the DDIs between antiandrogens and commonly used anticoagulants, with a focus on understanding the clinical implications of pharmacokinetics and drug metabolism.MethodsA comprehensive literature review of pharmacokinetic data, clinical trials, and prescribing information was performed. Drug metabolism of antiandrogens and anticoagulants was examined, including the effects of CYP450 enzyme and/or P-glycoprotein (P-gp) inhibition and induction on anticoagulant efficacy and safety.ResultsEnzalutamide and apalutamide are strong inducers of CYP3A4, which may reduce exposure to warfarin, apixaban, and rivaroxaban. Apalutamide induces P-gp, and therefore has DDIs with all direct oral anticoagulants (DOACs). Darolutamide and abiraterone exhibit minimal CYP450 induction and inhibition, and do not interact with warfarin or DOACs.ConclusionDrug-drug interactions between antiandrogens and anticoagulants are common and can affect therapeutic efficacy and safety. Clinical decision-making surrounding drug selection requires an interprofessional approach grounded in pharmacokinetic knowledge to ensure safe and effective care in patients with prostate cancer.},
}

@article {pmid41432537,
year = {2025},
author = {Zhang, Z and Ray, RM and An, R and Klonoff-Cohen, HS and Thomas, DB},
title = {Mammographic Density as a Mediator for Breast Cancer Risk: Pooled Analysis of Four Population-Based Case-Control Studies on Women with Screening Mammograms Under 50.},
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-25-0884},
pmid = {41432537},
issn = {1538-7755},
abstract = {BACKGROUND: Multiple risk factors influence breast cancer risk, but the role of percent mammographic density (PMD) in mediating these associations remains unclear.

METHODS: In this pooled analysis of women who had screening mammograms before age 50, we assessed whether PMD mediates associations between reproductive, structural, and lifestyle factors and breast cancer risk. Causal mediation analysis was used to estimate direct and indirect effects, and the proportion mediated by PMD.

RESULTS: PMD partially mediated 29.0% of the association between breast calcifications and breast cancer risk, with a natural indirect-effect odds ratio (ORNIE) of 1.16 (95% CI: 1.04-1.30; P = 0.009). A history of breast biopsies was marginally associated with increased risk (P = 0.083), with 83.1% of this effect mediated by PMD (ORNIE = 1.28; 95% CI: 1.11-1.49; P = 0.001). PMD mediated 48.6% of the reduced risk among parous versus nulliparous women (ORNIE = 0.76; 95% CI: 0.65-0.90; P = 0.001). No significant mediation by PMD was observed for first-degree family history of breast cancer, age at first live birth, or smoking. Adult BMI showed inconsistent mediation with opposing direct and indirect effects, reducing breast cancer risk via lower PMD but increasing risk through density-independent pathways, yielding a null total effect.

CONCLUSIONS: Our findings highlight PMD's important role as a mediator in linking certain reproductive and structural factors to breast cancer risk in younger women, offering insights into early-onset breast cancer.

IMPACT: This underscores PMD's potential as both a biomarker and a target for risk prediction and prevention.},
}

@article {pmid41428730,
year = {2025},
author = {Hyppa, RW and Smith, GR},
title = {Mutual, spatially limited control of meiotic DNA break formation by Mre11-Rad50-Nbs1 DNA repair complex and Tel1 (ATM) protein kinase.},
journal = {Nucleic acids research},
volume = {53},
number = {22},
pages = {},
pmid = {41428730},
issn = {1362-4962},
support = {NIH R35 GM118120//National Institutes of Health of the United States of America/ ; NIH P30 CA015704//National Institutes of Health of the United States of America/ ; },
mesh = {*Meiosis/genetics ; *Schizosaccharomyces pombe Proteins/metabolism/genetics/physiology ; *DNA Breaks, Double-Stranded ; *Schizosaccharomyces/genetics/metabolism ; Endodeoxyribonucleases/metabolism/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *Protein Serine-Threonine Kinases/metabolism/genetics/physiology ; Exodeoxyribonucleases/metabolism/genetics ; *Intracellular Signaling Peptides and Proteins/metabolism/genetics ; *Cell Cycle Proteins/metabolism/genetics ; *DNA Repair ; MRE11 Homologue Protein ; *Nuclear Proteins/metabolism ; Chromosomal Proteins, Non-Histone ; },
abstract = {Meiotic recombination is initiated by DNA double-strand breaks (DSBs); factors that control DSB frequencies are important to produce viable progeny. In many organisms, the ATM (Tel1) protein kinase prevents excessive meiotic DSBs, especially nearby DSBs on the same chromatid. Normally, two close DSBs are less frequent than expected from independence, a feature called DSB interference, which is lost in tel1Δ mutants. In the fission yeast Schizosaccharomyces pombe, high-level DSB formation depends on linear elements, Hop1, and meiotic cohesin complexes; we show here that these complexes impart competition between nearby DSB sites. When these complexes are impaired, Tel1 substantially represses DSB formation, and in its absence, two close DSBs on the same chromatid occur frequently and manifest high negative interference. After mitotic DNA damage, the conserved Mre11-Rad50-Nbs1 (MRN) complex is required for DNA resection, and the Tel1 kinase activity is needed to complete DSB repair. We found that during meiosis mre11Δ and rad50Δ mutants, like tel1Δ mutants, lack DSB interference and display highly negative DSB interference in meiotic complex mutants. Thus, MRN at a DSB site appears critical for Tel1 function in meiosis and reveals a complex interplay of positive and negative factors controlling meiotic DSB formation.},
}

*Meiosis/genetics
*Schizosaccharomyces pombe Proteins/metabolism/genetics/physiology
*DNA Breaks, Double-Stranded
*Schizosaccharomyces/genetics/metabolism
Endodeoxyribonucleases/metabolism/genetics
*DNA-Binding Proteins/metabolism/genetics
*Protein Serine-Threonine Kinases/metabolism/genetics/physiology
Exodeoxyribonucleases/metabolism/genetics
*Intracellular Signaling Peptides and Proteins/metabolism/genetics
*Cell Cycle Proteins/metabolism/genetics
*DNA Repair
MRE11 Homologue Protein
*Nuclear Proteins/metabolism
Chromosomal Proteins, Non-Histone

@article {pmid41428135,
year = {2025},
author = {Pinker, K and Comstock, C and Leung, JWT and LoGullo, R and Rahbar, H and Seely, JM and Trop, I and Sung, J},
title = {Image-guided biopsy of breast lesions-when to use what biopsy technique: the United States and Canadian perspective.},
journal = {Insights into imaging},
volume = {16},
number = {1},
pages = {289},
pmid = {41428135},
issn = {1869-4101},
}

@article {pmid41423715,
year = {2026},
author = {Nakao, M and Schwengfelder, J and Richter, C and Peters, N and Ozawa, S},
title = {Comparison of two established approaches for generating Hounsfield look-up tables for CT-based SPR prediction.},
journal = {Medical physics},
volume = {53},
number = {1},
pages = {e70236},
doi = {10.1002/mp.70236},
pmid = {41423715},
issn = {2473-4209},
support = {23K14869//Japan Society for the Promotion of Science/ ; },
mesh = {*Tomography, X-Ray Computed/instrumentation ; Humans ; Phantoms, Imaging ; *Radiotherapy Planning, Computer-Assisted/methods ; *Image Processing, Computer-Assisted/methods ; Calibration ; },
abstract = {BACKGROUND: To ensure consistency in treatment planning across institutions, inter-center variations in Hounsfield look-up tables (HLUTs) have been evaluated using different methods in Japan and Europe. In Japan, the Hiroshima High-Precision Radiotherapy Cancer Center (HIPRAC) developed the computed tomography number calibration audit (HIPRAC-CTCA) based on a stoichiometric method, while in Europe, the European Particle Therapy Network (EPTN) implemented a method using validated tissue-equivalent inserts. Comparing these approaches is essential to improving consistency and reliability.

PURPOSE: This study aims to enhance the reliability of the HIPRAC method by comparing it with the EPTN consensus guide-based HLUT generation methods used in multi-institutional evaluations.

METHODS: HLUTs were generated using the HIPRAC and EPTN methods for both head and body phantom configurations. The HIPRAC-based HLUT was created by measuring CT numbers of tough lung and tough bone inserts, applying the stoichiometric method, and calculating the theoretical HLUTs for representative tissues based on the International Commission on Radiological Protection Publication 110. The EPTN-based HLUT was generated by measuring the CT numbers of validated tissue-equivalent inserts, calculating the CT numbers of human tissues using the stoichiometric method, and determining the HLUT through piecewise linear regression between CT numbers and stopping-power ratios (SPRs) for both tissue-equivalent inserts and human tissues. ΔSPR values were calculated by subtracting the EPTN-based HLUT from the HIPRAC-based HLUT and were categorized into lung, soft tissue, and bone groups. Representative brain tumor and prostate cancer cases were analyzed to evaluate spot-wise range shifts (ΔR80) when applying the two HLUTs.

RESULTS: Both methods showed good agreement in lung, soft tissue, and bone, with all ΔSPR values within ± 2% and mean differences ≤ 1%. In cortical bone, ΔSPR reached approximately 2%-3%, leading to minor range shifts. In the clinical case analysis, mean ΔR80 were -0.28 mm for the brain tumor case and -0.45 mm for the prostate cancer case, indicating that proton range differences between the two HLUTs were negligibly small.

CONCLUSIONS: The established HLUT generation methods for CT-based SPR prediction developed in Japan and Europe were compared and showed good agreement across all tissue types. Range differences in clinical cases were minor, and ΔSPR variations in cortical bone corresponded to negligible proton range deviations. These findings indicate that the European and Japanese approaches are practically equivalent and support the validity and reliability of the HIPRAC-CTCA method.},
}

*Tomography, X-Ray Computed/instrumentation
Humans
Phantoms, Imaging
*Radiotherapy Planning, Computer-Assisted/methods
*Image Processing, Computer-Assisted/methods
Calibration

@article {pmid41415367,
year = {2025},
author = {Garza, R and Marchioni, JM and Honeycutt, JD and Hurlburt, NK and Torres, C and Garcia, A and Loranc, E and Yemington, E and Towers, D and Ssewanyana, I and Pancera, M and Lavinder, JJ and Jagannathan, P and Greenhouse, B and Bol, S and Bunnik, EM},
title = {The N-terminal region of malaria vaccine candidate Plasmodium falciparum asparagine-rich merozoite antigen is immunodominant and targeted by polyreactive antibodies.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41415367},
issn = {2692-8205},
support = {U19 AI089674/AI/NIAID NIH HHS/United States ; U01 AI150741/AI/NIAID NIH HHS/United States ; S10 OD030432/OD/NIH HHS/United States ; R01 AI153425/AI/NIAID NIH HHS/United States ; T32 GM145432/GM/NIGMS NIH HHS/United States ; F30 AI176697/AI/NIAID NIH HHS/United States ; P30 CA054174/CA/NCI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; },
abstract = {The development of malaria blood-stage vaccines has been hampered by sequence variation in many Plasmodium falciparum proteins involved in erythrocyte invasion. In the past few years, asparagine-rich merozoite antigen (PfARMA) has emerged as a potential vaccine candidate due to its low amino acid sequence diversity and the association between anti-PfARMA antibody levels and protection to malaria. Here, we used samples from P. falciparum-exposed individuals to study naturally acquired B cell and antibody responses to PfARMA. B cell responses to PfARMA were dominated by IgM[+] B cells that recognized the N-terminal intrinsically disordered region 1 (IDR1) of PfARMA. A human monoclonal antibody (hmAb) to IDR1 was non-neutralizing, while a second hmAb binding to the folded domain showed weak neutralizing activity. Both PfARMA-specific plasma IgM and IgG responses predominately targeted IDR1 and their levels increased with P. falciparum exposure. However, in contrast to previous reports, these antibody responses did not correlate with protection in age and exposure-matched children. Interestingly, approximately 30% of unexposed individuals had IgG that also targeted IDR1 and was polyreactive, binding to regions with high asparagine content. Finally, we determined that PfARMA is located in or near PfEBA-175[+] micronemes. These data suggest that while IgG to the folded domain of PfARMA may inhibit parasite growth, antibody responses to PfARMA are primarily directed to IDR1 and may not directly contribute to protection against malaria.},
}

@article {pmid41423517,
year = {2025},
author = {Chambwe, N and Kennedy, SR and Kohrn, BF and Lazarchuk, P and Leutert, M and Qin, G and Tercan, B and Sanchez-Contreras, M and Tang, W and Graber, JJ and Paddison, PJ and Villén, J and Shmulevich, I and Monnat, RJ},
title = {Cellular heterogeneity and therapeutic response profiling of human IDH + glioma stem cell cultures.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-33082-8},
pmid = {41423517},
issn = {2045-2322},
abstract = {Glioblastoma stem cell (GSC) cultures are initiated from glioblastoma (GBM) surgical resection tissue. When grown appropriately they can capture and propagate key GBM molecular and cellular features. We have characterized cellular, genomic and proteomic features of four isocitrate dehydrogenase (IDH)-expressing (IDH +) GSC cultures as cellular models for ~ 90% of adult GBMs. We demonstrate that GSC cultures can be continuously propagated in defined, serum-free media and 5% oxygen without specialized growth substrates; have culture-specific genomic and mtDNA variants together with gene/protein expression profiles; and display reproducible dose-survival curves for the GBM standard-of-care therapies ionizing radiation (IR) and temozolomide (TMZ). In order to better define GSC culture cellular heterogeneity and dynamics, we used lentiviral DNA barcoding, mtDNA variants and single cell gene expression profiling over 40 days after IR treatment. GSC cultures are versatile in their ability to support many in vitro protocols including high throughput screens as well as xenograft, organoid and other disease modeling protocols. They provide a simple cellular disease model for better understanding GBM biology, and for identifying new, potentially more effective GBM therapies and treatment regimens.},
}

@article {pmid41421757,
year = {2025},
author = {Onyeaka, HK and Mate-Kole, MN and Acheampong, IA and Arthur, A and Song, MT and Akhiwu, TO and Mensah, D and Ozoalor, C and Chido-Amajuoyi, OG and Amonoo, HL},
title = {Geographic location and clinical trial knowledge, invitation, and participation among adults in the United States.},
journal = {Contemporary clinical trials},
volume = {161},
number = {},
pages = {108193},
doi = {10.1016/j.cct.2025.108193},
pmid = {41421757},
issn = {1559-2030},
abstract = {BACKGROUND/AIMS: Clinical trials are essential to evaluating novel treatments and improving disease-related outcomes through innovative therapies. Despite underrepresentation of rural communities in clinical trial outreach and participation, geographic disparities in clinical trials have been minimally explored. We examined clinical trial knowledge, invitation, and participation among participants in urban and rural geographic locations in the United States.

METHODS: We conducted cross-sectional data analysis on self-reported data from Health Information National Trends Survey (HINTS) 5 Cycle 4. Population-level estimates were obtained using jack-knife replicate weights.

RESULTS: Geographic location was not associated with clinical trial knowledge, invitation, and participation. However, the relatively low absolute invitation rates across urban and rural populations may suggest that substantial gaps in recruitment persist universally, regardless of geographic location in the United States.

CONCLUSIONS: In this nationally representative study, we found no statistically significant differences in clinical trial knowledge, invitation or participation by geographical location in the United States. Our findings suggest that geographic residence may not be a primary barrier to clinical trial engagement once sociodemographic differences are accounted for. Targeted efforts to improve awareness and reduce structural barriers, along with continued investment in equitable recruitment strategies, will be important to ensuring that clinical trials reflect the diversity of the populations they aim to serve.},
}

@article {pmid41420827,
year = {2025},
author = {Godbey, EA and Draper, NL and Connelly-Smith, L and Alquist, C and Schwartz, J and Fernando, L and Jones, A and Schmidt, AE and Harmon, C and Lee, E and Linnik, Y and Cooling, L},
title = {Poor Mobilization and Plerixafor Use in Matched Related Peripheral Hematopoietic Progenitor Cell Donors.},
journal = {Journal of clinical apheresis},
volume = {40},
number = {6},
pages = {e70074},
pmid = {41420827},
issn = {1098-1101},
mesh = {Humans ; Cyclams ; Benzylamines ; *Hematopoietic Stem Cell Mobilization/methods ; *Heterocyclic Compounds/pharmacology ; Middle Aged ; Female ; Male ; Adult ; *Peripheral Blood Stem Cells/cytology ; Tissue Donors ; Aged ; },
abstract = {Plerixafor (PLX) is FDA approved for use in autologous peripheral blood stem cell donors but not in allogeneic donors. This study was completed by members of the ASFA HPC Donor Subcommittee to examine the incidence and characteristics of poor mobilizers (PM) among matched related donors (MRD), as well as factors associated with PLX use in MRD. Risks of poor mobilization in MRD were older age, especially donors older than 60 years, lower baseline platelet counts, and heavier recipients. PLX use in PM was low but safe, tripling the success rate for collection. This study adds evidence to the body of literature to support use of PLX in allogeneic donors who are PM.},
}

Humans
Cyclams
Benzylamines
*Hematopoietic Stem Cell Mobilization/methods
*Heterocyclic Compounds/pharmacology
Middle Aged
Female
Male
Adult
*Peripheral Blood Stem Cells/cytology
Tissue Donors
Aged

@article {pmid41420662,
year = {2025},
author = {Ignacio, RB and Pagkas-Bather, J and Gonsalves, G and Gianella, S},
title = {Why Americans are Dying Younger? NIH Is Not the Problem. Our Broken Healthcare Delivery Is.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf592},
pmid = {41420662},
issn = {1537-6613},
abstract = {The United States leads the world in biomedical innovation, with NIH-funded research driving transformative advances in cancer, HIV, and gene therapy. Yet, these breakthroughs cannot achieve their full impact in a fragmented and inequitable health system. Millions remain uninsured, preventive care is undervalued, and social determinants perpetuate life expectancy gaps. Political efforts to restrict or defund the NIH threaten progress and disproportionately harm underserved populations. Biomedical research alone cannot fix systemic failures but strengthening science while repairing care delivery systems is essential to improving population health and ensuring that innovations benefit all.},
}

@article {pmid41420651,
year = {2025},
author = {Ignacio, RB and Pagkas-Bather, J and Gonsalves, G and Gianella, S},
title = {Why Americans are Dying Younger? NIH Is Not the Problem. Our Broken Healthcare Delivery Is.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciaf671},
pmid = {41420651},
issn = {1537-6591},
abstract = {The United States leads the world in biomedical innovation, with NIH-funded research driving transformative advances in cancer, HIV, and gene therapy. Yet, these breakthroughs cannot achieve their full impact in a fragmented and inequitable health system. Millions remain uninsured, preventive care is undervalued, and social determinants perpetuate life expectancy gaps. Political efforts to restrict or defund the NIH threaten progress and disproportionately harm underserved populations. Biomedical research alone cannot fix systemic failures but strengthening science while repairing care delivery systems is essential to improving population health and ensuring that innovations benefit all.},
}

@article {pmid41419585,
year = {2025},
author = {Christie, JR and Eddy, K and Malthaner, RA and Qiabi, M and Verma, S and Breadner, D and Lang, P and Nair, VS and Mattonen, SA},
title = {Assessing clinician performance using a multi-modality clinical decision-support system for lung cancer prognostication.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-31204-w},
pmid = {41419585},
issn = {2045-2322},
support = {152218//Cancer Research Society/ ; T32CA009515/CA/NCI NIH HHS/United States ; RGPIN-2020-06498//Natural Sciences and Engineering Research Council of Canada/ ; },
abstract = {Surgery is the primary treatment for early-stage lung cancer. Adjuvant therapy is offered to patients who are at a high risk of recurrence, however, determining the patients that would benefit from additional therapy is often difficult. In this study, we aimed to develop a clinical decision support system (CDSS) for post-surgery lung cancer prognostication integrating a multi-modality deep learning model (DLM). Pre-operative medical images and clinical, surgical, and pathological information were fed into an externally validated DLM. A CDSS was then developed to display the patient information and DLM results for potential clinical use. Four oncologists evaluated each patient's recurrence probability, their confidence level, and their post-surgery recommendations both with and without the DLM information. The CDSS DLM information demonstrated the potential to improve user prediction performance and confidence. This exploratory study is the first to integrate a multi-modality DLM for prognostication with a CDSS, as well as the first study of clinician attitudes towards CDSSs for lung cancer.},
}

@article {pmid41419476,
year = {2025},
author = {Gustin, AT and Broedlow, CA and Hager, K and Coronado, E and Wangari, S and Iwayama, N and Ahrens, CY and Garrison, WD and Guerriero, KA and De Paris, K and Londono-Renteria, B and Gale, M and Klatt, NR and Kublin, JG and Manuzak, JA},
title = {Distinct gastrointestinal microbial signatures predict parasite levels in controlled Plasmodium infections in both rhesus macaques and humans.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-67241-2},
pmid = {41419476},
issn = {2041-1723},
support = {K01OD024876//U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD)/ ; },
abstract = {Functions of the gastrointestinal (GI) microbiome include maintenance of immune homeostasis and protection against infectious disease. Current assessments of the role of the GI microbiome in Plasmodium infection have been primarily conducted using mouse models and observational human cohorts. Here, we experimentally assessed associations between pre-infection GI microbiome composition and acute Plasmodium parasitemia using 16S rRNA sequencing and samples from rhesus macaques (RMs) and adult humans enrolled in a previously conducted controlled human malaria infection (CHMI) trial (NCT04072302) originally designed to test the efficacy of KAF156, a novel imidazolopiperazine class of antimalarial drugs. We identified distinct pre-infection 16S microbial signatures that were associated with increased risk for above median parasitemia in RMs infected with P. fragile and CHMI participants infected with P. falciparum. Further, we identified a Bifidobacterium feature set that accurately stratified parasitemia risk and could therefore serve as a foundation for a potential biomarker panel to aid prevention efforts in malaria endemic regions. Together, our findings demonstrate that pre-infection GI microbiome composition is indicative of risk for Plasmodium parasitemia, and our observation that the pre-infection microbiome-P. fragile dynamic in RMs mirrors the pre-infection microbiome-P. falciparum interaction in CHMI participants supports the future use of this model in pre-clinical investigations of novel microbiome-targeting approaches to reduce malaria burden.},
}

@article {pmid41419380,
year = {2025},
author = {Jadvar, H and Iravani, A},
title = {Therapy strategies to defeat prostate cancer heterogeneity.},
journal = {Seminars in nuclear medicine},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.semnuclmed.2025.11.025},
pmid = {41419380},
issn = {1558-4623},
abstract = {Metastatic prostate cancer heterogeneity is a multifactorial spatiotemporally dynamic process that leads to disease progression, emergence of treatment resistance and eventual treatment failure. Understanding of the root causes of tumor heterogeneity is the key to develop strategies for more effective therapies. The intra-patient (inter-tumor), and inter-patient heterogeneity demands combinatorial treatment strategies anchored to patient-specific disease biology that can successfully tackle the complexity of the disease in the hopes of overcoming the biological barriers to cancer control. The aim of this article is to briefly review the elements of metastatic prostate cancer heterogeneity and propose approaches to tackle the ensuing therapeutic challenges to achieve durable clinical efficacy in the context of radiopharmaceutical therapy.},
}

@article {pmid41394685,
year = {2025},
author = {Korber, B and Seaman, MS and Mkhize, NN and Greene, K and Gao, H and Shen, X and Domin, E and Tang, H and Theiler, J and Wagh, K and Moore, PL and Williamson, C and Mullins, JI and Doria-Rose, NA and Montefiori, D and Giorgi, EE},
title = {Contemporary HIV-1 envelope pseudovirus panels for detecting and assessing B cell lineages with broadly neutralizing antibody potential.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41394685},
issn = {2692-8205},
abstract = {Although a protective HIV-1 vaccine has not yet been realized, significant progress has been made in vaccine designs that trigger B cell lineages with potential to produce broadly neutralizing antibodies (bnAbs). Advancing these strategies by optimizing vaccine boosting regimens requires early detection of maturing antibodies with neutralizing activity against native envelope glycoprotein (Env) trimers and streamlined strategies to identify antibodies as they begin to manifest desired levels of breadth and potency. Thus, we designed three types of pseudovirus screening panels based on Envs of contemporary HIV-1 isolates to facilitate detection of bnAb lineages that are on favorable trajectories during a vaccination course. The panels were selected from Tier 2 Transmitted Founder Lineage (TFL) HIV-1 Envs from placebo participants in the Antibody Mediated Prevention (AMP) efficacy trials. Using 15 bnAbs to evaluate the neutralization sensitivity of the viruses, we selected 8-member bnAb class-specific panels most sensitive to bAbs representing their class: V2-apex, V3-glycan, CD4-receptor binding site (CD4bs), Membrane-Proximal External Region (MPER), or fusion peptide (FP). Next, we combined the most sensitive viruses among the class-specific panels to create a 12-virus panel to enable optimal detection of low-titer bnAb activity across epitope specificities. Finally, as HIV-1 continues to evolve greater levels of antigenic diversity and as current global pseudoviruses bnAb panels rely on viruses collected more than twenty years ago, we showed the importance of using contemporary viral panels to assess bnAb breadth and potency and designed a 12-virus panel representative of the spectrum neutralization profiles among AMP placebo viruses. We characterized pseudoviruses bearing each selected Env using standardized human sera to confirm their Tier 2 status and biological relevance. These updated panels enable sensitive screening of neutralization activity in vaccine studies and can also provide a realistic assessment of the expected breadth and potency of maturing responses against contemporary HIV-1 Envs.},
}

@article {pmid41282846,
year = {2025},
author = {Haack, AJ and Brown, LG and Zeng, Y and Khan, T and Robertson, IH and Kennedy, DS and Adams, KN and MacDonald, JW and Bammler, TK and Stefanovic, F and Moloney, K and Stolarczuk, JE and Takezawa, MG and Alizai, MY and Hassan, GW and Lim, FY and Chaussabel, D and Walker, EG and Errett, NA and Berthier, E and Theberge, AB},
title = {A Flexible and Responsive Remote Study Design to Assess Gene Expression Changes During Wildfire Smoke Exposure with homeRNA, an At-home Blood Sampling Kit.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41282846},
abstract = {Transcriptomic responses to wildfire smoke are difficult to study given the unpredictability of wildfires and the challenges of collecting blood during active disasters. To overcome these challenges, we developed a flexible study design leveraging homeRNA, our at-home blood collection and RNA stabilization kit. Between June 2021 and April 2022, 58 participants across 10 U.S. states collected 635 blood samples before, during, and after wildfire events. This responsive approach captured three exposure groups: high exposure in Okanogan County, Washington, medium exposure from transported smoke, and low exposure. During the 10-month study, 93% of participants (n=54/58) returned at least 6 samples. In a preliminary exploratory analysis, we analyzed 770 genes with a Nanostring panel from nine participants (6 high, 3 low-medium exposure) using the BloodGen3 framework. In the high exposure participants, we observed trends toward overexpression of inflammation (inflammation aggregates A33 and A35, and modules M13.1 and M13.12), with concurrent underexpression of adaptive immune responses (lymphocytic aggregates A1 and A6, B cell module M13.18, T cell modules M16.24 and M15.38). This study establishes that homeRNA enables flexible, responsive sampling during disasters, overcoming traditional logistical barriers to capture time-sensitive biological data across dispersed populations.},
}

@article {pmid41419161,
year = {2025},
author = {Chandrakasan, S and Westbrook, A and Griffith, LM and Hagin, D and Iyengar, S and Mangurian, C and Scalchunes, C and Sullivan, KE and Zablocki, A and Bakshi, N and Sinha, C and Burroughs, LM and Chan, AY and Dvorak, CC and Haddad, E and Heimall, J and Kohn, DB and Leiding, JW and Notarangelo, LD and Pai, SY and Puck, JM and Pulsipher, MA and Marsh, RA and Torgerson, T and Cowan, MJ and Ochs, HD and Parikh, S},
title = {Clinical spectrum of Wiskott-Aldrich syndrome carriers: Self-reported survey of 193 carriers.},
journal = {Clinical immunology (Orlando, Fla.)},
volume = {},
number = {},
pages = {110658},
doi = {10.1016/j.clim.2025.110658},
pmid = {41419161},
issn = {1521-7035},
abstract = {Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder with microthrombocytopenia, eczema, immunodeficiency, autoimmunity and malignancies resulting from WAS pathogenic variants. Prevalence of disease in heterozygous female carriers has not been described previously. An online Qualtrics survey was designed in collaboration with the Wiskott-Aldrich Foundation, the Immune Deficiency Foundation, the Primary Immune Deficiency Treatment Consortium and Emory University to describe the incidence of thrombocytopenia, eczema, infections, autoimmune disorders, malignancies, and psychosocial factors. 193 carriers with a median age of 39 years participated in this survey. Respondents were predominantly White and were mothers of WAS patients. We observed a high prevalence of thrombocytopenia (13 %), eczema (22 %), infections (33 %) and autoimmunity (24 %) in this self-reported survey. No hematological malignancies were reported. Guilt (91 %), anxiety (41 %) and depression (44 %) were very prevalent. Comprehensive clinical and immunologic studies of WAS carriers should be prioritized to define appropriate health screening, preventive approaches, and counselling for carriers. SUMMARY: This self-reported survey describes the disease burden in 193 carriers of X-linked Wiskott-Aldrich syndrome. It highlights the increased incidence of thrombocytopenia, eczema, infections and autoimmunity in WAS carriers and the need for more comprehensive studies of WAS carriers.},
}

@article {pmid41414919,
year = {2025},
author = {Ignacio, RB},
title = {Reply To Gianella: Redefining Science Together.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf644},
pmid = {41414919},
issn = {1537-6613},
}

@article {pmid41413856,
year = {2025},
author = {Harrison, TA and Zaidi, SH and Yin, H and Steinfelder, RS and Qu, C and Aglago, EK and Berndt, SI and Boardman, LA and Brenner, H and Buchanan, DD and Campbell, PT and Cao, Y and Chan, AT and Chanock, SJ and Doheny, KF and Drew, DA and Figueiredo, JC and French, AJ and Gallinger, S and Georgeson, P and Giannakis, M and Goode, EL and Gruber, SB and Gsur, A and Gunter, MJ and Harlid, S and Hoffmeister, M and Huang, WY and Hullar, MA and Huyghe, JR and Jenkins, MA and Lin, Y and Moreno, V and Murphy, N and Newcomb, PA and Newton, CC and Nowak, JA and Obón-Santacana, M and Ogino, S and Shelford, T and Song, M and Thomas, CE and Toland, AE and Ugai, T and Um, CY and Van Guelpen, B and Trinh, QM and Sun, W and Hudson, TJ and Hsu, L and Peters, U and Phipps, AI},
title = {Genomic characterization of colorectal tumors: insights into significantly mutated genes, pathways, and survival outcomes.},
journal = {BMC cancer},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12885-025-15440-x},
pmid = {41413856},
issn = {1471-2407},
support = {U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; P01 CA055075, UM1 CA167552, U01 CA167552, R01 CA137178, R01 CA151993, R35 CA197735//U.S. Department of Health and Human Services/ ; P01 CA055075, UM1 CA167552, U01 CA167552, R01 CA137178, R01 CA151993, R35 CA197735//U.S. Department of Health and Human Services/ ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; U01 CA167551/CA/NCI NIH HHS/United States ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; R01 CA068535//U.S. Department of Health and Human Services/ ; U19 CA148107/CA/NCI NIH HHS/United States ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; Z01 CP 010200, U01 HG004446, U01 HG 004438//U.S. Department of Health and Human Services/ ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; U01 CA167551/CA/NCI NIH HHS/United States ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; U01 CA167551/CA/NCI NIH HHS/United States ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; P01 CA055075, UM1 CA167552, U01 CA167552, R01 CA137178, R01 CA151993, R35 CA197735//U.S. Department of Health and Human Services/ ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; R01 CA215151/CA/NCI NIH HHS/United States ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; U01/U24 CA074783//U.S. Department of Health and Human Services/ ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; U01 CA137088, R01 CA059045, U01 CA164930, R01 CA248857//U.S. Department of Health and Human Services/ ; BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1, HO 5117/2-1, HE 5998/2-1, KL 2354/3-1, RO 2270/8-1, BR 1704/17-1//Deutsche Forschungsgemeinschaft/ ; 01KH0404, 01ER0814, 01ER0815, 01ER1505A, 01ER1505B, 01KD2104A//German Federal Ministry of Education and Research/ ; 509348, 209057, 251553, 504711//National Health and Medical Research Council/ ; 509348, 209057, 251553, 504711//National Health and Medical Research Council/ ; HHSN268201700006I//Center for Inherited Disease Research/ ; HHSN268201700006I//Center for Inherited Disease Research/ ; BRIDGE 829675//Austrian Research Funding Agency (FFG)/ ; BM1206//COST Action/ ; PI14-613//Federación Española de Enfermedades Raras/ ; PI14-613//Federación Española de Enfermedades Raras/ ; 2017SGR723//Agència de Gestió d'Ajuts Universitaris i de Recerca/ ; 2017SGR723//Agència de Gestió d'Ajuts Universitaris i de Recerca/ ; LE22A10-2//Junta de Castilla y León/ ; LE22A10-2//Junta de Castilla y León/ ; GCTRA18022MORE//Fundación Científica Asociación Española Contra el Cáncer/ ; GCTRA18022MORE//Fundación Científica Asociación Española Contra el Cáncer/ ; Genrisk//Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública/ ; Genrisk//Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública/ ; PT13/0010/0013 and ICOBIOBANC//Institut Catala d'Oncologia/ ; PT13/0010/0013 and ICOBIOBANC//Institut Catala d'Oncologia/ ; },
abstract = {BACKGROUND: Identifying significantly mutated genes in tumors aids in understanding disease etiology and survival and may aid in the discovery of new drug targets. We aimed to detect and characterize mutated genes from a large, well-characterized group of colorectal cancers.

METHODS: In tumor and paired normal samples from 6,111 colorectal patients, we sequenced 199 genes identified from whole exome sequencing of over 1,100 tumors. Analyses focused on non-silent mutations. We classified significantly mutated genes after stratification by hypermutation status, and estimated associations of mutated genes/pathways with disease-specific (DS)-survival using Cox regression, adjusting for age, sex, mutation burden, hypermutation status, and study while accounting for multiple comparisons (n = 4,874).

RESULTS: We identified 57 genes that were significantly mutated in colorectal cancer, including 9 that were not previously reported. Among individual genes, only BRAF p.V600E mutations were significantly associated with poorer survival after correction for multiple testing (HR 1.96, P = 2.07 × 10[- 10]), with a more pronounced association among those with non-hypermutated tumors (HR 2.24, P = 1.79 × 10[- 12]). We also observed statistically significant associations with survival for four mutated pathways: TP53/ATM (HR 1.24, P = 7.96 × 10[- 4]), RTK/RAS (HR 1.33, P = 3.81 × 10[- 6]), TGF-beta (HR 1.25, P = 1.85 × 10[- 3]), and WNT (HR 0.81, P = 2.52 × 10[- 03]).

CONCLUSIONS: We identified 9 significantly mutated genes, some of which are known drug targets. Among individual genes, only the BRAF p.V600E mutation was significantly associated with DS-survival, suggesting a limited survival impact from mutations driving colorectal cancer development.},
}

@article {pmid41383769,
year = {2025},
author = {Shen, BA and Asfahl, KL and Lim, B and Bertolli, SK and Minot, SS and Radey, MC and Penewit, K and Ngo, B and Salipante, SJ and Johnston, CD and Peterson, SB and Goodman, AL and Mougous, JD},
title = {The type VI secretion system governs strain maintenance in a wild mammalian gut microbiome.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41383769},
issn = {2692-8205},
abstract = {Bacteria inhabiting the mammalian gut coexist in dense communities where contact-dependent antagonism mechanisms are widespread. The type VI secretion system (T6SS) is an interbacterial toxin delivery pathway prevalent among gut Bacteroidales, yet its function in naturally evolved microbiomes remains poorly defined. Here, we examine the physiological role of the T6SS in Bacteroides within a gut community derived from wild mice (the WildR microbiome). Using newly developed genetic tools and a strategy for functional replacement of strains within the WildR community, we demonstrate that the WildR isolate B. acidifaciens employs a T6SS to antagonize co-resident Bacteroidales. We also show that loss of T6SS function compromises the long-term maintenance of B. acidifaciens in the community but not its initial colonization, establishing the system as a determinant of strain persistence. The T6SS we identified resides on an integrative and conjugative element (ICE). ICE-seq, a targeted sequencing approach, reveals that the T6SS-ICE is distributed among select Bacteroidales and Muribaculaceae species in the WildR microbiome, between which it appears to be recently exchanged. We also show that transfer of the T6SS-ICE to WildR isolate Phocaeicola vulgatus confers transient colonization benefits in mice, but an eventual fitness cost. Our findings demonstrate that the T6SS can stabilize the presence of specific strains within a complex, co-evolved gut microbiome, yet its value is context dependent and constrained by the ecological and physiological landscape of the host community.},
}

@article {pmid41281197,
year = {2025},
author = {Jennings-Shaffer, C and Chen, C and Palacios, JA and Matsen Iv, FA},
title = {Generalizing matrix representations to fully heterochronous ranked tree shapes.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {41281197},
issn = {2331-8422},
abstract = {Phylogenetic tree shapes capture fundamental signatures of evolution. We consider "ranked" tree shapes, which are equipped with a total order on the internal nodes compatible with the tree graph. Recent work has established an elegant bijection of ranked tree shapes and a class of integer matrices, called F -matrices, defined by simple inequalities. This formulation is for isochronous ranked tree shapes, where all leaves share the same sampling time, such as in the study of ancient human demography from present-day individuals. Another important style of phylogenetics concerns trees where the "timing" of events is by branch length rather than calendar time. This style of tree, called a rooted phylogram, is output by popular maximum-likelihood methods. These trees are broadly relevant, such as to study the affinity maturation of B cells in the immune system. Discretizing time in a rooted phylogram gives a fully heterochronous ranked tree shape, where leaves are part of the total order. Here we extend the F -matrix framework to such fully heterochronous ranked tree shapes. We establish an explicit bijection between a class of F -matrices and the space of such tree shapes. The matrix representation has the key feature that values at any entry are highly constrained via four previous entries, enabling straightforward enumeration of all valid tree shapes. We also use this framework to develop probabilistic models on ranked tree shapes. Our work extends understanding of combinatorial objects that have a rich history in the literature.},
}

@article {pmid41411147,
year = {2025},
author = {Curtis, DJ and Hill, GR},
title = {Posttransplant Cyclophosphamide in HLA-matched Peripheral Blood Transplantation: What's next?.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025030416},
pmid = {41411147},
issn = {1528-0020},
abstract = {The use of post-transplant cyclophosphamide was initially pioneered as a means of permitting haploidentical transplantation across HLA barriers. This approach has now become a standard of care for the prevention of significant acute and chronic GVHD after related and unrelated HLA-matched allogeneic peripheral blood stem cell transplant across a full spectrum of conditioning intensities. This spotlight article discusses recent advances, mechanisms of action, and important unresolved questions in the prevention of GVHD that will help inform new prospective clinical studies.},
}

@article {pmid41408582,
year = {2025},
author = {Reding, KW and L Vasbinder, A and Cheng, RK and Barac, A and Wang, Y and Szewczyk, WJ and Haque, R and Ballinger, TJ and Breathett, K and Shadyab, AH and Shih, R and Nuno, T and Wild, RA and Zhang, X and Nassir, R and Mouton, C and Lane, DS and Martin, LW and Manson, JE and Stefanick, ML and Simon, MS and Jones, V},
title = {Racial differences in breast cancer-specific mortality and CVD-specific mortality after breast cancer in post-menopausal women.},
journal = {Cardio-oncology (London, England)},
volume = {11},
number = {1},
pages = {112},
pmid = {41408582},
issn = {2057-3804},
abstract = {BACKGROUND: Racial disparities in all-cause mortality after breast cancer (BC) have been documented. While elevated risk of BC mortality experienced by Black women is clear, it is unclear the relative contribution of cardiovascular disease (CVD) mortality to the survival disparity in Black women.

METHODS: This analysis from the Women's Health Initiative (WHI) included 8,410 women diagnosed with invasive BC during follow-up. Cardiovascular (CV) events were defined as adjudicated myocardial infarction, heart failure, or stroke. Cause of death was determined through adjudication by medical chart review, ICD codes, death certificate, and/or autopsy report. 10-year cumulative incidence rates were calculated for CV events, CVD mortality, and BC mortality, stratified by race. Sub-distribution hazards ratios (sHR) were calculated using Fine and Gray models to account for competing risks.

RESULTS: In BC survivors (mean age = 70.9 years, median follow-up = 15.1 years), 8.5% self-reported as Black. Compared to White women, Black women had higher 10-year cumulative incidence of non-fatal CV events (10.9% vs. 8.2%, P = 0.001) and BC mortality (15.3% vs. 11.5%, P = 0.039). In contrast, White women had higher 10-year incidence of CVD mortality (7.2% vs. 10.1%, P = 0.001). BC mortality in Black women represented a higher proportion of death (35% vs. 20%), which was not true for White women.

CONCLUSION: Our study reinforces prior findings that racial disparities are experienced by Black women with BC. This may be in large part driven by BC mortality. However, if improvements in BC mortality are made to reduce this gap, disparities in CVD mortality may become more prominent due to racial disparities in CV events.},
}

@article {pmid41407856,
year = {2025},
author = {Dekker, J and Oksuz, BA and Zhang, Y and Wang, Y and Minsk, MK and Kuang, S and Yang, L and Gibcus, JH and Krietenstein, N and Rando, OJ and Xu, J and Janssens, DH and Henikoff, S and Kukalev, A and Andréa, W and Winick-Ng, W and Kempfer, R and Pombo, A and Yu, M and Kumar, P and Zhang, L and Belmont, AS and Sasaki, T and van Schaik, T and Brueckner, L and Peric-Hupkes, D and van Steensel, B and Wang, P and Chai, H and Kim, M and Ruan, Y and Zhang, R and Quinodoz, SA and Bhat, P and Guttman, M and Zhao, W and Chien, S and Liu, Y and Venev, SV and Plewczynski, D and Azcarate, II and Szabó, D and Thieme, CJ and Szczepińska, T and Chiliński, M and Sengupta, K and Conte, M and Esposito, A and Abraham, A and Zhang, R and Wang, Y and Wen, X and Wu, Q and Yang, Y and Liu, J and Boninsegna, L and Yildirim, A and Zhan, Y and Chiariello, AM and Bianco, S and Lee, L and Hu, M and Li, Y and Barnett, RJ and Cook, AL and Emerson, DJ and Marchal, C and Zhao, P and Park, PJ and Alver, BH and Schroeder, AJ and Navelkar, R and Bakker, C and Ronchetti, W and Ehmsen, S and Veit, AD and Gehlenborg, N and Wang, T and Li, D and Wang, X and Nicodemi, M and Ren, B and Zhong, S and Phillips-Cremins, JE and Gilbert, DM and Pollard, KS and Alber, F and Ma, J and Noble, WS and Yue, F},
title = {An integrated view of the structure and function of the human 4D nucleome.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {41407856},
issn = {1476-4687},
abstract = {The dynamic three-dimensional (3D) organization of the human genome (the 4D nucleome) is linked to genome function. Here we describe efforts by the 4D Nucleome Project[1] to map and analyse the 4D nucleome in widely used H1 human embryonic stem cells and immortalized fibroblasts (HFFc6). We produced and integrated diverse genomic datasets of the 4D nucleome, each contributing unique observations, which enabled us to assemble extensive catalogues of more than 140,000 looping interactions per cell type, to generate detailed classifications and annotations of chromosomal domain types and their subnuclear positions, and to obtain single-cell 3D models of the nuclear environment of all genes including their long-range interactions with distal elements. Through extensive benchmarking, we describe the unique strengths of different genomic assays for studying the 4D nucleome, providing guidelines for future studies. Three-dimensional models of population-based and individual cell-to-cell variation in genome structure showed connections between chromosome folding, nuclear organization, chromatin looping, gene transcription and DNA replication. Finally, we demonstrate the use of computational methods to predict genome folding from DNA sequence, which will facilitate the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.},
}

@article {pmid41406404,
year = {2025},
author = {Yeh, JM and Seguin, CL and Stratton, KL and Leisenring, WM and Armstrong, GT and Henderson, TO and Hudson, MM and Nathan, PC and Neglia, JP and Oeffinger, KC and Diller, LR and Knudsen, AB},
title = {Benefits, Harms, and Burden of Colorectal Cancer Screening Among Childhood Cancer Survivors Previously Treated With Abdominopelvic Radiation.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2500661},
doi = {10.1200/JCO-25-00661},
pmid = {41406404},
issn = {1527-7755},
abstract = {PURPOSE: Childhood cancer survivors treated with abdominopelvic radiation (RT) are at increased risk of colorectal cancer (CRC), yet adherence to Children's Oncology Group screening guidelines remains low. Estimating the benefits, burdens, and costs of all guideline-recommended screening modalities, including those not previously evaluated, may help identify strategies that align with survivors' preferences and access, potentially improving adherence.

METHODS: Using data from the Childhood Cancer Survivor Study and published studies, we adapted a CRC simulation model to evaluate CRC screening among 5-year survivors. Strategies included colonoscopy, multitarget stool DNA (mtsDNA), and fecal immunochemical testing (FIT) at various intervals, starting at age 25-45 years. Outcomes included CRC cases and deaths, additional colonoscopies per additional life-year gained (burden-to-benefit ratio [BBR]), and cost per quality-adjusted life-year gained (QALYG; incremental cost-effectiveness ratios [ICERs]).

RESULTS: At age 45 years, survivors had a 0.6% cumulative CRC risk (relative risk, 3.3 v average-risk individuals). Without screening, an estimated 75 per 1,000 survivors would be diagnosed with CRC in their lifetime and 30 would die from CRC. Screening averted 47-73 cases and 23-29 CRC deaths per 1,000. Based on average-risk BBR benchmarks, the optimal strategies by modality were colonoscopy every 10 years starting at age 30 years, mtsDNA every 3 years starting at age 30 years, and FIT every 3 years starting at age 25 years (then annually as of age 45 years, as recommended for average-risk individuals). ICERs were $146,000 in US dollars (USD)/QALYG, $166,000 (USD)/QALYG, and $123,000 (USD)/QALYG, respectively.

CONCLUSION: Early initiation of screening with colonoscopy or stool-based tests may substantially reduce CRC incidence and early mortality among survivors treated with abdominopelvic RT, with reasonable burden-to-benefit trade-offs, and be considered cost-effective. These findings can facilitate clinician-survivor discussions on CRC screening and inform guideline refinements.},
}

@article {pmid41405835,
year = {2025},
author = {Diaz, AE and Kwan, ML and Laurent, CA and Rillamas-Sun, E and Roh, JM and Iribarren, C and Rana, JS and Kushi, LH and Reding, KW and Quesenberry, CP and Greenlee, H and Cheng, RK},
title = {Disparities in cardiometabolic and cardiovascular risk after breast cancer: the pathways heart study.},
journal = {JNCI cancer spectrum},
volume = {},
number = {},
pages = {},
doi = {10.1093/jncics/pkaf117},
pmid = {41405835},
issn = {2515-5091},
abstract = {BACKGROUND: Cardiometabolic risk factors (CMRF) and cardiovascular disease (CVD) incidence in racially and ethnically underrepresented women with breast cancer (BC) are not well characterized.

METHODS: The Pathways Heart Study is a prospective cohort of 14,942 women diagnosed with invasive BC from 2005-2013 at Kaiser Permanente Northern California. Incidence of CMRF and CVD outcomes was determined from electronic records and calculated with competing risk framework for non-CVD death. Fine-Gray proportional hazards regression estimated sub-distribution hazard ratios by race and ethnicity compared with non-Hispanic White (NHW) women, with additional Asian subgroup analysis.

RESULTS: Participants were on average 61 years old at diagnosis and 65% NHW, 7.5% Black, 14.4% Asian, 11.9% Hispanic, 0.4% Pacific Islander, and 0.8% American Indian/Alaska Native. Black and Asian women had 1.2-1.3-times higher incident hypertension risk; Black, Asian, Hispanic, and Pacific Islander women had 1.5-3-times higher incident diabetes risk; Asian women had 1.2-times higher incident dyslipidemia risk.Black women had 1.3-1.4-times higher risk of incident ischemic heart disease (IHD), heart failure (HF) and overall CVD. Filipino women had 1.6-times higher risk of stroke. South Asian women had 2.5-2.6-times higher IHD and HF risk.

CONCLUSIONS: Compared with NHW women, racially and ethnically diverse women with BC experienced higher risk of incident diabetes, hypertension, and dyslipidemia. Black and Asian women, particularly Filipino and South Asian, had higher risk of incident CVD. Better characterization of health disparities in cardio-oncology is critical to inform future CVD prevention and treatment.},
}

@article {pmid41401851,
year = {2025},
author = {Barachini, S and Montali, M and Burzi, IS and Pardini, E and Infirri, GS and Cassano, RC and Petrini, I},
title = {The role of the bone marrow microenvironment in leukemic stem cell resistance: Pathways of persistence and selection.},
journal = {Critical reviews in oncology/hematology},
volume = {218},
number = {},
pages = {105090},
doi = {10.1016/j.critrevonc.2025.105090},
pmid = {41401851},
issn = {1879-0461},
abstract = {Chronic Myeloid Leukemia is driven by the BCR::ABL1 fusion gene, which transforms bone marrow stem cells. Tyrosine kinase inhibitors have markedly improved patients' outcomes. However, only about 20 % of patients are cured, remaining free of relapses after the achievement of a profound and durable molecular remission of the disease and the suspension of tyrosine kinase inhibitors. In most cases, leukemic stem cells persist and contribute to disease relapse after treatment suspension or the development of acquired resistance to tyrosine kinase inhibitors. Emerging evidence underscores the pivotal role of the bone marrow microenvironment in sustaining leukemic stem cells and contributing to drug resistance. Stromal progenitor cells within the bone marrow niche play a key role in supporting the persistence and survival of resistant leukemic stem cells. This review examines how the bone marrow microenvironment and its components promote drug resistance through mechanisms such as metabolic reprogramming, aberrant signaling, and protective cellular interactions. These insights reveal potential therapeutic strategies aimed at disrupting the leukemic stem cell supportive niche to achieve more effective eradication of resistant clones. Understanding the complex interplay between leukemic stem cells and their microenvironment is crucial for developing targeted treatments that can overcome resistance and achieve long-term remission in patients with chronic myeloid leukemia.},
}

@article {pmid40985256,
year = {2025},
author = {Jeon, JJ and Kim, YH and Son, H and Lee, JY and Ha, MC and Jung, SW and Lee, S},
title = {Incidence of cutaneous malignancy following the concomitant use of ciclosporin and narrowband ultraviolet B phototherapy in patients with vitiligo.},
journal = {Clinical and experimental dermatology},
volume = {51},
number = {1},
pages = {103-106},
doi = {10.1093/ced/llaf428},
pmid = {40985256},
issn = {1365-2230},
support = {//Korea Health Technology Research/ ; //Korea Health Industry Development Institute/ ; HI23C1506//Ministry of Health and Welfare/ ; },
mesh = {Humans ; *Vitiligo/therapy/drug therapy ; *Ultraviolet Therapy/adverse effects/methods ; Male ; Female ; *Cyclosporine/adverse effects/therapeutic use ; Adult ; *Skin Neoplasms/epidemiology/etiology ; Incidence ; Middle Aged ; Republic of Korea/epidemiology ; Young Adult ; Adolescent ; Aged ; *Dermatologic Agents/adverse effects ; Child ; Combined Modality Therapy ; *Immunosuppressive Agents/adverse effects ; Cohort Studies ; },
abstract = {This nationwide population-based cohort study investigates the incidence of cutaneous malignancies associated with the concomitant treatment of ciclosporin and narrowband ultraviolet B (NBUVB) phototherapy in patients with vitiligo, using the Korean National Health Insurance Service database. Concomitant ciclosporin and NBUVB phototherapy may not significantly increase the incidence of cutaneous malignancies. Given the chronic autoimmune nature of vitiligo and its economic impact, these findings provide novel insights into the potential safety of these combination regimens.},
}

Humans
*Vitiligo/therapy/drug therapy
*Ultraviolet Therapy/adverse effects/methods
Male
Female
*Cyclosporine/adverse effects/therapeutic use
Adult
*Skin Neoplasms/epidemiology/etiology
Incidence
Middle Aged
Republic of Korea/epidemiology
Young Adult
Adolescent
Aged
*Dermatologic Agents/adverse effects
Child
Combined Modality Therapy
*Immunosuppressive Agents/adverse effects
Cohort Studies

@article {pmid41400994,
year = {2025},
author = {Holland, M and Ahmed, M and Young, JM and Drurey, JR and McFadyen, S and Ostrowski, EA and Levin, TC},
title = {Hypermutable hotspot enables the rapid evolution of self/non-self recognition genes in Dictyostelium.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {51},
pages = {e2520843122},
doi = {10.1073/pnas.2520843122},
pmid = {41400994},
issn = {1091-6490},
support = {R35-GM150681//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01-GM74108//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; 1176659//Burroughs Wellcome Fund (BWF)/ ; },
mesh = {*Dictyostelium/genetics ; *Evolution, Molecular ; *Protozoan Proteins/genetics ; Phylogeny ; Genome, Protozoan ; Mutation ; Haplotypes ; },
abstract = {Cells require highly polymorphic receptors to perform accurate self/non-self recognition. In the amoeba Dictyostelium discoideum, polymorphic TgrB1 and TgrC1 proteins are used to bind sister cells and exclude cheaters, but it remains unknown how cells continually generate their extreme genetic diversity. Here, we created a collection of chromosome-length, whole genome sequences from 10 D. discoideum isolates and sister species to understand the evolution of the large tgr gene family. Our dataset includes AX2-214, a widely used D. discoideum lab strain, as well as complete genomes for two Chlamydia-like endosymbionts harbored within amoebae. We find that tgrB1 and C1 lie in a hypermutational hotspot, with haplotypes that undergo repeated intralocus recombination, duplications, transpositions, and inversions. These structural dynamics are highly localized adjacent to tgrB and C, resulting in the gain and loss of dozens of genes. The tgrBC genes themselves frequently duplicate and recombine, leading to the rapid generation of unique tgrBC repertoires. In the broader tgr gene family, some genes (e.g., tgrN) are single copy and syntenic across all the genomes, whereas others (e.g., tgrA) prolifically duplicate at similar rates to Dictyostelium transposons. Thus, the tgr genes are among the most rapidly evolving families genome-wide. We propose that the intense diversification within the tgrBC locus can help explain how these genes acquire such extreme levels of polymorphism, with parallels to the MHC immune genes in mammals and other allorecognition systems. This collection of amoeba genomes is also a useful resource for future comparative genomics and molecular evolution studies in Amoebozoa.},
}

*Dictyostelium/genetics
*Evolution, Molecular
*Protozoan Proteins/genetics
Phylogeny
Genome, Protozoan
Mutation
Haplotypes

@article {pmid41398395,
year = {2025},
author = {Zhou, X and Sevilla-Gonzalez, M and Phipps, AI and Udler, M and Castellví-Bel, S and Chan, AT and Pellatt, AJ and Schoen, RE and Giovannucci, E and Gunter, MJ and Florez, JC and Peters, U and Song, M and Merino, J},
title = {Diabetogenic processes for insulin resistance-linked hyperinsulinaemia are associated with colorectal cancer.},
journal = {Diabetologia},
volume = {},
number = {},
pages = {},
pmid = {41398395},
issn = {1432-0428},
support = {U01 CA137088/CA/NCI NIH HHS/United States ; R01 CA201407/CA/NCI NIH HHS/United States ; R01 CA273198/CA/NCI NIH HHS/United States ; },
abstract = {AIMS/HYPOTHESIS: Type 2 diabetes has been associated with increased risk of colorectal cancer (CRC), but the specific diabetogenic pathways contributing to this risk remain unclear.

METHODS: We analysed individual-level data from 129,420 participants of European ancestry in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and the Colon Cancer Family Registry (CCFR), comprising 58,531 patients with CRC and 70,889 control participants. We applied eight validated partitioned polygenic scores (PPSs) representing distinct diabetogenic processes: two related to relative insulin secretion insufficiency and six to insulin resistance with varying degrees of preserved insulin secretion. Adjusted ORs and 95% CIs for CRC and early-onset CRC were estimated using conditional logistic regression.

RESULTS: PPSs reflecting insulin resistance-linked hyperinsulinaemia, particularly those related to lipodystrophy, body fat and obesity, were associated with higher odds of CRC (p<0.001 for each). Compared with individuals in the lowest decile, those in the highest decile had ORs of 1.09 (95% CI 1.05, 1.14), 1.13 (1.09, 1.18) and 1.15 (1.10, 1.20) for lipodystrophy, body fat and obesity, respectively. In contrast, PPSs for insulin secretion insufficiency or insulin resistance without hyperinsulinaemia were not associated with CRC. The obesity-related hyperinsulinaemic insulin resistance PPS was also associated with higher odds of early-onset CRC (OR for top vs bottom decile=1.26; 95% CI 1.13, 1.41), with the strongest association among those with obesity (OR 1.75; 95% CI 1.46, 2.11; p value for interaction with BMI <0.001).

CONCLUSIONS/INTERPRETATION: Diabetogenic processes characterised by insulin resistance-linked hyperinsulinaemia were associated with increased odds of CRC, including early-onset disease. These findings offer new insights into diabetes-CRC pathogenesis, and may inform targeted prevention strategies.},
}

@article {pmid41358287,
year = {2025},
author = {Sevilla-González, M and Wang, N and Hanson, PA and Bebo, A and Hitchcock, D and Hsu, S and Westerman, KE and Cromer, SJ and Barry, VG and Borns-Weil, Y and Zhang, Y and Ben-Yossef, O and Patel, CJ and Franceschini, N and Taylor, KD and Ávila-Pacheco, J and Clish, CB and Gertzen, RE and Raffield, LM and Kooperberg, C and Rich, SS and Dupuis, J and Rotter, JI and Liu, CT and Meigs, JB and Manning, AK},
title = {Dissecting Genetic and Environmental Determinants of Plasma Molecular Signatures and Their Link to Type 2 Diabetes Risk.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41358287},
support = {75N92021D00005/WH/WHI NIH HHS/United States ; 75N92020D00001/HL/NHLBI NIH HHS/United States ; U01 HL120393/HL/NHLBI NIH HHS/United States ; 75N98025D00025/OD/NIH HHS/United States ; N01 HC095167/HL/NHLBI NIH HHS/United States ; P30 DK063491/DK/NIDDK NIH HHS/United States ; HHSN268201800001C/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; HHSN268201500003I/HL/NHLBI NIH HHS/United States ; 75N98025D00027/OD/NIH HHS/United States ; UL1 TR000040/TR/NCATS NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; 75N98025D00026/OD/NIH HHS/United States ; N01 HC095160/HL/NHLBI NIH HHS/United States ; 75N92020D00002/HL/NHLBI NIH HHS/United States ; 75N98025D00028/OD/NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; HHSN268201500003C/HL/NHLBI NIH HHS/United States ; N01 HC095161/HL/NHLBI NIH HHS/United States ; 75N92020D00005/HL/NHLBI NIH HHS/United States ; N01 HC095168/HL/NHLBI NIH HHS/United States ; R01 HL120393/HL/NHLBI NIH HHS/United States ; 75N98025D00024/OD/NIH HHS/United States ; UL1 TR001079/TR/NCATS NIH HHS/United States ; N01 HC095169/HL/NHLBI NIH HHS/United States ; K99 DK139461/DK/NIDDK NIH HHS/United States ; N01 HC095159/HL/NHLBI NIH HHS/United States ; 75N92020D00003/HL/NHLBI NIH HHS/United States ; R01 HL105756/HL/NHLBI NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; 75N92020D00004/HL/NHLBI NIH HHS/United States ; 75N98025D00022/OD/NIH HHS/United States ; N01 HC095163/HL/NHLBI NIH HHS/United States ; 75N92020D00007/HL/NHLBI NIH HHS/United States ; N01 HC095166/HL/NHLBI NIH HHS/United States ; UM1 DK078616/DK/NIDDK NIH HHS/United States ; 75N92020D00006/HL/NHLBI NIH HHS/United States ; R01 HL117626/HL/NHLBI NIH HHS/United States ; N01 HC095162/HL/NHLBI NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; N01 HC095165/HL/NHLBI NIH HHS/United States ; N01 HC095164/HL/NHLBI NIH HHS/United States ; },
abstract = {BACKGROUND: Type 2 diabetes (T2D) is a heterogeneous disease shaped by both genetic, environmental, cultural, and socioeconomic factors, with well-documented disparities in incidence across populations. The molecular pathways underlying these disparities, however, remain poorly understood. Plasma metabolites and proteins integrate both genetic and environmental influences on type 2 diabetes (T2D) risk, providing insight into disease mechanisms. We aimed to quantify the variance in these molecular profiles explained by environmental and genetic ancestry domains and to apply causal inference approaches to identify environmentally and genetic ancestry influenced pathways contributing to T2D risk.

METHODS: We analyzed plasma proteomic and metabolomic profiles from 3,360 MESA participants (51.6% female), and in 1,333 participants from the Women's Health Initiative. To characterize the sources of variance in plasma proteomic and metabolomic profiles, we performed variance decomposition partitioning into four domains: biological (age, sex, BMI), genetic ancestry (principal components), lifestyle (smoking, alcohol intake, diet), and social determinants (self-reported race and ethnicity, income, education). To assess causal pathways towards T2D risk, we applied two-sample Mendelian Randomization to disentangle environmental and genetic contributors to T2D risk.

RESULTS: The largest share of variance in proteomic and metabolomic profiles was explained by biological and lifestyle factors, while race and ethnicity and genetic ancestry accounted for smaller but non-redundant contributions. Genetic ancestry was primarily associated with lipid and apolipoprotein variation, whereas race and ethnicity and socioeconomic factors were associated with immune and inflammatory signatures. Environmentally influenced metabolites (e.g., diacylglycerols, phosphatidylethanolamines, lysophosphatidylcholines) and vascular-inflammatory proteins were consistently linked to higher T2D risk, while genetic ancestry influenced triglycerides and IGFBP3 reflected inherited risk pathways. Mediation analyses showed that selected lipids and proteins (e.g., IGFBP2, HGF, SSC4D) explained 10-25% of racial/ethnic disparities in T2D. Mendelian randomization identified causal roles for seven lipid species and IGFBP3 in T2D risk.

CONCLUSIONS: Our results reveal both genetic and non-genetic sources of variation in proteomic and metabolomic profiles, uncovering environmental and genetic pathways contributing to T2D risk. These findings advance precision medicine by identifying modifiable molecular mediators of disparities and potential causal targets for prevention.},
}

@article {pmid41333381,
year = {2025},
author = {Vasavada, A and Palazzo, L and Luce, C and Sanchez, M and Triplette, M and Ralston, JD and Carter-Bawa, L and Green, BB and Gao, H and Li, CI and Anderson, ML and Su, YR and Rogers, K and Wernli, KJ},
title = {"It's coming whether we want it to or not": A qualitative exploration of older adults' comfort with and perceptions of technology and digital health.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {41333381},
issn = {2693-5015},
support = {R01 CA262015/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Older adults bear a disproportionate cancer burden but remain underrepresented in digital health intervention trials compared to younger counterparts. Since the COVID-19 pandemic, engagement with telemedicine and patient portals through the electronic health record (EHR) has grown for all age groups, suggesting readiness to adopt digital health tools. This qualitative study primarily sought to understand how adults eligible for lung cancer screening (LCS) engage with technology and digital health in their daily lives. The secondary objective was to assess acceptability and compatibility of a video-based LCS health communication as a digital health tool.

METHODS: Semi-structured interviews were conducted with 15 participants aged 51-80 through videoconferencing or telephone. Transcripts were analyzed using a rapid team-based analysis approach. The Consolidated Framework for Implementation Research (CFIR) was used as a guiding framework from throughout the study, with constructs of interest informing interview guide questions in data collection, and CFIR-mapping to generate a code list in the analysis.

RESULTS: Our findings generated four CFIR-informed themes, with 8 subthemes: 1) Internal facilitators: comfort with technology, self-efficacy in troubleshooting; 2) External facilitators: leveraging internet for health information, use of wearable devices, patient portal functionalities; 3) Internal barriers: emotional response, social isolation; 4) External barriers: scamming and data privacy. When shown the LCS video-based health communication, participants described general approval of the content and delivery but expressed concerns about safety related to accessing the video due to its delivery via weblink.

CONCLUSIONS: Broadly, we found that older adults had high levels of technology use and leveraged various digital tools (such as wearable devices, mobile applications, and EHR patient portals) to manage their health care needs. Our findings underscore that older adults are active users of digital tools, yet persistent concerns about privacy, social isolation, and emotional burden must be addressed for digital health interventions to be acceptable and sustainable in this population.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT05747443; 2023-02-17.},
}

@article {pmid41332752,
year = {2025},
author = {Hsieh, HC and Gao, G and Han, Q and Brenes, D and Baraznenok, E and Yan, R and Serafin, R and Bishop, KW and Wang, R and Konnick, EQ and Pritchard, CC and Figiel, S and Hamdy, FC and Mills, IG and Reder, NP and Reddi, DM and Paulson, TG and Grady, WM and Valk, JE and True, LD and Haffner, MC and Rao, SR and Woodcock, DJ and Liu, JTC},
title = {3D pathology-guided microdissection.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41332752},
issn = {2692-8205},
support = {R01 CA268207/CA/NCI NIH HHS/United States ; P50 CA097186/CA/NCI NIH HHS/United States ; U01 CA182940/CA/NCI NIH HHS/United States ; U2C CA271902/CA/NCI NIH HHS/United States ; R01 CA220004/CA/NCI NIH HHS/United States ; R01 DK138948/DK/NIDDK NIH HHS/United States ; U54 DK137328/DK/NIDDK NIH HHS/United States ; R01 EB031002/EB/NIBIB NIH HHS/United States ; U01 CA152756/CA/NCI NIH HHS/United States ; U54 CA163060/CA/NCI NIH HHS/United States ; },
abstract = {Traditional micro- and macro-dissection techniques enable the extraction of localized regions in thin tissue sections for molecular analysis. Despite the growing use of 3D microscopy, analogous methods for volumetric microdissection are lacking. We have developed a 3D microdissection method based on computer numerical controlled (CNC) milling integrated with open-top light-sheet microscopy. We demonstrate the ability to study tumor evolution along convoluted 3D branching architectures, which is inaccessible to 2D methods.},
}

@article {pmid41332638,
year = {2025},
author = {McCutcheon, KR and Wu, J and Ozdemir, YC and McKinney, BJ and Srinivasan, S and Itokawa, A and Newsom, OJ and Vigil, A and Fox, DB and Sullivan, LB and Alvarez, JV},
title = {Recurrent Breast Cancer Cells Depend on De novo Pyrimidine Biosynthesis to Suppress Ferroptosis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41332638},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R01 CA285322/CA/NCI NIH HHS/United States ; R01 CA292658/CA/NCI NIH HHS/United States ; },
abstract = {Breast cancer recurrence remains a major clinical challenge, often associated with therapy resistance and altered metabolic states. To define metabolic vulnerabilities of recurrent disease, we performed a CRISPR knockout screen targeting 421 metabolic genes in paired primary and recurrent HER2-driven breast cancer cell lines. While both primary and recurrent tumors shared dependencies on core metabolic pathways, recurrent tumors exhibited selective essentiality for the de novo pyrimidine synthesis pathway, including Cad, Dhodh, and Ctps. Pharmacologic inhibition of the rate-limiting enzyme DHODH with BAY-2402234 selectively impaired the growth of recurrent tumor cells, while primary tumor cells were relatively resistant. BAY treatment robustly inhibited pyrimidine synthesis in all lines, but only recurrent cells underwent iron-dependent lipid peroxidation and ferroptotic cell death. Lipidomic profiling revealed enrichment of polyunsaturated ether phospholipids in recurrent cells, which may predispose them to ferroptosis. A sensitizer CRISPR screen in primary cells further identified nucleotide salvage and lipid metabolic pathways as modifiers of DHODH inhibitor sensitivity. Stable isotope tracing and nutrient depletion experiments showed that primary cells can compensate for DHODH inhibition through nucleotide salvage, whereas recurrent cells exhibit impaired salvage capacity, likely due to reduced expression of Slc28/Slc29 nucleoside transporters. Together, these findings reveal that breast cancer recurrence is associated with increased dependence on de novo pyrimidine synthesis to suppress ferroptosis, highlighting a therapeutically actionable metabolic vulnerability in recurrent disease.},
}

@article {pmid41397550,
year = {2025},
author = {Saultz, JN and Bolon, YT and Wang, T and Spellman, S and Lee, S and He, M and Camacho-Bydume, C and Krishna, C and Chowell, D and Shaffer, BC and Hsu, KC and Paczesny, S and Gadalla, SM and Marsh, SGE and Betts, BC and Arrieta-Bolaños, E},
title = {HIGHER HLA-DRB1 EVOLUTIONARY DIVERGENCE (HED) IS ASSOCIATED WITH REDUCED RELAPSE AND IMPROVED SURVIVAL AFTER MATCHED UNRELATED HEMATOPOIETIC CELL TRANSPLANTATION.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.12.949},
pmid = {41397550},
issn = {2666-6367},
abstract = {BACKGROUND: HLA evolutionary divergence (HED) can be used as a surrogate for the degree of immunopeptidome diversity of HLA phenotypes. Different degrees of HED in the patient-donor pair may influence the presentation of peptides relevant for alloreactive responses involved in graft-versus-host and graft-versus-leukemia (GvL) effects, potentially impacting outcomes after hematopoietic cell transplantation (HCT).

OBJECTIVE(S): To test whether higher HED scores (both class I and class II) correlate with improved GvL and survival after HLA-matched HCT.

STUDY DESIGN: Pediatric and adult patients (N=9,231) reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) database who underwent a first HCT from 8/8 matched unrelated donors between 2008 and 2018 for the treatment of acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, chronic myeloid leukemia, or lymphoma were included. HED was calculated on the amino acid sequences at HLA-A, HLA-B, HLA-C, and HLA-DRB1, and class I (HLA-A, HLA-B, HLA-C), and HLA-DRB1 HED scores were assigned to each patient-donor pair. The association between increasing HED (top quartile vs lower three quartiles) and HCT outcome was evaluated with malignant disease relapse and disease-free (DFS) and overall survival (OS) as primary endpoints. Secondary enpoints were transplant-related mortality (TRM), acute and chronic graft-versus-host disease (GvHD), and engraftment.

RESULTS: Greater HLA-DRB1 HED was associated with significantly decreased malignant disease relapse [HR 0.86; 95% CI, 0.79-0.94; P=0.0014], better disease free survival [HR 0.92; 95% CI, 0.86-0.98; P=0.0067] and improved OS [HR 0.91; 95% CI, 0.85-0.96; p=0.0019] in the total population after adjustment for other significant clinical variables. There was no significant association between HLA-DRB1 HED and TRM, or risk of acute or chronic GVHD. Conversely, higher (upper quartile) HLA class I HED did not significantly impact OS, DFS, TRM, relapse, or acute and chronic GVHD, compared with the lower three quartiles. In addition, neither class I nor HLA-DRB1 HED significantly impact neutrophil or platelet engraftment post transplant.

CONCLUSION(S): Higher HLA-DRB1 HED scores are associated with reduced relapse, improved DFS and OS in patients undergoing matched unrelated donor transplantation for hematological malignancies. These findings contribute to the growing evidence supporting the importance of HED in post-transplant outcomes. However, further refinement and validation are required before incorporating HED into clinical transplant risk assessment.},
}

@article {pmid41397238,
year = {2025},
author = {Cloos, J and Valk, PJM and Thiede, C and Döhner, K and Roboz, GJ and Wood, BL and Walter, RB and Wang, SA and Wierzbowska, A and Wei, AH and Wu, D and Vergez, F and Venditti, A and van der Reijden, BA and van de Loosdrecht, AA and Tiong, IS and Thol, FR and Subklewe, M and Roumier, C and Reuvekamp, T and Ravandi, F and Preudhomme, C and Plesa, A and Othman, J and Ossenkoppele, GJ and Ofran, Y and Mimoun, A and Maurillo, L and Majchrzak, A and de Leeuw, DC and Kern, W and Kim, DDHDH and Ikoma-Colturato, MRV and Haaksma, LH and Guzman, ML and Feuring, M and Depreter, B and Czyz, A and Bücklein, VL and Baer, C and Bachas, C and Freeman, SD and Buccisano, F and Hourigan, CS and Dillon, RJ and Heuser, M},
title = {2025 Update on MRD in Acute Myeloid Leukemia: A Consensus Document from the ELN-DAVID MRD Working Party.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025031480},
pmid = {41397238},
issn = {1528-0020},
abstract = {Measurable residual disease (MRD) monitoring has become a critical component in the management of acute myeloid leukemia (AML), to inform prognosis, guide therapy, and serve as a key endpoint in clinical trials. The 2025 update of the MRD guideline provides a comprehensive and refined framework for MRD assessment, aligned with the ELN 2022 genetic risk classification. Developed by members of the ELN-DAVID consortium, the guidelines incorporate expert consensus determined through a two-stage Delphi round. They address the clinical implementation of MRD methodologies, technical considerations, integration into clinical trials, and future directions. Importantly, MRD recommendations are tailored to individual prognostic and genetic subgroups. A new qualitative MRD response category, designated as optimal, warning, or high risk of treatment failure, has been introduced to facilitate contextual interpretation of the MRD burden and its clinical relevance. Notably, ultrahigh-sensitivity (UHS) NGS-based MRD assessment is now recommended for FLT3-ITD-mutated AML following intensive chemotherapy and prior to allogeneic hematopoietic cell transplantation. A total of 56 recommendations were formulated, with 53 achieving a high level of consensus (≥90%). These updated guidelines represent a major step forward toward harmonizing MRD assessments in AML and enhancing its clinical utility across diverse treatment settings.},
}

@article {pmid41397203,
year = {2025},
author = {Kouadio, C and Selukar, S and Othus, M and Chevret, S},
title = {Detecting the Cure Model Appropriateness in Randomized Clinical Trials With Long-Term Survivors.},
journal = {JCO clinical cancer informatics},
volume = {9},
number = {},
pages = {e2500084},
doi = {10.1200/CCI-25-00084},
pmid = {41397203},
issn = {2473-4276},
mesh = {Humans ; *Randomized Controlled Trials as Topic/methods ; *COVID-19/virology/mortality/epidemiology/therapy ; SARS-CoV-2/isolation & purification ; *Cancer Survivors/statistics & numerical data ; Computer Simulation ; *Models, Statistical ; },
abstract = {PURPOSE: To evaluate the appropriateness of a cure model when analyzing right-censored end points of a randomized clinical trial (RCT) in malignancy in the presence of long-term survivors. We aim to derive how the ratio estimation of censored cured subjects (RECeUS), previously proposed for a homogeneous population, could be extended for use in RCTs.

METHODS: Based on the RECeUS method, four decision rules were considered to assess the appropriateness of a cure model. They considered the eligibility conditions to be met: in both arms, in at least one randomized arm, in the entire sample, or when only considering an average of the conditions, respectively. A simulation study was performed to evaluate their performance and the impact of the link function when considering the appropriateness of cure models. We also illustrate the method using two real data examples from two RCTs conducted in patients with acute leukemia and COVID-19 disease.

RESULTS: Simulation results show that the best decision rule that can be applied in all considered treatment effect scenarios might be to check the criteria in at least one randomized arm. Regardless of the rules, the cure model appeared to be appropriate in both RCT data.

CONCLUSION: When analyzing survival data from RCTs, the appropriateness of a cure model could be considered in the face of a plateau shape of the survival curves. To ensure that the presence of such a plateau in the survival curves is a reliable indicator of the presence of cured patients in the population, the RECeUS method should be used in each randomized arm separately, with criteria met in at least one randomized arm.},
}

Humans
*Randomized Controlled Trials as Topic/methods
*COVID-19/virology/mortality/epidemiology/therapy
SARS-CoV-2/isolation & purification
*Cancer Survivors/statistics & numerical data
Computer Simulation
*Models, Statistical

@article {pmid41397186,
year = {2025},
author = {Huang, AH and Lee, GY and Lu, CA and Sahin, IH and King, GT and Safyan, RA and Cohen, SA and Zhen, DB and Shankaran, V and Harris, WP and Coveler, AL and Malhotra, J and Forbes, VE and Gold, PJ and Chiorean, EG and Hsieh, RW},
title = {Rechallenge With an Epidermal Growth Factor Receptor Inhibitor in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2500646},
doi = {10.1200/OP-25-00646},
pmid = {41397186},
issn = {2688-1535},
abstract = {PURPOSE: Clonal evolution is a mechanism of treatment resistance against epidermal growth factor receptor inhibitors (EGFRi) in metastatic colorectal cancer (mCRC). When EGFRi is discontinued, EGFRi-resistant tumor subclones decay with time, allowing for EGFRi rechallenge at later time. We conducted a meta-analysis to investigate the efficacy of EGFRi rechallenge in mCRC.

METHODS: Clinical trials and observational studies investigating the efficacy of EGFRi rechallenge in mCRC were included from PubMed and Embase from inception to December 8, 2024. Hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) were aggregated using Bayesian random-effects models. Objective response rates (ORRs) were aggregated using meta-random-effects models.

RESULTS: Twenty-nine studies were included. The pooled median PFS, median OS, and ORR were 3.83 months (95% CI, 3.25 to 4.50), 10.43 months (95% CI, 8.14 to 13.36), and 14.61% (95% CI, 8.70 to 23.51), respectively. EGFRi rechallenge was associated with significantly longer pooled PFS (HR, 0.54 [95% CI, 0.31 to 0.93]) and numerically longer pooled OS (HR, 0.71 [95% CI, 0.46 to 1.09]) than non-EGFRi systemic therapy. Patients without detectable RAS/RAF mutations by circulating tumor DNA (ctDNA) at the time of EGFRi rechallenge had significantly longer OS (HR, 0.43 [95% CI, 0.24 to 0.75]) and PFS (HR, 0.40 [95% CI, 0.26 to 0.62]) than those with ctDNA RAS/RAF mutations. Studies with EGFRi-free intervals ≥4 months before rechallenge (18.77%) had a numerically greater pooled ORR than those with EGFRi-free intervals <4 months (6.60%). No unexpected adverse events were reported, and treatment discontinuation because of adverse events was 2.7%.

CONCLUSION: EGFRi rechallenge is associated with significantly longer PFS, numerically longer OS, and clinically meaningful ORR as compared with non-EGFRi systemic therapy in mCRC, particularly for ctDNA RAS/RAF wild-type mCRC.},
}