@article {pmid40640959,
year = {2025},
author = {Cai, Y and Johnson, M and Haessler, J and Molstad, AJ and Hwang, SJ and Joehanes, R and Murabito, JM and Tahir, UA and Franceschini, N and Gerszten, RE and Sun, W and Levy, D and Raffield, LM and Kooperberg, C and Hsu, L and Reiner, AP},
title = {Protein quantitative trait locus analysis in African American and non-Hispanic White individuals.},
journal = {Genome biology},
volume = {26},
number = {1},
pages = {200},
pmid = {40640959},
issn = {1474-760X},
support = {R01 HL152439/HL/NHLBI NIH HHS/United States ; R01 HL152439/HL/NHLBI NIH HHS/United States ; R01 HL152439/HL/NHLBI NIH HHS/United States ; R01 HL152439/HL/NHLBI NIH HHS/United States ; R01 HL152439/HL/NHLBI NIH HHS/United States ; K08 HL161445-01A1/GF/NIH HHS/United States ; HHSN268201600034I, HL133870/GF/NIH HHS/United States ; U01-HG011720/HG/NHGRI NIH HHS/United States ; U01-HG011720/HG/NHGRI NIH HHS/United States ; },
abstract = {BACKGROUND: Substantial efforts have been dedicated to exploring the link between genetic regulation and the proteome, informing studies of complex trait mechanisms. Most of these efforts have been limited to populations of European ancestry.

RESULTS: We conduct an Olink protein quantitative trait locus (pQTL) analysis on 1245 proteins involving 1033 self-identified African American (AA) and 1764 non-Hispanic White (NHW) participants from the Women's Health Initiative and Framingham Heart Study. For replication of candidate pQTLs, we use data from 534 self-identified AA adults from the Jackson Heart Study and protein genome-wide association analysis statistics from the UK Biobank Pharma Proteomics Project, including 54,219 participants, of whom 931 are of African ancestry. In total, we identify and validate 5103 pQTLs (4496 or 88% cis- and 602 or 12% trans-pQTLs) for 983 proteins. Among these, 195 are previously unreported, with most (166 or 85%) identified in our AA sample, many of which were essentially monomorphic in European reference populations. Several of these newly identified African ancestry-specific pQTLs have been reported in ClinVar; our results suggest impact on circulating protein levels, potentially bolstering evidence for clinical significance. We identify a "cis pQTL hotspot" within the leukocyte receptor gene cluster on human chromosome 19q13.4. We also provide examples where a particular cis-pQTL, identified through conditional analysis, offers biological insights into an overlapping GWAS signal for disease susceptibility.

CONCLUSIONS: The identification of previously undescribed African ancestry-specific pQTLs contributes to understanding protein genetic regulation and highlights the significance of proteomic analysis in diverse populations.},
}

@article {pmid40639916,
year = {2025},
author = {Zheng, C and Casjens, SR and Davidson, AR and Amundsen, SK and Smith, GR},
title = {Lambdoid phages with abundant Chi recombination hotspots reflect diverse viral strategies for recombination-dependent growth.},
journal = {Genome research},
volume = {},
number = {},
pages = {},
doi = {10.1101/gr.280248.124},
pmid = {40639916},
issn = {1549-5469},
abstract = {Many phages encode recombination-mediating enzymes, but characterization of their roles in phage lifecycles is limited, and their impact on phage replication is controversial. To address these issues, we have searched for phages whose growth is impacted by the major recombination-promoting helicase-nuclease of Escherichia coli, the RecBCD enzyme. Although no phages inhibited by RecBCD are identified, growth of a newly isolated phage, named LLS, is enhanced by RecBCD. LLS's genome sequence reveals it is related to bacteriophage λ but encodes no recombination-promoting (Rec) proteins or associated RecBCD inhibitor. However, it contains an unexpectedly high number of Chi sites, activators of RecBCD-dependent recombination. Through analysis of 325 genomes of phages related to λ (lambdoid phages), we have found 71 other phage genomes that encode no Rec proteins but mostly possess large numbers of Chi sites. Conversely, phages encoding Rec proteins and a RecBCD inhibitor (collectively a Rec module) mostly lack Chi sites. Lambdoid phages of both diverse enteric bacteria and a pseudomonad have these properties. For this study, we thoroughly analyze the Rec modules of 246 lambdoid phage genomes. These analyses reveal a remarkable heterogeneity of Rec module protein types, both in sequence and in function, and allow us to identify phages that do not contain Rec modules. We conclude that phages lacking their own recombination systems have compensated by becoming enriched in Chi sites, enabling them to use the host's RecBCD to fulfill the requirement for recombination to efficiently replicate. This study highlights the importance of recombination for phage survival and the diversity of strategies to achieve it.},
}

@article {pmid40639796,
year = {2025},
author = {Parnes, M and Gonzalez, E and Tran, N and Stein, MA and Mendoza, J and Tandon, P},
title = {Adherence to 24-Hour Movement Guidelines and Behavioral Health in Children With Attention Deficit Hyperactivity Disorder in the United States.},
journal = {Journal of physical activity & health},
volume = {},
number = {},
pages = {1-10},
doi = {10.1123/jpah.2024-0497},
pmid = {40639796},
issn = {1543-5474},
abstract = {BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a 24-hour disorder that both impacts, and, is impacted by, daily activity and sleep. Children with ADHD are less likely to meet recommended 24-hour movement guidelines (ie, on average 60 min of moderate to vigorous physical activity and several hours of light activity per day, less than 2 h of screen time, and 9-11 h of sleep). The current study examined associations between meeting 24-hour movement guidelines with ADHD symptoms, sleep problems, and media use.

METHODS: Accelerometer data measured physical activity and sleep among a sample of 93 children with ADHD (mean age = 8.10, SDage = 1.37, 58.9% male). Parent-report measures assessed ADHD symptoms, sleep difficulties, and media use. Multivariate analysis of covariance analyses explored associations between meeting 24-hour movement guidelines and outcomes. Latent class analysis (LCA) identified unique combinations of 24-hour movement guideline adherence. Associations were examined between classes and outcomes.

RESULTS: Overall, 41.5% of children met physical activity guidelines, 23.4% met sedentary behavior guidelines, and 45.7% met sleep guidelines. Multivariate analysis of covariance analyses found that meeting more guidelines was associated with less sleep difficulties and problematic media use. LCA revealed 2 classes: Hypoactive children who were unlikely to meet activity guidelines and Work Hard, Play Hard children who were likely to meet activity and sleep guidelines. Children in the Work Hard, Play Hard class had less bedtime resistance compared with the Hypoactive class.

CONCLUSION: Findings have implications for clinicians and caregivers supporting children with ADHD to take a holistic approach to improve health behaviors throughout the whole day.},
}

@article {pmid40637727,
year = {2025},
author = {Dima, D and Logue, JM and Waqar, SHB and Peres, LC and Colin-Leitzinger, CM and De Avila, G and Smith, EC and Skelson, L and Matte, KL and Blue, B and Hovanky, VN and Gaballa, M and Pasvolsky, O and Oswald, LB and Fortuna, GGM and Wagner, CB and DeJarnette, S and Dillard, C and Perna, F and Mikkilineni, L and Hosoya, H and Freeman, CL and Shain, KH and Baz, RC and Grajales-Cruz, A and Puglianini, OC and Alsina, M and Locke, FL and Shune, LO and Sborov, DW and Patel, KK and Sidana, S and Hansen, DK},
title = {Cytopenias and infections following ciltacabtagene autoleucel in heavily-pretreated relapsed or refractory multiple myeloma.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2025.287783},
pmid = {40637727},
issn = {1592-8721},
abstract = {Ciltacabtagene autoleucel (cilta-cel) was FDA-approved in February 2022 for the treatment of relapsed/refractory multiple myeloma after 4 lines of therapy. On CARTITUDE-1 trial, grade ≥3 cytopenias and infections were common. Herein, we sought to characterize cytopenias and infections after cilta-cel infusion in the standard-of-care setting. This multicenter retrospective study included 105 patients who received cilta-cel; 91 reached day-90 and 49 reached day-180 follow-up. Grade ≥3 cytopenia was present among 52% of patients on day-30, and 24% of patients on day-90. Based on the newer immune effector cell-associated hematotoxicity (ICAHT) grading for neutropenia severity, 11 patients (10%) experienced grade ≥3 early ICAHT in the first 30 days, while only 3 (3.3%) experienced grade ≥3 late ICAHT after day-30. On univariate analysis, any grade thrombocytopenia at apheresis was associated with grade ≥3 cytopenia at both days 30 and 90. Granulocyte colony-stimulating factor was administered to 65%, transfusion support to 38%, thrombopoietin agonists to 10%, intravenous immunoglobulin to 52%, and CD34+ stem cell boosts to 9.5% of patients. Infections occurred in 49% of patients and were severe in 32%. Earlier infections in the first 30 days were equally bacterial (42%) and viral (42%). Later infections between days 31-100 and after day 100 were mostly viral (59% and 60%), with only 32% and 12% being grade ≥3 at each time period. On univariate analysis, worse ECOG performance status at lymphodepletion, higher maximum grade of CRS, delayed neurotoxicity, steroid and anakinra use, and lower IgA levels at day 90 were associated with severe infections.},
}

@article {pmid40635049,
year = {2025},
author = {Rosenthal, EA and Wei, WQ and Luo, Y and Namjou-Khales, B and Schaid, DJ and Esplin, ED and Lape, M and Kottyan, L and Pacheco, JA and Weng, C and Gordon, AS and Kullo, IJ and Crosslin, DR and Grady, WM and Hsu, L and Peters, U and Jarvik, GP},
title = {Phenome-wide association study identifies multiple traits associated with a polygenic risk score for colorectal cancer.},
journal = {Human genomics},
volume = {19},
number = {1},
pages = {77},
doi = {10.1186/s40246-025-00791-0},
pmid = {40635049},
issn = {1479-7364},
support = {U01HG008657, U01HG008685, U01HG008672, U01HG008666, U01HG006379, U01HG008679 , U01HG008680 , U01HG008684 , U01HG008673 , U01HG008701 , U01HG008676 , U01HG008664 , U54MD007593/HG/NHGRI NIH HHS/United States ; },
abstract = {BACKGROUND: Many factors, including environmental and genetic variables, contribute to Colorectal Cancer (CRC) risk. The genetic components of risk can be divided into monogenic and polygenic factors. Just as monogenic factors can increase risk for more than one condition, polygenic factors may also underlie multiple phenotypes, including behavioral traits. In order to understand the biology of CRC risk better, it is important to understand the shared polygenic genetic architecture contributing to CRC risk and other phenotypes, including CRC associated risk factors.

METHODS: We investigated potential shared genetics by performing a Phenome-wide association study (PheWAS) with a multi-ancestry CRC polygenic risk score (PRS). The discovery cohort (N = 426,464) consisted of ancestrally diverse participants from the United Kingdom Biobank. The replication cohort (N = 87,271) consisted of ancestrally diverse participants from the electronic Medical Records and Genomics Network phase 3. We used a mixed-effects model to adjust for the presence of related individuals. To preserve power, we limited the number of tests by restricting analysis to ancestor phecodes derived from the electronic health record (EHR) that were not likely to be a result of CRC or its treatment.

RESULTS: We discovered and replicated associations between the CRC PRS and breast cancer, prostate cancer, obesity, smoking and alcohol use (discovery p < 1.1e-4; replication p < 0.0019). The association between CRC risk and prostate cancer may be a novel finding, whereas the association with breast cancer has been previously observed using orthogonal methods. The association between CRC risk and behavioral risk factors corroborate previous studies, also using orthogonal methods, and may reveal potential prevention or treatment strategies.

CONCLUSIONS: As these results corroborate findings from other studies using orthogonal methods, we demonstrate that a CRC PRS can be used as a proxy for genetic risk for CRC when investigating shared genetics between CRC and other phenotypes. Further study of the relationship between PRS from multiple traits with EHR data may reveal additional shared genetic factors. Ultimately, understanding these underlying genetic correlations may identify prevention and treatment strategies for CRC.},
}

@article {pmid40634609,
year = {2025},
author = {Tortorici, MA and Choi, A and Gibson, CA and Lee, J and Brown, JT and Stewart, C and Joshi, A and Harari, S and Willoughby, I and Treichel, C and Leaf, EM and Bloom, JD and King, NP and Tait-Burkard, C and Whittaker, GR and Veesler, D},
title = {Loss of FCoV-23 spike domain 0 enhances fusogenicity and entry kinetics.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {40634609},
issn = {1476-4687},
abstract = {The ability of coronaviruses to recombine and cross species barriers affects human and animal health globally and is a pandemic threat[1,2]. FCoV-23 is a recently emerged, highly pathogenic recombinant coronavirus responsible for a widespread outbreak of feline infectious peritonitis. Here we report cryogenic electron microscopy structures of two FCoV-23 spike isoforms that correspond to the in-host loss of domain 0 observed in clinical samples. The loss of domain 0 markedly enhances the fusogenicity and kinetics of entry into cells and possibly enables biotype switching and lethality. We show that FCoV-23 can use several aminopeptidase N orthologues as receptors and reveal the molecular determinants of receptor species tropism, including a glycan that modulates human receptor engagement. We define antigenic relationships among alphacoronaviruses that infect humans and other mammalian species and identify a cross-reactive alphacoronavirus monoclonal antibody that inhibits FCoV-23 entry. Our results pave the way for the development of vaccines and therapeutics that target this highly pathogenic virus.},
}

@article {pmid40633624,
year = {2025},
author = {Chari, ST and Wu, B and Lopez, C and Lustigova, E and Chen, Q and Van Den Eeden, SK and Leimpeter, AD and Fisher, W and Wood, A and Alexander, AS and Valenta, J and Vege, SS and Carlson, EE and Rabe, KG and Hart, PA and Qian, L and Zhao, YQ and Yosuf, N and Matrisian, L and Kenner, B and Rinaudo, JA and Maitra, A and Feng, Z},
title = {RISK OF PANCREATIC CANCER IN GLYCEMICALLY DEFINED NEW-ONSET DIABETES: A PROSPECTIVE COHORT STUDY.},
journal = {Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.gastro.2025.06.025},
pmid = {40633624},
issn = {1528-0012},
abstract = {BACKGROUND: Increased 3-year incidence of pancreatic cancer following new-onset diabetes (NOD) observed in retrospective studies needs prospec4ive validation. It is unknown if incidence varies by race/ethnicity.

METHODS: In a prospective, observational study using active real-time surveillance of electronic health records we identified 18,838 adults >50 years of age with NOD defined by glycemic criteria (GNOD). In this interim analysis, we report 3-year Kaplan-Meier estimates of proportion diagnosed with pancreatic cancer following GNOD (absolute incidence (95% Confidence Intervals)) and associated Standardized Incidence Ratio (SIR) by race/ethnicity; overall 3-year incidence of pancreatic cancer adjusting for racial distribution of incident diabetes in the United States; and interval between GNOD and pancreatic cancer diagnosis.

RESULTS: During median follow-up of 2.3 years, 82 pancreatic cancers have been diagnosed (60% male, mean age 71±8 years). The 3-year estimates for proportion diagnosed with pancreatic cancer (95% CI) and associated SIR (95% CI) by race/ethnicity were: non-Hispanic Whites (n=6,518) 0.84% (CI: 0.60, 1.07) (SIR 6.4 (CI: 4.8, 8.4)); Hispanics (n=5,984) 0.40% (0.20, 0.60) (SIR 4.2 (2.6, 6.3)); African Americans (n=2,192) 0.37% (0.07, 0.67) (SIR 2.4 (1.0, 5.0), and Asian/Pacific Islander (n=3,360) 0.22% (.06, 0.39) (SIR 3.0 (1.4, 6.0). Overall, race-adjusted 3-year pancreatic cancer incidence was 0.62%. On average GNOD occurred 8 months prior to clinical diagnosis; 0-4 months in 30.5%, 4-12 months in 31.3%, 12-24 months in 19.5%, and 24-36 months in 18.7%.

CONCLUSIONS: Glycemically defined new-onset diabetes, identifiable in real-time using active surveillance of electronic health records, is associated with a high 3-year incidence of pancreatic cancer with marked racial/ethnic differences. Longer term risk needs further study.},
}

@article {pmid40633141,
year = {2025},
author = {Ramachandran, D and Wang, X and Laisk, T and Zheng, Y and Ingold, N and Canson, DM and Kho, PF and Naumann, BJ and Chapman, CJ and Bousset, K and Krause, AV and Schürmann, P and Wieland, B and Hanel, P and Hülse, F and Häfner, N and Runnebaum, I and Dubrowinskaja, N and Turmanov, N and Yugay, T and Yessimsiitova, ZB and Amant, F and Annibali, D and Beckmann, MW and Bodelon, C and Buchanan, DD and Chen, C and Clarke, MA and Cook, LS and De Vivo, I and De Wispelaere, W and Du, M and Easton, DF and Emons, J and Fasching, PA and Friedenreich, CM and Gallagher, G and Giles, GG and Goode, EL and Harris, HR and Hunter, DJ and Kolin, DL and Kraft, P and Lacey, JV and Lambrechts, D and Lu, L and Mutter, GL and Naduparambil, J and O'Connell, K and Patel, AV and Pharoah, PDP and Rebbeck, TR and Ricceri, F and Risch, HA and Ruebner, M and Sacerdote, C and Scott, RJ and Setiawan, VW and Shu, XO and Southey, MC and Tham, E and Tomlinson, I and Turman, C and Wentzensen, N and Xu, W and Yu, H and Zheng, W and Spurdle, AB and Yarden, Y and , and Mägi, R and Hillemanns, P and Glubb, DM and Dörk, T and O'Mara, TA},
title = {GWAS meta-analysis identifies five susceptibility loci for endometrial cancer.},
journal = {EBioMedicine},
volume = {118},
number = {},
pages = {105830},
doi = {10.1016/j.ebiom.2025.105830},
pmid = {40633141},
issn = {2352-3964},
abstract = {BACKGROUND: Endometrial cancer is the most common gynaecological cancer in high-income countries. In addition to environmental risk factors, genetic predisposition contributes towards endometrial cancer development but is still incompletely defined.

METHODS: Building on genome-wide association studies (GWASs) by the Endometrial Cancer Association Consortium, we conducted a GWAS meta-analysis of 17,278 endometrial cancer cases and 289,180 controls, incorporating biobank samples from the UK, Finland, Estonia and Japan.

FINDINGS: GWAS analysis identified five additional risk loci (3p25.2, 3q25.2, 6q22.31, 12q21.2, and 17q24.2). Corresponding gene-based analyses supported findings for three of the five loci, at NAV3 (12q21.2), PPARG (3p25.2), and BPTF (17q24.2), as well as two additional candidate risk regions at ATF7IP2 (16p13.2-p13.13) and RPP21 (6p22.1). Validation genotyping in further independent case-control series replicated the most significant locus at 12q21.2 and corroborated risk variants located intronic to NAV3, the gene for Neuron Navigator 3. Downregulation of NAV3 in endometrial cell lines accelerated cell division and wound healing capacity whereas NAV3 overexpression reduced cell survival and increased cell death, indicating that NAV3 acts as a tumour suppressor in endometrial cells.

INTERPRETATION: Our large study extends the number of genome-wide significant risk loci identified for endometrial carcinoma by about one-third and proposes a role of NAV3 as a tumour suppressor in this common cancer.

FUNDING: This study was mainly supported by funding from the Wilhelm Sander Foundation, Germany, and the National Health and Medical Research Council (NHMRC) of Australia. A complete list of funding organisations is provided in the acknowledgements.},
}

@article {pmid40632975,
year = {2025},
author = {Anbil, S and Seewald, NJ and Chiorean, EG and Hussein, M and Kasi, PM and Laux, DE and Schwartz, GK and Shapiro, GI and Lin, KK and Craib, M and Maloney, L and McLachlan, K and Tukachinsky, H and Schrock, AB and Wang, S and Sokol, ES and Decker, B and Nathanson, KL and Domchek, SM and Reiss, KA},
title = {LODESTAR: A Single-Arm Phase II Study of Rucaparib in Solid Tumors With Pathogenic Germline or Somatic Variants in Homologous Recombination Repair Genes.},
journal = {JCO precision oncology},
volume = {9},
number = {},
pages = {e2500090},
doi = {10.1200/PO-25-00090},
pmid = {40632975},
issn = {2473-4284},
mesh = {Humans ; Female ; Male ; Middle Aged ; *Neoplasms/drug therapy/genetics ; *Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Aged ; Adult ; *Indoles/therapeutic use ; *Recombinational DNA Repair/genetics ; Germ-Line Mutation ; },
abstract = {PURPOSE: To explore poly (ADP-ribose) polymerase inhibitor utility across solid tumors and identify biomarkers that predict sensitivity.

PATIENTS AND METHODS: This single-arm phase II study assessed rucaparib monotherapy in patients with solid tumors and pathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, and RAD51D (cohort A) or BARD1, BRIP1, FANCA, NBN, and RAD51B (cohort B). The primary end point was overall response rate (ORR) in cohort A. Secondary end points included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. A scar-based homologous recombination deficiency signature (HRDsig) and platinum sensitivity status were explored post hoc.

RESULTS: Fifty-one patients in cohort A and 12 in cohort B were evaluable for efficacy. ORR of cohort A was 18% (95% CI, 10 to 30). A significantly higher ORR was observed with HRDsig+ tumors compared with HRDsig- tumors (32%; 95% CI, 15 to 54 v 0%; 95% CI, 0 to 14; P < .01). In the entire study population, DCR was 65% (95% CI, 53 to 76), median PFS (mPFS) 5.5 months (95% CI, 3.68 to 7.82), and median OS 12.1 months (95% CI, 10.6 to inferred). PFS and hazard of death from any cause was significantly better for platinum-sensitive tumors (mPFS: 7.8 months v 3.5 months; P = .02; hazard ratio, 0.11 [95% CI, 0.02 to 0.55]). Tumor histology was not independently predictive of outcome. Tumors with PVs in cohort A genes were more likely to be HRDsig+ than tumors with PVs in cohort B genes. Analysis of a large commercial database showed that in noncanonical tumors with BRCA PVs, 30.2% were HRDsig+.

CONCLUSION: Rucaparib has activity in HRDsig+ solid tumors with PVs in homologous recombination repair genes, regardless of histology. Platinum sensitivity correlated with improved outcomes.},
}

Humans
Female
Male
Middle Aged
*Neoplasms/drug therapy/genetics
*Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use
Aged
Adult
*Indoles/therapeutic use
*Recombinational DNA Repair/genetics
Germ-Line Mutation

@article {pmid40632513,
year = {2025},
author = {Raychaudhuri, R and Lin, DW and Montgomery, RB},
title = {Complexity of Prostate Cancer-Reply.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2025.7193},
pmid = {40632513},
issn = {1538-3598},
}

@article {pmid40632085,
year = {2025},
author = {Han, C and Zhang, Z and Crosse, EI and Sajedi, S and Lu, B and Wang, X and Karma, S and Kostich, M and Rajendran, SH and Udy, DB and Chen, S and Arnuk, A and Lawal, AE and Koenig, KR and McKenna, M and Reville, PK and Abbas, HA and Abdel-Wahab, O and Miura, P and Bradley, RK and Wang, E},
title = {An isoform-specific RUNX1C-BTG2 axis governs AML quiescence and chemoresistance.},
journal = {Blood cancer discovery},
volume = {},
number = {},
pages = {},
doi = {10.1158/2643-3230.BCD-24-0327},
pmid = {40632085},
issn = {2643-3249},
abstract = {Aberrant levels or structures of RNA isoforms are a hallmark of many cancers, including acute myeloid leukemia (AML), yet its role in AML chemoresistance remains unclear. We conducted a paired analysis of RNA isoform changes in AML patients before therapy and at relapse post-chemotherapy, identifying and identified intragenic DNA methylation at the proximal promoter of the transcription factor RUNX1, which resulted in elevated expression of the long isoform RUNX1C through its alternative distal promoter. The N-terminal region of RUNX1C orchestrated an isoform-specific transcriptional program that promoted chemoresistance, with its direct target BTG2 playing a role in chemotherapy resistance. BTG2 promoted ribosomal RNA deadenylation, resulting in decreased mRNA expression and stability. Deletion of ribosomal RNA's increased cellular quiescence. Moreover, RNA-based targeting of RUNX1C reactivated quiescent leukemia cells and enhanced chemotherapy efficacy. These findings delineate an isoform-specific transcriptional circuit that governs chemotherapy response, providing a potential therapeutic strategy to mitigate AML recurrence.},
}

@article {pmid40629516,
year = {2025},
author = {Razzo, BM and Midha, S and Portuguese, AJ and Grajales-Cruz, AF and De Menezes Silva Corraes, A and Costello, P and Liu, Y and Sperling, AS and Nadeem, O and Dima, D and Banerjee, R and Cowan, AJ and Afrough, A and Anderson, LD and Lieberman-Cribbin, A and Kaur, G and Goyal, A and Atrash, S and Ferreri, CJ and Voorhees, PM and Pasvolsky, O and Lee, HC and Patel, KK and Julian, KL and Forsberg, PA and Herr, MM and Chhabra, S and Parrondo, RD and Lin, Y and Chen, A and Susanibar-Adaniya, SP and Khouri, J and Raza, S and Anwer, F and Vazquez-Martinez, M and Castaneda Puglianini, O and Sborov, DW and Davis, JA and Rossi, A and Shune, L and Bhurtel, J and Hwang, WT and Hansen, DK and Sidana, S and Garfall, AL and Richard, S},
title = {Real-World Experience with Teclistamab for Relapsed/ Refractory Multiple Myeloma from the U.S. Myeloma Immunotherapy Consortium.},
journal = {Blood cancer discovery},
volume = {},
number = {},
pages = {},
doi = {10.1158/2643-3230.BCD-24-0354},
pmid = {40629516},
issn = {2643-3249},
abstract = {Teclistamab is an anti-CD3xBCMA bispecific antibody approved for use in relapsed/refractory multiple myeloma (MM). We undertook a retrospective study of post-approval, real-world outcomes with teclistamab in the U.S. MM Immunotherapy Consortium. Among 509 patients, 89% would have been ineligible for the MajesTEC-1 trial, primarily due to prior BCMA-directed therapy, cytopenias, or diminished performance status. Cytokine release syndrome occurred in 54% (1.4% grade ≥3) and immune effector cell-associated neurotoxicity syndrome in 11% (2.2% grade ≥3) with no fatal events. Infections occurred in 42% and contributed to death in 5%. Partial response (PR) or better was achieved in 53% and very good PR (VGPR) or better in 45%. With 10.1 months median follow-up, estimated median progression-free survival (PFS) was 5.8 months, and 12-month overall survival was 61%. Independent predictors of }

@article {pmid40629152,
year = {2025},
author = {Simar, SR and Tran, TT and Rydell, KB and Atterstrom, RL and Sahasrabhojane, PV and Dinh, AQ and Schettino, MG and Slanis, HS and Deyanov, AE and DeTranaltes, AM and Axell-House, DB and Miller, WR and Munita, JM and Tobys, D and Seifert, H and Biehl, LM and Zervos, M and Suleyman, G and Kaur, J and Warzocha, V and Rosa, R and Cifuentes, RO and Abbo, LM and Shimose, L and Liu, C and Nguyen, K and Miller, A and Shelburne, SA and Hanson, BM and Arias, CA},
title = {Clinical and Genomic Characterization of Recalcitrant Enterococcal Bacteremia: A Multicenter Prospective Cohort Study (VENOUS).},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf358},
pmid = {40629152},
issn = {1537-6613},
abstract = {BACKGROUND: Patients with recalcitrant enterococcal bloodstream infections are at greater risk of adverse outcomes. We identified patients in the 2016-2022 Vancomycin-Resistant Enterococcal Bacteremia Outcomes Study (VENOUS) cohort experiencing recalcitrant bloodstream infections for further clinical and genomic characterization.

METHODS: Bacteremia episodes were considered "persistent" if there was a lack of clearance on day four while receiving ≥ 48 hours of active therapy and recurrent if there was clearance during hospitalization with a subsequent positive culture (collectively, "recalcitrant" bacteremia). A matched comparison group of non-recalcitrant bacteremia patients was chosen in a 2:1 control:case ratio. Isolates were subjected to short- and long-read whole-genome sequencing. Hybrid assemblies were created using a custom pipeline.

FINDINGS: A total of 46 recalcitrant infections from 41 patients were identified. Patients with persistent bacteremia were more often admitted to the ICU upon admission relative to controls. E. faecalis strains causing persistent infections had a significantly higher proportion of genes associated with carbohydrate utilization relative to controls. Representation of functional groups associated with mutated genes was disparate between E. faecium and E. faecalis index and persistent isolates, suggesting species-specific adaptation.

DISCUSSION: Enterococcal isolates causing recalcitrant bacteremia were genomically diverse, indicating that strain-specific signatures are not drivers of persistence. However, comparisons of index vs. persistent isolates revealed that E. faecium may be genetically pre-adapted to cause persistent infection, and site-specific structural variation during infection suggests the role of differential gene expression in adaptation and persistence. This data lays groundwork for future studies to define signatures of enterococcal adaptation during bacteremia.},
}

@article {pmid40628699,
year = {2025},
author = {Li, Z and Yang, W and Wu, G and Chang, TC and Cheng, Z and Devidas, M and Shago, M and Carroll, AJ and Heerema, NA and Gastier-Foster, JM and Wood, BL and Sanclemente, L and Raetz, EA and Hunger, SP and Loh, ML and Feingold, E and Rosser, TC and Allen, EG and Sherman, SL and Rabin, KR and Lupo, PJ and Yang, JJ},
title = {Inferring chromosome segregation error stage and crossover in trisomic disorders with application to Down syndrome.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {6316},
pmid = {40628699},
issn = {2041-1723},
mesh = {Humans ; *Down Syndrome/genetics ; *Chromosome Segregation/genetics ; *Crossing Over, Genetic ; Meiosis/genetics ; *Nondisjunction, Genetic/genetics ; Female ; Markov Chains ; *Trisomy/genetics ; Male ; Child ; },
abstract = {Errors in chromosome segregation during gametogenesis, such as nondisjunction (NDJ) errors, have severe consequences in human reproduction, and a better understanding of their etiology is of fundamental interest in genetics. Mapping NDJ errors to meiotic/mitotic stages typically requires proband-parent comparison, limiting its applicability. Herein, we develop Mis-segregation Error Identification through Hidden Markov Models (MeiHMM), a method for inferring NDJ error stage and crossover events based on only genomic data of trisomic probands. Guided by triallelic genotype/haplotype configurations, MeiHMM discerns the allelic origin at each locus, which informs NDJ error during gamete formation, without identifying the parental origin of the trisomy. In 152 Down syndrome (DS) cases, MeiHMM achieved an accuracy of 96.1% in classifying NDJ errors, with a sensitivity of 91.6% in crossover identification, compared to proband-parents trio analysis. 17% of Meiosis II errors were misclassified as Meiosis I, mainly due to small proximal crossover events. Applying MeiHMM to 509 children with DS-associated childhood leukemia, we demonstrate that NDJ error is associated with the age of disease onset, somatic genomic abnormalities, and prognosis. Thus, MeiHMM is an effective method for trisomic NDJ error classification and crossover identification that can be applied broadly to study the etiology of congenital aneuploidy conditions.},
}

Humans
*Down Syndrome/genetics
*Chromosome Segregation/genetics
*Crossing Over, Genetic
Meiosis/genetics
*Nondisjunction, Genetic/genetics
Female
Markov Chains
*Trisomy/genetics
Male
Child

@article {pmid40628395,
year = {2025},
author = {Farrell-Sherman, A and de la Force, N and Prator, CA and Valieris, R and Azam, W and Da Silva, I and Deeks, SG and Thanh, C and Bosch, RJ and Henrich, TJ and Cohn, LB},
title = {Antiviral Monocytes Increase Prior to Detectable HIV-1 Rebound Viremia.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf367},
pmid = {40628395},
issn = {1537-6613},
abstract = {The persistence of HIV-1 proviruses in latently infected cells allows viremia to resume upon treatment cessation. To characterize the resulting immune response, we compare plasma proteomics and single-cell transcriptomics of peripheral blood mononuclear cells (PBMCs) before, during, and after detectable plasma viremia. We observe unique transcriptional signatures prior to viral rebound including a significant increase in CD16++ monocytes with increased antiviral gene expression. Inflammatory proteins were identified in plasma after detectable rebound. Identifying early signals of imminent viral rebound after treatment cessation will aid in the development of strategies to prolong time to viral rebound and cure HIV-1.},
}

@article {pmid40627547,
year = {2025},
author = {Paatela, EM and St Amant, FG and Hamm, DC and Bennett, SR and Gujral, TS and van der Maarel, SM and Tapscott, SJ},
title = {A discrete region of the D4Z4 is sufficient to initiate epigenetic silencing.},
journal = {Human molecular genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/hmg/ddaf114},
pmid = {40627547},
issn = {1460-2083},
support = {P50AR065139/NH/NIH HHS/United States ; R01AR066248/NH/NIH HHS/United States ; },
abstract = {The DUX4 transcription factor is briefly expressed in the early embryo and is epigenetically repressed in somatic tissues. Loss of epigenetic repression can result in the aberrant expression of DUX4 in skeletal muscle and can cause facioscapulohumeral dystrophy (FSHD). Multiple factors have been identified as necessary to maintain epigenetic silencing of DUX4 in skeletal muscle, but whether specific sequences at the DUX4 locus are sufficient for initiating epigenetic silencing has not been known. We cloned fragments of the D4Z4 macrosatellite repeat, the DNA region that encompasses the DUX4 retrogene, adjacent to a reporter driven by a constitutive promoter and identified a single fragment sufficient to epigenetically repress reporter gene expression. Previously identified repressors of DUX4 expression-SETDB1, ATF7IP, SIN3A/B, and LRIF1-were necessary for silencing activity and p38 inhibitors enhanced suppression. These findings identify a key regulatory sequence for D4Z4 epigenetic repression and establish a model system for mechanistic and discovery studies.},
}

@article {pmid40627379,
year = {2025},
author = {Chatterjee, S and Rückert, T and Martin, I and Michaeli, E and Buescher, J and Apostolova, P and Erny, D and Lalioti, ME and Biavasco, F and Hartmann, A and Runge, S and Braun, LM and Talvard-Balland, N and Adams, RC and Schmitt-Graeff, A and Cook, J and Wenger, V and Athanassopoulos, D and Hasavci, D and Vallejo-Janeta, AP and Blank, T and Schaible, P and Vinnakota, JM and Zähringer, A and Ganal-Vonarburg, SC and Melchinger, W and Pfeifer, D and Köhler, N and Rosshart, SP and Michonneau, D and Socié, G and Andrieux, G and Cabezas-Wallscheid, N and Boerries, M and Prinz, M and Zeiser, R},
title = {Gut microbiota-derived TMAVA is a modulator of acute CNS-GVHD.},
journal = {The Journal of experimental medicine},
volume = {222},
number = {9},
pages = {},
doi = {10.1084/jem.20242180},
pmid = {40627379},
issn = {1540-9538},
support = {2021/A2-Fol//University of Freiburg/ ; 2021/B3-Fol//University of Freiburg/ ; 450392965//Deutsche Forschungsgemeinschaft/ ; 259373024//Deutsche Forschungsgemeinschaft/ ; 441891347//Deutsche Forschungsgemeinschaft/ ; 256073931//Deutsche Forschungsgemeinschaft/ ; 431984000//Deutsche Forschungsgemeinschaft/ ; 491676693//Deutsche Forschungsgemeinschaft/ ; 471011418//Deutsche Forschungsgemeinschaft/ ; 493802833//Deutsche Forschungsgemeinschaft/ ; 872/4-1//Deutsche Forschungsgemeinschaft/ ; ZE 872/7-1//Deutsche Forschungsgemeinschaft/ ; ZE 872/8-1//Deutsche Forschungsgemeinschaft/ ; RO 6247/1-1//Deutsche Forschungsgemeinschaft/ ; 446316360//Deutsche Forschungsgemeinschaft/ ; 256073931//Deutsche Forschungsgemeinschaft/ ; 491676693//Deutsche Forschungsgemeinschaft/ ; 101094168/ERC_/European Research Council/International ; 70114655//Deutsche Krebshilfe/ ; 70116490//Deutsche Krebshilfe/ ; DJCLS 09R/2022//Jose-Carreras Leukemia Foundation/ ; 7030-23//Leukemia and Lymphoma Society/ ; 390939984//Germany's Excellence Strategy/ ; 560868983//Germany's Excellence Strategy/ ; 10.001.317/SNSF_/Swiss National Science Foundation/Switzerland ; //European Hematology Association/ ; 24C246//Novartis Foundation for Biomedical Research/ ; 2015_A147//Else Kröner-Fresenius-Stiftung/ ; //Albert-Ludwigs-University of Freiburg/ ; 01ZZ2322A//German Federal Ministry of Education and Research/ ; 01ZZ2015//German Federal Ministry of Education and Research/ ; 101119855//Deutschen Konsortium für Translationale Krebsforschung/ ; },
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Microglia/metabolism/drug effects ; *Graft vs Host Disease/microbiology/metabolism/pathology/etiology ; Mice ; Toll-Like Receptor 4/metabolism ; Mice, Inbred C57BL ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Anti-Bacterial Agents/pharmacology ; Male ; p38 Mitogen-Activated Protein Kinases/metabolism ; Acute Disease ; *Central Nervous System/pathology ; T-Lymphocytes/immunology ; Female ; Specific Pathogen-Free Organisms ; },
abstract = {Acute graft-versus-host disease (aGVHD) can affect the central nervous system (CNS) through microglial activation and T cell infiltration, but the role of gut microbiota in CNS-aGVHD remains unclear. Here, we investigated the role of microbiota in microglial activation during aGVHD using antibiotic-treated specific pathogen-free (SPF), germ-free (GF), and wildling mice. Antibiotic-mediated microbiota depletion led to infiltration of IFN-γ-producing T cells in the brain, activation of microglia via the TLR4/p38 MAPK pathway, and neurocognitive deficits in SPF aGVHD mice. Microglial depletion reversed the neurocognitive deficits. GF and wildling mice treated with antibiotics exhibited similar microglial activation after allogeneic hematopoietic cell transplantation (allo-HCT). Mechanistically, the bacteria-derived metabolite N,N,N-trimethyl-5-aminovaleric acid (TMAVA) was decreased in microglia following antibiotic treatment. TMAVA administration suppressed TLR4/p38 MAPK pathway activity in microglia and alleviated gut microbiota depletion-mediated neurocognitive deficits. Additionally, TMAVA abundance decreased in patient blood after allo-HCT and after GVHD onset. In summary, we identify TMAVA loss as a central causative factor for CNS-aGVHD, opening new perspectives for a metabolite-based therapy.},
}

Animals
*Gastrointestinal Microbiome/drug effects
Microglia/metabolism/drug effects
*Graft vs Host Disease/microbiology/metabolism/pathology/etiology
Mice
Toll-Like Receptor 4/metabolism
Mice, Inbred C57BL
Hematopoietic Stem Cell Transplantation/adverse effects
Humans
Anti-Bacterial Agents/pharmacology
Male
p38 Mitogen-Activated Protein Kinases/metabolism
Acute Disease
*Central Nervous System/pathology
T-Lymphocytes/immunology
Female
Specific Pathogen-Free Organisms

@article {pmid40624354,
year = {2025},
author = {Baele, G and Ji, X and Hassler, GW and McCrone, JT and Shao, Y and Zhang, Z and Holbrook, AJ and Lemey, P and Drummond, AJ and Rambaut, A and Suchard, MA},
title = {BEAST X for Bayesian phylogenetic, phylogeographic and phylodynamic inference.},
journal = {Nature methods},
volume = {},
number = {},
pages = {},
pmid = {40624354},
issn = {1548-7105},
abstract = {Here we present the open-source and cross-platform BEAST X software that combines molecular phylogenetic reconstruction with complex trait evolution, divergence-time dating and coalescent demographics in an efficient statistical inference engine. BEAST X significantly advances the flexibility and scalability of evolutionary models supported. Novel clock and substitution models leverage a large variety of evolutionary processes; discrete, continuous and mixed traits with missingness and measurement errors; and fast, gradient-informed integration techniques that rapidly traverse high-dimensional parameter spaces.},
}

@article {pmid40624264,
year = {2025},
author = {Templin, T and Fort, S and Padmanabham, P and Seshadri, P and Rimal, R and Oliva, J and Hassmiller Lich, K and Sylvia, S and Sinnott-Armstrong, N},
title = {Framework for bias evaluation in large language models in healthcare settings.},
journal = {NPJ digital medicine},
volume = {8},
number = {1},
pages = {414},
pmid = {40624264},
issn = {2398-6352},
support = {2026498//National Science Foundation/ ; N/A//Public Health Sciences Klorfine Pilot Award/ ; N/A//Public Health Sciences Klorfine Pilot Award/ ; K01AI159233/AI/NIAID NIH HHS/United States ; },
abstract = {A critical gap in the adoption of large language models for AI-assisted clinical decisions is the lack of a standardized audit framework to evaluate models for accuracy and bias. Our framework introduces a five-step framework that guides practitioners through stakeholder engagement, model calibration to specific patient populations, and rigorous testing through clinically relevant scenarios. We provide open-access tools for stakeholder engagement and an example of an audit. As the regulation of models becomes more critical, we believe adoption of an audit framework that tests model outputs, rather than regulating specific hyperparameters or inputs, will encourage the responsible use of AI in clinical settings.},
}

@article {pmid40623313,
year = {2025},
author = {Aragaki, AK and Manson, JE and LeBlanc, ES and Chlebowski, RT and Tinker, LF and Allison, MA and Haring, B and Odegaard, AO and Wassertheil-Smoller, S and Saquib, N and Masaki, K and Harris, HR and Jager, LR and Bea, JW and Wactawski-Wende, J and Anderson, GL},
title = {Development and Validation of Body Mass Index-Specific Waist Circumference Thresholds in Postmenopausal Women : A Prospective Cohort Study.},
journal = {Annals of internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.7326/ANNALS-24-00713},
pmid = {40623313},
issn = {1539-3704},
abstract = {BACKGROUND: A 2020 consensus statement proposed body mass index (BMI)-specific waist circumference (WC) thresholds to improve patient care.

OBJECTIVE: To determine whether stratifying BMI categories by BMI-specific WC thresholds improves mortality risk prediction.

DESIGN: Prospective cohort study.

SETTING: Women's Health Initiative multicenter, population-based U.S. study, with enrollment from 1993 to 1998 and follow-up through 2021.

PARTICIPANTS: 139 213 postmenopausal women aged 50 to 79 years were included in a development cohort (n = 67 774) and 2 external validation cohorts. Validation Cohort 1 had high prevalence of overweight or obesity (n = 48 335), and Validation Cohort 2 included diverse, geographically separate centers (n = 23 104).

MEASUREMENTS: Height, weight, and WC measured at enrollment. BMI categories were normal weight (18.5 to <25 kg/m[2]), overweight (25 to <30 kg/m[2]), obesity-1 (30 to <35 kg/m[2]), obesity-2 (35 to <40 kg/m[2]), and obesity-3 (≥40 kg/m[2]), with further stratification by prespecified WC thresholds (≥80, ≥90, ≥105, ≥115, and ≥115 cm, respectively). Mortality was ascertained annually and was supplemented with serial National Death Index queries. Ten- and 20-year mortality prediction models that included BMI categories were compared to models with BMI categories stratified by WC thresholds using c-statistics and continuous net reclassification improvement (NRI).

RESULTS: Over a median of 24 years of follow-up, 69 297 participants died. Multivariable-adjusted mortality risk was consistently greater for BMI categories with large WC than those with normal WC. Compared with women with normal weight and normal WC, women with normal or overweight BMI but large WC (hazard ratios [HRs], 1.17 [95% CI, 1.12 to 1.21] and 1.19 [CI, 1.15 to 1.24], respectively) had risk similar to those with obesity-1 but normal WC (HR, 1.12 [CI, 1.08 to 1.16]). Mortality associated with obesity-1 and large WC (HR, 1.45 [CI, 1.35 to 1.55]) was similar to that with obesity-3 and normal WC (HR, 1.40 [CI, 1.28 to 1.54]). Models with BMI-specific WC thresholds improved discrimination and risk stratification at 10 years for Validation Cohort 1; c-statistics improved by 0.7% (CI, 0.3% to 1.0%) to 61.3% (CI, 60.2% to 62.5%), and continuous NRI was 20.4% (CI, 17.3% to 23.6%). Results were mixed for Validation Cohort 2; risk stratification improved (continuous NRI, 12.3% [CI, 8.5% to 16.0%]), but not discrimination. Results were similar at 20 years.

LIMITATION: The study did not include men or younger women.

CONCLUSION: Further stratifying BMI categories by WC thresholds modestly improved mortality risk stratification, with larger WC predicting greater mortality, although the degree of improvement varied by cohort. Discrimination did not improve consistently.

PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute of the National Institutes of Health.},
}

@article {pmid40623281,
year = {2025},
author = {Montano-Campos, JF and Hahn, E and Haupt, E and Radich, J and Bansal, A},
title = {Using Early Biomarker Change and Treatment Adherence to Predict Risk of Relapse Among Patients With Chronic Myeloid Leukemia Who Are in Remission.},
journal = {JCO clinical cancer informatics},
volume = {9},
number = {},
pages = {e2500003},
pmid = {40623281},
issn = {2473-4276},
mesh = {Humans ; *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/pathology/genetics/diagnosis ; Male ; Female ; Middle Aged ; *Biomarkers, Tumor ; Adult ; Aged ; *Neoplasm Recurrence, Local/epidemiology ; *Fusion Proteins, bcr-abl/genetics ; Remission Induction ; Prognosis ; *Treatment Adherence and Compliance ; Risk Assessment ; },
abstract = {PURPOSE: There is little guidance for decision making in chronic myeloid leukemia (CML) after patients achieve molecular remission. Our study addresses this gap by developing a risk prediction model for molecular relapse using early longitudinal factors, such as BCR::ABL1 biomarker-level changes and treatment adherence.

METHODS: We analyzed electronic health record data of patients with CML diagnosed between 2007 and 2019 from an integrated health system. We used a time-to-event modeling framework using a Cox proportional hazards approach where we evaluated time from molecular remission to molecular relapse. The main predictors were early changes in BCR::ABL1 levels from treatment initiation to the first follow-up measurement (typically around 3 months) and treatment adherence in the first 6 months, categorized as perfect (≥0.98) or less-than-perfect (<0.98). Model performance was assessed through five-fold cross-validation combined with 100 Monte Carlo bootstrapping iterations to ensure robustness and minimize bias.

RESULTS: Patients with early improvement in BCR::ABL1 levels had a 70% lower risk relapse (hazard ratio [HR], 0.30 [95% CI, 0.15 to 0.59]) compared with those without early molecular response. Perfect adherence during this critical early phase of treatment was associated with a 56% lower relapse risk (HR, 0.44 [95% CI, 0.22 to 0.85]). Predictive accuracy was high at 6 months (AUC, 0.90; 95% CI, 0.87 to 0.95) and 1-year postremission (AUC, 0.78; 95% CI, 0.74 to 0.81). Relapse risk was significantly higher among Black, Asian, and Hispanic patients compared with non-Hispanic White patients.

CONCLUSION: Early biomarker trends and adherence after treatment initiation are critical for accurately predicting relapse among patients who achieve molecular remission. The proposed model addresses a gap in guidance after molecular remission and has the potential to enable personalized monitoring and optimize surveillance strategies, offering transformative potential for CML care.},
}

Humans
*Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/pathology/genetics/diagnosis
Male
Female
Middle Aged
*Biomarkers, Tumor
Adult
Aged
*Neoplasm Recurrence, Local/epidemiology
*Fusion Proteins, bcr-abl/genetics
Remission Induction
Prognosis
*Treatment Adherence and Compliance
Risk Assessment

@article {pmid40623109,
year = {2025},
author = {Jochim, B and Topalidou, I and Lehrbach, N},
title = {Protein sequence editing defines distinct and overlapping functions of SKN-1A/Nrf1 and SKN-1C/Nrf2.},
journal = {PLoS genetics},
volume = {21},
number = {7},
pages = {e1011780},
doi = {10.1371/journal.pgen.1011780},
pmid = {40623109},
issn = {1553-7404},
abstract = {The Nrf/NFE2L family of transcription factors regulates redox balance, xenobiotic detoxification, metabolism, proteostasis, and aging. Nrf1/NFE2L1 is primarily responsible for stress-responsive upregulation of proteasome subunit genes and is essential for adaptation to proteotoxic stress. Nrf2/NFE2L2 is mainly involved in activating oxidative stress responses and promoting xenobiotic detoxification. Nrf1 and Nrf2 contain very similar DNA binding domains and can drive similar transcriptional responses. In C. elegans, a single gene, skn-1, encodes distinct protein isoforms, SKN-1A and SKN-1C, that function analogously to mammalian Nrf1 and Nrf2, respectively, and share an identical DNA binding domain. Thus, the extent to which SKN-1A/Nrf1 and SKN-1C/Nrf2 functions are distinct or overlapping has been unclear. Regulation of the proteasome by SKN-1A/Nrf1 requires post-translational conversion of N-glycosylated asparagine residues to aspartate by the PNG-1/NGLY1 peptide:N-glycanase, a process we term 'sequence editing'. Here, we reveal the consequences of sequence editing for the transcriptomic output of activated SKN-1A. We confirm that activation of proteasome subunit genes is strictly dependent on sequence editing. In addition, we find that sequence edited SKN-1A can also activate genes linked to redox homeostasis and xenobiotic detoxification that are also regulated by SKN-1C, but the extent of these genes' activation is antagonized by sequence editing. Using mutant alleles that selectively inactivate either SKN-1A or SKN-1C, we show that both isoforms promote optimal oxidative stress resistance, acting as effectors for distinct signaling pathways. These findings suggest that sequence editing governs SKN-1/Nrf functions by tuning the SKN-1A/Nrf1 regulated transcriptome.},
}

@article {pmid40623049,
year = {2025},
author = {Perales, MA and Awan, FT and Boumendil, A and Patel, J and Castagna, L and Angelucci, E and Finel, H and Kulagin, AD and Glass, B and Corradini, P and Herrera, AF and Blaise, D and Kharfan-Dabaja, MA and Halahleh, K and Ahmed, S and Martinez, C and Giebel, S and Montoto, S and Jones, RJ and Ahmed, N and Lynch, RC and de Lima, MJ and Shadman, M and Sauter, CS and Ahn, KW and Hamadani, M and Bazarbachi, A and Sureda, A},
title = {Outcomes of Allogeneic HCT in Hodgkin Lymphoma in the Era of Checkpoint Inhibitors: A Joint CIBMTR and EBMT Analysis.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024027197},
pmid = {40623049},
issn = {1528-0020},
abstract = {Checkpoint inhibitors (CPI) have shown remarkable efficacy in patients with Hodgkin lymphoma (HL) and are now used routinely for this disease. While allogeneic hematopoietic cell transplantation (alloHCT) remains a curative option for HL, there are concerns that prior CPI may exacerbate post alloHCT complications, particularly graft-versus-host disease (GVHD), and lead to worse outcomes. Given the relative paucity of data, we performed a CIBMTR/EBMT study to examine the impact of prior CPI in alloHCT outcomes. We included 2186 adult patients > 18 years who received a first alloHCT using a matched related, unrelated or haploidentical donor from 2008-2023. Twenty-seven percent of patients received prior CPI. GVHD prophylaxis was post-transplant cyclophosphamide in 55.8% patients in the CPI cohort and 35% in the non-CPI cohort. Median follow-up among survivors was longer for the non-CPI (39 months) than CPI cohort (16.5 months). In the multivariate analysis, prior CPI exposure did not affect overall survival or non-relapse mortality but resulted in improved progression-free survival (non-CPI vs. CPI HR 0.81, 0.67-0.98, p=0.03) and lower incidence of relapse (HR 0.58, 0.45-0.76, p<0001). While grade II-IV (HR1.26, 1.04-1.53; p=0.02) and III-IV (HR1.41, 1.04-1.92; p=0.03) acute GVHD were increased differences in chronic GVHD were not significant. Use of post-transplant cyclophosphamide based GVHD prophylaxis resulted in improved OS, lower grade II-IV acute GVHD and chronic GVHD in patients with prior CPI exposure. In summary, allo-HCT should still be considered a curative option for patients with HL in the era of checkpoint inhibitors.},
}

@article {pmid40623045,
year = {2025},
author = {Dhodapkar, MV and Paiva, B},
title = {Immune Alterations in Myeloma Evolution and Outcomes: Quo Vadis?.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024026227},
pmid = {40623045},
issn = {1528-0020},
abstract = {The pathogenesis of multiple myeloma (MM) and its precursor monoclonal gammopathy of undetermined significance (MGUS) is linked to an aging immune system. Chronic activation of B/plasma cells may contribute to the origin of MGUS, which is frequent in the elderly. However, only 1% of individuals with MGUS annually experience progression to MM. The immune system can specifically recognize MGUS lesions and preclinical MM models provide evidence for both innate and adaptive immune surveillance. Multiomic studies have identified several systemic alterations at the MGUS stage, suggesting accelerated immune aging prior to evolution into clinical malignancy. MM is further associated with spatial alterations in patterns of tumor growth and in-situ regulation of regional immunity. Both tumor and microenvironment-related factors contribute to immune paresis, which facilitates the dissemination of clonal plasma cells and increases the risk of infections in MM patients. Immune profiles in blood or marrow exhibit considerable heterogeneity and have been linked to outcomes following immune therapies including T cell redirection. Understanding how underlying systemic immune changes impact in-vivo function and durability of natural or synthetic tumor/antigen-specific immunity needs further study. Preserving or restoring immune function may be critical for long-term outcomes both in the context of prevention of clinical MM and of treating active disease. Benchmarking of immune biomarkers followed by its prospective integration into current risk models, together with improved understanding of mechanisms underlying tumor immunity in-vivo, are needed to optimize immune approaches and improve outcomes in MM.},
}

@article {pmid40622392,
year = {2025},
author = {Naidoo, N and Bell-Brown, A and Kimura, A and Akinsoto, N and Fang, V and Peck, A and Wood, J and Issaka, RB},
title = {Fecal Immunochemical Test (FIT) Completion by Instruction Type: A Randomized Clinical Trial Comparing QR-Code linked Video to Pictorial Instructions.},
journal = {The American journal of gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ajg.0000000000003637},
pmid = {40622392},
issn = {1572-0241},
abstract = {BACKGROUND AND AIMS: Low-literacy, pictorial instructions improve fecal immunochemical test (FIT) completion and might enhance colorectal cancer (CRC) screening. The aim of this study was to compare FIT completion among English- and Spanish-speaking patients in an organized CRC screening program based on the type of instructions received (quick response (QR)-code linked to a video vs. pictorial instructions).

METHODS: In this randomized controlled quality improvement study, English- and Spanish-speaking patients eligible for mailed outreach through an organized CRC screening program were randomized 1:1 to receive a FIT kit with either a QR-code linked video or pictorial instructions in their preferred language. Patient demographics (gender, age, race, ethnicity, and insurance type) and clinical outcomes (FIT completion and time to completion) were abstracted from electronic health records.

RESULTS: 13,471 English-speaking patients and 508 Spanish-speaking patients were included. Overall, 31.9% of patients who received mailed outreach completed CRC screening by FIT. However, FIT completion was higher among patients who received QR-code instructions vs. pictorial instructions (33.5% vs 30.4%, absolute difference 3.1%, 95% CI 1.5% - 4.6%). These findings were similar among English- and Spanish-speaking patients. The median time to FIT completion was two days longer (24 days, 95% CI 23-25) for patients who received QR-code instructions versus pictorial instructions, however there was no difference in time to FIT completion by language group.

CONCLUSION: Providing QR-code based education offers a promising format for delivering low literacy instructions, which might be a practical strategy to improve FIT completion for CRC screening.},
}

@article {pmid40622009,
year = {2025},
author = {Chen, W and Majovski, J and Bhatia, S and Chan, A and Grivas, P and Lee, S and Shah, S and Thompson, JA and Tykodi, SS and Veatch, JR and Schapira, L and Hall, ET},
title = {A mixed-method analysis of oncologist-patient communications about immune checkpoint inhibitors (COACH).},
journal = {The oncologist},
volume = {30},
number = {7},
pages = {},
pmid = {40622009},
issn = {1549-490X},
mesh = {Humans ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Female ; *Oncologists/psychology ; Male ; *Physician-Patient Relations ; Middle Aged ; *Communication ; *Neoplasms/drug therapy/immunology ; Aged ; Adult ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: Despite significant attention in the media and oncology community about improved outcomes associated with immune checkpoint inhibitors (ICIs), there remains a gap in our understanding of how oncologists describe ICIs to their patients. Communication around ICIs represents a challenge as some patients have durable, remarkable benefits while others experience severe toxicities. We investigated oncologist-patient communication practices by performing a mixed-methods study of in-clinic discussions about ICIs.

MATERIALS AND METHODS: This was a mixed-method study in which in-clinic conversations between oncologists and their patients with advanced cancers about ICIs as potential treatments were audio-recorded. Patients were asked to complete a post-discussion survey. Qualitative data was derived from a general inductive thematic approach while descriptive statistics were used to analyze the survey responses.

RESULTS: We recorded and analyzed 13 in-clinic conversations involving 8 oncologists and 13 patients. Twelve patients completed the post-discussion surveys. The conversations involved sophisticated discussions of immune function, cancer and ICI mechanisms, and trade-offs between anticancer benefits and toxicities. Oncologists incorporated metaphors and probabilistic information in their explanations. In the post-discussion surveys, patients indicated a preference for detailed information about ICIs and reported that they received the right depth of information in these discussions.

CONCLUSIONS: During in-clinic discussions of ICI therapy, oncologists provided detailed information about immunology and cancer, often aided by metaphors. Probabilities were commonly used to describe the likelihood of toxicities and benefits. The amount of information provided by the oncologists aligned with the patients' preference for detailed information about their cancer treatments.},
}

Humans
*Immune Checkpoint Inhibitors/therapeutic use/pharmacology
Female
*Oncologists/psychology
Male
*Physician-Patient Relations
Middle Aged
*Communication
*Neoplasms/drug therapy/immunology
Aged
Adult
Surveys and Questionnaires

@article {pmid40620045,
year = {2025},
author = {Kauffman, ZJ and Koesser, K and Helzer, KT and Sharifi, MN and Heninger, E and Li, C and Juang, DS and Jarrard, DF and Zhao, SG and Haffner, MC and Beebe, DJ and Lang, JM and Sperger, JM},
title = {Lossless Altered Histone Modification Analysis System (LAHMAS).},
journal = {Lab on a chip},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5lc00060b},
pmid = {40620045},
issn = {1473-0189},
abstract = {Miniaturized biological assays using microfluidics have the potential to enhance assay sensitivity, reduce reagent consumption, and increase throughput. However, challenges to miniaturization include increased platform complexity and increased surface to volume ratios leading to risk of evaporation and analyte loss through surface binding. Exclusive Liquid Repellency (ELR) enables open microfluidic systems that minimize these challenges through an oil phase that protects small aqueous volumes from temperature fluctuation and evaporation while eliminating surface fouling that leads to sample loss. Here we report a novel microfluidic platform leveraging ELR and Exclusion-based Sample Preparation (ESP) for the miniaturization of CUT&Tag, a complex multistep biological assay. The resultant Lossless Altered Histone Modification Analysis System (LAHMAS) employs a PDMS-silane treated glass surface immersed in silicone oil to facilitate lossless liquid handling and prevent sample evaporation. The device design, compatible with standard laboratory equipment, allows effective processing of cell inputs as low as 100 cells with higher specificity than macroscale CUT&Tag facilitating accurate chromatin profiling of low input and rare cell samples.},
}

@article {pmid40619101,
year = {2025},
author = {Jimenez Jimenez, AM and Spellman, SR and Politikos, I and McCurdy, SR and Devine, SM and Malki, MMA and Bolon, YT and Lee, SJ and Dehn, J and Pidala, J and Maiers, M and Askar, M and Malmberg, C and Auletta, JJ and Stefanski, H and Broglie, L and Qayed, M and Horwitz, M and Wilder, JS and Gooptu, M and Mehta, RS and Fernandez-Viña, M and Shaw, BE and Shaffer, BC},
title = {Allogeneic Hematopoietic Cell Donor Selection: Contemporary Guidelines from the NMDP/CIBMTR.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.07.004},
pmid = {40619101},
issn = {2666-6367},
abstract = {Allogeneic hematopoietic cell transplantation (HCT) remains a curative therapy for many patients with hematologic malignancies, bone marrow failure syndromes, inborn errors of immunity and metabolic disorders. Current donor selection strategies typically prioritize the selection of an HLA-matched donor over HLA mismatched ("alternative") donor sources, with a hierarchical approach to the donor search. More recent data challenge this rubric, particularly in the context of novel graft versus host disease (GVHD) prophylaxis strategies that demonstrate improved outcomes in alternative donor HCT recipients. In this setting, an increased emphasis on non-HLA factors (both donor characteristics and systemic factors) in determining donor selection is now feasible. In this guideline, we review recent evidence from prospective clinical trials as well as high-quality observational studies and provide expert panel recommendations on donor selection algorithms and prioritization in the era of novel GVHD prophylaxis. We then highlight important questions still to be answered in our field.},
}

@article {pmid40619005,
year = {2025},
author = {Hullar, MAJ and Kahsai, O and Curtis, KR and Navarro, SL and Zhang, Y and Randolph, TW and Levy, L and Shojaie, A and Kratz, M and Neuhouser, ML and Lampe, PD and Raftery, D and Lampe, JW},
title = {Metabolic plasticity of the gut microbiome in response to diets differing in glycemic load in a randomized, crossover, controlled feeding study.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajcnut.2025.06.026},
pmid = {40619005},
issn = {1938-3207},
abstract = {BACKGROUND: Dietary patterns characterized by low-glycemic, minimally processed plant foods are associated with lower risk of several chronic diseases.

OBJECTIVE: Evaluate the effects of a low glycemic load (LGL) versus a high glycemic load (HGL) dietary pattern on stool bacterial community structure and metabolism.

METHODS: Participants in this crossover-controlled feeding study were healthy men and women (n=69). We identified genera, species, and genes and transcripts of metabolic pathways and bacterial enzymes using 16S rRNA gene, metagenomic and metatranscriptomic sequencing, and bioinformatic analysis.

RESULTS: Overall community structure measured by alpha and beta diversity were not significantly different across the diets although diet did significantly increase the abundance of 13 out of 161 genera (padj<0.05) and 5 species in the LGL and 7 species in the HGL diet. Gene expression in the hexitol fermentation pathway (β=-1.15, SE=0.24 with 95% CI (-1.63, -0.67); padj=0.002) was significantly higher in the HGL diet, whereas expression in the L-lysine biosynthesis pathway (β =0.20, SE=0.05 with 95% CI (0.09, 0.30); padj=0.03); was enriched in the LGL diet. The beta diversity of expressed carbohydrate-active enzymes (CAZymes) was significantly different between the diets (MiRKAT, p<0.001). CAZymes enriched in the HGL diet reflected dietary additives while CAZymes enriched in the LGL diet reflected diverse phytochemical intake. There was a significant interaction between HOMA IR and the Coenzyme A biosynthesis I pathway involved in bacterial fatty acid biosynthesis (padj=0.035) that was positive in the HGL diet (β=0.20, SE=0.09 with 95% CI (0.02, 0.39)) and negative in the LGL diet (β =-0.23, SE=0.09 with 95% CI (-0.40, -0.06)).

CONCLUSION: In healthy humans, diet impacts microbial metabolism and enzymatic activity but not the overall diversity of the gut microbiome. This emphasizes the relevance of dietary components in activating expression of specific bacterial genes and their impact on host metabolism. This trial was registered at clinicaltrials.gov as NCT00622661.},
}

@article {pmid40618773,
year = {2025},
author = {White, RG and Churchyard, GJ and Horton, KC and Fiore-Gartland, A and Behr, MA and Clark, RA and Cobelens, F and Ernst, JD and Esmail, H and Garcia-Basteiro, AL and Hadinegoro, SR and Hanekom, WA and Hatherill, M and Hill, PC and Muloiwa, R and Pelzer, PT and Rangaka, L and Rees, H and Schrager, L and Stanley, M and Tufet, M and Wong, EB and Houben, RMGJ},
title = {Evidence required to evaluate the use of bacteriologically confirmed asymptomatic tuberculosis disease as a primary endpoint in prevention of tuberculosis disease vaccine licensure trials.},
journal = {The Lancet. Respiratory medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2213-2600(25)00164-X},
pmid = {40618773},
issn = {2213-2619},
abstract = {Current licensure trials of new vaccines to prevent tuberculosis disease use bacteriologically confirmed symptomatic tuberculosis disease as the primary endpoint. Globally, the incidence of symptomatic tuberculosis disease is low, making licensure trials large, long, and expensive. New data suggest that bacteriologically confirmed asymptomatic tuberculosis disease might occur more frequently than symptomatic tuberculosis disease. Therefore, if vaccines have efficacy against asymptomatic disease, tuberculosis vaccine licensure trials could include it in the primary endpoint, potentially leading to smaller or shorter trials. We describe the potential benefits and risks of this inclusion in the primary endpoint of tuberculosis vaccine licensure trials. We also simulate licensure trial endpoint accrual and summarise feedback from anonymous regulators and policy makers on the knowledge needed to consider this proposal and research studies needed to fill these evidence gaps. If bacteriologically confirmed asymptomatic tuberculosis disease could be included in the primary endpoint of tuberculosis disease licensure trials, it could lead to cheaper and more rapid tuberculosis vaccine development.},
}

@article {pmid40617679,
year = {2025},
author = {Petersdorf, EW},
title = {Semper Progrediens.},
journal = {Transplantation and cellular therapy},
volume = {31},
number = {7},
pages = {399-400},
doi = {10.1016/j.jtct.2025.06.005},
pmid = {40617679},
issn = {2666-6367},
}

@article {pmid40617637,
year = {2025},
author = {Rafati, DM and Wang, Y and Koppayi, AL and Savage, SA and Godley, LA and Williams, KM and Porter, C and Jones, K and Hicks, B and Spellman, SR and He, M and Atshan, R and Bolon, YT and Arrieta-Bolaños, E and Saultz, JN and Benjamin, CL and Lee, SJ and Saber, W and Gadalla, SM},
title = {REMOVED: Conditioning Regimen Considerations for Allogeneic Hematopoietic Cell Transplantation in Recipients with Germline Pathogenic Variants in Base-Excision Repair Pathway Genes.},
journal = {Transplantation and cellular therapy},
volume = {31},
number = {2S},
pages = {S338},
doi = {10.1016/j.jtct.2025.01.521},
pmid = {40617637},
issn = {2666-6367},
mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/methods ; *Transplantation Conditioning/methods ; *DNA Repair/genetics ; Transplantation, Homologous/methods ; *Germ-Line Mutation ; Male ; Female ; Excision Repair ; },
abstract = {This abstract has been removed: please see Elsevier policy on article withdrawal (https://www.elsevier.com/about/policies-and-standards/article-withdrawal). This article has been removed at the request of the author. This abstract has been removed because it was not presented at the 2025 BMT Tandem Meeting.},
}

Humans
*Hematopoietic Stem Cell Transplantation/methods
*Transplantation Conditioning/methods
*DNA Repair/genetics
Transplantation, Homologous/methods
*Germ-Line Mutation
Male
Female
Excision Repair

@article {pmid40617636,
year = {2025},
author = {Rafati, DM and Pirsl, F and Katki, HA and Wu, D and Luo, W and Liu, J and Jones, K and Zhou, W and Spellman, SR and Bolon, YT and Lee, SJ and Deeg, HJ and Gupta, V and Saber, W and Gadalla, SM},
title = {REMOVED: Genetic Landscape in Myelofibrosis Impacts Post-Hematopoietic Cell Transplantation Outcomes.},
journal = {Transplantation and cellular therapy},
volume = {31},
number = {2S},
pages = {S337},
doi = {10.1016/j.jtct.2025.01.520},
pmid = {40617636},
issn = {2666-6367},
mesh = {Humans ; *Primary Myelofibrosis/genetics/therapy ; *Hematopoietic Stem Cell Transplantation/methods ; Treatment Outcome ; },
abstract = {This abstract has been removed: please see Elsevier policy on article withdrawal (https://www.elsevier.com/about/policies-and-standards/article-withdrawal). This article has been removed at the request of the author. This abstract has been removed because it was not presented at the 2025 BMT Tandem Meeting.},
}

Humans
*Primary Myelofibrosis/genetics/therapy
*Hematopoietic Stem Cell Transplantation/methods
Treatment Outcome

@article {pmid40617294,
year = {2025},
author = {Chloe, TB and Taara, EB and Kenna, S and Lynn, OM and Stephanie, JL},
title = {Serositis associated with chronic graft-versus-host disease.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.07.002},
pmid = {40617294},
issn = {2666-6367},
abstract = {Serositis is a recognized complication associated with chronic graft-versus-host disease (cGVHD) in patients who undergo allogeneic hematopoietic cell transplantation (HCT). Although it is uncommon, serositis after HCT can have significant negative clinical impacts. There are limited data describing the patient population, incidence, risk factors and management strategies of cGVHD-associated serositis. We retrospectively identified 50 adult patients who underwent HCT at the Fred Hutchinson Cancer Center between 1998 and 2021 and developed serositis attributed to cGVHD. Most patients developed pericardial effusions (n=31) and/or pleural effusions (n=38). 94% of patients with pleural effusion and 87% of patients with pericardial effusion received medical management for their serositis. Eleven patients experienced at least one recurrence of serositis. The median overall survival for all serositis types at one-year post-serositis diagnosis was 86%, and 69% for three-years post-serositis diagnosis. Serositis is a serious atypical cGVHD manifestation and prospective data collected from a larger cohort of patients is required to better understand favorable treatment strategies and outcomes of this complication.},
}

@article {pmid40616435,
year = {2025},
author = {Huang, Y and Zhang, B and Zhang, L and Mayer, BT and Martin, T and Hahn, W and Hyrien, O and Gelderblom, HC},
title = {Dose finding in early-phase human immunodeficiency virus type 1 prevention monoclonal antibody clinical trials.},
journal = {Clinical trials (London, England)},
volume = {},
number = {},
pages = {17407745251347280},
doi = {10.1177/17407745251347280},
pmid = {40616435},
issn = {1740-7753},
abstract = {Human immunodeficiency virus type 1 remains a major public health burden with 39 million people living with human immunodeficiency virus type 1 and 1.3 million new diagnoses in 2023, despite the recent approval of multiple antiretroviral-based prevention products. While the development of a safe and effective human immunodeficiency virus type 1 vaccine remains the ultimate goal for controlling the worldwide pandemic, progress has been hindered by unprecedented challenges, including the extraordinary genetic diversity of human immunodeficiency virus type 1, the inability of current vaccines to induce broadly reactive antibody responses, and the lack of clear immune correlates of protection to serve as benchmarks for vaccine development. Passive administration of broadly neutralizing monoclonal antibodies that are engineered versions of naturally occurring antibodies has emerged as a potential complement to current human immunodeficiency virus type 1 prevention modalities. These antibodies are isolated from people with human immunodeficiency virus type 1 and can neutralize a broad range of human immunodeficiency virus type 1 viruses. Importantly, advances in antibody engineering have improved the pharmacokinetics of these monoclonal antibodies, offering potential for lower levels and/or less frequent monoclonal antibody dosing with greater feasibility and accessibility for human immunodeficiency virus type 1 prevention. Evaluating monoclonal antibody candidates in human immunodeficiency virus type 1 prevention trials, dose-finding and optimization requires a careful balance between virus-neutralization coverage, cost considerations, and practical constraints. To achieve this, pharmacokinetic modeling of antibody concentrations over time, combined with pharmacodynamics modeling of the relationship between neuralization titers and prevention efficacy, serves as a core of the statistical framework. In addition, for human immunodeficiency virus type 1 monoclonal antibodies administered to individuals without human immunodeficiency virus type, neutralization titers can be reliably predicted from antibody concentrations, owning to the preservation of neutralization function post-administration of these monoclonal antibodies. Within this framework, the antibody-mediated prevention efficacy trials of VRC01, an human immunodeficiency virus type 1 monoclonal antibody, and a meta-analysis of 16 different monoclonal antibodies in non-human primates provided consistent evidence that neutralization titer is a potential pharmacodynamics biomarker of monoclonal antibody prevention efficacy. These findings support the use of integrated pharmacokinetics/pharmacodynamics modeling as a foundation for dose finding of human immunodeficiency virus type 1 monoclonal antibodies. However, in the context of combination monoclonal antibody regimens, additional challenges arise. The total dose cost, operational feasibility, and the influence of dosing ratios on neutralization breadth and potency across diverse human immunodeficiency virus type 1 viral strains are important areas for further research. While monoclonal antibody clinical trials share some common design features with therapeutic small molecule drug trials, monoclonal antibodies possess unique safety, pharmacokinetics and pharmacodynamics profiles that require dedicated statistical and clinical considerations, particularly when used for prevention of viral infections. In this article, we highlight dose-finding efforts particularly for combination monoclonal antibodies regimens, including the selection of optimal dosing ratio and total dose amount in the context of human immunodeficiency virus type 1 prevention. Looking ahead, future directions in monoclonal antibody-based human immunodeficiency virus type 1 prevention include efforts to enhance dose-associated cost-effectiveness, and the identification and validation of robust pharmacokinetic and pharmacodynamic markers that are predictive of the prevention efficacy of combination monoclonal antibodies.},
}

@article {pmid40616382,
year = {2025},
author = {Lakkaraja, M and Baker, KS},
title = {Precision transplant and cell therapies for non-malignant disorders-The path forward.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.20245},
pmid = {40616382},
issn = {1365-2141},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; //American Society of Hematology/ ; },
abstract = {The number of patients undergoing haematopoietic stem cell transplant (HCT) and cell therapies for non-malignant disorders is steadily increasing with more genetic diseases being identified and newer gene therapy products being introduced for various indications. By combining individualized conditioning, novel graft manipulation techniques, using cutting edge methods to monitor post HCT response and offering exceptional survivorship care, one can achieve excellent survival and improved quality of life for these patients.},
}

@article {pmid40614969,
year = {2025},
author = {Kennedy, VE and Ahmed, N and Artz, A and Bhatt, NS and Custatis, R and Espinoza-Gutarra, MR and Farhan, S and Ferguson, RJ and Hamilton, B and Katz, H and Kelly, DL and Knight, JM and Lee, C and Lin, A and Lin, R and Mohanraj, L and Munshi, P and Nawas, M and Nelson, AM and Odstracil, S and Olin, R and Phelan, R and Rentscher, KE and Schoemans, H and Sung, A and Taylor, MR and Wood, W and Yuen, CH and Jayani-Kosarzycki, RV},
title = {Assessing Cognitive Function in Transplantation and CAR-T Recipients: Expert Recommendations from the Survivorship, Aging and Biobehavioral Special Interest Groups of ASTCT.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.06.026},
pmid = {40614969},
issn = {2666-6367},
abstract = {Cognitive impairment is a prevalent yet underexplored comorbidity and complication in hematopoietic stem cell transplantation (HCT) and chimeric antigen receptor (CAR) T-cell therapy. Affecting up to half of patients, cognitive impairment may include acute phases, manifesting as transplant-associated altered mentation and encephalopathy (TAME) or immune effector cell-associated neurotoxicity syndrome (ICANS), and may persist for years post-treatment as cancer-related cognitive impairment (CRCI). Such dysfunction undermines autonomy, healthcare management, work reintegration, and quality of life. This consensus review synthesizes current evidence on CRCI across the timeline of transplant and cellular therapy, organized into pre-, peri-, and post-therapy phases, with additional focus on specific populations, such as older adults and pediatric patients. It highlights gaps in understanding of cognitive impairment risks, trajectory, and impact, alongside the challenges of standardizing assessments in diverse practice settings. Key recommendations, endorsed by the American Society for Transplantation and Cellular Therapy (ASTCT) Aging, Biobehavioral Research, and Survivorship Special Interest Groups, advocate for cognitive assessment pre- and post-therapy using validated instruments, like the Montreal Cognitive Assessment (MoCA) or Blessed Orientation-Memory-Concentration Test (BOMC). We additionally recommend supplementing with patient-reported outcomes (PROs) measures for comprehensive evaluation. If cognitive impairment is identified, we recommend action items, including exclusion of alternative etiologies, reconsideration of therapy or caregiving plan, and referrals for additional evaluation and rehabilitation, among others. Practical guidance for implementation across clinical and research settings is provided, emphasizing the need for multidisciplinary strategies to address identified impairments. This work aims to establish a framework for systematic cognitive monitoring, improving patient outcomes and quality of life while guiding future research to address significant knowledge and implementation gaps.},
}

@article {pmid40614783,
year = {2025},
author = {Corn, BW and Paulus, R and Gondi, V and Mehta, MP and Fogh, S and Wefel, JS and Videtic, GM and Sun, A and Yoon, H and Heinzerling, JH and McGarry, RC and Kundapur, V and Devisetty, K and Wu, A and McCarron, EC and Pollock, J and Kanner, AA and Feldman, DB and Pugh, SL and Kachnic, LA and Movsas, B},
title = {"Hope" Drives Quality of Life in Patients with Brain Metastases, But, the "Hope Center" Remains Elusive: An Analysis of NRG-CC003.},
journal = {International journal of radiation oncology, biology, physics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ijrobp.2025.06.3884},
pmid = {40614783},
issn = {1879-355X},
abstract = {PURPOSE: xxxxx randomized 393 patients with small cell lung cancer to prophylactic cranial irradiation (PCI) with or without Hippocampal Avoidance (HA). "Hopefulness" is a cognitive construct with 3 components: goals, pathways and agency. Hope is measurable with validated instruments. Since hope is cognitive in nature, the existence of a "hope center" in the brain - most likely in the hippocampus - has been hypothesized. One exploratory objective of xxxxx posited that if hope levels were better maintained in patients randomized to PCI+HA, then the hippocampus would be implicated in the mechanism of hopefulness.

METHODS & MATERIALS: PCI consisted of 10 fractions of 2.5 Gy. The Adult Hope Scale (AHS) was administered at time-zero and at 6-months. Regarding patient reported outcome (PRO) measures, the EORTC QLQ-C30 was administered at baseline and at 3, 6-, 12-, 18- and 24-month intervals. Comparisons of AHS scores by arm were made using Wilcoxon-Mann-Whitney tests, and correlation of AHS with EORTC QLQ-C30 by Pearson correlation coefficients.

RESULTS: Approximately 95% completed the AHS at baseline and 67% filled out the questionnaire at 6-months paralleling the completion rates of the conventional tools for QOL and neurocognition. When comparing hope levels (change from baseline to 6 months) there was no significant difference (p > 0.05) between the two arms of the trial. There was a correlation for the components of hopefulness with QOL; specifically, between change in agency score and QLQ-C30 global health status (rho=0.27, p<0.0001) as well as between change in pathways score and QLQ-C30 global health status (rho=0.16, p=0.022).

CONCLUSIONS: It is feasible to study hopefulness in the context of prospective trials conducted within the National Clinical Trials Network (NCTN). The hippocampus could not be implicated as a critical structure in a central pathway that coordinates hopefulness. For the first time, validated tools established a relationship between hope and quality of life among cancer patients.},
}

@article {pmid40614134,
year = {2025},
author = {Marchak, JG and Seidel, KD and Cherven, BO and Klosky, JL and Ritenour, CWM and Leisenring, WM and Sklar, CA and Ford, JS and Krull, KR and Robison, LL and Armstrong, GT and Meacham, LR},
title = {Comprehensive assessment of sexual function in male survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.},
journal = {Cancer},
volume = {131},
number = {14},
pages = {e35967},
doi = {10.1002/cncr.35967},
pmid = {40614134},
issn = {1097-0142},
support = {CA21765/CA/NCI NIH HHS/United States ; CA55727/CA/NCI NIH HHS/United States ; //American Lebanese Syrian Associated Charities/ ; //Lance Armstrong Foundation/ ; },
mesh = {Humans ; Male ; Adult ; Middle Aged ; Young Adult ; *Neoplasms/complications ; *Sexual Dysfunction, Physiological/epidemiology/etiology ; Surveys and Questionnaires ; *Survivors ; *Cancer Survivors ; Child ; Risk Factors ; *Sexual Dysfunctions, Psychological/epidemiology/etiology ; Sexual Behavior ; },
abstract = {BACKGROUND: Assessment of sexual dysfunction among adult male survivors of childhood cancer has primarily been limited to erectile dysfunction. This study aimed to characterize sexual functioning more comprehensively among a large population of male survivors of childhood cancer.

METHODS: Male survivors (N = 1595, 22.0-59.4 years, median age, 37.8 years) and siblings (N = 269, 21.5-60.8 years, median age, 38.9 years) from the Childhood Cancer Survivor Study completed the Sexual Functioning Questionnaire (SFQ) to assess interest, desire, arousal, satisfaction, activity, orgasm, masturbation, relationship, and problems. Poor sexual functioning was defined as SFQ Total scores >2 standard deviations below siblings' mean. Multivariable logistic regression identified risk factors for poor sexual function.

RESULTS: Survivors (8.3%) were more likely to report poor sexual functioning as compared to siblings (4.9%, odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.4) and reported lower SFQ total scores (p < .001) and lower means on seven subscales. Poor sexual functioning among survivors was associated with older age (40-49 years: OR, 3.81; 95% CI, 1.78-8.18; 50-59 years: OR, 6.45; 95% CI, 2.28-18.30), not being married (OR, 4.39; 95% CI, 2.66-7.26), lower education (OR, 3.07; 95% CI, 1.32-7.14), learning/memory problems (OR, 1.83; 95% CI, 1.02-3.27), and high-dose cranial (≥40 Gy: OR, 3.45; 95% CI, 1.58-7.51) or high-dose testicular (≥10 Gy: OR, 4.16; 95% CI, 1.66-10.39) radiation.

CONCLUSIONS: Adult male survivors report poor sexual functioning at twice the rate expected before age 60 years. High-dose cranial or testicular radiation, as well as social and cognitive factors, contributes to risk. Improved awareness of sexual dysfunction prevalence and risk factors in male childhood cancer survivors can help clinicians better assess and treat those at highest risk.},
}

Humans
Male
Adult
Middle Aged
Young Adult
*Neoplasms/complications
*Sexual Dysfunction, Physiological/epidemiology/etiology
Surveys and Questionnaires
*Survivors
*Cancer Survivors
Child
Risk Factors
*Sexual Dysfunctions, Psychological/epidemiology/etiology
Sexual Behavior

@article {pmid40613977,
year = {2025},
author = {Mezzanotte-Sharpe, J and Hsu, CY and Choi, D and Sheffield, H and Zelinskas, S and Proskuriakova, E and Montalvo, M and Lee, DS and Whisenant, JG and Gaffney, K and Thompson, MS and Blenman, K and Tawagi, K and Symonds, L and Santa-Maria, C and Unni, N and Quiroga, D and Shyr, Y and Kennedy, LC},
title = {Adverse events in patients treated with neoadjuvant chemo/immunotherapy for triple negative breast cancer: results from seven academic medical centers.},
journal = {Breast cancer research and treatment},
volume = {},
number = {},
pages = {},
pmid = {40613977},
issn = {1573-7217},
support = {2T32CA217834-07//VOLT T32/ ; },
abstract = {PURPOSE: The standard-of-care neoadjuvant treatment for early-stage or locally advanced triple negative breast cancer (TNBC) is the KEYNOTE-522 regimen that combines pembrolizumab and chemotherapy. Although this approach has superior response and survival rates, high-grade adverse events (AEs) are common. Real-world data from a diverse patient population is needed to better understand practice patterns and the impact of immunotherapy in TNBC patients.

METHODS: Medical records from TNBC patients were retrospectively reviewed during neoadjuvant and adjuvant treatment with pembrolizumab and chemotherapy. CTCAE version 5.0 was used to grade AEs. Variables were reported with descriptive statistics, and AE, pCR and hospitalization rates were estimated with 95% confidence intervals.

RESULTS: We identified 415 patients from seven academic medical centers; 60% identified as White and 21% as Black. pCR rate was 52%. 88% of patients experienced an AE, 38% experienced a grade 3+ AE, and 31% stopped pembrolizumab early. Hospitalization rate was 26%. There were no statistically significant differences in AE, pCR or hospitalization rates between White and Black patients. Obese patients had a statistically significant higher hospitalization rate (p = 0.014). There were 18 deaths during treatment, mainly from progressive TNBC.

CONCLUSION: This is one of the largest real-world, diverse patient cohorts for TNBC patients treated with chemotherapy and pembrolizumab. pCR rate was lower than that reported in the KEYNOTE-522 study and in smaller real-world studies, potentially due to high rates of pembrolizumab and chemotherapy discontinuation. AEs and hospitalizations were common, with obese patients more likely to be hospitalized than patients with a normal BMI.},
}

@article {pmid40613577,
year = {2025},
author = {Fourment, M and Macaulay, M and Swanepoel, CJ and Ji, X and Suchard, MA and Iv, FAM},
title = {torchtree: flexible phylogenetic model development and inference using PyTorch.},
journal = {Systematic biology},
volume = {},
number = {},
pages = {},
doi = {10.1093/sysbio/syaf047},
pmid = {40613577},
issn = {1076-836X},
abstract = {Bayesian inference has predominantly relied on the Markov chain Monte Carlo (MCMC) algorithm for many years. However, MCMC is computationally laborious, especially for complex phylogenetic models of time trees. This bottleneck has led to the search for alternatives, such as variational Bayes, which can scale better to large datasets. In this paper, we introduce torchtree, a framework written in Python that allows developers to easily implement rich phylogenetic models and algorithms using a fixed tree topology. One can either use automatic differentiation, or leverage torchtree's plug-in system to compute gradients analytically for model components for which automatic differentiation is slow. We demonstrate that the torchtree variational inference framework performs similarly to BEAST in terms of speed, and delivers promising approximation results, though accuracy varies across scenarios. Furthermore, we explore the use of the forward KL divergence as an optimizing criterion for variational inference, which can handle discontinuous and non-differentiable models. Our experiments show that inference using the forward KL divergence is frequently faster per iteration compared to the evidence lower bound (ELBO) criterion, although the ELBO-based inference may converge faster in some cases. Overall, torchtree provides a flexible and efficient framework for phylogenetic model development and inference using PyTorch. phylogenetics, Bayesian inference, variational Bayes, PyTorch.},
}

@article {pmid40610289,
year = {2025},
author = {Keyes, M and Sturdza, AE and Crook, J and Anderson, B and Boldrini, L and Chino, J and Corradini, S and Deufel, C and Farach, A and Folkert, MR and Frank, SJ and Hannoun-Levi, JM and Hoskin, P and Jurgenliemk-Schulz, I and Kamrava, M and Kollmeier, M and McKee, MM and Iii, POF and Rossi, P and Pieters, BR and Strnad, V and Shah, C and Siebert, FA and Stewart, A and Taggar, AS and Tagliaferri, L and Morton, G},
title = {Joint ABS/GEC-ESTRO Consensus Statement on the objectives of training in brachytherapy for physicians.},
journal = {Brachytherapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.brachy.2025.05.006},
pmid = {40610289},
issn = {1873-1449},
abstract = {Brachytherapy is an essential skill in the practice of radiation oncology and is an important component of high-quality, full-service radiation oncology departments. With rapidly changing technology, the role of brachytherapy is constantly evolving, but it remains critically important for optimal patient care in several disease sites. As a procedural aspect of radiation oncology practice, brachytherapy requires a fundamentally different and more focused training approach, with specific training objectives, a unique knowledge base, and specialized training environment. The existing gap in brachytherapy training and experience is compounded with a lack of standardized training objectives. Consensus statement objectives were in part adapted with permission from the Royal College of Physician and Surgeons of Canada, and then further reviewed, modified and enriched with expert knowledge by all authors. Training objectives were further synchronized with the US Accreditation Council for Graduate Medical Education (ACGME). This ABS/GEC-ESTRO Consensus Statement of training objectives will facilitate brachytherapy training by outlining the necessary knowledge and procedural skills for successful practice in brachytherapy. The final brachytherapy curriculum development for any individual program, country and regions, is the responsibility of the individual programs and licensing jurisdictions and should be tailored to their patient population, available equipment and facilities.},
}

@article {pmid40609744,
year = {2025},
author = {Banerjee, R and Amonoo, HL and Barata, A and Bhatt, NS and Espinoza-Gutarra, MR and Jayani-Kosarzycki, RV and Katz, H and Kennedy, VE and Nawas, M and Steineck, A and Wanjiku, C and Costanzo, E and Cusatis, RN and Knight, JM and Schoemans, H and Sidana, S and Wood, WA and Sung, AD and Lee, CJ and Hamilton, BK},
title = {Assessing Quality of Life and Symptoms in Transplantation and CAR-T Recipients: Expert Panel Recommendations from the Survivorship Special Interest Group of ASTCT.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.06.030},
pmid = {40609744},
issn = {2666-6367},
abstract = {Patient-reported outcomes (PROs) to measure quality of life (QOL) and other symptoms play an increasingly important role in clinical trials and regulatory approvals for hematopoietic cell transplantation (HCT) and chimeric antigen receptor T-cell (CAR-T) therapy. However, their adoption has been hindered by wide heterogeneity in the choice of PRO measures for clinical research, including the Functional Assessment of Cancer Therapy Bone Marrow Transplantation (FACT-BMT) and the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) inventories. Additionally, the potential for PRO integration into routine standard-of-care (SOC) practice for patients undergoing HCT or CAR-T therapy has not yet been realized. As part of a coordinated effort by three American Society for Transplantation and Cellular Therapy (ASTCT) Special Interest Groups, we developed best practices for PRO integration in adult and pediatric recipients of HCT and CAR-T therapy. We strongly encourage the use of Patient-Reported Outcomes Measurement Information System (PROMIS) or PRO version of Common Terminology Criteria for Adverse Events (PRO-CTCAE) instruments as the primary PRO measures for most HCT and CAR-T trials. Measures such as the PROMIS-29 inventory can be used for QOL assessments, while PRO-CTCAE item banks can be used for specific symptoms. Rationales for our strong recommendation to move from FACT-BMT and EORTC QLQ-C30 to PROMIS/PRO-CTCAE instruments include: (1) free licensing and ease of implementation, including in electronic medical records; (2) psychometric validation in a variety of oncologic settings, including during inpatient hospitalizations; (3) translation into multiple languages, with validation in both adult and pediatric settings; and (4) adoption into centrally-collected PRO protocols from the Center for International Blood and Marrow Transplant Research for both HCT and CAR-T recipients. Steps to operationalize these PRO measures are discussed, as are methods to migrate existing data from legacy PRO instruments. We similarly recommend the consideration of PRO integration into SOC clinical practice, including the development of threshold-based workflows to both personalize and standardize care in this setting. Other panel recommendations include the use of standardized timepoints for longitudinal PRO assessments and the inclusion of patient advocates when implementing PRO measures. Implementing these steps will improve the ability of PROs to improve outcomes for patients undergoing HCT or CAR-T therapy, both in trials and - more importantly - in SOC practice.},
}

@article {pmid40609573,
year = {2025},
author = {Layman, RM and Han, HS and Rugo, HS and Stringer-Reasor, EM and Specht, JM and Dees, EC and Kabos, P and Suzuki, S and Mutka, SC and Sullivan, BF and Gorbatchevsky, I and Wesolowski, R},
title = {Overall survival in patients with hormone receptor-positive, HER2-negative advanced breast cancer treated in a phase 1b trial evaluating gedatolisib in combination with palbociclib and endocrine therapy.},
journal = {The Lancet. Oncology},
volume = {26},
number = {7},
pages = {e332-e333},
doi = {10.1016/S1470-2045(25)00236-0},
pmid = {40609573},
issn = {1474-5488},
}

@article {pmid40609538,
year = {2025},
author = {Severson, TM and Minnee, E and Zhu, Y and Schuurman, K and Nguyen, HM and Brown, LG and Hakkola, S and Menezes, R and Gregoricchio, S and Kim, Y and Kneppers, J and Linder, S and Stelloo, S and Lieftink, C and van der Heijden, MS and Nykter, M and van der Noort, V and Sanders, J and Morris, B and Jenster, G and van Leenders, GJ and Pomerantz, M and Freedman, ML and Beijersbergen, RL and Urbanucci, A and Wessels, L and Nelson, PS and Corey, E and Prekovic, S and Zwart, W and Bergman, AM},
title = {Epigenetic profiling identifies markers of endocrine resistance and therapeutic options for metastatic castration-resistant prostate cancer.},
journal = {Cell reports. Medicine},
volume = {},
number = {},
pages = {102215},
doi = {10.1016/j.xcrm.2025.102215},
pmid = {40609538},
issn = {2666-3791},
abstract = {Androgen receptor (AR) signaling inhibitors, including enzalutamide, are treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC), but resistance inevitably develops. Using metastatic samples from a prospective phase 2 clinical trial, we epigenetically profile enhancer/promoter activities with acetylation of lysine residue 27 on histone 3 (H3K27ac) chromatin immunoprecipitation followed by sequencing, before and after AR-targeted therapy. We identify a distinct subset of H3K27ac-differentially marked regions that are associated with treatment responsiveness, which we successfully validate in mCRPC patient-derived xenograft (PDX) models. In silico analyses reveal histone deacetylase (HDAC)3 to critically drive resistance to hormonal interventions, which we validate in vitro. Critically, we identify the pan-HDAC inhibitor vorinostat to be effective in decreasing tumor cell proliferation, both in vitro and in vivo. Moreover, we uncover evidence for HDAC3 working together with glucocorticoid receptor (GR) as a potential mechanism for this therapeutic effect. These findings demonstrate the rationale for therapeutic strategies including HDAC inhibitors to improve patient outcome in advanced stages of mCRPC.},
}

@article {pmid40609469,
year = {2025},
author = {Chen, J and Hart, JE and VoPham, T and Elliott, EG and Jones, RR and Ward, MH and Laden, F and Birmann, BM},
title = {Ambient dioxin exposure and incidence of lymphoid malignancies in large prospective US cohorts of female nurses.},
journal = {Journal of hazardous materials},
volume = {495},
number = {},
pages = {139115},
doi = {10.1016/j.jhazmat.2025.139115},
pmid = {40609469},
issn = {1873-3336},
abstract = {BACKGROUND: Limited evidence exists from prospective cohorts on residential dioxin exposure and incident non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). We assessed the associations in two US nationwide cohorts - the Nurses' Health Study (NHS, 1986-2012) and NHSII (1989-2019).

METHODS: We estimated residential proximity, duration of residence and emissions from industrial dioxin-emitting facilities within 3 km, 5 km, and 10 km radii. Outcomes included overall NHL, major NHL subtypes, and MM. Using time-varying Cox proportional hazards models, we estimated hazard ratios (HRs) with 95 % confidence intervals (CIs) and meta-analyzed cohort-specific results.

RESULTS: We observed 984 NHL and 227 MM cases in NHS (1,921,802 person-years), and 396 NHL and 61 MM cases in NHSII (2,845,710 person-years). We did not observe consistent associations between dioxin exposure and overall NHL or MM incidence. Results were heterogeneous across major NHL subtypes. Increased follicular lymphoma incidence was suggestively associated with residential proximity to dioxin-emitting facilities (HRyes vs. no and 95 % CI: 1.26, 0.95 -1.68) and duration of residence near these facilities (HR≤median vs. non-exposed and 95 % CI: 1.44, 0.98 -2.12) and significantly with dioxin emission levels (HR≤median vs. non-exposed and 95 % CI: 1.52, 1.07 -2.16) within 3 km. These positive associations remained suggestive for up to 10 km.

CONCLUSION: Dioxin exposure showed no consistent association with overall NHL or MM, but a positive association with follicular lymphoma was suggested.},
}

@article {pmid40608157,
year = {2025},
author = {Barrero, DJ and Hedouin, S and Mao, Y and Asbury, CL and Stergachis, AB and O'Toole, E and Biggins, S},
title = {Centromeres in the thermotolerant yeast K. marxianus mediate attachment to a single microtubule.},
journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology},
volume = {33},
number = {1},
pages = {14},
pmid = {40608157},
issn = {1573-6849},
support = {R35 GM149357/NH/NIH HHS/United States ; R35 GM149357/GM/NIGMS NIH HHS/United States ; DP5 OD029630/OD/NIH HHS/United States ; DP5-OD029630/NH/NIH HHS/United States ; R35 GM134842/GM/NIGMS NIH HHS/United States ; R35GM134842/NH/NIH HHS/United States ; },
mesh = {*Centromere/metabolism/genetics ; *Microtubules/metabolism ; Kinetochores/metabolism ; *Kluyveromyces/genetics/metabolism ; Nucleosomes/metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Chromosome Segregation ; Centromere Protein A ; Thermotolerance ; },
abstract = {Eukaryotic chromosome segregation requires spindle microtubules to attach to chromosomes through kinetochores. The chromosomal locus that mediates kinetochore assembly is the centromere and is epigenetically specified in most organisms by a centromeric histone H3 variant called CENP-A. An exception to this is budding yeast, which have short, sequenced-defined point centromeres. In S. cerevisiae, a single CENP-A nucleosome is formed at the centromere and is sufficient for kinetochore assembly. The thermophilic budding yeast Kluyveromyces marxianus also has a point centromere, but its length is nearly double the S. cerevisiae centromere and the number of centromeric nucleosomes and kinetochore attachment sites is unknown. Purification of native kinetochores from K. marxianus yielded a mixed population, with one subpopulation that appeared to consist of doublets, making it unclear whether K. marxianus shares the same attachment architecture as S. cerevisiae. Here, we demonstrate that though the doublet kinetochores have a functional impact on kinetochore strength, kinetochore localization throughout the cell cycle appears conserved between these two yeasts. In addition, whole spindle electron tomography demonstrates that a single microtubule binds to each chromosome. Single-molecule nucleosome mapping analysis suggests the presence of a single centromeric nucleosome. Taken together, we propose that the K. marxianus point centromere assembles a single centromeric nucleosome that mediates attachment to one microtubule.},
}

*Centromere/metabolism/genetics
*Microtubules/metabolism
Kinetochores/metabolism
*Kluyveromyces/genetics/metabolism
Nucleosomes/metabolism
Saccharomyces cerevisiae/genetics/metabolism
Chromosome Segregation
Centromere Protein A
Thermotolerance

@article {pmid40607811,
year = {2025},
author = {Simonich, CAL and McMahon, TE and Ju, X and Yu, TC and Brunette, N and Stevens-Ayers, T and Boeckh, MJ and King, NP and Greninger, AL and Bloom, JD},
title = {RSV F evolution escapes some monoclonal antibodies but does not strongly erode neutralization by human polyclonal sera.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0053125},
doi = {10.1128/jvi.00531-25},
pmid = {40607811},
issn = {1098-5514},
abstract = {Vaccines and monoclonal antibodies targeting the respiratory syncytial virus (RSV) fusion protein (F) have recently begun to be widely used to protect infants and high-risk adults. Some other viral proteins evolve to erode polyclonal antibody neutralization and escape individual monoclonal antibodies. However, the impact of RSV F evolution on antibody neutralization is not yet thoroughly understood. Here, we develop an experimental system for measuring neutralization titers against RSV F using pseudotyped lentiviral particles. This system is easily adaptable to evaluate neutralization of relevant clinical strains. We apply this system to demonstrate that the natural evolution of RSV F leads to escape from some monoclonal antibodies, but at most modestly affects neutralization by polyclonal serum antibodies. Overall, our work sheds light on RSV antigenic evolution and describes a tool to measure the ability of antibodies and sera to neutralize contemporary RSV strains.IMPORTANCEWe describe an efficient approach to measure how antibodies inhibit infection by historical and recent human strains of respiratory syncytial virus (RSV). This approach is useful for understanding how viral evolution affects antibody immunity. We apply this approach to demonstrate that RSV evolution can escape some monoclonal antibodies, but polyclonal serum antibodies are less impacted by viral evolution. This information is relevant given the recent development of RSV preventative measures, including monoclonal antibodies and vaccines.},
}

@article {pmid40605797,
year = {2025},
author = {Orozco, JJ and Matesan, MC and Lundberg, SJ and Haaf, RL and Miyaoka, RS and Fisher, DR and Gooley, TA and Green, DJ and Sandmaier, BM and Martin, PS and Gopal, AK},
title = {Pretargeted Anti-CD20 Radioimmunotherapy with scFv Fusion Protein Safely Combines with BEAM and ASCT in patients with High-Risk B-cell Lymphomas.},
journal = {Molecular cancer therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.1158/1535-7163.MCT-24-0550},
pmid = {40605797},
issn = {1538-8514},
abstract = {Despite new therapies, many patients with NHL relapse and need more effective salvage therapies. This study (NCT02483000) evaluated the safety of B9E9-FP, a tetrameric single-chain anti-CD20-streptavidin fusion protein used in pre-targeted radioimmunotherapy (PRIT), when combined with BEAM and autologous stem cell transplantation (ASCT) for NHL patients. High-risk NHL patients received B9E9-FP on day -17, clearing agent on day -15, and DOTA-biotin (DOTA-Bt) equally divided and labeled with dose-escalated yttrium-90 (90Y), or with indium-111 (111In for imaging) on day -14. BEAM chemotherapy started day -7 before stem cell infusion. Three NHL patients (MCL, transformed DLBCL, and de novo DLBCL), ages 52-62 years, were treated with 30, 50, or 70 mCi (1110, 1850, or 2590 MBq) 90Y/m2 before ASCT without any dose-limiting toxicity. One case of diarrhea (grade 2) and one case of rash (grade 1) were possibly associated with B9E9-FP or DOTA-Bt, respectively. Pharmacokinetic (PK) studies showed peak blood biological percent injected dose per gram blood (% ID/g) of 90Y-DOTA-Bt at 15 min after infusion (14.8 - 49.4 % ID), with only 0.82 - 2.59 % ID after 72 hours. Uptake was preferential at bone marrow (1.73 - 5.96 cGy/mCi injected) and spleen (2.4 - 4.17 cGy/mCi injected) compared to lungs (0.19 - 0.48 cGy/mCi). Unbound 90Y-DOTA-Bt was excreted renally without any renal dysfunction noted up to 2 years later. Two of the 3 enrolled patients are alive and in remission 3.5 to 4.9 years after transplant. PK, dosimetry, and outcomes data support that B9E9-FP PRIT and 90Y-augmented ASCT DOTA-Bt is feasible.},
}

@article {pmid40605713,
year = {2025},
author = {Danilov, AV and Li, H and Shadman, M and Rimsza, L and Zebari, A and Smith, SM and LeBlanc, M and Friedberg, JW and Carlson, C and Song, JY},
title = {Minimal residual disease status predicts outcomes in patients with follicular lymphoma treated with chemo-immunotherapy on the SWOG S0016 trial.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2025.288057},
pmid = {40605713},
issn = {1592-8721},
abstract = {Not available.},
}

@article {pmid40605619,
year = {2025},
author = {Pearson, RA and Krish, KN and Whatney, WE and Jaoko, W and Mandaliya, K and Overbaugh, J and Graham, SM and McClelland, RS and Hicks, SL and Maurer, J and Scharer, CD and Day, CL},
title = {Single-cell transcriptomics reveals depletion and dysregulation of Mycobacterium tuberculosis-specific Th1 and Th17 cells early after acquisition of HIV.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf354},
pmid = {40605619},
issn = {1537-6613},
abstract = {HIV significantly increases the risk of developing tuberculosis (TB) and is associated with impaired CD4 T cell responses to Mycobacterium tuberculosis (Mtb). We evaluated the frequency and functional capacity of Mtb-specific CD4 T cells in individuals with and without HIV using flow cytometry and performed single-cell RNA sequencing on these cells longitudinally in a subset of individuals before and after acquisition of HIV. Our findings reveal preferential depletion and functional impairment of Mtb-specific CD4 T cells early after acquisition of HIV, characterized by reduced cytokine production, loss of effector functions, and transcriptional dysregulation. Mtb-specific Th1 and Th17 cells decreased, whereas TCF7+ stem-like cells were enriched following acquisition of HIV. Pathway analysis revealed upregulation of hypoxia and WNT signaling, and downregulation of cell adhesion, migration, antigen processing, and cytokine signaling pathways. These findings provide novel insights into HIV-mediated dysregulation of CD4 T cell responses to Mtb.},
}

@article {pmid40603473,
year = {2025},
author = {Banjoko, AW and Ng'uni, T and Naidoo, N and Ramsuran, V and Hyrien, O and Ndhlovu, ZM},
title = {High resolution class I HLA-A, -B, and -C diversity in Eastern and Southern African populations.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {23667},
pmid = {40603473},
issn = {2045-2322},
support = {SANTHE COL018//Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE)/ ; INV-027499/GATES/Gates Foundation/United States ; INV-032929/GATES/Gates Foundation/United States ; INV-032929/GATES/Gates Foundation/United States ; INV-048833//Bill and Melinda Gates Foundation/ ; R01A1181690//National Institutes of Health, NIH/NIAID/ ; INV-027090/GATES/Gates Foundation/United States ; },
mesh = {Humans ; *Genetic Variation ; Gene Frequency ; Haplotypes ; *Black People/genetics ; *HLA-A Antigens/genetics ; *HLA-B Antigens/genetics ; Alleles ; *HLA-C Antigens/genetics ; Linkage Disequilibrium ; Africa, Southern ; Genetics, Population ; Africa, Eastern ; },
abstract = {Africa, being one of the most genetically diverse regions in the world, remains significantly underrepresented in high-resolution Human Leukocyte Antigen (HLA) data. The extensive genetic variation in HLA alleles across the region underscores the need for population-specific immunogenetic data to guide T-cell vaccine development. This study analysed Class I HLA data from Eastern and Southern African populations to assess regional genetic diversity. Analyses included allele and haplotype frequency distributions, deviations from Hardy-Weinberg equilibrium, linkage disequilibrium, and homozygosity test of neutrality across various populations. To further contextualise African HLA diversity, comparisons were made among African populations and also with African American and European American populations using the Hellinger diversity index and multidimensional scaling methods. The results revealed that South African populations exhibited an estimated average of 34.1% genetic diversity with respect to other African populations. Rwanda demonstrated an estimated 26.9% genetic diversity, Kenya (26.5%), Zambia (26.5%), and Uganda (24.7%). Additionally, in-country analyses revealed variations in HLA diversity among different tribes within each country. The estimated average in-country diversity was 51% in Kenya, 35.8% in Uganda, and 33.2% in Zambia. These results reveal various levels of genetic diversity among African populations. The highlighted differences in HLA Class I allele frequencies between Eastern and Southern African populations compared to US populations, demonstrate that it is inappropriate to extrapolate HLA data from US populations including that of African Americans when designing T-cell-inducing vaccines tailored to African populations. Our findings underscore the urgent need to generate high-resolution HLA data to guide vaccine development tailored to African populations.},
}

Humans
*Genetic Variation
Gene Frequency
Haplotypes
*Black People/genetics
*HLA-A Antigens/genetics
*HLA-B Antigens/genetics
Alleles
*HLA-C Antigens/genetics
Linkage Disequilibrium
Africa, Southern
Genetics, Population
Africa, Eastern

@article {pmid40601110,
year = {2025},
author = {Hyde, ET and Evenson, KR and Howard, AG and Parada, H and Di, C and LaMonte, MJ and Bellettiere, J and Cuthbertson, CC and Lee, IM and LaCroix, AZ},
title = {Sitting time and risk of cancer incidence and cancer mortality in postmenopausal women: the Women's Health Accelerometry Collaboration.},
journal = {Cancer causes & control : CCC},
volume = {},
number = {},
pages = {},
pmid = {40601110},
issn = {1573-7225},
support = {T32HL07989/HL/NHLBI NIH HHS/United States ; 75N92021D00002, HL153462, HL151885, HL150170, and HL130591/HL/NHLBI NIH HHS/United States ; U54 CA285117 & U54 CA285115//SDSU/UCSD Cancer Center Comprehensive Partnership/ ; P30 AG059299/AG/NIA NIH HHS/United States ; K01 CA234317/CA/NCI NIH HHS/United States ; 31KT1501//Tobacco-Related Disease Research Program/ ; },
abstract = {PURPOSE: Few studies have explored whether accelerometer-measured sedentary behavior increases cancer risk. We examined the associations of accelerometer-measured daily sitting time and mean sitting bout duration classified by the Convolutional Neural Network Hip Accelerometer Posture (CHAP) machine-learned algorithm with incidence of any cancer, incidence of 13 physical activity-related cancers, and cancer mortality among postmenopausal women.

METHODS: We used data from 22,097 women (mean age = 73.3 years, standard deviation [SD] = 6.7) in the Women's Health Accelerometry Collaboration, a consortium of two US-based cohort studies of postmenopausal women: the Women's Health Study and the Women's Health Initiative Objective Physical Activity and Cardiovascular Health Study. Women who completed hip-worn triaxial accelerometry for ≥ 4 of 7 consecutive days were included. Associations between sedentary behaviors and physician-adjudicated invasive cancer incidence and mortality were tested using Cox regression.

RESULTS: Women were followed on average 8.0 years to identify cancer cases (n = 1,861) and deaths (n = 601). Overall, mean sitting time was 567 (SD = 113) min/day and mean sitting bout duration was 12.8 (SD = 4) min/bout. In covariate-adjusted models, one-SD increment higher in sitting time was associated with a 6% increased risk of incident cancer (hazard ratio [HR] = 1.06, 95% CI: 1.01-1.11); associations were similar for bout duration (HR = 1.05, 95% CI: 1.00-1.10). Estimates were similar for the 13 physical activity-related cancers (sitting time: HR = 1.10, 95% CI: 1.04-1.17; bout duration: HR = 1.08, 95% CI: 1.02-1.14) and for cancer mortality (sitting time: 1.06, 95% CI: 0.98-1.16; bout duration: HR = 1.05, 95% CI: 0.97-1.13).

CONCLUSION: Among postmenopausal women, sedentary behavior was associated with increased cancer risk, particularly for physical activity-related cancers and cancer mortality.},
}

@article {pmid40600502,
year = {2025},
author = {Stansfield, SE and Moore, M and Jamieson, L and Meyer-Rath, G and Johnson, LF and Kaftan, D and Bershteyn, A and Smith, J and Cambiano, V and Bansi-Matharu, L and Phillips, A and Heitner, J and Barnabas, RV and Hanscom, B and Donnell, DJ and Boily, MC and Dimitrov, D},
title = {Estimated impact of long-acting injectable PrEP in South Africa: a model comparison analysis.},
journal = {Journal of the International AIDS Society},
volume = {28 Suppl 2},
number = {Suppl 2},
pages = {e26453},
pmid = {40600502},
issn = {1758-2652},
support = {UM1 068617//the NIH NIAID/ ; R01 AI179417/AI/NIAID NIH HHS/United States ; 019496//Bill and Melinda Gates Foundation/ ; INV-007145/GATES/Gates Foundation/United States ; MR/T042796/1/MRC_/Medical Research Council/United Kingdom ; MR/X020258/1//MRC Centre for Global Infectious Disease Analysis/ ; //UK Medical Research Council/ ; //Global Health EDCTP3 Joint Undertaking/ ; },
mesh = {South Africa/epidemiology ; *Pre-Exposure Prophylaxis/methods ; *HIV Infections/prevention & control/epidemiology/transmission ; Humans ; *Anti-HIV Agents/administration & dosage ; Male ; Female ; *Pyridones/administration & dosage ; Tenofovir/administration & dosage ; Adult ; Injections ; Emtricitabine/administration & dosage ; Diketopiperazines ; },
abstract = {INTRODUCTION: Long-acting injectable cabotegravir (CAB-LA) demonstrated superiority to daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) in two clinical trials. This analysis projects the impact of expanding PrEP coverage with CAB-LA in South Africa between 2022 and 2042.

METHODS: Three independently calibrated models of HIV transmission in South Africa (Synthesis, EMOD-HIV, Thembisa) projected HIV acquisitions and effective coverage (average PrEP coverage across exposure groups, weighted by HIV incidence in the absence of PrEP in each group) over 20 years under multiple scenarios of PrEP expansion compared to no PrEP expansion. PrEP expansion scenarios differed in targeted overall coverage, speed of expansion, coverage of high-exposure groups, and relative coverage of women and men.

RESULTS: Achieving 5% PrEP coverage with CAB-LA by 2032 prioritizing high-exposure groups resulted in 49% (Synthesis), 18% (EMOD-HIV), and 8% (Thembisa) effective coverage and averted a median of 43%, 29% and 10% of new HIV acquisitions, respectively. Similar expansion with TDF/FTC resulted in lower impact by 19 percentage points (pp), 18pp and 3pp, respectively. Increasing CAB-LA coverage to 15% led to an additional 7pp, 12pp and 16pp, respectively, of HIV acquisitions averted. Achieving 5% CAB-LA coverage expanding to women only resulted in a lower impact by 16pp (Synthesis) and 13pp (EMOD-HIV), and a higher impact by 2pp (Thembisa). Scenarios with similar effective coverage resulted in comparable impact estimates across models.

CONCLUSIONS: Offering CAB-LA in South Africa may substantially impact the HIV epidemic based on these projections. Effective coverage proved to be a good predictor of intervention effectiveness.},
}

South Africa/epidemiology
*Pre-Exposure Prophylaxis/methods
*HIV Infections/prevention & control/epidemiology/transmission
Humans
*Anti-HIV Agents/administration & dosage
Male
Female
*Pyridones/administration & dosage
Tenofovir/administration & dosage
Adult
Injections
Emtricitabine/administration & dosage
Diketopiperazines

@article {pmid40600473,
year = {2025},
author = {Noller, K and Botsis, T and Camara, PG and Ciotti, L and Cooper, LA and Goecks, J and Griffith, M and Haas, BJ and Ideker, T and Karchin, R and Kontos, D and Lai, J and Marcus, D and Meyer, CA and Naegle, K and Pati, S and Peters, B and Pratt, D and Raphael, BJ and Reich, M and Savova, GK and Wright, C and Fertig, EJ and Bakas, S},
title = {Informatics at the Frontier of Cancer Research.},
journal = {Cancer research},
volume = {},
number = {},
pages = {},
doi = {10.1158/0008-5472.CAN-24-2829},
pmid = {40600473},
issn = {1538-7445},
abstract = {Digitized healthcare data, high-throughput profiling technologies, and data repositories have facilitated the emergence of a new era of cancer research. Each data stream requires specialized analysis methods for interpretation. The data-driven era of cancer research requires the development, enhancement, and sustainment of informatics technology software infrastructure, including fundamental methodology development in artificial intelligence and data science. We review current and emerging informatics technology developments for cancer research and discovery, spanning molecular and cellular characterization, image analysis, informatics, and therapeutics. Summarizing the diverse methods and applications of informatics throughout cancer research identifies themes and emerging areas for the next generation of cancer research.},
}

@article {pmid40598755,
year = {2025},
author = {Grinsztejn, B and Appay, V and Bekker, LG and Beyrer, C and Donnell, D and Sanchez, J and Canagasabey, D and Coutinho, C and Ganor, Y and Muturi-Kioi, V and Ortblad, KF and Cooney, E and Devisich, G and Ellenberg, P and Ghiglione, Y and K'Orimba, K and Ssemambo, PK and Ludwig-Barron, NT and Mielke, DK and Mullick, R and Muthui, MK and Radusky, PD and Sendaula, E and Tirmizi, SRH and Sanchez, AVM and Vega, J and Pebody, R},
title = {The science at HIVR4P 2024: The era of choice in biomedical HIV prevention.},
journal = {Journal of the International AIDS Society},
volume = {28},
number = {7},
pages = {e70001},
pmid = {40598755},
issn = {1758-2652},
support = {//Roger Pebody and Dr Wendy Smith/ ; //International AIDS Society/ ; },
mesh = {Humans ; AIDS Vaccines/administration & dosage/immunology ; Anti-HIV Agents/therapeutic use ; *HIV Infections/prevention & control ; Peru ; *Pre-Exposure Prophylaxis/methods ; Congresses as Topic ; },
abstract = {INTRODUCTION: HIVR4P 2024, the 5th HIV Research for Prevention Conference, took place in Lima, Peru, 6-10 October 2024. The conference focused on new developments in HIV prevention from basic research to new product development and implementation science.

METHODS: Sessions were assigned to one of five tracks: basic science; pre-exposure prophylaxis (PrEP) and antiretroviral (ARV)-based prevention; vaccines and broadly neutralizing antibodies (bNAbs); applied and implementation science; and other prevention modalities and cross-cutting issues. A team of rapporteurs covered each track and identified conference highlights.

RESULTS: Strategies to elicit bNAb responses by vaccination are advancing to clinical trials, while combination bNAbs show promise as an alternative to ARV-based products. There is promising diversity in the PrEP product pipeline and twice-yearly lenacapavir has demonstrated exceptional efficacy, but barriers to widespread access and implementation remain, compounded by new challenges from the significant policy changes and funding reductions of the new US administration. Innovative ways of delivering PrEP to vulnerable communities that could benefit are being explored and, in some cases, have been successfully implemented.

DISCUSSION: Choice in HIV prevention products and differentiated delivery models that enable clients to select options that meet their preferences and changing needs is essential. Additionally, the involvement of the community throughout the design, implementation and dissemination process is necessary to maximize the impact of HIV prevention. Ensuring equitable access in a rapidly changing context will involve policy changes, partnerships with local organizations and addressing social determinants that impact health outcomes.

CONCLUSIONS: We are in an era with more tools than ever before to prevent HIV acquisition; now, we need to facilitate collaborations between diverse stakeholders, including researchers, community members, policymakers, healthcare providers and funders. The future of HIV prevention should lie in a holistic approach that respects individual choice, enhances service accessibility and is flexible to meet evolving challenges and opportunities. However, policy changes since the conference ended have profoundly altered the HIV prevention landscape and threaten the advances described in this report.},
}

Humans
AIDS Vaccines/administration & dosage/immunology
Anti-HIV Agents/therapeutic use
*HIV Infections/prevention & control
Peru
*Pre-Exposure Prophylaxis/methods
Congresses as Topic

@article {pmid40598383,
year = {2025},
author = {Mangale, DI and Heitner, J and Ortblad, KF and Mogere, P and Kiptinness, C and Mugo, NR and Baeten, JM and Ngure, K and Barnabas, R},
title = {Opportunity for cost savings with a novel differentiated model of PrEP delivery: a comparative costing analysis of six-month PrEP supported by interim HIV self-testing and standard of care PrEP dispensing in Kenya.},
journal = {BMC health services research},
volume = {25},
number = {1},
pages = {865},
pmid = {40598383},
issn = {1472-6963},
support = {R00 MH121166/MH/NIMH NIH HHS/United States ; R01 MH113572/MH/NIMH NIH HHS/United States ; R01MH113572/MH/NIMH NIH HHS/United States ; },
mesh = {Humans ; Kenya ; *Pre-Exposure Prophylaxis/economics/methods ; *HIV Infections/prevention & control/diagnosis/economics ; *Cost Savings ; *Anti-HIV Agents/economics/therapeutic use/administration & dosage ; Male ; *Self-Testing ; Female ; },
abstract = {BACKGROUND: Cost remains an important barrier to HIV pre-exposure prophlyaxis (PrEP) delivery in Africa. Simplified delivery models that reduce costs without compromising PrEP outcomes are needed. The JiPime-JiPrEP trial tested a model of six-month PrEP dispensing supported with interim HIV self-testing (HIVST) and found non-inferior HIV testing, PrEP refilling, and adherence compared to three-month PrEP dispensing and quarterly clinic visits, the standard-of-care (SOC). We estimated the cost of this novel differentiated PrEP delivery model compared to SOC in Kenya.

METHODS: Using activity-based micro-costing (payer perspective) and time-and-motion observations, we estimated the cost of PrEP delivery (per client-month) in the intervention and SOC between May 2018 to December 2019. Data from budgets and expense reports, published documents, and interviews informed our estimates. We calculated costs over a one-year horizon for: 1) the trial scenario (i.e., costs within the trial), and 2) the Ministy of Health (MOH) scenario (i.e., hypothetical costs at public clinics). Estimates were in 2019 US dollars and excluded research-related costs.

RESULTS: The mean personnel time attributable to PrEP delivery was 76 minutes per visit and 152 minutes projected over a year in the intervention and 54 minutes per visit and 282 minutes per year in the SOC. In the trial scenario, PrEP delivery cost $17.73 per client-month in the intervention (n=2039 PrEP-months) and $25.50 in the SOC (n=913 PrEP-months). The projected cost of PrEP delivery in the MOH scenario was $11.94 in the intervention and $14.76 in the SOC, with the addition of HIVST kits in the intervention more than offset by personnel savings. In this scenario, personnel (intervention: 55%; SOC: 44%) and medication (intervention: 16%; SOC: 32%) were the primary cost drivers. Including serum creatine testing twice a year in the MOH scenario resulted in a slight increase in the cost of PrEP delivery in the intervention ($12.88 per client-month) versus SOC ($16.17 per client-month).

CONCLUSIONS: Six-month PrEP with interim HIVST demonstrated lower costs than three-month dispensing, with decreased personnel time. Scale-up of PrEP delivery requires efficient use of limited resources; the savings in this model of PrEP delivery could be redirected towards currently unmet medical needs.

CLINIAL TRIAL NUMBER: NCT03593629|| https://www.

CLINICALTRIALS: gov/ with the Clinical Trial Registry (Registration date: 2018-07-20).},
}

Humans
Kenya
*Pre-Exposure Prophylaxis/economics/methods
*HIV Infections/prevention & control/diagnosis/economics
*Cost Savings
*Anti-HIV Agents/economics/therapeutic use/administration & dosage
Male
*Self-Testing
Female

@article {pmid40595741,
year = {2025},
author = {Zheng, Y and Caron, DP and Kim, JY and Jun, SH and Tian, Y and Mair, F and Stuart, KD and Sims, PA and Gottardo, R},
title = {ADTnorm: robust integration of single-cell protein measurement across CITE-seq datasets.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {5852},
pmid = {40595741},
issn = {2041-1723},
support = {U19 AI128949/AI/NIAID NIH HHS/United States ; T32 AI106711/AI/NIAID NIH HHS/United States ; K99 HG012797/HG/NHGRI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; R00 HG012797/HG/NHGRI NIH HHS/United States ; U19 AI128914/AI/NIAID NIH HHS/United States ; HG012797//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
mesh = {*Single-Cell Analysis/methods ; Humans ; Antibodies/immunology ; Transcriptome ; *Epitopes/genetics/immunology ; Gene Expression Profiling/methods ; *Membrane Proteins/genetics/metabolism ; High-Throughput Nucleotide Sequencing/methods ; COVID-19/virology ; },
abstract = {Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) enables paired measurement of surface protein and mRNA expression in single cells using antibodies conjugated to oligonucleotide tags. Due to the high copy number of surface protein molecules, sequencing antibody-derived tags (ADTs) allows for robust protein detection, improving cell-type identification. However, variability in antibody staining leads to batch effects in the ADT expression, obscuring biological variation, reducing interpretability, and obstructing cross-study analyses. Here, we present ADTnorm, a normalization and integration method designed explicitly for ADT abundance. Benchmarking against 14 existing scaling and normalization methods, we show that ADTnorm accurately aligns populations with negative- and positive-expression of surface protein markers across 13 public datasets, effectively removing technical variation across batches and improving cell-type separation. ADTnorm enables efficient integration of public CITE-seq datasets, each with unique experimental designs, paving the way for atlas-level analyses. Beyond normalization, ADTnorm includes built-in utilities to aid in automated threshold-gating as well as assessment of antibody staining quality for titration optimization and antibody panel selection. Applying ADTnorm to an antibody titration study, a published COVID-19 CITE-seq dataset, and a human hematopoietic progenitors study allowed for identifying previously undetected phenotype-associated markers, illustrating a broad utility in biological applications.},
}

*Single-Cell Analysis/methods
Humans
Antibodies/immunology
Transcriptome
*Epitopes/genetics/immunology
Gene Expression Profiling/methods
*Membrane Proteins/genetics/metabolism
High-Throughput Nucleotide Sequencing/methods
COVID-19/virology

@article {pmid40595413,
year = {2025},
author = {Luecken, MD and Gigante, S and Burkhardt, DB and Cannoodt, R and Strobl, DC and Markov, NS and Zappia, L and Palla, G and Lewis, W and Dimitrov, D and Vinyard, ME and Magruder, DS and Mueller, MF and Andersson, A and Dann, E and Qin, Q and Otto, DJ and Klein, M and Botvinnik, OB and Deconinck, L and Waldrant, K and Yasa, SN and Szałata, A and Benz, A and Li, Z and , and Bloom, JM and Pisco, AO and Saez-Rodriguez, J and Wulsin, D and Pinello, L and Saeys, Y and Theis, FJ and Krishnaswamy, S},
title = {Defining and benchmarking open problems in single-cell analysis.},
journal = {Nature biotechnology},
volume = {},
number = {},
pages = {},
pmid = {40595413},
issn = {1546-1696},
support = {T15//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 860329 Marie-Curie ITN "STRATEGY-CKD"//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 1F31CA257625//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; 1SF3822N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; 101054957//European Commission (EC)/ ; 101054957//European Commission (EC)/ ; },
}

@article {pmid40593602,
year = {2025},
author = {Cuénod, A and Chac, D and Khan, AI and Chowdhury, F and Hyppa, RW and Markiewicz, SM and Rice, A and Kholwadwala, A and Calderwood, SB and Ryan, ET and Harris, JB and LaRocque, RC and Bhuiyan, TR and Smith, GR and Qadri, F and Lypaczewski, P and Weil, AA and Shapiro, BJ},
title = {Prevalent chromosome fusion in Vibrio cholerae O1.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {5830},
pmid = {40593602},
issn = {2041-1723},
support = {P500PB_214356//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; T32 HD007233/HD/NICHD NIH HHS/United States ; R01 AI106878/AI/NIAID NIH HHS/United States ; R35 GM118120/GM/NIGMS NIH HHS/United States ; K08 AI123494/AI/NIAID NIH HHS/United States ; R56 AI106878/AI/NIAID NIH HHS/United States ; R37 AI106878/AI/NIAID NIH HHS/United States ; },
mesh = {*Chromosomes, Bacterial/genetics ; *Vibrio cholerae O1/genetics/isolation & purification/pathogenicity ; *Cholera/microbiology/transmission ; Humans ; Bangladesh ; Biofilms/growth & development ; Virulence Factors/genetics ; Genome, Bacterial ; },
abstract = {Two circular chromosomes are a defining feature of the bacterial family Vibrionaceae, including the pathogen Vibrio cholerae, with rare reports of isolates with a single, fused chromosome. Here, we use long-read sequencing to analyse 467 V. cholerae O1 isolates from 47 cholera patients and household contacts in Bangladesh. We identify several independent chromosome fusion events that are likely transmissible within a household. Fusions occur in a 12 kilobase-pair homologous sequence shared between the two chromosomes and are stable for at least 200 generations under laboratory conditions. We find no detectable effect of fusion on V. cholerae growth, virulence factor expression, or biofilm formation. The factors promoting fusion, affecting chromosome stability, and subtle phenotypic or clinical consequences merit further investigation.},
}

*Chromosomes, Bacterial/genetics
*Vibrio cholerae O1/genetics/isolation & purification/pathogenicity
*Cholera/microbiology/transmission
Humans
Bangladesh
Biofilms/growth & development
Virulence Factors/genetics
Genome, Bacterial

@article {pmid40593437,
year = {2025},
author = {Grivas, P and Moon, HH},
title = {A Podcast on Real-World Evidence with Avelumab First-Line Maintenance and Treatment Sequencing in Locally Advanced or Metastatic Urothelial Carcinoma.},
journal = {Targeted oncology},
volume = {},
number = {},
pages = {},
pmid = {40593437},
issn = {1776-260X},
abstract = {Avelumab first-line maintenance is an approved treatment for cisplatin-eligible or -ineligible patients with advanced urothelial carcinoma (UC) who are progression free following first-line platinum-based chemotherapy, based on the results of the JAVELIN Bladder 100 phase 3 trial. In recent years, an increasing number of real-world studies have examined the effectiveness and safety of avelumab first-line maintenance in heterogeneous populations from different countries, expanding the clinical evidence base. In this podcast, we discuss findings from these real-world studies, which have complemented clinical trials and provided additional insights about overall effectiveness, treatment sequencing involving second-line enfortumab vedotin monotherapy or other options, and healthcare resource utilization. We also briefly discuss the evolving treatment landscape in advanced UC in addition to benefits and limitations of real-world studies in general. Overall, across multiple studies involving more than 3000 patients worldwide, real-world outcomes with avelumab first-line maintenance treatment have been consistent with findings from the JAVELIN Bladder 100 trial, confirming the clinical benefits of this treatment approach for patients with advanced UC who are encountered in day-to-day practice.},
}

@article {pmid40592341,
year = {2025},
author = {Clark, ML and Simeonov, KP and Mowel, WK and Michieletto, MF and Joannas, L and Wright, JM and Erickson, I and Johnson, LR and Krishnan, R and de la Fuente-Núñez, C and Minn, AJ and Henao-Mejia, J},
title = {Mitochondrial complex IV remodeling in tumor-associated macrophages amplifies interferon signaling and promotes anti-tumor immunity.},
journal = {Immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.immuni.2025.06.006},
pmid = {40592341},
issn = {1097-4180},
abstract = {Tumor-associated macrophages (TAMs) influence tumor progression and immune checkpoint blockade (ICB) efficacy. Interferon (IFN)-TAMs predict better survival and ICB responses, yet the mechanisms governing IFN-TAMs remain unclear. Here, we identify NDUFA4, a complex IV subunit of the electron transport chain, as a functional switch controlling TAM function and anti-tumor immunity. NDUFA4 expression sustained pro-tumoral TAMs. However, intratumoral IFNs decreased NDUFA4 expression in TAMs via the cooperative action of NDUFA4L3 and miR-147, co-encoded by a conserved bifunctional transcript. Mechanistically, NDUFA4 repression increased mitochondrial DNA release into the cytoplasm and subsequent STING activation, thereby amplifying anti-tumor IFN-induced transcriptional programs in TAMs. Finally, we designed RNA-based therapeutics that leveraged the specificity of miR-147 for the Ndufa4 transcript to enhance ICB efficacy and inhibit B16 melanoma tumor growth. These findings uncover mitochondrial complex IV remodeling as a critical mechanism governing the functional adaptation of macrophages to distinct microenvironments with broad implications for immunotherapy.},
}

@article {pmid40590852,
year = {2025},
author = {Levis, MJ and Hamadani, M and Logan, BR and Jones, RJ and Singh, AK and Litzow, MR and Wingard, JR and Papadopoulos, EB and Perl, AE and Soiffer, RJ and Ustun, C and Ueda Oshima, M and Uy, GL and Waller, EK and Vasu, S and Solh, MM and Mishra, A and Muffly, LS and Kim, HJ and Stelljes, M and Najima, Y and Onozawa, M and Thomson, KJ and Chen, C and Hasabou, N and Rosales, M and Hill, JE and Gill, SC and Nuthethi, R and King, D and Mendizabal, AM and Devine, SM and Horowitz, MM and Chen, YB},
title = {Impact of transplant conditioning, NPM1 mutations, and measurable residual disease in FLT3-ITD acute myeloid leukemia.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025016306},
pmid = {40590852},
issn = {2473-9537},
abstract = {We conducted a post-hoc analysis of data from BMT CTN 1506 (MORPHO), a randomized trial of gilteritinib versus placebo as post-transplantation maintenance for patients with FLT3-ITD-mutated acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT), focusing the interactions between conditioning regimen intensity, measurable residual disease (MRD), and NPM1 co-mutation status reported from diagnosis. Comparing FLT3-ITD MRD before and after conditioning, there was no difference between myeloablative conditioning (MAC) and reduced intensity conditioning (RIC) in eradication or reduction of FLT3-ITD MRD. For participants who were FLT3-ITD MRD-negative pre-HCT, there was no difference in the cumulative incidence of relapse during follow-up between those receiving MAC versus RIC. NPM1 co-mutation was associated with the largest magnitude of relapse-free survival benefit from post-HCT gilteritinib, and in these participants, post-HCT gilteritinib in the setting of RIC appeared to be as effective as MAC at preventing relapse. Only in participants who were NPM1 wild-type at diagnosis and were FLT3-ITD MRD-positive prior to HCT did MAC appear superior to RIC in preventing relapse. Our findings suggest that only a subset of patients with FLT3-ITD AML undergoing HCT may benefit from myeloablative conditioning, and that, much like AML therapy prior to HCT, the intensity of the HCT regimen should be adapted according to the molecular features of the disease. (NCT02997202).},
}

@article {pmid40590661,
year = {2025},
author = {Søgaard, MT and Tseng, D and Gibbs, S and Wu, W and Nolan, LG and Yang, PY and Lai, M and Cao, J and Pipavath, S and Mayer-Blackwell, K and Newell, EW and Houghton, AM and Payne, KK and Chiou, SH and Nair, VS},
title = {T cell receptor profiling of blood to detect lung cancer.},
journal = {Cancer immunology research},
volume = {},
number = {},
pages = {},
doi = {10.1158/2326-6066.CIR-24-1109},
pmid = {40590661},
issn = {2326-6074},
abstract = {The blood T cell receptor (TCR) repertoire broadly reflects current and lifetime immune responses against infectious pathogens and cancer, but the circulating T cell repertoire remains a largely untapped resource for cancer biomarker studies due to repertoire complexity and limited profiling data. Here, we investigated the use of blood TCR sequencing for early detection of lung cancer. We sequenced the leukocyte fraction of peripheral blood from 633 individuals divided into a case-control (n=511) and a lung cancer screening cohort (n=122) representing over 12.6 million unique clonotypes. Based on the TCR repertoires in these individuals, we devised a Tumor Immune Lymphocyte Score (TILS) using either TCR specificity groups (TILS-A) or highly recurrent, 'public' TCR clonotypes (TILS-B) capable of detecting lung cancer. TILS-A consisted of 125 TCR specificity groups that outperformed the TILS-B classifier of 49 public, TCR(?)-V(?)-defined clonotypes for cancer detection. TILS classifiers provided predictive value after accounting for age, smoking status and nodule size in the lung cancer screening cohort and improved cancer prediction for individuals with indeterminate lung cancer risk. In the subgroup analysis, TILS-A was associated with lung cancer in both early- and late-stage disease, had improved accuracy when accounting for HLA status and was validated in an external dataset studying lung cancer initiation. Collectively, these data suggest that profiles of the circulating T cell response can provide value for lung cancer detection and supports its use as a diagnostic tool.},
}

@article {pmid40590452,
year = {2025},
author = {Brown, TT and Arao, RF and Warsi, M and Phanuphak, N and Vasconcelos, R and Oyedele, T and Sullivan, PA and Hanscom, B and Rooney, JF and Rinehart, AR and McCauley, M and Grinsztejn, B and Landovitz, RJ},
title = {Bone Changes With Long-Acting Cabotegravir or Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Prevention in Cisgender Men and Transgender Women: HPTN 083.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciaf221},
pmid = {40590452},
issn = {1537-6591},
abstract = {In a randomized clinical trial, pre-exposure prophylaxis (PrEP) with long-acting cabotegravir (CAB-LA) had a better bone safety profile than tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) over 105 weeks. For individuals with low bone mineral density or other fracture risk factors, CAB-LA PrEP should be considered over TDF-based PrEP. Clinical Trials Registration. clinicaltrials.gov (NCT02720094).},
}

@article {pmid40589281,
year = {2025},
author = {Wright, JD and Prest, MT and Ferris, JS and Chen, L and Xu, X and Rouse, KJ and Melamed, A and Hur, C and Heckman-Stoddard, BM and Samimi, G and Bickell, NA and Layne, TM and Myers, ER and Havrilesky, LJ and Blank, SV and Stout, NK and Hazelton, WD and Kong, CY and Elkin, EB},
title = {Projected Trends in the Incidence and Mortality of Uterine Cancer in the United States.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {34},
number = {7},
pages = {1156-1166},
pmid = {40589281},
issn = {1538-7755},
support = {U01 CA265739/CA/NCI NIH HHS/United States ; 1U01 CA265739//National Cancer Institute (NCI)/ ; },
mesh = {Humans ; Female ; *Uterine Neoplasms/mortality/epidemiology ; Incidence ; United States/epidemiology ; Middle Aged ; Aged ; Adult ; White People/statistics & numerical data ; Black or African American/statistics & numerical data ; White ; },
abstract = {BACKGROUND: To develop a natural history model for uterine cancer calibrated to population-based incidence and mortality data to project future trends in the disease through 2050.

METHODS: We developed a state-transition microsimulation model of uterine cancer. The model begins at 18 years of age and simulates Black and White patients, includes transition states for precursor lesions, and separately models endometrioid and nonendometrioid tumors. The model was calibrated to population-based incidence and mortality data using parameter extrapolation.

RESULTS: The model closely fit population-based incidence and mortality data of uterine cancer. From 2020 to 2050, the incidence of uterine cancer is projected to increase in White women to 74.2 cases per 100,000 (compared with 57.7 cases per 100,000 in 2018) and increase to 86.9 per 100,000 (compared with 56.8 cases per 100,000 in 2018) in Black women. Among White women, incidence-based mortality will increase from 6.1 per 100,000 in 2018 to 11.2 per 100,000 in 2050, whereas incidence-based mortality in Black women will increase from 14.1 per 100,000 to 27.9 per 100,000. Endometrioid tumors are expected to increase considerably in both White and Black women; White women will experience only a slight increase in nonendometrioid tumors, whereas the incidence of these tumors will increase substantially in Black women.

CONCLUSIONS: The incidence and mortality of uterine cancer are projected to increase substantially over the next three decades. Black women will experience a disproportionate increase in the disease.

IMPACT: Projecting the incidence and mortality of uterine cancer can facilitate future cancer control efforts.},
}

Humans
Female
*Uterine Neoplasms/mortality/epidemiology
Incidence
United States/epidemiology
Middle Aged
Aged
Adult
White People/statistics & numerical data
Black or African American/statistics & numerical data
White

@article {pmid40588476,
year = {2025},
author = {Banerjee, R and Hosoya, H and Mikkilineni, L and Hansen, DK and Wolf, JL and Lin, Y},
title = {Managing IEC-associated enterocolitis following CAR-T therapy in multiple myeloma.},
journal = {Blood cancer journal},
volume = {15},
number = {1},
pages = {112},
pmid = {40588476},
issn = {2044-5385},
}

@article {pmid40588371,
year = {2025},
author = {Patel, SP and Fisher, J and Chae, YK and Soto, LS and Kasi, A and Konda, B and Walshauser, M and Parra, E and Zhang, J and Duault, C and Gonzalez-Kozlova, E and Manyam, G and Zhang, J and Chen, H and Duose, DY and Laberiano Fernandez, C and Luthra, R and Al-Atrash, G and Kim-Schulze, S and Maecker, HT and Wistuba, II and Gnjatic, S and Lee, JJ and Zhang, J and Magner, CM and Chen, HX and Sharon, E and Othus, M and Ryan, CW and Blanke, C and Haymaker, CL and Kurzrock, R},
title = {Phase II basket trial of Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: pancreatic neuroendocrine neoplasm (PNEN) cohort.},
journal = {Journal for immunotherapy of cancer},
volume = {13},
number = {6},
pages = {},
pmid = {40588371},
issn = {2051-1426},
support = {UG1 CA233331/CA/NCI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; UG1 CA233320/CA/NCI NIH HHS/United States ; U24 CA224319/CA/NCI NIH HHS/United States ; R33 CA263705/CA/NCI NIH HHS/United States ; U01 DK124165/DK/NIDDK NIH HHS/United States ; U10 CA180821/CA/NCI NIH HHS/United States ; U24 CA224316/CA/NCI NIH HHS/United States ; U24 CA224285/CA/NCI NIH HHS/United States ; U10 CA180828/CA/NCI NIH HHS/United States ; UG1 CA233198/CA/NCI NIH HHS/United States ; U10 CA180819/CA/NCI NIH HHS/United States ; U24 CA224309/CA/NCI NIH HHS/United States ; U10 CA180888/CA/NCI NIH HHS/United States ; P30 CA196521/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Male ; *Pancreatic Neoplasms/drug therapy/mortality/pathology ; Female ; Middle Aged ; Aged ; Adult ; *CTLA-4 Antigen/antagonists & inhibitors ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Nivolumab/therapeutic use/pharmacology ; *Neuroendocrine Tumors/drug therapy ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; Ipilimumab/therapeutic use/pharmacology ; },
abstract = {PURPOSE: SWOG S1609 Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) studied the efficacy of ipilimumab combined with nivolumab across multiple rare tumor types. We report the results of the pancreatic neuroendocrine neoplasm (PNEN) cohort.

EXPERIMENTAL DESIGN: Treatment consisted of ipilimumab 1 mg/kg intravenously every 6 weeks with nivolumab 240 mg intravenously every 2 weeks. The primary endpoint was overall response rate (ORR) (Response Evaluation Criteria In Solid TumorsRECIST V.1.1). Secondary endpoints include progression-free survival (PFS), overall survival (OS), and toxicity. Clinical benefit rate (includes ORR plus stable disease (SD)>6 months was examined. Correlative studies were performed. The trial was conducted by the National Cancer Institute/Southwest Oncology Group Early Therapeutics and Rare Cancers Committee and opened at >1,000 sites.

RESULTS: 19 patients with PNEN were enrolled. The median number of lines of prior therapy was 2 (range: 0-4). The ORR was 11% (2/19 patients); the clinical benefit rate (CBR; stable disease >6 months+partial response+complete response), 26% (5/19). The median PFS was 3 months; median OS, 24 months. The longest PFSs were 26 (intermediate grade PNEN), 31 (low grade) and 39+months (intermediate grade). The most common toxicities were fatigue (47% of patients) and aspartate aminotransferase (AST) elevation (32%); the most common grade 3/4 immune-related adverse event (AE) was AST (32%) and bilirubin elevation (26%), with no grade 5 events. Programmed death-ligand 1 expression by chromogenic immunohistochemistry (N=12 patients assessed) did not associate with ORR; tumor mutation burden (TMB) was high in three patients; one of the two patients with partial remission (PFS=26 months) had high TMB (150 mutations/mb). Peripheral effector memory T-cell activation (N=11 patients assessed by cytometry by time-of-flight with 5 having longitudinal analysis) was associated with response, though the number of patients evaluated was limited.

CONCLUSIONS: Low-dose ipilimumab plus nivolumab demonstrated an 11% ORR and 26% CBR (includes SD>6 months) in patients with refractory PNEN, with durable benefit (>2 years) in 3 (16%) patients.

TRIAL REGISTRATION NUMBER: NCT02834013.},
}

Humans
Male
*Pancreatic Neoplasms/drug therapy/mortality/pathology
Female
Middle Aged
Aged
Adult
*CTLA-4 Antigen/antagonists & inhibitors
*Programmed Cell Death 1 Receptor/antagonists & inhibitors
*Immune Checkpoint Inhibitors/therapeutic use/pharmacology
*Nivolumab/therapeutic use/pharmacology
*Neuroendocrine Tumors/drug therapy
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects
Ipilimumab/therapeutic use/pharmacology

@article {pmid40586142,
year = {2025},
author = {Glover, R and Yeboah, B and Vassallo, RR and Stolla, M and Panch, SR and Khan, J and Kogler, VJ and Luckey, CJ and Gorham, JD},
title = {It is time to eliminate the one-hour corrected count increment in the diagnostic workup of platelet transfusion refractoriness.},
journal = {Transfusion},
volume = {},
number = {},
pages = {},
doi = {10.1111/trf.18327},
pmid = {40586142},
issn = {1537-2995},
}

@article {pmid40585005,
year = {2025},
author = {Brittain, JS and Tsui, J and Inward, R and Gutierrez, B and Mwanyika, G and Tegally, H and Huynh, T and Githinji, G and Tessema, SK and McCrone, JT and Bhatt, S and Dasgupta, A and Ratcliffe, S and Kraemer, MUG},
title = {GRAPEVNE - Graphical Analytical Pipeline Development Environment for Infectious Diseases.},
journal = {Wellcome open research},
volume = {10},
number = {},
pages = {279},
pmid = {40585005},
issn = {2398-502X},
abstract = {The increase in volume and diversity of relevant data on infectious diseases and their drivers provides opportunities to generate new scientific insights that can support 'real-time' decision-making in public health across outbreak contexts and enhance pandemic preparedness. However, utilising the wide array of clinical, genomic, epidemiological, and spatial data collected globally is difficult due to differences in data preprocessing, data science capacity, and access to hardware and cloud resources. To facilitate large-scale and routine analyses of infectious disease data at the local level (i.e. without sharing data across borders), we developed GRAPEVNE (Graphical Analytical Pipeline Development Environment), a platform enabling the construction of modular pipelines designed for complex and repetitive data analysis workflows through an intuitive graphical interface. Built on the Snakemake workflow management system, GRAPEVNE streamlines the creation, execution, and sharing of analytical pipelines. Its modular approach already supports a diverse range of scientific applications, including genomic analysis, epidemiological modeling, and large-scale data processing. Each module in GRAPEVNE is a self-contained Snakemake workflow, complete with configurations, scripts, and metadata, enabling interoperability. The platform's open-source nature ensures ongoing community-driven development and scalability. GRAPEVNE empowers researchers and public health institutions by simplifying complex analytical workflows, fostering data-driven discovery, and enhancing reproducibility in computational research. Its user-driven ecosystem encourages continuous innovation in biomedical and epidemiological research but is applicable beyond that. Key use-cases include automated phylogenetic analysis of viral sequences, real-time outbreak monitoring, forecasting, and epidemiological data processing. For instance, our dengue virus pipeline demonstrates end-to-end automation from sequence retrieval to phylogeographic inference, leveraging established bioinformatics tools which can be deployed to any geographical context. For more details, see documentation at: https://grapevne.readthedocs.io.},
}

@article {pmid40581741,
year = {2025},
author = {Harlass, M and Knudsen, AB and Nieboer, D and van Duuren, LA and Kuntz, KM and Rutter, CM and Nascimento de Lima, P and Collier, N and Ozik, J and Hahn, AI and Alarid-Escudero, F and Zauber, AG and Inadomi, JM and Meester, RGS and Lansdorp Vogelaar, I},
title = {Benefits of colorectal cancer screening using FIT with varying positivity thresholds by age and sex.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf149},
pmid = {40581741},
issn = {1460-2105},
abstract = {BACKGROUND: Fecal immunochemical test (FIT) performance for colorectal cancer (CRC) screening varies by age and sex, yet most FIT-based screening programs use uniform thresholds. This study assessed the potential benefits of stratifying FIT thresholds based on age and sex.

METHODS: We conducted a meta-analysis of FIT sensitivity and specificity at various positivity thresholds by age and sex. We then used these estimates in two microsimulation models of CRC and projected lifetime clinical outcomes, incremental costs, and quality-adjusted life-years gained (QALYG) from age- and sex-stratified FIT strategies. FIT thresholds ranged from 10 to 50 µg hemoglobin/g feces (µg/g).

RESULTS: For current uniform FIT screening (20 µg/g), models projected 85.67 to 122.15 QALYG at incremental costs of -$982 to $504 per 1,000 individuals compared to no screening. At equivalent costs to current uniform screening, only one model found stratified FIT approaches cost-effective, yielding a marginal increase of 1.04 and 1.10 QALYG/1,000 females and males, respectively. At a willingness-to-pay threshold of $100,000/QALYG, both models found stratified FIT cut-offs to be the best strategy, with cut-offs being equal or higher for men and lowest at older ages. Uniform strategies showed comparable effectiveness, falling within one quality-adjusted life day per person of efficient strategies at up to $112 more per person. Results were sensitive to FIT test performance characteristics and one-time setup costs.

CONCLUSION: Stratifying FIT thresholds by age and sex may be cost-effective compared to current screening. However, the gain in expected health benefits with stratified FIT screening is likely small.},
}

@article {pmid40581613,
year = {2025},
author = {Maurice, NJ and Erickson, JR and DeJong, CS and Mair, F and Taber, AK and Frutoso, M and Islas, LV and Vigil, ALBG and Lawler, RL and McElrath, J and Newell, E and Sullivan, LB and Shree, R and McCartney, SA},
title = {Cytokine and metabolite networks shape T cell residency and functionality at the term human maternal-fetal interface.},
journal = {Journal of immunology (Baltimore, Md. : 1950)},
volume = {},
number = {},
pages = {},
doi = {10.1093/jimmun/vkaf093},
pmid = {40581613},
issn = {1550-6606},
support = {R21 AI144677/NH/NIH HHS/United States ; F31 HD098769/NH/NIH HHS/United States ; F99 CA245735/CA/NCI NIH HHS/United States ; R01 CA264646/CA/NCI NIH HHS/United States ; //Andy Hill Endowment Distinguished Researcher/ ; //Institute of Translational Health Sciences/ ; K12 HD000849/HD/NICHD NIH HHS/United States ; //Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; //Burroughs Wellcome Fund/ ; //Doris Duke Foundation/ ; },
abstract = {Placentation presents immune conflict between mother and fetus, yet in normal pregnancy maternal immunity against infection is maintained without expense to fetal tolerance. This is believed to result from adaptations at the maternal-fetal interface (MFI), which affect T cell programming, but the identities (i.e. memory subsets and antigenic specificities) of T cells and the signals that mediate T cell fates and functions at the MFI remain poorly understood. We found intact recruitment programs as well as proinflammatory cytokine networks that can act on maternal T cells in an antigen-independent manner. These inflammatory signals elicit T cell expression of costimulatory receptors necessary for tissue retention, which can be engaged by local macrophages. Although proinflammatory molecules elicit T cell effector functions, we show that additional cytokine (transforming growth factor β1) and metabolite (kynurenine) networks may converge to tune T cell function to those of sentinels. Together, these data demonstrate that T cells at the MFI are broadly recruited and restrained in an antigen-independent, cytokine/metabolite-dependent manner. These mechanisms provide insight into antigen-nonspecific T cell regulation, especially in tissue microenvironments in which they are enriched.},
}

@article {pmid40581329,
year = {2025},
author = {Kalkeri, R and Zhu, M and Cloney-Clark, S and Parekh, A and Gorinson, D and Cai, Z and Cai, MR and Mahato, S and Chau, G and Babu, TM and Wald, A and Ramanathan, P and Aurelia, LC and Selva, KJ and Marchese, AM and Fries, L and Dunkle, LM and Chung, AW and Plested, JS},
title = {Anti-spike IgG4 and Fc effector responses: The impact of SARS-CoV-2 vaccine platform-specific priming and immune imprinting.},
journal = {The Journal of infection},
volume = {91},
number = {2},
pages = {106543},
doi = {10.1016/j.jinf.2025.106543},
pmid = {40581329},
issn = {1532-2742},
abstract = {Proportional increases in anti-Spike (S) IgG4 associated with decreased Fc effector functions have been reported following repeated mRNA, but not recombinant protein-based (rS) (NVX-CoV2373, Novavax, Inc.), SARS-CoV-2 vaccination. We demonstrate the first evidence of a negative correlation between anti-S IgG4 and neutralizing antibody (nAb), as well as antibody-dependent surrogate Fc effector functions. Priming with two NVX-CoV2373 vaccines followed by a third dose was associated with higher IgG1 and IgG3, lower IgG4, higher nAb titers and surrogate Fc effector functions versus mRNA. Immune imprinting of anti-S IgG4 and nAbs, and Fc effector function imprinting after mRNA priming was observed. This effect was partially overcome by updated XBB.1.5 protein subunit vaccination, but not by ancestral vaccine strains. We establish correlation of anti-S IgG4 responses to reduced nAbs and surrogate Fc effector functions and demonstrate the impact of additional booster vaccination on subsequent immune response and Fc effector functions in the context of ancestral and XBB.1.5 strains.},
}

@article {pmid40581305,
year = {2025},
author = {Khawaja, F and Zamora, D and Yong, MK and Hakki, M and Goscicki, BK and Danziger-Isakov, L and Lin, A and Carpenter, PA and Boeckh, M and Papanicolaou, GA and Dadwal, SS and Chemaly, RF},
title = {American Society for Transplantation and Cellular Therapy Series #11: Updated Cytomegalovirus Guidelines in Hematopoietic Cell Transplant and Cellular Therapy Recipients.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.06.025},
pmid = {40581305},
issn = {2666-6367},
abstract = {The Practice Guidelines Committee of the American Society of Transplantation and Cellular Therapy partnered with the society's Transplant Infectious Diseases Special Interest Group to update its previous infectious disease guidelines for the prevention and management of cytomegalovirus (CMV) infection and disease following hematopoietic cell transplantation (HCT)[1]. The two updates, published in 2021, focused on the prevention and management of CMV infection, respectively, including refractory and resistant CMV infections. To best serve clinical providers, each standalone topic in the infectious diseases series has been published in a concise format of frequently asked questions (FAQs). Adult and pediatric infectious diseases and HCT content experts developed the FAQs and the answers; recommendations were graded according to their strength (A-E) and the level of the supporting evidence (I-III). Several advances in CMV prevention and management since 2021 warranted an update to the original third and fourth topics in the series. This eleventh topic in the series focuses on new antiviral treatments for CMV, expanded indications of existing antiviral therapy for the prevention of CMV, and the treatment of CMV in special populations such as CAR T-cell therapy recipients and pediatric transplant recipients.},
}

@article {pmid40580948,
year = {2025},
author = {Khor, S and Carlson, JJ and Basu, A and Bansal, A and Yu, K and Fedorenko, CR and Ramsey, S and Shankaran, V},
title = {The association between new cancer therapy innovations and financial toxicity.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf152},
pmid = {40580948},
issn = {1460-2105},
abstract = {BACKGROUND: Recent advancements in cancer treatments have improved survival rates, but rising costs associated with these innovations raise concerns about their financial impact on patients. This study investigates the trade-off between improved survival and the financial toxicity over time in advanced non-small cell lung cancer (NSCLC).

METHODS: We conducted a retrospective cohort study using linked data from the Western Washington SEER cancer registry and TransUnion credit records, focusing on adults diagnosed with advanced NSCLC, bladder, uterine, head and neck, and liver cancers between 2013 and 2017. Financial toxicity was assessed through major adverse financial events (AFEs), including collections, charge offs, liens, delinquent payments, foreclosures, repossessions, and bankruptcies. Multivariable multinomial logistic regression evaluated trends in a composite outcome of survival and AFEs for NSCLC patients within two years post-diagnosis. A falsification test evaluated a negative control group of advanced cancers lacking new therapies.

RESULTS: Our study included 6548 patients (mean age 69; 42% female; 86% non-Hispanic White). Two-year survival for NSCLC patients increased from 15.2% to 19.2% between 2013 and 2017 (mean change 4.0%pt, 95%CI 0.7, 7.3). The proportion of survivors without AFEs increased by 2.2%pt (95%CI -0.6, 5.1), while those alive with major AFEs increased by 1.9%pt (95%CI 0.02, 3.6). This trend was absent in the negative control group.

CONCLUSIONS AND RELEVANCE: The trade-off between survival gains and increased economic hardships linked to treatment innovations underscores the need to expand our focus beyond clinical outcomes and implement protective measures that ensure healthcare advancements promote population health without inducing financial distress.},
}

@article {pmid40579877,
year = {2025},
author = {Dudakov, JA and van den Brink, MRM},
title = {Burning Down the House: Thymic Repair and Regeneration After Acute Damage.},
journal = {Immunological reviews},
volume = {332},
number = {1},
pages = {e70050},
doi = {10.1111/imr.70050},
pmid = {40579877},
issn = {1600-065X},
support = {R01-HL123340/HL/NHLBI NIH HHS/United States ; R01-HL145276/HL/NHLBI NIH HHS/United States ; R01-HL147584/HL/NHLBI NIH HHS/United States ; R01-HL165673/HL/NHLBI NIH HHS/United States ; R35-HL-171556/HL/NHLBI NIH HHS/United States ; P01-CA023766/CA/NCI NIH HHS/United States ; R01-CA228308/CA/NCI NIH HHS/United States ; R01-CA228358/CA/NCI NIH HHS/United States ; P01-AG052359/AG/NIA NIH HHS/United States ; U01-AI70035//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Humans ; *Thymus Gland/physiology/immunology/radiation effects ; *Regeneration ; Animals ; Signal Transduction ; Cytokines/metabolism ; },
abstract = {The thymus is extremely sensitive to insult but also has a remarkable capacity for endogenous repair. However, even though there is continual thymic involution and regeneration in response to everyday insults like stress and infection, profound thymic damage such as ionizing radiation leads to prolonged T cell lymphopenia for which there is currently no therapeutic treatment. We and others have been focusing in recent years on untangling the cellular and molecular mechanisms underlying endogenous thymic regeneration in the hope of being able to exploit them for clinical benefit. To date, multiple molecular mechanisms have been identified that are centered on several distinct cell axes, including interleukin-22 produced by innate lymphoid cells, BMP4 by endothelial cells, and type 2 cytokines from eosinophils, ILCs, and Tregs. Notably, one of the uniting triggers for these pathways of repair centers on the balance of cell death detection. In this review, we will highlight the current state of play with regard to cellular and molecular pathways of regeneration as well as the mechanisms triggering them. We will also highlight recent work that sheds light on the limitations of thymus repair and speculate as to what will be needed for an effective thymus-boosting therapy.},
}

Humans
*Thymus Gland/physiology/immunology/radiation effects
*Regeneration
Animals
Signal Transduction
Cytokines/metabolism

@article {pmid40578716,
year = {2025},
author = {Morrell, ED and Cheng, GS},
title = {Lumpers vs. Splitters: The Search for Treatable Traits in Post-Transplant BOS.},
journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.healun.2025.06.010},
pmid = {40578716},
issn = {1557-3117},
}

@article {pmid40578660,
year = {2025},
author = {Mitsunami, M and Soria-Contreras, DC and Ortiz-Panozo, E and Harris, HR and Missmer, SA and Chavarro, JE},
title = {Soy consumption and the risk of laparoscopically confirmed endometriosis in a prospective cohort study.},
journal = {Fertility and sterility},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.fertnstert.2025.06.028},
pmid = {40578660},
issn = {1556-5653},
abstract = {OBJECTIVE: To investigate the association of soy and isoflavone intake with the risk of laparoscopically confirmed endometriosis.

DESIGN: The Nurses' Health Study II, a prospective cohort study from 1991 to 2021.

SUBJECTS: 82,084 premenopausal participants aged 27-44 years in 1991 EXPOSURE: Soy and isoflavone intake was evaluated from 1991 and every 4 years using a food frequency questionnaire.

MAIN OUTCOME MEASURES: Self-reported laparoscopically confirmed endometriosis in biennial follow-up questionnaires. Cox proportional hazard models with age in months were used to calculate hazard ratios and 95% confidence intervals for laparoscopically-confirmed endometriosis. Restricted cubic splines were used to examine the possibility of non-linear relations between isoflavone intake and the risk of endometriosis.

RESULTS: 3,829 incident cases of laparoscopically confirmed endometriosis were reported over 1,038,888 person-years of follow-up (incidence rate = 369 per 100 000 person-years). Increasing soy intake by 1 serving per week was associated with a 8% lower risk of laparoscopically confirmed endometriosis (Hazard ratio=0.92, 95% confidence interval [0.87-0.98]). This association was present among participants without a concurrent report of infertility (Hazard ratio=0.92, 95% confidence interval [0.86, 0.99]) although not among participants with a concurrent infertility diagnosis (Hazard ratio=0.97, 95% confidence interval [0.83, 1.13], Test for heterogeneity 1.00). There was evidence of a non-linear inverse association of isoflavones intake with the risk of laparoscopically confirmed endometriosis (P, non-linearity = 0.02), in which the inverse association between isoflavones and endometriosis was approximately linear up until an intake of 4mg/day (∼95[th] percentile of intake), which plateaued thereafter.

CONCLUSION: In a population with a modest intake of soy products, consistent with levels seen in other Western populations, soy intake is associated with a lower risk of laparoscopically confirmed endometriosis.},
}

@article {pmid40578047,
year = {2025},
author = {Ssenyonga, N and Stiller, CA and Marcos-Gragera, R and Kuehni, CE and Saint-Jacques, N and Bulliard, JL and Redaniel, MT and Nakata, K and Schwartz, S and De, P and Ragusa, R and Troussard, X and Curado, MP and Girardi, F and Maynadié, M and Valkov, M and Guilloteau, A and Lima, C and Coleman, MP and Allemani, C and , },
title = {Conditional survival of children, adolescents and young adults (0-24 years) diagnosed with leukaemia during 2000-2014 world-wide: (CONCORD-3).},
journal = {European journal of cancer (Oxford, England : 1990)},
volume = {225},
number = {},
pages = {115445},
doi = {10.1016/j.ejca.2025.115445},
pmid = {40578047},
issn = {1879-0852},
abstract = {BACKGROUND: Population-based survival estimates provide valuable insights into cancer care patterns world-wide. Access to optimal treatment leads to better outcomes, however, treatment pathways vary globally. Conditional survival is the probability that patients who have already survived for a given number of years since diagnosis will live for an additional number of years. It is a useful proxy to assess the success of initial treatment or remission of leukaemia.

METHODS: We analysed data for 164,563 patients aged 0-24 years diagnosed during 2000-2014, from 258 population-based cancer registries in 61 countries. Using the Pohar-Perme estimator, we estimated net survival at five years, conditional on surviving at least one year, and at 10 years conditional on surviving five years. To control for background mortality, we used life tables of all-cause mortality by single year of age, sex, country and calendar year. All-ages survival estimates were standardised to the marginal age distribution.

FINDINGS: During 2010-2014, age-standardised five-year conditional net survival ranged from 61.8 % in Mexico to 90 % or more in 20 countries. By 2010-2014, five-year conditional survival in most high-income countries exceeded 90 % for children, but not for older patients, and for acute myeloid leukaemia it was typically 5-10 % lower than for lymphoid leukaemia. Ten-year conditional survival was 90 % or higher in most countries, with less variation world-wide.

INTERPRETATION: World-wide variation in survival was less marked for patients who survived the first year(s) after diagnosis. Notable gains occurred in countries with initially lower five-year survival (e.g., China or Mexico), where legislative changes contributed to improved access to treatment for young patients with cancer. Nonetheless, inequalities persisted between high-income and low- and middle-income countries. Population-based cancer registry data remain essential to monitor further improvements.

FUNDING: Children with Cancer UK; the Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, US National Cancer Institute and the American Cancer Society.},
}

@article {pmid40577227,
year = {2025},
author = {Perazzolo, S and Flexner, CW and Stephen, ZR and Acosta, EP and Bender Ignacio, RA and Ho, RJY},
title = {Long-acting Injectable Containing Lopinavir Eliminates Reliance on Ritonavir Pharmacokinetic Enhancement.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf319},
pmid = {40577227},
issn = {1537-6613},
abstract = {High-extraction protease inhibitors (e.g., for HIV and COVID-19) typically require ritonavir to enhance bioavailability by overcoming first-pass metabolism. However, in the long-acting subcutaneous injectable dosage form TLC-ART 101, lopinavir persisted in plasma for 57 days, while ritonavir was detectable for only 3-7 days. The remarkable duration of lopinavir suggests that ritonavir may be unnecessary in long-acting injectable products, potentially reducing side effects and drug-drug interactions.},
}

@article {pmid40576898,
year = {2025},
author = {Goodsell, KE and Chauhan, SSB and Pillarisetty, VG and Sham, JG},
title = {Somatostatin Analogs for Preventing Postoperative Pancreatic Fistula: Past Evidence Reveals New Opportunities.},
journal = {Annals of surgical oncology},
volume = {},
number = {},
pages = {},
pmid = {40576898},
issn = {1534-4681},
abstract = {Postoperative pancreatic fistula (POPF) is the defining complication following pancreatectomy. The incidence of POPF after pancreatic resection remains high even at experienced centers, with associated patient morbidity, increased healthcare costs, and poorer oncologic outcomes. There is evidence that POPF is more frequent after distal pancreatectomy. On the basis of the premise that reduction in pancreatic exocrine secretion reduces the risk of fistula formation, somatostatin analogs (SSA) to prevent POPF and its sequelae have been studied for more than 30 years. However, evidence regarding their efficacy remains mixed. Early multicenter randomized control trials demonstrated a benefit of octreotide in reducing POPF, although subsequent single-center studies failed to confirm these results. Despite additional studies demonstrating a significant reduction in POPF with the use of newer SSAs including pasireotide and lanreotide, surgical practices in the use of somatostatin analogs in preventing POPF are highly variable. Herein, we review three decades of available data on SSA for POPF prophylaxis and highlight the need for pragmatic, focused, and data-driven design for future trials with modern agents.},
}

@article {pmid40576840,
year = {2025},
author = {Mayer, J and Blanco-Melo, D and Coffin, JM and Gifford, RJ and Johnson, WE and Lindemann, D and Peeters, M and Sato, K and Stoye, J and Tachedjian, G and Hatziioannou, T},
title = {2024 taxonomy update for the family Retroviridae.},
journal = {Archives of virology},
volume = {170},
number = {8},
pages = {164},
pmid = {40576840},
issn = {1432-8798},
mesh = {*Retroviridae/classification/genetics ; Genome, Viral ; Phylogeny ; Terminology as Topic ; Humans ; },
abstract = {The Retroviridae are a family of viruses that reverse transcribe their RNA genome and integrate the resulting double-stranded DNA copy into the genome of the host cell. Retroviruses are well-documented pathogens that have been associated with a variety of diseases. The International Committee on Taxonomy of Viruses (ICTV) currently lists 65 species of retroviruses. As required by the ICTV, we have converted the species nomenclature to a binomial format comprised of the genus and a freeform epithet. Assigning binomial species names to classify new retroviruses will be facilitated when following the epithet rules described herein.},
}

*Retroviridae/classification/genetics
Genome, Viral
Phylogeny
Terminology as Topic
Humans

@article {pmid40576634,
year = {2025},
author = {Figueiredo, JC and Redwood, D and Li, L and Donato, E and Fort, D and Fox, EE and Grady, WM and Green, H and Harrison, TA and Haupt, C and Hsu, L and Hullar, MAJ and Huyghe, JR and Johnson, W and Koehne, AL and LaBrie, SD and Lakey, MA and Lin, M and Loroña, NC and Maresh, GA and Matrana, M and Mizrahi, JD and Nash, SH and Nguyen, NT and Paruch, JL and Phipps, AI and Qu, C and Randolph, TW and Romo, S and Thomas, CE and Thomas, S and Tiesinga, J and Whitlow, C and Yeung, CCS and Yin, H and Zibilich, CM and Li, CI and Thomas, TK and Peters, U},
title = {The Translational Research Program in Cancer Differences across Populations.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-24-1711},
pmid = {40576634},
issn = {1538-7755},
abstract = {BACKGROUND: Colorectal cancer (CRC) incidence and mortality vary substantially across populations. The Translational Research Program in Cancer Differences across Populations (TRPCDP) was established in 2020 to address differences in CRC incidence and mortality rates within the United States.

METHODS: TRPCDP centralized data acquisition and harmonization across three sites in the U.S. to create a well-annotated resource of CRC tumors across four populations: African American/Black, Alaska Native, Hispanic/Latino/a, and non-Hispanic White. Using a case-control framework, patients with lethal CRC were matched to two controls with non-lethal CRC. Formalin-fixed paraffin-embedded tumor and normal tissue were retrieved and sent for centralized pathology review, followed by DNA and RNA extraction and tissue microarray development. Multi-omics and spatial profiling are underway to evaluate the transcriptome, proteome, and microbiome. Patient demographic and clinical data were obtained by medical record review, patient self-report, or linkage to cancer registries. Additional health-related factors were assessed using geospatial linkage.

RESULTS: The virtual biorepository includes 7,181 patients [African American (n=1,345), Alaska Native (n=1,640), Hispanic (n=1,659), and non-Hispanic White (n=2,537)]. Tissue blocks (1,594 tumor, 728 normal colon) were selected for 938 patients. To date, DNA and RNA have been extracted (n=831) and tissue microarrays have been constructed (n=414). Transcriptomic, spatial tumor profiling (multiplex immunofluorescence, PhenoCycler, GeoMx) and microbiome data (16S rRNAseq, ddPCR) are available.

CONCLUSION: The TRPCDP has developed a clinically annotated biorepository for future molecular epidemiology studies.

IMPACT: TRPCDP is a unique program that supports collaborative research, community engagement, and pipeline development for the next generation of scientists.},
}

@article {pmid40576334,
year = {2025},
author = {Lee, EM and Srinivasan, S and Purvine, SO and Fiedler, TL and Leiser, OP and Proll, SC and Minot, SS and Djukovic, D and Raftery, D and Johnston, C and Fredricks, DN and Deatherage Kaiser, BL},
title = {Syntrophic bacterial and host-microbe interactions in bacterial vaginosis.},
journal = {The ISME journal},
volume = {19},
number = {1},
pages = {},
pmid = {40576334},
issn = {1751-7370},
support = {P41 GM103493/GM/NIGMS NIH HHS/United States ; S10 OD021562/OD/NIH HHS/United States ; R01 AI061628/AI/NIAID NIH HHS/United States ; U19 AI113173/AI/NIAID NIH HHS/United States ; S10OD021562/RI/ORIP NIH HHS/United States ; R01AI061628/NH/NIH HHS/United States ; GM103493/GM/NIGMS NIH HHS/United States ; U19 AI113173/NH/NIH HHS/United States ; },
mesh = {Female ; *Vaginosis, Bacterial/microbiology ; Humans ; Vagina/microbiology ; *Host Microbial Interactions ; *Bacteria/metabolism/classification/genetics/isolation & purification ; Formates/metabolism ; Adult ; Putrescine/metabolism ; Proteomics ; Microbiota ; Bacterial Proteins/metabolism ; },
abstract = {Bacterial vaginosis (BV) is a common, polymicrobial condition of the vaginal microbiota that is associated with symptoms such as malodor and excessive discharge, along with increased risk of various adverse sequelae. Host-bacteria and bacteria-bacteria interactions are thought to contribute to the condition, but many of these functions have yet to be elucidated. Using untargeted metaproteomics, we identified 1068 host and 1418 bacterial proteins in a set of cervicovaginal lavage samples collected from 20 participants with BV and 9 who were negative for the condition. We identified Dialister micraerophilus as a major producer of malodorous polyamines and identified a syntrophic interaction between this organism and Fannyhessea vaginae that leads to increased production of putrescine, a metabolite characteristic of BV. Although formate synthesis has not previously been noted in BV, we discovered diverse bacteria associated with the condition express pyruvate formate-lyase enzymes in vivo and confirm these organisms secrete formic acid in vitro. Sodium hypophosphite efficiently inhibited this function in multiple taxa. We also found that the fastidious organism Coriobacteriales bacterium DNF00809 can metabolize formic acid secreted by Gardnerella vaginalis, representing another syntrophic interaction. We noted an increased abundance of the host epithelial repair protein transglutaminase 3 in the metaproteomic data, which we confirmed by enzyme-linked immunosorbent assay. Other proteins identified in our samples implicate Finegoldia magna and Parvimonas micra in the production of malodorous trimethylamine. Some bacterial proteins identified represent novel targets for future therapeutics to disrupt BV communities and promote vaginal colonization by commensal lactobacilli.},
}

Female
*Vaginosis, Bacterial/microbiology
Humans
Vagina/microbiology
*Host Microbial Interactions
*Bacteria/metabolism/classification/genetics/isolation & purification
Formates/metabolism
Adult
Putrescine/metabolism
Proteomics
Microbiota
Bacterial Proteins/metabolism

@article {pmid40571676,
year = {2025},
author = {Muskara, A and Parthasarathy, PB and Oyarbide, U and Ma, Y and Ganguly, S and Imamura, J and Liao, R and Rubin, BP and Macaskill, A and Murphy, ES and Anderson, PM and Gryder, BE and Scott, JG and Zahler, SG and Mian, OY},
title = {Transcriptomic Profiling of Relapsed Rhabdomyosarcoma: Pre- and Post-Treatment Tissue Analysis Reveals Molecular Characteristics of Treatment Failure.},
journal = {Pediatric blood & cancer},
volume = {},
number = {},
pages = {e31864},
doi = {10.1002/pbc.31864},
pmid = {40571676},
issn = {1545-5017},
support = {//VeloSano Foundation Research/ ; P30CA043703//Case Comprehensive Cancer Center NIH/ ; P30CA043703//Case Comprehensive Cancer Center NIH/ ; //Case Comprehensive Cancer Center, Case Western Reserve University/ ; L30CA220908//NIH/NCI/ ; },
abstract = {BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. Historically classified based on histology, advances in molecular profiling have allowed further sub-classification, which has improved risk stratification. Although molecular profiling has improved our understanding of disease progression and risk, the molecular evolution of therapy resistance in RMS remains poorly characterized. Transcriptomic profiling of patients with high-risk, relapsed RMS was undertaken with the goal of uncovering insights into the biology of RMS treatment failure.

PROCEDURE: Formalin-fixed, paraffin-embedded (FFPE) tissue samples from patients with relapsed RMS who had samples archived at diagnosis and relapse were obtained. Histologic subtype and PAX3/7::FOXO1 fusion status were confirmed. Transcriptomic profiling of the FFPE tissue samples was performed using the high-throughput genomics (HTG) whole transcriptome panel.

RESULTS: We identified 11 patients with relapsed RMS who had FFPE tissue samples archived at diagnosis and relapse following multimodality therapy. All patients were stratified as high risk, including five with PAX3/7::FOXO1 fusion-positive RMS (FP-RMS) and six with PAX3/7::FOXO1 fusion-negative RMS (FN-RMS). The transcriptomic analysis revealed that the myogenesis pathway and markers associated with myogenic differentiation were enriched pre-treatment in patients with FP-RMS and enriched post-treatment in patients with FN-RMS. Post-treatment enrichment of the inflammatory response pathway was observed in both FP-RMS and FN-RMS samples.

CONCLUSIONS: Using a probe-based transcriptome panel to characterize matched pre- and post-treatment tissue samples from patients with RMS, we report that relapsed RMS follows a fusion status-dependent evolutionary trajectory, marked by differential expression of myogenesis-associated genes, myogenic differentiation markers, and inflammatory response pathways.},
}

@article {pmid40570746,
year = {2025},
author = {Giacani, L and Romeis, E and Haynes, A and Molini, BJ and Tantalo, LC and Xu, LH and Trejos, AT and Keane, J and Mohamed, Z and Armstrong, TD and Wieland, BA and Phung, Q and Vyshenska, D and Campbell, VL and Godornes, C and Koelle, DM and Reid, TB and Wang, Y and Vorobieva, AA and Wald, A and Lieberman, NAP and Greninger, AL},
title = {Immunization with full-length TprC variants induces a broad response to surface-exposed epitopes of the Treponema pallidum repeat protein family and is partially protective in the rabbit model of syphilis.},
journal = {Vaccine},
volume = {61},
number = {},
pages = {127406},
doi = {10.1016/j.vaccine.2025.127406},
pmid = {40570746},
issn = {1873-2518},
abstract = {An effective vaccine against syphilis could aid current control measures to reduce the incidence of infection. Protective immunity from the syphilis agent, Treponema pallidum subsp. pallidum (T. pallidum), is associated with pathogen clearance by phagocytosis, supporting that immunization with an effective vaccine candidate should elicit opsonic antibodies to key epitopes at the host-pathogen interface. The T. pallidumrepeat (Tpr) proteins are putative β-barrel outer membrane porins with ten predicted extracellular loops. Here, we immunized three groups of eight rabbits with either a combination of three recombinant variants of the full-length TprC antigen, the TprD2 protein, or the conserved NH2-terminal region of TprK, with the latter antigen already known to induce incomplete protection in immunized rabbits. Compared to unimmunized controls, rabbits immunized with the three TprC variants or the TprK fragment exhibited attenuated primary chancres, reduced treponemal burden at the challenge sites, and limited pathogen dissemination to lymph nodes. Immunization with TprD2, alone did not produce comparable results. Strong humoral and cellular responses against TprC and TprK were elicited by immunization, and functional analyses supported the induction of opsonizing antibodies. Epitope mapping performed using TprC- and TprK-specific synthetic peptides and phage immunoprecipitation-sequencing identified a subset of highly reactive sequences and demonstrated immunity to predicted surface-exposed epitopes across multiple Tpr paralogs, which explained the significant, albeit incomplete protection measured post-challenge. These data advance TprC and TprK as syphilis vaccine candidates and highlight several correlates of their protection that deserve further examination.},
}

@article {pmid40569916,
year = {2025},
author = {Ortblad, KF and Brown, ER and Heffron, R and Ngure, K and Mujugira, A and Donnell, D},
title = {Research designs to generate evidence of HIV post-exposure prophylaxis effectiveness for new long-acting agents.},
journal = {Journal of the International AIDS Society},
volume = {28 Suppl 1},
number = {Suppl 1},
pages = {e26475},
pmid = {40569916},
issn = {1758-2652},
support = {R00 MH121166/MH/NIMH NIH HHS/United States ; K24 MH123371/MH/NIMH NIH HHS/United States ; K24 MH123371/NH/NIH HHS/United States ; R00 MH121166/NH/NIH HHS/United States ; },
mesh = {Humans ; *HIV Infections/prevention & control/drug therapy ; *Post-Exposure Prophylaxis/methods ; *Research Design ; *Anti-HIV Agents/administration & dosage/therapeutic use ; Treatment Outcome ; Pre-Exposure Prophylaxis ; },
abstract = {INTRODUCTION: New longer-acting antiretroviral (ARV) drugs-that is single doses with antiviral activity for at least a month-are being utilized for HIV treatment and pre-exposure prophylaxis (PrEP) but have not been explored for post-exposure prophylaxis (PEP). A "one-and-done" simplification of PEP has the potential to serve the HIV prevention needs of individuals not being met with traditional services and expand overall biomedical HIV prevention coverage. We discuss challenges with the assessment of PEP effectiveness in human trials and potential study designs that could generate evidence needed to inform the use of new, single-administered, long-acting ARVs for PEP.

DISCUSSION: Challenges with determining the effectiveness of new long-acting PEP agents in human trials include the low likelihood of observing an HIV acquisition and the short period for outcome assessment (likely 1 month) following PEP administration. Additional challenges include recruiting individuals in the brief window in which they could benefit (<72 hours of a potential HIV exposure) and ethics of conducting informed consent during a period of high stress/vulnerability. Consequently, design approaches where the efficacy goal is to establish that the HIV incidence rate following PEP administration (of the standard or a novel agent) approaches zero should be considered. HIV RNA testing conducted within 5 days of a potential exposure could define prevention per exposure. Novel recruitment venues-such as community-based retail or online pharmacies-could be used to reach individuals after a potential exposure. Potential study designs include one- or two-arm individual-level product assignment aimed at demonstration of short-course efficacy or longer-term effectiveness compared to a background rate; cluster-randomized controlled trials of recruitment venues; and novel individual-level approaches that either do not or do utilize randomization in combination with choice, enabling assessment of preferences and effectiveness.

CONCLUSIONS: Over the past decade, multiple new HIV PrEP products-but no new PEP products-have been developed to meet the diverse needs of individuals seeking HIV prevention services. Challenges exist with generating PEP effectiveness evidence, but they are not insurmountable. Effectiveness research on new PEP products could advance the number of HIV prevention options available.},
}

Humans
*HIV Infections/prevention & control/drug therapy
*Post-Exposure Prophylaxis/methods
*Research Design
*Anti-HIV Agents/administration & dosage/therapeutic use
Treatment Outcome
Pre-Exposure Prophylaxis

@article {pmid40569884,
year = {2025},
author = {Roche, SD and Omollo, V and Mogere, P and Asewe, M and Gakuo, S and Banerjee, P and Harkey, K and Sharma, M and Pintye, J and Mugambi, ML and Shah, P and Odoyo, J and Ong'wen, P and Were, D and Bukusi, EA and Ngure, K and Ortblad, KF},
title = {A modified pharmacy provider-led delivery model of oral HIV pre- and post-exposure prophylaxis in Kenya: a pilot study extension.},
journal = {Journal of the International AIDS Society},
volume = {28 Suppl 1},
number = {Suppl 1},
pages = {e26467},
pmid = {40569884},
issn = {1758-2652},
support = {INV-033052/GATES/Gates Foundation/United States ; R34 MH120106/MH/NIMH NIH HHS/United States ; R00MH121166/MH/NIMH NIH HHS/United States ; R01HD108041//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; },
mesh = {Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *Anti-HIV Agents/administration & dosage/therapeutic use ; *HIV Infections/prevention & control ; Kenya/epidemiology ; Pharmacies ; Pilot Projects ; *Post-Exposure Prophylaxis/methods ; *Pre-Exposure Prophylaxis/methods ; },
abstract = {INTRODUCTION: Private pharmacies in Africa reach individuals with ongoing and periodic HIV risk, yet few countries currently leverage pharmacies as an HIV service delivery platform. We conducted a 6-month pilot to evaluate a model for pharmacy provider-led delivery of HIV pre- and post-exposure prophylaxis (PrEP and PEP) in Kenya.

METHODS: At 12 private pharmacies in Kisumu and Kiambu Counties, licensed pharmacy providers initiated and managed eligible clients ≥18 years on PrEP and PEP under remote clinician supervision (NCT04558554); four of these pharmacies additionally offered sextually transmitted infection (STI) testing. PrEP/PEP clients were scheduled for follow-up 1 month later and then quarterly (PrEP clients only). Primary outcomes included PrEP and PEP initiation and continuation during the pilot period. Client and providers rated the model across multiple constructs of acceptability and feasibility from established frameworks.

RESULTS: From January to July 2022, 1028 clients interested in PrEP, PEP and/or STI testing were screened and 829 initiated one or more service: 661 PrEP, 162 PEP and 52 STI testing. About half of clients (48%, 398/829) were male, most were unmarried (78%, 644/829) and PrEP-naïve (89%, 737/829), and the median age was 25 years (IQR 22-31). Most PrEP clients reported inconsistent condom use (88%, 581/661) or sex with partners of unknown HIV status (70%, 460/661) in the past 6 months. Most PEP clients reported condomless sex (48%, 78/162) or a condom break (46%, 75/162) in the past 72 hours; 4% (6/162) reported sexual assault. Among PrEP clients eligible for a refill, 73% (479/658) refilled at least once and 60% (197/328) twice. Among PEP clients eligible for follow-up, 44% (65/148) completed follow-up HIV testing and 20% (30/148) transitioned to PrEP. Among STI clients, 19% (10/52) tested positive for gonorrhoea (n = 7) and/or chlamydia (n = 5). Most clients and providers (≥92%) found the delivery model and its implementation strategies acceptable. All providers (n = 12) thought it was possible to deliver PrEP and PEP at pharmacies in Kenya.

CONCLUSIONS: Pharmacy PrEP/PEP delivery achieved high uptake, continuation and acceptability among eligible clients that could benefit, highlighting the potential of pharmacies to expand HIV prevention service coverage in Kenya, particularly to individuals not accessing these services at clinics.},
}

Adolescent
Adult
Female
Humans
Male
Middle Aged
Young Adult
*Anti-HIV Agents/administration & dosage/therapeutic use
*HIV Infections/prevention & control
Kenya/epidemiology
Pharmacies
Pilot Projects
*Post-Exposure Prophylaxis/methods
*Pre-Exposure Prophylaxis/methods

@article {pmid40569864,
year = {2025},
author = {Kiptinness, C and Naik, P and Kareithi, T and Thuo, N and Okello, P and Culquichicon, C and Rafferty, M and Abdulrashid, S and Jomo, E and Nyamasyo, N and Wood, T and Mendonca, R and Malen, RC and Dettinger, JC and Pintye, J and Mwangi, J and Stergachis, A and Onentia, J and Curran, K and Mugambi, ML and Were, D and Ngure, K and Sharma, M and Ortblad, KF and , },
title = {Online delivery of oral HIV pre- and post-exposure prophylaxis: findings from the ePrEP Kenya pilot.},
journal = {Journal of the International AIDS Society},
volume = {28 Suppl 1},
number = {Suppl 1},
pages = {e26468},
pmid = {40569864},
issn = {1758-2652},
support = {INV-037646/GATES/Gates Foundation/United States ; R00 MH121166/MH/NIMH NIH HHS/United States ; K01 MH115789/MH/NIMH NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Administration, Oral ; *Anti-HIV Agents/administration & dosage/therapeutic use ; *HIV Infections/prevention & control ; Kenya ; Pilot Projects ; *Post-Exposure Prophylaxis/methods ; *Pre-Exposure Prophylaxis/methods ; *Telemedicine ; },
abstract = {INTRODUCTION: The expansion of telecommunication networks and smartphones in many African countries could be leveraged to deliver HIV prevention products directly to consumers. In collaboration with a private e-commerce platform and online pharmacy in Kenya, MYDAWA, we piloted a new model of HIV pre- and post-exposure prophylaxis (PrEP/PEP) delivery.

METHODS: In the ePrEP Kenya pilot (NCT05377138), individuals living in Nairobi and Mombasa Counties could complete a free telehealth visit with a remote clinician to assess eligibility for online PrEP/PEP (i.e. ≥18 years; no medical contraindications). Eligible individuals could order HIV testing services-courier delivered to clients' choice location-for a fee of 250 KES (∼$2 USD) for self-testing or 150 KES (∼$1 USD) for provider-administered rapid diagnostic testing. Following confirmation of clients' HIV-negative status (via an uploaded test result image), free PrEP/PEP drugs from government supply were courier delivered with or separately from HIV testing services. Clients paid a delivery fee ≤149 KES (∼$1 USD) per courier visit.

RESULTS: From October 2022 to December 2023, we screened 2257 individuals and enrolled 1915. Most PrEP/PEP clients were men (63%, 1428/1915), ≥25 years (72%, 1631/1915) and never married (80%, 1796/1915); few had ever used PrEP (3%, 48/1915) or PEP (14%, 263/1915). At enrolment, 227 (12%) were preliminarily eligible for PrEP and 1688 (88%) for PEP. Among PrEP-eligible clients, 89% (203/227) completed HIV testing and 92% (208/227) received PrEP; among PEP-eligible clients, 92% (1551/1688) completed HIV testing and 92% (1549/1688) received PEP. Most PrEP/PEP clients completed HIV testing within 6 hours of their telehealth visit (53%, 927/1757) and had drugs delivered with testing services (88%, 1546/1757). Among PrEP clients eligible for follow-up, 47% (120/256) continued PrEP and 4% (10/256) initiated PEP following PrEP discontinuation. Among PEP clients eligible for follow-up, 7% (99/1428) repeated PEP use and 6% (83/1428) transitioned from PEP to PrEP.).

CONCLUSIONS: Online PrEP/PEP delivery could expand access to prevention services by reaching individuals not engaged in existing delivery platforms. The uptake of online PEP was five times greater than PrEP, underscoring an unmet demand for PEP and highlighting the potential for online pharmacies to deliver time-sensitive PEP services.},
}

Adolescent
Adult
Female
Humans
Male
Middle Aged
Young Adult
Administration, Oral
*Anti-HIV Agents/administration & dosage/therapeutic use
*HIV Infections/prevention & control
Kenya
Pilot Projects
*Post-Exposure Prophylaxis/methods
*Pre-Exposure Prophylaxis/methods
*Telemedicine

@article {pmid40569643,
year = {2025},
author = {Rashidi, A},
title = {Microbiota and chronic GVHD: a plasmablast link.},
journal = {Blood},
volume = {145},
number = {26},
pages = {3073-3075},
doi = {10.1182/blood.2025029521},
pmid = {40569643},
issn = {1528-0020},
}

@article {pmid40569290,
year = {2025},
author = {Biernacki, MA and Lok, J and Foster, KA and Cummings, C and Busch, S and Black, RG and Ray, S and Baquero Galvis, L and Monahan, T and Oh, ST and Oehler, VG and Stirewalt, DL and Wu, D and Deeg, HJ and Doulatov, S and Bleakley, M},
title = {SF3B1K700E neoantigen is a CD8+ T-cell target shared across human myeloid neoplasms.},
journal = {Cancer immunology research},
volume = {},
number = {},
pages = {},
doi = {10.1158/2326-6066.CIR-24-0091},
pmid = {40569290},
issn = {2326-6074},
abstract = {Acquired mutations in spliceosome genes in early hematopoietic stem/progenitor cells are common events in myelodysplastic neoplasms (MDS) and related myeloid malignancies. Mutations in the spliceosome factor subunit B1 (SF3B1) gene occur in ≥20% of MDS cases at conserved hotspots and in early neoplastic clones as driver events. Neoantigens from aberrant SF3B1 proteins could serve as shared T-cell therapy targets for SF3B1-mutated myeloid neoplasms. We identified a candidate neoantigen from the prevalent SF3B1K700E variant using in silico predictions of epitope processing and presentation, then validated presentation and immunogenicity in vitro. CD8+ T cells recognizing SF3B1K700E demonstrated high functional avidity and killed neoplastic myeloid cell lines and primary cells in an antigen-specific manner. We then sequenced, cloned, and transduced a SF3B1K700E-specific T-cell receptor (TCR) into 3rd-party T cells and confirmed that TCR transfer conferred antigen specificity and killing of neoplastic myeloid cells in vitro and in vivo. The data indicate that the SF3B1K700E neoantigen represents a promising T-cell target for patients with SF3B1-mutated MDS and acute myeloid leukemia.},
}

@article {pmid40569102,
year = {2025},
author = {Cheng, GS and Sheshadri, A and Turner, J and Williams, KM and Hsu, JL and Agoritsas, T and Ali, MH and Bondeelle, L and Bouguet, G and Chanez, P and Cooke, KR and Galban, CJ and Goldfarb, S and Hallstrand, TS and Johnson, S and Lam, DCL and Michonneau, D and O'Dwyer, DN and Paczesny, S and Sharifi, H and Todd, JL and Wolff, D and Yadav, H and Yanik, GA and Bergeron, A},
title = {Addressing Knowledge Gaps in the Early Detection of Bronchiolitis Obliterans Syndrome After Hematopoietic Cell Transplantation. An Official American Thoracic Society Research Statement.},
journal = {American journal of respiratory and critical care medicine},
volume = {},
number = {},
pages = {},
doi = {10.1164/rccm.202506-1352ST},
pmid = {40569102},
issn = {1535-4970},
abstract = {BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a late onset noninfectious pulmonary complication of allogeneic hematopoietic cell transplantation (HCT) that is often diagnosed in advanced stage with severe lung impairment. Increasing utilization of HCT for the treatment of hematologic diseases worldwide translates to an increasing burden of BOS, particularly for the community pulmonologist. Early recognition of BOS, which offers the best opportunity to mitigate morbidity and mortality, is hampered by incomplete knowledge of the clinical course and disease process. The goal of this research statement is to survey our current understanding of BOS and to define the research agenda for the early detection of BOS.

METHODS: We convened a multidisciplinary panel that included community representatives for an in-depth survey of the published literature followed by an online workshop.

RESULTS: Major knowledge gaps were identified within interrelated themes of natural history and pathogenesis, risk factors, and the clinical diagnostic approach.

CONCLUSIONS: This statement reflects the detailed assessment of identified knowledge gaps with associated key research questions, as well as a proposed research roadmap to stimulate cross-disciplinary collaborations from pre-clinical to clinical investigations.},
}

@article {pmid40568722,
year = {2025},
author = {Hogan, LE and Bhatla, T and Xu, X and Gore, L and Raetz, EA and Bhojwani, D and Teachey, DT and Hunger, SP and Loh, ML and Brown, PA and Ji, L},
title = {Severe toxicity and poor efficacy of reinduction chemotherapy are associated with overall poor outcomes in relapsed B-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group AALL1331 trial.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2025.287386},
pmid = {40568722},
issn = {1592-8721},
abstract = {Children's Oncology Group AALL1331 utilized an intensive chemotherapy induction (Block 1) based on UK ALLR3 induction for children, adolescents, and young adults with acute lymphoblastic leukemia in first relapse, followed by risk-stratified therapy. High/intermediate risk patients were subsequently randomized to receive 2 blocks of chemotherapy or 2 blocks of blinatumomab followed by hematopoietic stem cell transplant. Low risk patients were randomized to chemotherapy or chemotherapy cycles intercalated with three blinatumomab blocks. Patients who had an early treatment failure were eligible to receive blinatumomab for up to 2 salvage cycles. We reviewed Block 1 responses, risk stratification, randomization rates, adverse events (AE), and event-free survival and overall survival for all enrolled patients. AALL1331 enrolled 661 patients: 24 died during Block 1 and 42 experienced early treatment failure. Overall, 531/661 (80.3%) attained complete remission with 586 risk-assigned and only 471 were randomized. Of 532 patients with marrow involvement, 290 (54.5%) were minimal residual disease positive (≥0.01%) after Block 1. Grade 3/4/5 AE occurred in Block 1 in 44.9, 24.1, and 3.6% patients respectively, with febrile neutropenia, infections, and sepsis most frequent. Notably, 190 enrolled patients (28.7%) did not proceed with post-induction therapy, including 115 (17.4%) risk stratified but not randomized. These patients had dismal survival. More effective and less toxic reinduction strategies are needed for B-ALL in first relapse. Trial Registration Number: NCT02101853.},
}

@article {pmid40568668,
year = {2025},
author = {Mendez, JS and Queme, B and Fu, Y and Morrison, J and Lewinger, JP and Kawaguchi, E and Mi, H and Obón-Santacana, M and Moratalla-Navarro, F and Martín, V and Moreno, V and Lin, Y and Bien, SA and Qu, C and Su, YR and White, E and Harrison, TA and Huyghe, JR and Tangen, CM and Newcomb, PA and Phipps, AI and Thomas, CE and Conti, DV and Wang, J and Platz, EA and Keku, TO and Newton, CC and Um, CY and Kundaje, A and Shcherbina, A and Murphy, N and Gunter, MJ and Dimou, N and Papadimitriou, N and Bézieau, S and van Duijnhoven, FJ and Männistö, S and Rennert, G and Wolk, A and Hoffmeister, M and Brenner, H and Chang-Claude, J and Tian, Y and Le Marchand, L and Cotterchio, M and Tsilidis, KK and Bishop, DT and Melaku, YA and Lynch, BM and Buchanan, DD and Ulrich, CM and Ose, J and Peoples, AR and Pellatt, AJ and Li, L and Devall, MA and Campbell, PT and Albanes, D and Weinstein, SJ and Berndt, SI and Gruber, SB and Ruiz-Narvaez, E and Song, M and Joshi, AD and Drew, DA and Petrick, JL and Chan, AT and Giannakis, M and Hsu, L and Peters, U and Gauderman, WJ and Stern, MC},
title = {Red meat intake interacts with a TGF-β-pathway-based polygenic risk score to impact colorectal cancer risk: Application of a novel approach for polygenic risk score construction.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40568668},
support = {U01 HG004438/HG/NHGRI NIH HHS/United States ; U01 HG004446/HG/NHGRI NIH HHS/United States ; K05 CA154337/CA/NCI NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; U01 CA164930/CA/NCI NIH HHS/United States ; R01 CA066635/CA/NCI NIH HHS/United States ; U01 CA167551/CA/NCI NIH HHS/United States ; R01 CA042182/CA/NCI NIH HHS/United States ; UM1 CA167552/CA/NCI NIH HHS/United States ; U01 CA122839/CA/NCI NIH HHS/United States ; R01 CA059045/CA/NCI NIH HHS/United States ; R01 CA197350/CA/NCI NIH HHS/United States ; R35 CA197735/CA/NCI NIH HHS/United States ; U2C CA252971/CA/NCI NIH HHS/United States ; U10 CA037429/CA/NCI NIH HHS/United States ; U54 CA233465/CA/NCI NIH HHS/United States ; P01 CA087969/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; P30 CA006973/CA/NCI NIH HHS/United States ; Z01 CP010200/ImNIH/Intramural NIH HHS/United States ; P01 CA055075/CA/NCI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; R01 CA151993/CA/NCI NIH HHS/United States ; U01 CA167552/CA/NCI NIH HHS/United States ; R01 CA048998/CA/NCI NIH HHS/United States ; U01 CA137088/CA/NCI NIH HHS/United States ; R01 CA242218/CA/NCI NIH HHS/United States ; R01 CA137178/CA/NCI NIH HHS/United States ; P30 CA014089/CA/NCI NIH HHS/United States ; R01 CA081488/CA/NCI NIH HHS/United States ; R01 CA143237/CA/NCI NIH HHS/United States ; R01 CA201407/CA/NCI NIH HHS/United States ; R01 CA063464/CA/NCI NIH HHS/United States ; P01 CA033619/CA/NCI NIH HHS/United States ; U01 CA086308/CA/NCI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; R01 CA060987/CA/NCI NIH HHS/United States ; R01 CA136726/CA/NCI NIH HHS/United States ; UM1 CA182883/CA/NCI NIH HHS/United States ; R37 CA054281/CA/NCI NIH HHS/United States ; U19 CA148107/CA/NCI NIH HHS/United States ; U01 AG018033/AG/NIA NIH HHS/United States ; },
abstract = {BACKGROUND: High intake of red and/or processed meat are established colorectal cancer (CRC) risk factors. Genome-wide association studies (GWAS) have reported 204 variants (G) associated with CRC risk. We used functional annotation data to identify subsets of variants within known pathways and constructed pathway-based Polygenic Risk Scores (pPRS) to model pPRS x environment (E) interactions.

METHODS: A pooled sample of 30,812 cases and 40,504 CRC controls of European ancestry from 27 studies were analyzed. Quantiles for red and processed meat intake were constructed. The 204 GWAS variants were annotated to genes with AnnoQ and assessed for overrepresentation in PANTHER-reported pathways. pPRS's were constructed from significantly overrepresented pathways. Covariate-adjusted logistic regression models evaluated pPRSxE interactions with red or processed meat intake in relation to CRC risk.

RESULTS: A total of 30 variants were overrepresented in four pathways: Alzheimer disease-presenilin, Cadherin/WNT-signaling, Gonadotropin-releasing hormone receptor, and TGF-β signaling. We found a significant interaction between TGF-β-pPRS and red meat intake (p = 0.003). When variants in the TGF-β pathway were assessed, significant interactions with red meat for rs2337113 (intron SMAD7 gene, Chr18), and rs2208603 (intergenic region BMP5, Chr6) (p = 0.013 & 0.011, respectively) were observed. We did not find evidence of pPRS x red meat interactions for other pathways or with processed meat.

CONCLUSIONS: This pathway-based interaction analysis revealed a significant interaction between variants in the TGF-β pathway and red meat consumption that impacts CRC risk.

IMPACT: These findings shed light into the possible mechanistic link between CRC risk and red meat consumption.},
}

@article {pmid40564099,
year = {2025},
author = {Wang, H and Wang, C and Qin, R and He, J and Zhang, X and Ma, C and Li, S and Fan, L and Wang, L and Cao, L},
title = {Integrative Analysis of Plasma Proteomics and Transcriptomics Reveals Potential Therapeutic Targets for Psoriasis.},
journal = {Biomedicines},
volume = {13},
number = {6},
pages = {},
pmid = {40564099},
issn = {2227-9059},
support = {82304250//National Natural Science Foundation of China/ ; 82273734//National Natural Science Foundation of China/ ; YQ2022H005//Heilongjiang Province Natural Science Foundation/ ; },
abstract = {Background Psoriasis (PsO): is an immune-mediated inflammatory disease that imposes a significant burden on patients. Many patients experience relapse or inadequate responses, and PsO subtypes also lack effective therapies, highlighting the need for new therapeutic targets. Methods: We performed a proteome-wide Mendelian randomization (MR) to explore potential therapeutic targets for PsO. Protein quantitative trait loci (pQTLs) data were obtained from the Pharma Proteomics Project (54,219 UK Biobank participants, 2923 proteins), and PsO phenotype and subtype data were sourced from FinnGen (10,312 cases; 397,564 controls) for discovery. Replication MR utilized integrated protein data (Iceland and Norfolk) and phenotype data from multiple databases (UK Biobank and GWAS Catalog). Reverse MR and colocalization were used to support causal relationships. Single-cell RNA-seq analysis revealed distinct expression patterns of protein-coding genes across different cell types in PsO biopsy samples and normal skin tissues. Protein-protein interactions (PPI) and molecular docking were used to evaluate druggability. Results: MR analysis identified 13 proteins significantly associated with PsO risk (p < 2.56×10-5), including 10 proteins associated with PsO subtypes. Decreased levels of eight proteins (IFNLR1, APOF, TDRKH, DDR1, HLA-E, LTA, MOG, and ICAM3) and increased levels of five proteins (IFNGR2, HCG22, IL12B, BTN3A2, and TRIM40) showed protective effects against PsO progression. Robust colocalization (PPH4 > 0.9) identified IFNLR1, IFNGR2, APOF, and TDRKH as top candidates. Single-cell RNA sequencing analysis revealed that IFNLR1, IFNGR2, LTA, TDRKH, and DDR1 were specifically expressed in T cells of psoriatic biopsy specimens compared to healthy controls. Molecular docking indicated the druggability of IFNLR1 and IFNGR2. Conclusions: We identified several potential therapeutic targets for PsO, with IFNLR1, IFNGR2, APOF, and TDRKH emerging as promising candidates, particularly IFNLR1 and IFNGR2, which are associated with the IFN family. These findings may provide new perspectives on PsO therapy and pathogenesis.},
}

@article {pmid40562770,
year = {2025},
author = {Dima, D and Vazquez-Martinez, MA and Davis, JA and Goel, U and Afrough, A and Sannareddy, A and Pasvolsky, O and Razzo, B and Banerjee, R and Khouri, J and Grajales-Cruz, A and Lieberman-Cribbin, A and Rana, MS and Julian, K and DeJarnette, S and Portuguese, AJ and Gaballa, MR and De Avila, G and Susaniba Adaniya, S and Raza, S and Herr, MM and Ouchveridze, E and Richards, T and Hosoya, H and Mikkilineni, L and Kaur, G and Castaneda Puglianini, O and Rossi, A and Lin, Y and Atrash, S and Sborov, D and Shain, KH and Voorhees, PM and Richard, S and Garfall, AL and Hansen, DK and Sidana, S and Patel, KK and Cowan, AJ and Anderson, LD and Lee, HC and Anwer, F and Ferreri, CJ and Shune, L},
title = {Outcomes of teclistamab in patients with relapsed/refractory multiple myeloma with prior exposure to BCMA-directed therapy: a multicenter study from the U.S. Multiple Myeloma Immunotherapy Consortium.},
journal = {Blood cancer journal},
volume = {15},
number = {1},
pages = {111},
pmid = {40562770},
issn = {2044-5385},
mesh = {Humans ; *Multiple Myeloma/drug therapy/mortality/pathology ; Male ; Female ; Middle Aged ; Aged ; *B-Cell Maturation Antigen/antagonists & inhibitors ; Retrospective Studies ; Adult ; Aged, 80 and over ; Treatment Outcome ; United States ; *Antineoplastic Agents, Immunological/therapeutic use/adverse effects ; },
abstract = {Data describing outcomes of teclistamab in multiple myeloma patients with prior exposure to BCMA-directed therapy (BCMA-DT) are limited. The goal of this multicenter retrospective analysis was to report the efficacy and safety of standard-of-care teclistamab in patients with prior BCMA-DT. A total of 385 patients were included, of whom 193 (50%) had received prior BCMA-DT, including 47 (24%) patients with prior antibody-drug conjugate (ADC)-only, 99 (51%) with chimeric antigen receptor T-cell therapy (CAR T)-only, 36 (19%) with both ADC and CAR T, 6 (3%) with bispecific antibody-only, and 5 (3%) with other combinations. Most safety parameters between cohorts were comparable. The prior BCMA-DT cohort had a lower overall response rate (ORR: 48.7% versus 61.5%; p = 0.012), and median progression-free survival (PFS: 4.6 versus 8.2 months; p = 0.017) compared to the cohort without prior BCMA-DT. However, in multivariable analysis, despite a clear trend, ultimately receipt of a prior BCMA-DT was not independently associated with ORR or PFS (p = 0.057 and p = 0.1, respectively). No significant differences in PFS were noted when stratifying patients by number of prior BCMA-DTs, types of all prior BCMA-DTs received, type of most recent prior BCMA-DT, or depth of response to most recent BCMA-DT. Using the maximally selected rank statistics method, the optimal cut-off for time from the last BCMA-DT exposure to teclistamab initiation was identified as 8.7 months. Patients with >8.7 months between their last exposure to prior BCMA-DT and teclistamab initiation had a significantly improved median PFS with teclistamab (8.1 months, 95% CI: 4.6-11.7) compared to patients with <8.7 months (2.5 months, 95% CI: 1.1-5.7), p = 0.001. Altogether, our findings support the use of teclistamab as a viable treatment option in patients previously exposed to BCMA-DT.},
}

Humans
*Multiple Myeloma/drug therapy/mortality/pathology
Male
Female
Middle Aged
Aged
*B-Cell Maturation Antigen/antagonists & inhibitors
Retrospective Studies
Adult
Aged, 80 and over
Treatment Outcome
United States
*Antineoplastic Agents, Immunological/therapeutic use/adverse effects

@article {pmid40562030,
year = {2025},
author = {Banerjee, R and Yamshon, S},
title = {Double trouble: Non-relapse mortality with bispecific antibodies in lymphoma and myeloma.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {33},
number = {7},
pages = {2966-2967},
doi = {10.1016/j.ymthe.2025.06.014},
pmid = {40562030},
issn = {1525-0024},
}

@article {pmid40561681,
year = {2025},
author = {Coleman, RL and Fleming, GF and Brady, MF and Swisher, EM and Steffensen, KD and Friedlander, M and Okamoto, A and Moore, KN and Leath, CA and Cella, D and Sun, Z and Patel, S and Tang, Z and Ratajczak, CK and Aghajanian, C and Bookman, MA},
title = {Veliparib concomitant with first-line chemotherapy and as maintenance therapy in ovarian cancer: Final overall survival and disease-related symptoms results.},
journal = {European journal of cancer (Oxford, England : 1990)},
volume = {225},
number = {},
pages = {115587},
doi = {10.1016/j.ejca.2025.115587},
pmid = {40561681},
issn = {1879-0852},
abstract = {INTRODUCTION: In the VELIA trial, the addition of veliparib to standard first-line platinum-based chemotherapy and continued as maintenance resulted in significantly longer median progression-free survival (PFS) compared with carboplatin plus paclitaxel induction therapy alone (23.5 vs 17.3 months; p < 0.001) in patients with ovarian cancer. We now report final overall survival (OS) and updated safety and disease-related symptoms (DRS) from patient-reported outcomes of the trial.

METHODS: This randomized, placebo-controlled, double-blind, multicenter, phase 3 study enrolled adult women with an initial diagnosis of stage III/IV high-grade serous ovarian cancer undergoing primary or interval cytoreductive surgery. Patients were randomized 1:1:1 to chemotherapy plus veliparib followed by veliparib maintenance (veliparib-throughout), chemotherapy plus veliparib followed by placebo maintenance (veliparib-combination-only), or chemotherapy plus placebo followed by placebo maintenance (placebo-throughout). PFS was the primary endpoint; OS and DRS were secondary endpoints.

RESULTS: In the intention-to-treat population (N = 1140), median OS was 59.2 months (95 % confidence interval: 52.1, 68.2) for the veliparib-throughout group, 58.0 (50.6, 64.1) months for veliparib-combination-only, and 57.8 (52.3, 63.8) months for placebo-throughout. OS outcomes were not significantly different between arms overall or in the BRCA-deficient and homologous recombination-deficient cohorts. No new safety signals were identified during the longer follow-up period and DRS analyses indicated there was no significant additional symptom-related burden overall when veliparib was added to chemotherapy or used for maintenance.

CONCLUSION: No OS or DRS benefit of addition of veliparib to platinum-based chemotherapy and continued as maintenance therapy was detected in this study, despite an observed benefit over chemotherapy alone in PFS.},
}

@article {pmid40561385,
year = {2025},
author = {Zeiser, R and Russo, D and Ram, R and Hashmi, SK and Chakraverty, R and Middeke, JM and Musso, M and Giebel, S and Uzay, A and Langmuir, P and Hamad, N and Burock, K and Gowda, M and Stefanelli, T and Lee, SJ and Teshima, T and Locatelli, F},
title = {Ruxolitinib in Patients With Corticosteroid-Refractory or Corticosteroid-Dependent Chronic Graft-Versus-Host Disease: 3-Year Final Analysis of the Phase III REACH3 Study.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2402477},
doi = {10.1200/JCO-24-02477},
pmid = {40561385},
issn = {1527-7755},
abstract = {In REACH3 (ClinicalTrials.gov identifier: NCT03112603), ruxolitinib was investigated versus best available therapy (BAT) for 3 years in patients with steroid-refractory/dependent chronic graft-versus-host-disease (SR/D-cGVHD). Patients received ruxolitinib (10 mg twice daily) or BAT for 24 weeks; thereafter (weeks 24-156), patients continued randomized treatment, entered long-term survival follow-up, or crossed over from BAT to ruxolitinib. In 329 randomly assigned patients (ruxolitinib: 165; BAT: 164), the median failure-free survival (FFS) was 38.4 months for ruxolitinib versus 5.7 months for BAT (hazard ratio, 0.36 [95% CI, 0.27 to 0.49]). Median duration of response (DOR) was not reached for ruxolitinib versus 6.4 months for BAT. Ruxolitinib-treated patients had a higher probability of FFS (ruxolitinib: 56.5%; BAT: 18.2%) and maintaining a response (ruxolitinib: 59.6%; BAT: 26.7%) at 36 months. Median overall survival was not reached. Nonrelapse mortality and malignancy relapse/recurrence events were low. In 70 patients who crossed over to ruxolitinib, the overall response rate (50.0%) at week 24 and best overall response (81.4%) during the crossover period were consistent with the primary analysis of randomly assigned patients. No new safety signals were observed. Ruxolitinib provided longer FFS and DOR than BAT, demonstrating sustained efficacy and manageable safety over 3 years of follow-up in patients with SR/D-cGVHD.},
}

@article {pmid40561376,
year = {2025},
author = {Bardia, A and Rugo, HS and Sedrak, MS and Loibl, S and Tolaney, SM and Punie, K and Hurvitz, SA and Kalinsky, KM and Cortés, J and O'Shaughnessy, JA and Dieras, V and Piccart-Gebhart, MJ and Dasgupta, A and Kaushik, A and Lai, C and Shi, L and Brufsky, A},
title = {Q-TWiST Analysis to Assess Benefit-Risk of Sacituzumab Govitecan in Previously Treated Patients With Metastatic Triple-Negative Breast Cancer.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2400806},
doi = {10.1200/OP-24-00806},
pmid = {40561376},
issn = {2688-1535},
abstract = {PURPOSE: In ASCENT, sacituzumab govitecan (SG) showed significantly longer overall survival and progression-free survival than chemotherapy of physician's choice with similar rates of treatment-emergent adverse events (TEAEs) in previously treated patients with metastatic triple-negative breast cancer (mTNBC). We assessed the benefit-risk of SG versus chemotherapy by integrating patient preferences (health utilities) with clinical benefits in this analysis.

METHODS: Quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment (Q-TWiST) methodology was used to compare treatments where survival was partitioned into three health states using the intention-to-treat ASCENT population: (1) toxicity (grade ≥3 TEAE after random assignment and before disease progression), (2) TWiST (progression-free period without grade ≥3 TEAE), and (3) relapse (disease progression until death or end of follow-up, whichever came first). Health state utilities were derived from published literature. Q-TWiST was calculated as utility-weighted sum of mean health state durations. The established threshold for relative Q-TWiST improvement considered clinically important is 10% and clearly clinically important is 15%.

RESULTS: SG had significantly longer Q-TWiST (8.3 months; 95% CI, 7.6 to 9.1 months) than chemotherapy (4.8 months; 95% CI, 4.3 to 5.4 months) in patients with mTNBC, a difference of 3.5 months (95% CI, 2.6 to 4.4 months; P < .0001). Relative Q-TWiST improvement with SG was 39.5%, exceeding the clearly clinically important threshold. Q-TWiST benefits of SG over chemotherapy increased over the available 31-month follow-up. Restricted mean time with toxicity was numerically higher with SG versus chemotherapy; this difference stabilized with longer follow-up.

CONCLUSION: The Q-TWiST analysis supports a positive benefit-risk ratio for SG versus chemotherapy in patients with previously treated mTNBC. Net benefits of SG continued to accrue over time.},
}