@article {pmid40936721,
year = {2025},
author = {Parrish, AG and Holland, EC},
title = {Seq-ing answers: exploring meningioma biology utilizing bulk RNA-seq-based reference landscapes.},
journal = {Frontiers in oncology},
volume = {15},
number = {},
pages = {1631573},
pmid = {40936721},
issn = {2234-943X},
abstract = {Meningiomas are the most common primary brain tumors, accounting for 40% of all central nervous system neoplasms. While usually benign, these tumors can vary in aggressiveness. Traditional classification and grading systems, which primarily rely on histopathological features, are not always reliable in capturing tumor behavior and predicting patient outcomes. In contrast, modern systems-based on factors such as copy number alterations, DNA methylation, and gene expression-offer a more accurate framework for identifying distinct biological signatures and aggressive subtypes, as well as for predicting recurrence. Transcriptomic profiling using bulk whole-genome RNA sequencing (RNA-seq), which provides insights into alternative splicing, gene expression, fusion events, non-coding RNAs, and pathway activity, further enhances our understanding of meningioma tumorigenesis, enables the projection of new samples onto dimension-reduced reference landscapes, and helps accurately predict recurrence. As bulk RNA-seq becomes more accessible, it holds great potential for refining prognostic tools, informing personalized treatment approaches, and ultimately improving outcomes for meningioma patients.},
}

@article {pmid40935830,
year = {2025},
author = {Granadier, D and Cooper, K and Acenas, D and Kousa, A and Warren, M and Hernandez, V and Iovino, L and deRoos, P and Lederer, EE and Shannon-Sevillano, S and Kinsella, S and Evandy, C and van den Brink, MRM and Lemarquis, A and Dudakov, JA},
title = {Damage-induced IL-18 stimulates thymic NK cells limiting endogenous tissue regeneration.},
journal = {Nature immunology},
volume = {},
number = {},
pages = {},
pmid = {40935830},
issn = {1529-2916},
support = {R01-HL145276//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R35-HL171556//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL165673//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; U01-AI70035//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/ ; P01-AG052359//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; P30-CA015704//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; F30-HL165761//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; },
abstract = {Interleukin-18 (IL-18) is an acute-phase proinflammatory molecule crucial for mediating viral clearance by activating T helper 1 CD4[+] T cells, cytotoxic CD8[+] T cells and natural killer (NK) cells. Here, we show that mature IL-18 is generated in the thymus following numerous distinct forms of tissue damage, all of which cause caspase-1-mediated immunogenic cell death. We report that IL-18-stimulated cytotoxic NK cells limit endogenous thymic regeneration, a critical process that ensures the restoration of immune competence after acute insults such as stress, infection, chemotherapy and radiation. NK cells suppress thymus recovery by aberrantly targeting thymic epithelial cells, which act as the master regulators of organ function and regeneration. Together, our data reveal a new pathway regulating tissue regeneration in the thymus and suggest IL-18 as a potential therapeutic target to boost thymic function. Moreover, given the enthusiasm for IL-18 as a cancer immunotherapy due to its capacity to elicit a type 1 immune response, these findings also offer insight into potential off-target effects.},
}

@article {pmid40935610,
year = {2025},
author = {Uribe, C and Iravani, A and Savir-Baruch, B and Jacene, H and Graves, SA and Dewaraja, YK and Heath, CL and Hope, TA},
title = {Summary: SNMMI/ACNM Procedure Standard for Posttreatment Imaging of [177]Lu-Based Radiopharmaceuticals.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.125.270979},
pmid = {40935610},
issn = {1535-5667},
}

@article {pmid40934451,
year = {2025},
author = {Necchi, A and Galsky, MD and Dizman, N and Aggen, DH and Agarwal, N and Al-Ahmadie, H and Apolo, AB and Ballas, L and Bangs, R and Black, PC and Brausi, M and Brembilla, G and Cheng, L and Chiti, A and Cimadamore, A and Colecchia, M and Daneshmand, S and Di Stasi, S and Efstathiou, JA and Filicevas, A and Geynisman, DM and Grivas, P and Gupta, S and Iasonos, A and James, ND and Lerner, SP and Loriot, Y and Makaroff, LE and Maluf, F and Moschini, M and Ostrovnaya, I and Pal, SK and Plimack, ER and Prakash, G and Psutka, SP and Rosenberg, JE and Sadeghi, S and Schmidt, B and Schwartz, LH and Sonpavde, GP and St Laurent, MP and Ye, D and Spiess, PE and Kamat, AM},
title = {End Points for the Next-Generation Bladder-Sparing Perioperative Trials for Patients With Muscle-Invasive Bladder Cancer.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2501608},
pmid = {40934451},
issn = {1527-7755},
support = {ZIA BC011351/ImNIH/Intramural NIH HHS/United States ; },
abstract = {PURPOSE: The evolving treatment landscape of muscle-invasive bladder cancer (MIBC) increasingly warrants novel trial design to evaluate perioperative strategies aimed at bladder preservation. To establish standardized outcome measures for evaluating organ preservation strategies in MIBC, the International Bladder Cancer Group (IBCG) and the Global Society of Rare Genitourinary Tumors (GSRGT) assembled an international, multidisciplinary consensus panel.

METHODS: The IBCG and GSRGT gathered global bladder cancer experts and patient advocates to establish a framework for risk-adapted bladder-sparing treatment approaches for MIBC. Working groups reviewed the literature and developed draft recommendations, which were discussed at a live meeting in December 2024 in Milan. This was followed by voting by the members using a modified Delphi process. Recommendations achieving ≥75% agreement during the meeting were further refined and presented.

RESULTS: Clinical complete response (cCR) definition should encompass the absence of high-grade malignancy on pathology and malignant cells on urine cytology and no evidence of local or metastatic disease on cross-sectional imaging. Although cCR remains immature as a primary or coprimary end point in registrational trials, it could serve as a suitable end point in early-phase studies and risk-adapted investigations. Event-free survival (EFS) remains the preferred primary end point as it could reliably capture the durability of clinically meaningful benefit after omittance of surgical consolidation or chemoradiation. Given the composite nature of EFS, events should be prespecified, evaluated in an intention-to-treat approach, and meticulously collected. Continuous assessment of individual patient preferences should begin at the outset of perioperative therapy discussions, with informed decision making prioritized throughout.

CONCLUSION: The consensus definition of cCR and the framework presented in this study can serve as a foundation for thorough testing of risk-adapted bladder-sparing treatment paradigms for MIBC.},
}

@article {pmid40934429,
year = {2025},
author = {Esmaeili, S and Owens, K and Avila-Ponce de Leon, U and Standing, JF and Lowe, DM and Zhang, S and Watson, JA and Schilling, WH and Wagoner, J and Polyak, SJ and Schiffer, JT},
title = {Molnupiravir clinical trial simulation suggests that polymerase chain reaction underestimates antiviral potency against SARS-CoV-2.},
journal = {The Journal of clinical investigation},
volume = {},
number = {},
pages = {},
doi = {10.1172/JCI192052},
pmid = {40934429},
issn = {1558-8238},
abstract = {Molnupiravir is an antiviral medicine that induces lethal copying errors during SARS-CoV-2 RNA replication. Molnupiravir reduced hospitalization in one pivotal trial by 50% and had variable effects on reducing viral RNA levels in three separate trials. We used mathematical models to simulate these trials and closely recapitulated their virologic outcomes. Model simulations suggest lower antiviral potency against pre-omicron SARS-CoV-2 variants than against omicron. We estimate that in vitro assays underestimate in vivo potency 6-7 fold against omicron variants. Our model suggests that because polymerase chain reaction detects molnupiravir mutated variants, the true reduction in non-mutated viral RNA is underestimated by ~0.4 log10 in the two trials conducted while omicron variants dominated. Viral area under the curve estimates differ significantly between non-mutated and mutated viral RNA. Our results reinforce past work suggesting that in vitro assays are unreliable for estimating in vivo antiviral drug potency and suggest that virologic endpoints for respiratory virus clinical trials should be catered to the drug mechanism of action.},
}

@article {pmid40934225,
year = {2025},
author = {Mkhize, NN and Li, SS and Hu, J and Robinson, ST and Hoosain, Z and Garrett, N and Chirenje, ZM and Fleurs, L and Kaldine, H and Modise, T and Moore, PL and Randhawa, AK and Sholukh, AM and Hutter, J and Polakowski, L and Corey, L and Gill, K and Montefiori, DC and Janes, H and Karuna, S and , },
title = {Neutralizing antibody responses over time in a demographically and clinically diverse cohort of individuals recovered from SARS-CoV-2 acquisition in Africa: A cohort study.},
journal = {PLOS global public health},
volume = {5},
number = {9},
pages = {e0005156},
pmid = {40934225},
issn = {2767-3375},
support = {UM1 AI068614/AI/NIAID NIH HHS/United States ; UM1 AI068618/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; },
abstract = {COVID-19 has affected millions worldwide. Research characterized immune responses of individuals who acquired SARS-CoV-2 and identified co-factors, such as HIV, associated with greater likelihood of poor clinical outcomes. SARS-CoV-2-specific neutralizing antibodies (nAbs) are a strong correlate of protection but their elicitation in people living with HIV (PLWH), and particularly in southern Africa, is less well characterized. HVTN 405/HPTN 1901 was an observational cohort study of individuals recently recovered from SARS-CoV-2. We describe 323 participants enrolled early in the pandemic (June 2020 to January 2021) in Zambia (n = 12), Malawi (n = 13), Zimbabwe (n = 59), and South Africa (n = 239), profiling their SARS-CoV-2-specific nAb responses and associations with demographics, comorbidities, disease severity, and time since diagnosis based on linear and logistic regression. Participants' median age was 39 years, 63.5% were assigned female sex at birth, 71.2% were black African, and 39 (12.1%) were PLWH. Approximately one in four participants (25.7%) had asymptomatic SARS-CoV-2, 47.4% were symptomatic but not hospitalized, and 26.9% were hospitalized with COVID-19. Participants in these groups were enrolled at a median of 51.5 days, 53 days, and 60 days post-SARS-CoV-2 diagnosis, respectively. SARS-CoV-2 nAbs were measured in serum using one of two calibrated assays. Most (291/322, 90.4%) participants had positive nAb responses at enrollment. Across all participants, nAb responses generally declined in magnitude between enrollment and 2-3 months thereafter, then increased through month 12 coincident with epidemiologically observed new waves of acquisition. In a multivariate model adjusted for potentially confounding factors, PLWH had a 65% lower geometric mean (GM) nAb ID50 titer compared to people without HIV (PWOH) (GMR: 0.35, p = 0.003, q = 0.006). Greater disease severity, older age (>55 years), high BMI (≥30) and diabetes were associated with higher nAb ID50 titers (all p < 0.05, all q < 0.20).These findings are important, as nAb titers are predictive of vulnerability to COVID-19.},
}

@article {pmid40934109,
year = {2025},
author = {Azhideh, A and Haseli, S and Schaub, SK and Amini, B and Hosseini, N and Mansoori, B and Chalian, H and Mirghaderi, P and Hall, ET and Chalian, M},
title = {Musculoskeletal Complications of Radiation Therapy and Immunotherapy.},
journal = {Radiographics : a review publication of the Radiological Society of North America, Inc},
volume = {45},
number = {10},
pages = {e250014},
doi = {10.1148/rg.250014},
pmid = {40934109},
issn = {1527-1323},
mesh = {Humans ; *Immunotherapy/adverse effects ; *Musculoskeletal Diseases/etiology/diagnostic imaging ; *Radiation Injuries/diagnostic imaging/etiology ; *Radiotherapy/adverse effects ; },
abstract = {Radiation therapy (RT) and immunotherapy are widely used in modern oncologic care and are both associated with a broad spectrum of musculoskeletal complications. These adverse effects can be acute or delayed and include bone fragility, insufficiency fractures, osteoradionecrosis, cartilage degeneration, inflammatory arthritis, myositis, and tendinopathy. Many of these complications can closely mimic metastatic disease or infection, creating diagnostic challenges. RT-induced musculoskeletal injuries are influenced by factors such as total dose, fractionation, and technique, with newer modalities such as stereotactic body RT and proton beam therapy associated with specific imaging appearances and complication profiles. Immunotherapy, particularly immune checkpoint inhibitor medication, has introduced a distinct set of immune-related adverse events affecting the musculoskeletal system, including inflammatory arthropathy, myositis, and enthesitis, often occurring in seronegative patterns and overlapping with other systemic toxicities. The authors provide an in-depth overview of the radiobiologic principles underlying RT, the evolving landscape of immunotherapy, and the diverse musculoskeletal complications that arise from both therapies. Emphasis is placed on the clinical context and imaging features that aid in recognizing and differentiating these conditions from neoplastic or infectious processes. A thorough understanding of these complications is essential for accurate diagnosis, timely management, and improved patient outcomes. [©]RSNA, 2025 Supplemental material is available for this article.},
}

Humans
*Immunotherapy/adverse effects
*Musculoskeletal Diseases/etiology/diagnostic imaging
*Radiation Injuries/diagnostic imaging/etiology
*Radiotherapy/adverse effects

@article {pmid40909752,
year = {2025},
author = {Gieselmann, L and DeLaitsch, AT and Rohde, M and Gruell, H and Kreer, C and Ercanoglu, MS and Gristick, HB and Schommers, P and Ahmadov, E and Radford, C and Mazzolini, A and Zhang, L and West, AP and Worczinski, J and Momot, A and Reichwein, ML and Knüfer, J and Stumpf, R and Mkhize, NN and Kaldine, H and Bhebhe, S and Deshpande, S and Giovannoni, F and Stefanutti, E and Benigni, F and Havenar-Daughton, C and Corti, D and Kroidl, A and Adhikari, A and Nanfack, AJ and Ambada, GE and Duerr, R and Maganga, L and William, W and Ntinginya, NE and Wolf, T and Geldmacher, C and Hoelscher, M and Lehmann, C and Moore, PL and Mora, T and Walczak, AM and Gilbert, PB and Doria-Rose, NA and Huang, Y and Bloom, JD and Seaman, MS and Bjorkman, PJ and Klein, F},
title = {Profiling a large HIV-1 elite neutralizer cohort reveals remarkable CD4bs bNAb for HIV-1 prevention and therapy.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40909752},
issn = {2692-8205},
support = {INV-036842/GATES/Gates Foundation/United States ; U54 AI170856/AI/NIAID NIH HHS/United States ; INV-002143/GATES/Gates Foundation/United States ; U01 AI169385/AI/NIAID NIH HHS/United States ; P01 AI100148/AI/NIAID NIH HHS/United States ; R01 AI140891/AI/NIAID NIH HHS/United States ; },
abstract = {Administration of HIV-1 neutralizing antibodies can suppress viremia and prevent infection in vivo. However, clinical use is challenged by broad envelope sequence diversity and rapid emergence of viral escape[1-9]. Here, we performed single B cell profiling of 32 top HIV-1 elite neutralizers to identify broadly neutralizing antibodies (bNAbs) with highest potency and breadth for clinical application. From 831 expressed monoclonal antibodies, we identified 04_A06, a new VH1-2-encoded CD4 binding site bNAb with remarkable breadth and potency against extended multiclade pseudovirus panels (GeoMean IC50 = 0.059 μg/ml, breadth = 98.5%, 332 virus strains). Moreover, 04_A06 was not susceptible to classic viral CD4bs escape variants and maintained full viral suppression in HIV-1-infected humanized mice. Structural analyses revealed that antiviral activity is mediated by an unusually long 11-amino acid heavy chain insertion. This insertion facilitates inter-protomer contacts and interactions with highly conserved residues on the adjacent gp120 protomer. Finally, 04_A06 demonstrated high activity against contemporaneously circulating viruses from the Antibody Mediated Prevention (AMP) trials (GeoMean IC50 = 0.082 μg/ml, breadth = 98.4%, 191 virus strains) and in silico modeling for 04_A06LS predicted HIV-1 prevention efficacy of >93%. Thus, 04_A06 will provide unique opportunities for effective treatment and prevention strategies of HIV-1 infection.},
}

@article {pmid40909728,
year = {2025},
author = {Romero, EV and Clyde, AE and Giorgi, EE and Westfall, DH and Azam, W and Taylor, ML and Caskey, M and Feder, AF and Cohn, LB},
title = {Distinct modes of evolution drive HIV escape from two broadly neutralizing antibodies.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40909728},
issn = {2692-8205},
support = {DP2 CA280623/CA/NCI NIH HHS/United States ; U01 AI169385/AI/NIAID NIH HHS/United States ; },
abstract = {Broadly neutralizing antibodies (bNAbs) show promise for HIV treatment and prevention, but are vulnerable to resistance evolution. Comprehensively understanding in vivo viral escape from individual bNAbs is necessary to design bNAb combinations that will provide durable responses. We characterize viral escape from two such bNAbs, 10-1074 and 3BNC117, using deep, longitudinal sequencing of full length HIV envelope (env) genes from study participants treated with bNAb monotherapy. Improved sequencing depth and computational evolutionary analyses permit us to identify in vivo routes and parallelism underlying HIV escape from each bNAb, providing new insights into this evolutionary process: 10-1074 escape is restricted to a small number of previously documented pathways, but these escape mutations 1) pre-exist in intra-host viral populations before therapy, 2) are not all equally preferred, and 3) emerge with a high degree of genetic parallelism within and across viral populations. In contrast, 3BNC117 escape follows background-specific patterns in which specific escape mutations present in one population rarely emerge or spread in other populations, but often still exhibit parallel evolutionary responses within their host. That bNAbs elicit starkly different in vivo escape profiles depending on their Env target exposes the limitations of generalizing escape patterns across therapies and highlights the substantial challenges in predicting a viral population's bNAb susceptibility from genetic diversity alone.},
}

@article {pmid40909710,
year = {2025},
author = {Gautier, O and Blum, JA and Nguyen, TP and Klemm, S and Yamakawa, M and Sinnott-Armstrong, N and Zeng, Y and Davis, CO and Bombosch, J and Nakayama, L and Guttenplan, KA and Chen, D and Kathira, A and Zhao, L and Rexach, JE and Greenleaf, WJ and Gitler, AD},
title = {An emergent disease-associated motor neuron state precedes cell death in a mouse model of ALS.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40909710},
issn = {2692-8205},
support = {R01 AG075802/AG/NIA NIH HHS/United States ; R01 NS128028/NS/NINDS NIH HHS/United States ; RF1 NS128800/NS/NINDS NIH HHS/United States ; U54 NS123743/NS/NINDS NIH HHS/United States ; R01 AG064690/AG/NIA NIH HHS/United States ; S10 RR025518/RR/NCRR NIH HHS/United States ; RM1 HG010461/HG/NHGRI NIH HHS/United States ; R35 NS137159/NS/NINDS NIH HHS/United States ; },
abstract = {To uncover molecular determinants of motor neuron degeneration and selective vulnerability in amyotrophic lateral sclerosis (ALS), we generated longitudinal single-nucleus transcriptomes and chromatin accessibility profiles of spinal motor neurons from the SOD1-G93A ALS mouse model. Vulnerable alpha motor neurons showed thousands of molecular changes, marking a transition into a novel cell state we named 'disease-associated motor neurons' (DAMNs). We identified transcription factor regulatory networks that govern how healthy cells transition into DAMNs as well as those linked to vulnerable and resistant motor neuron subtypes. Using spatial transcriptomics, we found reactive glia located near motor neurons early in disease, suggesting early signaling events between motor neurons and glia. Finally, we found that the human orthologs of genomic regions with differential accessibility in SOD1-G93A alpha motor neurons are enriched for single nucleotide polymorphisms associated with human ALS, providing evidence that the genetic underpinnings of motor neuron vulnerability are conserved.},
}

@article {pmid40932993,
year = {2025},
author = {Repele, A and Pande, D and Enstrom, MR and Perez, AM and Cui, M and Madhu, R and Nelson, V and Kiem, HP and Radtke, S},
title = {GroβT rapidly and reliably mobilizes primitive hematopoietic stem and progenitor cells in nonhuman primates.},
journal = {Molecular therapy. Methods & clinical development},
volume = {33},
number = {3},
pages = {101558},
pmid = {40932993},
issn = {2329-0501},
abstract = {Autologous hematopoietic stem cell (HSC) gene therapy has gone through remarkable advancements in recent years, especially for the treatment of sickle cell disease (SCD). However, the collection of HSCs from SCD patients requires unique considerations, as granulocyte colony-stimulating factor (G-CSF)-mediated mobilization is contraindicated, and plerixafor-only mobilization is highly variable. Consequently, alternative mobilization regimens that are safe for SCD patients and generate better cell yields are desirable for SCD HSC gene therapy. Here, we evaluated a combination of plerixafor (AMD3100, a CXCR4 antagonist) with GroβT (MGTA-145/GroβT, a CXCR2 agonist) against the current gold-standard G-CSF for HSC gene therapy in nonhuman primates (NHPs) for HSC mobilization, leukapheresis, ex vivo gene editing to reactivate fetal hemoglobin, and transplantation. AMD3100/GroβT rapidly and reliably mobilized phenotypically primitive HSCs within hours even in a G-CSF non-responder. Average CD34/CD90 frequency in the blood and yields after enrichment were comparable in both mobilization regimens. Rapid recovery and robust multilineage long-term engraftment of gene-modified HSCs was achieved in the bone marrow and blood of animals. In summary, AMD3100/GroβT allows highly efficient and reliable mobilization of HSCs, providing a G-CSF-free regimen specifically for SCD but also any other hematological disease or disorder treatable with HSC gene therapy.},
}

@article {pmid40931630,
year = {2025},
author = {Ball-Burack, M and Menssen, A and Eidenschink Brodersen, L and Nalla, A and Loken, M and Pardo, L and Dahlberg, A and Hudson, C and Meshinchi, S and Tarlock, K},
title = {A Case of Blinatumomab Efficacy in RAM Immunophenotype/CBFA2T3::GLIS2 Fusion AML.},
journal = {Pediatric blood & cancer},
volume = {},
number = {},
pages = {e32035},
doi = {10.1002/pbc.32035},
pmid = {40931630},
issn = {1545-5017},
}

@article {pmid40931545,
year = {2025},
author = {Poh, C and Chen, X and Voutsinas, J and Naresh, K and Dizon, JJ and Shadman, M and Lynch, RC and Till, BG and Ujjani, CS and Di, M and Raghunathan, V and Warren, EH and Smith, SD and Wu, QV and Cherian, S and Gopal, AK},
title = {Impact of immunophenotype on clinical disease characteristics and outcomes in T-cell prolymphocytic leukaemia.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.70113},
pmid = {40931545},
issn = {1365-2141},
}

@article {pmid40931081,
year = {2025},
author = {Wen, L and Miyagi, H and Spiess, PE and Yu, A and Mendelsohn, CL and Tan, WS and Psutka, SP and Lerner, SP and Cheng, L and Dyrskjøt, L and Meeks, JJ and Shariat, SF and Gontero, P and Pradere, B and Steinberg, GD and Kamat, AM and Li, R},
title = {Low-grade non-muscle-invasive bladder cancer: molecular landscape, treatment strategies and emerging therapies.},
journal = {Nature reviews. Urology},
volume = {},
number = {},
pages = {},
pmid = {40931081},
issn = {1759-4820},
abstract = {Low-grade non-muscle invasive bladder cancer is a specific category of bladder cancer with a favourable prognosis; however, its management presents several challenges. The risk of stage progression is very low, but approximately half of patients will experience recurrence within the first 5 years after diagnosis. This high propensity for recurrence, coupled with the threat of progression, mandates ongoing surveillance. However, the optimal frequency and duration of follow-up monitoring remain undefined. Current management strategies for low-grade non-muscle invasive bladder cancer rely heavily on routine office cystoscopy, with few advances in diagnostic and treatment options over the past 25 years. Our basic understanding of disease biology has substantially advanced. However, at present, considerable variations in clinical practice exist, with implications for increased financial and treatment burden for patients and health care systems. Molecular signatures and biomarker discoveries are crucial to understand disease behaviour and inform novel treatment strategies. Emerging therapies, such as advanced drug-delivery systems, immunomodulatory agents and targeted therapies, offer the potential to improve patient outcomes, streamline management and reduce the need for surveillance cystoscopies. Actionable avenues for future research in the field include prospective validation of novel biomarkers and therapies with the ultimate aim of optimizing patient care and reducing health care costs.},
}

@article {pmid40930249,
year = {2025},
author = {Newsom, OJ and Zheng, E and Sullivan, LB},
title = {Defined media reveals the essential role of lipid scavenging in supporting cancer cell proliferation.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {110693},
doi = {10.1016/j.jbc.2025.110693},
pmid = {40930249},
issn = {1083-351X},
abstract = {Fetal bovine serum (FBS) is an undefined additive that is ubiquitous to mammalian cell culture media and whose functional contributions to promoting cell proliferation remain poorly understood. Efforts to replace serum supplementation in culture media have been hindered by an incomplete understanding of the environmental requirements fulfilled by FBS. Here, we use a combination of live-cell imaging and quantitative lipidomics to elucidate the role of serum in supporting proliferation. We show that serum provides consumed factors that enable proliferation, with serum metal and lipid components serving as crucial metabolic resources. Despite access to a wide range of lipid classes available in serum, we find albumin-bound lipids are the primary species consumed by cancer cells. Furthermore, we find that supplementing with additives that contain necessary metals and any of the albumin-associated lipid classes can obviate the FBS requirement for cancer cell proliferation. Using this defined system, we investigated cancer cell lipid consumption dynamics, finding that albumin-associated lipids are primarily consumed through a mass-action mechanism with minimal competition within or amongst lipid classes. We also find that lipid scavenging is a dominant lipid acquisition route and is necessary for cancer cell proliferation. This work therefore identifies metabolic contributions of serum and provides a framework for building defined culture systems that sustain cell proliferation without the undefined contributions of serum.},
}

@article {pmid40930223,
year = {2025},
author = {Portuguese, AJ and Tuazon, SA and Pont, MJ and Cole, GO and Sather, BD and Song, X and Thomas, S and Wood, BL and Blake, M and Works, MG and Shadman, M and Liang, EC and Wu, VQ and Voutsinas, JM and Gooley, TA and Turtle, CJ and Till, BG and Coffey, DG and Maloney, DG and Libby, EN and Chapuis, AG and Milano, F and Riddell, SR and Green, DJ and Cowan, AJ},
title = {Impact of Gamma-Secretase Inhibition on Outcomes Following BCMA CAR-T Therapy in Multiple Myeloma: A Comparison of Two Phase 1 Trials.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.09.003},
pmid = {40930223},
issn = {2666-6367},
abstract = {BACKGROUND: BCMA-directed chimeric antigen receptor (CAR)-T cell therapy represents a major therapeutic breakthrough for relapsed/refractory multiple myeloma (RRMM), offering deep and durable responses in heavily pretreated patients. However, a subset of patients experience early relapse or fail to respond, highlighting the need for strategies to enhance efficacy. Gamma-secretase inhibitors (GSIs) have been shown to increase surface BCMA expression on malignant plasma cells and may potentiate the activity of BCMA CAR-T cells, particularly in patients with low baseline BCMA antigen density. Two contemporaneous phase 1 trials (FH9952 and FH9762) evaluated the fully human BCMA-targeted CAR-T product FCARH143, with FH9952 incorporating GSI co-administration.

OBJECTIVE: To determine whether GSI use improves clinical outcomes following FCARH143 CAR-T therapy in RRMM, with particular focus on overall survival (OS), progression-free survival (PFS), and subgroup differences based on prior BCMA-targeted therapy and baseline tumor BCMA levels.

STUDY DESIGN: This retrospective analysis compared outcomes from two single-arm, single-center phase 1 trials of the fully human BCMA-targeted CAR-T cell product FCARH143 in RRMM: FH9952 (n=18), which incorporated the GSI crenigacestat, and FH9762 (n=25), which did not. Both studies had extended follow-up beyond previously published reports. Eligible patients had measurable RRMM with ≥10% bone marrow plasma cell involvement and confirmed BCMA expression. BCMA-naïve patients were defined as those without prior exposure to BCMA-targeted therapies (e.g., BCMA CAR-T, bispecific antibodies, or antibody-drug conjugates); BCMA-exposed patients had received at least one such therapy. All participants received lymphodepletion with fludarabine and cyclophosphamide followed by infusion of FCARH143. In FH9952, crenigacestat (25 mg orally, three times weekly) was administered from day 0 through day +18. Outcomes included response rates, adverse events, OS, and PFS. Cox proportional hazards models were used for survival analysis.

RESULTS: With extended follow-up (median 5.8 years), the overall cohort (n=43) had a median OS of 2.7 years (95% CI 1.9-4.8) and median PFS of 1.1 years (95% CI 0.72-2.2). Baseline characteristics were generally similar, though BCMA-exposed status was more frequent in FH9952 (39% vs. 8%). Rates of cytokine release syndrome, immune effector cell-associated neurotoxicity, and early immune effector cell-associated hematotoxicity were comparable between trials. Among BCMA-naïve patients (n=34), GSI use was associated with improved OS (not reached vs. 2.3 years; adjusted HR 0.30, 95% CI 0.10-0.88, p=0.028) and a trend toward improved PFS (2.6 vs. 1.3 years; adjusted HR 0.47, 95% CI 0.22-1.04, p=0.062). No benefit was observed among BCMA-exposed patients. Exploratory spline modeling suggested GSI mitigated the adverse impact of low tumor BCMA levels, with inferior outcomes at low BCMA expression observed only in the non-GSI cohort.

CONCLUSIONS: Co-administration of a GSI with BCMA CAR-T therapy was associated with improved survival in BCMA-naïve RRMM patients, particularly those with low baseline tumor BCMA levels. These findings suggest GSI modulation of BCMA surface expression may enhance CAR-T efficacy in select patients and support further prospective investigation.},
}

@article {pmid40930044,
year = {2025},
author = {Diemert, DJ and Graciaa, DS and Zhang, B and Rouphael, NG and Branche, AR and Martin, TCS and Jackson, LA and Presti, RM and Kamidani, S and Mahgoub, SM and Babu, TM and Magaret, CA and Simon, V and van Bakel, H and Roberts, PC and Beigel, JH and Gilbert, PB and Follmann, D and , },
title = {Effect of Omicron BA.1-based compared to prototype booster mRNA vaccination on incidence of COVID-19 in the COVAIL trial.},
journal = {Vaccine},
volume = {64},
number = {},
pages = {127718},
doi = {10.1016/j.vaccine.2025.127718},
pmid = {40930044},
issn = {1873-2518},
abstract = {BACKGROUND: Covid-19 vaccines are updated to match circulating strains based on reasoning that better strain-matched immunogenicity should provide better protection. Randomized evidence with disease endpoints to support strain matching is lacking. We evaluated COVID-19 incidence among adults randomized to a second booster of Prototype or Omicron-based vaccines.

METHODS: COVAIL was a four-stage Phase 2 clinical trial; results from Stages 1 (mRNA-1273 [Moderna]) and 2 (BNT162b2 [Pfizer/BioNTech]) are described here. Adults who had received a primary series and one booster of an authorized COVID-19 vaccine were eligible. Participants received one dose of either Prototype vaccine or a monovalent or bivalent Omicron BA.1 vaccine. SARS-CoV-2 neutralization titers (ID50) were measured pre- and post-vaccination. Covariate-adjusted cumulative COVID-19 incidence and Cox regression analyses were conducted separately for each stage.

RESULTS: 706 participants with pre- and day 15 post-vaccination ID50 titers (n = 503 in Stage 1, n = 203 in Stage 2) were included. Within stages, participant characteristics and baseline ID50 titers were similar between Prototype and Omicron-based arms. There was no difference in cumulative COVID-19 incidence for Prototype vs. Omicron-based vaccine in Stage 1 (RR 1.04, 95 % CI 0.73-1.48), while incidence was higher among Prototype recipients in Stage 2 (RR 2.56, 1.44-4.52). Cox regression analysis showed no difference in Stage 1 (HR 1.04, 0.68-1.58), but higher incidence for Prototype recipients in Stage 2 (HR 2.95, 1.52-5.72).

CONCLUSIONS: Omicron-based vaccines as second boosters were more protective against COVID-19 relative to Prototype among those receiving BNT162b2 but not mRNA-1273. Differences between stages such as force of infection, antigen matching, and vaccine differences may explain this finding.

CLINICALTRIALS: govRegistry Number: NCT05289037.},
}

@article {pmid40929366,
year = {2025},
author = {Goya, S and Greninger, AL},
title = {Distinct Evolutionary Signatures of Human Parainfluenza Viruses 2 and 4 Reveal Host Antagonism Divergence and Phylogenetic Discordance.},
journal = {Molecular biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/molbev/msaf217},
pmid = {40929366},
issn = {1537-1719},
abstract = {Human parainfluenza virus 2 (HPIV-2) and human parainfluenza virus 4 (HPIV-4) are significant but underappreciated respiratory pathogens, particularly among high-risk populations including children, the elderly, and immunocompromised individuals. In this study, we sequenced 101 HPIV-2 and HPIV-4 genomes from respiratory samples collected in western Washington State and performed comprehensive evolutionary analyses using both new and publicly available sequences. Phylogenetic and phylodynamic analyses revealed that both HPIV-2 and HPIV-4 evolve at significantly faster rates compared to mumps virus, a reference human orthorubulavirus. Notably, while HPIV-2 demonstrated the highest evolutionary rates in the surface glycoprotein HN, consistent with humoral immune-driven selection, the innate immune antagonist V/P gene evolved fastest in HPIV-4. We identified a hypervariable region within the HPIV-4 V/P protein (residues 35-75), which structural modeling placed in a loop overlapping a known interferon antagonism domain in other paramyxovirus V proteins, though HPIV-4 is functionally incompetent in this activity. Expanded phylogenetic analysis across the Paramyxoviridae family uncovered a striking evolutionary discordance: while the HN glycoprotein and L polymerase of HPIV-4 and its two closest bat-derived viruses clustered within the Orthorubulavirus genus, their nucleoprotein (N), phosphoprotein (P), matrix (M), and fusion (F) proteins formed a distinct lineage outside the Rubulavirinae subfamily. Together, these findings highlight the distinct evolutionary trajectories of HPIV-2 and HPIV-4, raise hypotheses around complex Paramyxoviridae zoonotic events including recombination-like patterns, and demonstrate limitations of current L protein-based taxonomic classification schemes.},
}

@article {pmid40929264,
year = {2025},
author = {Hollis, JA and Chan, MC and Malik, HS and Campbell, MG},
title = {Molecular exaptation by the integrin αI domain.},
journal = {Science advances},
volume = {11},
number = {37},
pages = {eadx9567},
pmid = {40929264},
issn = {2375-2548},
mesh = {Cryoelectron Microscopy ; Protein Domains ; Animals ; Humans ; Protein Binding ; Ligands ; Evolution, Molecular ; Models, Molecular ; *Integrin alpha Chains/chemistry/metabolism ; Binding Sites ; },
abstract = {Integrins bind ligands between their alpha (α) and beta (β) subunits and transmit signals through conformational changes. Early in chordate evolution, some α subunits acquired an "inserted" (I) domain that expanded integrin's ligand-binding repertoire but obstructed the ancestral ligand pocket, seemingly blocking conventional integrin activation. Here, we compare cryo-electron microscopy structures of apo and ligand-bound states of the I domain-containing αEβ7 integrin and the I domain-lacking α4β7 integrin to illuminate how the I domain intrinsically mimics an extrinsic ligand to preserve integrin function. We trace the I domain's evolutionary origin to an ancestral collagen-collagen interaction domain, identifying an ancient molecular exaptation that facilitated integrin activation immediately upon I domain insertion. Our analyses reveal the evolutionary and biochemical basis of expanded cellular communication in vertebrates.},
}

Cryoelectron Microscopy
Protein Domains
Animals
Humans
Protein Binding
Ligands
Evolution, Molecular
Models, Molecular
*Integrin alpha Chains/chemistry/metabolism
Binding Sites

@article {pmid40929164,
year = {2025},
author = {Colegrove, HL and Monnat, RJ and Feder, AF},
title = {Epithelial competition determines gene therapy potential to suppress Fanconi Anemia oral cancer risk.},
journal = {PLoS computational biology},
volume = {21},
number = {9},
pages = {e1012915},
doi = {10.1371/journal.pcbi.1012915},
pmid = {40929164},
issn = {1553-7358},
abstract = {Fanconi Anemia (FA) is a heritable syndrome characterized by DNA damage repair deficits, frequent malformations and a significantly elevated risk of bone marrow failure, leukemia, and mucosal head and neck squamous cell carcinomas (HNSCC). Hematopoietic stem cell gene therapy can prevent marrow failure and lower leukemia risk, but mucosal gene therapy to lower HNSCC risk remains untested. Major knowledge gaps include an incomplete understanding of how rapidly gene-corrected cellular lineages could spread through the oral epithelium, and which delivery parameters are critical for ensuring efficient gene correction. To answer these questions, we extended an agent-based model of the oral epithelium to include the delivery of gene correction in situ to FA cells and the competitive dynamics between cellular lineages with and without gene correction. We found that only gene-corrected lineages with substantial proliferative advantages (probability of resisting displacement out of the basal layer [Formula: see text]) could spread on clinically relevant timelines, and that these lineages were initially at high risk of loss in the generations following correction. Delivering gene correction to many cells minimizes the risk of loss, while delivery to many distinct locations within a tissue maximizes the rate of spread. To determine the impact of mucosal gene therapy in preventing the clonal expansion of pre-cancerous mutations, we compared the expected burden of TP53 mutations in simulated tissue sections with and without gene correction. We found that when FA cells have elevated genome instability or a TP53-dependent proliferative advantage, gene correction can substantially reduce the accumulation of pro-tumorigenic mutations. This model illustrates the power of computational frameworks to identify critical determinants of therapeutic success to enable experimental optimization and support novel and effective gene therapy applications.},
}

@article {pmid40929058,
year = {2025},
author = {Haas, JS and Todd, KW and Mclerran, D and Tiro, JA and Vachani, A and Kobrin, S and Saia, C and Sugg Skinner, C and Zheng, Y and Chubak, J and Corley, DA and Greenlee, RT and Halm, EA and Li, CI},
title = {Gaps in care across the cancer screening continuum for cervical, colorectal and lung cancer.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf248},
pmid = {40929058},
issn = {1460-2105},
abstract = {BACKGROUND: While screening for cervical, colorectal, and lung cancers reduce cancer-specific mortality, the full benefits of screening are only realized when coupled with timely care across the subsequent "screening continuum" steps, including surveillance (results warranting frequent monitoring), diagnostic evaluation (results that require additional testing), and treatment (detected cancers). Our goal was to describe the proportion of individuals receiving timely cervical, colorectal, and lung cancer care at each step in the screening continuum.

METHODS: This retrospective cohort study used data from the 10 health care settings that participate in the Population-based Research to Optimize the Screening Process (PROSPR II) consortium and included individuals who were eligible for a step along the cancer screening continuum in 2018. Proportions of individuals who received timely testing were calculated for screening, surveillance, and diagnostic tests for each of the three cancers and treatment (colorectal only), and the association of these outcomes with patient characteristics was evaluated using multivariate logistic regression.

RESULTS: The overall proportions of timely screening, surveillance, and diagnostic testing were 41.8%, 37.3%, and 61.2%, for cervical cancer; 82.4%, 45.5%, and 73.5% for colorectal (94.1% for timely treatment); and 73.8%, 80.5%, and 80.7% for lung cancer. Across all three cancers, there were differences across the screening continuum by insurance status, race/ethnicity, and socioeconomic status.

CONCLUSIONS: There are important gaps in care across the screening continuum beyond common metrics for screening uptake. Comparison across organ types may facilitate the identification of interventions and policies that could broadly improve cancer prevention and promote health equity.},
}

@article {pmid40928768,
year = {2025},
author = {Gunnell, L and Hippe, DS and Park, SY and Fu, A and Akaike, T and Lachance, K and Cahill, K and Doolittle-Amieva, C and Nghiem, P},
title = {Polyomavirus Antibodies for Merkel Cell Carcinoma Recurrence Detection.},
journal = {JAMA dermatology},
volume = {},
number = {},
pages = {},
pmid = {40928768},
issn = {2168-6084},
abstract = {IMPORTANCE: Merkel cell carcinoma (MCC) is typically caused by the Merkel cell polyomavirus (MCPyV) and recurs in 40% of patients. Half of patients with MCC produce antibodies to MCPyV oncoproteins, the titers of which rise with disease recurrence and fall after successful treatment.

OBJECTIVE: To assess the utility of MCPyV oncoprotein antibodies for early detection of first recurrence of MCC in a real-world clinical setting.

This prospective cohort study used a data and specimen repository from 2008 to 2020 in Seattle, Washington. Patients with MCC with locoregional disease underwent serum antibody testing at diagnosis. Statistical analysis was conducted between 2020 and 2025.

MAIN OUTCOMES AND MEASURES: The first posttreatment titer was necessary to establish a trend and was not used to assess risk (deferred). Subsequent titers were defined as (1) falling or negative, (2) rising, or (3) stable compared with the preceding titer.

RESULTS: Among the 503 patients in the cohort (median [IQR] age at diagnosis, 70 [62-77] years; 40% female), 1402 tests were performed; 247 (49%) were seropositive. A total of 877 were falling or negative, 62 were rising, 317 were stable, and 146 were deferred. Median (IQR) follow-up was 4.2 (1.8-7.4) years. On average, antibody titers fell by half every 3 months among patients not experiencing a recurrence. After a falling or negative titer, the likelihood that a given patient would remain recurrence-free for 3 months was 99.3% (95% CI, 98.6%-99.8%). In contrast, after a single rising titer, the risk of recurrence over the next 3 months was 36% (95% CI, 22%-52%), increasing to 58% (95% CI, 40%-78%) by 12 months and 68% (95% CI, 48%-86%) by 24 months. A rising titer preceded clinical or radiographic evidence of recurrence in 57% of cases (20/35). The median (IQR) interval between a rising titer and clinical disease detection was 3.7 (1.1-7.5) months, with 90% of recurrences (18/20) occurring within 14 months of the rising titer. Recurrences and antibody titers were analyzed in 196 patients with multiple blood draws.

CONCLUSIONS AND RELEVANCE: In this prospective cohort study, given a negative predictive value of 99.3%, a falling or negative titer may obviate the need for imaging, reducing radiation and contrast dye exposure. Conversely, a rising antibody titer should trigger closer follow-up, as it may lead to earlier detection of clinical recurrence and initiation of therapy.},
}

@article {pmid40927245,
year = {2025},
author = {Wilson, MH and Krantz, EM and Pergam, SA and Mielcarek, M and Elgar, S and Rosen, E and Swetky, M and Liu, C and Hill, JA and Cohen, S and McCulloch, DJ},
title = {Limited yield of SARS-CoV-2 screening in asymptomatic hematopoietic cell transplant and chimeric antigen receptor T-cell therapy patients.},
journal = {Antimicrobial stewardship & healthcare epidemiology : ASHE},
volume = {5},
number = {1},
pages = {e195},
pmid = {40927245},
issn = {2732-494X},
abstract = {Early in the COVID-19 pandemic, screening was initiated in several settings to mitigate asymptomatic transmission of SARS-CoV-2. However, this practice was later discouraged by the Society for Healthcare Epidemiology of America. This single-center retrospective study demonstrates limited utility of SARS-CoV-2 screening tests in asymptomatic HCT and CAR T-cell patients.},
}

@article {pmid40926591,
year = {2025},
author = {Shaik, F and Uldrick, TS and Mazinu, M and Gwebushe, N and Mosam, A},
title = {Cytokine biomarkers and their relationship to symptoms and quality of life in people with HIV-associated Kaposi sarcoma.},
journal = {HIV medicine},
volume = {},
number = {},
pages = {},
doi = {10.1111/hiv.70107},
pmid = {40926591},
issn = {1468-1293},
support = {//South African Medical Research Council/ ; },
abstract = {INTRODUCTION: Quality of life (QOL) is an essential component of care in people with HIV-associated Kaposi sarcoma (HIV-KS). Kaposi sarcoma herpes virus (KSHV) promotes cytokine expression and a dysfunctional inflammatory environment, contributing to KS pathogenesis and progression. However, disease-related inflammatory factors influencing QOL and symptoms remain underexplored. This study examines the relationship between baseline QOL parameters and inflammatory cytokine biomarkers in treatment-naïve Africans with HIV-KS participating in the randomized controlled KAART study. We hypothesized that inflammatory cytokines are linked with reduced QOL and symptom burden.

METHODS: Twenty-eight cytokines were measured from stored baseline serum using the Milliplex® multiplex assay. QOL was assessed using the validated EORTC QLQ-C30. Spearman Rho-Rank correlation was used to assess relationships between cytokine levels and QOL parameters, with p ≤ 0.01 considered statistically significant.

RESULTS: Paired cytokine and QOL data were available for 68 participants. IL-8 showed significant negative correlations with summary scores, a reliable indicator of overall QOL (rs = -0.35, p = 0.005). Increased IL-8 also correlated significantly with reduced emotional functioning scales (rs = -0.33, p = 0.01) and increased pain (rs = 0.32, p = 0.01). By contrast, increased IL-10 correlated significantly with reduced pain (rs = -0.31, p = 0.01). VEGF and MCP-1 levels correlated negatively with role functioning (rs = -0.32, p = 0.01; rs = -0.30, p = 0.01).

CONCLUSION: IL-8 is a key cytokine affecting QOL in HIV-KS. Elevations have a negative impact on pain, emotional functioning and overall QOL. IL-10, VEGF and MCP-1 perturbations also impact QOL. These findings enhance understanding of cytokine involvement in KS pathogenesis.},
}

@article {pmid40926209,
year = {2025},
author = {Selvaraj, MS and Li, X and Li, Z and Van Buren, E and Haidermota, S and Postupaka, D and Hornsby, W and Bis, JC and Brody, JA and Cade, BE and Chung, RH and Curran, JE and Damrauer, SM and de Las Fuentes, L and de Vries, PS and Duggirala, R and Freedman, BI and Graff, M and Guo, X and Hidalgo, BA and Hou, L and Irvin, R and Judy, R and Kalyani, RR and Kelly, TN and Konigsberg, IR and Kral, BG and Kwee, LC and Levy, D and Li, C and Manichaikul, AW and Martin, LW and Montasser, ME and Morrison, AC and Naseri, T and North, KE and O'Connell, JR and Palmer, ND and Peyser, PA and Reiner, AP and Shah, SH and Smit, RAJ and Smith, JA and Taylor, KD and Tiwari, H and Tsai, MY and Viali, S and Wang, Z and Wang, Y and Zhao, W and Arnett, DK and Blangero, J and Boerwinkle, E and Bowden, DW and Carlson, JC and Chen, YI and Ellinor, PT and Fornage, M and He, J and Heard-Costa, N and Kaplan, RC and Kardia, SLR and Kooperberg, C and Kraus, WE and Lange, LA and Loos, RJF and Mitchell, BD and Psaty, BM and Rader, DJ and Redline, S and Rich, SS and Yanek, LR and Gibbs, R and Gabriel, S and Viaud-Martinez, KA and Dutcher, SK and Germer, S and Kim, R and Rotter, JI and Lin, X and Peloso, GM and , and Natarajan, P},
title = {Whole genome sequence analysis of low-density lipoprotein cholesterol across 246 K individuals.},
journal = {Genome biology},
volume = {26},
number = {1},
pages = {273},
pmid = {40926209},
issn = {1474-760X},
support = {75N92021F00229//NHLBI TOPMed fellowship/ ; R01HL142711//National Institutes of Health (NIH)/ ; R01HL142711//National Institutes of Health (NIH)/ ; },
mesh = {Humans ; *Cholesterol, LDL/genetics/blood ; *Whole Genome Sequencing ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; Genome, Human ; Genetic Variation ; },
abstract = {BACKGROUND: Rare genetic variation provided by whole genome sequence datasets has been relatively less explored for its contributions to human traits. Meta-analysis of sequencing data offers advantages by integrating larger sample sizes from diverse cohorts, thereby increasing the likelihood of discovering novel insights into complex traits. Furthermore, emerging methods in genome-wide rare variant association testing further improve power and interpretability.

RESULTS: Here, we conduct the largest meta-analysis of whole genome sequencing for low-density lipoprotein cholesterol (LDL-C), a therapeutic target for coronary artery disease, analyzing data from 246 K participants and integrating 1.23B variants from the UK Biobank and the Trans-Omics for Precision Medicine (TOPMed) program. We identify numerous rare coding and non-coding gene associations related to LDL-C, with replication across 86 K participants in All of Us. Our findings are based on single-variant analyses, rare coding and non-coding variant aggregation tests, and sliding window approaches. Through this comprehensive analysis, we identify 704 novel single-variant associations, 25 novel rare coding variant aggregates, 28 novel rare non-coding variant aggregates, and one novel sliding window aggregate.

CONCLUSIONS: This study provides a meta-analysis framework for large-scale whole genome sequence association analyses from diverse population groups, yielding novel rare non-coding variant associations.},
}

Humans
*Cholesterol, LDL/genetics/blood
*Whole Genome Sequencing
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Genome, Human
Genetic Variation

@article {pmid40925936,
year = {2025},
author = {Lawrenson, K and Kar, S and McCue, K and Kuchenbaeker, K and Michailidou, K and Tyrer, J and Beesley, J and Ramus, SJ and Li, Q and Delgado, MK and Lee, JM and Aittomäki, K and Andrulis, IL and Anton-Culver, H and Arndt, V and Arun, BK and Arver, B and Bandera, EV and Barile, M and Barkardottir, RB and Barrowdale, D and Beckmann, MW and Benitez, J and Berchuck, A and Bisogna, M and Bjorge, L and Blomqvist, C and Blot, W and Bogdanova, N and Bojesen, A and Bojesen, SE and Bolla, MK and Bonanni, B and Børresen-Dale, AL and Brauch, H and Brennan, P and Brenner, H and Bruinsma, F and Brunet, J and Buhari, SA and Burwinkel, B and Butzow, R and Buys, SS and Cai, Q and Caldes, T and Campbell, I and Cannioto, R and Chang-Claude, J and Chiquette, J and Choi, JY and Claes, KBM and , and Cook, LS and Cox, A and Cramer, DW and Cross, SS and Cybulski, C and Czene, K and Daly, MB and Damiola, F and Dansonka-Mieszkowska, A and Darabi, H and Dennis, J and Devilee, P and Diez, O and Doherty, JA and Domchek, SM and Dorfling, CM and Dörk, T and Dumont, M and Ehrencrona, H and Ejlertsen, B and Ellis, S and , and Engel, C and Lee, E and Evans, DG and Fasching, PA and Feliubadalo, L and Figueroa, J and Flesch-Janys, D and Fletcher, O and Flyger, H and Foretova, L and Fostira, F and Foulkes, WD and Fridley, BL and Friedman, E and Frost, D and Gambino, G and Ganz, PA and Garber, J and García-Closas, M and Gentry-Maharaj, A and Ghoussaini, M and Giles, GG and Glasspool, R and Godwin, AK and Goldberg, MS and Goldgar, DE and González-Neira, A and Goode, EL and Goodman, MT and Greene, MH and Gronwald, J and Guénel, P and Haiman, CA and Hall, P and Hallberg, E and Hamann, U and Hansen, TVO and Harrington, PA and Hartman, M and Hassan, N and Healey, S and , and Heitz, F and Herzog, J and Høgdall, E and Høgdall, CK and Hogervorst, FBL and Hollestelle, A and Hopper, JL and Hulick, PJ and Huzarski, T and Imyanitov, EN and , and , and Isaacs, C and Ito, H and Jakubowska, A and Janavicius, R and Jensen, A and John, EM and Johnson, N and Kabisch, M and Kang, D and Kapuscinski, M and Karlan, BY and Khan, S and Kiemeney, LA and Kjaer, SK and Knight, JA and Konstantopoulou, I and Kosma, VM and Kristensen, V and Kupryjanczyk, J and Kwong, A and de la Hoya, M and Laitman, Y and Lambrechts, D and Le, N and De Leeneer, K and Lester, J and Levine, DA and Li, J and Lindblom, A and Long, J and Lophatananon, A and Loud, JT and Lu, K and Lubinski, J and Mannermaa, A and Manoukian, S and Le Marchand, L and Margolin, S and Marme, F and Massuger, LFAG and Matsuo, K and Mazoyer, S and McGuffog, L and McLean, C and McNeish, I and Meindl, A and Menon, U and Mensenkamp, AR and Milne, RL and Montagna, M and Moysich, KB and Muir, K and Mulligan, AM and Nathanson, KL and Ness, RB and Neuhausen, SL and Nevanlinna, H and Nord, S and Nussbaum, RL and Odunsi, K and Offit, K and Olah, E and Olopade, OI and Olson, JE and Olswold, C and O'Malley, D and Orlow, I and Orr, N and Osorio, A and Park, SK and Pearce, CL and Pejovic, T and Peterlongo, P and Pfeiler, G and Phelan, CM and Poole, EM and Pylkäs, K and Radice, P and Rantala, J and Rashid, MU and Rennert, G and Rhenius, V and Rhiem, K and Risch, HA and Rodriguez, G and Rossing, MA and Rudolph, A and Salvesen, HB and Sangrajrang, S and Sawyer, EJ and Schildkraut, JM and Schmidt, MK and Schmutzler, RK and Sellers, TA and Seynaeve, C and Shah, M and Shen, CY and Shu, XO and Sieh, W and Singer, CF and Sinilnikova, OM and Slager, S and Song, H and Soucy, P and Southey, MC and Stenmark-Askmalm, M and Stoppa-Lyonnet, D and Sutter, C and Swerdlow, A and Tchatchou, S and Teixeira, MR and Teo, SH and Terry, KL and Terry, MB and Thomassen, M and Tibiletti, MG and Tihomirova, L and Tognazzo, S and Toland, AE and Tomlinson, I and Torres, D and Truong, T and Tseng, CC and Tung, N and Tworoger, SS and Vachon, C and van den Ouweland, AMW and van Doorn, HC and van Rensburg, EJ and Van't Veer, LJ and Vanderstichele, A and Vergote, I and Vijai, J and Wang, Q and Wang-Gohrke, S and Weitzel, JN and Wentzensen, N and Whittemore, AS and Wildiers, H and Winqvist, R and Wu, AH and Yannoukakos, D and Yoon, SY and Yu, JC and Zheng, W and Zheng, Y and Khanna, KK and Simard, J and Monteiro, AN and French, JD and Couch, FJ and Freedman, ML and Easton, DF and Dunning, AM and Pharoah, PD and Edwards, SL and Chenevix-Trench, G and Antoniou, AC and Gayther, SA},
title = {Author Correction: Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {8237},
doi = {10.1038/s41467-025-63507-x},
pmid = {40925936},
issn = {2041-1723},
}

@article {pmid40909820,
year = {2025},
author = {Lim, R and O'Connor, C and Pan, J and Tang, TT and Castelo, AH and He, Y and Titt, U and Mohan, R and Liao, Z and Brock, KK},
title = {Weekly changes in ventilation response for photon and proton lung cancer patients during radiotherapy.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40909820},
abstract = {PURPOSE: Conformal dose distributions in proton radiotherapy promise to reduce normal tissue toxicity such as radiation-induced pneumonitis, but this has not been fully realized in clinical trials. To further investigate dose and toxicity, we employ voxel-based normal tissue evaluation techniques such as ventilation maps throughout treatment. We hypothesize that ventilation change after 1 week of treatment (WK1) predicts for ventilation change at the end of treatment (EOT).

METHODS: For 48 photon and 23 proton lung cancer patients, 4DCT-based ventilation maps were generated using stress-based methods at planning, WK1, and EOT. Voxel-wise ventilation change from planning to WK1 and EOT was calculated and binned by planned dose, and median ventilation change at WK1 and EOT was calculated across all patients in each dose bin. Patients were stratified into 6 groups based on modality and increased, decreased, or stable ventilation at WK1. Mann-Whitney U tests were performed to determine if median ventilation change at WK1 and EOT in each dose bin was significantly different from zero. Univariate analysis was performed to correlate ventilation change at EOT with change at WK1 and other clinical factors. A linear regression model was developed to predict ventilation at EOT using a variety of input features including ventilation at planning, ventilation at WK1, tumor response information, and tumor location. Accuracy of the model was assessed through R[2].

RESULTS: For patients that decreased in ventilation at WK1, 90% of photon patients and 92% of proton patients were stratified similarly at EOT. Patients that were stratified as increased ventilation at WK1 were stratified similarly (72% for photon, 80% for proton) at EOT. These patients were more likely to develop Grade 2+ pneumonitis though the difference was not significant when computing a Fisher's exact test. Univariate analysis indicated that only ventilation change at WK1 was correlated with ventilation change at EOT. The linear regression model achieved R[2] of 0.65.

CONCLUSION: Ventilation changes at EOT can be predicted using ventilation information from planning and WK1. Patients that increased in ventilation at WK1 were more likely to develop pneumonitis. Further work is needed to characterize the relationship between ventilation change with pneumonitis development.},
}

@article {pmid40924774,
year = {2025},
author = {Mugwany, KK and Saina, M and Mugo, NR and MaWhinney, S and Morrow, M and Schaafsma, TT and Donnell, D and Glidden, DV and Ngure, K and Brown, CE and Rechkina, EA and Chohan, BH and Wu, L and Hill, E and Koome, E and Akelo, N and Mbaire, S and Morrison, SA and Kibatha, M and Njeru, I and Muriithi, M and Coppinger, C and Bushman, L and Baeten, JM and Anderson, PL and , },
title = {Adherence thresholds for emtricitabine-tenofovir disoproxil fumarate preexposure prophylaxis against HIV acquisition in cisgender women: A randomized directly observed dosing study.},
journal = {PLoS medicine},
volume = {22},
number = {9},
pages = {e1004732},
doi = {10.1371/journal.pmed.1004732},
pmid = {40924774},
issn = {1549-1676},
abstract = {BACKGROUND: Oral emtricitabine/tenofovir disoproxil fumarate (F/TDF) preexposure prophylaxis (PrEP) effectiveness against HIV acquisition highly depends on adherence. For men who have sex with men, a dosing study in the United States (US) population defined clinically meaningful tenofovir diphosphate (TFV-DP) thresholds in dried blood spots (DBS) based on the rounded 25th percentile for 2, 4, and 7 doses/week as 350, 700, and 1,250 fmol/punch. However, divergent efficacy results in the first generation randomized clinical trials of F/TDF PrEP among African women led to several hypotheses to question whether the pharmacology and adherence requirement for oral F/TDF PrEP may be different in cisgender women compared to what is already established for men.

METHODS AND FINDINGS: We conducted an open-label, parallel, randomized study of directly observed oral F/TDF PrEP among women without HIV who were not pregnant or breastfeeding in Kenya. Participants were randomly assigned to 2, 4, or 7 DOD doses/week for 8 weeks. Blood was collected weekly, and TFV-DP and emtricitabine triphosphate (FTC-TP) concentrations in DBS and peripheral blood mononuclear cells (PBMCs) were quantified using validated liquid chromatography-tandem mass spectrometry. For DBS, concentrations were quantified from a 3-mm punch using the 70% methanol/30% water (70:30) extraction method as the primary process-the same method used for the original TFV-DP benchmarks derived in US adults, and additionally with 50% methanol/50% water (50:50) extraction using punches from the same DBS spot to compare the extraction performance of 70:30 versus 50:50 methods. The primary outcome was the steady-state fitted concentrations of TFV-DP and dose proportionality in DBS and the observed PBMC TFV-DP levels by study dosing groups. Secondary outcomes included the quantitative concentrations of FTC-TP in DBS, TFV-DP half-life in DBS, and the relative TFV-DP recovery from DBS using the 70:30 versus 50:50 extraction method. One-compartment population pharmacokinetic models were fit to estimate steady-state DBS concentrations. Descriptive statistics were summarized as range, means, and medians with interquartile range (IQR) for continuous outcomes and proportions for categorical variables. Fifty-four women were enrolled and randomized. Median age was 22 (IQR, 20-25) years. The observed median (IQR) week 8 TFV-DP concentrations in DBS were 359 (266-464), 749 (596-923), and 1,389 (1,151-1,551) fmol/punch after 2, 4, and 7 doses/week, respectively. At week 8, FTC-TP was quantifiable in 71%, 19%, and 0% DBS samples for 7, 4, and 2 doses/week groups, respectively. Fitted median (IQR) steady-state DBS TFV-DP concentrations were 416 (316, 516), 832 (631, 1,033), and 1,457 (1,106, 1,808) fmol/punch for 2, 4, and 7 doses/week, respectively, similar to previous estimates in US adults. TFV-DP exhibited a mean half-life of 17.5 days (95%CI: 16.7, 18.4) in DBS and steady-state TFV-DP concentrations varied in direct proportion to the dosing frequency [slope: 1.02 90% confidence interval 0.84, 1.20]. The 50:50 DBS extraction method yielded 1.27 (95% CI 1.25, 1.28) higher TFV-DP concentrations compared to the 70:30 method. When the 1.27 conversion factor was applied to the original 70:30 method-derived TFV-DP thresholds, the updated TFV-DP adherence interpretation benchmarks based on the 50:50 extraction were: <450 for <2 dose/week, 450-899 for 2-3 doses/week, 900-1,599 for 4-6 doses/week, and ≥1,600 fmol/punch for 7 doses/week. The observed mean (standard deviation) steady-state PBMC TFV-DP concentrations was 11.99 ± 8.47, 31.81 ± 15.66, and 63.1 ± 28.97 fmol/106 cells after 2, 4, and 7 doses/week, respectively. Overall, oral F/TDF PrEP was well tolerated. No grade 3 or higher adverse events were observed during the dosing phase. The primary study limitation was dosing for 8 weeks, but population pharmacokinetic modeling enabled steady-state estimates.

CONCLUSIONS: Steady-state DBS TFV-DP concentrations from directly observed F/TDF PrEP dosing in African cisgender women participants are similar to previous estimates defined from US-based participants. These data demonstrate that cisgender women achieve similar DBS and PBMC TFV-DP concentrations as men for the same adherence level and validate the original TFV-DP benchmarks to interpret F/TDF adherence in HIV prevention studies and PrEP programs among cisgender women.

TRIAL REGISTRATION: Clinicaltrials.gov: NCT05057858.},
}

@article {pmid40924642,
year = {2025},
author = {Blinka, S and Yu, EY},
title = {Drug targets in prostate cancer: an appetite for KLK2-mediated destruction.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-25-2546},
pmid = {40924642},
issn = {1557-3265},
abstract = {Human Kallikrein 2 (KLK2) is a prostate cancer tissue specific protein that is regulated by androgen receptor (AR) signaling. KLK2 was not previously recognized as a therapeutic target as it is secreted. It has now been demonstrated that KLK2 is expressed on the cell surface and targetable by various methodologies.},
}

@article {pmid40923785,
year = {2025},
author = {Rossenkhan, R and Giorgi, EE and Shao, D and Ludwig, J and Labuschagne, P and Magaret, CA and Ndung'u, T and Muema, D and Gounder, K and Dong, KL and Walker, BD and Rolland, M and Robb, ML and Eller, LA and Sawe, F and Nitayaphan, S and Grebe, E and Busch, MP and Delaney, KP and Facente, S and Carpp, LN and deCamp, AC and Huang, Y and Korber, B and Juraska, M and Rudnicki, E and Kosmider, E and Reeves, DB and Mayer, BT and Hural, J and Deng, W and Westfall, DH and Yssel, A and Matten, D and Bhattacharya, T and Corey, L and Gilbert, PB and Williamson, C and Mullins, JI and Edlefsen, PT},
title = {Bayesian estimation of HIV acquisition dates for prevention trials.},
journal = {mBio},
volume = {},
number = {},
pages = {e0188125},
doi = {10.1128/mbio.01881-25},
pmid = {40923785},
issn = {2150-7511},
abstract = {Accurate timing estimates of when participants acquire HIV in HIV prevention trials are necessary for determining antibody levels at acquisition. The Antibody-Mediated Prevention (AMP) Studies showed that a passively administered broadly neutralizing antibody can prevent the acquisition of HIV from a neutralization-sensitive virus. We developed a pipeline for estimating the date of detectable HIV acquisition (DDA) in AMP Study participants using diagnostic and viral sequence data. Using a Bayesian strategy that combines three streams of data (REN [rev/vpu/env/Δnef] sequence, GP [gag/Δpol] sequence, and diagnostic) where their 95% credible intervals overlap based on pre-specified criteria and decision rules. We evaluated the performance of our AMP pipeline using PacBio viral sequence data from 41 participants across two prospective acute HIV acquisition cohort studies, FRESH and RV217, with twice-weekly sampling. These cohort studies enrolled young women in South Africa and men and women in Kenya and Thailand, respectively, with a high likelihood of HIV acquisition. In evaluating performance, "true DDA" was the center of bounds between last-negative and first-positive RNA diagnostic tests (median time 4 days, range 2-7 days); bias was the mean difference between estimated and true DDA. Using diagnostic data alone yielded timing estimates with a bias of 2.4 days and root mean square error (RMSE) of 7.9 days. These results were improved using sequence + diagnostic data (bias 1.5 days, RMSE 6.9 days), as well as by restricting sequence-based estimation to samples from ≤5 weeks post-DDA (bias 0.2 days, RMSE 7.8 days).IMPORTANCEIn HIV prevention trials, accurate timing estimates of when individual participants acquire HIV can be used to estimate antibody levels at the time of acquisition, which is useful for projecting antibody levels needed for prevention. The results we report here suggest that if sequence-based estimation of acquisition timing is used in future clinical trials of combination broadly neutralizing antibody (bnAb) regimens or multispecific bnAbs for HIV prevention, a sampling frequency of at least monthly is needed. Moreover, in the samples analyzed here, we observed less bias in sequence-based timing estimation for samples taken <5 weeks post-DDA. This observation is consistent with the timing of immune-driven selective pressures that may negatively impact the power to detect acquisition sieve effects.},
}

@article {pmid40923321,
year = {2025},
author = {Song, Q and Zheng, M and Li, Q and Wu, X and Lin, B and Kang, TH and Qin, H and Kujawski, M and Pillai, RK and Lin, JL and Nakamura, R and Shively, J and Martin, PJ and Zeng, D},
title = {Intestinal epithelial Ceacam1 deficiency prevents steroid-refractory acute gut graft-versus-host disease.},
journal = {JCI insight},
volume = {10},
number = {17},
pages = {},
doi = {10.1172/jci.insight.186984},
pmid = {40923321},
issn = {2379-3708},
mesh = {*Graft vs Host Disease/immunology/prevention & control/genetics ; Animals ; Mice ; Humans ; *Intestinal Mucosa/immunology/metabolism/pathology ; Disease Models, Animal ; *Cell Adhesion Molecules/genetics ; Hematopoietic Stem Cell Transplantation/adverse effects ; *Antigens, CD/genetics/metabolism ; Interleukin-22 ; Male ; Mice, Inbred C57BL ; Interleukins/metabolism ; Female ; Epithelial Cells/metabolism/immunology ; Mice, Knockout ; Steroids ; T-Lymphocytes, Regulatory/immunology ; CEACAM1 Protein ; Carcinoembryonic Antigen ; },
abstract = {Steroid-refractory gut acute graft-versus-host disease (SR-Gut-aGVHD) is the major cause of nonrelapse death after allogeneic hematopoietic cell transplantation. High numbers of donor-type IL-22+ T cells, IL-22-dependent dysbiosis, and loss of antiinflammatory CX3CR1hi mononuclear phagocytes (MNPs) play critical roles in SR-Gut-aGVHD pathogenesis. CEACAM1 on intestinal epithelial cells (IECs) is proposed to regulate bacterial translocation and subsequent immune responses in the intestine. Here, with imaging mass cytometry (IMC), combined scRNA-Seq with ATAC-Seq, and high-dimensional flow cytometry analysis, we show that CEACAM1 expression was enhanced on IECs in murine and human SR-Gut-aGVHD. Ceacam1 deficiency on host IECs effectively prevented SR-Gut-aGVHD in murine models. Ceacam1 deficiency on IECs resulted in (i) higher numbers of IL-22+IL-10+Foxp3+CD4+ peripheral Tregs (pTregs) and lower numbers of conventional IL-22+CD4+ T (Tcon), Th/Tc1, and Th17 cells in the intestine; (ii) higher prevalence of beneficial commensal bacteria that augment colonic pTreg expansion, with lower prevalence of pathogenic bacteria; and (iii) higher numbers of antiinflammatory CD103-CX3CR1hi MNPs that produce indoleamine 2,3-dioxygenase (IDO) and IL-10, with lower numbers of proinflammatory CD103+CX3CR1lo MNPs that produce IL-6. Thus, specifically targeting IEC CEACAM1 represents a promising approach for prevention of SR-Gut-aGVHD.},
}

*Graft vs Host Disease/immunology/prevention & control/genetics
Animals
Mice
Humans
*Intestinal Mucosa/immunology/metabolism/pathology
Disease Models, Animal
*Cell Adhesion Molecules/genetics
Hematopoietic Stem Cell Transplantation/adverse effects
*Antigens, CD/genetics/metabolism
Interleukin-22
Male
Mice, Inbred C57BL
Interleukins/metabolism
Female
Epithelial Cells/metabolism/immunology
Mice, Knockout
Steroids
T-Lymphocytes, Regulatory/immunology
CEACAM1 Protein
Carcinoembryonic Antigen

@article {pmid40923286,
year = {2025},
author = {Malik, H},
title = {The viral arms race: an interview with Harmit Malik.},
journal = {Disease models & mechanisms},
volume = {18},
number = {9},
pages = {},
doi = {10.1242/dmm.052591},
pmid = {40923286},
issn = {1754-8411},
}

@article {pmid40920995,
year = {2025},
author = {Thakur, R and Al Hadidi, S},
title = {From Physician-Driven to Patient-Centered: Transforming Multiple Myeloma Care Decisions.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2500712},
doi = {10.1200/OP-25-00712},
pmid = {40920995},
issn = {2688-1535},
}

@article {pmid40920992,
year = {2025},
author = {Bashore, L and Peterson, RK and Li, C and Liu, W and Wang, M and Jiwani, ZM and McDonald, AJ and Lupo, PJ and King, A and Srivastava, D and Leisenring, WM and Howell, RM and Gibson, TM and Oeffinger, K and Armstrong, GT and Bowman, WP and Krull, KR and Edelstein, K},
title = {Chronic Health Conditions and Academic Achievement: A Childhood Cancer Survivor Study Report.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2500414},
pmid = {40920992},
issn = {2688-1535},
support = {P30 CA021765/CA/NCI NIH HHS/United States ; U24 CA055727/CA/NCI NIH HHS/United States ; },
abstract = {PURPOSE: To examine associations between special education, chronic health conditions (CHCs), and college graduation in survivors of childhood cancer and their siblings.

METHODS: Childhood Cancer Survivor Study participants included 23,082 5-year survivors (53.7% male; median [IQR] age at diagnosis, 6 [3-13] years; age at evaluation, 31.0 [24-39] years; treated between 1970 and 1999) and 5,037 siblings (47.7% male; 36.0 [28-44] years at evaluation). Special education use, reasons for special education, CHCs, and college graduation were self-reported. Primary cancer diagnosis and treatment exposures were abstracted from medical records. Comparisons between survivors and siblings were made using chi-square statistics; demographic and treatment factors associated with outcomes were examined using modified Poisson regression models.

RESULTS: More survivors reported special education use than siblings (26.5% v 8.6%; relative risk [RR], 2.55 [95% CI, 2.32 to 2.80]). Of those survivors and siblings who had special education services, use was highest between kindergarten and fifth grade (64.4% of survivors and 71.9% of siblings in kindergarten-fifth grade, 14.4% of survivors and 12.5% of siblings in sixth-eighth grade, and 9.2% of survivors and 9.0% of siblings in ninth-12th grade), and primarily attributable to learning and concentration problems. Despite receiving special education, survivors were less likely to graduate college compared with siblings requiring special education (RR, 0.76 [95% CI, 0.66 to 0.88]). Risk for not graduating college included history of CNS tumor (RR, 1.47 [95% CI, 1.40 to 1.55]), cranial irradiation (20-29 Gy, RR, 1.16 [95% CI, 1.09 to 1.25]; 30-49 Gy, RR, 1.37 [95% CI, 1.26 to 1.49]; ≥50 Gy, RR, 1.35 [95% CI, 1.28 to 1.42]), or the presence of a severe, disabling or life-threatening CHC (Common Terminology Criteria for Adverse Events grade 3-4, RR, 1.15 [95% CI, 1.07 to 1.24]).

CONCLUSION: Cognitive problems and CHCs increase risk for not graduating college; these problems are not alleviated by special education.},
}

@article {pmid40920378,
year = {2025},
author = {Lee, JR and Morehead, D and Young, B and Tolbert, V and Masembe, J and Britt, G and Neuenschwander, L and Schuppe, K and Pelman, R and Johnson, D and Henderson, V and Darst, BF and Egwuatu, P and Kim, SM and Wolff, EM and Gore, JL and Nyame, YA},
title = {Patient and Physician Perceptions of Prostate-Specific Antigen Testing Among Black Individuals.},
journal = {JAMA network open},
volume = {8},
number = {9},
pages = {e2530946},
pmid = {40920378},
issn = {2574-3805},
mesh = {Adult ; Aged ; Humans ; Male ; Middle Aged ; *Attitude of Health Personnel ; *Black or African American/psychology/statistics & numerical data ; *Early Detection of Cancer/psychology ; *Health Knowledge, Attitudes, Practice ; *Prostate-Specific Antigen/blood ; *Prostatic Neoplasms/diagnosis/ethnology ; Qualitative Research ; United States ; },
abstract = {IMPORTANCE: Black individuals have a twofold higher rate of prostate cancer death in the US compared with the average population with prostate cancer. Few guidelines support race-conscious screening practices among at-risk Black individuals.

OBJECTIVE: To examine structural factors that facilitate or impede access to prostate cancer screening among Black individuals in the US.

This qualitative, mixed-methods study was conducted between September 1, 2021, and December 31, 2023, in clinical and community settings across Washington, Wyoming, Alaska, Montana, Idaho, and Oregon. It included semistructured interviews with Black adults (aged ≥18 years) at risk for prostate cancer with or without a history of prostate-specific antigen (PSA) testing and a survey of primary care practitioners (PCPs) and urologists.

MAIN OUTCOMES AND MEASURES: Patient and physician experiences, knowledge, attitudes, and practices of PSA testing and prostate cancer screening were evaluated. Consensus coding and thematic analysis were used to analyze interviews; surveys were analyzed using descriptive statistics.

RESULTS: A total of 29 Black men (median [range] age, 59 [32-72] years) participated in the interviews, and 31 PCPs (including 30 phyicians and 1 physician assistant) and 32 urologists (45 of 63 aged 30-59 years [71.4%]; 40 male [63.5%]) participated in the survey. Interview participants perceived that PCPs function as gatekeepers in accessing PSA testing but may lack knowledge specific to Black men's risk for prostate cancer and hold attitudes about PSA testing that do not support its use. Interview participants also reported a lack of trusted relationships with PCPs to support shared decision-making. While both urologists and PCPs were highly aware of US Preventive Services Task Force guidelines, PCPs were much less likely than urologists to believe in the value of PSA testing or the role of early detection to prevent prostate cancer-related mortality (2 [6.5%] vs 24 [75.0%], respectively).

CONCLUSIONS AND RELEVANCE: In this qualitative study examining structural factors associated with access to prostate cancer screening among Black individuals, findings from the survey supported participants' perceptions that PCPs do not value PSA testing for prostate cancer early detection or appreciate its role in reducing the risk of prostate cancer-related mortality. Primary care practitioner reliance on USPSTF guidelines, which currently do not provide guideline recommendations for screening high-risk groups, including Black individuals, suggests that incorporating evidence-driven guidance for PSA screening among Black individuals into these guidelines may substantially improve prostate cancer early detection among this high-risk population.},
}

Adult
Aged
Humans
Male
Middle Aged
*Attitude of Health Personnel
*Black or African American/psychology/statistics & numerical data
*Early Detection of Cancer/psychology
*Health Knowledge, Attitudes, Practice
*Prostate-Specific Antigen/blood
*Prostatic Neoplasms/diagnosis/ethnology
Qualitative Research
United States

@article {pmid40920226,
year = {2025},
author = {Wang, LH and Sonbas Cobb, B and Riem, L and DuCharme, O and Shaw, DW and Walker, M and Eichinger, K and Lewis, L and Tawil, R and Hamel, JI and Mul, K and Blemker, SS and Tapscott, SJ and Friedman, SD and Rutkove, SB and Statland, JM},
title = {Electrical impedance myography captures features of muscle structure measured by MRI and transcriptomic analysis in facioscapulohumeral muscular dystrophy.},
journal = {Journal of neuromuscular diseases},
volume = {},
number = {},
pages = {22143602251369246},
doi = {10.1177/22143602251369246},
pmid = {40920226},
issn = {2214-3602},
abstract = {BACKGROUND: Electrical impedance myography (EIM) has been proposed as an efficient, non-invasive biomarker of muscle composition in facioscapulohumeral muscular dystrophy (FSHD).

OBJECTIVE: We investigate whether EIM parameters are associated with muscle structure measured by magnetic resonance imaging (MRI), muscle histology, and transcriptomic analysis as well as strength at the individual leg muscle level.

METHODS: We performed a multi-center cross-sectional study enrolling 33 patients with FSHD. EIM measurements were recorded from bilateral vastus lateralis, tibialis anterior (TA), and medial gastrocnemius muscles and compared to quantitative muscle volume measures by MRI as well as knee extension and ankle dorsiflexion strength by quantitative muscle testing. EIM measurements of the bilateral TA were further compared to histology and transcriptomic analysis (RNAseq) of muscle and fat content.

RESULTS: EIM phase at multiple frequencies was positively associated to the amount of muscle measured by MRI (ρ = 0.48 to 0.70, p ≤ 0.001) and negatively associated to the amount of fat replacement of muscle (ρ = -0.53 to -0.73, p ≤ 0.001). EIM phase of the vastus lateralis and TA was positively associated with knee extension and ankle dorsiflexion strength normalized to age and sex (ρ = 0.45 to 0.60, p < 0.0001). The bilateral TA muscles were analyzed at the histopathological and molecular (transcriptomic) levels and showed that EIM phase was positively associated with amount of muscle (ρ = 0.33 to 0.35, p < .01) and negatively associated with amount of fat (ρ = -0.36 to -0.56, p < .001) by transcriptomic analysis.

CONCLUSIONS: This study supports the hypothesis that the amount and quality of muscle tissue as assessed by EIM is associated with the amount and quality of muscle tissues as assessed by MRI and muscle biopsy, with all measures ultimately being strongly associated with muscle strength. These data provide further convergent validity for the use of EIM as a potential non-invasive biomarker to assess muscle health in FSHD.},
}

@article {pmid40919994,
year = {2025},
author = {Choe, M and Kirkey, D and Lira, I and Hawkins, G and Blankenfeld, M and Menashe, S and Ries, R and Wrightson, B and Root, C and McKay, CN and Peplinski, JH and Glabman, R and Davis, LE and Malhotra, SV and Gorlick, R and Loggers, ET and Meshinchi, S},
title = {Preclinical evaluation of folate receptor-alpha chimeric antigen receptor T cells (FOLR1-CART) exhibit highly efficient anti-tumor activity against osteosarcoma.},
journal = {Cancer research communications},
volume = {},
number = {},
pages = {},
doi = {10.1158/2767-9764.CRC-25-0086},
pmid = {40919994},
issn = {2767-9764},
abstract = {Metastatic and relapsed osteosarcoma (OS) remains difficult to treat despite advanced surgical techniques, intensified chemotherapy, and targeted therapies. Adoptive immunotherapies such as chimeric antigen receptor (CAR) T cells, are in their nascent stage, but remain a viable therapeutic strategy for patients with aggressive solid tumors such as OS. Folate receptor-(?) (FOLR1) has been functionally implicated in OS pathophysiology, providing rationale as a potential therapeutic target. We recently advanced a FOLR1-specific CAR T cell product (FH FOLR1-CART) into a trial in infant AML (NCT06609928) and now evaluate this CAR construct against OS. We provide comprehensive FOLR1 transcript and protein expression profile in OS patients, cell lines and patient-derived xenografts, substantiating its significance as a therapeutic target. We further evaluate in vitro and in vivo efficacy of FH FOLR1-CART in both standard and patient-derived OS cell lines and xenograft models. FOLR1 transcript is expressed in the overwhelming majority of OS primary patient specimens, in OS cell lines, and patient-derived models. FH FOLR1-CART exhibit robust in vitro activation and potent cytotoxicity against FOLR1-expressing OS cell lines and primary OS patient samples. More importantly, FH FOLR1-CART demonstrates potent anti-tumor activity in both localized and metastatic in vivo cell-derived and patient-derived xenograft models, with complete tumor eradication. These results demonstrate a potential therapeutic option for patients with advanced OS. FH FOLR1 CART is advancing to an early phase trial in relapsed/refractory OS at Fred Hutch Cancer Center and Seattle Children's Hospital.},
}

@article {pmid40919233,
year = {2025},
author = {Wallace, M and Mathey, B and Yeung, CCS and Appelbaum, JS and Wallace, M},
title = {Coexistence of Essential Thrombocythemia and Waldenström Macroglobulinemia: A Case Report.},
journal = {Case reports in hematology},
volume = {2025},
number = {},
pages = {3390770},
pmid = {40919233},
issn = {2090-6560},
abstract = {Waldenström macroglobulinemia (WM) and essential thrombocythemia (ET) are distinct hematologic malignancies that have only been reported to co-occur in one previous patient. We present a 64-year-old man with a significant family history for WM who was found to have both ET and WM. He had symptomatic ET, diagnosed by elevated platelets and a positive JAK2 V617F mutation, and asymptomatic WM was found on serum electrophoresis done for screening due to family history. Genomic evaluation of the myeloid and lymphoid cells suggested independent neoplastic transformation. This is the second reported case of a patient with both WM and ET. There was no evidence for a shared mechanism in these dual malignancies.},
}

@article {pmid40918924,
year = {2025},
author = {Nriagu, BN and Rosario, KF and Hansen, S and Luciano, PD and Joshi, P and Mehta, A and Khera, AV and Kaplan, R and Sofer, T and McClelland, RL and Rodriguez, CJ},
title = {Hispanic/Latino ethnic background and genetic ancestry in relation to atherosclerotic cardiovascular disease risk estimation: Findings from the Multi-Ethnic Study of Atherosclerosis (MESA).},
journal = {American journal of preventive cardiology},
volume = {23},
number = {},
pages = {101268},
pmid = {40918924},
issn = {2666-6677},
abstract = {BACKGROUND: Hispanics/Latinos are a heterogenous population with no validated atherosclerotic cardiovascular disease (ASCVD) risk estimation tool. We examined performance of the pooled cohort equation (PCE) across Hispanic/Latino background groups and quantiles of African, Amerindian, and European genetic ancestry.

METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) was used to evaluate the performance of the non-Hispanic Black (NHB) and non-Hispanic White (NHW) PCE defined by predicted to observed (P/O) ratios of 10-year ASCVD events. Risk calibration was expressed as P/O ratios and risk discrimination was assessed with Harrell's C-statistic based on Cox models.

RESULTS: Our study included 966 Hispanics/Latinos [age 58 years at baseline (SD=9); 52 % females], comprising 504 Hispanics/Latinos of Mexican descent (MX), 284 Hispanics/Latinos of Caribbean descent (CA) and 178 Other Hispanics (O). At 10-years, there were 54 ASCVD events: MX (33); CA (13) and O (8). The PCE overestimated ASCVD risk across disaggregated Hispanic/Latino background groups. Both NHW and NHB PCE models performed best with increasing European genetic ancestry (NHW PCE: P/O ratio decreasing from 1.5 to 1.0; NHB PCE: from 2.4 to 1.5 between the 20th and 80th quantile threshold of European genetic ancestry). In contrast, PCE performance worsened with increasing African genetic ancestry (NHW PCE: P/O ratio increasing from 1.5 to 2.6; NHB PCE: from 1.5 to 2.9 between the 20th and 80th quantile threshold of African genetic ancestry).

CONCLUSIONS: Disaggregating Hispanics/Latinos by background and ancestry led to variability in PCE performance with greater overestimation of ASCVD risk for those of Caribbean background and those with increasing quantiles of African genetic ancestry.},
}

@article {pmid40917113,
year = {2025},
author = {Chakraborty, H and Sun, Q and Bhupathiraju, SN and Schenk, JM and Mishchuk, DO and Bain, JR and He, X and Sun, J and Harnly, J and Simmons, W and Raftery, D and Liang, L and Newman, JW and Fiehn, O and Clish, CB and Lampe, JW and Bennett, BJ and Navarro, SL and Wang, Y and Zheng, C and Mossavar-Rahmani, Y and McCullough, ML and Huang, Y and Shojaie, A and Zhu, W and Djukovic, D and Sacks, F and Williams, J and Steinberg, FM and Adams, SH and Hu, FB and Neuhouser, ML and Slupsky, CM and Maruvada, P},
title = {Corrigendum to "The Dietary Biomarkers Development Consortium: An Initiative for Discovery and Validation of Dietary Biomarkers for Precision Nutrition. [Current Developments in Nutrition, Volume 9, Issue 5, May 2025, 107435]".},
journal = {Current developments in nutrition},
volume = {9},
number = {8},
pages = {107517},
doi = {10.1016/j.cdnut.2025.107517},
pmid = {40917113},
issn = {2475-2991},
abstract = {[This corrects the article DOI: 10.1016/j.cdnut.2025.107435.].},
}

@article {pmid40916416,
year = {2025},
author = {Giorgi, EE and Abrahams, MR and Fouda, G and John-Stewart, G and Goga, A and Mullins, JI and Permar, SR and Janes, HE and Martin, TM},
title = {Characterization of Early Viral Populations in Infants Acquiring HIV Through Perinatal and Breastmilk Transmission: A Review of what is Currently Known and the Gaps that Need to be Addressed to Guide Passive HIV Immunization of Breastfeeding Infants.},
journal = {Current HIV research},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570162X357975250902104402},
pmid = {40916416},
issn = {1873-4251},
abstract = {Newborns represent only 1% of the population. Yet, HIV vertical transmissions represent 10% of all new infections globally, even though antiretroviral therapy (ART) has been shown to reduce the risk of vertical transmission to less than 2%. While vaccines still represent the most efficient and cost-effective intervention to eradicate new infections, HIV immunogens that can effectively elicit broad-spectrum protection are still at least a decade away. In contrast, passive immunization with broadly neutralizing antibody (bnAb) combinations has the potential to provide a more immediate pathway to HIV prophylaxis. Early-phase infant trials are underway to establish the safety and pharmacokinetics of bnAb combinations selected for their potency against viruses acquired via adult transmissions. However, the specific characteristics and phenotypic differences of vertically transmitted viruses in infants compared to those in adults remain uncertain, including their susceptibility to known broadly neutralizing antibodies (bnAbs). We review the current knowledge of vertically transmitted HIV viruses, including their genetics and phenotypic features. Differences in immunity between adults and infants lead us to hypothesize that distinct selection and evolutionary pressures act on the virus at the time of transmission and during the early phases of infection, and these may in turn affect the choice of bnAb combinations needed for protection against vertical transmission of HIV.},
}

@article {pmid40915872,
year = {2025},
author = {MacKay, EJ and Zhang, B and Beaty, JM and Devine, KA and O'Reilly-Shah, V and Mathis, MR and Szeto, WY and Groeneveld, PW and Augoustides, JG},
title = {Practice Pattern Variability in the Use of Pulmonary Arterial Catheters in Cardiac Surgery.},
journal = {Journal of cardiothoracic and vascular anesthesia},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.jvca.2025.08.013},
pmid = {40915872},
issn = {1532-8422},
abstract = {OBJECTIVES: To quantify intraoperative pulmonary arterial catheter (PAC) use during cardiac surgery and identify hospital-, anesthesiologist-, and patient-level factors associated with PAC utilization.

DESIGN: A cross-sectional, observational study using generalized logistic mixed models to examine variations in PAC use.

SETTING: Fifty-three US academic hospitals participating in the Multicenter Perioperative Outcomes Group (MPOG) national registry PARTICIPANTS: 145,343 adult patients undergoing cardiac surgery between January 1, 2016, and December 31, 2022.

INTERVENTION(S): Receipt of intraoperative PAC, defined by ≥60 minutes of physiologically plausible pulmonary arterial pressures.

The primary outcome was PAC utilization. Mixed-effects logistic regression quantified fixed-effect predictors, and variation attributable to anesthesiologists and then to anesthesiologists nested within a hospital was characterized using median odds ratio (MOR). Of the 145,343 cardiac surgeries performed across 53 hospitals, 104,626 (72%) included PAC monitoring. PAC use varied widely across hospitals (0-98%) and across anesthesiologists (0-100%). PAC was used most frequently in heart transplants (94%) and lung transplants (87%) and least frequently in pulmonic valve procedures (30%). A patient's likelihood of receiving a PAC was influenced most strongly by hospital (MOR, 15.00; 95% confidence interval [CI], 8.98-28.32), with substantially less variation attributable to an anesthesiologist within the same hospital (MOR, 1.70; 95% CI, 1.61-1.81).

CONCLUSIONS: Intraoperative PAC monitoring is used in nearly three-quarters of cardiac surgeries at US academic centers, with hospital practice pattern the factor most closely associated with PAC utilization.},
}

@article {pmid40914769,
year = {2025},
author = {Upreti, M and Petrosyan, A and Thornton, ME and Hovsepyan, A and Fernandez, GE and Koos, DS and Byrum, SD and Mackintosh, SG and Al-Husseini, JK and Porras, T and Ha, J and Tackett, AJ and Zhang, M and Johal, MS and Erdreich-Epstein, A and Durham, S and Krieger, MD and Margol, AS and Grubbs, BH and Chambers, TC and Asgharzadeh, S and Moats, RA and Chiarelli, PA},
title = {Multicellular tumor-stromal interactions recapitulate aspects of therapeutic response and human oncogenic signaling in a 3D disease model for H3K27M-altered DIPG.},
journal = {Oncogene},
volume = {},
number = {},
pages = {},
pmid = {40914769},
issn = {1476-5594},
support = {CDMRP RA210290//United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP)/ ; CDMRP RA210290//United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP)/ ; CDMRP RA210290//United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP)/ ; K08NS125175-01A1//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; K08NS125175-01A1//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R24GM137786//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R24GM137786//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R24GM137786//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; },
abstract = {It has become evident from decades of clinical trials that multimodal therapeutic approaches with focus on cell intrinsic and microenvironmental cues are needed to improve understanding and treat the rare, inoperable, and ultimately fatal diffuse intrinsic pontine glioma (DIPG), now categorized as a diffuse midline glioma. In this study we report the development and characterization of an in vitro system utilizing 3D Tumor Tissue Analogs (TTA), designed to replicate the intricate DIPG microenvironment. The innate ability of fluorescently labeled human brain endothelial cells, microglia, and patient-derived DIPG cell lines to self-assemble has been exploited to generate multicellular 3D TTAs that mimic tissue-like microstructures, enabling an in- depth exploration of the spatio-temporal dynamics between neoplastic and stromal cells. The 3D-TTA model recapitulates clinical patterns of DIPG growth, evidenced by resistance to chemotherapy, HDAC and proteasome inhibitors, as well as sensitization to the antibody-activated innate immune microenvironment including complement proteins and surrounding microglia. Multimodal fluorescence imaging platforms integrated with high-throughput omics revealed that alterations in tumor cell motility and growth in the 3D-TTA model compared to tumor cell only spheroids correlated with specific transcriptomic and proteomic changes. STAT3, ITGA5, LGALS1, SOD2, MVP, and CLIC1, associated with microenvironment signaling, DNA replication, and immune regulation, were identified as potential novel targets in the 3D model. The results indicate that the 3D TTA platform developed here represents a powerful tool for preclinical studies, paving the way for identification/validation of tissue specific biomarkers and novel drug targets, thus advancing disease management strategies for DIPG in children.},
}

@article {pmid40914661,
year = {2025},
author = {de la Calle, CM and Jing, Y and Fountain, J and Fletcher, SA and Mamawala, MM and Landis, P and Macura, KJ and Lotan, TL and Trock, BJ and Isaacs, WB and Pavlovich, CP},
title = {Family History of Prostate, Breast, Ovarian, and/or Pancreatic Cancer and Associations with Grade Reclassification in a Large Prostate Cancer Active Surveillance Cohort.},
journal = {European urology oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.euo.2025.07.008},
pmid = {40914661},
issn = {2588-9311},
abstract = {BACKGROUND AND OBJECTIVE: The effect of family history (FH) on prostate cancer active surveillance outcomes is unknown. Our objective is to evaluate FH of prostate, breast, ovarian, and/or pancreatic cancer in a large prospective active surveillance cohort.

METHODS: Patients with recorded FH data (N = 1421) were selected. Association between grade reclassification to Gleason grade (GG) ≥2 and GG ≥3, and FH of prostate cancer (FH-Pr); FH of breast, ovarian, and/or pancreatic cancer (FH-BOPa); and FH-Pr and/or FH-BOPa in first-degree relatives was evaluated by a competing risk analysis. Association with adverse pathologic features (APFs; GG ≥3, seminal vesicle, and/or lymph node involvement) at radical prostatectomy was assessed with multivariable logistic regression.

KEY FINDINGS AND LIMITATIONS: Of the 1421 patients, 41/362 (11.3%) with FH-Pr, 37/336 (11.0%) with FH-BOPa, and 67/600 (11.2%) with FH-Pr and/or FH-BOPa were reclassified to GG ≥3. FH-Pr was associated with reclassification to GG ≥2 and GG ≥3 (adjusted hazard ratio [HR] 1.49 for GG ≥3 [95% confidence interval {CI}
1.02-2.17], p = 0.039), as was FH-Pr and/or FH-BOPa (HR 1.52 for GG ≥3 [95% CI 1.07-2.17], p = 0.020). FH-BOPa however was not associated with any grade reclassification (HR 1.30 for GG ≥3 [95% CI 0.88-1.94], p = 0.190). In the 349 patients who underwent radical prostatectomy, no FH status was associated with APFs. Our study is limited by having information on first-degree relatives only.

Patients with FH-Pr had a higher risk of grade reclassification, including extreme grade reclassification (GG ≥3), but no FH status led to more APFs at radical prostatectomy. Patients with FH can safely be managed on surveillance, but might benefit from closer monitoring.},
}

@article {pmid40909667,
year = {2025},
author = {Ju, X and Hannon, WW and Kaszuba, T and Radford, CE and Larsen, BB and Nelson, SS and Nelson, CA and Baltazar-Perez, I and Zimmerman, O and Fremont, DH and Diamond, MS and Bloom, JD},
title = {Determinants of human versus mosquito cell entry by the Chikungunya virus envelope proteins.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40909667},
issn = {2692-8205},
abstract = {Chikungunya virus (CHIKV) infects both humans and mosquitoes during its transmission cycle. How the virus's envelope proteins mediate entry in cells from such different species is unclear. MXRA8 is a receptor for CHIKV in mammalian cells, but the receptor(s) in mosquito cells remains unknown. Here we use pseudovirus deep mutational scanning to measure how nearly all amino-acid mutations to the CHIKV envelope proteins affect entry in MXRA8-expressing human and mosquito cells. Most mutations similarly affect entry in both types of cells, and our comprehensive measurements of these effects define functional constraints related to protein folding and fusion activity. However, some mutations differentially affect entry in MXRA8-expressing human cells versus mosquito cells. Sites where mutations specifically impair entry in MXRA8-expressing human cells are often involved in MXRA8 binding, and we hypothesize sites where mutations specifically impair entry in mosquito cells are involved in binding the unknown mosquito receptor(s). We use the deep mutational scanning data to design loss-of-tropism mutant viruses that are impaired in their ability to infect either mosquito cells or MXRA8-expressing human cells. Our findings provide insights into the species-specific determinants of CHIKV cell entry that can help guide receptor identification and vaccine development.},
}

@article {pmid40291665,
year = {2025},
author = {Bakker, RA and Nicholson, OB and Park, H and Xiao, YL and Tang, W and Subramaniam, AR and Lapointe, CP},
title = {Deaminase-based RNA recording enables high throughput mutational profiling of protein-RNA interactions.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40291665},
issn = {2692-8205},
abstract = {Protein-RNA interactions govern nearly every aspect of RNA metabolism and are frequently dysregulated in disease. While individual protein residues and RNA nucleotides critical for these interactions have been characterized, scalable methods that jointly map protein- and RNA-level determinants remain limited. RNA deaminase fusions have emerged as a powerful strategy to identify transcriptome-wide targets of RNA-binding proteins by converting binding events into site-specific nucleotide edits. Here, we demonstrate that this 'RNA recording' approach enables high-throughput mutational scanning of protein-RNA interfaces. Using the λN-boxB system as a model, we show that editing by a fused TadA adenosine deaminase directly correlates with binding affinity between protein and RNA variants in vitro. Systematic variation of RNA sequence context reveals a strong bias for editing at UA dinucleotides by the engineered TadA8.20, mirroring wild-type TadA preferences. We further demonstrate that stepwise recruitment of the deaminase using nanobody and protein A/G fusions maintains both sequence and binding specificity. Stable expression of the TadA fusion in human cells reproduces in vitro editing patterns across a library of RNA variants. Finally, comprehensive single amino acid mutagenesis of λN in human cells reveals critical residues mediating RNA binding. Together, our results establish RNA recording as a versatile and scalable tool for dissecting protein-RNA interactions at nucleotide and residue resolution, both in vitro and in cells.},
}

@article {pmid40914571,
year = {2025},
author = {Vuong, W and Lo, SS},
title = {A Case for Widening the Window of Opportunity.},
journal = {International journal of radiation oncology, biology, physics},
volume = {123},
number = {2},
pages = {331-332},
doi = {10.1016/j.ijrobp.2025.03.089},
pmid = {40914571},
issn = {1879-355X},
}

@article {pmid40910475,
year = {2025},
author = {Moore, A and Kane, E and Teras, LR and Machiela, MJ and Arias, J and Panagiotou, OA and Monnereau, A and Doo, NW and Wang, Z and Slager, SL and Vermeulen, RCH and Vajdic, CM and Smedby, KE and Spinelli, JJ and Vijai, J and Giles, GG and Link, BK and Arslan, AA and Nieters, A and Bracci, PM and Camp, NJ and Salles, G and Cozen, W and Hjalgrim, H and De Vivo, I and Adami, HO and Albanes, D and Becker, N and Benavente, Y and Bisanzi, S and Boffetta, P and Brennan, P and Brooks-Wilson, AR and Canzian, F and Clavel, J and Conde, L and Cox, DG and Curtin, K and Foretova, L and Ghesquières, H and Glimelius, B and Habermann, TM and Hofmann, JN and Lan, Q and Liebow, M and Lincoln, A and Maynadie, M and McKay, J and Melbye, M and Miligi, L and Milne, RL and Molina, TJ and Morton, LM and North, KE and Offit, K and Padoan, M and Piro, S and Patel, AV and Purdue, MP and Ravichandran, V and Riboli, E and Severson, RK and Southey, MC and Staines, A and Tinker, LF and Travis, RC and Wang, SS and Weiderpass, E and Weinstein, S and Zheng, T and Chanock, SJ and Rothman, N and Birmann, BM and Cerhan, JR and Berndt, SI},
title = {Genetically determined body mass index is associated with diffuse large B-cell lymphoma in polygenic and Mendelian randomization analyses.},
journal = {International journal of cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijc.70039},
pmid = {40910475},
issn = {1097-0215},
support = {/CP/NCI NIH HHS/United States ; },
abstract = {Obesity has been associated with non-Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome-wide association studies of European ancestry (N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.18, 95% confidence interval (95% CI): 1.05-1.33, p = .005]. This finding was consistent with Mendelian randomization analyses, which demonstrated a similar increased risk of DLBCL with higher genetically determined BMI (ORper SD = 1.12, 95% CI: 1.02-1.23, p = .03). No significant associations were observed with other NHL subtypes. Our study demonstrates a positive link between a genetically determined BMI and an increased risk of DLBCL, providing additional support for increased adiposity as a risk factor for DLBCL.},
}

@article {pmid40909725,
year = {2025},
author = {Hong, A and Liu, M and Truta, A and Talaie, A and Smith, GR and Bondy-Denomy, J},
title = {Gabija restricts phages that antagonize a conserved host DNA repair complex.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40909725},
issn = {2692-8205},
abstract = {Anti-bacteriophage systems like restriction-modification and CRISPR-Cas have DNA substrate specificity mechanisms that enable identification of invaders. How Gabija, a highly prevalent nuclease-helicase anti-phage system, executes self- vs. non-self-discrimination remains unknown. Here, we propose that phage-encoded DNA end-binding proteins that antagonize host RecBCD sensitize phages to Gabija. When targeting a temperate Lambda-like phage in Pseudomonas aeruginosa, Gabija protects the cell by preventing phage genome circularization and subsequent replication. Phage and plasmid sensitivity to Gabija is licensed by DNA end-binding complexes such as a phage exonuclease together with a ssDNA-annealing protein or GamMu dimers, which prevent loading of host repair complex RecBCD. Escape phages lacking these end-binding proteins become protected from Gabija by RecBCD translocation activities. RecBCD activity on the bacterial genome also prevents Gabija from targeting self-DNA. Therefore, we propose that Gabija antagonizes circularization of linear DNA devoid of RecBCD as a mechanism to identify foreign invaders.},
}

@article {pmid40909540,
year = {2025},
author = {Ockerman, F and Chen, B and Sun, Q and Kharitonova, EV and Chen, W and Zhou, LY and Loos, RJF and Kooperberg, C and Peters, U and Haessler, J and Reiner, A and Jung, SY and Manson, JE and Nassir, R and North, KE and Buyske, S and Haiman, CA and Conti, DV and Wilkens, LR and Lange, EM and Cox, NJ and Cao, H and Raffield, LM and Li, Y and Tao, R},
title = {An Efficient Lasso Framework for Admixture-Aware Polygenic Scores.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40909540},
issn = {2692-8205},
abstract = {Polygenic scores (PGS) have promising clinical applications for risk stratification, disease screening, and personalized medicine. However, most PGS are trained on predominantly European ancestry cohorts and have limited portability to external populations. While cross-population PGS methods have demonstrated greater generalizability than single-ancestry PGS, they fail to properly account for individuals with recent admixture between continental ancestry groups. GAUDI is a recently proposed PGS method which overcomes this gap by leveraging local ancestry to estimate ancestry-specific effects, penalizing but allowing ancestry-differential effects. However, the modified fused LASSO approach used by GAUDI is computationally expensive and does not readily accommodate more than two-way admixture. To address these limitations, we introduce HAUDI, an efficient LASSO framework for admixed PGS construction. HAUDI re-parameterizes the GAUDI model as a standard LASSO problem, allowing for extension to multi-way admixture settings and far superior computational speed than GAUDI. In extensive simulations, HAUDI compares favorably to GAUDI while dramatically reducing computation time. In real data applications, HAUDI uniformly out-performs GAUDI across 18 clinical phenotypes, including total triglycerides (TG), C-reactive protein (CRP), and mean corpuscular hemoglobin concentration (MCHC), and shows substantial benefits over an ancestry-agnostic PGS for white blood cell count (WBC) and chronic kidney disease (CKD).},
}

@article {pmid40908355,
year = {2025},
author = {Chu, HY and Janes, H and Carone, M and Gilbert, PB and Plotkin, S},
title = {Improving the evidence base for COVID-19 vaccines.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {40908355},
issn = {1546-170X},
}

@article {pmid40907772,
year = {2025},
author = {Ali, M and Correa, RJM and Pryor, D and Higgs, B and Sridharan, S and Sidhom, M and Muacevic, A and Onishi, H and Swaminath, A and Grubb, W and Yang, DX and Grant, A and Morgan, SC and Ponsky, L and Cury, FL and Teh, BS and Lo, SS and Mahadevan, A and Kaplan, ID and Chu, W and Hannan, R and Staehler, M and Zaorsky, NG and Warner, A and Louie, AV and Siva, S},
title = {Efficacy of Stereotactic Ablative Body Radiotherapy (SABR) in uncommon subtypes of primary kidney cancer: An analysis from the International Radiosurgery Oncology Consortium of the Kidney.},
journal = {International journal of radiation oncology, biology, physics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ijrobp.2025.08.043},
pmid = {40907772},
issn = {1879-355X},
abstract = {BACKGROUND: While stereotactic ablative body radiotherapy (SABR) is associated with excellent local control for primary renal cell carcinoma (RCC), outcomes based on clear-cell (ccRCC) and non-clear cell (nccRCC) histologies are not well defined.

METHODS AND MATERIALS: Individual data of adult patient with biopsy confirmed primary RCC receiving SABR between 2007 and 2021 from 16 institutions in Australia, Canda, Germany, Japan and USA pooled. Patients with metastatic disease or upper tract urothelial carcinoma were excluded. The primary outcome was local failure (LF), based on the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Distant failure (DF), cancer-specific survival (CSS), treatment related toxicity and renal function changes following SABR were defined as secondary outcomes. Kaplan-Meier estimates were generated for LF, DF and CSS stratified by clear cell vs. non-clear cell histology, compared using the log-rank test (CSS) or Gray's test (LF and DF).

RESULTS: Two hundred and eleven patients with a biopsy confirmed ccRCC (n=167) or nccRCC (n=44) were included. In the nccRCC group, 59% (n=26/44) and 11% (n=5/44) were papillary and chromophobe histologies, respectively. Patients with nccRCC were more likely to be older (median age at SABR 77.2 years vs. 71.5, p=0.009) and to be treated with multifraction SABR (82% [n=36/44] vs. 38% [n=63/167]; p < 0.001) than the ccRCC group. The median follow-up was 4.02 years (IQR: 3.43-4.94) and 4.25 years (IQR: 3.02-5.00) for ccRCC and nccRCC groups, respectively. The 5-year cumulative incidence of LF was 1.5% (95% confidence interval [CI]: 0.3-4.8%) in ccRCC group vs. 2.4% (95% CI: 0.2-11.0%) in nccRCC group (hazard ratio [HR]: 0.90, 95% CI: 0.10-8.31, p=0.922). The corresponding cumulative incidence of DF at 5-years was 6.0% in ccRCC group vs. 2.9% in nccRCC group (HR: 0.34, 95% CI: 0.04-2.68, p=0.304). The 5-year estimated CSS was 96.4% in ccRCC group vs. 96.4% in nccRCC group (HR: 2.04, p=0.561). From baseline, eGFR reduced by 11.4 ± 13.4 mL/min at 3 years and by 12.2 ± 14.0 mL/min at 5 years. Sixteen patients (7.6%) experienced grade-2 or higher toxicities, with grade-2 fatigue (5.7%) being the most common.

CONCLUSION: SABR provides excellent oncologic outcomes, irrespective of ccRCC or nccRCC histology.},
}

@article {pmid40907516,
year = {2025},
author = {Gui, C and Wang, JZ and Patil, V and Landry, AP and Singh, O and Castelo-Branco, P and Tabori, U and Aldape, K and Behling, F and Barnholtz-Sloan, JS and Horbinski, C and Tabatabai, G and Ajisebutu, A and Liu, J and Patel, Z and Yakubov, R and Kaloti, R and Ellenbogen, Y and Wilson, C and Cohen-Gadol, A and Tatagiba, M and Holland, EC and Sloan, AE and Chotai, S and Chambless, LB and Gao, A and Makarenko, S and Yip, S and Nassiri, F and Zadeh, G and , },
title = {Analysis of TERT association with clinical outcome in meningiomas: a multi-institutional cohort study.},
journal = {The Lancet. Oncology},
volume = {26},
number = {9},
pages = {1191-1203},
doi = {10.1016/S1470-2045(25)00267-0},
pmid = {40907516},
issn = {1474-5488},
mesh = {Humans ; *Telomerase/genetics ; *Meningioma/genetics/pathology/mortality/surgery ; Male ; Female ; Middle Aged ; Promoter Regions, Genetic ; Mutation ; Retrospective Studies ; *Meningeal Neoplasms/genetics/pathology/mortality/surgery ; Aged ; Adult ; Prognosis ; Progression-Free Survival ; *Biomarkers, Tumor/genetics ; Canada ; Cohort Studies ; },
abstract = {BACKGROUND: TERT promoter mutation is a rare biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival. Although high TERT expression is characteristic of tumours with TERT promoter mutations, it has also been observed in tumours with wildtype TERT promoters. This study aimed to investigate the prevalence and prognostic association of TERT expression in meningiomas.

METHODS: This multi-institutional cohort study retrospectively collected clinical and molecular data from 1241 meningiomas surgically resected between Jan 1, 2000, and Dec 31, 2024, at Toronto Western Hospital, Canada (n=380; discovery cohort) and external institutions in Canada, Germany, and the USA (n=861; validation cohort). All patients were aged 18 years and older. TERT promoter mutation and TERT expression were determined by Sanger and bulk RNA sequencing. The primary outcomes were TERT expression (presence or absence) in meningiomas with and without TERT promoter mutations, and the difference in progression-free survival between tumours expressing TERT and those not expressing TERT. Survival analysis was assessed using Cox regression and Kaplan-Meier analysis.

FINDINGS: Between Jan 1, 2000, and Dec 31, 2024, clinical demographics and tumour characteristics were collected. Median follow-up was 6·2 years (IQR 1·7-12·5) in the discovery cohort and 3·3 years (1·3-3·8) in the validation cohort. 777 (65·8%) of 1181 patients with sex data in the overall cohort were female; 404 (34·2%) were male. TERT was expressed in 157 (28·7%) of 547 wildtype TERT promoter meningiomas and in 193 (32·0%) of 604 overall with RNA data. TERT expression overall conferred an intermediate progression-free survival, shorter than that in patients with TERT-negative tumours but longer than in those with TERT promoter mutations. In the discovery cohort, median progression-free survival was 3·2 years (95% CI 1·7-6·5) in patients with wildtype TERT promoter tumours expressing TERT, 16·0 years (7·1 to not reached; p=0·0021) in patients with TERT-negative wildtype TERT promoter tumours, and 1·6 years (0·9 to not reached; p=0·039) in patients with TERT promoter mutations. These findings were replicated in the validation cohort. Within each WHO grade, TERT expression conferred a progression-free survival equivalent to TERT-negative meningiomas of one grade higher. Grade 1 tumours with TERT expression had a progression-free survival similar to TERT-negative grade 2 tumours (median not reached [95% CI 16·0 to not reached] vs 8·2 years [95% CI 4·5 to not reached]; p=0·59). Grade 2 tumours with TERT expression had a similar progression-free survival to TERT-negative grade 3 tumours (median 3·6 years [2·4 to 5·3] vs 3·8 years [2·3 to not reached]; p=0·42). Multivariable regression showed that TERT expression remained associated with shorter progression-free survival even after adjusting for TERT promoter mutations, CDKN2A/B loss, chromosome 1p/22q status, and WHO grade (hazard ratio 1·85 [95% CI 1·33-2·57]; p=0·0002).

INTERPRETATION: TERT expression in meningiomas predicted earlier disease progression, independent of TERT promoter mutation and other markers, and might warrant reclassification of meningiomas that express TERT to a higher WHO grade.

FUNDING: Canadian Institutes of Health Research, Brain Tumour Charity UK, University Health Network Foundation, Mary Hunter Meningioma Research Fund, V Foundation, and National Institutes of Health.},
}

Humans
*Telomerase/genetics
*Meningioma/genetics/pathology/mortality/surgery
Male
Female
Middle Aged
Promoter Regions, Genetic
Mutation
Retrospective Studies
*Meningeal Neoplasms/genetics/pathology/mortality/surgery
Aged
Adult
Prognosis
Progression-Free Survival
*Biomarkers, Tumor/genetics
Canada
Cohort Studies

@article {pmid40907068,
year = {2025},
author = {Beckers, F and Karkada, N and Yang, Y and Scott, J and Huang, L and Klinglmüller, F and Fay, MP and Englert, S and Spiessens, B and Van Dromme, I and Shekar, T and Zhou, H and Deng, Q and Casula, D and Janes, H and Moulton, LH},
title = {Adopting the estimand framework in prophylactic vaccine trials.},
journal = {Vaccine},
volume = {64},
number = {},
pages = {127645},
doi = {10.1016/j.vaccine.2025.127645},
pmid = {40907068},
issn = {1873-2518},
abstract = {The estimand framework as outlined in ICH E9(R1) has been extensively discussed and implemented in clinical trials of therapeutic products. However, there is limited literature on the application of the framework in preventive vaccine trials, which has many unique characteristics, including emphasis on estimating the per-protocol or "biological" effect. We provide a comprehensive review of the application of the framework to preventive vaccine trials evaluating clinical outcome and immunogenicity, focusing on commonly encountered intercurrent events including but not limited to: noncompliance with vaccination schedule and blood sampling window, infection not meeting protocol definition, death, and use of prohibited products. We discuss various considerations in choosing strategies to handle intercurrent events in terms of their utility in addressing the scientific questions. Finally, we provide considerations and examples for summarizing study estimands and data handling which may be incorporated into the protocol and statistical analysis plan.},
}

@article {pmid40906481,
year = {2025},
author = {Osazuwa-Peters, N and Gao, MZ and Kahmke, RR and Ramkumar, SP and Bates, NE and Scherrer, JF},
title = {Preexisting Psychiatric Risk Factors and Any and Long-Term Opioid Use in Head and Neck Cancer.},
journal = {JAMA otolaryngology-- head & neck surgery},
volume = {},
number = {},
pages = {},
pmid = {40906481},
issn = {2168-619X},
abstract = {INTRODUCTION: Head and neck cancer (HNC), one of the most emotionally distressing cancers, carries a significant burden of psychiatric comorbidities. While opioids are commonly prescribed in cancer care, the association between preexisting psychiatric risk factors and prescription opioid use in HNC remains unclear.

OBJECTIVE: To test the hypothesis that preexisting psychiatric risk factors are associated with any opioid prescription and long-term opioid therapy in patients with HNC.

This retrospective longitudinal cohort study used deidentified data from the Optum electronic health record database, comprising a random sample of 5 million patients across the US between January 2010 and December 2018. Eligible patients were adults diagnosed with HNC. Using a 2-year look-back prior to the index date of HNC diagnosis, patients who used prescription opioids prior to HNC diagnosis were excluded. The data analysis was conducted between July 2022 and July 2023.

MAIN OUTCOMES AND MEASURES: Outcomes of interest were receipt of any prescription opioid within 12 months of index HNC and long-term opioid therapy (LTOT), defined as 10 or more opioid prescriptions within 12 months of index HNC. Psychiatric risk factors included anxiety disorders, depression, smoking/nicotine dependence, substance use disorders, and benzodiazepine prescription. Multivariate logistic regression estimated the odds of opioid use based on preexisting psychiatric factors.

RESULTS: Of 20 286 patients with an HNC diagnosis, 11 335 met all eligibility criteria. Patients in the analytic cohort had a mean (SD) age of 57.1 (15.5) years, and 55.4% were female. Within 12 months of HNC diagnosis, 23.4% received an opioid prescription, and 4.9% received LTOT. In fully adjusted models, depression (adjusted odds ratio [aOR], 1.21; 95% CI, 1.01-1.45), nicotine dependence (aOR, 1.56; 95% CI, 1.40-1.73), and benzodiazepine comedication (aOR, 1.44; 95% CI, 1.22-1.70) were associated with increased odds of receiving any opioid prescription. Furthermore, male patients had 49% greater odds of receiving opioid prescriptions (aOR, 1.49; 95% CI, 1.36-1.64). Only smoking/nicotine dependence was associated with increased odds of LTOT (aOR, 1.77; 95% CI, 1.21-2.61).

CONCLUSIONS AND RELEVANCE: Preexisting psychiatric comorbidities, especially depression and smoking/nicotine dependence, were associated with increased odds of prescription opioid use and LTOT in patients with HNC in this longitudinal cohort study. Screening for these comorbidities during the management of patients with HNC can be impactful in informing clinical decisions that contribute to safer opioid prescribing.},
}

@article {pmid40906475,
year = {2025},
author = {Issaka, RB and Matrajt, L and de Lima, PN and Rutter, CM},
title = {Modeled Cost-Effectiveness of a Rideshare Program to Facilitate Colonoscopy Completion.},
journal = {JAMA network open},
volume = {8},
number = {9},
pages = {e2530515},
pmid = {40906475},
issn = {2574-3805},
mesh = {Humans ; *Colonoscopy/economics/statistics & numerical data ; *Cost-Benefit Analysis ; *Colorectal Neoplasms/diagnosis/economics/prevention & control ; Male ; Female ; Middle Aged ; *Early Detection of Cancer/economics/methods/statistics & numerical data ; Aged ; Occult Blood ; *Mass Screening/economics ; },
abstract = {IMPORTANCE: In colorectal cancer (CRC) screening, too many patients fail to receive follow-up colonoscopy after an abnormal fecal immunochemical test (FIT), and transportation is a frequently reported barrier.

OBJECTIVE: To determine the outcomes and cost-effectiveness of providing a rideshare intervention to patients with abnormal FIT results.

The CRC-Simulated Population Model for Incidence and Natural History microsimulation model was used to simulate the outcomes and cost-effectiveness of a rideshare intervention to improve colonoscopy completion in a population-based CRC screening program. Cohorts were adherent to annual FIT-based screening; baseline analyses assumed that 35% would complete a follow-up colonoscopy. Data were analyzed from November 14, 2023, to July 8, 2025.

INTERVENTION: A $40 or $100 rideshare to increase completion of follow-up colonoscopy.

MAIN OUTCOMES AND MEASURES: Lifetime outcomes included the number of CRC cases, deaths, and life-years gained (LYG) per 1000 people screened and costs associated with improved completion of a colonoscopy after an abnormal FIT result.

RESULTS: Four single-age cohorts (ages 45, 55, 65, and 70 years on January 1, 2024) of 10 million people each were simulated. In cohorts with similar sex distribution as the US population (aged 45 years, 50.0% male; aged 55 years, 49.4% male); aged 65 years, 48.0% male; and aged 70 years, 46.9% male), compared with no intervention, using a rideshare intervention starting at age 45 years that costs $100 per ride to increase colonoscopy completion from 35% to 70% was associated with a reduction in CRC cases per 1000 by 26.3% (30.7 vs 41.6 cases per 1000), CRC deaths per 1000 by 32.5% (9.8 vs 14.6 cases per 1000), 24.9 LYG per 1000, and at $100 per ride cost $43 308 per 1000 people screened and saved $330 587 per 1000 people screened.

CONCLUSIONS AND RELEVANCE: In a microsimulation model, increasing colonoscopy completion in a population with abnormal FIT results via a rideshare intervention was cost saving up to $100 per ride due to the combined outcome of cancer prevention and early detection.},
}

Humans
*Colonoscopy/economics/statistics & numerical data
*Cost-Benefit Analysis
*Colorectal Neoplasms/diagnosis/economics/prevention & control
Male
Female
Middle Aged
*Early Detection of Cancer/economics/methods/statistics & numerical data
Aged
Occult Blood
*Mass Screening/economics

@article {pmid40906320,
year = {2025},
author = {Ilozumba, MN and Gomez, MF and Lin, T and Himbert, C and Round, JL and Zac Stephens, W and Warby, CA and Hardikar, S and Li, CI and Figueiredo, JC and Damerell, V and Fillmore, GC and Pickron, B and Toriola, AT and Shibata, D and Holowatyj, AN and Kahlert, C and Sankar, K and Siegel, EM and Jedrzkiewicz, J and Gigic, B and Byrd, DA and Ose, J and Ulrich, CM},
title = {Pre-surgery gut microbial diversity and abundance are associated with post-surgery onset of cachexia in colorectal cancer patients: the ColoCare Study.},
journal = {Cancer causes & control : CCC},
volume = {},
number = {},
pages = {},
pmid = {40906320},
issn = {1573-7225},
support = {U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; 01KD2101D//the German Ministry of Education and Research project PerMiCCion/ ; 01KD2101D//the German Ministry of Education and Research project PerMiCCion/ ; },
abstract = {BACKGROUND: Cachexia accounts for about 20% of all cancer-related deaths and it is indicative of poor prognosis and progressive functional impairment. The role of the gut microbiome in the development of cachexia in colorectal cancer (CRC) patients has not been established.

METHODS: Pre-surgical stool samples from n = 103 stage I-III CRC patients in the ColoCare Study were analyzed using 16S rRNA gene sequencing (Illumina) to characterize fecal bacteria. We calculated estimates of alpha- and beta-diversity and a priori- and exploratory-selected bacterial relative abundance. Using Fearon criteria, cachexia onset at 6 months post-surgery was defined as > 5% weight loss over the past 6 months and/or body mass index (BMI) of < 20 kg/m[2] and weight loss of > 2%. Associations of microbial metrics with cachexia onset were estimated using multivariable logistic regression models.

RESULTS: Higher alpha-diversity was positively associated with cachexia onset, with stronger associations in females, patients < 65 years, those receiving adjuvant treatment, consuming high fiber, or with energy intake outside USDA recommendations (p < 0.05). Porphyromonas (OR = 0.51, 95% CI 0.26-0.89, p = 0.03) and Actinomyces (OR = 0.72, 95% CI 0.48-1.03, p = 0.08) were inversely associated with cachexia, although the association for Actinomyces did not reach statistical significance. Stratified analyses revealed a stronger inverse association between Porphyromonas and cachexia onset in males, patients with rectal or stage III tumors, those receiving neoadjuvant treatment, physically inactive individuals, and those consuming low fiber. However, these associations did not reach statistical significance (0.05 ≤ p < 0.10).

CONCLUSION: Higher gut microbial alpha-diversity and lower relative abundances of the genera Porphyromonas and Actinomyces in pre-surgery stool samples were associated with onset of cachexia in CRC patients six months post-surgery. This is the first study to explore a link between the gut microbiome and cachexia in CRC patients, providing novel insights into the biology of cachexia and potential clinical interventions.},
}

@article {pmid39651144,
year = {2024},
author = {Swan, DA and Krantz, EM and Byrne, C and Okuku, F and Nankoma, J and Mutyaba, I and Phipps, W and Schiffer, JT},
title = {Human Herpes Virus-8 Oral Shedding Heterogeneity is Due to Varying Rates of Reactivation from Latency and Immune Containment.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39651144},
issn = {2692-8205},
abstract = {Human herpesvirus-8 (HHV-8) is a gamma herpesvirus linked to the development of Kaposi sarcoma (KS). KS is more common in persons living with HIV (PLWH), but endemic KS in HIV-negative individuals is also common in sub-Saharan Africa. HHV-8 shedding occurs in the oral mucosa and is likely responsible for transmission. The mechanistic drivers of different HHV-8 shedding patterns in infected individuals are unknown. We applied stochastic mathematical models to a longitudinal study of HHV-8 oral shedding in 295 individuals in Uganda who were monitored daily with oral swabs. Participants were divided into four groups based on whether they were HIV-negative or positive as well as KS-negative or positive. In all groups, we observed a wide variance of shedding patterns, including no shedding, episodic low viral load shedding, and persistent high viral load shedding. Our model closely replicates patterns in individual data and attributes higher shedding rates to increased rates of viral reactivation, and lower median viral load values to more rapid and effective engagement of cytolytic immune responses. Our model provides a framework for understanding different shedding patterns observed in individuals with HHV-8 infection.},
}

@article {pmid40905821,
year = {2025},
author = {Lawson-Michod, KA and Johnson, CE and Barnard, ME and Davidson, NR and Collin, LJ and Nix, DA and Huff, CD and Berchuck, A and Salas, LA and Greene, CS and Marks, JR and Peres, LC and Doherty, JA and Schildkraut, JM},
title = {Homologous recombination deficiency and survival in ovarian high-grade serous carcinoma by self-reported race.},
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-25-0762},
pmid = {40905821},
issn = {1538-7755},
abstract = {BACKGROUND: Half of ovarian high-grade serous carcinomas (HGSC) have homologous recombination deficiency (HRD). However, HRD is not well-characterized in Black individuals who experience worse survival after a diagnosis of HGSC. The objective of this study was to characterize ovarian HGSC HRD and examine its association with survival by self-reported race.

METHODS: HRD features were identified using matched tumor-normal whole-exome and RNA sequencing in a HGSC cohort. We calculated age and stage-adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for survival, comparing individuals with a feature to those without, separately by self-reported race.

RESULTS: Any HRD was associated with a 32% reduced risk of death in Black individuals compared with a 62% reduction in White individuals (Black HR=0.68, 95%CI 0.43-1.09; White HR=0.38, 95%CI 0.14-1.04). More of the germline and somatic variants detected among Black individuals were unannotated or variants of uncertain significance (VUS; germline 65% versus 45%; somatic 62% versus 50%, respectively). Black individuals with germline unannotated/VUS were more likely to have tumors with HRD scarring and a first-degree family history of breast or ovarian cancer compared with those without (HRD scar 71.4% versus 49.6%; family history 68.4% versus 34.6%).

CONCLUSIONS: HRD testing informs precision-based medicine approaches that improve outcomes, but a higher proportion of VUS among Black individuals may complicate referral for such care leading to worse outcomes for Black individuals.

IMPACT: Our findings emphasize the importance of recruiting diverse individuals in genomics research and better characterizing VUS.},
}

@article {pmid40905566,
year = {2025},
author = {Merli, P and Masetti, R and Pigazzi, M and Girardi, K and Miele, E and Bresolin, S and Baccelli, F and Peplinski, JH and Becilli, M and Paganelli, V and Strocchio, L and Buldini, B and Pagliara, D and Meshinchi, S and Locatelli, F},
title = {Sensitivity of Pediatric Myelodysplastic Syndromes With Excess of Blasts With UBTF-TD to Venetoclax/Azacitidine.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70056},
pmid = {40905566},
issn = {1096-8652},
support = {//Fondazione Umberto Veronesi (F.L.)/ ; AIRCIG26039//Fondazione AIRC/ ; },
abstract = {UBTF-TD has been reported in a significant percentage of childhood MDS-EB and has been associated with inferior survival compared to that of patients with the wild-type gene. We treated three consecutive pediatric patients affected by UBTF-TD MDS-EB with venetoclax and azacitidine (ven/aza) in combination as 28-day cycles on a compassionate use basis three consecutive pediatric patients affected by UBTF-TD MDS-EB as a bridge to allogeneic HSCT. Treatment with ven/aza was well-tolerated, and all patients responded to the ven/aza course, achieving CR with flow-cytometry negativity. All three patients were bridged to myeloablative HSCT. All patients are disease-free and graft-versus-host disease-free at last follow-up. Comprehensive biological characterization of the disease showed (i) high expression of the BCL2 gene, paralleled by a low expression of BCL2A1 and MCL1; (ii) overexpression of both HOXA and HOXB; and (iii) a distinct methylation signature of patients with UBTF-TD myeloid neoplasms.},
}

@article {pmid40905099,
year = {2025},
author = {Gem, H and Ebadi, M and Sebastian, G and Abasaeed, R and Lloid, M and Minot, SS and Dean, DR and Rashidi, A},
title = {Dental plaque microbiota following allogeneic hematopoietic cell transplantation and risk of chronic graft-versus-host disease.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2025.288279},
pmid = {40905099},
issn = {1592-8721},
abstract = {Microbiota disruptions have been associated with short-term complications after allogeneic hematopoietic cell transplantation (alloHCT). However, only a few studies have examined the relationship between dysbiosis and chronic graft-versus-host disease (cGVHD), the main long-term immunologic toxicity of alloHCT. Considering the role of oral microbiota in systemic inflammatory diseases, we evaluated whether oral microbiota at day 28 post-HCT corresponding to clinical recovery from the acute events after transplantation is associated with subsequent cGVHD. Shotgun metagenomic sequencing of 207 saliva and supragingival plaque samples collected longitudinally at baseline (pre-conditioning), day +28, and day +84 from 37 patients (11 with subsequent moderate/severe cGVHD) revealed a significant association between day +28 plaque microbiota composition and cGVHD. Two orthogonal statistical approaches demonstrated Streptococcus sanguinis and Prevotella loescheii in day +28 plaque to be associated with cGVHD. Metagenome-based functional analysis identified 4 microbial metabolic pathways associated with future cGVHD, two of which were highly attributed to S. sanguinis. These pathways - ethanolamine utilization and glycerol metabolism - increase bacterial fitness by providing an alternative carbon/nitrogen source and improving survival in inflamed tissues. Our findings propose a novel mechanism by which the early post-transplant dental biofilm may contribute to cGVHD months later, offering a potential target for early prophylactic intervention.},
}

@article {pmid40904946,
year = {2025},
author = {Cho, Y and Zheng, C and Qi, L and Prentice, RL and Zhang, MJ},
title = {Causal effect estimation for competing risk data in randomized trial: adjusting covariates to gain efficiency.},
journal = {Journal of applied statistics},
volume = {52},
number = {11},
pages = {2094-2112},
pmid = {40904946},
issn = {0266-4763},
abstract = {The double-blinded randomized trial is considered the gold standard to estimate the average causal effect (ACE). The naive estimator without adjusting any covariate is consistent. However, incorporating the covariates that are strong predictors of the outcome could reduce the issue of unbalanced covariate distribution between the treated and controlled groups and can improve efficiency. Recent work has shown that thanks to randomization, for linear regression, an estimator under risk consistency (e.g. Random Forest) for the regression coefficients could maintain the convergence rate even when a nonparametric model is assumed for the effect of covariates. Also, such an adjusted estimator will always lead to efficiency gain compared to the naive unadjusted estimator. In this paper, we extend this result to the competing risk data setting and show that under similar assumptions, the augmented inverse probability censoring weighting (AIPCW) based adjusted estimator has the same convergence rate and efficiency gain. Extensive simulations were performed to show the efficiency gain in the finite sample setting. To illustrate our proposed method, we apply it to the Women's Health Initiative (WHI) dietary modification trial studying the effect of a low-fat diet on cardiovascular disease (CVD) related mortality among those who have prior CVD.},
}

@article {pmid40903320,
year = {2025},
author = {Bakaloudi, DR and Koehne, EL and Voutsinas, JM and Diamantopoulos, LΝ and Makrakis, D and Grivas, P and True, LD and Tretiakova, MS and Vakar-Lopez, F and Psutka, SP and Holt, SK and Gore, JL and Lin, DW and Schade, GR and Nyame, YA and Hsieh, AC and Yezefski, T and Hawley, JE and Schweizer, MT and Cheng, HH and Yu, EY and Montgomery, RB and Wu, QV and Wright, JL},
title = {Agreement between transurethral resection of bladder tumor and radical cystectomy pathology in patients with bladder cancer subtype histology: A retrospective cohort study.},
journal = {Urologic oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.urolonc.2025.07.024},
pmid = {40903320},
issn = {1873-2496},
abstract = {INTRODUCTION AND OBJECTIVES: Transurethral Resection of Bladder Tumor (TURBT) is a diagnostic staging procedure for bladder cancer (BC). Its pathologic interpretation may be limited by cautery artifact, lack of spatial orientation of tumor specimens, inter-pathologist variance in identifying subtypes, and sampling bias. Accurately identifying subtype histology (SH) on TURBT is critical for clinical decisions. We compared the agreement between TURBT and radical cystectomy (RC) pathology in patients with SH BC.

METHODS: We examined TURBT and RC pathology of patients who underwent RC at our institution. We included patients with pure SH and mixed histologies in either TURBT or RC specimens. Cohen's kappa coefficient was used to determine the degree of agreement between TURBT and RC.

RESULTS: From 1135 RC performed, 650 (57%) patients had SH in either TURBT or RC; 225 patients were (y)pT0 at the time of RC and 36 patients had rare histologies, leaving 389 patients for analysis. 172 (44%) patients had an exact match between TURBT and RC. We found a high level of agreement between TURBT and RC in pure non-UC histology (kappa range: 0.82-0.98). In contrast, we found substantial (sarcomatoid; kappa 0.70), moderate (squamous, glandular, plasmacytoid, small cell/neuroendocrine; kappa range: 0.42-0.55) and fair (micropapillary; kappa 0.38) concordance between TURBT and RC in patients with UC mixed with SH.

CONCLUSIONS: We found variable levels of agreement of SH detection between TURBT and RC. Agreement was high in pure non-UC histology. Further, we found that NAT, completeness of TURBT, and >50% SH at TURBT are associated with the persistence of SH at RC. Future efforts are needed to develop reproducible diagnostic tools for accurate characterization of SH in UC.},
}

@article {pmid40902330,
year = {2025},
author = {Colbert, CM and Kruse, E and Jacqmin, D and Pichardo, JC and Wang, C and Schubert, LK and Bennett, S and Lin, MH and Olsen, L and Li, B and Kim, M},
title = {Virtual radiotherapy plan quality education: Perspectives from a global setting.},
journal = {Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)},
volume = {137},
number = {},
pages = {105069},
doi = {10.1016/j.ejmp.2025.105069},
pmid = {40902330},
issn = {1724-191X},
abstract = {PURPOSE: Evaluation of treatment plan quality is a critical element of training for radiotherapy professionals. With the increased adoption of intensity modulated radiotherapy internationally, this training is crucial to address patient care inequity. We aim to evaluate learning outcomes from a 14-session remote training course targeting critical elements of plan quality with advanced modalities.

METHODS: The virtual training course was delivered to over 500 radiotherapy professionals in North Africa. Attendees completed online pre- and post-course knowledge assessments, and surveys of their confidence in core competencies. Paired t-tests, general linear regression, and ANOVA were used to evaluate learning outcomes.

RESULTS: On the pre-course knowledge assessment, attendees scored a mean of 3.97 ± 1.54 out of 10. After the course, remaining attendees' scores increased to a mean of 4.88 ± 1.86 (p < 0.001). Mean confidence scores increased from 2.28 ± 1.22 to 3.70 ± 0.76 out of 5. Confidence scores varied significantly with enrollees' years of experience, clinical role, and involvement in treatment planning (p < 0.05). However, pre-course knowledge scores only varied based on clinicians' current involvement in advanced treatment planning (p < 0.01). The improvement in knowledge score from baseline increased significantly with course attendance (p = 0.02).

CONCLUSIONS: This course produced positive overall learning outcomes, particularly with advanced treatment planning modalities. Attendees gained practical experience applying rigorous plan quality criteria. The study results support the crucial importance of continuing education and hands-on experience in the rapidly advancing technological environment of radiation oncology.},
}

@article {pmid40899409,
year = {2025},
author = {Johnson, T and Spieler, BO and Toskich, BB and Wang, DS and Folkert, MR and Russo, S and Sharma, NK and Kim, CY and Wright, CL and Kappadath, SC and Farsad, K and Muzahir, S and Chundury, A and Parent, EE and Sio, TT and Mercier, GA and Ghesani, MV and Subramaniam, RM and Caplin, D and Small, W and Schechter, NR},
title = {ACR-ABS-ACNM-ARS-SIR-SNMMI Practice Parameter for Radioembolization of Liver Malignancies.},
journal = {American journal of clinical oncology},
volume = {},
number = {},
pages = {},
doi = {10.1097/COC.0000000000001234},
pmid = {40899409},
issn = {1537-453X},
abstract = {OBJECTIVES: The practice parameter was revised collaboratively by the American College of Radiology (ACR), the American Brachytherapy Society (ABS), the American College of Nuclear Medicine (ACNM), the American Radium Society (ARS), the Society of Interventional Radiology (SIR), and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). This document summarizes current evidence-based guidelines for the administration of Yttrium radioembolic therapy to the liver, including training requirements, evidence-based guidelines for administration, and safe practice for administration.

METHODS: This practice parameter was revised according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters-Interventional and Cardiovascular Radiology of the ACR Commission on Interventional and Cardiovascular, Committee on Practice Parameters and Technical Standards-Nuclear Medicine and Molecular Imaging of the ACR Commission on Nuclear Medicine and Molecular Imaging and the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ABS, the ACNM, the ARS, the SIR, and the SNMMI.

RESULTS: This review seeks not to be a comprehensive discussion of radiotherapy to the liver, but rather, seeks to provide a parameter for safe and effective therapy. We discuss the qualifications of physicians involved in this therapy, basic indications, contraindications, procedural work-up, safe-handling, and regulatory requirement for the administration of selective internal radiation therapy to patients that are likely to benefit. The goal of this document is not to define which patients are best treated by these therapies, as this is best determined for individual patients after multidisciplinary review. A consistent and evidence-based approach to therapy, however, would benefit all patients who are offered this therapy. This document seeks to provide a framework for current best practices for the administration of the 2 currently available radioembolization devices.

CONCLUSIONS: As Yttrium-90 radiotherapy to the liver occupies a growing role in the treatment of primary and metastatic liver cancer, this review seeks to assist clinicians of all involved specialties to optimize the efficacy and safety of these procedures.},
}

@article {pmid40895774,
year = {2025},
author = {Malik, NH and Plastaras, JP and Corradini, S and Dawson, LA and Hawkins, MA and Salerno, KE and Mayo, CS and Dunne, EM and Gabryś, D and Grassberger, C and Lawrence, TS and Sharma, M and Bergman, AM and Owen, D and Zaila, A and Rudra, S and Velec, M and Murrell, DH},
title = {Reirradiation clinical practice in gastrointestinal abdominal malignancies: an international reirradiation collaborative group (ReCOG) systematic review.},
journal = {Clinical and translational radiation oncology},
volume = {55},
number = {},
pages = {101033},
pmid = {40895774},
issn = {2405-6308},
abstract = {PURPOSE: Reirradiation in abdominal malignancies has grown more common with advanced radiotherapy techniques. However, clinical use and implementation varies, and there remains limited consensus on best practices for reirradiation. In this systematic review, a multidisciplinary team treating gastrointestinal and hepatobiliary malignancies within the Reirradiation Collaborative Group (ReCOG) convened to review published literature on reirradiation in the abdomen to offer insights into patient selection, radiotherapy planning, risk management, and assessing knowledge gaps for future development of guidelines.

METHODS AND MATERIALS: A systematic search of Cochrane Central, CINAHL Plus, EMBASE, and PubMed up to August 30, 2024, was conducted as per Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) framework. Data on patient characteristics, radiation doses, dose constraints, treatment outcomes, and toxicities were extracted. Where feasible, pooled weighted analyses were performed.

RESULTS: Thirty-three studies involving 1,264 patients met inclusion criteria: 30 were retrospective and 3 prospective. The median number of patients reported per study was 26 (range 2-245). Of the reported tumor sites, 718 patients had liver tumors and 277 pancreas, with smaller numbers of mixed/lymph node targets. Reirradiation doses, fractionation schemes, and dose constraints varied widely; only half of the studies provided explicit organ-at-risk constraints. Three studies included patients treated with palliative intent. Median overall survival ranged from 5.9 to 44 months, with a pooled weighted median OS of 19.6 months across 20 studies that reported it. One-year local control rates ranged from 19 % to 93 %, with severe (grade ≥ 3) toxicities typically reported in 5-15 % of patients, although one study reported 25 % lethal RILD in liver reirradiation.

CONCLUSION: Reirradiation in abdominal malignancies appears to be able to achieve meaningful local control and survival in select patients, though heterogeneity in planning, dosing, and toxicity reporting remains a major challenge for establishing best practices. Standardized reporting of doses, constraints, and dose-volume relationships are needed to guide safe and effective reirradiation in this setting.},
}

@article {pmid40894770,
year = {2025},
author = {Dadonaite, B and Harari, S and Larsen, BB and Kampman, L and Harteloo, A and Elias-Warren, A and Chu, HY and Bloom, JD},
title = {Spike mutations that affect the function and antigenicity of recent KP.3.1.1-like SARS-CoV-2 variants.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40894770},
issn = {2692-8205},
abstract = {SARS-CoV-2 is under strong evolutionary selection to acquire mutations in its spike protein that reduce neutralization by human polyclonal antibodies. Here we use pseudovirus-based deep mutational scanning to measure how mutations to the spike from the recent KP.3.1.1 SARS-CoV-2 strain affect cell entry, binding to ACE2 receptor, RBD up/down motion, and neutralization by human sera and clinically relevant antibodies. The spike mutations that most affect serum antibody neutralization sometimes differ between sera collected before versus after recent vaccination or infection, indicating these exposures shift the neutralization immunodominance hierarchy. The sites where mutations cause the greatest reduction in neutralization by post-vaccination or infection sera include receptor-binding domain (RBD) sites 475, 478 and 487, all of which have mutated in recent SARS-CoV-2 variants. Multiple mutations outside the RBD affect sera neutralization as strongly as any RBD mutations by modulating RBD up/down movement. Some sites that affect RBD up/down movement have mutated in recent SARS-CoV-2 variants. Finally, we measure how spike mutations affect neutralization by three clinically relevant SARS-CoV-2 antibodies: VYD222, BD55-1205, and SA55. Overall, these results illuminate the current constraints and pressures shaping SARS-CoV-2 evolution, and can help with efforts to forecast possible future antigenic changes that may impact vaccines or clinical antibodies.},
}

@article {pmid40892926,
year = {2025},
author = {Willcox, AC and Gobillot, TA and Kikawa, C and Baumgarten, NE and Stoddard, CI and Sung, K and Bhattacharya, T and Freeman, TS and Marceau, J and Humes, D and Overbaugh, J},
title = {Identification of AMOTL2 as an antiviral factor that enhances the human type I interferon response against Zika virus.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {36},
pages = {e2507955122},
doi = {10.1073/pnas.2507955122},
pmid = {40892926},
issn = {1091-6490},
support = {T32 AI083203/AI/NIAID NIH HHS/United States ; F30 AI181359/AI/NIAID NIH HHS/United States ; F30 AI142870/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; *Zika Virus/immunology/physiology ; *Interferon Type I/metabolism/immunology ; *Zika Virus Infection/immunology/virology/genetics ; Virus Replication ; Signal Transduction ; Angiomotins ; STAT1 Transcription Factor/metabolism/genetics ; HEK293 Cells ; Animals ; Immunity, Innate ; Antigens, Differentiation ; },
abstract = {Zika virus (ZIKV) has caused multiple human outbreaks, with more recent epidemics associated with severe outcomes in infants. Today, ZIKV is endemic to many countries and presents a persistent threat for future epidemics. The host innate immune proteins that regulate ZIKV replication are incompletely defined. We developed a CRISPR knockout screen to identify host factors that impact ZIKV replication, resulting in the finding of angiomotin-like protein 2 (AMOTL2), a protein that inhibits ZIKV by regulating the host type I interferon (IFN) response. AMOTL2 affects IFN signaling by modulating STAT1 levels and activation in response to type I IFN. Thus, AMOTL2, which has largely been studied for its role in cancer, represents an antiviral protein that interacts with the IFN signaling pathway to promote downstream expression of IFN stimulated genes, resulting in restriction of ZIKV.},
}

Humans
*Zika Virus/immunology/physiology
*Interferon Type I/metabolism/immunology
*Zika Virus Infection/immunology/virology/genetics
Virus Replication
Signal Transduction
Angiomotins
STAT1 Transcription Factor/metabolism/genetics
HEK293 Cells
Animals
Immunity, Innate
Antigens, Differentiation

@article {pmid40892436,
year = {2025},
author = {Nguyen, E and Korolkova, A and Ahmed, A and Meanley, S and Dee, L and Hussain, M and Wan, F and Hoh, R and Rodriguez, A and Figueroa, T and Cohn, LB and Deeks, SG and Peluso, MJ and Eskaf, S and Sugarman, J and Sauceda, JA and Dubé, K},
title = {Participant Perspectives in an HIV Treatment Interruption Study in San Francisco, United States.},
journal = {AIDS research and human retroviruses},
volume = {},
number = {},
pages = {},
doi = {10.1177/08892229251375470},
pmid = {40892436},
issn = {1931-8405},
support = {R01 MH126768/MH/NIMH NIH HHS/United States ; },
abstract = {HIV cure-related clinical research studies often include analytical treatment interruptions (ATIs), in which participants pause antiretroviral treatment (ART). During ATIs, researchers closely monitor laboratory values and adverse events. We assessed and compared the perspectives of two distinct groups of participants: HIV noncontrollers and controllers in a San Francisco-based ATI study focused on identifying biomarkers predicting HIV viral rebound. Data were collected from 2021 to 2024 over five study time points to assess motivations, understanding of the study, decisional regret, and partner protections. All participants (n = 16) endorsed the goal of helping advance HIV research as a motivator, about half were also driven by interest in their body's response to the ATI, and some indicated monetary compensation as a key motivator. Most participants (6 of 10 noncontrollers and 4 of 6 controllers) did not view personal health benefit as a primary study goal. All understood the option for an extended ATI if they had not met ART restart criteria after 28 days. At the study's onset, all sexually active participants (n = 14) were informed about the risk of transmission to sex partners and the need for partner protections during ATIs. Among noncontrollers, 2 of 5 reported using condoms, being abstinent or partner use of pre-exposure prophylaxis (PrEP) during sexual activity. Among controllers, 3 of 5 reported sexual activity: one with a partner on PrEP, one with a partner on ART, and one using other protection methods. Decisional regret about study participation, measured on a scale of 0-100, was low among both noncontrollers (range 1.67-13.57), and controllers (range 8.33-10) during the ATI, and remained low following it (noncontroller M = 5.07, SD = 4.52; controller M = 10.00, SD = 11.31). Participants generally understood the study, highlighted the need for partner protection support during ATI, and reported low decisional regret.},
}

@article {pmid40891586,
year = {2025},
author = {Velloza, J and Ortblad, KF and Kemp, CG},
title = {"Measuring the gap": advances and practical considerations in assessment of adoption, penetration, and sustainment of HIV prevention services.},
journal = {Current opinion in HIV and AIDS},
volume = {},
number = {},
pages = {},
doi = {10.1097/COH.0000000000000979},
pmid = {40891586},
issn = {1746-6318},
abstract = {PURPOSE OF REVIEW: Prior reviews have documented lack of consistency around implementation outcome measurement and gaps in assessing adoption, penetration or reach, and sustainment in HIV research. Our review sought to summarize approaches to measuring adoption, penetration, and sustainment in the HIV research literature, with a focus on the preexposure prophylaxis (PrEP) field which is ripe for exploration as long-acting PrEP formulations become available and oral PrEP programs become increasingly sustained.

RECENT FINDINGS: Our literature search of adoption, penetration, and sustainment measurement in HIV research identified 250 manuscripts. We developed a conceptual heuristic of latent and manifest measures for HIV implementation research. Few PrEP studies measured adoption according to our heuristic and latent adoption measurements were often conflated with acceptability, while manifest measurements were conflated with penetration. Most PrEP studies measuring penetration focused on the client level, with fewer measuring penetration among organizations or providers. Sustainment measurement across studies was diverse and included mixed methods assessment at organization, provider, and client levels.

SUMMARY: Heterogeneity persists in operationalizing adoption, penetration, and sustainment. Future work is needed to develop and validate pragmatic and robust measures of these constructs that can be used in evolving HIV implementation contexts.},
}

@article {pmid40890722,
year = {2025},
author = {Henderson, V and Carnahan, L and Cohn, EB and Waite, AW and Mersha, T and Block, R and Kolpack, M and Sommers, J and Salum, K and Hoskins, KF and Nguyen, R},
title = {"The more I know, the more you know" Using culturally responsive marketing strategies to develop tools that increase awareness about clinical trials among Black communities.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {3003},
pmid = {40890722},
issn = {1471-2458},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Black or African American/psychology/statistics & numerical data ; *Clinical Trials as Topic ; *Cultural Competency ; Focus Groups ; *Marketing/methods ; Neoplasms/ethnology/therapy ; },
abstract = {BACKGROUND: Ineffective dissemination of cancer research and information among the public contributes to cancer inequities. Dissemination rarely involves efforts to engage non-research audiences and end-users in developing effective messaging. Efforts to promote equity in clinical trial participation may benefit from marketing strategies traditionally applied in the business sector. Black Americans suffer the highest death rates from most cancers than any other race/ethnicity, yet only 5% of patients enrolled in cancer clinical trials are Black. Our team used a marketing strategy framework to create a culturally responsive public service announcement (PSA) video to increase awareness of clinical trials among Black audiences.

METHODS: We partnered with a marketing recruitment firm and a marketing agency to conduct six focus groups (n = 54) with social support networks of Black cancer survivors and Black community members. Maximum variation sampling was used to recruit a national sample of eligible participants that varied in age, education, geographic region, and gender. Focus groups were conducted over three phases that informed script development, script and storyline testing, and sought feedback on the PSA video post-production. We used the Marketing and Clinical Trials Reference Model to guide marketing strategies, data collection, video content development and production. We used rapid qualitative data analysis techniques to identify themes for each phase to guide PSA development.

RESULTS: Partnered with a film production company, we produced a 2-min PSA video that uses professional actors and storytelling and marketing techniques to describe clinical trials, provide relevant statistics, address barriers to participation expressed by participants, and provide credible resources to seek further information. We also produced 30 s and 60 s versions of the PSA to accommodate different marketing media outlets. Participants felt the videos were engaging and relatable and that the messaging was clear. The videos ignited meaningful discussions about clinical trial participation and motivated participants to share the information learned.

CONCLUSIONS: Using marketing communication strategies is a low-tech, pragmatic approach to effectively produce health information that is meaningful, can be tailored for specific audiences, and disseminated to broader audiences.},
}

Adult
Aged
Female
Humans
Male
Middle Aged
*Black or African American/psychology/statistics & numerical data
*Clinical Trials as Topic
*Cultural Competency
Focus Groups
*Marketing/methods
Neoplasms/ethnology/therapy

@article {pmid40887511,
year = {2025},
author = {Cimino, PJ and Keiser, DJ and Parrish, AG and Holland, EC and Szulzewsky, F},
title = {C-terminal fusion partner activity contributes to the oncogenic functions of YAP1::TFE3.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {32013},
pmid = {40887511},
issn = {2045-2322},
support = {R35 CA253119/CA/NCI NIH HHS/United States ; R35 CA253119-01A1//National Institutes of Health,United States/ ; U54 CA243125/NH/NIH HHS/United States ; U54 CA243125/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; Start-up funds//University of Utah Department of Neurosurgery and Huntsman Cancer Institute/ ; },
mesh = {*Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics/metabolism/chemistry ; YAP-Signaling Proteins ; Humans ; Animals ; Mice ; *Adaptor Proteins, Signal Transducing/genetics/metabolism ; *Transcription Factors/genetics/metabolism ; *Oncogene Proteins, Fusion/genetics/metabolism ; Cell Line, Tumor ; Carcinogenesis/genetics ; Protein Domains ; *Phosphoproteins/genetics/metabolism ; },
abstract = {YAP1 gene fusions are found in a multitude of human tumors and are the likely tumor-initiating events in these tumors. We have previously shown that YAP1 fusion proteins exert TEAD-dependent oncogenic YAP1 activity. However, the contributions of the C-terminal fusion partners to the oncogenic functions of YAP1 fusion proteins are understudied. Here, we expressed eight different YAP1 gene fusions in vivo. Tumors induced by YAP1::TFE3 displayed a significantly different histomorphology compared to tumors induced by other YAP1 fusions or activated non-fusion YAP1. To assess the extent to which TFE3 activity and the functional TFE3 domains (DNA binding: leucine zipper (LZ) and basic-helix-loop-helix (bHLH); activation domain (AD)) contribute to the oncogenic functions of YAP1::TFE3, we generated several mutant variants and performed functional in vitro and in vivo assays. In vitro, mutation or deletion of the TFE3 DNA binding domains (LZ, bHLH) resulted in reduced TFE3 activity but increased YAP1 activity of YAP1::TFE3. In vivo, deletion of the LZ and bHLH domains did not result in a decrease in tumor incidence but induced the formation of more YAP1-like tumors that lacked prominent features of YAP1::TFE3-driven tumors. By contrast, loss of the TFE3 AD almost completely abrogated tumor formation. Our results suggest that the TFE3 domains significantly contribute to the oncogenic activity of YAP1::TFE3.},
}

*Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics/metabolism/chemistry
YAP-Signaling Proteins
Humans
Animals
Mice
*Adaptor Proteins, Signal Transducing/genetics/metabolism
*Transcription Factors/genetics/metabolism
*Oncogene Proteins, Fusion/genetics/metabolism
Cell Line, Tumor
Carcinogenesis/genetics
Protein Domains
*Phosphoproteins/genetics/metabolism

@article {pmid40889272,
year = {2025},
author = {Kazemian, E and Mo, Q and Matejcic, M and Tsai, YY and Sobieski, D and Li, X and Hoogland, AI and Crowder, SL and Gonzalez, BD and Oswald, LB and Sleight, AG and Nguyen, N and Loroña, NC and Damerell, V and Komrokji, KR and Mooney, K and Playdon, MC and Ulrich, CM and Li, CI and Shibata, D and Toriola, AT and Ose, J and Peoples, AR and Hardikar, S and Kahlert, C and Siegel, EM and Bower, JE and Schmit, SL and Gigic, B and Jim, HSL and Figueiredo, JC},
title = {Genetic predisposition to persistent fatigue after a diagnosis of colorectal cancer.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf140},
pmid = {40889272},
issn = {1460-2105},
abstract = {BACKGROUND: Cancer-related fatigue (fatigue) is a common and persistent symptom after cancer treatment, yet the role of genetic susceptibility remains unclear.

METHODS: We leveraged data from a prospective cohort study, ColoCare Study (ie, five U.S. sites and Germany). Fatigue was assessed at five timepoints using the EORTC QLQ-C30 fatigue subscale and analyzed as (1) a binary summary measure of the trajectory from diagnosis into survivorship (defined as severe: yes, no), (2) a mean score across all time points, and (3) the highest (ie, worst) score across all time points. We genotyped samples using Infinium Global Diversity Array with imputation using the TOPMed reference panel to conduct a genome-wide analysis (GWAS). SuSiE was used to identify independent secondary signals. Transcriptome-wide association studies (TWAS) using S-PrediXcan and MultiXcan were conducted to examine genetic regulation of gene expression. COLOC assessed whether variants identified in the GWAS influence gene expression through colocalization analysis.

RESULTS: Among 1,219 participants, 31.0% experienced severe fatigue over the course of their diagnosis. A locus near LINC02505 on chromosome 4 was associated with severe fatigue (rs6531463, OR = 3.25, p = 3.88 × 10-8). When modeling mean fatigue levels, significantly associated variants were identified in or near NEK10 and SLC4A7. Integrative analyses linked the predicted expression of NEK10 in liver tissue to risk of fatigue (p < 4.36 × 10-6). Colocalization analysis identified genetic loci and gene expression near NEK10 (posterior probabilities > 0.9).

CONCLUSIONS: This study identified novel genetic loci associated with fatigue in CRC patients and may be useful for identifying high-risk individuals for preventative strategies.},
}

@article {pmid40888442,
year = {2025},
author = {Grivas, P and Tagawa, ST and Jain, RK and Bupathi, M and Balar, A and Rezazadeh Kalebasty, A and George, S and Palmbos, P and Nordquist, L and Petrylak, DP and Davis, N and Sternberg, CN and Agarwal, N and Park, C and Tonelli, J and Zhou, H and Bangs, R and Loriot, Y},
title = {A plain language summary of the TROPHY-U-01 study (Cohort 2): use of sacituzumab govitecan after immunotherapy in people with metastatic urothelial cancer who cannot take cisplatin-based chemotherapy.},
journal = {Future oncology (London, England)},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/14796694.2025.2548757},
pmid = {40888442},
issn = {1744-8301},
}

@article {pmid40886051,
year = {2025},
author = {Li, R and Gagliano Taliun, SA and Liao, K and Flickinger, M and Sobell, JL and Genovese, G and Locke, AE and Chiu, RR and LeFaive, J and Wang, J and Martins, T and Chapman, S and Neumann, A and Handsaker, RE and Arnett, DK and Barnes, KC and Boerwinkle, E and Braff, D and Cade, BE and Fornage, M and Gibbs, RA and Hoth, KF and Hou, L and Kooperberg, C and Loos, RJF and Metcalf, GA and Montgomery, CG and Morrison, AC and Qin, ZS and Redline, S and Reiner, AP and Rich, SS and Rotter, JI and Taylor, KD and Viaud-Martinez, KA and , and , and Bigdeli, TB and Gabriel, S and Zollner, S and Smith, AV and Abecasis, G and McCarroll, S and Pato, MT and Pato, CN and Boehnke, M and Knowles, J and Kang, HM and Ophoff, RA and Ernst, J and Scott, LJ},
title = {Whole genome sequence-based association analysis of African American individuals with bipolar disorder and schizophrenia.},
journal = {HGG advances},
volume = {},
number = {},
pages = {100499},
doi = {10.1016/j.xhgg.2025.100499},
pmid = {40886051},
issn = {2666-2477},
abstract = {In studies of individuals of primarily European genetic ancestry, common and low- frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole genome sequencing (∼27X) of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study). We increased power by incorporating 14,812 jointly called psychiatrically unscreened ancestry-matched controls from the Trans-Omics for Precision Medicine (TOPMed) Program for a total of 17,463 controls (∼37X). To identify variants and sets of variants associated with BD and/or SZ, we performed single-variant tests, gene-based tests for singleton protein truncating variants, and rare and low-frequency variant annotation-based tests with conservation and universal chromatin states and sliding windows. We found suggestive evidence of BD association with single-variants on chromosome 18 and of lower BD risk associated with rare and low-frequency variants on chromosome 11 in a region with multiple BD GWAS loci, using a sliding window approach. We also found that chromatin and conservation state tests can be used to detect differential calling of variants in controls sequenced at different centers and to assess the effectiveness of sequencing metric covariate adjustments. Our findings reinforce the need for continued whole genome sequencing in additional samples of African American individuals and more comprehensive functional annotation of non-coding variants.},
}

@article {pmid40885199,
year = {2025},
author = {Necchi, A and Guerrero-Ramos, F and Crispen, PL and Herrera-Imbroda, B and Garje, R and Powles, T and Peyton, CC and Pradere, B and Ku, JH and Shore, N and Bögemann, M and Preston, MA and Xylinas, E and Sanchez de Llano, C and Hasan, M and Stitou, H and Bhanvadia, S and Sweiti, H and Psutka, SP},
title = {TAR-200 plus cetrelimab versus cetrelimab monotherapy as neoadjuvant therapy in patients with muscle-invasive bladder cancer who are ineligible for or decline neoadjuvant cisplatin-based chemotherapy (SunRISe-4): interim analysis of a randomised, open-label phase 2 trial.},
journal = {The Lancet. Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1470-2045(25)00358-4},
pmid = {40885199},
issn = {1474-5488},
abstract = {BACKGROUND: Effective treatments are needed for patients with muscle-invasive bladder cancer scheduled for radical cystectomy who are ineligible for or decline to receive neoadjuvant cisplatin-based chemotherapy. We aimed to evaluate neoadjuvant TAR-200 plus cetrelimab (anti-PD-1) versus cetrelimab monotherapy in this setting.

METHODS: SunRISe-4 is a randomised, open-label, phase 2 trial being conducted at 109 investigative centres in ten countries worldwide. Eligible patients were aged 18 years or older, were newly diagnosed with histologically confirmed muscle-invasive bladder cancer (stage cT2-cT4 N0M0), had an Eastern Cooperative Oncology Group performance status of 0-1, were scheduled to undergo radical cystectomy, and were deemed ineligible for or declined platinum-based neoadjuvant chemotherapy. Patients were randomly assigned (5:3) in blocks of eight using an interactive web response system to receive four cycles of intravesical TAR-200 (225 mg gemcitabine) plus intravenous cetrelimab (360 mg) every 21 days or four cycles of intravenous cetrelimab (360 mg) monotherapy every 21 days. Randomisation was stratified by results of transurethral resection of bladder tumour (visibly complete vs incomplete and ≤3 cm) and tumour stage (cT2 vs cT3-4a at initial diagnosis). The primary endpoint was centrally confirmed pathological complete response in the efficacy-evaluable set. As this was a prespecified interim analysis and all patients had not completed treatment, efficacy-evaluable set was defined as all patients who had radical cystectomy or progressive disease or death before radical cystectomy. Safety was analysed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04919512, and is ongoing.

FINDINGS: From July 7, 2022, to May 31, 2024, 196 patients were assessed for eligibility and 122 were randomly assigned (TAR-200 plus cetrelimab n=80, cetrelimab monotherapy n=42). 120 patients received at least one dose of study drug. Mean age was 70·7 years (SD 7·9); 102 (85%) participants were male, 18 (15%) were female, 81 (68%) were White, 28 (23%) were Asian, and 11 (9%) were other races. In the efficacy-evaluable set (TAR-200 plus cetrelimab n=53, cetrelimab monotherapy n=31), at a median follow up of 23·5 weeks (IQR 8·6-42·0), pathological complete response rates were 42% (22 of 53 patients; 95% CI 28-56) in the TAR-200 plus cetrelimab cohort and 23% (seven of 31 patients; 10-41) in the cetrelimab monotherapy cohort. In the safety set, at a median follow-up of 10·2 weeks (IQR 1·1-36·9), treatment-related adverse events occurred in 57 (72%) of 79 patients in the TAR-200 plus cetrelimab cohort and in 18 (44%) of 41 patients in the cetrelimab monotherapy cohort. Grade 3 or worse treatment-related adverse events occurred in nine (11%) patients in the TAR-200 plus cetrelimab cohort and two (5%) in the cetrelimab monotherapy cohort, the most common being haematuria (two [3%] in the TAR-200 plus cetrelimab cohort). Serious treatment-related adverse events occurred in nine (11%) patients in the TAR-200 plus cetrelimab cohort and one (2%) patient in the cetrelimab monotherapy cohort. In the TAR-200 plus cetrelimab cohort, seven (9%) patients had treatment-related adverse events leading to discontinuation of TAR-200 and six (8%) had treatment-related adverse events leading to discontinuation of cetrelimab; there were no treatment related deaths. In the cetrelimab monotherapy cohort, no patients discontinued due to treatment-related adverse events; there was one death from a treatment-related adverse event due to hyperglycaemic, hyperosmolar, non-ketotic syndrome.

INTERPRETATION: Neoadjuvant TAR-200 plus cetrelimab showed a high pathological complete response rate with a manageable safety profile. These results support continued investigation of TAR-200 in patients with muscle-invasive bladder cancer planned for radical cystectomy.

FUNDING: Johnson & Johnson.},
}

@article {pmid40885198,
year = {2025},
author = {von Lilienfeld-Toal, M and Khawaja, F and Compagno, F and Robin, C and Piñana, JL and Cesaro, S and Einsele, H and Ljungman, P and Navarro, D and Boeckh, M and Chemaly, RF and Hirsch, HH},
title = {Community-acquired respiratory virus infections in patients with haematological malignancies or undergoing haematopoietic cell transplantation: updated recommendations from the 10th European Conference on Infections in Leukaemia.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(25)00365-2},
pmid = {40885198},
issn = {1474-4457},
abstract = {To update recommendations of the 4th European Conference on Infections in Leukaemia (ECIL-4) on community-acquired respiratory virus (CARV) infections published in 2013, we reviewed publications from between Jan 1, 2014, and June 30, 2024 on adenovirus, bocavirus, coronavirus, influenzavirus, metapneumovirus, parainfluenzavirus, respiratory syncytial virus (RSV), and rhinovirus in patients with haematological malignancies or undergoing haematopoietic cell transplantation (HCT), or both. In the current ECIL recommendations (ECIL-10), we outline a common approach to infection control, laboratory testing, and diagnosis for all CARVs (including SARS-CoV-2) and specific management and deferral strategies for CARVs other than SARS-CoV-2. For influenzavirus, seasonal inactivated-vaccines and early antivirals are recommended, whereas routine antiviral prophylaxis is discouraged for immunocompromised patients. For RSV, licensed vaccines can be considered according to local approval, despite scarce evidence for patients with haematological malignancies and those undergoing HCT. Passive immunisation with palivizumab or nirsevimab is recommended for children younger than 2 years, but data are insufficient for pre-exposure or post-exposure prophylaxis, or treatment of older children and adults. Oral ribavirin or intravenous immunoglobulins, or a combination of the two, are recommended for patients undergoing HCT with severe immunodeficiency scores. For other CARVs, recommendations include only supportive care, improving immune functions, correcting hypogammaglobulinaemia, and judicious lowering of corticosteroids. We highlight unmet needs in immunisation and antivirals for reducing CARV-associated morbidity and mortality in patients with haematological malignancies and those undergoing HCT.},
}

@article {pmid40884510,
year = {2025},
author = {Bhole, S and Grimm, LJ and Parikh, JR and Dontchos, BN and Reig, B and Jacobs, SA and Coffey, K and Dashevsky, BZ and Mullen, LA and Daly, C and Dodelzon, K},
title = {Breast Imaging Staffing Shortages: Defining the Problem and Addressing Root Causes.},
journal = {Journal of breast imaging},
volume = {},
number = {},
pages = {},
doi = {10.1093/jbi/wbaf031},
pmid = {40884510},
issn = {2631-6129},
abstract = {OBJECTIVE: To assess the current perceptions of breast imaging staffing shortages and contributing factors among breast imaging radiologists.

METHODS: A survey assessing current perception of breast radiologists regarding breast imaging-specific staffing shortages and contributing factors was developed by the Patient Care and Delivery Committee of the Society of Breast Imaging (SBI) and emailed to SBI active physician members. Bivariable analysis (chi-squared, t test) was performed between the survey demographics and survey response questions of interest.

RESULTS: There were 309 responses (response rate of 15.7%). Most respondents perceived their practices to be short-staffed for breast radiologists (79%, 239/302), US technologists (74%, 216/290), mammography technologists (70%, 211/301), and support staff (66%, 201/302). Of the respondents who indicated they were short-staffed for breast imaging radiologists, 92% (226/246) believed it was due to insufficient number of radiologists, 67% (164/246) thought it was due to increase in volume, and 63% (154/246) attributed it to both increase in volume and insufficient number of breast imaging radiologists. Practices were more likely to be short-staffed if they had more practice sites (mean, 8.2 ± 7.1 vs 6.4 ± 8.4; P = .002), had fewer breast imaging radiologists (mean, 10.1 ± 9.6 vs 11.3 ± 11.5; P = .009), and were academic practices (35.1% vs 25.7%; P = .028).

CONCLUSIONS: Most breast imaging radiologists perceive their current breast imaging practices to be short-staffed for radiologists, mammography technologists, US technologists, and support staff. Understanding contributing factors is crucial to addressing root causes and mitigating impact on patient care and burnout across breast imaging team members.},
}

@article {pmid40884418,
year = {2025},
author = {Yu, N and Panch, S and Mepani, K and Stanworth, S and Bonet-Bub, C and Gragert, L and Menard, V and Mangiola, M and Maiers, M and Berka, N},
title = {"Epitope-based matching for platelet transfusion overview: Is it time?"-Insights and future directions from the 2024 American Red Cross symposium on platelet component selection.},
journal = {Transfusion},
volume = {},
number = {},
pages = {},
doi = {10.1111/trf.18392},
pmid = {40884418},
issn = {1537-2995},
}

@article {pmid40883483,
year = {2025},
author = {Urgessa, F and Jenkins, I and Tsegaye, A and Nigussie, H and Kuru, T and Gebremedhin, A and Abdela, F and Tadesse, F and Radich, J},
title = {MicroRNAs as prognostic and predictive biomarkers among chronic myeloid leukemia patients in Addis Ababa, Ethiopia.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {31844},
pmid = {40883483},
issn = {2045-2322},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics/drug therapy/diagnosis/blood ; *MicroRNAs/genetics/blood ; Male ; Female ; Ethiopia ; *Biomarkers, Tumor/genetics/blood ; Adult ; Middle Aged ; Prognosis ; Imatinib Mesylate/therapeutic use ; Protein Kinase Inhibitors/therapeutic use ; Young Adult ; Aged ; Gene Expression Regulation, Leukemic ; Adolescent ; },
abstract = {Approximately 1.5 million people worldwide suffer from chronic myeloid leukemia (CML). MicroRNAs (miRs) are important regulators of gene expression and offer an attractive option as biomarkers for cancer detection, diagnosis, and prognosis assessment in solid and liquid tumors. To assess miRs as prognostic and predictive biomarkers among CML patients at the Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia from April 2021 to May 2023. Blood samples were collected from newly diagnosed CML patients before initiation of tyrosine kinase inhibitor (TKI), imatinib treatment, and while on therapy. The expression level of miRs were determined using the NanoString platform. LIMMA analysis was used to identify differentially expressed miR between TKI response groups and disease phases. Fifty-two study participants were enrolled in the study. From each sample, 798 hsa-miRs included on the Nanostring assay were measured. Comparing TKI naive new CML patients (n = 14) with those progressed or had blast crisis (BC) on TKI therapy (n = 12), 97 miRs were differentially expressed (|log2FC|, FDR, and P-value at > 1, < 0.001, and < 0.0001, respectively). Most miRs showed upregulation in BC CML patients compared to new CML cases except miR-223-3p, miR-4454, miR-7975, and miR-630 which were downregulated in patients with BC. In addition, eight miRs were differentially expressed comparing poor molecular responder (n = 12) with good molecular responder (n = 28) patients (P < 0.05). MiR-223-3p, miR-4454, miR-7975, and miR-630 were commonly deregulated in BC and poor molecular response groups. MiRs have significant potential as prognostic and predictive biomarkers for CML patients. MiR-223-3p, miR-4454, miR-7975 and miR-630 could be considered as prognostic and predictive biomarkers for disease progression and treatment response if validated by other large studies.},
}

Humans
*Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics/drug therapy/diagnosis/blood
*MicroRNAs/genetics/blood
Male
Female
Ethiopia
*Biomarkers, Tumor/genetics/blood
Adult
Middle Aged
Prognosis
Imatinib Mesylate/therapeutic use
Protein Kinase Inhibitors/therapeutic use
Young Adult
Aged
Gene Expression Regulation, Leukemic
Adolescent

@article {pmid40879331,
year = {2025},
author = {Sung, K and Johnson, MM and Dumm, W and Simon, N and Haddox, H and Fukuyama, J and Matsen, FA},
title = {Thrifty wide-context models of B cell receptor somatic hypermutation.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
pmid = {40879331},
issn = {2050-084X},
support = {2919.02//Gordon and Betty Moore Foundation/ ; S10 OD028685/OD/NIH HHS/United States ; R01 AI146028/AI/NIAID NIH HHS/United States ; S10OD028685/NH/NIH HHS/United States ; PHY-2309135//National Science Foundation/ ; R01-AI146028/NH/NIH HHS/United States ; },
mesh = {*Somatic Hypermutation, Immunoglobulin ; *Receptors, Antigen, B-Cell/genetics ; Humans ; },
abstract = {Somatic hypermutation (SHM) is the diversity-generating process in antibody affinity maturation. Probabilistic models of SHM are needed for analyzing rare mutations, understanding the selective forces guiding affinity maturation, and understanding the underlying biochemical process. High-throughput data offers the potential to develop and fit models of SHM on relevant data sets. In this article, we model SHM using modern frameworks. We are motivated by recent work suggesting the importance of a wider context for SHM; however, assigning an independent rate to each k-mer leads to an exponential proliferation of parameters. Thus, using convolutions on 3-mer embeddings, we develop 'thrifty' models of SHM of various sizes; these can have fewer free parameters than a 5-mer model and yet have a significantly wider context. These offer a slight performance improvement over a 5-mer model, and other modern model elaborations worsen performance. We also find that a per-site effect is not necessary to explain SHM patterns given nucleotide context. Also, the two current methods for fitting an SHM model-on out-of-frame sequence data and on synonymous mutations-produce significantly different results, and augmenting out-of-frame data with synonymous mutations does not aid out-of-sample performance.},
}

*Somatic Hypermutation, Immunoglobulin
*Receptors, Antigen, B-Cell/genetics
Humans

@article {pmid40880210,
year = {2025},
author = {Dahlberg, A and Milano, F},
title = {Targeted GVL through HLA mismatch in double cord blood transplant.},
journal = {Blood advances},
volume = {9},
number = {17},
pages = {4470-4471},
doi = {10.1182/bloodadvances.2025016876},
pmid = {40880210},
issn = {2473-9537},
}

@article {pmid40832168,
year = {2025},
author = {Mout, L and Moreno-Rodriguez, T and Grillo, G and Nand, A and Keshavarzian, T and Bahl, S and Kang, K and Bootsma, M and Minnee, E and Zhou, S and Burns, KH and Corey, E and Nelson, P and Dehm, SM and Zhao, SG and Zwart, W and Feng, F and Quigley, D and Lupien, M},
title = {Genetic and Epigenetic Reprogramming of Transposable Elements Drives ecDNA-Mediated Metastatic Prostate Cancer.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40832168},
issn = {2692-8205},
support = {P50 CA275741/CA/NCI NIH HHS/United States ; R01 CA174777/CA/NCI NIH HHS/United States ; P50 CA097186/CA/NCI NIH HHS/United States ; R01 CA276112/CA/NCI NIH HHS/United States ; P01 CA163227/CA/NCI NIH HHS/United States ; UG3 NS132127/NS/NINDS NIH HHS/United States ; R01 CA289390/CA/NCI NIH HHS/United States ; R01 CA240816/CA/NCI NIH HHS/United States ; },
abstract = {Extrachromosomal DNAs (ecDNAs), which replicate and segregate in a non-Mendelian manner, serve as vectors for accelerated tumor evolution. By integrating chromatin accessibility, whole-genome sequencing, and Hi-C-based genome topology data from a cohort of metastatic Castration-Resistant Prostate Cancer (mCRPC) cases, we show that epigenetically activated repeat DNA, amplified in ecDNAs, drive oncogene overexpression. Specifically, we identify a subgroup of mCRPCs (20%) characterized by clusters of accessible LINE1 repeat DNA elements flanking the androgen receptor (AR) gene. These LINE1 elements are co-amplified with AR and provide binding sites for prostate-lineage transcription factors, including AR, FOXA1 and HOXB13. Accessible LINE1 elements establish novel 3D chromatin interactions with the AR gene, forging a new regulatory plexus driving AR overexpression and confers resistance to androgen signaling inhibitors. Our findings indicate how tumor evolution is driven by the convergence of genetic and epigenetic alterations on repeat DNA, activating and amplifying them to allow oncogene overexpression.},
}

@article {pmid40832049,
year = {2025},
author = {Ralph, DK and Bakis, AG and Galloway, J and Vora, AA and Araki, T and Victora, GD and Song, YS and DeWitt, WS and Matsen, FA},
title = {Inference of germinal center evolutionary dynamics via simulation-based deep learning.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {40832049},
issn = {2331-8422},
support = {U01 AI150747/AI/NIAID NIH HHS/United States ; R01 AI146028/AI/NIAID NIH HHS/United States ; R56 HG013117/HG/NHGRI NIH HHS/United States ; R01 HG013117/HG/NHGRI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; },
abstract = {B cells and the antibodies they produce are vital to health and survival, motivating research on the details of the mutational and evolutionary processes in the germinal centers (GCs) from which mature B cells arise. It is known that B cells with higher affinity for their cognate antigen (Ag) will, on average, tend to have more offspring. However the exact form of this relationship between affinity and fecundity, which we call the "affinity-fitness response function", is not known. Here we use deep learning and simulation-based inference to learn this function from a unique experiment that replays a particular combination of GC conditions many times. All code is freely available at https://github.com/matsengrp/gcdyn, while datasets and inference results can be found at https://doi.org/10.5281/zenodo.15022130.},
}

@article {pmid40879300,
year = {2025},
author = {Nieto, C and Kadan-Lottick, NS and Ross, WL and Santiago-Rivera, Y and Sandbo, C and Hild, M and Bryant, S and Barnhorst, M and Appel, B and Mendoza, JA},
title = {Increasing Physical Activity in Children During Cancer Treatment: A Qualitative Study of Parents' Perspectives.},
journal = {Pediatric blood & cancer},
volume = {},
number = {},
pages = {e31961},
doi = {10.1002/pbc.31961},
pmid = {40879300},
issn = {1545-5017},
support = {//Georgetown Lombardi Comprehensive Cancer Center/ ; //Fred Hutchinson Cancer Research Center/ ; },
abstract = {This qualitative study explored barriers, facilitators, and preferences for promoting physical activity (PA) in children undergoing cancer therapy by interviewing 36 parents of children aged 4-15 years, on-therapy or less than 1 year post-therapy at three hospitals. Key barriers included safety concerns, risk of infection, and treatment side effects. Facilitators included social support and oncologist recommendations for PA. Parents preferred interventions that were flexible, varied, gamified, low-burden, and tailored to the child. Parents also expressed a desire for family involvement, connection to other parents, online social media groups, and activity trackers. These findings can inform PA interventions for children undergoing cancer therapy.},
}

@article {pmid40876913,
year = {2025},
author = {Sandmaier, BM},
title = {Profile of a Pioneer: Rainer F. Storb.},
journal = {Transplantation and cellular therapy},
volume = {31},
number = {9},
pages = {599-604},
doi = {10.1016/j.jtct.2025.08.001},
pmid = {40876913},
issn = {2666-6367},
}

@article {pmid40875889,
year = {2025},
author = {Boothby, AB and Ruiz Lopez, JN and Hegerova, L and Manogna, D and Chintapatla, R and Harris, S and Teramura, G and Tirschwell, DL and Taylor, B and Keel, SB},
title = {Addition of ADAMTS13 Testing to Cryptogenic Stroke Evaluation: Index Case and Single-Center Screening Initial Experience.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017702},
pmid = {40875889},
issn = {2473-9537},
}

@article {pmid40875887,
year = {2025},
author = {Galarza Fortuna, GM and Peres, LC and Nazarenko, E and De Menezes Silva Corraes, A and Hovanky, V and Shune, L and McGuirk, JP and de Avila, G and Khouri, J and Dima, D and Gaballa, MR and Dhakal, B and Forsberg, PA and Godara, A and Afrough, A and Anderson, LD and Herr, MM and Davis, JA and Mann, H and Purvey, S and Clark, WB and Htut, MM and Beitinjaneh, AM and Pereira, DL and Kocoglu, M and Ferreri, CJ and Atrash, S and Voorhees, PM and Rossi, AC and Richard, S and Hashmi, H and Patel, KK and Sidana, S and Lin, Y and Hansen, DK and Sborov, DW},
title = {Safety and Efficacy of BCMA directed Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Plasma Cell Leukemia.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025016966},
pmid = {40875887},
issn = {2473-9537},
abstract = {Despite significant therapeutic advances in multiple myeloma (MM), outcomes in patients with plasma cell leukemia (PCL) remain dismal. We conducted a multicenter retrospective analysis of patients with PCL treated with the B-cell Maturation Antigen (BCMA)-directed Chimeric Antigen Receptor T-Cell (CAR-T) products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). We identified 34 patients, 19 patients received ide-cel and 15 received cilta-cel. With a median follow-up of 11.9 months, the overall median progression free survival (mPFS) was 9.0 months (95% CI 4-15 months) and the median overall survival (mOS) was 13.0 months (95% CI 8-not estimable (NE) months). The 1-year cumulative incidence of progression or death was 72% and the 1-year cumulative incidence of death was 47%. Patients receiving cilta-cel had a longer mPFS (19.0 months vs 6.0 months) and mOS (>23 months (NE) vs 9.0 months) compared to those treated with ide-cel. Similarly, the 1-year cumulative incidence of disease progression or death was 37.5% (95% CI 17.4%-68.5%) with cilta-cel, while all patients treated with ide-cel progressed or died within 12 months of infusion. Rates of hematological and non-hematological toxicities were similar between those patients treated with cilta-cel and ide-cel and consistent with those reported in patients with MM. In this first multicenter study evaluating patients with PCL treated with standard of care CAR-T products, we show that CAR-T is safe, feasible, and associated with improved outcomes compared to historical standards.},
}

@article {pmid40875591,
year = {2025},
author = {Hall, K and Lazaryan, A and Der Laan, MV and Lee, CJ and Logan, AC and Gruber, S and Kabadi, S and Khan, I and Nicholls, C and Rota, LM and Nikai, E and Ponomareva, E and Koumas, A and Waller, EK},
title = {Efficacy and Safety of Belumosudil as Compared with Best Available Therapy for the Treatment of cGVHD in the US.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025015832},
pmid = {40875591},
issn = {2473-9537},
abstract = {Belumosudil was FDA-approved in the United States (US) for the treatment of relapsed/refractory chronic graft-versus-host disease (cGVHD) based on a randomized phase II trial comparing two belumosudil doses. The efficacy and safety of belumosudil versus the best available therapy (BAT) have not been studied. Applying rigorous statistical methodology to real-world data, this study estimated the efficacy of belumosudil versus BAT in cGVHD patients whose disease failed to respond to 2-5 prior lines of therapy (LOTs). Retrospective data between March 2015 and 2024 was collected across 8 US sites on 196 patients contributing 113 belumosudil and 245 BAT LOTs. The primary outcome was 6-month overall response rate (ORR), defined as the proportion of complete or partial responses based on 2014 NIH consensus criteria, physician assessment, or corticosteroid dose taper of ≥ 50% without cGVHD progression. Death, relapse, and beginning a new LOT were considered a lack of response. Targeted maximum likelihood estimation (TMLE) was used to estimate the 6-month ORR following belumosudil versus BAT (38.7% versus 26.8%, respectively, or 44.2% improvement with belumosudil (one-sided 95% confidence interval (CI): [4.4%, ∞); p: 0.031)). TMLE was also used to estimate 1-year failure-free survival (FFS) when treated with belumosudil (61.2%) or BAT (47.8%), a 13.5% difference (95% CI: [1.5%, 100.0%), p: 0.032). Descriptive assessment of safety showed adverse events recorded in 27% of belumosudil and 36% of BAT LOTs. Findings demonstrated that belumosudil improved clinical outcomes versus BAT in cGVHD patients with 2-5 prior LOTs, and safety was consistent with belumosudil's established profile.},
}

@article {pmid40870354,
year = {2025},
author = {Han, Z and Li, T and You, J and Balakrishnan, N},
title = {Varying-Coefficient Additive Models with Density Responses and Functional Auto-Regressive Error Process.},
journal = {Entropy (Basel, Switzerland)},
volume = {27},
number = {8},
pages = {},
pmid = {40870354},
issn = {1099-4300},
support = {21YJA910001//Humanities and Social Science Fund of Ministry of Education of China/ ; 11971291//National Natural Science Foundation of China (NSFC)/ ; },
abstract = {In many practical applications, data collected over time often exhibit autocorrelation, which, if unaccounted for, can lead to biased or misleading statistical inferences. To address this issue, we propose a varying-coefficient additive model for density-valued responses, incorporating a functional auto-regressive (FAR) error process to capture serial dependence. Our estimation procedure consists of three main steps, utilizing spline-based methods after mapping density functions into a linear space via the log-quantile density transformation. First, we obtain initial estimates of the bivariate varying-coefficient functions using a B-spline series approximation. Second, we estimate the error process from the residuals using spline smoothing techniques. Finally, we refine the estimates of the additive components by adjusting for the estimated error process. We establish theoretical properties of the proposed method, including convergence rates and asymptotic behavior. The effectiveness of our approach is further demonstrated through simulation studies and applications to real-world data.},
}

@article {pmid40875480,
year = {2025},
author = {Friedland, BA and Browne, EN and Roberts, ST and Ngure, K and Nakalega, R and Macdonald, P and Mpongo, CN and Tenza, S and Mhlanga, N and Szydlo, D and Johnson, S and McClure, T and Nair, G and Celum, C and Hillier, S and van der Straten, A and , },
title = {Higher acceptability of the monthly dapivirine ring versus daily oral pre-exposure prophylaxis among adolescent girls and young women in sub-Saharan Africa in the REACH trial.},
journal = {Journal of acquired immune deficiency syndromes (1999)},
volume = {},
number = {},
pages = {},
doi = {10.1097/QAI.0000000000003756},
pmid = {40875480},
issn = {1944-7884},
abstract = {BACKGROUND: Oral pre-exposure prophylaxis (PrEP) is effective for HIV prevention, yet use has been inconsistent in adolescent girls and young women (AGYW). We compared PrEP to the dapivirine vaginal ring (ring) among AGYW in MTN-034 (REACH).

METHODS: We randomized 247 16-21-yr-old AGYW (South Africa, Uganda, Zimbabwe) to the sequence of using the ring and oral PrEP for 6m each (February 2019-September 2021). Participants rated overall product acceptability (1, dislike very much to 5, like very much) after 3m and 6m, and product characteristics/use attributes after 3m. We compared proportions of participants rating each product a "5" (binomial model with generalized estimating equations). We assessed associations between product characteristics/use attribute ratings at 3m and overall acceptability after 6m (Chi-square).

RESULTS: 65% and 41% of participants rated the ring versus PrEP a "5" (adjusted risk difference [aRD] 24%, 95% CI: 15%, 32%; p<0.001). For both products, high overall acceptability was associated with "excellent" self-rated adherence (ring, p< 0.001; PrEP, p = 0.03), product appearance (ring, p = 0.005; PrEP, p < 0.001), and ease of use (ring, p = 0.001; PrEP, p = 0.003). Not worrying about/or experiencing side effects were also associated with high acceptability of oral PREP.

CONCLUSIONS: The dapivirine ring was highly acceptable to substantially more individuals than oral PrEP, although a significant minority rated oral PrEP highly, even after using the ring. As has been found in the contraceptive field, offering AGYW a choice of PrEP products is likely to increase the use of any HIV prevention method in this vulnerable population.},
}

@article {pmid40873297,
year = {2025},
author = {Duong, VA and Pan, E and Dabral, P and Utzschneider, KM and Lampe, JW and Chen, R and A J Hullar, M},
title = {Metaproteomic Analysis to Assess the Impact of Storage Media on Human Gut Microbiome in Fecal Samples.},
journal = {Proteomics},
volume = {},
number = {},
pages = {e70035},
doi = {10.1002/pmic.70035},
pmid = {40873297},
issn = {1615-9861},
support = {R01CA211892//National Institutes of Health (NIH)/ ; R01CA276173//National Institutes of Health (NIH)/ ; },
abstract = {The human gut microbiome is a diverse community of microorganisms residing in the gastrointestinal tract. The storage condition of fecal samples may impact the taxonomic and protein compositions of microbiomes in these samples. Here, we performed a mass spectrometry-based metaproteomic study to assess the impact of storage media on human gut microbiome in fecal samples. We evaluated FDA-authorized OMNIgene·GUT (OG), phosphate-buffered saline (PBS), and RNALater (RNAL) buffers and identified 38,185 microbial peptides corresponding to 7348 microbial proteins, which matched 16 phyla, 20 classes, 50 orders, 104 families, 332 genera, and 453 species. We found a high similarity among the fecal microbiomes preserved in OG, PBS, and RNAL in terms of the identification of proteins, taxa, and functional annotations. Both alpha and beta diversity suggested the high similarity among samples stored in the three media. Nonetheless, we also found some notable differences among buffers regarding the abundances of a few taxon groups. A partial human proteome (over 400 proteins) was identified in the fecal samples, with most of these proteins associated with the membrane and extracellular regions. The findings indicate the similarity among microbiomes in the fecal samples stored in OG, PBS, and RNAL regarding proteome profile, taxa, and functional capacity. SUMMARY: This study thoroughly analyzed and compared the metaproteomes of fecal samples preserved at -80°C in PBS, RNALater, and OMNIgene·GUT Dx buffers, offering novel insights into the effectiveness of these buffers in maintaining the stability and composition of the human gut microbiome. We found a high similarity in the identification and quantification of proteins, taxa, and functional annotations across the three buffers, with notable quantitative differences highlighting subtle yet important variations in preservation efficacy. The unique datasets and findings could offer valuable revelations into the impact of fecal sample preservation on translational and clinical analyses of the human gut microbiome.},
}

@article {pmid40867077,
year = {2025},
author = {Ebadi, M and Reddi, S and Senyshyn, L and Minot, SS and Gooley, T and Kabage, AJ and Lee, SJ and Hill, GR and Khoruts, A and Rashidi, A},
title = {Effect of fecal microbiota transplantation on gut microbiota functional profile in recipients of allogeneic hematopoietic cell transplantation.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2551882},
pmid = {40867077},
issn = {1949-0984},
mesh = {Humans ; *Fecal Microbiota Transplantation ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Male ; Middle Aged ; Female ; Adult ; Bacteria/classification/genetics/isolation & purification/metabolism ; *Dysbiosis/therapy/microbiology ; Transplantation, Homologous ; Feces/microbiology ; Aged ; },
abstract = {Intestinal dysbiosis has been associated with both the effectiveness and toxicity of immunotherapy in cancer patients, inspiring multiple trials investigating fecal microbiota transplantation (FMT) in these patients. FMT restores microbial community structures damaged by antibiotics and enriches the microbiota with beneficial bacteria. However, the precise mechanism through which FMT exerts its effects and provides clinical benefits remains incompletely understood. Efforts to date have primarily focused on characterizing taxonomic changes following FMT. We hypothesized that FMT may also modify the functional pathways and metabolic capabilities of the gut microbiota, with possible clinical impact. To investigate this, we conducted a study involving 17 patients with blood disorders who received prophylactic FMT from one of the three healthy donors shortly after hematopoietic cell transplantation (HCT). By analyzing shotgun metagenomic profiles of the baseline, pre-FMT, and post-FMT gut microbiota, we demonstrate that FMT effectively restored pathways that had been depleted following HCT. However, it did not significantly reduce pathways that had expanded, indicating that FMT operates primarily through a restorative mechanism, reestablishing lost functional capabilities in the microbiota rather than suppressing overactive pathways. These findings highlight the potential for optimizing FMT protocols and identifying patient populations where FMT may be particularly beneficial.},
}

Humans
*Fecal Microbiota Transplantation
*Hematopoietic Stem Cell Transplantation/adverse effects
*Gastrointestinal Microbiome
Male
Middle Aged
Female
Adult
Bacteria/classification/genetics/isolation & purification/metabolism
*Dysbiosis/therapy/microbiology
Transplantation, Homologous
Feces/microbiology
Aged

@article {pmid40864714,
year = {2025},
author = {Craig, E and Keyes, TJ and Sarno, J and D'Silva, JP and Domizi, P and Zaslavsky, M and Tsai, A and Glass, D and Nolan, GP and Hastie, T and Tibshirani, R and Davis, KL},
title = {Annotation-free discovery of disease-relevant cells in single-cell datasets.},
journal = {Science advances},
volume = {11},
number = {35},
pages = {eadv5019},
pmid = {40864714},
issn = {2375-2548},
mesh = {Humans ; *Single-Cell Analysis/methods ; *Leukemia/pathology ; Neoplasm, Residual/pathology ; Algorithms ; },
abstract = {In single-cell datasets, patient labels indicating disease status (e.g., "sick" or "not sick") are typically available, but individual cell labels indicating which of a patient's cells are associated with their disease state are generally unknown. To address this, we introduce mixture modeling for multiple-instance learning (MMIL), an expectation-maximization approach that trains cell-level binary classifiers using only patient-level labels. Applied to primary samples from patients with acute leukemia, MMIL accurately separates leukemia from nonleukemia baseline cells, including rare minimal residual disease (MRD) cells; generalizes across tissues and treatment time points; and identifies biologically relevant features with accuracy approaching that of a hematopathologist. MMIL can also incorporate cell labels when they are available, creating a robust framework for leveraging both labeled and unlabeled cells. MMIL provides a flexible modeling framework for cell classification, especially in scenarios with unknown gold-standard cell labels.},
}

Humans
*Single-Cell Analysis/methods
*Leukemia/pathology
Neoplasm, Residual/pathology
Algorithms

@article {pmid40864016,
year = {2025},
author = {Ezzat, D and Uddin, MM and Xue, L and Pershad, Y and Zhang, S and Collins, JM and Kitzman, JO and Jaiswal, S and Desai, P and Kooperberg, C and Bick, AG and Natarajan, P and Manson, JE and Whitsel, EA and Reiner, AP and Honigberg, MC},
title = {Clonal Hematopoiesis and Cardiovascular Outcomes in Older Women.},
journal = {Journal of the American College of Cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jacc.2025.07.058},
pmid = {40864016},
issn = {1558-3597},
abstract = {BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) is an emerging aging-related risk factor for cardiovascular disease (CVD). However, previous studies suggest that CHIP's relevance to CVD may diminish with advancing age.

OBJECTIVES: This study aimed to test the association of CHIP and its key subtypes with incident CVD in an older population.

METHODS: Participants in the Women's Health Initiative Long Life Study completed study assessments in 2012-2013 and underwent high-coverage sequencing (median depth 4,580×). The co-primary exposures were composite CHIP and TET2 CHIP. DNMT3A, ASXL1, JAK2, and non-DNMT3A CHIP were examined as secondary exposures. The primary outcome was incident coronary heart disease. Secondary outcomes were incident heart failure with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF), ischemic stroke, venous thromboembolism, and cardiovascular death. Multivariable-adjusted Cox models tested associations between CHIP and incident CVD.

RESULTS: Among 6,677 women (median age 80 years; median follow-up 10.1 years), 2,176 (32.6%) had any CHIP. TET2 CHIP was independently associated with incident coronary heart disease (aHR: 1.36 [95% CI: 1.05-1.77]; P = 0.02), whereas composite CHIP was not (aHR: 1.07 [95% CI: 0.89-1.28]; P = 0.49). Secondarily, TET2 CHIP was associated with HFpEF (aHR: 1.40 [95% CI: 1.03-1.90]; P = 0.03), ASXL1 CHIP with HFrEF (aHR: 3.16 [95% CI: 1.53-6.55]; P = 0.002), and JAK2 CHIP with ischemic stroke (aHR: 2.49 [95% CI: 1.17-5.30]; P = 0.02), venous thromboembolism (aHR: 2.71 [95% CI: 1.11-6.65]; P = 0.03), and cardiovascular death (aHR: 2.62 [95% CI: 1.68-4.11]; P < 0.001). No other significant associations were observed for composite or DNMT3A CHIP.

CONCLUSIONS: In an older female cohort, key CHIP subtypes (TET2, ASXL1, and JAK2) were associated with incident CVD, with associations that appeared to differ by CVD outcome. These findings suggest that CHIP remains associated with cardiovascular health into later life. (Women's Health Initiative [WHI]; NCT00000611).},
}

@article {pmid40863730,
year = {2025},
author = {Lai, Y-T and Dingens, AS and DeMouth, M and Helmold Hait, S and O'Dell, S and Schon, A and Olia, AS and Wang, T and Shrader, HR and Lovelace, SE and Pegu, A and Doria-Rose, NA and Mascola, JR and Bloom, JD and Kwong, PD},
title = {Fostemsavir analog BMS-818251 has enhanced viral neutralization potency and similar escape mutation profile.},
journal = {Antimicrobial agents and chemotherapy},
volume = {},
number = {},
pages = {e0191024},
doi = {10.1128/aac.01910-24},
pmid = {40863730},
issn = {1098-6596},
abstract = {BMS-818251, a fostemsavir analog, is a next-generation HIV-1 attachment inhibitor with enhanced potency and a similar resistance profile. By using ex vivo viral outgrowth assays with HIV+ donor samples, we demonstrate here that BMS-818251 exhibits superior viral suppression compared to temsavir, the active form of fostemsavir. To map potential resistance pathways, we employed deep mutational scanning and pseudotyped virus neutralization assays to identify escape mutations within the HIV-1 envelope glycoprotein (Env). These mutations were largely clustered around the BMS-818251 binding site, with key resistance mutations reducing drug-binding affinity. Several of the enriched mutations, such as S375I/N, M426L, and M475I, have been previously observed in fostemsavir-treated patients, highlighting their clinical relevance. Isothermal titration calorimetry revealed reduced binding affinity as the primary mechanism of resistance, though with notable exceptions, such as R429G, suggesting additional factors to influence viral escape. Ex vivo Env sequencing confirmed selection of resistance mutations under BMS-818251 pressure, reinforcing the predictive value of deep mutational scanning for in vivo resistance monitoring. Compared to fostemsavir, BMS-818251 achieved more effective viral suppression at lower concentrations, even in donor samples harboring preexisting resistance mutations. These findings support the continued development of BMS-818251 as a promising alternative to fostemsavir, with potential benefits for patients with multidrug-resistant HIV-1.},
}

@article {pmid40860163,
year = {2025},
author = {Westover, T and Walsh, MP and Abdelhamed, S and Xiong, E and Ma, J and Song, G and Thomas, ME and Umeda, M and Maciaszek, JL and Wong, JC and Wintering, A and Wang, L and Emanuel, PD and Loh, ML and Tasian, SK and Stieglitz, E and Schwartz, JR and Shannon, KM and Klco, JM},
title = {Genomic landscape and clonal architecture in pediatric myeloid neoplasms with chromosome 7 deletions.},
journal = {Blood neoplasia},
volume = {2},
number = {2},
pages = {100093},
pmid = {40860163},
issn = {2950-3280},
support = {R01 HL144653/HL/NHLBI NIH HHS/United States ; },
}

@article {pmid40857443,
year = {2025},
author = {O'Connor, TM and Garza, T and Alam, U and Vadathya, AK and Moreno, JP and Beltran, A and Haidar, S and Haidar, N and Hughes, SO and Thompson, D and Musaad, SMA and Baranowski, T and Mendoza, JA and Young, J and Sano, A and Veeraraghavan, A},
title = {The feasibility of passively tracking children's TV viewing and mobile device use in naturalistic settings.},
journal = {Behaviour & information technology},
volume = {},
number = {},
pages = {},
pmid = {40857443},
issn = {0144-929X},
support = {P01 HD109876/HD/NICHD NIH HHS/United States ; R01 DK113269/DK/NIDDK NIH HHS/United States ; },
abstract = {Research on children's technology and digital media (TDM) is hampered by a lack of robust approaches for assessing TDM use. This study assessed the feasibility of passively measuring children's TV screens and mobile devices (TDM) in a naturalistic setting. In the three-day feasibility study, FLASH-TV was set up on one to two TVs the child (5-12 year olds) typically used in the home (n=20). Children's mobile device use was assessed with either the Chronicle App or ScreenTime screenshots. Parents completed three TDM diaries. An exit interview with the parent explored their perceptions of the assessments and the child's TDM use report. Complete data were obtained on 86.7% of days for passive assessment of TV viewing and 84.3% of days for mobile device use. Fifteen parents reviewed complete TDM use reports for their child, with most stating the reports appeared correct for TV (80%) and mobile device (80%). Almost two-thirds had no concerns about having the FLASH-TV installed in their home, while some reported issues about feeling observed. Parents described high burden and frustration with the TDM diaries. Data provided preliminary evidence that passive measurement is feasible for assessing children's TV and mobile device use, with reduced burden for parents.},
}

@article {pmid40859413,
year = {2025},
author = {Lu, G and Han, F and Wang, Y and Yuan, C and Zhu, Q and Xia, T and Chen, L and Dong, X and Ding, Y and Xiao, W and Zhang, Y and Pan, J and Xu, H and Chen, W and Tu, B and Li, W and Wang, F and Gong, W and Hu, L},
title = {Src Reduces Neutrophil Extracellular Traps Generation and Resolves Acute Organ Damage.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e06028},
doi = {10.1002/advs.202506028},
pmid = {40859413},
issn = {2198-3844},
support = {82070668//National Natural Science Foundation/ ; 82241043//National Natural Science Foundation/ ; 82270680//National Natural Science Foundation/ ; 82270679//National Natural Science Foundation/ ; 82400763//National Natural Science Foundation/ ; BK20240028//Natural Science Foundation of Jiangsu Province/ ; BK20240500//Natural Science Foundation of Jiangsu Province/ ; ZD2022011//The Medical research Project of Jiangsu Provincial Health Commission/ ; YZ2022080//Yangzhou key research and development plan/ ; YZ2022207//Yangzhou Policy guidance Program/ ; SZS2023001//Suzhou Innovation Platform Construction Projects- Municipal Key Laboratory Construction/ ; },
abstract = {Neutrophil extracellular traps (NETs) are key factors mediating acute inflammatory injury. However, the underlying mechanisms and potential therapeutic targets remain unclear. Previous results suggest Src may be involved in regulating the NETs formation. Here, Src is found activated in the NETs model in vitro, in the murine- and human-derived neutrophils (acute pancreatitis and sepsis). Moreover, p-Src expression correlates with the clinical prognosis of acute pancreatitis and sepsis patients. Meanwhile, the inhibition of Src activity (gene silencing or inhibitors) inhibits NETs formation in vitro. Mechanistically, Src directly activates RAF1 by regulating phosphorylation at the Ser 621 site and mediates the RAF/MEK/ERK pathway, thereby affecting the intracellular ROS production. Alternatively, Src activates the RAF/MEK/ERK pathway by mediating PKC phosphorylation. In vivo, neutrophil Src - specific defect significantly reduces acute inflammatory response, organ damage, and the NETs formation in damaged tissue. Eventually, Src inhibitors are used and validated their pharmacological effects. These results identify Src as a key mediator in intracellular ROS production, NETs formation, and acute organ injury. Hence, Src inhibition may represent a promising therapeutic strategy for treating acute organ injury.},
}

@article {pmid40858972,
year = {2025},
author = {Kendra, KL and Bellasea, SL and Eroglu, Z and Hu-Lieskovan, S and Campbell, KM and Carson, WE and Wada, DA and Plaza, JA and Sosman, JA and In, GK and Ikeguchi, A and Hyngstrom, J and Brohl, AS and Khushalani, NI and Markowitz, J and Negrea, G and Kasbari, S and Doolittle, GC and Swami, U and Roberts, T and Mathew, BN and Medina, E and Baselga-Carretero, I and Gonzalez, CR and Garcilazo, IP and Vega-Crespo, A and Chen, JM and Naser Al-Deen, N and Patel, SP and Sharon, E and Moon, J and Wu, MC and Ribas, A},
title = {Publisher Correction: Anti-PD-1 therapy in unresectable desmoplastic melanoma: the phase 2 SWOG S1512 trial.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41591-025-03975-2},
pmid = {40858972},
issn = {1546-170X},
}