@article {pmid40152978,
year = {2025},
author = {Orenduff, MC and Pieper, CF and Allott, EH and Coleman, MF and Jung, SY and Vitolins, MZ and Fenton, JI and Chen, C and Kroenke, CH and Tabung, FK and Barac, A and Paskett, ED and Pollak, MN and Hays-Grudo, J and Chang, S and Hursting, SD},
title = {Plasma Insulin-Like Growth Factor Binding Protein-7 is Positively Associated with Age, Obesity, Mortality, and Cancer in Postmenopausal Women.},
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-24-1644},
pmid = {40152978},
issn = {1538-7755},
abstract = {BACKGROUND: Predictors of premature death and cancer development are needed to more precisely identify individuals who may warrant preventive intervention. Circulating IGF binding protein-7 (IGFBP7) and, to lesser extent, the IGFBP7/IGF-1 ratio are emerging biomarkers of renal and cardiovascular morbidity. However, their relationships with aging, obesity, mortality and cancer risk remain unclear.

METHODS: This hypothesis-generating study investigated plasma IGFBP7, IGF-1, and their ratio as predictors of all-cause mortality, any cancer (excluding nonmelanoma skin cancer), obesity-related cancer (composite of 13 cancer types), and breast cancer incidence in a large longitudinal cohort of postmenopausal women. We assessed relationships of each biomarker with age, body mass index (BMI), and each outcome (bivariately and controlling for age, BMI, race, physical activity, education, income, marital status, alcohol intake, smoking, diabetes, and hormone therapy) in 793 Women's Health Initiative-Observational Study participants (mean 19.4 year follow-up).

RESULTS: In adjusted analyses, IGFBP7 increased with age and obesity, and was positively associated with risks of all-cause mortality [hazard ratio (HR)=2.42 (95% CI: 1.37-4.26), p=0.002], any cancer [HR=2.04 (1.05-3.94), p=0.035], and obesity-related cancer [HR=1.58 (0.99-2.51), p=0.053]. Also in adjusted analyses, the IGFBP7/IGF-1 ratio increased with age and was positively associated with all-cause mortality [HR=1.51 (1.14-1.99), p=0.004] and any cancer incidence [HR=5.44 (1.13-26.1), p=0.034].

CONCLUSIONS: Plasma IGFBP7 and the IGFBP7/IGF1 ratio are positively associated with age, obesity (IGFBP7 only), mortality, and cancer in postmenopausal women.

IMPACT: Plasma IGFBP7 may represent an age- and obesity-sensitive biomarker of increased risk of developing cancer and/or dying prematurely.},
}

@article {pmid40151933,
year = {2025},
author = {Wang, X and Singh, P and Cejas, RB and Zhou, L and Sharafeldin, N and Trainor, PJ and Landier, W and Cheng, C and Hageman, L and Wang, F and Sapkota, Y and Yasui, Y and Hudson, MM and Chow, EJ and Armenian, SH and Neglia, JP and Hawkins, DS and Ginsberg, JP and Burridge, PW and Armstrong, GT and Bhatia, S},
title = {DNA Damage Response and Repair Genes and Anthracycline-Induced Cardiomyopathy in Childhood Cancer Survivors: A Report From the Children's Oncology Group and the Childhood Cancer Survivor Study.},
journal = {Circulation. Genomic and precision medicine},
volume = {},
number = {},
pages = {e004813},
doi = {10.1161/CIRCGEN.124.004813},
pmid = {40151933},
issn = {2574-8300},
abstract = {BACKGROUND: Anthracyclines induce cardiotoxicity via DNA double-strand breaks and reactive oxygen species formation, resulting in cardiomyocyte dysfunction. The role of DNA damage response/repair (DDR) genes in anthracycline-induced cardiomyopathy remains unstudied.

METHODS: We conducted a gene-based and pathway-based analysis to examine the main effect and gene-anthracycline interaction effect between DDR genes and anthracycline-induced cardiomyopathy. A discovery analysis performed with a matched case-control set of anthracycline-exposed non-Hispanic White childhood cancer survivors from Children's Oncology Group-ALTE03N1 (113 cases; 226 controls) was replicated using a cohort of anthracycline-exposed non-Hispanic White childhood cancer survivors from the Childhood Cancer Survivor Study cohort (n=1658; 97 cases). Functional analyses were performed by examining the response to doxorubicin of human-induced pluripotent stem cell-derived cardiomyocytes with CRISPR/Cas9-mediated knockout of prioritized genes.

RESULTS: Successfully replicated DDR genes demonstrating main-effect association included FANCC (P=0.037) and XRCC5 (P=0.001) and demonstrated gene-anthracycline interaction included MGMT (P=0.041). Knockouts of FANCC and MGMT in human-induced pluripotent stem cell-derived cardiomyocytes demonstrated significant resistance to doxorubicin, suggesting that these genes play a role in anthracycline-induced cardiotoxicity. Successfully replicated DDR pathways demonstrating main-effect association included base excision repair (P=2.7×10[-4]); role of BRCA1 in DDR (P=9.2×10[-5]); p53 signaling (P<1×10[-16]); role of checkpoint kinases proteins in cell cycle checkpoint control (P<1×10[-16]); mismatch repair (P<10[-16]); and double-strand break repair by homologous recombination (P<1×10[-16]). Successfully replicated DDR pathways demonstrating significant interaction effects included role of BRCA1 in DDR (P=1.4×10[-4]); p53 signaling (P<1×10[-16]); the role of checkpoint kinases proteins in cell cycle checkpoint control (P<1×10[-16]); mismatch repair (P<1×10[-16]); cell cycle: G2/M DNA damage checkpoint regulation (P=0.002); double-strand break repair by homologous recombination (P=0.009); GADD45 signaling (P=4.8×10[-4]); and cell cycle control of chromosomal replication (P=4.5×10[-4]).

CONCLUSIONS: These findings provide evidence for the role of DDR genes and pathways in anthracycline-induced cardiomyopathy and provide a framework for targeted therapeutic interventions.},
}

@article {pmid40147465,
year = {2025},
author = {Luetkemeyer, AF and Donnell, D and Cohen, SE and Dombrowski, JC and Grabow, C and Haser, G and Brown, C and Cannon, C and Malinski, C and Perkins, R and Nasser, M and Lopez, C and Suchland, RJ and Vittinghoff, E and Buchbinder, SP and Scott, H and Charlebois, ED and Havlir, DV and Soge, OO and Celum, C},
title = {Doxycycline to prevent bacterial sexually transmitted infections in the USA: final results from the DoxyPEP multicentre, open-label, randomised controlled trial and open-label extension.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(25)00085-4},
pmid = {40147465},
issn = {1474-4457},
abstract = {BACKGROUND: Doxycycline post-exposure prophylaxis (doxy-PEP) is a promising intervention to reduce bacterial sexually transmitted infections (STIs). We evaluated the effect of doxy-PEP on STI incidence and antimicrobial resistance in men who have sex with men and transgender women for up to 12 months of follow-up, inlcuding an open-label extension.

METHODS: DoxyPEP, an open-label trial in Seattle (WA, USA) and San Francisco (CA, USA) among men who have sex with men and transgender women with at least one bacterial STI in the past year, randomly assigned participants by clinic (with computer-generated variable block sizes) 2:1 to doxy-PEP (200 mg doxycycline delayed-release tablets 24-72 h after condomless sex) or standard care. The independent endpoint adjudication committee was masked to group assignment. The primary outcome was presence of one or more bacterial STIs (Neisseria gonorrhoeae, Chlamydia trachomatis, or early syphilis) each quarter. This outcome was assessed in the modified intention-to-treat cohort, which included participants with at least one follow-up quarter (ie, ∼3 months) in their as-randomised assignment. After early termination of the randomised phase for efficacy, all participants still enrolled were offered doxy-PEP in an open-label extension (OLE). We report quarterly incidence of bacterial STIs for the as-randomised and OLE periods. Safety was assessed in all participants with any follow-up data. The trial was registered with ClinicalTrials.gov (NCT03980223) and is completed.

FINDINGS: From Aug 19, 2020, to May 13, 2022, we enrolled 637 participants; 592 participants completed at least one follow-up quarter in the randomised phase (411 in the doxy-PEP group and 181 in the standard-care group) and 282 in the OLE phase (207 in the doxy-PEP group and 82 in the standard-care group). STIs were present in 129 (12·0%) of 1077 quarters in the doxy-PEP group versus 139 (30·5%) of 455 quarters in the standard-care group during the as-randomised period, showing an absolute difference of 19 percentage points and a relative risk of 0·39 (95% CI 0·31-0·49, p<0·0001). During the OLE, STIs were diagnosed in 51 (13%) of 388 quarters among those continuing doxy-PEP and 25 (17%) of 145 quarters among standard-care participants who initiated doxy-PEP. Throughout all quarters for participants on doxy-PEP, there was one grade 2 laboratory abnormality and five grade 3 adverse events that were possibly or probably related to doxy-PEP. No serious adverse events were attributed by site investigators to doxycycline. Of participants with positive gonorrhoea cultures during the study, eight (27%) of 29 taking doxy-PEP versus five (24%) of 21 not taking doxy-PEP had tetracycline resistance (minimum inhibitory concentration ≥2 μg/mL).

INTERPRETATION: Doxy-PEP was effective in reducing bacterial STIs in this population of men who have sex with men and transgender women, including during an open-label extension when doxy-PEP efficacy was known. Doxy-PEP was well tolerated, highly acceptable, and with no new safety signals.

FUNDING: US National Institutes of Health.},
}

@article {pmid40147439,
year = {2025},
author = {Dubocanin, D and Hartley, GA and Sedeño Cortés, AE and Mao, Y and Hedouin, S and Ranchalis, J and Agarwal, A and Logsdon, GA and Munson, KM and Real, T and Mallory, BJ and Eichler, EE and Biggins, S and O'Neill, RJ and Stergachis, AB},
title = {Conservation of dichromatin organization along regional centromeres.},
journal = {Cell genomics},
volume = {},
number = {},
pages = {100819},
doi = {10.1016/j.xgen.2025.100819},
pmid = {40147439},
issn = {2666-979X},
abstract = {The attachment of the kinetochore to the centromere is essential for genome maintenance, yet the highly repetitive nature of satellite regional centromeres limits our understanding of their chromatin organization. We demonstrate that single-molecule chromatin fiber sequencing (Fiber-seq) can uniquely co-resolve kinetochore and surrounding chromatin architectures along point centromeres, revealing largely homogeneous single-molecule kinetochore occupancy. In contrast, the application of Fiber-seq to regional centromeres exposed marked per-molecule heterogeneity in their chromatin organization. Regional centromere cores uniquely contain a dichotomous chromatin organization (dichromatin) composed of compacted nucleosome arrays punctuated with highly accessible chromatin patches. CENP-B occupancy phases dichromatin to the underlying alpha-satellite repeat within centromere cores but is not necessary for dichromatin formation. Centromere core dichromatin is conserved between humans and primates, including along regional centromeres lacking satellite repeats. Overall, the chromatin organization of regional centromeres is defined by marked per-molecule heterogeneity, buffering kinetochore attachment against sequence and structural variability within regional centromeres.},
}

@article {pmid40146127,
year = {2025},
author = {Lee, CI and Lowry, KP},
title = {Identifying Who Is at Risk of Interval Breast Cancers.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaoncol.2025.0101},
pmid = {40146127},
issn = {2374-2445},
}

@article {pmid40146038,
year = {2025},
author = {Unger, JM and McAneny, BL and Osarogiagbon, RU},
title = {Cancer in rural America: Improving access to clinical trials and quality of oncologic care.},
journal = {CA: a cancer journal for clinicians},
volume = {},
number = {},
pages = {},
doi = {10.3322/caac.70006},
pmid = {40146038},
issn = {1542-4863},
support = {UG1CA189974//National Institutes of Health, National Cancer Institute/ ; 5U10CA180819//National Institutes of Health, National Cancer Institute/ ; },
abstract = {Individuals from rural areas in the United States suffer higher rates of morbidity and mortality from cancer than their urban counterparts. This review is based on the idea that equity-the elimination of unnecessary and preventable differences between groups of individuals-should underlie access to cancer care resources for patients from rural areas. Access to cancer clinical trials serves as the framework for identifying and understanding barriers in access to quality oncologic care. The authors discuss the interplay between rural living, socioeconomic status, culture, and health; and they highlight how economic considerations in rural areas often limit access to clinical trials and oncologic care because economies of scale do not apply in these regions given the requirement for high-quality oncology care even with lower patient volumes. The authors propose solutions to enhance access to clinical trials and improve the quality of oncologic care in rural areas, viewing these aims as ethical and moral imperatives.},
}

@article {pmid40141440,
year = {2025},
author = {Germain, A and Jaycox, JR and Emig, CJ and Ring, AM and Hanson, MR},
title = {An In-Depth Exploration of the Autoantibody Immune Profile in ME/CFS Using Novel Antigen Profiling Techniques.},
journal = {International journal of molecular sciences},
volume = {26},
number = {6},
pages = {},
pmid = {40141440},
issn = {1422-0067},
support = {U54NS105541/GF/NIH HHS/United States ; U54AI178855/GF/NIH HHS/United States ; UL1 TR 002384/GF/NIH HHS/United States ; 3P30CA016359-40S4//Yale Cancer Center Support/ ; DP5OD023088/GF/NIH HHS/United States ; T32GM007205//Yale Medical Scientist Training Program/ ; },
mesh = {Humans ; *Autoantibodies/immunology ; Female ; Male ; *Fatigue Syndrome, Chronic/immunology ; Middle Aged ; Adult ; Autoantigens/immunology ; },
abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder characterized by serious physical and cognitive impairments. Recent research underscores the role of immune dysfunction, including the role of autoantibodies, in ME/CFS pathophysiology. Expanding on previous studies, we analyzed 7542 antibody-antigen interactions in ME/CFS patients using two advanced platforms: a 1134 autoantibody Luminex panel from Oncimmune and Augmenta Bioworks, along with Rapid Extracellular Antigen Profiling (REAP), a validated high-throughput method that measures autoantibody reactivity against 6183 extracellular human proteins and 225 human viral pathogen proteins. Unlike earlier reports, our analysis of 172 participants revealed no significant differences in autoantibody reactivities between ME/CFS patients and controls, including against GPCRs such as β-adrenergic receptors. However, subtle trends in autoantibody ratios between male and female ME/CFS subgroups, along with patterns of herpesvirus reactivation, suggest the need for broader and more detailed exploration.},
}

Humans
*Autoantibodies/immunology
Female
Male
*Fatigue Syndrome, Chronic/immunology
Middle Aged
Adult
Autoantigens/immunology

@article {pmid40140386,
year = {2025},
author = {Beddows, I and Djirackor, S and Omran, DK and Jung, E and Shih, NN and Roy, R and Hechmer, A and Olshen, A and Adelmant, G and Tom, A and Morrison, J and Adams, M and Rohrer, DC and Schwartz, LE and Pearce, CL and Auman, H and Marto, JA and Drescher, CW and Drapkin, R and Shen, H},
title = {Impact of BRCA mutations, age, surgical indication, and hormone status on the molecular phenotype of the human Fallopian tube.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {2981},
pmid = {40140386},
issn = {2041-1723},
mesh = {Humans ; Female ; *Fallopian Tubes/metabolism/pathology ; *BRCA2 Protein/genetics/metabolism ; *BRCA1 Protein/genetics/metabolism ; Middle Aged ; Adult ; Aged ; Ovarian Neoplasms/genetics/metabolism ; Epigenesis, Genetic ; Germ-Line Mutation ; Fallopian Tube Neoplasms/genetics/metabolism/pathology ; Phenotype ; Mutation ; Age Factors ; Whole Genome Sequencing ; Proteomics/methods ; Heterozygote ; Pregnancy ; },
abstract = {The human Fallopian tube (FT) is an important organ in the female reproductive system and has been implicated as a site of origin for pelvic serous cancers, including high-grade serous tubo-ovarian carcinoma (HGSC). We have generated comprehensive whole-genome bisulfite sequencing, RNA-seq, and proteomic data of over 100 human FTs, with detailed clinical covariate annotations. Our results challenge existing paradigms that extensive epigenetic, transcriptomic and proteomic alterations exist in the FTs from women carrying heterozygous germline BRCA1/2 pathogenic variants. We find minimal differences between BRCA1/2 carriers and non-carriers prior to loss of heterozygosity. Covariates such as age and surgical indication can confound BRCA1/2-related differences reported in the literature, mainly through their impact on cell composition. We systematically document and highlight the degree of variations across normal human FT, defining five groups capturing major cellular and molecular changes across various reproductive stages, pregnancy, and aging. We are able to associate gene, protein, and epigenetic changes with these and other clinical covariates, but not heterozygous BRCA1/2 mutation status. This sheds new light into prevention and early detection of tumorigenesis in populations at high-risk for ovarian cancer.},
}

Humans
Female
*Fallopian Tubes/metabolism/pathology
*BRCA2 Protein/genetics/metabolism
*BRCA1 Protein/genetics/metabolism
Middle Aged
Adult
Aged
Ovarian Neoplasms/genetics/metabolism
Epigenesis, Genetic
Germ-Line Mutation
Fallopian Tube Neoplasms/genetics/metabolism/pathology
Phenotype
Mutation
Age Factors
Whole Genome Sequencing
Proteomics/methods
Heterozygote
Pregnancy

@article {pmid40139185,
year = {2025},
author = {Tenthorey, JL and Del Banco, S and Ramzan, I and Klingenberg, H and Liu, C and Emerman, M and Malik, HS},
title = {Indels allow antiviral proteins to evolve functional novelty inaccessible by missense mutations.},
journal = {Cell genomics},
volume = {},
number = {},
pages = {100818},
doi = {10.1016/j.xgen.2025.100818},
pmid = {40139185},
issn = {2666-979X},
abstract = {Antiviral proteins often evolve rapidly at virus-binding interfaces to defend against new viruses. We investigated whether antiviral adaptation via missense mutations might face limits, which insertion or deletion mutations (indels) could overcome. Using high-throughput saturation missense mutagenesis, we identify one such case of a nearly insurmountable evolutionary challenge: the human anti-retroviral protein TRIM5α requires more than five missense mutations in its specificity-determining v1 loop to restrict a divergent simian immunodeficiency virus (SIV). However, through a novel saturating indel scanning methodology, we find that duplicating just one amino acid in v1 enables human TRIM5α to potently restrict SIV in a single evolutionary step. Moreover, natural primate TRIM5α v1 loops have evolved indels that confer novel antiviral specificities. Thus, indels enable antiviral proteins to overcome viral challenges otherwise inaccessible by missense mutations. Our findings reveal the potential of often-overlooked indel mutations in driving protein innovation.},
}

@article {pmid40138611,
year = {2025},
author = {Aggarwal, RR and Vuky, J and VanderWeele, D and Rettig, M and Heath, EI and Quigley, D and Huang, J and Chumber, A and Cheung, A and Foye, A and Leung, S and Abbey, J and Dorr, A and Nasoff, M and Hunter, J and Wang, S and Flavell, RR and Fong, L and Liu, B and Small, EJ},
title = {Phase I, First-in-Human Study of FOR46 (FG-3246), an Immune-Modulating Antibody-Drug Conjugate Targeting CD46, in Patients With Metastatic Castration-Resistant Prostate Cancer.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2401989},
doi = {10.1200/JCO-24-01989},
pmid = {40138611},
issn = {1527-7755},
abstract = {PURPOSE: FOR46, a fully human antibody conjugated to monomethyl auristatin E, targets a tumor-selective epitope of CD46, which is overexpressed in metastatic castration-resistant prostate cancer (mCRPC). FOR46 demonstrates potent nonclinical activity in enzalutamide-resistant CRPC models.

PATIENTS AND METHODS: This was a phase I, first-in-human, dose escalation/expansion study in patients with progressive mCRPC after treatment with ≥one androgen signaling inhibitors (ClinicalTrials.gov identifier: NCT03575819). The starting dose of FOR46 was 0.1 mg/kg given intravenously every 3 weeks. The primary objective was to determine the maximally tolerated dose (MTD). Whole-blood mass cytometry (cytometry by time of flight) was used to characterize peripheral immune response and CD46 expression in CRPC tissue that underwent central pathology review.

RESULTS: Fifty-six patients were enrolled. Dose-limiting toxicities included neutropenia (n = 4), febrile neutropenia (n = 1), and fatigue (n = 1). The MTD was 2.7 mg/kg using adjusted body weight. The most common grade ≥3 adverse events across all dose levels were neutropenia (59%), leukopenia (27%), lymphopenia (7%), anemia (7%), and fatigue (5%). One grade 3 febrile neutropenia event was observed. There were no treatment-related deaths. In the efficacy evaluable subset (patients with adenocarcinoma treated with a starting dose ≥1.2 mg/kg, n = 40), the median radiographic progression-free survival was 8.7 months (range, 0.1-33.9). Fourteen of 39 evaluable patients (36%) achieved a PSA50 response. The confirmed objective response rate was 20% (5 of 25 RECIST-evaluable patients). The median duration of response was 7.5 months. Responders had a significantly higher on-treatment frequency of circulating effector CD8[+] T cells.

CONCLUSION: FOR46 demonstrated encouraging preliminary clinical activity with a manageable safety profile. Targeting CD46 elicited an immune priming effect that was associated with clinical outcomes.},
}

@article {pmid40138497,
year = {2025},
author = {Jana, S and Glabman, RA and Koehne, AL},
title = {Bridging the gap between histopathology and genomics: Spotlighting spatial omics.},
journal = {Veterinary pathology},
volume = {},
number = {},
pages = {3009858251322729},
doi = {10.1177/03009858251322729},
pmid = {40138497},
issn = {1544-2217},
abstract = {Spatial biology has emerged as a transformative field, offering insights into cellular interactions and organization within tissues. The field has evolved rapidly since the coining of the term "spatial omics." Now, the ability to spatially resolve proteins, RNA, chromatin, and lipids is becoming widespread, and the technologies are continually refined. Reagents to support the analysis of veterinary species are available and more are emerging. These new tools will allow pathologists and scientists to unravel the intricate interplay between tissue architecture and diverse cellular phenotypes. By integrating histological observations with spatially resolved genomic data, spatial biology holds immense potential for advancing diagnostic and therapeutic strategies in veterinary medicine. These tools will undoubtedly equip veterinary pathologists to better decipher complex disease processes and identify novel therapeutic targets.},
}

@article {pmid40138454,
year = {2025},
author = {Hart, TM and Cui, Y and Telford, SR and Marín-López, A and Calloway, K and Dai, Y and Matias, J and DePonte, K and Jaycox, J and DeBlasio, M and Hoornstra, D and Belperron, AA and Cibichakravarthy, B and Johnson, EE and Alameh, MG and Dwivedi, G and Hovius, JWR and Bockenstedt, LK and Weissman, D and Ring, AM and Fikrig, E},
title = {Tick feeding or vaccination with tick antigens elicits immunity to the Ixodes scapularis exoproteome in guinea pigs and humans.},
journal = {Science translational medicine},
volume = {17},
number = {791},
pages = {eads9207},
doi = {10.1126/scitranslmed.ads9207},
pmid = {40138454},
issn = {1946-6242},
mesh = {Animals ; Guinea Pigs ; *Ixodes/immunology ; Humans ; *Antigens/immunology ; *Vaccination ; *Immunoglobulin G/immunology ; Mice ; Proteome/metabolism/immunology ; Tick Bites/immunology ; Lyme Disease/immunology/prevention & control ; },
abstract = {Ixodes scapularis is a primary vector of tick-borne pathogens in North America. Repeated exposure to these ticks can induce a humoral response to tick antigens and acquired tick resistance. However, identifying antigens contributing to this resistance is challenging because of the vast number of I. scapularis proteins secreted during feeding. To address this, we developed I. scapularis rapid extracellular antigen monitoring (IscREAM), a technique to detect antibody responses to more than 3000 tick antigens. We validated IscREAM with immunoglobulin G (IgG) from guinea pigs vaccinated with tick antigens, including a cement antigen cocktail that induced tick resistance. Furthermore, we explored the natural response to tick bites by profiling antigens recognized by IgG isolated from a tick-resistant individual, as well as from others with Lyme disease and tick-bitten guinea pigs and mice, to identify 199 recognized antigens. We observed that several antigens contained histamine-binding domains. This work enhances our understanding of the host immune response to I. scapularis and defines immunogen candidates for future antitick vaccines.},
}

Animals
Guinea Pigs
*Ixodes/immunology
Humans
*Antigens/immunology
*Vaccination
*Immunoglobulin G/immunology
Mice
Proteome/metabolism/immunology
Tick Bites/immunology
Lyme Disease/immunology/prevention & control

@article {pmid40133165,
year = {2025},
author = {Astigarraga, CC and Mpms, K and Iovino, L and Milano, F},
title = {Haploidentical transplantation: An optimal platform for graft manipulation and cellular therapies.},
journal = {Blood reviews},
volume = {},
number = {},
pages = {101286},
doi = {10.1016/j.blre.2025.101286},
pmid = {40133165},
issn = {1532-1681},
abstract = {Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a curative therapeutic option for patients with high-risk hematologic malignancies. When a fully matched donor is unavailable, haploidentical hematopoietic stem cell transplantation (haplo-HCT) provides a viable alternative. Over time, haplo-HCT procedures have significantly evolved, improving outcomes in treatment related mortality (TRM), especially in graft-versus-host disease (GvHD). However, challenges such as delayed immune reconstitution and disease relapse persist. Advances in in vivo graft manipulation techniques, such as post-transplant cyclophosphamide (PTCy) and ex vivo approaches, including TCRα/β and CD19 depletion, have shown promise in reducing the risk of severe GvHD without increasing the relapse rates. Innovative strategies, such as haploidentical donor lymphocyte infusions, "suicide-switch" mechanisms, ORCA-Q product infusions, and CAR based therapies offer potential to further optimize outcomes. This review examines the graft manipulation modalities in the haplo-HCT setting, highlighting their role in advancing cellular therapies and providing new hope in the fight against life-threatening diseases.},
}

@article {pmid40132580,
year = {2025},
author = {Larsen, BB and McMahon, T and Brown, JT and Wang, Z and Radford, CE and Crowe, JE and Veesler, D and Bloom, JD},
title = {Functional and antigenic landscape of the Nipah virus receptor-binding protein.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2025.02.030},
pmid = {40132580},
issn = {1097-4172},
abstract = {Nipah virus recurrently spills over to humans, causing fatal infections. The viral receptor-binding protein (RBP or G) attaches to host receptors and is a major target of neutralizing antibodies. Here, we use deep mutational scanning to measure how all amino-acid mutations to the RBP affect cell entry, receptor binding, and escape from neutralizing antibodies. We identify functionally constrained regions of the RBP, including sites involved in oligomerization, along with mutations that differentially modulate RBP binding to its two ephrin receptors. We map escape mutations for six anti-RBP antibodies and find that few antigenic mutations are present in natural Nipah strains. Our findings offer insights into the potential for functional and antigenic evolution of the RBP that can inform the development of antibody therapies and vaccines.},
}

@article {pmid40131862,
year = {2025},
author = {MacLean, F and Tsegaye, AT and Graham, JB and Swarts, JL and Vick, SC and Potchen, NB and Cruz Talavera, I and Warrier, L and Dubrulle, J and Schroeder, LK and Saito, A and Mar, C and Thomas, KK and Mack, M and Sabo, MC and Chohan, BH and Ngure, K and Mugo, NR and Lingappa, JR and Lund, JM},
title = {Bacterial vaginosis associates with dysfunctional T cells and altered soluble immune factors in the cervicovaginal tract.},
journal = {The Journal of clinical investigation},
volume = {},
number = {},
pages = {},
doi = {10.1172/JCI184609},
pmid = {40131862},
issn = {1558-8238},
abstract = {BACKGROUND: Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome that is prevalent among reproductive-age females worldwide. Adverse health outcomes associated with BV include an increased risk of sexually-acquired HIV, yet the immunological mechanisms underlying this association are not well understood.

METHODS: To investigate BV-driven changes to cervicovaginal tract (CVT) and circulating T cell phenotypes, Kinga Study participants with or without BV provided vaginal tract (VT) and ectocervical (CX) tissue biopsies and PBMC samples.

RESULTS: High-parameter flow cytometry revealed an increased frequency of cervical conventional CD4+ T cells (Tconv) expressing CCR5. However, we found no difference in number of CD3+CD4+CCR5+ cells in the CX or VT of BV+ versus BV- individuals, suggesting that BV-driven increased HIV susceptibility may not be solely attributed to increased CVT HIV target cell abundance. Flow cytometry also revealed that individuals with BV have an increased frequency of dysfunctional CX and VT CD39+ Tconv and CX tissue-resident CD69+CD103+ Tconv, reported to be implicated in HIV acquisition risk and replication. Many soluble immune factor differences in the CVT further support that BV elicits diverse and complex CVT immune alterations.

CONCLUSION: Our comprehensive analysis expands on potential immunological mechanisms that may underlie the adverse health outcomes associated with BV including increased HIV susceptibility.},
}

@article {pmid40131369,
year = {2025},
author = {Ito, S and Geramita, E and Ventura, K and Neupane, B and Bhise, S and Moore, EM and Furlan, S and Shlomchik, WD},
title = {IFN-γand donor leukocyte infusions for relapsed myeloblastic malignancies after allogeneic hematopoietic stem cell transplantation .},
journal = {JCI insight},
volume = {},
number = {},
pages = {},
doi = {10.1172/jci.insight.190655},
pmid = {40131369},
issn = {2379-3708},
abstract = {BACKGROUND: The graft-vs-leukemia (GVL) effect contributes to the efficacy of allogeneic stem cell transplantation (alloSCT). However, relapse, indicative of GVL failure, is the greatest single cause of treatment failure. Based on preclinical data showing that IFN-γ is important to sensitize myeloblasts to alloreactive T cells, we performed a phase I trial of IFN-γ combined with donor leukocyte infusions (DLI) in myeloblastic malignancies that relapsed post-HLA-matched alloSCT.

METHODS: Patients with relapsed acute myeloid leukemia or myelodysplastic syndrome after alloSCT were eligible. Patients self-administered IFN-γ for 4 weeks (cohort 1) or 1 week (cohort 2), followed by DLI and concurrent IFN-γ for a total of 12 weeks. Bone marrow samples were analyzed by single-cell RNA sequencing (scRNAseq) to assess in vivo responses to IFN-γ by malignant myeloblasts.

RESULTS: IFN-γ monotherapy was well tolerated by all subjects (n=7). Treatment-related toxicities after DLI included: grade I-II graft-versus-host disease (n=5), immune effector cell-associated neurotoxicity syndrome (n=2), and idiopathic pulmonary syndrome (n=1), all of which resolved with corticosteroids. Four of 6 DLI recipients achieved minimal residual disease-negative complete remissions and full donor hematopoietic recovery. Median overall survival was 579 days (range, 97-906) in responders. ScRNAseq confirmed in vivo activation of IFN-γ response pathway in hematopoietic stem cell-like or myeloid progenitor cells after IFN-γ in analyzed samples.

CONCLUSIONS: IFN-γ was safe and well tolerated in this phase I study of IFN-γ for relapsed AML/MDS post-alloSCT, with a promising efficacy signal when combined with DLI. Larger studies are needed to formally test the efficacy of this approach.TRIAL RESGISTRATION.

CLINICALTRIALS: gov NCT04628338.

FUNDING: The research was supported by The UPMC Hillman Cancer Center Cancer Immunology and Immunotherapy Program (CIIP) Pilot Award and Cure Within Reach: Drug Repurposing Clinical Trials to Impact Blood Cancers. Recombinant IFN-gamma (Actimmune®) was donated by Horizon Therapeutics.},
}

@article {pmid40130874,
year = {2025},
author = {Dadonaite, B and Burrell, AR and Logue, J and Chu, HY and Payne, DC and Haslam, DB and Staat, MA and Bloom, JD},
title = {SARS-CoV-2 neutralizing antibody specificities differ dramatically between recently infected infants and immune-imprinted individuals.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0010925},
doi = {10.1128/jvi.00109-25},
pmid = {40130874},
issn = {1098-5514},
abstract = {The immune response to viral infection is shaped by past exposures to related virus strains, a phenomenon known as imprinting. For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), much of the population has been imprinted by a viral spike from an early strain, either through vaccination or infection during the early stages of the COVID-19 pandemic. As a consequence of this imprinting, infection with more recent SARS-CoV-2 strains primarily boosts cross-reactive antibodies elicited by the imprinting strain. Here we compare the neutralizing antibody specificities of imprinted individuals versus infants infected with a recent strain. Specifically, we use pseudovirus-based deep mutational scanning to measure how spike mutations affect neutralization by the serum antibodies of adults and children imprinted by the original vaccine versus infants with a primary infection by an XBB* variant. While the serum neutralizing activity of the imprinted individuals primarily targets the spike receptor-binding domain (RBD), the serum neutralizing activity of infants infected with only XBB* mostly targets the spike N-terminal domain. In these infants, secondary exposure to the XBB* spike via vaccination shifts more of the neutralizing activity toward the RBD, although the specific RBD sites targeted are different from imprinted adults. The dramatic differences in neutralization specificities among individuals with different exposure histories likely impact SARS-CoV-2 evolution.IMPORTANCEWe show that a person's exposure history to different SARS-CoV-2 strains strongly affects which regions on the viral spike that their neutralizing antibodies target. In particular, infants who have just been infected once with a recent viral strain make neutralizing antibodies that target different regions of the viral spike than adults or children who have been exposed to both older and more recent strains. This person-to-person heterogeneity means that the same viral mutation can have different impacts on the antibody immunity of different people.},
}

@article {pmid40127395,
year = {2025},
author = {Lust, H and Schultz, LM and Kwon, S and Roloff, GW and Aldoss, I and Baggott, C and John, S and Rossoff, J and McNerney, KO and Fabrizio, VA and Talano, JA and Moskop, A and Curran, KJ and Phillips, CL and Karras, NA and Baumeister, SHC and Cooper, S and Hermiston, ML and Satwani, P and Qayed, M and Raikar, SS and MacMillan, ML and Hall, EM and Nguyen, K and Cassaday, RD and Kopmar, NE and Kota, VK and Mathews, J and Shaughnessy, PJ and Schwartz, MS and Ladha, A and Yaghmour, G and Kumaran, M and Bachanova, V and Tracy, SI and Othman, T and Luskin, MR and Chen, EC and Advani, AS and Jeyakumar, N and Miller, K and Zhang, A and Shah, BD and Muffly, LS and Faramand, RG},
title = {Real World Outcomes for Young Adult Patients Receiving CD19 CAR T-cell Therapy.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024014846},
pmid = {40127395},
issn = {2473-9537},
abstract = {Tisagenlecleucel (tisa-cel) and brexucabtagene autoleucel (brexu-cel) are approved CD19 CAR T products for young adults (YAs) with relapsed/refractory B-ALL. A distinct analysis of YAs receiving commercial CD19 CAR T has not been reported. Utilizing retrospective data from the Pediatric Real-World CAR T Consortium and the Real-World Outcomes of CAR T in Adult ALL collaboration, we describe efficacy and safety of tisa-cel and brexu-cel in 70 young adults (18-26 years; tisa-cel: 50, brexu-cel: 20). Cytokine release syndrome (CRS) and immune-effector cell associated neurotoxicity syndrome (ICANS) were observed more frequently for brexu-cel vs tisa-cel (CRS= 85% vs 56%, p=0.01; ICANS= 40% vs 18%, p=0.05). CR rates were similar between products at 80% for brexu-cel and 88% for tisa-cel (p=0.39). Relapse free survival (RFS) at 12 months was 46% for brexu-cel (95% CI 31-81%) and 36% for tisa-cel (95% CI 26-52%, p=0.79). Durability of remission over 12 months was 61% for brexu-cel (95% CI 41-93%) vs 41% for tisa-cel (95% CI 27-61%, p=0.12). 12-month overall survival (OS) for brexu-cel was 84% (95% CI 81-100) vs 68% for tisa-cel (95% CI 56-85, HR 1.9, p=0.35). In multivariate analysis, low disease burden was associated with improved OS (HR 0.23, 95% CI 0.06-0.86, p=0.03), while inotuzumab pre-CAR T was associated with inferior outcomes (OS HR 6.32, 95% CI 1.48-27, p=0.01; RFS HR 3.65, 95% CI 1.41-9.46, p=0.008). This study demonstrates comparable real-world efficacy among young adults receiving CD19 CAR T therapy irrespective of CAR T construct, however, rates of toxicity appear higher with brexu-cel.},
}

@article {pmid40124489,
year = {2025},
author = {Bender Ignacio, RA and Chew, KW and Moser, C and Currier, JS and Eron, JJ and Javan, AC and Giganti, MJ and Ritz, J and Gibbs, M and Kouekam, HT and Esser, MT and Daar, ES and Choudhary, M and Deo, R and Fletcher, CV and Li, JZ and Hughes, MD and Smith, D and Wohl, DA and , },
title = {Tixagevimab/cilgavimab or placebo for COVID-19 in ACTIV-2: Safety, pharmacokinetics and neutralizing and anti-drug antibodies.},
journal = {iScience},
volume = {28},
number = {3},
pages = {111938},
pmid = {40124489},
issn = {2589-0042},
abstract = {Monoclonal antibodies have potential as rapidly developable agents for treatment and prevention of emerging viruses. The ACTIV-2 trial randomized persons with mild-moderate COVID-19 to the monoclonal antibody combination tixagevimab/cilgavimab via intramuscular injection (600 mg IM) or infusion (300 mg IV) versus placebo. We present final safety and laboratory outcomes; primary outcomes were previously reported. The analyzed IM group included 214 participants, and the IV group, 106 participants. Adverse events were not different between treatment and placebo. The half-life of both components was >90 days for IM or 75 days for IV. New anti-drug antibodies were about 3 times more likely in active vs. placebo recipients. SARS-CoV-2 neutralizing antibodies increased 157-fold at 7 days and 127-fold at 1 month (IM-treated) but were less robust in IV participants. These data can inform future development of monoclonal antibodies against SARS-CoV-2 and other viruses, even if this intervention is of low utility for contemporary SARS-CoV-2 variants.},
}

@article {pmid40122815,
year = {2025},
author = {Thomson, RM and Cunningham, JA and Gatton, MM and Murphy, SC and de la Paz Ade, M and Ding, XC and Incardona, S and Legrand, E and Lucchi, N and Menard, D and Nsobya, SL and Saez, AC and Shrivastava, J and Chiodini, PL},
title = {WHO malaria nucleic acid amplification test external quality assessment scheme: results of eleven distributions over 6 years.},
journal = {Malaria journal},
volume = {24},
number = {1},
pages = {94},
pmid = {40122815},
issn = {1475-2875},
mesh = {*Nucleic Acid Amplification Techniques/standards/methods ; *Malaria/diagnosis ; Humans ; *World Health Organization ; Quality Control ; Plasmodium/isolation & purification/genetics ; Molecular Diagnostic Techniques/standards/methods ; },
abstract = {BACKGROUND: The World Health Organization (WHO) recommends parasite-based diagnosis of malaria before treatment. The use of nucleic-acid amplification (NAAT) for detection of Plasmodium spp. has expanded rapidly in recent years, for epidemiological research globally and clinical care in high-resource settings. Data from NAATs are frequently used to inform policy decisions, so quality control is essential to ensure results are reliable and comparable. Therefore, robust quality control, including an external quality assessment (EQA) scheme targeting malaria NAATs, is essential. The WHO Global Malaria Programme and the UK National External Quality Assessment Service (UK NEQAS) have collaborated since 2017 to implement a global malaria NAAT EQA scheme.

METHODS: Panels of specimens containing five major species of human-infecting Plasmodium at various parasite concentrations and negative samples were created in lyophilized blood (LB) and dried blood spot (DBS) formats. Two distributions per year were sent, containing five LB and five DBS specimens. Samples were validated by expert referee laboratories prior to distribution. Between 37 and 51 laboratories participated in each distribution and submitted results online. Participants were scored based on their laboratory's stated capacity to identify Plasmodium species, and individual laboratory reports were sent which included performance comparison with anonymized peers. Change in performance over time was calculated using a generalized mixed model with a logit link function.

RESULTS: Participating laboratories were located in 42 countries. Sample format (DBS or LB) and parasite density were found to significantly affect performance, while referee labs performed better at identifying P. falciparum samples than non-referee labs. Performance of laboratories improved significantly over time, especially for lower density and P. falciparum samples.

CONCLUSIONS: Results from the first eleven distributions indicate that the EQA scheme has facilitated improved performance of laboratories over time, highlighting the value of implementing such programmes. EQA schemes are critical to safeguarding the reliability of data and diagnoses, especially in situations where NAAT methodologies and protocols are used. In future, funders should make participation in an EQA scheme a requirement for laboratories, and countries can take initiatives to embed such schemes into their own national assessment programmes.},
}

*Nucleic Acid Amplification Techniques/standards/methods
*Malaria/diagnosis
Humans
*World Health Organization
Quality Control
Plasmodium/isolation & purification/genetics
Molecular Diagnostic Techniques/standards/methods

@article {pmid40119775,
year = {2025},
author = {Rostad, CA and Campbell, JD and Paulsen, GC and Schnyder Ghamloush, S and Xu, W and Zheng, L and McElrath, MJ and De Rosa, SC and Girard, B and Das, R and Anderson, EJ and Creech, CB},
title = {Evaluation of Cellular Immune Responses After mRNA-1273 Vaccination in Children 6 Months to 11 Years of Age.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf144},
pmid = {40119775},
issn = {1537-6613},
abstract = {BACKGROUND: Cell-mediated immunity (CMI) may help protect against emerging SARS-CoV-2 variants that are less susceptible to neutralizing antibodies. We present CMI data after the mRNA-1273 primary series in a subset of participants aged 6 months to 11 years from the phase 2/3 KidCOVE trial.

METHODS: T-cell responses were assessed after 2 doses of mRNA-1273 (6 months-5 years: 25 μg; 6-11 years: 50 μg) or placebo administered 28 days apart. Magnitude, phenotype, and percentage of ancestral SARS-CoV-2 spike (S) protein T-cell responses to pooled peptides were assessed by intracellular cytokine staining and polyfunctionality analyses.

RESULTS: A total of 68 children aged 6 months to 11 years received either the 2-dose mRNA-1273 primary series or placebo (51:17, respectively) at 28-day interval. mRNA-1273 induced S protein-specific CD4+ T-cell responses exhibiting a type 1 T helper (Th1)-biased profile at Day 43 and Day 209 compared with placebo. S-protein-specific CD8+ T-cell responses were less frequently detected in children <5 years and undetectable in those <2 years. Compared with placebo, mRNA-1273 induced higher frequencies of S-specific polyfunctional CD4+ T cells at Day 43; frequencies declined but remained detectable at Day 209. Correlation between Th1 CD4+ responses and neutralizing antibodies was observed across age groups following mRNA-1273 vaccination.

CONCLUSIONS: The 2-dose mRNA-1273 primary series elicited robust and durable (≥6 months) Th1-biased CD4+ T-cell responses in children aged 6 months to 11 years. CD8+ T-cell responses varied by age.Trial registration number and URL NCT04796896 (https://clinicaltrials.gov/study/NCT04796896).},
}

@article {pmid40119478,
year = {2025},
author = {Georgakis, MK and Malik, R and Bounkari, OE and Hasbani, NR and Li, J and Huffman, JE and Shakt, G and Tack, RWP and Kimball, TN and Asare, Y and Morrison, AC and Tsao, NL and Judy, R and Mitchell, BD and Xu, H and Montasser, ME and Do, R and Kenny, EE and Loos, RJF and Terry, JG and Carr, JJ and Bis, JC and Psaty, BM and Longstreth, WT and Young, KA and Lutz, SM and Cho, MH and Broome, J and Khan, AT and Wang, FF and Heard-Costa, N and Seshadri, S and Vasan, RS and Palmer, ND and Freedman, BI and Bowden, DW and Yanek, LR and Kral, BG and Becker, LC and Peyser, PA and Bielak, LF and Ammous, F and Carson, AP and Hall, ME and Raffield, LM and Rich, SS and Post, WS and Tracy, RP and Taylor, KD and Guo, X and Mahaney, MC and Curran, JE and Blangero, J and Clarke, SL and Haessler, JW and Hu, Y and Assimes, TL and Kooperberg, C and Bernhagen, J and Anderson, CD and Damrauer, SM and Zand, R and Rotter, JI and de Vries, PS and Dichgans, M},
title = {Rare damaging CCR2 variants are associated with lower lifetime cardiovascular risk.},
journal = {Genome medicine},
volume = {17},
number = {1},
pages = {27},
pmid = {40119478},
issn = {1756-994X},
mesh = {Humans ; *Receptors, CCR2/genetics ; Male ; Female ; Middle Aged ; Cardiovascular Diseases/genetics ; Genetic Predisposition to Disease ; Chemokine CCL2/genetics ; Aged ; Monocytes/metabolism ; },
abstract = {BACKGROUND: Previous work has shown a role of CCL2, a key chemokine governing monocyte trafficking, in atherosclerosis. However, it remains unknown whether targeting CCR2, the cognate receptor of CCL2, provides protection against human atherosclerotic cardiovascular disease.

METHODS: Computationally predicted damaging or loss-of-function (REVEL > 0.5) variants within CCR2 were detected in whole-exome-sequencing data from 454,775 UK Biobank participants and tested for association with cardiovascular endpoints in gene-burden tests. Given the key role of CCR2 in monocyte mobilization, variants associated with lower monocyte count were prioritized for experimental validation. The response to CCL2 of human cells transfected with these variants was tested in migration and cAMP assays. Validated damaging variants were tested for association with cardiovascular endpoints, atherosclerosis burden, and vascular risk factors. Significant associations were replicated in six independent datasets (n = 1,062,595).

RESULTS: Carriers of 45 predicted damaging or loss-of-function CCR2 variants (n = 787 individuals) were at lower risk of myocardial infarction and coronary artery disease. One of these variants (M249K, n = 585, 0.15% of European ancestry individuals) was associated with lower monocyte count and with both decreased downstream signaling and chemoattraction in response to CCL2. While M249K showed no association with conventional vascular risk factors, it was consistently associated with a lower risk of myocardial infarction (odds ratio [OR]: 0.66, 95% confidence interval [CI]: 0.54-0.81, p = 6.1 × 10[-5]) and coronary artery disease (OR: 0.74, 95%CI: 0.63-0.87, p = 2.9 × 10[-4]) in the UK Biobank and in six replication cohorts. In a phenome-wide association study, there was no evidence of a higher risk of infections among M249K carriers.

CONCLUSIONS: Carriers of an experimentally confirmed damaging CCR2 variant are at a lower lifetime risk of myocardial infarction and coronary artery disease without carrying a higher risk of infections. Our findings provide genetic support for the translational potential of CCR2-targeting as an atheroprotective approach.},
}

Humans
*Receptors, CCR2/genetics
Male
Female
Middle Aged
Cardiovascular Diseases/genetics
Genetic Predisposition to Disease
Chemokine CCL2/genetics
Aged
Monocytes/metabolism

@article {pmid40119158,
year = {2025},
author = {Cole, FM and Laszlo, GS and Lunn-Halbert, MC and Kehret, AR and Zweidler-McKay, PA and Rodríguez-Arbolí, E and Wu, D and Nyberg, K and Li, J and Lim, SYT and Pettenger-Willey, CM and Lakshmikanthan, S and Walter, RB},
title = {Preclinical characterization of the anti-leukemia activity of the CD123 antibody-drug conjugate, pivekimab sunirine (IMGN632).},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {40119158},
issn = {1476-5551},
}

@article {pmid40117529,
year = {2025},
author = {Wagner, MJ and Pimenta, EM and Sweeney, NW and Loggers, ET and Roberts, JL and Brinkman, E and Chen, EY and Ricciotti, R and Haddox, CL and Berg, R and Yilma, B and Stoppler, MC and Chen, JL and Cranmer, LD},
title = {Genomic Characterization of Chondrosarcoma Reveals Potential Therapeutic Targets.},
journal = {JCO precision oncology},
volume = {9},
number = {},
pages = {e2400592},
doi = {10.1200/PO-24-00592},
pmid = {40117529},
issn = {2473-4284},
mesh = {Humans ; *Chondrosarcoma/genetics ; Male ; Female ; Middle Aged ; Aged ; Adult ; Bone Neoplasms/genetics ; Aged, 80 and over ; Genomics ; Young Adult ; Mutation ; Isocitrate Dehydrogenase/genetics ; },
abstract = {PURPOSE: Chondrosarcomas are rare cancers of cartilage with limited systemic therapy options. To identify potential therapeutic targets, this study investigated the molecular and immune landscape of three chondrosarcoma subtypes using a large database of clinical-grade sequencing results.

METHODS: Deidentified records from patients with a histologic diagnosis of conventional, dedifferentiated, or mesenchymal chondrosarcoma sequenced by the Tempus xT DNA assay were included. Microsatellite instability (MSI) and tumor mutational burden (TMB) were determined from sequencing data. The expression of PD-L1 and mismatch repair enzymes was evaluated in cases with available immunohistochemistry (IHC) data.

RESULTS: Of the 149 patients, 103 had conventional chondrosarcoma, 31 dedifferentiated chondrosarcoma, and 15 mesenchymal chondrosarcoma. Across the cohort, 44% (n = 65) had an IDH1 or IDH2 mutation. No cases were MSI high. One conventional chondrosarcoma patient had a TMB >10 mut/Mb. Among 112 patients with available PD-L1 IHC, 10% of conventional (n = 7), 45% of dedifferentiated (n = 13), and 17% of mesenchymal cases (n = 2) were PD-L1-positive. The most common somatic alterations were in IDH1 (34%) and TP53 (28%) in conventional chondrosarcoma; TP53 (68%), TERT (65%), IDH1 (39%), IDH2 (39%), CDKN2A (35%), and CDKN2B (35%) in dedifferentiated chondrosarcoma; and HEY1-NCOA2 fusions (87%) and CDKN2A (20%) in mesenchymal chondrosarcoma. MTAP was deleted in >10% of each subtype, and potentially actionable PDGFRB mutations were identified in 13% of dedifferentiated chondrosarcomas.

CONCLUSION: These findings reinforce therapeutic efforts to target IDH signaling in chondrosarcoma, provide insight into varied subpopulation response to immune checkpoint inhibitors, and identify new potential therapeutic targets for clinical development in chondrosarcoma.},
}

Humans
*Chondrosarcoma/genetics
Male
Female
Middle Aged
Aged
Adult
Bone Neoplasms/genetics
Aged, 80 and over
Genomics
Young Adult
Mutation
Isocitrate Dehydrogenase/genetics

@article {pmid40116910,
year = {2025},
author = {Lewis, FM and Ganschow, P and Manst, D and Derry-Vick, H and Tercyak, KP and Griffith, KA and Oxford, M and Fukui, J and Gadi, VK and Phillips, F},
title = {Behavioral-Emotional Functioning of Children of Parents with Early Compared to Advanced Cancer.},
journal = {Journal of palliative medicine},
volume = {},
number = {},
pages = {},
doi = {10.1089/jpm.2024.0326},
pmid = {40116910},
issn = {1557-7740},
abstract = {Background: Parental cancer represents a substantial psychological threat to children, but little is known about the relative impact of advanced compared to early-stage cancer on children's behavioral-emotional functioning. Objectives: To compare the behavioral-emotional functioning in children of parents with early compared to advanced cancer. Design: Single occasion, two-group design with historical comparison group. Setting/Participants: Participants were recruited through cancer centers, oncologists, service organizations, and self-referrals in the United States. Eligible parents had advanced or early-stage cancer, a child 5-17 years old, and spoke and read English. The Child Behavior Checklist was administered to parents to assess their children's Internalizing and Externalizing Problems. Data were obtained from 236 diagnosed parents, 176 with early and 57 with advanced cancer. Results: Internalizing and Externalizing Problems and Anxious/Depressed Mood were significantly greater for children of parents with advanced compared to early-stage cancer, even after controlling for covariates. Differences in children's functioning were not affected by parents' anxiety, depressed mood, treatment, or measures of social determinants of health. Conclusions: This is the first study to systematically compare the effects of parents' stage of cancer on children's behavioral-emotional functioning while controlling for potential confounders. Results demonstrate significantly elevated levels of behavioral-emotional problems in children affected by advanced compared to early-stage cancer that were explained by parents' stage of cancer, not other sources. Future studies need to identify mutable protective and risk factors to reduce the threat of parental cancer.},
}

@article {pmid40116755,
year = {2025},
author = {Yun, J and Indorf, AL},
title = {Optimizing intermittent dosing of oral small molecule inhibitors.},
journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners},
volume = {},
number = {},
pages = {10781552251327598},
doi = {10.1177/10781552251327598},
pmid = {40116755},
issn = {1477-092X},
abstract = {IntroductionWith recent expansion of oral small molecule inhibitors, the drug development studies need to provide insight into optimal dose selection for these agents with vastly different mechanism and pharmacokinetic considerations compared to our traditional chemotherapy agents. Currently there is one published meta-analysis that examines intermittent and alternative dosing of oral small molecule inhibitors and it is unclear what guidance is available for treatment personalization beyond package insert labeling for patients undergoing toxicities from treatment.MethodsA systematic review of oral small molecule inhibitors with intermittent dosing was conducted in the National Library of Medicine PubMed database. Studies were selected based on predefined inclusion/exclusion criteria. Data was extracted to summarize findings on available guidance for intermittent or alternative dosing of oral small molecule inhibitors. Studies were categorized based on food and drug administration (FDA) approved or non-FDA approved agents, and further characterized by comparison of different dosing schemas.ResultsFifty-five trials were included in the final review and data analysis. Thirty-three trials were phase 1 trials, 26 trials for FDA approved agents and 29 non-FDA approved agents. Most trials reported on agents used in solid tumors, particularly renal cell carcinoma, with most trials examining sunitinib. Of the 55 trials, 28 compared different dosing strategies with 26 of the 28 trials examining efficacy outcomes with 27 of the 28 trials examining safety outcomes.ConclusionsThis systematic review found limited guidance for clinicians in optimizing dosing for intermittently dosed oral small molecule inhibitors.},
}

@article {pmid40116305,
year = {2025},
author = {Labaf, M and Han, W and Zhang, S and Liu, M and Patten, ND and Li, M and Patalano, S and Macoska, JA and Balk, SP and Han, D and Zarringhalam, K and Cai, C},
title = {Heterogeneous Responses to High-Dose Testosterone in Castration-Resistant Prostate Cancer Tumors with Mixed Rb-Proficient and Rb-Deficient Cells.},
journal = {Molecular cancer therapeutics},
volume = {},
number = {},
pages = {OF1-OF12},
doi = {10.1158/1535-7163.MCT-24-0716},
pmid = {40116305},
issn = {1538-8514},
support = {R01CA211350//National Cancer Institute (NCI)/ ; U54CA156734//National Cancer Institute (NCI)/ ; P50CA090381//National Cancer Institute (NCI)/ ; W81XWH-19-1-0361//U.S. Department of Defense (DOD)/ ; HT9425-24-1-0472//U.S. Department of Defense (DOD)/ ; },
abstract = {Androgen deprivation therapy remains a cornerstone in managing prostate cancer. However, its recurrence often leads to the more aggressive castration-resistant prostate cancer (CRPC). Although second-line androgen receptor signaling inhibition treatments such as enzalutamide and abiraterone are available, their effectiveness against CRPC is only transient. High-dose testosterone (Hi-T) has recently emerged as a promising treatment for CRPC, primarily through the suppression of E2F and MYC signaling. However, the roles of Rb family proteins in influencing this therapeutic response remain debated. In this study, we utilized a CRPC patient-derived xenograft model that includes both Rb pathway-proficient and -deficient cell populations based on the positive or negative expression of RB family genes. Single-cell RNA sequencing analysis revealed that Rb-proficient cells displayed a robust response to Hi-T, whereas Rb-deficient cells exhibited significant resistance. Notably, our analysis indicated increased enrichment of the hypoxia signature in the Rb-deficient cell population. Further studies in RB1-silenced CRPC cell lines showed that treatment with a hypoxia-inducible factor-1α inhibitor can restore the sensitivity of Rb-deficient cells to high-dose dihydrotestosterone treatment. In conclusion, our research provides new molecular insights into CRPC tumor cell responses to Hi-T and proposes a new strategy to resensitize Rb-deficient CRPC cells to Hi-T treatment.},
}

@article {pmid40115173,
year = {2025},
author = {Ghobadi, A and Caimi, PF and Reese, JS and Goparaju, K and di Trani, M and Ritchey, J and Jackson, Z and Tomlinson, B and Schiavone, JM and Kleinsorge-Block, S and Zamborsky, K and Eissenberg, L and Schneider, D and Boughan, KM and Zabor, EC and Metheny, L and Gallogly, M and Kruger, W and Kadan, M and Worden A S, A and Sharma, A and Cooper, BW and Otegbeye, F and Sekaly, RP and Wald, DN and Carlo-Stella, C and DiPersio, J and Orentas, R and Dropulic, B and de Lima, M},
title = {Treatment of non-Hodgkin lymphoma with point-of-care manufactured CAR T cells: a dual institution, phase 1 trial.},
journal = {EClinicalMedicine},
volume = {81},
number = {},
pages = {103138},
pmid = {40115173},
issn = {2589-5370},
abstract = {BACKGROUND: Point-of-care manufacture of chimeric antigen receptor (CAR)-T cells can significantly reduce the time from apheresis to infusion. We conducted a dual-institution phase I trial aimed evaluating the safety and feasibility of this manufacturing model.

METHODS: CASE 2417 was a phase I clinical trial. Adults with relapsed or refractory CD19 positive non-Hodgkin lymphoma (R/R NHL) treated with ≥2 prior systemic therapies were eligible. MB-CART-19 is an anti-CD19 CAR T-cell product manufactured using the CliniMACS Prodigy device with 4-1BB and CD3ζ costimulatory domains. Lymphodepletion included fludarabine 25 mg/m[2] for 3 days and cyclophosphamide 60 mg/kg for 1 day. Prophylactic tocilizumab was allowed. Three dose levels (0.5, 1.0 and 2.0 × 10[6] cells/kg) were tested using a 3 + 3 dose-escalation schema. The primary outcome of this study was to determine the safety as defined by the dose limiting toxicities of MB-CART-19 in patients with relapsed and refractory NHL, co-primary outcome was determining the phase 2 dose of MB-CART-19. Secondary outcomes include defining the toxicity profile and to evaluate the initial efficacy of MB-CART-19 against relapsed or refractory NHL. This study was registered in ClinicalTrials.govNCT03434769.

FINDINGS: Thirty-one patients were enrolled between July 2018 and January 2021. Twenty-four (77%) had aggressive lymphoma, 7 (24%) had indolent lymphoma (follicular lymphoma and marginal zone lymphoma). The median number of previous therapies was 5 (range 2-13, interquartile range [IQR] 3-5). All enrolled patients received MB-CART-19. Median apheresis to infusion time was 13 days (range 9-20, IQR 9-13). One dose limiting toxicity (DLT) was observed in dose escalation (fatal cytokine release syndrome [CRS]), whereas one patient died in dose expansion secondary to hemophagocytic syndrome. Both deaths were considered treatment-related. Twenty (65%) patients had CRS, three (10%) grade ≥3. Ten patients (32%) experienced immune effector cell neurotoxicity syndrome (ICANS), four (13%) grade ≥3. Neutropenia (n = 28, 90%), thrombocytopenia (n = 15, 48%) and anaemia (n = 13, 42%) were the most frequent grade ≥3 adverse events. Twenty-five out of 29 (86%, 95% confidence interval [CI]: 68-96%) response-evaluable patients had disease response and 22 (76%, 95% CI: 56-90%) had complete response; the overall and complete response rates for response-evaluable aggressive lymphoma patients (n = 22) were 82% (n = 18, 95% CI: 60-95%) and 73% (n = 16, 95% CI: 50-89%). Median follow up was 24.5 (IQR 17-32) months, median progression free survival (PFS) was 26 months (95% CI: 19-not reached [NR]) and median PFS was not reached (95% CI: 25 months-NR). Two-year estimates of PFS and overall survival (OS) were 63% (95% CI: 47-83%) and 68% (95% CI: 52-88%), respectively. Median PFS was 26 months (95% CI: 7-NR) for aggressive lymphoma patients with 2-year PFS estimate of 53% (95% CI: 36-78%), while median OS had not been reached for aggressive lymphoma patients (95% CI: 19 months-NR), and 2-year OS estimate was 60% (95% CI: 43-85%).

INTERPRETATION: Point-of-care CAR T-cell manufacture was feasible and replicable across sites. MB-CART-19 has a safety profile comparable to other CAR T-cell products and high response rates. The recommended phase 2 dose is 2 × 10[6] MB-CART-19 cells/kg. Short CAR T-cell manufacturing time permits treatment of patients with rapidly progressive lymphoma, a group of patients with high risk disease for whom access to autologous immune effector cellular therapies is usually limited.

FUNDING: This clinical trial was funded through University Hospitals Seidman Cancer Center and Washington University School of Medicine Institutional Funds. Correlative analyses were funded in part by the European Union-Next Generation EU-NRRP M6C2-Investment 2.1 Enhancement and strengthening of biomedical research in the NHS (project #PNRR-MAD-2022-12376059), and the Italian Ministry of Health Ricerca Finalizzata 2019 (project #RF-2019-12370243).},
}

@article {pmid40114218,
year = {2025},
author = {Takeuchi, T and Flannery, AH and Liu, LJ and Ghazi, L and Cama-Olivares, A and Fushimi, K and Chen, J and Huen, SC and Tolwani, AJ and Neyra, JA},
title = {Epidemiology of sepsis-associated acute kidney injury in the ICU with contemporary consensus definitions.},
journal = {Critical care (London, England)},
volume = {29},
number = {1},
pages = {128},
pmid = {40114218},
issn = {1466-609X},
support = {K23DK128562/DK/NIDDK NIH HHS/United States ; R01DK128208//National Institute of Diabetes and Digestive and Kidney Diseases,United States/ ; },
mesh = {Humans ; *Acute Kidney Injury/epidemiology/etiology/diagnosis ; *Sepsis/epidemiology/complications ; *Intensive Care Units/organization & administration/statistics & numerical data ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; *Consensus ; Cohort Studies ; Hospital Mortality ; Adult ; },
abstract = {BACKGROUND: The definition of sepsis-associated acute kidney injury (SA-AKI) was updated in 2023. This study aims to describe the epidemiology of SA-AKI using updated consensus definition and to evaluate clinical outcomes.

METHODS: The study was a retrospective cohort analysis conducted at two academic medical centers. Adult patients admitted to intensive care units (ICU) between 2010 and 2022 were included and categorized as SA-AKI, sepsis alone, or AKI alone. SA-AKI was further classified by time of onset (early < 2 days from sepsis diagnosis vs. late 2-7 days following sepsis diagnosis) and presence of septic shock. Clinical outcomes included hospital mortality and major adverse kidney events (MAKE = death, kidney replacement therapy, or reduced kidney function from baseline) at discharge.

RESULTS: 187,888 adult ICU patients were included, and SA-AKI was found in nearly half of sepsis patients and about 1 in 6 ICU admissions. 1 in 4 patients with SA-AKI died during hospitalization and 37.7% experienced at least one MAKE by hospital discharge. Compared to sepsis or AKI alone, SA-AKI was associated with higher mortality (adjusted HR 1.59; 95% CI 1.51-1.66) and higher odds of MAKE (adjusted OR 3.35; 95% CI 3.19-3.51). The early clinical phenotype of SA-AKI was most common, with incident AKI decreasing daily from sepsis onset. The presence of septic shock significantly worsened outcomes.

CONCLUSIONS: Applying updated consensus definitions highlights the high prevalence of SA-AKI in the ICU and its significant associated morbidity and mortality. Outcomes differ based on clinical phenotypes, including the timing of SA-AKI onset and the presence of shock.},
}

Humans
*Acute Kidney Injury/epidemiology/etiology/diagnosis
*Sepsis/epidemiology/complications
*Intensive Care Units/organization & administration/statistics & numerical data
Male
Female
Retrospective Studies
Middle Aged
Aged
*Consensus
Cohort Studies
Hospital Mortality
Adult

@article {pmid40112242,
year = {2025},
author = {Abida, W and Beltran, H and Raychaudhuri, R},
title = {State of the Art: Personalizing Treatment for Patients With Metastatic Castration-Resistant Prostate Cancer.},
journal = {American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting},
volume = {45},
number = {3},
pages = {e473636},
doi = {10.1200/EDBK-25-473636},
pmid = {40112242},
issn = {1548-8756},
mesh = {Humans ; Male ; *Prostatic Neoplasms, Castration-Resistant/drug therapy/pathology ; *Precision Medicine ; Neoplasm Metastasis ; Biomarkers, Tumor ; Molecular Targeted Therapy ; },
abstract = {Until recently, the treatment of metastatic castration-resistant prostate cancer (mCRPC) relied exclusively on hormonal therapies and taxane chemotherapy. The advent of modern molecular profiling methods applied in the clinic, namely, next-generation sequencing and advanced positron emission tomography (PET) imaging, has allowed for the development of biomarker-driven therapeutics including anti-PD-L1 therapy for microsatellite instability-high or tumor mutation burden-high disease, poly(ADP-ribose) polymerase (PARP) inhibitors for patients with DNA damage repair mutations, and lutetium 177 vipivotide tetraxetan ([177]Lu-PSMA-617) for patients with prostate-specific membrane antigen (PSMA) PET-avid disease. While these targeted therapies have improved outcomes, there is an opportunity to refine biomarkers to optimize patient selection, understand resistance, and develop novel combination strategies. In addition, studies in the laboratory and in patient-derived samples have shown that a subset of mCRPC tumors lose expression of common prostate cancer markers such as prostate-specific antigen and PSMA because of lineage plasticity and the development of non-androgen receptor (AR)-driven disease. Non-AR-driven prostate cancer has been associated with aggressive behavior and poor prognosis, including in some cases histologic transformation to a poorly differentiated neuroendocrine prostate cancer (NEPC). The clinical management of NEPC typically follows the treatment paradigm for small cell lung cancer and increasingly relies on genomic and phenotypic characterization of disease, including loss of tumor suppressors and expression of cell surface markers such as DLL3. Therefore, both genomic subtyping and phenotypic subtyping are important to consider and can guide the clinical management of patients with advanced prostate cancer.},
}

Humans
Male
*Prostatic Neoplasms, Castration-Resistant/drug therapy/pathology
*Precision Medicine
Neoplasm Metastasis
Biomarkers, Tumor
Molecular Targeted Therapy

@article {pmid40111318,
year = {2025},
author = {Yeh, JM and Ward, ZJ and Stratton, KL and McMahon, MV and Taylor, CS and Armstrong, GT and Chow, EJ and Hudson, MM and Morton, LM and Oeffinger, KC and Diller, LR and Leisenring, WM},
title = {Accelerated Aging in Survivors of Childhood Cancer-Early Onset and Excess Risk of Chronic Conditions.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
pmid = {40111318},
issn = {2374-2445},
abstract = {IMPORTANCE: The lifetime risk of aging-related diseases among survivors of childhood cancer, accelerated by cancer treatment exposures, is unknown. Understanding this risk can provide a more comprehensive assessment of long-term health across the lifespan of survivors and guide adult care.

OBJECTIVE: To estimate the lifetime risks of 8 treatment-related cancers and cardiovascular conditions among childhood cancer survivors and compare them with the general population.

DESIGN, SETTING, PARTICIPANTS: Using data from the Childhood Cancer Survivor Study and national databases, this simulation modeling study projected long-term outcomes for 5-year survivors diagnosed between 1970 and 1999 based on treatment exposures and age-related risks. The general population comparator was simulated using age-, sex-, and calendar year-matched individuals who faced only age-related risks.

EXPOSURES: Treatment era (1970s, 1980s, 1990s), original cancer diagnosis, radiation treatment for primary diagnosis (any, none).

MAIN OUTCOMES AND MEASURES: Estimated lifetime risks of 8 health conditions (breast cancer, colorectal cancer, glial tumors, sarcomas, heart failure, coronary heart disease/myocardial infarction, stroke, and valvular disease). Risks were projected and compared with the general population, stratified by radiation exposure.

RESULTS: In the general population, 20% developed at least 1 health condition by age 65.0 years; in 5-year survivors this threshold was reached at age 47.3 years, representing a 17.7-year (95% uncertainty interval [UI], 14.0-21.0) acceleration in disease onset. By age 65 years, 55% of survivors were projected to develop at least 1 condition, indicating a 2.7-fold (95% UI, 2.2-3.5) higher relative risk and 34.2% (95% UI, 28.3-42.5) absolute excess risk compared with the general population. Risks were higher among those treated with radiation therapy for childhood cancer (22.0 years earlier onset [95% UI, 18.0-25.0]; 37.3% excess risk [95% UI, 31.6%-44.7%]) but still elevated for those without radiation exposure (13.5 years earlier onset [95% UI, 10.0-16.0]; 31.0% excess risk [95% UI, 23.9%-40.3%]). Reaching middle age was still associated with increased health risks. Compared with the general population, survivors who reached age 40 years had a 6.2-fold higher risk (95% UI, 4.8-9.4) of developing a new condition within 10 years.

CONCLUSIONS AND RELEVANCE: This study found that survivors of childhood cancer experience accelerated onset of aging-related diseases, regardless of prior radiation exposure. These findings underscore the importance of prioritizing cancer and cardiovascular disease prevention among survivors decades earlier than for the general population.},
}

@article {pmid40109220,
year = {2025},
author = {Yeung, CC and Jones, DC and Woolston, DW and Seaton, B and Donato, EL and Lin, M and Backman, C and Oehler, V and Robinson, KL and Shimp, K and Kulikauskas, R and Long, AN and Sowerby, D and Elz, AE and Smythe, KS and Newell, EW},
title = {Spatial proteomics and transcriptomics characterization of tissue and multiple cancer types including decalcified marrow.},
journal = {Cancer biomarkers : section A of Disease markers},
volume = {42},
number = {1},
pages = {18758592241308757},
doi = {10.1177/18758592241308757},
pmid = {40109220},
issn = {1875-8592},
mesh = {Humans ; *Proteomics/methods ; *Bone Marrow/metabolism/pathology ; *Neoplasms/genetics/pathology/metabolism ; Transcriptome ; Gene Expression Profiling/methods ; Tissue Array Analysis/methods ; Biomarkers, Tumor/genetics/metabolism ; Immunohistochemistry/methods ; Decalcification Technique/methods ; Paraffin Embedding ; Tissue Fixation/methods ; },
abstract = {BackgroundRecent technologies enabling the study of spatial biology include multiple high-dimensional spatial imaging methods that have rapidly emerged with different capabilities evaluating tissues at different resolutions for different sample formats. Platforms like Xenium (10x Genomics) and PhenoCycler-Fusion (Akoya Biosciences) enable single-cell resolution analysis of gene and protein expression in archival FFPE tissue slides. However, a key limitation is the absence of systematic methods to ensure tissue quality, marker integrity, and data reproducibility.ObjectiveWe seek to optimize the technical methods for spatial work by addressing preanalytical challenges with various tissue and tumor types, including a decalcification protocol for processing FFPE bone marrow core specimens to preserve nucleic acids for effective spatial proteomics and transcriptomics. This study characterizes a multicancer tissue microarray (TMA) and a molecular- and protein-friendly decalcification protocol that supports downstream spatial biology investigations.MethodsWe developed a multi-cancer tissue microarray (TMA) and processed bone marrow core samples using a molecular- and protein-friendly decalcification protocol. PhenoCycler high-plex immunohistochemistry (IHC) generated spatial proteomics data, analyzed with QuPath and single-cell analysis. Xenium provided spatial transcriptomics data, analyzed via Xenium Explorer and custom pipelines.ResultsResults showed that PhenoCycler and Xenium platforms applied to TMA sections of tonsil and various tumor types achieved good marker concordance. Bone marrow decalcification with our optimized protocol preserved mRNA and protein markers, allowing Xenium analysis to resolve all major cell types while maintaining tissue morphology.ConclusionsWe have shared our preanalytical verification of tissues and demonstrate that both the PhenoCycler-Fusion high-plex spatial proteomics and Xenium spatial transcriptomics platforms work well on various tumor types, including marrow core biopsies decalcified using a molecular- and protein-friendly decalcificationprotocol. We also demonstrate our laboratory's methods for systematic quality assessment of the spatial proteomic and transcriptomic data from these platforms, such that either platform can provide orthogonal confirmation for the other.},
}

Humans
*Proteomics/methods
*Bone Marrow/metabolism/pathology
*Neoplasms/genetics/pathology/metabolism
Transcriptome
Gene Expression Profiling/methods
Tissue Array Analysis/methods
Biomarkers, Tumor/genetics/metabolism
Immunohistochemistry/methods
Decalcification Technique/methods
Paraffin Embedding
Tissue Fixation/methods

@article {pmid40109218,
year = {2025},
author = {Tang, TM and Zhang, Y and Kenney, AM and Xie, C and Xiao, L and Siddiqui, J and Srivastava, S and Sanda, MG and Wei, JT and Feng, Z and Tosoian, JJ and Zheng, Y and Chinnaiyan, AM and Yu, B and , },
title = {A simplified MyProstateScore2.0 for high-grade prostate cancer.},
journal = {Cancer biomarkers : section A of Disease markers},
volume = {42},
number = {1},
pages = {18758592241308755},
doi = {10.1177/18758592241308755},
pmid = {40109218},
issn = {1875-8592},
mesh = {Humans ; Male ; *Prostatic Neoplasms/genetics/diagnosis ; *Biomarkers, Tumor/genetics ; *Neoplasm Grading ; Prostate-Specific Antigen/blood ; },
abstract = {Background: The limited diagnostic accuracy of prostate-specific antigen screening for prostate cancer (PCa) has prompted innovative solutions, such as the state-of-the-art 18-gene urine test for clinically-significant PCa (MyProstateScore2.0 (MPS2)). Objective: We aim to develop a non-invasive biomarker test, the simplified MPS2 (sMPS2), which achieves similar state-of-the-art accuracy as MPS2 for predicting high-grade PCa but requires substantially fewer genes than the 18-gene MPS2 to improve its accessibility for routine clinical care. Methods: We grounded the development of sMPS2 in the Predictability, Computability, and Stability (PCS) framework for veridical data science. Under this framework, we stress-tested the development of sMPS2 across various data preprocessing and modeling choices and developed a stability-driven PCS ranking procedure for selecting the most predictive and robust genes for use in sMPS2. Results: The final sMPS2 model consisted of 7 genes and achieved a 0.784 AUROC (95% confidence interval, 0.742-0.825) for predicting high-grade PCa on a blinded external validation cohort. This is only 2.3% lower than the 18-gene MPS2, which is similar in magnitude to the 1-2% in uncertainty induced by different data preprocessing choices. Conclusions: The 7-gene sMPS2 provides a unique opportunity to expand the reach and adoption of non-invasive PCa screening.},
}

Humans
Male
*Prostatic Neoplasms/genetics/diagnosis
*Biomarkers, Tumor/genetics
*Neoplasm Grading
Prostate-Specific Antigen/blood

@article {pmid40109190,
year = {2025},
author = {Curran, E and Luskin, MR and Alachkar, H and Aldoss, I and Burke, PW and Cassaday, RD and Karol, SE and Perissinotti, AJ and Rank, CU and Schmiegelow, K and Webster, J and Douer, D},
title = {Recognition, prevention, and management of adverse events associated with asparaginase / pegaspargase treatment of acute lymphoblastic leukemia in adults: consensus of an expert panel.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2024.286744},
pmid = {40109190},
issn = {1592-8721},
abstract = {Asparaginase (ASNase)-based chemotherapy regimens significantly improve survival outcomes in children, adolescent and young adult (AYA), and even adults with acute lymphoblastic leukemia/lymphoma (ALL); however, the incidence and severity of ASNase-associated adverse events (AEs) in adults may differ significantly from those reported in children. Strategies to mitigate, monitor for, and manage toxicities that allow adult ALL patients to receive full ASNase courses are needed. A representative 12-member panel of experts who treat AYA and adult ALL patients, incorporate ASNase into their treatment regimens, and conduct related research was assembled to consider opportunities to optimize the use of pediatric-inspired ALL regimens in these adult patients. Following 2 systematic biomedical literature searches from April 2009 through April 2024, a modified Delphi method was used to distill expert opinion into clinical statements that met a standardized definition of consensus. After 2 iterative Delphi method surveys, 23 statements met the standardized definition of consensus, whereas 19 statements did not. Five statements were merged to avoid redundancy. The clinical statements were grouped into 5 distinct categories: 1) hepatotoxicity; 2) hypersensitivity reactions; 3) thromboembolic and coagulopathy complications; 4) pancreatitis and metabolic complications; and 5) dosing. The intent of these statements is to provide health care providers with information that will help them mitigate, monitor for, and manage the most common and/or unique ASNase-induced AEs in adult ALL patients, allowing these patients to receive more or all the planned ASNase doses and thereby improve outcomes.},
}

@article {pmid40108454,
year = {2025},
author = {Pae, J and Schwan, N and Ottino-Loffler, B and DeWitt, WS and Garg, A and Bortolatto, J and Vora, AA and Shen, JJ and Hobbs, A and Castro, TBR and Mesin, L and Matsen, FA and Meyer-Hermann, M and Victora, GD},
title = {Transient silencing of hypermutation preserves B cell affinity during clonal bursting.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {40108454},
issn = {1476-4687},
abstract = {In the course of antibody affinity maturation, germinal centre (GC) B cells mutate their immunoglobulin heavy- and light-chain genes in a process known as somatic hypermutation (SHM)[1-4]. Panels of mutant B cells with different binding affinities for antigens are then selected in a Darwinian manner, which leads to a progressive increase in affinity among the population[5]. As with any Darwinian process, rare gain-of-fitness mutations must be identified and common loss-of-fitness mutations avoided[6]. Progressive acquisition of mutations therefore poses a risk during large proliferative bursts[7], when GC B cells undergo several cell cycles in the absence of affinity-based selection[8-13]. Using a combination of in vivo mouse experiments and mathematical modelling, here we show that GCs achieve this balance by strongly suppressing SHM during clonal-burst-type expansion, so that a large fraction of the progeny generated by these bursts does not deviate from their ancestral genotype. Intravital imaging and image-based cell sorting of a mouse strain carrying a reporter of cyclin-dependent kinase 2 (CDK2) activity showed that B cells that are actively undergoing proliferative bursts lack the transient CDK2[low] 'G0-like' phase of the cell cycle in which SHM takes place. We propose a model in which inertially cycling B cells mostly delay SHM until the G0-like phase that follows their final round of division in the GC dark zone, thus maintaining affinity as they clonally expand in the absence of selection.},
}

@article {pmid40061317,
year = {2025},
author = {Fuller, H and Agasaro, OP and Darst, BF},
title = {Pre-diagnostic circulating metabolomics and prostate cancer risk: A systematic review and meta-analysis.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40061317},
support = {P50 CA097186/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Metabolomic dysregulation contributes to prostate cancer (PCa) pathogenesis, and studies suggest that circulating metabolites have strong clinical potential to act as biomarkers. However, evidence of circulating metabolite associations has not been quantitively aggregated.

METHODS: Systematic searches were performed in PubMed and Embase (October 17[th], 2024) to identify pre-diagnostic untargeted serum metabolomic studies of PCa risk. After harmonizing metabolite names across studies, restricted maximum likelihood was used to conduct meta-analyses to quantify associations between metabolites and risk of overall PCa, low- to intermediate-risk PCa, high- to very high-risk PCa and lethal PCa, as defined by the NCCN. Statistical significance was defined as FDR-adjusted P<0.05. Enrichment analyses were conducted on significant metabolites to identify biologically relevant pathways. Correlation of effect estimates between PCa outcomes was assessed via Pearson correlation.

RESULTS: We identified 12 untargeted pre-diagnostic circulating metabolomic studies in a systematic review and meta-analyzed associations between up to 408 metabolites with four PCa outcomes. Three, eleven and nineteen metabolites were significantly associated with risk of overall, high/very high-risk and lethal PCa, respectively. Metabolites associated with high/very high-risk PCa were significantly enriched for lipids. Limited evidence of correlation between metabolite effects across outcomes was identified, highlighting potentially unique metabolite drivers of high-risk and lethal PCa. Follow-up analyses found that 13 of the significant metabolites were drug and/or dietary modifiable.

CONCLUSIONS: These findings suggest the strong potential for metabolites to inform risk of lethal PCa, which could inform risk-stratified screening strategies and facilitate the identification of targets for PCa prevention.},
}

@article {pmid40108332,
year = {2025},
author = {Shah, BD and Cassaday, RD and Park, JH and Houot, R and Logan, AC and Boissel, N and Leguay, T and Bishop, MR and Topp, MS and O'Dwyer, KM and Tzachanis, D and Arellano, ML and Lin, Y and Baer, MR and Schiller, GJ and Subklewe, M and Abedi, M and Minnema, MC and Wierda, WG and DeAngelo, DJ and Stiff, P and Jeyakumar, D and Mao, D and Adhikary, S and Zhou, L and Hadjivassileva, T and Damico Khalid, R and Ghobadi, A and Oluwole, OO},
title = {Three-year analysis of adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {40108332},
issn = {1476-5551},
abstract = {Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 CAR T-cell therapy approved in the US to treat adults aged ≥18 years (≥26 years in the EU) with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Brexu-cel showed an overall complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate of 73% (CR rate 60%) and median overall survival (OS) of 25.4 months in 78 patients with R/R B-ALL after 2 years in ZUMA-3. Here, we report updated outcomes after >3 years median follow-up. As of July 23, 2022, median follow-up in all patients (N = 78) was 41.6 months. Median OS (95% CI) was 25.6 months (1.2-47.0; N = 78) and was 38.9 months (25.4-not estimable) for responders (n = 58), with 9 patients in ongoing remission without subsequent therapies. Five deaths (none deemed brexu-cel-related) occurred since prior data cut. Benefits from brexu-cel were maintained regardless of age, prior therapies, and subsequent allogeneic stem cell transplantation (alloSCT). Subsequent alloSCT was not associated with survival benefit among responders versus responders without subsequent alloSCT. No secondary T-cell malignancies were reported in ZUMA-3 with long-term follow-up.},
}

@article {pmid40107155,
year = {2025},
author = {Gupta, S and Climent Duran, MA and Sridhar, SS and Powles, T and Bellmunt, J and Park, SH and Gurney, H and Tsuchiya, N and Petrylak, DP and Tomita, Y and di Pietro, A and Manitz, J and Tyroller, K and Hoffman, J and Jacob, N and Grivas, P},
title = {Avelumab first-line maintenance for advanced urothelial carcinoma: long-term outcomes from the JAVELIN Bladder 100 trial in older patients.},
journal = {ESMO open},
volume = {10},
number = {4},
pages = {104506},
doi = {10.1016/j.esmoop.2025.104506},
pmid = {40107155},
issn = {2059-7029},
abstract = {BACKGROUND: In the JAVELIN Bladder 100 phase III trial, avelumab first-line (1L) maintenance plus best supportive care (BSC) significantly prolonged overall survival (OS) versus BSC alone in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) without progression following platinum-based chemotherapy. Older age (≥65 years) is a known risk factor for bladder cancer with a median age at diagnosis of 73.0 years. We report exploratory analyses in subgroups based on older age (≥65 years).

MATERIALS AND METHODS: Eligible patients with la/mUC without progression after 1L platinum-based chemotherapy were randomized to receive avelumab plus BSC (n = 350) or BSC alone (n = 350). This exploratory analysis included subgroups aged ≥65 years, ≥65-<75 years, ≥75 years, and the subset aged ≥80 years. OS (primary endpoint) and progression-free survival (PFS) from randomization were analyzed using the Kaplan-Meier method.

RESULTS: Of 700 patients, 464 (66.3%) were aged ≥65 years. Median OS with avelumab plus BSC versus BSC alone was 26.1 versus 15.5 months (hazard ratio 0.70, 95% confidence interval 0.56-0.89) in all patients aged ≥65 years and 28.7 versus 17.1, 24.0 versus 13.5, and 24.9 versus 10.0 months, respectively, in patients aged ≥65-<75, ≥75, and ≥80 years. PFS analyses favored avelumab plus BSC versus BSC alone in all subgroups. No new safety concerns were identified in patients aged ≥65 years, including those treated for ≥12 months. Quality-adjusted time without symptoms or toxicity was 4.57 months longer with avelumab plus BSC versus BSC alone (a 30.35% relative improvement). Limitations include small sample size for the ≥80-year age subgroup and the exploratory design.

CONCLUSIONS: These exploratory analyses support the efficacy and tolerability of avelumab 1L maintenance in patients aged ≥65 years with la/mUC that has not progressed following chemotherapy, suggesting that older age should not solely prevent a patient from receiving avelumab 1L maintenance.},
}

@article {pmid40106531,
year = {2025},
author = {Haring, B and Aragaki, AK and Shimbo, D and Rapp, SR and Eaton, CB and LaMonte, MJ and Wactawski-Wende, J and Allison, MA and Shadyab, AH and Rossouw, JE and Whitsel, EA and Franceschini, N and Kooperberg, C and Desai, P and Simon, MS and Böhm, M and Natarajan, P and Wassertheil-Smoller, S and Manson, JE},
title = {Clonal Hematopoiesis of Indeterminate Potential and Incident Hypertension: Results From the Women's Health Initiative.},
journal = {Hypertension (Dallas, Tex. : 1979)},
volume = {82},
number = {4},
pages = {e70-e72},
pmid = {40106531},
issn = {1524-4563},
support = {75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; R01 HL148565/HL/NHLBI NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; },
}

@article {pmid40106482,
year = {2025},
author = {Soneson, C and Shepherd, L and Ramos, M and Rue-Albrecht, K and Rainer, J and Pagès, H and Carey, VJ},
title = {Eleven quick tips for writing a Bioconductor package.},
journal = {PLoS computational biology},
volume = {21},
number = {3},
pages = {e1012856},
pmid = {40106482},
issn = {1553-7358},
}

@article {pmid40104982,
year = {2025},
author = {Chen, YA and Kazerouni, AS and Phelps, MD and Hippe, DS and Youn, I and Lee, JM and Partridge, SC and Rahbar, H},
title = {Time to Enhancement Measured From Ultrafast Dynamic Contrast-Enhanced MRI for Improved Breast Lesion Diagnosis.},
journal = {Journal of breast imaging},
volume = {},
number = {},
pages = {},
doi = {10.1093/jbi/wbae089},
pmid = {40104982},
issn = {2631-6129},
support = {R01CA207290, R01CA203883, and K99CA293004/CA/NCI NIH HHS/United States ; },
abstract = {OBJECTIVE: Breast MRI affords high sensitivity with intermediate specificity for cancer detection. Ultrafast dynamic contrast-enhanced (DCE) MRI assesses early contrast inflow with potential to supplement or replace conventional DCE-MRI kinetic features. We sought to determine whether radiologist's evaluation of ultrafast DCE-MRI can increase specificity of a clinical MRI protocol.

METHODS: In this IRB-approved, HIPAA-compliant study, breast MRIs from March 2019 to August 2020 with a BI-RADS category 3, 4, or 5 lesion were identified. Ultrafast DCE-MRI was acquired during the first 40 seconds after contrast injection and before conventional DCE-MRI postcontrast acquisitions in the clinical breast MRI protocol. Three radiologists masked to outcomes retrospectively determined lesion time to enhancement (TTE) on ultrafast DCE-MRI. Interreader agreement, differences between benign and malignant lesion TTE, and TTE diagnostic performance were evaluated.

RESULTS: Ninety-five lesions (20 malignant, 75 benign) were included. Interreader agreement in TTE was moderate to substantial for both ultrafast source images and subtraction maximum intensity projections (overall κ = 0.63). Time to enhancement was greater across benign lesions compared with malignancies (P <.05), and all lesions demonstrating no enhancement during the ultrafast series were benign. With a threshold TTE ≥40 seconds, ultrafast DCE-MRI yielded an average 40% specificity (95% CI, 30%-48%) and 92% sensitivity (95% CI, 81%-100%), yielding a potential reduction in 31% (95% CI, 23%-39%) of benign follow-ups based on conventional DCE-MRI.

CONCLUSION: Ultrafast imaging can be added to conventional DCE-MRI to increase diagnostic accuracy while adding minimal scan time. Future work to standardize evaluation criteria may improve interreader agreement and allow for more robust ultrafast DCE-MRI assessment.},
}

@article {pmid40103823,
year = {2025},
author = {Tisoncik-Go, J and Lewis, TB and Whitmore, LS and Voss, K and Niemeyer, S and Dai, J and Kim, P and Hubbell, K and Iwayama, N and Ahrens, C and Wangari, S and Murnane, R and Edlefsen, PT and Guerriero, KA and Gale, M and Fuller, DH and O'Connor, MA},
title = {Persistent innate immune dysfunction and ZIKV replication in the gastrointestinal tract during SIV infection in pigtail macaques.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1535807},
pmid = {40103823},
issn = {1664-3224},
support = {P51 OD010425/OD/NIH HHS/United States ; U19 AI113173/AI/NIAID NIH HHS/United States ; U42 OD011123/OD/NIH HHS/United States ; R01 AI145296/AI/NIAID NIH HHS/United States ; K01 MH123258/MH/NIMH NIH HHS/United States ; UL1 TR000423/TR/NCATS NIH HHS/United States ; },
mesh = {Animals ; *Immunity, Innate ; *Simian Acquired Immunodeficiency Syndrome/immunology/virology ; *Simian Immunodeficiency Virus/immunology/physiology ; *Virus Replication ; *Zika Virus Infection/immunology/virology ; *Zika Virus/immunology/physiology ; *Gastrointestinal Tract/immunology/virology ; *Macaca nemestrina ; Viremia/immunology ; Disease Models, Animal ; Leukocytes, Mononuclear/immunology ; Coinfection/immunology ; Humans ; },
abstract = {Mosquito-borne flaviviruses, including dengue (DENV) and Zika (ZIKV) viruses, have caused widespread epidemics in areas with high HIV prevalence, partly due to the expanded geographic range of arthropod vectors. Despite the occurrence of large flavivirus outbreaks in areas with high HIV prevalence, little is known about the effects of flavivirus infection in people living with HIV (PLWH). Here, we use a pigtail macaque model of HIV/AIDS to investigate the impact of simian immunodeficiency virus (SIV)-induced immunosuppression on ZIKV replication and pathogenesis. During acute SIV infection, peripheral ZIKV cellular targets expanded and innate immune activation increased. In vitro, peripheral blood mononuclear cells (PBMC) from SIV infected pigtail macaques were less permissive to ZIKV infection. In vivo, ZIKV viremia was delayed and ZIKV was more persistent in the gastrointestinal tissues of SIV-ZIKV co-infected animals. This persistence was associated with changes in innate cellular (monocytes, neutrophils) recruitment to the blood and tissues, reduced anti-ZIKV immunity, and sustained expression of peripheral inflammatory and innate immune genes. Collectively, these findings uniquely suggest that untreated SIV infection may promote inflammatory cellular innate responses and create a state of persistent immune activation that contributes to prolonged ZIKV viremia and persistence in the gastrointestinal tract. Furthermore, these results suggest that PLWH and other immunocompromised individuals could be at higher risk for prolonged ZIKV infection, potentially extending the window of ZIKV transmission. These insights highlight the importance of including PLWH in strategies for deploying vaccines and treatments against ZIKV.},
}

Animals
*Immunity, Innate
*Simian Acquired Immunodeficiency Syndrome/immunology/virology
*Simian Immunodeficiency Virus/immunology/physiology
*Virus Replication
*Zika Virus Infection/immunology/virology
*Zika Virus/immunology/physiology
*Gastrointestinal Tract/immunology/virology
*Macaca nemestrina
Viremia/immunology
Disease Models, Animal
Leukocytes, Mononuclear/immunology
Coinfection/immunology
Humans

@article {pmid40103753,
year = {2025},
author = {Wolock, CJ and Gilbert, PB and Simon, N and Carone, M},
title = {Assessing variable importance in survival analysis using machine learning.},
journal = {Biometrika},
volume = {112},
number = {2},
pages = {asae061},
pmid = {40103753},
issn = {0006-3444},
abstract = {Given a collection of features available for inclusion in a predictive model, it may be of interest to quantify the relative importance of a subset of features for the prediction task at hand. For example, in HIV vaccine trials, participant baseline characteristics are used to predict the probability of HIV acquisition over the intended follow-up period, and investigators may wish to understand how much certain types of predictors, such as behavioural factors, contribute to overall predictiveness. Time-to-event outcomes such as time to HIV acquisition are often subject to right censoring, and existing methods for assessing variable importance are typically not intended to be used in this setting. We describe a broad class of algorithm-agnostic variable importance measures for prediction in the context of survival data. We propose a nonparametric efficient estimation procedure that incorporates flexible learning of nuisance parameters, yields asymptotically valid inference and enjoys double robustness. We assess the performance of our proposed procedure via numerical simulations and analyse data from the HVTN 702 vaccine trial to inform enrolment strategies for future HIV vaccine trials.},
}

@article {pmid40102030,
year = {2025},
author = {Batalha, MA and LeCroy, MN and Lin, J and Peters, BA and Qi, Q and Wang, Z and Wang, T and Gallo, LC and Talavera, GA and McClain, AC and Thyagarajan, B and Daviglus, ML and Hou, L and Llabre, M and Cai, J and Kaplan, RC and Isasi, CR},
title = {Life-course socioeconomic position and the gut microbiome in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2479772},
doi = {10.1080/19490976.2025.2479772},
pmid = {40102030},
issn = {1949-0984},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Hispanic or Latino/statistics & numerical data ; Female ; Male ; Adult ; *Feces/microbiology ; Middle Aged ; United States/epidemiology ; Bacteria/classification/genetics/isolation & purification ; Cohort Studies ; Young Adult ; Socioeconomic Factors ; Adolescent ; Child ; Social Class ; White ; },
abstract = {Socioeconomic position (SEP) in childhood and beyond may influence the gut microbiome, with implications for disease risk. Studies evaluating the relationship between life-course SEP and the gut microbiome are sparse, particularly among Hispanic/Latino individuals, who have a high prevalence of low SEP. We use the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a population-based cohort study conducted in four field centers in the United States (U.S.), to evaluate the association between life-course SEP and gut microbiome composition. Life-course SEP indicators included parental education (proxy of childhood SEP), current SEP (n = 2174), and childhood (n = 988) and current economic hardship (n = 994). Shotgun sequencing was performed on stool samples. Analysis of Compositions of Microbiomes was used to identify associations of life-course SEP indicators with gut microbiome species and functions. Parental education and current SEP were associated with the overall gut microbiome composition; however, parental education and current education explained more the gut microbiome variance than the current SEP. A lower parental education and current SEP were associated with a lower abundance of species from genus Bacteroides. In stratified analysis by nativity, we found similar findings mainly among foreign-born participants. Early-life SEP may have long-term effects on gut microbiome composition underscoring another biological mechanism linking early childhood factors to adult disease.},
}

Humans
*Gastrointestinal Microbiome
*Hispanic or Latino/statistics & numerical data
Female
Male
Adult
*Feces/microbiology
Middle Aged
United States/epidemiology
Bacteria/classification/genetics/isolation & purification
Cohort Studies
Young Adult
Socioeconomic Factors
Adolescent
Child
Social Class
White

@article {pmid40101246,
year = {2025},
author = {Sorror, ML and Saber, W and Logan, BR and Geller, NL and Bellach, A and Kou, J and Wood, WA and McCarty, J and Knight, TG and Runaas, L and Johnston, LJ and Walston, JD and Nakamura, R and Jarrett, L and Mishra, A and Uberti, J and Dahi, PB and Saultz, JN and McCurdy, SR and Morris, LE and Imus, P and Hogan, WJ and Nadiminti, KVG and Bhatt, VR and Olin, RL and Maakaron, J and Sobecks, RM and Wall, SA and Mattila, D and Protz, B and Devine, SM and Horowitz, MM and Artz, AS},
title = {Novel Composite Health Assessment Risk Model for Older Allogeneic Transplant Recipients: BMT-CTN 1704.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025015793},
pmid = {40101246},
issn = {2473-9537},
abstract = {Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for older adults with hematologic malignancies. Concerns about non-relapse mortality (NRM) in older adults limit allo-HCT utilization. We executed a prospective, observational study (BMT-CTN 1704) enrolling allo-HCT recipients aged ≥60 years from 49 centers in the U.S. We analyzed associations between 13 measurements of older adult health and NRM within 1-year to construct a comprehensive health assessment risk model (primary-CHARM) using amultivariate Fine-Gray model and grouped penalized variable selection. Two (Cox and pseudovalue Boosting) Machine-Learning (ML) models were also explored. Models' performances were compared using area under the receiver operating curve (AUC), with bootstrap and crossvalidation sampling to correct for optimism, decision-curve analysis (DCA), calibration, and Brierscores. Among 1105 patients with median age of 67 years (range 60-82) who received alloHCT, NRM was 14.4% and overall survival (OS), 71.7% at 1-year. Factors statistically selected for inclusion in primary-CHARM were: higher comorbidity-burden, lower albumin, higher Creactive protein, older age, higher weight loss percentage, lower patient-reported performance score, and cognitive impairment. Primary-CHARM scores were independently associated with higher NRM (hazard ratio [HR]:2.72, p<0.0001) and worse OS (HR:2.09, p<0.0001). Bootstrap bias-corrected AUC for primary-CHARM was 0.591. Comparing primary-CHARM to HCTcomorbidity index and 2 ML-CHARM models, calibration, Brier score, and DCA analysis favored primary-CHARM. The primary-CHARM, comprised of mostly simple and readily available parameters, risk-stratifies older adults for allo-HCT. Adopting primary-CHARM in practice maypromote broader use of HCT by quantifying risk and enhance the design of strategies to improve outcomes. Clinicaltrials.gov number: (NCT03992352).},
}

@article {pmid40100600,
year = {2025},
author = {Graves, SS and Zellmer, E and Storb, R},
title = {Canine Hematopoietic Cell Transplantation for Graft-Versus-Host Disease.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2907},
number = {},
pages = {207-236},
pmid = {40100600},
issn = {1940-6029},
mesh = {*Graft vs Host Disease/therapy/prevention & control ; Dogs ; Animals ; *Hematopoietic Stem Cell Transplantation/methods/adverse effects ; *Disease Models, Animal ; Transplantation Conditioning/methods ; Transplantation, Homologous/methods ; },
abstract = {Graft-versus-host disease (GVHD) is a risk of hematopoietic cell transplantation (HCT) in the clinical setting. The acute form of the disease is well managed, but the chronic form is more problematic. The canine HCT model, instrumental in establishing successful clinical HCT protocols, reproducibly recapitulates the clinical manifestations of GVHD. Thus, therapies for the prevention and treatment of GVHD in the canine model may be applicable to the clinic. Here, we present the methods necessary to establish both acute and chronic GVHD models in dogs.},
}

*Graft vs Host Disease/therapy/prevention & control
Dogs
Animals
*Hematopoietic Stem Cell Transplantation/methods/adverse effects
*Disease Models, Animal
Transplantation Conditioning/methods
Transplantation, Homologous/methods

@article {pmid40093208,
year = {2025},
author = {Zhao, K and Pershad, Y and Poisner, HM and Ma, X and Quade, K and Vlasschaert, C and Mack, T and Khankari, NK and von Beck, K and Brogan, J and Kishtagari, A and Corty, RW and Li, Y and Xu, Y and Reiner, AP and Scheet, P and Auer, PL and Bick, AG},
title = {Genetic drivers and clinical consequences of mosaic chromosomal alterations in 1 million individuals.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40093208},
support = {U01 HL120393/HL/NHLBI NIH HHS/United States ; HHSN268201800001C/HL/NHLBI NIH HHS/United States ; R01 AG083736/AG/NIA NIH HHS/United States ; T32 GM007347/GM/NIGMS NIH HHS/United States ; R01 HL117626/HL/NHLBI NIH HHS/United States ; DP5 OD029586/OD/NIH HHS/United States ; R01 HL120393/HL/NHLBI NIH HHS/United States ; },
abstract = {Mosaic chromosomal alterations of the autosomes (aut-mCAs) are large structural somatic mutations which cause clonal hematopoiesis and increase cancer risk. Here, we detected aut-mCAs in 1,011,269 participants across four biobanks. Through integrative analysis of the minimum critical region and inherited genetic variation, we found that proto-oncogenes exclusively drive chromosomal gains, tumor suppressors drive losses, and copy-neutral events can be driven by either. We identified three novel inherited risk loci in CHI3L2, HLA class II, and TERT that modulate aut-mCA risk and ten novel aut-mCA-specific loci. We found specific aut-mCAs are associated with cardiovascular, cerebrovascular, or kidney disease incidence. High-risk aut-mCAs were associated with elevated plasma protein levels of therapeutically actionable targets: NPM1, PARP1, and TACI. Participants with multiple high-risk features such as high clonal fraction, more than one aut-mCA, and abnormal red cell morphology had a 50% cumulative incidence of blood count abnormalities over 2 years. Leveraging inherited variation, we causally established aut-mCAs as premalignant lesions for chronic lymphocytic leukemia. Together, our findings provide a framework integrating somatic mosaicism, germline genetics, and clinical phenotypes to identify individuals who could benefit from preventative interventions.},
}

@article {pmid40093158,
year = {2025},
author = {Latorre-Crespo, E and Robertson, NA and Kosebent, EG and MacGillivray, L and Murphy, L and Uddin, M and Whitsel, E and Honigberg, M and Bick, A and Reiner, AP and Orrù, V and Marongiu, M and Cucca, F and Fiorillo, E and Deary, IJ and Harris, S and Cox, S and Marioni, R and Schumacher, L and Chandra, T and Kirschner, K},
title = {Clinical progression of clonal hematopoiesis is determined by a combination of mutation timing, fitness, and clonal structure.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40093158},
issn = {2692-8205},
support = {/WT_/Wellcome Trust/United Kingdom ; U01 AG083829/AG/NIA NIH HHS/United States ; },
abstract = {Clonal hematopoiesis (CH) is characterized by expanding blood cell clones carrying somatic mutations in healthy aged individuals and is associated with various age-related diseases and all-cause mortality. While CH mutations affect diverse genes associated with myeloid malignancies, their mechanisms of expansion and disease associations remain poorly understood. We investigate the relationship between clonal fitness and clinical outcomes by integrating data from three longitudinal aging cohorts (n=713, observations=2,341). We demonstrate pathway-specific fitness advantage and clonal composition influence clonal dynamics. Further, the timing of mutation acquisition is necessary to determine the extent of clonal expansion reached during the host individual's lifetime. We introduce MACS120, a metric combining mutation context, timing, and variant fitness to predict future clonal growth, outperforming traditional variant allele frequency measurements in predicting clinical outcomes. Our unified analytical framework enables standardized clonal dynamics inference across cohorts, advancing our ability to predict and potentially intervene in CH-related pathologies.},
}

@article {pmid40093114,
year = {2025},
author = {Visani, GM and Pun, MN and Minervina, AA and Bradley, P and Thomas, P and Nourmohammad, A},
title = {T-cell receptor specificity landscape revealed through de novo peptide design.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40093114},
issn = {2692-8205},
support = {R01 AI136514/AI/NIAID NIH HHS/United States ; R35 GM141457/GM/NIGMS NIH HHS/United States ; R35 GM142795/GM/NIGMS NIH HHS/United States ; },
abstract = {T-cells play a key role in adaptive immunity by mounting specific responses against diverse pathogens. An effective binding between T-cell receptors (TCRs) and pathogen-derived peptides presented on Major Histocompatibility Complexes (MHCs) mediate an immune response. However, predicting these interactions remains challenging due to limited functional data on T-cell reactivities. Here, we introduce a computational approach to predict TCR interactions with peptides presented on MHC class I alleles, and to design novel immunogenic peptides for specified TCR-MHC complexes. Our method leverages HERMES, a structure-based, physics-guided machine learning model trained on the protein universe to predict amino acid preferences based on local structural environments. Despite no direct training on TCR-pMHC data, the implicit physical reasoning in HERMES enables us to make accurate predictions of both TCR-pMHC binding affinities and T-cell activities across diverse viral epitopes and cancer neoantigens, achieving up to 72% correlation with experimental data. Leveraging our TCR recognition model, we develop a computational protocol for de novo design of immunogenic peptides. Through experimental validation in three TCR-MHC systems targeting viral and cancer peptides, we demonstrate that our designs-with up to five substitutions from the native sequence-activate T-cells at success rates of up to 50%. Lastly, we use our generative framework to quantify the diversity of the peptide recognition landscape for various TCR-MHC complexes, offering key insights into T-cell specificity in both humans and mice. Our approach provides a platform for immunogenic peptide and neoantigen design, opening new computational paths for T-cell vaccine development against viruses and cancer.},
}

@article {pmid40100459,
year = {2025},
author = {Nguyen, NH and Nguyen, MP and Mai, HK and Do, ST and Pham, VH and Vuong, DTP and Maturi, JR and Le, HVT and Cluskey, PM and Pham, VT},
title = {The correlation of clinical and histopathological features of eyelid malignancies: a 5-year retrospective study in Vietnam.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {107},
pmid = {40100459},
issn = {1573-2630},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; Vietnam/epidemiology ; *Eyelid Neoplasms/epidemiology/pathology/diagnosis ; Aged ; Adult ; Incidence ; *Carcinoma, Basal Cell/pathology/epidemiology/diagnosis ; Aged, 80 and over ; Eyelids/pathology ; Melanoma/epidemiology/pathology/diagnosis ; Young Adult ; Sebaceous Gland Neoplasms/pathology/epidemiology/diagnosis ; Adolescent ; },
abstract = {PURPOSE: To analyze the correlation between the clinical and histopathological features of eyelid malignancies in Vietnam.

METHODS: An observational retrospective study was conducted on 190 patients who were diagnosed histopathologically after surgery with eyelid malignancies between 2017 and 2021 at Vietnam National Eye Hospital. Demographic, clinical manifestations, pathological features and outcomes were analyzed.

RESULTS: Basal cell carcinoma was the most common histopathologic type, accounting for 57.9% of cases, followed by sebaceous gland carcinoma at 27.4%. The match between clinical diagnosis and pathological diagnosis was 57.4% across all cases. The majority of basal cell carcinoma cases presented on the lower eyelid, while the majority of sebaceous gland carcinoma cases presented on the upper eyelid. Clinical features with the highest clinical correlation were ulceration (76.4%) for basal cell carcinoma and ill-defined edges (84.6%) among malignant cutaneous melanoma.

CONCLUSION: Eyelid malignancies present significant challenges in clinical diagnosis, with only moderate concordance between clinical and histopathological findings. Basal cell carcinoma is the most common eyelid malignancy in Vietnam, though its incidence is significantly lower than in Western countries. Clinical findings with the most consistent clinical correlation were high rates of ulceration in basal cell carcinoma and ill-defined edges in malignant melanoma.},
}

Humans
Retrospective Studies
Male
Female
Middle Aged
Vietnam/epidemiology
*Eyelid Neoplasms/epidemiology/pathology/diagnosis
Aged
Adult
Incidence
*Carcinoma, Basal Cell/pathology/epidemiology/diagnosis
Aged, 80 and over
Eyelids/pathology
Melanoma/epidemiology/pathology/diagnosis
Young Adult
Sebaceous Gland Neoplasms/pathology/epidemiology/diagnosis
Adolescent

@article {pmid40100220,
year = {2025},
author = {Duncan, FC and Triplette, M},
title = {Adherence to Follow-Up Lung Cancer Screening-A Critical Target for Intervention.},
journal = {JAMA network open},
volume = {8},
number = {3},
pages = {e250949},
doi = {10.1001/jamanetworkopen.2025.0949},
pmid = {40100220},
issn = {2574-3805},
}

@article {pmid40099861,
year = {2025},
author = {Othus, M and Sharon, E and Wu, MC and Sondak, VK and Ribas, A and Patel, SP},
title = {Design considerations for randomized comparisons of neoadjuvant-adjuvant versus adjuvant-only cancer immunotherapy when tumor measurement schedules do not align (SWOG S1801).},
journal = {Clinical trials (London, England)},
volume = {},
number = {},
pages = {17407745251321371},
doi = {10.1177/17407745251321371},
pmid = {40099861},
issn = {1740-7753},
abstract = {BackgroundIn 2022, SWOG S1801 was the first trial to demonstrate that single-agent anti-PD-1 checkpoint inhibition used as neoadjuvant-adjuvant therapy leads to significantly improved outcomes compared to adjuvant-only therapy. Endpoints in trials comparing neoadjuvant-adjuvant to adjuvant strategies need special consideration to ensure that event measurement timing is appropriately accounted for in analyses to avoid biased comparisons artificially favoring one arm over another.MethodsThe S1801 trial is used a case study to evaluate the issues involved in selecting endpoints for trials comparing neoadjuvant-adjuvant versus adjuvant-only strategies.ResultsDefinitions and timing of measurement of events is provided. Trial scenarios when recurrence-free versus event-free survival should be used are provided.ConclusionsIn randomized trials comparing neoadjuvant-adjuvant to adjuvant-only strategies, event-free survival endpoints measured from randomization are required for unbiased comparison of the arms. The time at which events can be measured on each arm needs to be carefully considered. If measurement of events occurs at different times on the randomized arms, modified definitions of event-free survival must be used to avoid bias.},
}

@article {pmid40099838,
year = {2025},
author = {Lama, JR and Bender Ignacio, RA and Duerr, A},
title = {Acute retroviral syndrome.},
journal = {Current opinion in HIV and AIDS},
volume = {},
number = {},
pages = {},
doi = {10.1097/COH.0000000000000933},
pmid = {40099838},
issn = {1746-6318},
abstract = {PURPOSE OF REVIEW: To review the most important recent literature on the definition, epidemiology, clinical presentation, pathogenesis and treatment of the acute retroviral syndrome (ARS), a constellation of nonspecific symptoms and transient illness occuring in at least 50% of persons shortly after HIV acquisition. ARS is driven by initial rapid HIV viral replication and dissemination after acquisition, followed by immune activation and massive systemic inflammation. A more detailed understanding of ARS is important for the implementation of early detection efforts, treatment and public health strategies to control HIV.

RECENT FINDINGS: Recent research has provided deeper insights into ARS. Key findings include associations of ARS with heightened immune activation and elevated levels of IFNγ and multiple other cytokines, particularly IP-10, as well as with higher viral load and more severe CD4+ depletion during acute infection. These negative impacts can be mitigated by early antiretroviral therapy initiation and long-term outcomes are generally similar in treated individals with or without ARS.

SUMMARY: Current findings underscore the importance of early detection and intervention in ARS to mitigate long-term health impacts and inform the development of targeted therapeutic strategies.},
}

@article {pmid40099002,
year = {2025},
author = {Gong, E and Zawacki, L and Fan, X and Hippe, DS and Menon, AA and Remington, AJ and Lachance, K and Akaike, T and Tachiki, L and Park, SY and Nghiem, P},
title = {Immunotherapy response in immunosuppressed patients with Merkel cell carcinoma: analysis of 183 patients.},
journal = {BMJ oncology},
volume = {4},
number = {1},
pages = {e000654},
pmid = {40099002},
issn = {2752-7948},
abstract = {OBJECTIVE: Merkel cell carcinoma (MCC) is an aggressive skin cancer with poor outcomes in immunosuppressed patients. While immune checkpoint inhibitors (ICIs) achieve ~60% response rates in immunocompetent MCC patients, their efficacy in immunosuppressed patients remains unclear due to exclusion from trials. This study compares ICI outcomes, safety and the impact of immunosuppression subtypes between these groups.

METHODS AND ANALYSIS: This retrospective study analysed 183 advanced MCC patients on first-line ICIs from a Seattle-based data repository. Of these, 147 were immunocompetent, and 36 were immunosuppressed (chronic lymphocytic leukaemia (CLL) n=10, autoimmune disorders n=10, other haematologic malignancies n=9, solid organ transplants n=4 and HIV/AIDS n=3). Outcomes included objective response rate, disease progression, MCC-specific and overall survival probability, adjusted for age, sex and stage at ICI initiation.

RESULTS: Initial ICI response rates at 6 months were 50% in immunosuppressed and 61.5% in immunocompetent patients (HR=0.71, p=0.17). Immunosuppressed patients had higher risks of disease progression (2 years: 53.9% vs 42.1%, HR=1.65, p=0.05) and MCC-specific mortality (2 years: 38.7% vs 24.4%, HR=1.85, p=0.04). CLL patients (n=10) had a particularly low response rate (response rate: 20.0% vs 61.5%, HR=0.18, p=0.02) and high progression risk (2 years: 80.0% vs 42.1%, HR=4.09, p=0.01). Immunosuppressed patients faced higher rates of ICI toxicity (6-month risk: 51.6% vs 36.6%, HR=1.79, p=0.03).

CONCLUSIONS: ICIs provide meaningful benefits to immunosuppressed MCC patients, though their response rates are lower, and progression risk is higher compared with immunocompetent patients.},
}

@article {pmid40098997,
year = {2025},
author = {Xia, T and Han, F and Wang, Y and Xie, X and Yuan, C and Lu, G and Xiao, W and Tu, B and Ren, H and Gong, W and Wang, Y},
title = {Inhibition of CD53 Reduces the Formation of ROS-Induced Neutrophil Extracellular Traps and Protects Against Inflammatory Injury in Acute Pancreatitis.},
journal = {Journal of inflammation research},
volume = {18},
number = {},
pages = {3725-3739},
pmid = {40098997},
issn = {1178-7031},
abstract = {BACKGROUND: The tetraspanin CD53 transmembrane protein is vital in immune cells like B cells and T cells, playing a crucial role in various inflammatory conditions. However, its involvement in neutrophils regarding inflammation remains uncertain. This study aims to examine the impact of CD53 on neutrophil extracellular traps (NETs) formation.

METHODS: Phorbol 12-myristate 13-acetate (PMA) was utilized to establish an in vitro classical NETs model to investigate the influence of CD53 on NETs formation and its regulatory mechanisms. Subsequently, the link between CD53 and acute pancreatitis (AP), a model of aseptic inflammatory responses connected to NETs, was verified. Peripheral blood neutrophils from clinical AP patients were collected to explore the role of CD53 in AP, while an AP mouse model induced by caerulein was employed to confirm the impact of CD53 inhibition on AP mice pancreatic tissue.

RESULTS: Our study has shown that CD53 is significantly elevated in in vitro NETs models and neutrophils from AP patients. The expression of CD53 is closely related to the clinical prognosis of AP patients. At the same time, CD53 neutralizing antibody (Anti-CD53) can significantly inhibit the formation of NETs in vitro, inflammatory injury in AP mice and the formation of NETs in damaged tissues. Mechanistically, CD53 can modulate the PI3K/AKT pathway and promote the formation of NETs. Finally, targeted regulation of CD53 can effectively reduce inflammatory injury and NETs formation in damaged tissues of AP mice.

CONCLUSION: The results of this study mark the first confirmation that CD53 plays a crucial role in NETs formation. Targeting CD53 inhibition could potentially serve as a novel therapeutic approach for the treatment of AP.},
}

@article {pmid40098681,
year = {2025},
author = {Orouskhani, M and Rauniyar, S and Morella, N and Lachance, D and Minot, SS and Dey, N},
title = {Deep learning imaging analysis to identify bacterial metabolic states associated with carcinogen production.},
journal = {Discover imaging},
volume = {2},
number = {1},
pages = {2},
pmid = {40098681},
issn = {3004-9776},
abstract = {BACKGROUND: Colorectal cancer (CRC) is a globally prevalent cancer. Emerging research implicates the gut microbiome in CRC pathogenesis. Bacteria such as Clostridium scindens can produce the carcinogenic bile acid deoxycholic acid (DCA). It is unknown whether imaging methods can differentiate DCA-producing and DCA-non-producing C. scindens cells.

METHODS: Light microscopy images of anaerobically cultured C. scindens in four conditions were acquired at 100× magnification using the Tissue FAX system: C. scindens in media alone (DCA-non-producing state), C. scindens in media with cholic acid (DCA-producing state), or C. scindens in co-culture with one of two Bacteroides species (intermediate DCA production states). We evaluated three approaches: whole-image classification, per-cell classification, and image segmentation-based classification. For whole-image classification, we used a custom Convolutional Neural Network (CNN), pre-trained DenseNet, pre-trained ResNet, and ResNet enhanced by integrating the Digital Images of Bacterial Species (DIBaS) dataset. For cell detection and classification, we applied thresholding (OTSU or adaptive thresholding) followed by a ResNet model. Finally, image segmentation-based classification was performed using nnU-Net.

RESULTS: For whole-image analysis, DIBaS-enhanced ResNet models achieved the best performance in distinguishing C. scindens states in monoculture (accuracy 0.89 ± 0.006) and in co-cultures (accuracy 0.86 ± 0.004). Per-cell analysis was optimal at a C constant value of 3, with the ResNet model achieving 62-74% accuracy for C. scindens states in monoculture. Segmentation-based analysis using nnU-Net resulted in Dice coefficients of 87% for C. scindens and 74-76% for the Bacteroides species.

CONCLUSIONS: This study demonstrates feasibility of image-based deep learning models in identifying health-relevant gut bacterial metabolic states.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s44352-025-00006-1.},
}

@article {pmid40098097,
year = {2025},
author = {Berry, AA and Richie, TL and Church, LWP and Laurens, MB and Boyce, C and Kc, N and Joshi, S and Koudjra, AR and Butler, L and Chen, MC and Abebe, Y and Murshedkar, T and James, ER and Billingsley, PF and Sim, BKL and Hoffman, SL and Lyke, KE},
title = {Safety, tolerability and immunogenicity of a condensed, multi-dose prime regimen of PfSPZ Vaccine for the prevention of Plasmodium falciparum malaria infection.},
journal = {Malaria journal},
volume = {24},
number = {1},
pages = {88},
pmid = {40098097},
issn = {1475-2875},
support = {U44AI167783//National Institute of Allergy and Infectious Diseases,United States/ ; },
mesh = {*Malaria Vaccines/immunology/administration & dosage/adverse effects ; Humans ; *Malaria, Falciparum/prevention & control/immunology ; Adult ; Female ; Male ; *Plasmodium falciparum/immunology ; Double-Blind Method ; Young Adult ; Adolescent ; Middle Aged ; Vaccines, Attenuated/immunology/administration & dosage/adverse effects ; Antibodies, Protozoan/blood ; Sporozoites/immunology ; },
abstract = {BACKGROUND: The World Health Organization (WHO) has called for new malaria vaccines with > 90% efficacy against Plasmodium falciparum infection to expand the anti-disease benefit provided by the RTS,S/AS01 and R21/Matrix M subunit vaccines currently administered to infants and young children in sub-Saharan Africa. Attenuated P. falciparum sporozoites (PfSPZ) are being developed as a traveller's vaccine and to fulfill WHO's call for high-level efficacy in endemic countries to support malaria elimination.

METHODS: PfSPZ Vaccine, comprised of radiation-attenuated PfSPZ, was compared with normal saline placebo in a randomized, double-blind trial targeting 60 malaria-naive US adults to assess safety, tolerability, immunogenicity, and efficacy against heterologous controlled human malaria infection three and twelve weeks after immunization. Pharmacists provided syringes to blinded clinicians using 3:1 (vaccine:placebo) blocked randomization, for administration by direct venous inoculation on days 1 and 8 (multidose prime) and day 29 (boost), a condensed regimen with superior efficacy. Primary outcomes included adverse events and antibody responses to the P. falciparum circumsporozoite protein (PfCSP).

RESULTS: 31 participants were screened, randomized and immunized twice (V1, V2) 5-7 days apart, with one withdrawal after an intercurrent adverse event. A vial issue, later traced to the vial manufacturer, halted further immunizations. Solicited local and systemic adverse events recorded for 2 and 7 days after immunizations, respectively, occurred with equal frequency and severity in the 23 vaccinees and 7 controls receiving two immunizations, as did unsolicited adverse events recorded for 28 days and laboratory abnormalities 1 and 5 weeks after V2. Four of 23 vaccinees and one of 7 controls (p = 1.00) developed grade 2 adverse events including subjective fever, headache, malaise, fatigue, rigors, arthralgia and myalgia after V2 but not V1, these symptoms generally resolving within 24 h. Twenty-two of 23 (96%) vaccinees developed IgG (median 99-fold increase over baseline) and IgM (median 1,110-fold increase) antibodies to PfCSP one week after V2. Antibody responses were not associated with reactogenicity.

CONCLUSIONS: The two-dose priming immunization regimen was safe, well tolerated and highly immunogenic. Larger studies may better define the adverse event profile of condensed regimens of PfSPZ Vaccine in malaria-naive adults.

TRIAL REGISTRATION NUMBER: clinicaltrial.gov NCT05604521.},
}

*Malaria Vaccines/immunology/administration & dosage/adverse effects
Humans
*Malaria, Falciparum/prevention & control/immunology
Adult
Female
Male
*Plasmodium falciparum/immunology
Double-Blind Method
Young Adult
Adolescent
Middle Aged
Vaccines, Attenuated/immunology/administration & dosage/adverse effects
Antibodies, Protozoan/blood
Sporozoites/immunology

@article {pmid40097658,
year = {2025},
author = {Simon, S and Bugos, G and Prins, R and Rajan, A and Palani, A and Heyer, K and Stevens, A and Zeng, L and Thompson, KA and Atilla, PA and Price, JP and Kluesner, MG and Jaeger-Ruckstuhl, CA and Shabaneh, TB and Olson, JM and Su, X and Riddell, SR},
title = {Design of sensitive monospecific and bispecific synthetic chimeric T cell receptors for cancer therapy.},
journal = {Nature cancer},
volume = {},
number = {},
pages = {},
pmid = {40097658},
issn = {2662-1347},
support = {R01 CA114536/CA/NCI NIH HHS/United States ; P01 CA18029//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; SCOR 1023-20//Leukemia and Lymphoma Society (Leukemia & Lymphoma Society)/ ; SCOR 1023-20//Leukemia and Lymphoma Society (Leukemia & Lymphoma Society)/ ; 3405-21//Leukemia and Lymphoma Society (Leukemia & Lymphoma Society)/ ; SRA220501//Bristol-Myers Squibb (Bristol-Myers Squibb Company)/ ; },
abstract = {The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) is effective in B cell malignancies. However, the persistence of cancer cells with low levels or complete absence of the target antigen, thereby evading detection by CAR T cells, leads to relapse. These evasion mechanisms highlight the need for receptors with enhanced sensitivity and multispecificity. We introduce a synthetic chimeric T cell receptor (ChTCR) that confers superior antigen sensitivity compared with CARS and previous hybrid TCR designs and is readily adapted for bispecific targeting. ChTCRs replicate the structure of natural TCRs, form classical immune synapses and demonstrate TCR-like signaling. T cells expressing bispecific ChTCRs (Bi-ChTCRs) are more effective than bispecific CAR T cells in eradicating tumors with heterogeneous antigen expression in vivo in female mice. The Bi-ChTCR architecture is resilient and can be designed to target pairs of B cell and multiple myeloma antigens. These findings provide a widely applicable strategy to combat tumor heterogeneity and prevent relapse.},
}

@article {pmid40095530,
year = {2025},
author = {Gwin, WR and Hurvitz, SA},
title = {TOP-1 Priority: Advancing Biomarker-Driven Patient Selection for the use of ADCs.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-25-0166},
pmid = {40095530},
issn = {1557-3265},
abstract = {A recent study reports the emergence of TOP1 mutations as a potential mechanism of resistance to topoisomerase inhibitor-ADCs in advanced breast cancer. This is a crucial first step in identifying biomarkers to guide ADC therapy selection and underscores the need for caution when sequencing ADCs with similar payloads.},
}

@article {pmid40089329,
year = {2025},
author = {Tseng, D and Lee, S},
title = {Tumor-Infiltrating Lymphocyte Therapy: A New Frontier.},
journal = {Transplantation and cellular therapy},
volume = {31},
number = {3S},
pages = {S599-S609},
doi = {10.1016/j.jtct.2024.11.014},
pmid = {40089329},
issn = {2666-6367},
mesh = {Humans ; *Lymphocytes, Tumor-Infiltrating/immunology/transplantation ; *Neoplasms/therapy/immunology ; *Immunotherapy, Adoptive/methods ; Immunotherapy/methods ; Animals ; Melanoma/therapy/immunology/pathology ; },
abstract = {In recent years, the successful use of tumor-infiltrating lymphocyte (TIL) therapy to treat melanoma not only culminated in a landmark Food and Drug Administration approval, but has also fueled the emergence of a new, rapidly growing field in TIL cellular immunotherapy surrounding novel enhancements in TIL design, refined manufacturing strategies to enrich for more potent TIL populations, as well as numerous clinical trials now investigating TIL therapy in additional solid tumor types beyond melanoma. This review provides a summary of the latest advances in TIL therapy and what lies ahead for the field. The first section explores several solid cancers that demonstrate the greatest potential for future indications of TIL therapy. The second section provides insight into the promising innovations for designing the next generation of TIL with greater specificity, persistence, safety, and function.},
}

Humans
*Lymphocytes, Tumor-Infiltrating/immunology/transplantation
*Neoplasms/therapy/immunology
*Immunotherapy, Adoptive/methods
Immunotherapy/methods
Animals
Melanoma/therapy/immunology/pathology

@article {pmid40088973,
year = {2025},
author = {Prentice, RL and Aragaki, AK and Zheng, C and Manson, JE and Tinker, LF and Schoeller, DA and Ravelli, MN and Raftery, D and Gowda, GAN and Navarro, SL and Huang, Y and Mossavar-Rahmani, Y and Wallace, RB and Johnson, KC and Lampe, JW and Neuhouser, ML},
title = {Energy intake is associated with dietary macronutrient densities: inversely with protein and monounsaturated fat and positively with polyunsaturated fat and carbohydrate among postmenopausal females.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajcnut.2025.03.011},
pmid = {40088973},
issn = {1938-3207},
abstract = {BACKGROUND: Associations of the macronutrient composition of the diet with total energy intake (EI) are uncertain, as are associations of macronutrient composition with self-reported energy underreporting.

OBJECTIVES: We aim to estimate associations of biomarker-assessed EI with both biomarker-assessed and self-reported macronutrient component densities in a Women's Health Initiative (WHI) sub-cohort of postmenopausal U.S. females. Secondarily, we examine energy underreporting using food records, recalls and frequencies, for association with macronutrient densities.

DESIGN AND METHODS: We used a previously proposed EI biomarker equation based on doubly-labeled water (DLW) and updated biomarker equations for several macronutrient component densities, to estimate EI and macronutrient component densities in a WHI nutritional biomarkers sub-cohort (n=436; 2007-2009). We used linear regression of EI biomarker values on biomarker and self-reported macronutrient component densities, and of log-EI underreporting values on biomarker densities, to examine targeted associations.

RESULTS: Using biomarker assessments, the geometric mean (95% CI) for EI corresponding to a 20% increment in carbohydrate density was 2.0% (0.1%, 3.9%) higher, and for a 20% protein density increment was 2.1% (0.5%, 3.7%) lower. The former was attributable to added sugars. Similarly, EI values for 20% increments in polyunsaturated (PUFA), and monounsaturated (MUFA) fatty acids densities were respectively 1.4% (0.3%, 2.6%) higher, and 1.5% (0.1%, 2.9%) lower. Pertinent associations were either not detected or were substantially attenuated if instead self-reported macronutrient densities were used. Also, EI underreporting was strongly related to self-reported macronutrient densities using food records, recalls, or frequencies.

CONCLUSIONS: Among U.S. postmenopausal females lower EI was associated with diets relatively high in protein or MUFA, and higher EI was associated with diets relatively high in PUFA or added sugars. These associations are of public health importance, but are mostly missed using self-reported dietary density assessments. Self-reported energy underestimation is substantially associated with self-reported macronutrient densities. This study is registered with clinicaltrials.gov identifier: NCT00000611.},
}

@article {pmid40088909,
year = {2025},
author = {Stranix-Chibanda, L and Hamilton, EL and Ngo, J and Jiao, Y and Hanscom, B and Choudhury, RP and Agyei, Y and Piwowar-Manning, E and Marzinke, M and Delany-Moretlwe, S and Mgodi, N and Siziba, B and Naidoo, I and Gati Mirembe, B and Kamira, B and McCoig, C and Adeyeye, A and Spiegel, HML and Hosek, S and , },
title = {Safety, tolerability, and acceptability of long-acting injectable cabotegravir for HIV prevention in cisgender female adolescents (HPTN 084-01): a single-arm, open-label, phase 2b trial.},
journal = {The lancet. HIV},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2352-3018(24)00310-2},
pmid = {40088909},
issn = {2352-3018},
abstract = {BACKGROUND: Long-acting formulations of HIV pre-exposure prophylaxis (PrEP) appear particularly well suited to adolescents. We aimed to establish the safety, tolerability, and acceptability of long-acting injectable cabotegravir as PrEP in cisgender adolescent girls.

METHODS: HPTN 084-01 is a single-arm, open-label, phase 2b trial conducted at three clinical research sites in South Africa, Uganda, and Zimbabwe. Girls were recruited via community study-outreach teams, reproductive health clinics, and peer referral. Sexually active adolescent girls (younger than 18 years) willing to use long-acting contraception, weighing at least 35 kg, and able to participate with parental or guardian consent (unless an emancipated minor) were eligible. After an oral lead-in, if no adverse events occurred, participants received a 3 mL intramuscular gluteal injection (long-acting injectable cabotegravir 600 mg) at weeks 5, 9, 17, 25, and 33. The product was discontinued for grade 3 or higher toxic effects or pregnancy. The primary outcomes were safety, tolerability, and acceptability. Safety (ie, proportions of grade 2 or higher clinical and laboratory events) was assessed at weeks 6, 10, 18, 26, and 34 in all enrolled participants. Injection tolerability (ie, proportions of premature discontinuation due to intolerability, frequency of injections, or burden of study procedures) and product acceptability (ie, proportions of scheduled injections completed and participants preferring long-acting injectable cabotegravir for future use) were assessed in all participants who received at least one injection at study end. The trial was registered with ClinicalTrials.gov (NCT04824131) and is completed.

FINDINGS: Between Nov 1, 2020, and Aug 31, 2021, 69 participants were assessed for eligibility and 55 met inclusion criteria. The mean age was 16·0 years (SD 1·1), 39 (71%) had a recent primary sexual partner, 12 (22%) reported transactional sex, and 22 (40%) had sexually transmitted infections at baseline. Two participants dropped out and did not initiate long-acting injectable cabotegravir due to adverse events unrelated to the study drug during the oral lead-in. One participant stopped long-acting injectable cabotegravir after three injections due to pregnancy. 51 (93%) participants reported at least one adverse event of grade 2 or higher, mostly unrelated, transient laboratory abnormalities. There were no long-acting injectable cabotegravir discontinuations due to intolerability. Of the 52 participants who completed step 2, all scheduled injections were completed and 32 (62%) participants reported they would consider using long-acting injectable cabotegravir for HIV prevention in the future.

INTERPRETATION: Long-acting injectable cabotegravir is a safe, tolerable, and acceptable option for the prevention of HIV in adolescent girls. Our study findings expand the HIV prevention options available to adolescent girls.

FUNDING: National Institute of Allergy and Infectious Diseases, National Institute of Mental Health, National Institute on Drug Abuse, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, ViiV Healthcare, and The Bill & Melinda Gates Foundation.},
}

@article {pmid40088674,
year = {2025},
author = {Kumaraswamy, A and Mannan, R and Swaim, OA and Rodansky, E and Wang, XM and Udager, A and Mehra, R and Li, H and Morrissey, C and Corey, E and Haffner, MC and Nelson, PS and Chinnaiyan, AM and Yates, JA and Alumkal, JJ},
title = {LSD1+8a is an RNA biomarker of neuroendocrine prostate cancer.},
journal = {Neoplasia (New York, N.Y.)},
volume = {63},
number = {},
pages = {101151},
doi = {10.1016/j.neo.2025.101151},
pmid = {40088674},
issn = {1476-5586},
abstract = {BACKGROUND: Lysine-specific demethylase 1 (LSD1) is a histone demethylase and regulator of differentiation, including in cancer. A neuronal-specific isoform of LSD1-LSD1+8a-has been shown to play a key role in promoting neuronal differentiation in the developing brain. We previously determined that LSD1+8a transcripts were detected in an aggressive subtype of prostate cancer harboring a neuronal program-neuroendocrine prostate cancer (NEPC)-but not in prostate adenocarcinomas harboring a glandular program. However, the number of samples examined was limited.

METHODS: Using a large collection of prostate cancer patient cell lines and patient-derived xenografts (PDXs), we measured LSD1+8a using quantitative polymerase chain reaction (qPCR), RNA in situ hybridization (RNA-ISH), and protein detection methods. We then validated our findings using an independent cohort of patient tumor samples.

RESULTS: LSD1+8a mRNA expression was detected in every NEPC cell line and PDX examined by qPCR and RNA-ISH but in none of the prostate adenocarcinomas. We validated the RNA-ISH results in patient tumors, confirming that LSD1+8a was expressed in all NEPC tumors but in none of the adenocarcinomas. Finally, we generated a rabbit monoclonal antibody specific to LSD1+8a protein and confirmed its specificity using normal neuronal tissue samples. However, LSD1+8a protein was not detectable in NEPC tumors-likely due to the substantially lower levels of LSD1+8a mRNA in NEPC tumors vs. normal neuronal tissues.

CONCLUSIONS: Measuring LSD1+8a mRNA is a sensitive and specific method for the diagnosis of NEPC, which is often challenging.},
}

@article {pmid40088469,
year = {2025},
author = {Banerjee, R and Richards, A and Midha, S and Afrough, A and Anwer, F and Atanackovic, D and Atrash, S and Bachanova, V and Beitinjaneh, AM and Ouchveridze, E and Castaneda Puglianini, O and Chhabra, S and Cicero, KI and Davis, JA and Dhakal, B and Dima, D and Ferreri, CJ and Forsberg, PA and Freeman, CL and Herr, MM and Jain, T and Janakiram, M and Khouri, J and Kocoglu, MH and Kumar, AD and Liu, Y and Locke, FL and McGuirk, JP and Mikkilineni, L and Nadeem, O and Parrondo, RD and Pasvolsky, O and Peres, LC and Purvey, S and Raza, S and Reshef, R and Richard, S and Rossi, AC and Sborov, DW and Shune, L and Wagner, CB and Zanwar, SS and Sidana, S and Patel, KK and Hansen, DK and Kumar, SK and Lin, Y and Martin, TG and Voorhees, PM and Anderson, LD and Cowan, AJ and Kaur, G},
title = {Universal driving restrictions beyond 4 weeks appear unnecessary following CAR-T therapy in multiple myeloma.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025016131},
pmid = {40088469},
issn = {2473-9537},
}

@article {pmid40086733,
year = {2025},
author = {Antonarelli, G and Pérez-García, JM and Gion, M and Rugo, H and Schmid, P and Bardia, A and Hurvitz, S and Harbeck, N and Tolaney, SM and Curigliano, G and Llombart-Cussac, A and Cortés, J},
title = {Redefining Clinical Trial Strategic Design to Support Drug Approval in Medical Oncology.},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.annonc.2025.03.005},
pmid = {40086733},
issn = {1569-8041},
abstract = {Randomized clinical trials represent the gold standard for the introduction of innovative therapies in medical oncology, and they provide the highest level of evidence to ascertain the clinical activity of new drugs or novel combinations. However, the current infrastructure of clinical trials supporting innovative drug approvals is challenged by an increased body of knowledge concerning tumor biology and therapy resistance, a fast-growing armamentarium of novel anti-cancer compounds, an impressively upscaled data analysis capacity, as well as increasing costs related to clinical trials' management. In this scenario, modern clinical trial designs need to evolve to expedite new drug approvals by tailoring patients' treatment strategies according to their medical needs. Balanced, patient-oriented, clinical trial designs are eagerly warranted to increase their efficiency, to include the fast-pace of technological innovations and scientific discoveries, and ultimately to face the challenges of the modern medical oncology field.},
}

@article {pmid40086461,
year = {2025},
author = {Diallo, F and Haidara, FC and Tapia, MD and Dominguez Islas, CP and Alderson, MR and Hausdorff, WP and Martellet, L and Hosken, N and Kapse, D and Kulkarni, PS and Townsend-Payne, K and Vanni, F and Posavad, CM and Sow, SO and Kotloff, KL and Chen, WH and , },
title = {Safety and immunogenicity of a pentavalent meningococcal conjugate vaccine targeting serogroups A, C, W, Y, and X when co-administered with routine childhood vaccines at ages 9 months and 15 months in Mali: a single-centre, double-blind, randomised, controlled, phase 3, non-inferiority trial.},
journal = {Lancet (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1016/S0140-6736(25)00046-7},
pmid = {40086461},
issn = {1474-547X},
abstract = {BACKGROUND: Invasive meningococcal disease is a devastating public health problem for the African meningitis belt. We assessed the safety and immunogenicity of a pentavalent meningococcal conjugate vaccine targeting serogroups A, C, Y, W, and X (NmCV-5) relative to a licensed, quadrivalent meningococcal conjugate vaccine (MenACWY-TT) when co-administered with routine childhood vaccines at ages 9 months and 15 months.

METHODS: In this single-centre, double-blind, randomised, controlled, phase 3, non-inferiority trial, children aged 9-11 months who had completed their local infant Expanded Program on Immunization (EPI) vaccines were recruited at the Centre pour le Développement des Vaccins in Bamako, Mali. Participants were randomly assigned (1:1·2) at their 9-month EPI visits to receive a meningococcal vaccine at either their 9-month or 15-month EPI vaccination visits. At each participant's designated EPI visit, they were randomly assigned a second time (2:1) to receive either NmCV-5 or MenACWY-TT. Study vaccines and designated EPI vaccines were prepared and administered by assigned unmasked study personnel. Parents or guardians, investigators, and all other trial staff were masked to meningococcal vaccine assignments. The meningococcal vaccines were co-administered with a measles and rubella vaccine (first dose) and a yellow fever vaccine at age 9 months or with a measles and rubella vaccine (second dose) at age 15 months. The primary endpoint, seroprotective response, was defined as a rabbit complement serum bactericidal antibody titre of 8 or higher, with the estimand, given as the difference in the proportions of participants for each of the five meningococcal serogroups who showed this response 28 days after vaccination, assessed in the per-protocol population. The prespecified non-inferiority margin was -10% for all five serogroups in both age groups. The non-inferiority of the NmCV-5 seroprotective response to serogroup X was evaluated in comparison with the lowest seroprotective response for MenACWY-TT among serogroups A, C, W, or Y. Safety was a secondary endpoint, assessed over 6 months in a modified intention-to-treat population that included all participants who received a randomly assigned meningococcal vaccine. This trial is registered with ClinicalTrials.gov, NCT05093829.

FINDINGS: Between March 24 and Aug 15, 2022, 1325 participants were enrolled and randomly assigned to receive a meningococcal vaccine at either age 9 months (n=602) or age 15 months (n=723). Meningococcal vaccines were administered to 600 of the 602 participants assigned to the 9-month vaccination group during that same period. Between Sept 27, 2022, and Feb 6, 2023, 600 participants received meningococcal vaccines at their 15-month visits. In both groups, 400 participants received NmCV-5 and 200 participants received MenACWY-TT. The per-protocol population assessed in the non-inferiority analysis included 564 participants vaccinated at age 9 months (373 who received NmCV-5 and 191 who received MenACWY-TT) and 549 participants vaccinated at age 15 months (367 who received NmCV-5 and 182 who received MenACWY-TT). Among the participants in the per-protocol population who received NmCV-5 at age 9 months, the difference in seroprotection prevalence for NmCV-5 relative to MenACWY-TT was 0·0% (95% CI -1·0 to 2·0) for serogroup A, -0·5% (-2·3 to 1·9) for serogroup C, -3·0% (-6·3 to 0·8) for serogroup W, and -3·0% (-5·4 to -0·4) for serogroup Y. For serogroup X, non-inferiority was assessed relative to seroprotection for serogroup W in participants who received MenACWY-TT, with a difference of 2·3% (95% CI 0·3 to 4·7). The difference in the prevalence of seroprotection among the participants who received NmCV-5 at age 15 months relative to participants who received MenACWY-TT at age 15 months was 0·8% (95% CI -0·6 to 3·7) for serogroup A, -0·8% (-3·3 to 2·5) for serogroup C, 0·3% (-1·8 to 3·5) for serogroup W, and 1·4% (-0·6 to 4·8) for serogroup Y. For serogroup X, non-inferiority was assessed in relation to seroprotection for serogroup Y in participants who received MenACWY-TT, with a difference of 1·9% (95% CI 0·0 to 4·4). NmCV-5 responses in both age groups were non-inferior to MenACWY-TT responses for all five serogroups. Six serious adverse events were recorded but none were deemed related to vaccination.

INTERPRETATION: When compared with a licensed, quadrivalent meningococcal conjugate vaccine, and given alongside other routine vaccines, a single dose of NmCV-5 was safe and elicited a non-inferior immune response in infants aged 9 months and young children aged 15 months.

FUNDING: US National Institutes of Health, UK Foreign, Commonwealth & Development Office, and Serum Institute of India.},
}

@article {pmid40086122,
year = {2025},
author = {Dale, R and He, H and Chen, Y},
title = {Absorbing Markov chain model of PrEP drug adherence to estimate adherence decay rate and probability distribution in clinical trials.},
journal = {Journal of theoretical biology},
volume = {604},
number = {},
pages = {112086},
doi = {10.1016/j.jtbi.2025.112086},
pmid = {40086122},
issn = {1095-8541},
abstract = {Pre-exposure prophylaxis (PrEP) is increasingly used to prevent the transmission of H.I.V. in at-risk populations. However, PrEP users may discontinue use of the medicine due to side effects, lower perceived risk, or other reasons. The usage metrics of 594 individuals was tracked over 350 days using the Wisepill electronic monitoring system. We model the PrEP drug adherence level using an absorbing Markov chain with a unique absorbing state. The transition matrix T obtained from the Wisepill data will have a trivial eigenvector (eigendistribution) associated with the first (i.e., largest) eigenvalue 1. The 2nd eigenvalue(s) then become important in determining the asymptotic behavior of the Markov chain, dictating how fast the Markov chain decays to the absorbing state. Under a fairly general assumption, we prove that the second positive eigenvalue is unique and the corresponding eigenvector will have nonnegative entries with exceptions at absorbing states. In addition, we define the asymptotic half life of the absorbing Markov chain directly from the 2nd eigenvalue. We then determine the 2nd eigenvalue of T and the asymptotic half life of the Markov chain, which turns out to be very close to the real half life of the Markov chain. Finally, we interpret the 2nd eigenvector as the relative probability distribution of X∞ with respect to the decay rate of the 2nd eigenvalue. By applying these methods to the Wisepill data, we estimate the half-life of population adherence to be 46 weeks. The bi-weekly decay rate observed in these data from 90 to 100 % adherence is 3 %. This work produces an estimate at which adherence falls over time, given no external intervention is applied. These results suggest an eigenvector-based approach to estimate adherence trends, as well as the timing of interventions to improve adherence.},
}

@article {pmid40084542,
year = {2025},
author = {Cox, SN and Roychoudhury, P and Frivold, C and Acker, Z and Babu, TM and Boisvert, CL and Carone, M and Ehmen, B and Englund, JA and Feldstein, LR and Gamboa, L and Grindstaff, S and Grioni, HM and Han, PD and Hoffman, KL and Kim, HG and Kuntz, JL and Lo, NK and Lockwood, CM and McCaffrey, K and Mularski, RA and Hatchie, TL and Reich, SL and Schmidt, MA and Smith, N and Starita, LM and Varga, A and Yetz, N and Naleway, AL and Weil, AA and Chu, HY},
title = {Household Transmission and Genomic Diversity of Respiratory Syncytial Virus (RSV) in the United States, 2022-2023.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciaf048},
pmid = {40084542},
issn = {1537-6591},
support = {75D30121C12297/CC/CDC HHS/United States ; },
abstract = {BACKGROUND: Household transmission of respiratory viruses may drive community spread. Few recent studies have examined household respiratory syncytial virus (RSV) transmission in the United States.

METHODS: We conducted a prospective community-based cohort study from 1 June 2022 to 31 May 2023. Participants had blood samples collected and completed nasal swabs and surveys at least weekly, irrespective of symptoms. We tested serum for RSV antibody, nasal swabs by quantitative reverse transcription polymerase chain reaction (RT-qPCR), and performed whole genome sequencing. We evaluated secondary RSV transmission and associated risk factors based on a log-linear Poisson regression model.

RESULTS: RSV was detected among 310 (10%) participants within 200 (20%) households. Most (94%) index cases were symptomatic. We identified 37 cases of potential secondary transmission within 14 days of a distinct index case (10%, 95% confidence interval [CI]: 7%, 14%); median age of index and secondary cases were 6 (interquartile range [IQR]: 3-10) and 35 (7-41) years, respectively, with 89% (24/27) of index cases aged 6 months to 12 years. Factors associated with increased risk of RSV transmission included index case viral detection ≥1 week and contact age ≤12 years. Of 120 sequenced specimens, the main lineages represented were A.d.5.2 (n = 37) and A.d.1 (n = 30). Sequenced viruses from households with ≥2 RSV infections were similar when occurring within ≤14 days (mean pairwise difference 4 [range 0-13], n = 17 households), compared to those >14 days (137 [37-236], n = 2).

CONCLUSIONS: Most RSV household transmission occurs from infants and young children to adults. Viral genome sequencing demonstrated that multiple household infections within a 14-day period are likely due to within-household transmission.},
}

@article {pmid40084371,
year = {2025},
author = {Santiago-Torres, M and Westmaas, JL and Ostroff, JS and Mull, KE and Sullivan, BM and Unger, JM and Bricker, JB},
title = {Overcoming challenges of recruiting cancer patients into clinical trials: insights from a randomized trial of app-based smoking cessation interventions.},
journal = {American journal of cancer research},
volume = {15},
number = {2},
pages = {601-617},
pmid = {40084371},
issn = {2156-6976},
support = {R01 CA253975/CA/NCI NIH HHS/United States ; },
abstract = {Behavioral clinical trials among cancer patients often fail to meet recruitment goals - especially for underrepresented groups. Comparing recruitment strategies on participant accrual and cost can inform the use of cost-effective recruitment strategies for enrollment of diverse populations of cancer patients. In this study, we compared social media, internet sites, and clinic-based recruitment on accrual, cost, and characteristics of cancer patients (i.e., sociodemographic, cancer type/stage, and smoking habits) enrolled in a randomized trial of app-based smoking cessation interventions. Fisher's exact tests for categorical variables and analysis of variance for continuous variables were used to compared data between recruitment strategies. In 35 months, 427 cancer patients from 45 US states enrolled in the trial out of 3,936 screened (rate of participation, 10.8%). Social media recruited over eight times the number of enrolled participants (n=340, 79.6%) compared with Internet sites (n=43, 10.1%) and clinics (n=42, 9.8%). Most (80.1%) participants were women, with mean age 52.3 years. About 20.4% of participants were from underrepresented racial/ethnic backgrounds, 23.0% were rural residents, and 23.7% were uninsured. Over 32 cancer types and all cancer stages were represented. Breast cancer was the most common diagnosis (n=129/427, 30.2%), followed by lung cancer (n=96/427, 23.8%). Internet recruitment generated a higher proportion of men (30.2% vs. 26.2% clinics vs. 17.4% social media, P=.005). Clinics generated a higher proportion of Hispanic participants (9.5% vs. 7.0% Internet vs. 2.6% social media, P=.04) and cancer patients aged 65 and older (28.6% vs. 11.5% social media vs. 4.7% Internet, P=.01). Social media recruited a higher proportion of participants with low income (<$20,000: 39.1% vs. 23.3% Internet vs. 19.0% clinics, P<.001), who tended to have later stage cancers (stage IV: 17.4% vs. 14.0% Internet vs. 7.1% clinics, P=.05). Cost per randomized participant ranged from $270 via social media to $454 via Internet sites to $2,240 via clinic-based recruitment. In conclusion, social media was the most efficient and cost-effective method for recruiting a quality sample of racially/ethnically, geographically, socioeconomically, and clinically diverse sample of cancer patients into a smoking cessation clinical trial. Social media has solid potential for recruiting cancer patients into behavioral clinical trials.},
}

@article {pmid40083364,
year = {2025},
author = {Selby, LD and Wallner, K and Hall, E and Mayr, N and Chvetsov, A and Stacey, AW},
title = {Simultaneous conjunctival melanomas in one eye treated with both adjuvant brachytherapy and proton beam radiotherapy.},
journal = {American journal of ophthalmology case reports},
volume = {38},
number = {},
pages = {102281},
pmid = {40083364},
issn = {2451-9936},
abstract = {PURPOSE: We describe a rare case of two simultaneous primary conjunctival melanomas in the same eye that were treated sequentially with both plaque brachytherapy and proton beam radiotherapy following wide surgical excision.

OBSERVATIONS: A 66-year-old male presented with two pigmented lesions that were concerning for conjunctival melanoma. One of the lesions was on the bulbar conjunctiva near the corneal limbus, and the other in the lower fornix. The lesions were surgically removed using the "no touch" technique, and pathology confirmed invasive melanoma in two separate locations on the same eye. The two lesions were then treated separately with two different forms of adjuvant radiation therapy. The forniceal tumor was treated with proton beam radiotherapy and the limbal lesion was treated with plaque brachytherapy. 30 months after radiation therapy was completed, there were no signs of local recurrence.

CONCLUSIONS AND IMPORTANCE: The appropriate treatment for two primary malignancies in the same eye can be determined independently and, in some cases, can involve two different forms of radiation therapy.},
}

@article {pmid40082827,
year = {2025},
author = {He, Y and Xiao, H and Liu, F and Dai, X and Wang, H and Yang, H and Liu, Z and Unger, JM},
title = {Healthcare utilization in the departments of obstetrics and gynecology during the first two years of the COVID-19 pandemic: time series analysis in Jining, China.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {996},
pmid = {40082827},
issn = {1471-2458},
support = {82204132//National Natural Science Foundation of China/ ; 2021J01721//Natural Science Foundation of Fujian Province/ ; XRCZX2020007//Startup Fund for High-level Talents of Fujian Medical University/ ; },
mesh = {Humans ; *COVID-19/epidemiology ; China/epidemiology ; Female ; *Interrupted Time Series Analysis ; *Obstetrics and Gynecology Department, Hospital/statistics & numerical data ; *Patient Acceptance of Health Care/statistics & numerical data ; Adult ; Pregnancy ; Gynecology/statistics & numerical data ; Obstetrics/statistics & numerical data ; Hospitalization/statistics & numerical data ; Pandemics ; SARS-CoV-2 ; Tertiary Care Centers ; },
abstract = {INTRODUCTION: Healthcare utilization in China decreased precipitously during the initial outbreak of the COVID-19 pandemic, and women were disproportionately affected. As the COVID-19 pandemic has proven to be far more pervasive and persistent than many first surmised, a vital question is whether the utilization of non-COVID related healthcare has remained low under China's dynamic zero-COVID policy. This study aimed to estimate the initial and enduring collateral effects of the COVID-19 pandemic on the utilization of obstetrics and gynecology care at a tertiary hospital in Jining, Shandong Province, China.

METHODS: An interrupted time series analysis was conducted to estimate the impact of the COVID-19 pandemic and mobility restrictions on monthly counts of outpatient visits, inpatient admissions, and surgeries in the obstetrics and gynecology departments at a tertiary hospital in Jining, China. Outpatient visits and surgery volume were abstracted from the hospital's monthly healthcare delivery report, while inpatient admissions were obtained from de-identified individual electronic medical records of inpatients admitted between January 1, 2017 to December 31, 2021. Incidence Rate Ratios (IRRs) representing monthly service counts compared with counterfactual counts (had the pandemic not happened) and the volume (number) of patients lost due to the pandemic were estimated.

RESULTS: During the study period, there were a total of 1 181 120 outpatient visits, 89 550 inpatient admissions and 49 056 surgeries in the obstetrics department; and 847 124 outpatient visits, 42 644 inpatient admissions and 39 653 surgeries of these totals occurred in the gynecology department. Compared to the expected estimates had the pandemic not occurred, a 55.4% (95% CI: 52.6-57.9%; p < 0.001), 31.1% (95% CI: 27.2 - 34.7%; p < 0.001), and 27.6% (95% CI: 23.2- 31.8%; p < 0.001) decrease was observed in obstetric outpatient visits, inpatient admissions, and surgeries, respectively in the month of February 2020 when the lockdown was enforced; and a 87.4% (95% CI: 86.0 - 88.4%; p < 0.001), 74.6% (95% CI: 71.0 -79.2%; p < 0.001), and 75.5% (95% CI: 70.9 - 77.8%; p < 0.001) decrease was observed in gynecologic outpatient visits, inpatient admissions, and surgeries, respectively. As of December 2021, outpatient (IRR = 0.86; 95% CI: 0.80-0.94; p < 0.001), surgery (IRR = 0.88; 95% CI: 0.82-0.95; p < 0.001), and inpatient (IRR = 0.73; 95% CI: 0.68-0.79; p < 0.0001) services in the obstetrics department, and outpatient visits (IRR = 0.90; 95% CI: 0.82-0.89; p = 0.007) in the gynecology department had not fully recovered to pre-pandemic levels. Rural residents experienced a larger immediate decrease in inpatient care utilization in both obstetrics and gynecology in the month of February 2020, and the return to pre-pandemic levels in care utilization was also slower than that of urban residents.

CONCLUSIONS: The COVID-19 pandemic led to sizable disruptions in routine delivery and utilization of obstetrics and gynecology care. Disruptions were particularly substantial during the initial wave of the outbreak, and full recovery to pre-pandemic levels has not yet been achieved. The impact was more dramatic for women from rural areas, highlighting the need for policies and programs that address inequities in pandemic response and preparedness.},
}

Humans
*COVID-19/epidemiology
China/epidemiology
Female
*Interrupted Time Series Analysis
*Obstetrics and Gynecology Department, Hospital/statistics & numerical data
*Patient Acceptance of Health Care/statistics & numerical data
Adult
Pregnancy
Gynecology/statistics & numerical data
Obstetrics/statistics & numerical data
Hospitalization/statistics & numerical data
Pandemics
SARS-CoV-2
Tertiary Care Centers

@article {pmid40082098,
year = {2025},
author = {Ramirez, M and Shah, PD and Chu, HY and Garza, L and Linde, S and Garrison, MM and Zhou, C and Bishop, S and Ibarra, G and Ko, LK},
title = {Corrigendum to "Reopening schools safely and educating youth (ROSSEY) study: Protocol for a community-based, cluster randomized controlled trial" [Contemporary Clinical Trials, 139 (2024) 107480].},
journal = {Contemporary clinical trials},
volume = {},
number = {},
pages = {107873},
doi = {10.1016/j.cct.2025.107873},
pmid = {40082098},
issn = {1559-2030},
}

@article {pmid40080774,
year = {2025},
author = {Banegas, MP and Nightingale, CL and Dressler, EV and Cooley, ME and Kamen, C and Wagner, LI and Kittel, CA and Flores, EJ and Carlos, R and Milton, A and Park, E and Parsons, SK and Wood, EG and Loh, KP and Ramsey, S and , and , },
title = {Screening and Referral for Health-Related Social Needs and Financial Distress: Current Processes Among National Cancer Institute Community Oncology Research Program Practices.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2400902},
doi = {10.1200/OP-24-00902},
pmid = {40080774},
issn = {2688-1535},
abstract = {PURPOSE: Health-related social needs (HRSNs) are associated with adverse cancer health outcomes. We assessed the processes for screening and responding to both HRSNs and financial distress and described the methods used across National Cancer Institute Community Oncology Research Program (NCORP) practices.

METHODS: The NCORP 2022 Landscape Assessment survey focused on services to screen for and respond to HRSNs and financial distress within a national network of community oncology practices. We calculated the proportions of oncology practices that screened for and responded to HRSNs and financial distress, separately, and described the staff, tools, and methods used for each process. Multivariable logistic regression models estimated the associations between oncology practice characteristics and screening for HRSNs and financial distress.

RESULTS: The majority of community oncology practices reported screening for HRSNs (79%), and of those, most inquired about transportation (96%), family and social support (93%), housing (80%), and food security (80%). Most oncology practices reported screening for financial distress (78%). Social worker evaluation was the most common method used to screen for both HRSNs (77%) and financial distress (65%). Most oncology practices reported social work referral as the method for responding to HRSNs (89%) and financial distress (96%). Oncology practice characteristics such as having a survivorship clinic and geographic region were associated with screening for HRSNs and financial distress.

CONCLUSION: Research is needed to understand the impact of different HRSN screening and referral approaches on care delivery, clinic costs, care quality, and health outcomes of patients with cancer. These efforts are critical to generate evidence to inform best practices, clinical guidelines, and novel interventions aimed to improve cancer health equity.},
}

@article {pmid40080017,
year = {2025},
author = {Gupta, A and Till, C and Vaidya, R and Hershman, DL and Unger, JM},
title = {Health Care Contact Days for Older Adults Enrolled in Cancer Clinical Trials.},
journal = {JAMA network open},
volume = {8},
number = {3},
pages = {e250778},
pmid = {40080017},
issn = {2574-3805},
mesh = {Humans ; Aged ; Male ; Female ; United States ; Aged, 80 and over ; *Neoplasms/therapy ; *Clinical Trials as Topic/statistics & numerical data ; Cohort Studies ; Medicare/statistics & numerical data ; },
abstract = {IMPORTANCE: Contact days-days with health care contact outside the home-are a measure of how much of a patient's life is consumed by health care. Clinical trials, with a more uniform patient mix and protocolized care, provide a unique opportunity to assess whether burdens differ by individuals' sociodemographic backgrounds.

OBJECTIVE: To characterize patterns of contact days for older adults with cancer participating in clinical trials.

In this cohort study, data from 6 SWOG Cancer Research Network trials across prostate, lung, and pancreatic cancers that recruited patients aged 65 years or older from 1999 to 2014 were linked with Medicare claims data. Data were analyzed from December 14, 2023, to September 26, 2024.

EXPOSURES: Demographic variables, including age, sex, self-reported race and ethnicity, and insurance status; clinical factors, such as cancer type and study-specific prognostic risk score; and social factors, such as neighborhood socioeconomic deprivation.

MAIN OUTCOMES AND MEASURES: Number of contact days, defined as number of days with contact with the health care system, percentage of health care contact days (number of contact days divided by follow-up), and sources of contact days (eg, ambulatory or inpatient) in the first 12 months after trial enrollment. Sociodemographic and clinical factors associated with contact days were examined using negative binomial regression, including an offset variable for duration of observation.

RESULTS: The study included 1429 patients (median age, 71 years [range, 65-91 years]; 1123 men [78.6%]; and 332 patients [23.5%] with rural residence). The median number of contact days was 48 (IQR, 26-71), of a median of 350 days (IQR, 178-365 days) of observation; the median percentage of contact days was 19% (IQR, 13%-29%). The most common sources of contact days were ambulatory clinician visits (median, 17 [IQR, 7-25]), tests (median, 12 [IQR, 3-24]), and treatments (median, 11 [IQR, 3-22]). A median of 70% (IQR, 50%-88%) of ambulatory contact days had only a single service performed on that day (eg, only tests). In multivariable regression, factors associated with increased contact days included age (relative risk [RR] per year, 1.02 [95% CI, 1.01-1.02]), insurance type (Medicare alone or with Medicaid or private insurance vs other: RR, 2.47 [95% CI, 2.16-2.83]), prognostic risk score (above the median vs at or below the median: RR, 1.14 [95% CI, 1.04-1.25]), and type of cancer (pancreatic vs prostate cancer: RR, 1.69 [95% CI, 1.51-1.89]; lung vs prostate cancer: RR, 1.69 [95% CI, 1.54-1.85]).

CONCLUSIONS AND RELEVANCE: In this cohort study of older adults with advanced stage cancer participating in phase 3 randomized clinical trials, patients spent nearly 1 in 5 days with health care contact. These findings highlight the need to simplify trial requirements to minimize participant burden.},
}

Humans
Aged
Male
Female
United States
Aged, 80 and over
*Neoplasms/therapy
*Clinical Trials as Topic/statistics & numerical data
Cohort Studies
Medicare/statistics & numerical data

@article {pmid40061351,
year = {2025},
author = {Siegel, SJ and DeWolf, S and Schmalz, J and Saber, W and Dong, J and Martens, MJ and Logan, B and Albanese, A and Iovino, L and Chen, E and Kaminski, J and Neuberg, D and Hebert, K and Keskula, P and Zavistaski, J and Steinberg, L and Schichter, I and Cagnin, L and Hernandez, V and Warren, M and Applegate, K and Bar, M and Chhabra, S and Choi, SW and Clark, W and Das, S and Jenq, R and Jones, RJ and Levine, JE and Murthy, H and Rashidi, A and Riches, M and Sandhu, K and Sung, AD and Larkin, K and Al Malki, MM and Gooptu, M and Elmariah, H and Alousi, A and Runaas, L and Shaffer, B and Rezvani, A and El Jurdi, N and Loren, AW and Scheffey, D and Sanders, C and Hamadani, M and Dudakov, J and Bien, S and Robins, H and Horowitz, M and Bolaños-Meade, J and Holtan, S and Bhatt, AS and Perales, MA and Kean, LS},
title = {Graft-versus-host disease prophylaxis shapes T cell biology and immune reconstitution after hematopoietic cell transplant.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40061351},
support = {U10 HL069294/HL/NHLBI NIH HHS/United States ; U24 HL138660/HL/NHLBI NIH HHS/United States ; },
abstract = {Successful hematopoietic cell transplant requires immunosuppression to prevent graft-versus-host disease (GVHD), a lethal, T-cell-mediated post-transplant complication. The phase 3 BMT CTN 1703 trial demonstrated superior GVHD-free/relapse-free survival for post-transplant cyclophosphamide (PT-Cy)-based GVHD prophylaxis versus tacrolimus/methotrexate (Tac/MTX), but did not improve overall survival. To compare T-cell biology between GVHD prophylaxis regimens, 324 patients were co-enrolled onto BMT CTN 1801 (NCT03959241). We quantified T-cell immune reconstitution using multi-modal analysis, including T-cell receptor (TCR) sequencing of 2,359 longitudinal samples (180,432,350 T-cells). Compared to Tac/MTX, PT-Cy was associated with an early, substantial reduction in TCR diversity that was sustained for 2 years. PT-Cy led to a T-cell reconstitution bottleneck, including reduced thymic output and virus-associated TCRs. Decreased D+14 TCR diversity predicted prevention of chronic GVHD, but also correlated with increased moderate-to-severe infections. This study reveals how distinct immunosuppression strategies have significant effects on the global immune repertoire, underpinning post-transplant clinical outcomes.},
}

@article {pmid40060686,
year = {2025},
author = {Singh, S and Islam, SMS and Liu, R and Adeniji, OS and Giron, LB and Saini, P and Danesh, A and Denton, PW and Jones, B and Xiao, H and Abdel-Mohsen, M},
title = {HIV-Induced Sialoglycans on Infected Cells Promote Immune Evasion from Myeloid Cell-Mediated Killing.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40060686},
issn = {2692-8205},
support = {R01 AA029859/AA/NIAAA NIH HHS/United States ; R15 AI178516/AI/NIAID NIH HHS/United States ; R01 DK123733/DK/NIDDK NIH HHS/United States ; R01 NS117458/NS/NINDS NIH HHS/United States ; R01 AI165079/AI/NIAID NIH HHS/United States ; R01 AG062383/AG/NIA NIH HHS/United States ; P20 GM103427/GM/NIGMS NIH HHS/United States ; },
abstract = {Sialic acid-containing glycans (sialoglycans) on pathological cells interact with Siglecs, glycol-immune checkpoint receptors expressed on myeloid cells such as monocytes and neutrophils. This interaction suppresses the cytotoxic functions of these immune cells. We show that HIV infection reprograms the glycosylation machinery of infected cells to increase the expression of specific sialoglycan ligands for Siglecs-3, -7, and -9. These ligands engage Siglecs on myeloid cells, impairing their ability to target HIV-infected cells. Selective disruption of these interactions using 10-1074-Sia, an HIV-specific antibody conjugated to sialidase-an enzyme that removes sialic acids-significantly enhances monocyte- and neutrophil-mediated killing of HIV-infected cells in autologous assays. Treatment with 10-1074-Sia in humanized mice infected with HIV reduces viral load and decreases inflammation. These findings reveal a novel immune evasion mechanism exploited by HIV to evade myeloid cell immune surveillance and highlight the potential of targeting sialoglycan-Siglec interactions to improve immune clearance of HIV-infected cells.},
}

@article {pmid40060420,
year = {2025},
author = {Rosero, M and Bai, J},
title = {AFD Thermosensory Neurons Mediate Tactile-Dependent Locomotion Modulation in C. elegans.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40060420},
issn = {2692-8205},
support = {R01 NS115974/NS/NINDS NIH HHS/United States ; F31 NS129545/NS/NINDS NIH HHS/United States ; T32 GM136534/GM/NIGMS NIH HHS/United States ; R01 NS109476/NS/NINDS NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; },
abstract = {Sensory neurons drive animal behaviors by detecting environmental stimuli and relaying information to downstream circuits. Beyond their primary roles in sensing, these neurons often form additional synaptic connections outside their main sensory modality, suggesting broader contributions to behavior modulation. Here, we uncover an unexpected role for the thermosensory neuron AFD in coupling tactile experience to locomotion modulation in Caenorhabditis elegans. We show that while AFD employs cGMP signaling for both thermotaxis and tactile-dependent modulation, the specific molecular components of the cGMP pathway differ between these two processes. Interestingly, disrupting the dendritic sensory apparatus of AFD, which is essential for thermotaxis, does not impair tactile-based locomotion modulation, indicating that AFD can mediate tactile-dependent behavior independently of its thermosensory apparatus. In contrast, ablating the AFD neuron eliminates tactile-dependent modulation, pointing to an essential role for AFD itself, rather than its sensory dendritic endings. Further, we find tactile-dependent modulation requires the AIB interneuron, which connects AFD to touch circuits via electrical synapses. Removing innexins expressed in AFD and AIB abolishes this modulation, while re-establishing AFD-AIB connections with engineered electrical synapses restores it. Collectively, these findings uncover a previously unrecognized function of AFD beyond thermosensation, highlighting its influence on context-dependent neuroplasticity and behavioral modulation through broader circuit connectivity.},
}

@article {pmid40060404,
year = {2025},
author = {Park, L and Tsai, YT and Lim, HK and Faulhaber, LD and Burleigh, K and Faulhaber, EM and Bose, M and Shih, AY and Hirayama, AY and Turtle, CJ and Annesley, CE and Gardner, RA and Gustafson, HH and Gust, J},
title = {Cytokine-mediated increase in endothelial-leukocyte interaction mediates brain capillary plugging during CAR T cell neurotoxicity.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40060404},
issn = {2692-8205},
support = {K08 NS118138/NS/NINDS NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; R37 CA275954/CA/NCI NIH HHS/United States ; },
abstract = {CD19-directed CAR T cells treat cancer, but also cause immune effector cell associated neurotoxicity syndrome (ICANS). Despite strong epidemiologic links between cytokine release syndrome and ICANS, it is uncertain how elevated systemic cytokines and activated immune cells cause brain dysfunction. We previously showed that leukocytes plug brain capillaries in an immunocompetent mouse model of CD19-CAR neurotoxicity. Here, we used the same model to explore how integrin activation and endothelial adhesion molecule expression contribute to capillary plugging. In vivo two-photon imaging revealed increased expression of ICAM-1 on brain capillaries, with spatially restricted VCAM-1 increases. TNF, IFN-γ, and IL-1β at concentrations equivalent to CAR T cell patient blood levels upregulated ICAM-1 and VCAM-1 in brain microendothelial cells. In mice, CAR T cells strongly upregulated VLA-4 (integrin α4β1) affinity to VCAM-1, but not affinity of LFA-1 (integrin αLβ2) to ICAM-1. Blocking integrin α4 but not integrin αL improved ICANS behavior in mice. In human CAR T cell patients, increased soluble ICAM-1 and VCAM-1 are associated with ICANS, and integrin α4 but not integrin αL is upregulated in CAR T cells after infusion. Our study highlights that cytokine-driven upregulation of endothelial-leukocyte adhesion may be sufficient to induce neurovascular dysfunction in CAR T cell patients.},
}

@article {pmid40079983,
year = {2025},
author = {Gomez-Castillo, L and Cushing-Haugen, KL and Useche, M and Norouzi, A and Rizvi, Z and Ferrandino, R and Futran, N and Marchiano, E and Rodriguez, T and Harris, HR and Barber, B},
title = {High Sugar-Sweetened Beverage Intake and Oral Cavity Cancer in Smoking and Nonsmoking Women.},
journal = {JAMA otolaryngology-- head & neck surgery},
volume = {},
number = {},
pages = {},
pmid = {40079983},
issn = {2168-619X},
abstract = {IMPORTANCE: The incidence of oral cavity cancer (OCC) is increasing among nonsmokers and young individuals without traditional risk factors worldwide. High sugar-sweetened beverage (SSB) intake is associated with various gastrointestinal cancers, but its association with OCC has not been explored.

OBJECTIVE: To evaluate the association between SSB intake and the risk of OCC among smoking and nonsmoking women participating in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII).

This longitudinal cohort study analyzed data from women in the NHS (follow-up, 1986-2016) and NHSII (follow-up, 1991-2017) after excluding those with a history of cancer, implausible caloric intake, or missing SSB intake data. Participants were followed up until the diagnosis of OCC. Data analysis was performed from July 2023 to June 2024.

EXPOSURE: SSB intake, quantified by frequency of consumption ranging from less than 1 SSB monthly to 1 or more SSBs daily.

MAIN OUTCOME AND MEASURE: Cox proportional hazards regression models with age and questionnaire period as the time scale were used to estimate hazard ratios (HRs) and 95% CIs associated with the development of OCC for each category of SSB intake, with less than 1 SSB per month as the reference group.

RESULTS: A total of 162 602 women (mean [SD] age, 43.0 [9.9] years) were evaluated. During 30 years of follow-up, 124 invasive OCC cases were documented. In multivariable-adjusted models, participants consuming 1 or more SSB daily (5 people per 100 000 population) had a 4.87 times (95% CI, 2.47-9.60 times) higher risk of OCC compared with those consuming less than 1 SSB monthly (2 people per 100 000 population), increasing the rate of OCC to 3 more people per 100 000 population. When restricted to both nonsmokers or light smokers and nondrinkers or light drinkers, the risk of OCC was 5.46 times (95% CI, 1.75-17.07 times) higher, increasing the rate of OCC to 3 more people per 100 000 population.

CONCLUSIONS AND RELEVANCE: In this study, high SSB intake was associated with a significantly increased risk of OCC in women, regardless of smoking or drinking habits, yet with low baseline risk. Additional studies are needed in larger cohorts, including males, to validate the impact of these findings.},
}

@article {pmid40079097,
year = {2025},
author = {Portuguese, AJ and Huang, JJ and Jeon, Y and Taheri, M and Albittar, A and Liang, EC and Hirayama, AV and Kimble, EL and Iovino, L and Poh, C and Gopal, AK and Shadman, M and Till, BG and Milano, F and Chapuis, AG and Otegbeye, F and Cassaday, RD and Basom, RS and Wu, QV and Maloney, DG and Gauthier, J},
title = {Real-world comparison of lisocabtagene maraleucel and axicabtagene ciloleucel in large B-cell lymphoma: an inverse probability of treatment weighting analysis with 3-year follow up.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2024.287010},
pmid = {40079097},
issn = {1592-8721},
abstract = {Lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) are FDA- and EMAapproved chimeric antigen receptor (CAR) T-cell therapies for relapsed/refractory large B-cell lymphoma (LBCL). However, comparative real-world analyses of their efficacy and toxicity with extended follow-up are lacking. We conducted a retrospective study of 160 LBCL patients treated at the Fred Hutchinson Cancer Center with commercial liso-cel or axi-cel per standard of care. Using inverse probability of treatment weighting (IPTW) to mitigate treatment allocation bias and multivariable adjustments to minimize other sources of confounding, we assessed the impact of CAR T-cell product type on outcomes. Axi-cel was associated with significantly higher rates of cytokine release syndrome (CRS; G1+: adjusted OR [aOR] 4.27, p=0.004; G2+: aOR 2.88, p=0.006), immune effector cell-associated neurotoxicity syndrome (ICANS; G1+: aOR 2.10, p=0.048), and immune effector cell-associated hematotoxicity (ICAHT; G1+: aOR 8.09, p.},
}

@article {pmid40075650,
year = {2025},
author = {Bar, M and El Anbari, M and Rinchai, D and Toufiq, M and Kizhakayil, D and Manjunath, HS and Mathew, R and Cavattoni, I and Forer, S and Recla, M and Bibawi, H and Alater, A and Yahia, R and Brown, C and Miles, NL and Vo, P and Bedognetti, D and Tomei, S and Saleh, A and Cugno, C and Chaussabel, D and Deola, S},
title = {Whole-Blood Longitudinal Molecular Profiling Maps the Road of Graft Versus Host Disease (GVHD).},
journal = {Cancers},
volume = {17},
number = {5},
pages = {},
pmid = {40075650},
issn = {2072-6694},
support = {NPRP13S-0107-200023 to Sara Deola//QNRF/ ; },
abstract = {Background: Graft versus host disease (GVHD) and the graft versus tumor (GVT) effect after allogeneic hematopoietic cell transplantation (allo-HCT) result from complex interactions between the donor immune system and the recipient environment. High-temporal longitudinal monitoring might be necessary to identify triggering events of GVHD and GVT and to intercept these events before their occurrence. But it would require an overall considerable amount of blood by venipuncture, which is unfeasible in such a fragile population. Methods: In this study, we implemented a targeted multiplex microfluidics q-PCR-based transcriptional fingerprint assay (TFA) on 50 µL of blood collected by a simple fingerstick to evaluate post-allo-HCT systemic immune perturbations associated with the development of GVHD. Fluctuations of a panel of 264 genes were measured in 31 allo-HCT patients by frequent (weekly or biweekly) analysis of 50 µL serial blood samples. Cross-sectional and longitudinal analyses correlated with detailed clinical annotations were performed. Results: Signatures of neutrophil activation and interferon (IFN) characterized the onset of acute GVHD, while an ongoing cytotoxic response was modulated in chronic mild GVHD and protein-synthesis and B-cell-related signatures characterized late acute/overlap GVHD. An unexpected erythroid signature distinguished patients with acute and mild chronic GVHD. Conclusions: Our micro-invasive approach unveiled the molecular heterogeneity of GVHD and identified hierarchically important biological processes conducive to different forms of GVHD. These findings increase our understanding of GVHD and reveal potentially targetable alterations. This approach might be implemented clinically to intercept GVHD before its occurrence and to modulate therapeutic interventions accordingly.},
}

@article {pmid40075647,
year = {2025},
author = {Roeker, LE and Burke, JM and Rhodes, JM and Emechebe, N and Jawaid, D and Manzoor, BS and Jensen, CE and Ryland, L and Liu, Y and Marx, SE and Sinai, W and Roser, J and Shadman, M},
title = {Real-World Effectiveness of Frontline Treatments Among Patients with Chronic Lymphocytic Leukemia: Results from ConcertAI.},
journal = {Cancers},
volume = {17},
number = {5},
pages = {},
pmid = {40075647},
issn = {2072-6694},
support = {N/A//AbbVie (United States)/ ; },
abstract = {Background: The long-term follow-up of clinical trials of novel first-line (1L) therapies for chronic lymphocytic leukemia (CLL) demonstrates 6-10-year progression-free survival. We describe the effectiveness of 1L CLL treatments in real-world settings, with an emphasis on the important real-world outcome of time to next treatment or death (TTNT-D). Methods: This retrospective, observational study utilized de-identified electronic health records from the ConcertAI RWD360™ database with linked administrative open claims. Adults with CLL who initiated an approved 1L CLL therapy (June 2019-March 2023) were included. Duration of therapy (DoT), TTNT-D, and overall survival were assessed. Results: At 1L, 39.8% of 1843 patients received first-generation covalent Bruton tyrosine kinase inhibitors (cBTKis), 23.0% second-generation cBTKis, 12.4% venetoclax-obinutuzumab (VenO), 7.4% chemotherapy/chemoimmunotherapy (CT/CIT), and 17.4% anti-CD20 monotherapy. Median (range) follow-up in months was 24.9 (13.1-36.6) for first-generation cBTKis, 13.4 (7.3-21.7) for second-generation cBTKis, 16.0 (8.4-27.8) for VenO, 21.8 (11.2-32.7) for CT/CIT, and 19.7 (10.0-33.4) for anti-CD20 monotherapy. Median (range) DoT was 11.5 (4.2-25.0) and 8.6 (3.0-16.1), 9.1 (5.9-12.2), 5.6 (3.2-5.8), and 1.6 (1.6-4.5) months for first- and second-generation cBTKis, VenO, CT/CIT, and anti-CD20 monotherapy, respectively. Regarding TTNT-D, at 2 years' follow-up, 69.1%, 82.5%, 86.3%, 79.1%, and 53.0% of patients treated with first- and second-generation cBTKis, VenO, CT/CIT, and anti-CD20 monotherapy, respectively, had not initiated subsequent treatment or experienced death. Conclusions: TTNT-D is an important real-world outcome in CLL. Our findings demonstrated the utility of time-limited VenO, with potentially more time off treatment, relative to continuous 1L cBTKi therapies.},
}

@article {pmid40074150,
year = {2025},
author = {Paulson, KG and Park, SY and Bhatia, S and Hippe, DS and Nghiem, P},
title = {Improved survival at the population level for patients with advanced Merkel cell carcinoma following availability of immunotherapy.},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.03.006},
pmid = {40074150},
issn = {1097-6787},
abstract = {BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive skin cancer with poor survival rates. Immune checkpoint inhibitors (ICIs) were FDA-approved for advanced MCC in 2017, but their real-world survival impact remains unclear.

OBJECTIVE: Evaluate whether ICI introduction in the US corresponded with improved survival.

METHODS: This cohort study analyzed SEER data for MCC patients diagnosed from 2010 to 2021, grouped by 3-year periods, to calculate 2-year overall and relative survival.

RESULTS: For 453 patients with metastatic MCC, 2-year relative survival improved from 23% (2010-2012) to 37% (2013-2015), 42% (2016-2018), and 54% (2019-2021) (p < 0.001). Median overall survival also increased from 9 to 16 months among these patients. In 4,786 MCC patients overall, 2-year relative survival rose from 73% (2010-2012) to 81% (2019-2021) (p = 0.004), while overall survival improved from 67% to 72% (p = 0.012).

LIMITATIONS: SEER lacks case-level data to link ICI treatment directly to survival, although ICIs represent the major recent treatment advance for MCC.

CONCLUSIONS: The introduction of ICIs aligns with a >2-fold increase in survival for advanced MCC patients at the population level, translating to ∼220 fewer deaths per year in the U.S.},
}

@article {pmid40073862,
year = {2025},
author = {Khyzha, N and Ahmad, K and Henikoff, S},
title = {Profiling transcriptome composition and dynamics within nuclear compartments using SLAM-RT&Tag.},
journal = {Molecular cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.molcel.2025.02.012},
pmid = {40073862},
issn = {1097-4164},
abstract = {Nuclear compartments are membrane-less regions enriched in functionally related molecules. RNA is a major component of many nuclear compartments, but the identity and dynamics of transcripts within nuclear compartments are poorly understood. Here, we applied reverse transcribe and tagment (RT&Tag) to human cell lines to identify the transcript populations of Polycomb domains and nuclear speckles. We also developed SLAM-RT&Tag, which combines RNA metabolic labeling with RT&Tag, to quantify transcript dynamics within nuclear compartments. We observed unique transcript populations with differing structures and dynamics within each compartment. Intriguingly, exceptionally long genes are transcribed adjacent to Polycomb domains and are transiently associated with chromatin. By contrast, nuclear speckles act as quality control checkpoints that transiently confine incompletely spliced polyadenylated transcripts and facilitate their post-transcriptional splicing. In summary, we demonstrate that transcripts at Polycomb domains and nuclear speckles undergo distinct RNA processing mechanisms, highlighting the pivotal role of compartmentalization in RNA maturation.},
}

@article {pmid40073837,
year = {2025},
author = {Gajjar, A and Mahajan, A and Bale, T and Bowers, DC and Canan, L and Chi, S and Cluster, A and Cohen, K and Cole, B and Coven, S and Darlington, W and Dorris, K and Elster, J and Ermoian, R and Franson, A and George, E and Helgager, J and Landi, D and Lin, C and Metrock, L and Nanda, R and Palmer, J and Partap, S and Plant, A and Pruthi, S and Reynolds, R and Stearns, D and Storm, P and Wang, A and Wang, LD and Whipple, N and Zaky, W and McMillian, N and Ramakrishnan, S},
title = {Pediatric Central Nervous System Cancers, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {23},
number = {3},
pages = {113-130},
doi = {10.6004/jnccn.2025.0012},
pmid = {40073837},
issn = {1540-1413},
mesh = {Humans ; Child ; *Central Nervous System Neoplasms/therapy/diagnosis ; Adolescent ; *Medical Oncology/standards/methods ; Glioma/therapy/diagnosis/pathology ; Medulloblastoma/therapy/diagnosis/pathology ; Child, Preschool ; },
abstract = {The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Central Nervous System Cancers provide multidisciplinary diagnostic workup, staging, and treatment recommendations for diffuse high-grade gliomas and medulloblastomas in children and adolescents. This article summarizes the studies and panel discussion that serve as the rationale for comprehensive care recommendations included in the NCCN Guidelines for Pediatric Central Nervous System Cancers.},
}

Humans
Child
*Central Nervous System Neoplasms/therapy/diagnosis
Adolescent
*Medical Oncology/standards/methods
Glioma/therapy/diagnosis/pathology
Medulloblastoma/therapy/diagnosis/pathology
Child, Preschool

@article {pmid40073835,
year = {2025},
author = {Greenberg, PL and Stone, RM and Abaza, Y and Al-Kali, A and Anand, S and Ball, B and Bennett, JM and Borate, U and Brunner, AM and Chai-Ho, W and Curtin, P and DeZern, AE and Gaensler, K and Gahvari, Z and Garcia-Manero, G and Griffiths, EA and Haque, T and Jacoby, M and Jonas, BA and Keel, S and Khanal, R and Kishtagari, A and Madanat, Y and Maness, LJ and McCurdy, SR and McMahon, C and Odenike, O and Osman, A and Reddy, VV and Sallman, DA and Sayar, H and Shallis, R and Singh, A and Tanaka, T and Thota, S and Kovach, E and Nguyen, J and Hochstetler, C},
title = {NCCN Guidelines® Insights: Myelodysplastic Syndromes, Version 2.2025.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {23},
number = {3},
pages = {66-75},
doi = {10.6004/jnccn.2025.0013},
pmid = {40073835},
issn = {1540-1413},
mesh = {*Myelodysplastic Syndromes/diagnosis/therapy ; Humans ; Prognosis ; Disease Management ; },
abstract = {The NCCN Guidelines for Myelodysplastic Syndromes (MDS) provide recommendations for the evaluation, diagnosis, and comprehensive care of patients with MDS based on a review of recent clinical evidence that has led to important advances in treatment or has yielded new information on biologic factors that may have prognostic significance in MDS. The multidisciplinary panel of MDS experts is convened at least on an annual basis. During the annual meeting, the panel evaluates new and emerging data to inform their recommendations. These NCCN Guidelines Insights review the recent updates, including treatment recommendations both for lower-risk and higher-risk MDS, preference stratification of therapeutic agents, and emerging data on novel therapeutics.},
}

*Myelodysplastic Syndromes/diagnosis/therapy
Humans
Prognosis
Disease Management

@article {pmid40073834,
year = {2025},
author = {Narkhede, M and Ujjani, CS},
title = {Immune Dysfunction and Consequences in Chronic Lymphocytic Leukemia.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {23},
number = {3},
pages = {},
doi = {10.6004/jnccn.2024.7090},
pmid = {40073834},
issn = {1540-1413},
mesh = {Humans ; *Leukemia, Lymphocytic, Chronic, B-Cell/immunology/therapy ; },
abstract = {Infectious complications are among the leading causes of mortality in chronic lymphocytic leukemia (CLL). Over the past decade, several advances have been made in treating CLL through inhibition of Bruton tyrosine kinase and the antiapoptotic protein BCL-2. As mortality from CLL progression is expected to decline in the next several years, mortality from severe infections is anticipated to increase. Therefore, understanding the nature of immune defects in CLL and developing strategies to augment the impaired immune system are needed to keep pace with advancements in treatment. This review article summarizes the available data on immune dysfunctions, their clinical consequences, therapeutic implications, and current strategies to enhance immune function in patients with CLL.},
}

Humans
*Leukemia, Lymphocytic, Chronic, B-Cell/immunology/therapy

@article {pmid40073280,
year = {2025},
author = {Barros, M and Leon, A and Crivera, C and Cusson, E and Kodjamanova, P and Bagnall, R and Panch, SR},
title = {Literature review of occurrence, effectiveness, safety, and hospitalization burden of blood transfusion in the management of warm autoimmune hemolytic anemia.},
journal = {Hematology (Amsterdam, Netherlands)},
volume = {30},
number = {1},
pages = {2472489},
doi = {10.1080/16078454.2025.2472489},
pmid = {40073280},
issn = {1607-8454},
mesh = {Humans ; *Anemia, Hemolytic, Autoimmune/therapy ; *Hospitalization ; Erythrocyte Transfusion/adverse effects ; Blood Transfusion/methods ; },
abstract = {INTRODUCTION: Cases of warm autoimmune hemolytic anemia (wAIHA) often present with life-threatening levels of hemoglobin requiring red blood cell (RBC) transfusion support.

AIM: This literature review assessed the occurrence, safety, effectiveness, and hospitalization burden of RBC transfusions in the management of patients with wAIHA.

METHODS: Electronic databases (Embase, MEDLINE) were searched from inception to December 2021 along with additional searches conducted up to March 2024.

RESULTS: Of the 1478 articles screened, 17 observational studies and reviews were included. These studies demonstrated the use of 1-50 red blood cell transfusions to reach clinically acceptable hemoglobin levels in patients with wAIHA. In general, pre-transfusion hemoglobin levels were 6 g/dL and increased by an average 1.2 g/dL following a transfusion. Approximately 50% of patients with primary or secondary wAIHA suffered relapses. No data was available to distinguish between RBC transfusions used at initial presentation versus during relapse. Five studies found no increase in hemolysis or serious adverse reactions following transfusions and two studies reported mild transfusion-related adverse effects. Limited data was available regarding the hospitalization burden of RBC transfusion. Patients with wAIHA requiring transfusions had a median hospital stay from 15 to 17 days, which is considerably higher than all causes hospitalization of 4.5 days for 2023 U.S.

CONCLUSION: In patients with wAIHA, data supports wide variability in occurrence, but relative safety and effectiveness of RBC transfusions as supportive therapy. Additional studies are needed to assess the occurrence, safety, and hospitalization burden of RBC transfusions relative to other therapies in chronic relapsing wAIHA.},
}

Humans
*Anemia, Hemolytic, Autoimmune/therapy
*Hospitalization
Erythrocyte Transfusion/adverse effects
Blood Transfusion/methods

@article {pmid40072429,
year = {2025},
author = {Heng, F and Sun, Y and Li, L and B Gilbert, P},
title = {Estimation and Hypothesis Testing of Strain-Specific Vaccine Efficacy With Missing Strain Types With Application to a COVID-19 Vaccine Trial.},
journal = {Statistics in medicine},
volume = {44},
number = {6},
pages = {e10345},
pmid = {40072429},
issn = {1097-0258},
support = {R37 AI054165/AI/NIAID NIH HHS/United States ; AI068635/NH/NIH HHS/United States ; U01 AI068635/AI/NIAID NIH HHS/United States ; DMS1915829//National Science Foundation/ ; R37AI054165/NH/NIH HHS/United States ; },
mesh = {Humans ; *COVID-19 Vaccines/immunology ; *SARS-CoV-2/immunology/genetics ; *COVID-19/prevention & control ; *Computer Simulation ; *Vaccine Efficacy ; Genotype ; Randomized Controlled Trials as Topic ; Models, Statistical ; },
abstract = {Based on data from a randomized, controlled vaccine efficacy trial, this article develops statistical methods for assessing vaccine efficacy (VE) to prevent COVID-19 infections by a discrete set of genetic strains of SARS-CoV-2. Strain-specific VE adjusting for possibly time-varying covariates is estimated using augmented inverse probability weighting to address missing viral genotypes under a competing risks model that allows separate baseline hazards for different risk groups. Hypothesis tests are developed to assess whether the vaccine provides at least a specified level of VE against some viral genotypes and whether VE varies across genotypes. Asymptotic properties providing analytic inferences are derived and finite-sample properties of the estimators and hypothesis tests are studied through simulations. This research is motivated by the fact that previous analyses of COVID-19 vaccine efficacy did not account for missing genotypes, which can cause severe bias and efficiency loss. The theoretical properties and simulations demonstrate superior performance of the new methods. Application to the Moderna COVE trial identifies several SARS-CoV-2 genotype features with differential vaccine efficacy across genotypes, including lineage (Reference, Epsilon, Gamma, Zeta), indicators of residue match vs. mismatch to the vaccine-strain residue at Spike amino acid positions (identifying signatures of differential VE), and a weighted Hamming distance to the vaccine strain. The results show VE decreases against genotypes more distant from the vaccine strain, highlighting the need to update COVID-19 vaccine strains.},
}

Humans
*COVID-19 Vaccines/immunology
*SARS-CoV-2/immunology/genetics
*COVID-19/prevention & control
*Computer Simulation
*Vaccine Efficacy
Genotype
Randomized Controlled Trials as Topic
Models, Statistical

@article {pmid40071691,
year = {2025},
author = {Huang, Y and Kwan, ML and Heckbert, SR and Smith, NL and Othus, M and Laurent, CA and Roh, JM and Rillamas-Sun, E and Lee, VS and Kolevska, T and Cheng, RK and Irribarren, C and Nguyen-Huynh, M and Hershman, DL and Kushi, LH and Greenlee, H},
title = {Endocrine therapy and risk of cardiovascular disease and mortality in postmenopausal breast cancer survivors.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf063},
pmid = {40071691},
issn = {1460-2105},
abstract = {BACKGROUND: There are increasing concerns of cardiovascular safety related to endocrine therapy use in women with breast cancer (BC). We examined risk of cardiovascular disease (CVD) events and mortality associated with endocrine therapy use in postmenopausal women with early-stage BC.

METHODS: Postmenopausal women diagnosed with stage I-III hormone receptor-positive BC from 2005 to 2013 were included (n = 8,495). Women were classified as aromatase inhibitor (AI) users, tamoxifen users, and non-users of endocrine therapy in the 12 months after BC diagnosis. Likelihood ratio tests examined whether the association of endocrine therapy use with CVD and mortality outcomes varied by body mass index (BMI) and history of CVD before BC diagnosis.

RESULTS: Over a median follow-up of 7.5 years, women who used AIs were less likely to develop major adverse cardiovascular events (MACE) (HR = 0.84, 95% CI: 0.73-0.97) and heart failure (HR = 0.81, 95% CI: 0.66-0.99) compared with non-users of endocrine therapy. No associations between tamoxifen use and CVD outcomes were observed. AI use was associated with lower risk all-cause, CVD-related, and non-CVD-related mortality, compared with non-use of endocrine therapy. Tamoxifen use was associated with lower risk of all-cause mortality and non-CVD-related mortality, compared with non-use of endocrine therapy, and the association was modified by BMI (P for interaction <0.05).

CONCLUSION: Our findings suggest endocrine therapy use reduces all-cause mortality risk and may not increase CVD risk in postmenopausal women with early-stage hormone receptor-positive BC.},
}

@article {pmid40071498,
year = {2025},
author = {Mehta, RS and Choe, H and Saultz, J and Gong, Z and Sharma, P and Al-Juhaishi, T and Petitto, GS and Lazaryan, A and Singh, A and Xue, E and Dimitrova, D and Hyder, M and McCurdy, S and Im, A and Huber, B and Aljawai, YM and Kanakry, J and Milano, F and Kanakry, CG},
title = {Impact of Donor Age and Donor Cytomegalovirus Serostatus on Outcomes After Related Donor Allogeneic Hematopoietic Stem Cell Transplantation.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.27662},
pmid = {40071498},
issn = {1096-8652},
abstract = {Cytomegalovirus (CMV) infection post-hematopoietic cell transplantation (HCT) remains a significant cause of morbidity and mortality. While letermovir prophylaxis is available for CMV-seropositive recipients, optimal donor selection for CMV-seronegative recipients remains unclear, with donor age often prioritized over CMV serostatus. We investigated the relative impact of donor age and CMV serostatus in CMV-seronegative recipients (n = 1013) with either CMV-seropositive (n = 318) or CMV-seronegative donors (n = 695), who underwent HCT with HLA-matched sibling donors with calcineurin inhibitor-based or post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease prophylaxis, or haploidentical donors with PTCy. Multiple conventional and machine-learning approaches were employed to account for confounding factors. Across all analyses, CMV-seropositive donor status was consistently associated with significantly inferior overall survival (OS) and disease-free survival, primarily driven by increased non-relapse mortality (NRM). Older donor age showed a statistically significant association with OS and DFS in some but not all models, and its effect size was small (about 1% increased hazard per year in Cox proportional hazard model) compared to the substantial impact of CMV-seropositive donors (about 27%-33% increased hazards for worse OS, approximately 50%-60% higher NRM in Cox proportional hazard model). However, our machine learning model revealed a more nuanced and complex non-linear effect of donor age, further demonstrating the adverse impact of donor CMV serostatus. Our findings suggest that prioritizing a CMV-seronegative donor may be associated with improved outcomes in CMV-seronegative recipients. Further research is needed to validate these findings and explore underlying mechanisms.},
}

@article {pmid40071446,
year = {2025},
author = {Julceus, EF and Liese, AD and Alfalki, AM and Brown, AD and Pihoker, C and Qu, P and Malik, FS and Jones-Smith, JC and Crow, S and Loots, B and Reboussin, BA and Dolan, LM and Igudesman, D and Sauder, KA and Shapiro, ALB and Turley, CB and Mendoza, JA},
title = {The Association of Levels of Food Insecurity and Disordered Eating Behaviors Among Youth and Young Adults With Diabetes: The SEARCH for Diabetes in Youth Study.},
journal = {The International journal of eating disorders},
volume = {},
number = {},
pages = {},
doi = {10.1002/eat.24411},
pmid = {40071446},
issn = {1098-108X},
support = {1UC4DK108173/DK/NIDDK NIH HHS/United States ; R01DK117461/DK/NIDDK NIH HHS/United States ; /CC/CDC HHS/United States ; },
abstract = {OBJECTIVE: To examine the relationship between levels of household food insecurity and disordered eating behaviors (DEB) among youth and young adults with youth-onset type 1 (T1D) and type 2 diabetes (T2D).

METHOD: We used cross-sectional data from the multicenter SEARCH for Diabetes in Youth Study (2015-2020). The Household Food Security Survey Module and the Diabetes Eating Problem Survey-Revised (DEPS-R) were utilized to measure household food insecurity and continuous scores for DEB. In each stratum of diabetes type, we evaluated the association of household food insecurity levels with DEB through linear regression adjusting for potential confounders.

RESULTS: Participants (n = 2669) were on average 21.5 ± 5.1 years old and had a mean diabetes duration of 11.2 ± 3.3 years; 54.2% were female, 64.0% non-Hispanic white, and respectively 12.9%, 11.1%, and 8.43% experienced marginal, low, and very low food security. The overall unadjusted mean DEPS-R score was 13.5 ± 9.5, with scores of 18.6 ± 11.8 and 21.1 ± 11.7 among T1D and T2D participants with very low food security, and scores of 11.5 ± 8.9 and 15.2 ± 8.8 among T1D and T2D participants with high food security. Compared to participants who reported high food security, adjusted DEPS-R scores among those with very low food security were 5.8 points (95% CI: 4.3, 7.4) and 6.6 points (95% CI: 3.3, 9.2) higher, respectively, in those with T1D (n = 2274) and T2D (n = 395). Less severe levels of household food insecurity showed similar associations with smaller effect sizes.

DISCUSSION: Addressing household food insecurity may decrease DEB and future adverse health outcomes for youth and young adults with diabetes.},
}

@article {pmid40070357,
year = {2025},
author = {Gust, J and Cole, BL and Ronsley, R and Wilson, AL and Seidel, K and Wendler, J and Pattabhi, S and Brown, C and Rawlings-Rhea, SD and Shtanukhina, N and Browd, SR and Hauptman, JS and Lee, A and Ojemann, JG and Crotty, EE and Leary, SES and Perez, FA and Wright, JN and Albert, CM and Pinto, N and Gardner, RA and Vitanza, NA and Jensen, MC and Park, JR},
title = {Locoregional Infusion of EGFR806-CAR T Cells for Recurrent or Refractory Pediatric CNS Tumors: Results of the Completed BrainChild02 Phase 1 Clinical Trial.},
journal = {Neuro-oncology},
volume = {},
number = {},
pages = {},
doi = {10.1093/neuonc/noaf064},
pmid = {40070357},
issn = {1523-5866},
abstract = {BACKGROUND: Relapsed/refractory pediatric CNS tumors have a poor prognosis. EGFR is commonly overexpressed, but EGFRvIII mutations are uncommon. To target these tumors, we used chimeric antigen receptor (CAR) T cells with a binder based on mAb806 which recognizes ectopically expressed wild-type EGFR and EGFRvIII.

METHODS: In this open-label phase 1 clinical trial, patients age 1-26 years with EGFR+ CNS tumors received weekly infusions of 1-2.5 x 107 CAR T cells into the tumor resection bed or the lateral ventricle via an implanted catheter. No lymphodepletion was used.

RESULTS: Eleven patients were enrolled. Four (3 with high-grade glioma, 1 with atypical teratoid-rhabdoid tumor) were treated and received 5-10 CAR T cell infusions without dose-limiting toxicities. The trial closed prior to reaching planned dose regimens. All treatment-related adverse events were no higher than CTCAE grade 2. The most common were headache and nausea. One patient had a grade 1 seizure, and three had new sensory changes, weakness and/or urinary changes (grade 1-2) that were possibly related to CAR T cell infusion. Three of the four treated patients had progressive disease. One patient with spinal cord diffuse midline glioma had progressive peritumoral edema that could not be conclusively attributed to either progression or pseudoprogression and was therefore defined as stable disease, followed by a complete response to subsequent chemotherapy.

CONCLUSIONS: Intracranially infused EGFR806-CAR T cells were tolerable at tested doses, with a best response of stable disease. EGFR is a potentially useful target for cellular therapy against pediatric brain tumors, particularly high-grade gliomas.},
}

@article {pmid40067465,
year = {2025},
author = {Nelson, JL and Lambert, NC},
title = {The when, what, and where of naturally-acquired microchimerism.},
journal = {Seminars in immunopathology},
volume = {47},
number = {1},
pages = {20},
pmid = {40067465},
issn = {1863-2300},
support = {117737/HL/NHLBI NIH HHS/United States ; 45659//Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Humans ; *Chimerism ; Pregnancy ; Female ; Maternal-Fetal Exchange/immunology ; HLA Antigens/genetics/immunology ; Autoimmune Diseases/etiology/immunology ; Animals ; },
abstract = {Naturally acquired microchimerism (Mc) is increasingly recognized as an aspect of normal biology. Maternal-fetal bi-directional exchange during pregnancy creates a Mc legacy for the long-term in both individuals. Maternal Mc in her offspring and Mc of fetal origin in women with previous births are best studied. Other sources include from a known or vanished twin, miscarriage or pregnancy termination, older sibling, or previous maternal pregnancy loss. Mc is pleotropic and protean, present in diverse forms, and changing over time as other aspects of biology. Mc acquired from multiple sources, at different lifespan times, and taking on an array of diverse forms, creates a "forward, reverse, and horizontal inheritance" Mc landscape. Mc is found in adaptive and innate immune cells, as resident tissue-specific cells in a wide variety of human tissues, and among other forms as extracellular vesicles. HLA molecules function in a myriad of ways as key determinants for health and are of central importance in interactions between genetically disparate individuals. Studies of autoimmune disease have firmly established a primary role of HLA molecules. Studies of iatrogenic chimerism have established benefit of donor-recipient HLA-disparity against recurrent malignancy after transplantation. HLA molecules and HLA-relationships of families are therefore of particular interest in seeking to understand the role(s) of Mc at the interface of auto-immunity and healthy allo-immunity. This review will begin by providing perspective on Mc in biology followed by a primary focus on persistent Mc according to the human lifespan, in healthy individuals and with illustrative examples of autoimmune diseases.},
}

Humans
*Chimerism
Pregnancy
Female
Maternal-Fetal Exchange/immunology
HLA Antigens/genetics/immunology
Autoimmune Diseases/etiology/immunology
Animals

@article {pmid40067336,
year = {2025},
author = {Shadman, M and Fakhri, B and Jain, N},
title = {Consensus in CLL: global needs matter.},
journal = {Blood advances},
volume = {9},
number = {5},
pages = {1210-1212},
doi = {10.1182/bloodadvances.2024015355},
pmid = {40067336},
issn = {2473-9537},
}

@article {pmid40060430,
year = {2025},
author = {Colegrove, HL and Monnat, RJ and Feder, AF},
title = {Epithelial competition determines gene therapy potential to suppress Fanconi Anemia oral cancer risk.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40060430},
issn = {2692-8205},
support = {DP2 CA280623/CA/NCI NIH HHS/United States ; },
abstract = {Fanconi Anemia (FA) is a heritable syndrome characterized by DNA damage repair deficits, frequent malformations and a significantly elevated risk of bone marrow failure, leukemia, and mucosal head and neck squamous cell carcinomas (HNSCC). Hematopoietic stem cell gene therapy can prevent marrow failure and lower leukemia risk, but mucosal gene therapy to lower HNSCC risk remains untested. Major knowledge gaps include an incomplete understanding of how rapidly gene-corrected cellular lineages could spread through the oral epithelium, and which delivery parameters are critical for ensuring efficient gene correction. To answer these questions, we extended an agent-based model of the oral epithelium to include the delivery of gene correction in situ to FA cells and the competitive dynamics between cellular lineages with and without gene correction. We found that only gene-corrected lineages with substantial proliferative advantages (probability of resisting displacement out of the basal layer ≥ 0.1) could spread on clinically relevant timelines, and that these lineages were initially at high risk of loss in the generations following correction. Delivering gene correction to many cells minimizes the risk of loss, while delivery to many distinct locations within a tissue maximizes the rate of spread. To determine the impact of mucosal gene therapy in preventing the clonal expansion of pre-cancerous mutations, we compared the expected burden of T P 53 mutations in simulated tissue sections with and without gene correction. We found that when FA cells have elevated genome instability or a T P 53 -dependent proliferative advantage, gene correction can substantially reduce the accumulation of pro-tumorigenic mutations. This model illustrates the power of computational frameworks to identify critical determinants of therapeutic success to enable experimental optimization and support novel and effective gene therapy applications.},
}

@article {pmid40067123,
year = {2025},
author = {Wuliji, N and Jones, SMW and Gooley, TA and Gerds, AT and Medeiros, BC and Shami, PJ and Galvin, JP and Adekola, KUA and Luger, SM and Baer, MR and Rizzieri, DA and Wildes, T and Wang, ES and Sekeres, MA and Mukherjee, S and Smith, J and Garrison, M and Kojouri, K and Appelbaum, JS and Percival, MM and Sandmaier, BM and Lee, SJ and Appelbaum, F and Rouce, RH and Sorror, ML},
title = {Social Determinants of Health and Access to Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024027543},
pmid = {40067123},
issn = {1528-0020},
abstract = {Whether allogeneic hematopoietic cell transplant (allo-HCT) to treat acute myeloid leukemia (AML) is equitably accessible regardless of social determinants of health (SDOH) remains unknown. We examined associations of SDOH with access to allo-HCT and other outcomes. Patients presenting for treatment (n=692) at 13 AML treatment centers were prospectively recruited to a registered clinical trial (#NCT01929408). Various patient, AML, and SDOH specific variables were collected. Outcomes included mortality without allo-HCT, receipt of allo-HCT, and mortality after allo-HCT. Individual multivariable models (Fine-Gray for the first two outcomes, Cox regression for the third) were fit for each SDOH variable, adjusting for relevant patient- and AML-specific variables. Allo-HCT was used to treat 46% of patients. A 10% increase in the proportion with less than a high-school education, in households receiving Supplemental Nutrition Assistance Program, receiving Supplemental Security Income, or in poverty led to modeled adjusted hazard ratios (aHRs) of 1.21 (0.99-1.46), 1.13 (0.97-1.31), 1.41 (1.01-1.97), and 1.16 (0.96-1.39) for death without allo-HCT. The aHRs were 0.67 (0.55-0.83), 0.88 (0.76-1.01), 0.71 (0.48-1.05), and 0.91 (0.75-1.09), for lessened receipt of allo-HCT. Among those who received allo-HCT, aHRs for mortality were 1.18 (0.87-1.60), 1.13 (0.92-1.38), 1.21 (0.81-1.82), and 1.04 (0.79-1.36). Results highlight increased mortality without allo-HCT and decreased access to allo-HCT, but lesser magnitude of increased mortality after allo-HCT, among patients from lower resourced areas due to limited education and/or increased poverty. Targeted interventions and policy changes are needed to ensure that marginalized patient populations have equitable chances for AML cure compared to others.},
}

@article {pmid40066650,
year = {2025},
author = {Donzella, SM and Bryer, BN and VoPham, T and Weaver, MD and Watson, NF and Zhong, C and Patel, AV and Phipps, AI},
title = {Chronotype, sleep timing, sleep regularity, and cancer risk: A systematic review.},
journal = {Sleep},
volume = {},
number = {},
pages = {},
doi = {10.1093/sleep/zsaf059},
pmid = {40066650},
issn = {1550-9109},
abstract = {Sleep is a multidimensional modifiable lifestyle factor related to cancer risk. Prior research has primarily focused on sleep duration, despite the increasing importance of sleep timing and sleep regularity in the health research field. The objective of this systematic review was to synthesize the existing literature on the relationship of chronotype, sleep timing, and sleep regularity with cancer risk. We searched four databases (PubMed, CINAHL, PsychInfo, and Embase) in October 2024. The sleep exposures of interest included sleep timing, sleep regularity, sleep midpoint, social jetlag, chronotype, and weekend catch-up sleep, and the outcome of interest was cancer incidence (overall or site-specific). A total of 22 studies were included, of which 18 investigated chronotype, two investigated social jetlag, two investigated sleep midpoint, and one investigated weekend catch-up sleep as the sleep exposure. The majority of studies assessed sleep using self-reported questionnaires (95%) and investigated site-specific cancer incidence (91%). We found no consistent evidence linking late chronotype, later sleep midpoint, increased social jetlag, or weekend catch-up sleep to elevated risk of cancer. This review highlights the heterogeneity in how sleep timing and sleep regularity are assessed. Future research should standardize measures on how to quantify sleep timing and sleep regularity and replication studies in diverse populations are needed. Current evidence on linking sleep timing, sleep regularity, and chronotype with cancer risk remains inconclusive.},
}

@article {pmid40065283,
year = {2025},
author = {Venkataraman, A and Jia, T and Ruderman, SA and Haas, CB and Nance, RM and Mixson, LS and Mayer, KH and Saag, MS and Chander, G and Moore, RD and Jacobson, J and Napravnik, S and Christopolous, K and Lee, WJ and Whitney, BM and Peter, I and Crane, HM and Delaney, JAC and Lindström, S},
title = {A genome-wide association study of methamphetamine use among people with HIV.},
journal = {BMC medical genomics},
volume = {18},
number = {1},
pages = {46},
pmid = {40065283},
issn = {1755-8794},
support = {R01 HG010649/HG/NHGRI NIH HHS/United States ; R24 AI067039/AI/NIAID NIH HHS/United States ; R24AI067039/AA/NIAAA NIH HHS/United States ; R01HG010649/NH/NIH HHS/United States ; },
mesh = {Humans ; *Methamphetamine/adverse effects ; *Genome-Wide Association Study ; *HIV Infections/genetics ; *Polymorphism, Single Nucleotide ; Male ; Female ; Adult ; Amphetamine-Related Disorders/genetics ; Middle Aged ; Cohort Studies ; },
abstract = {BACKGROUND: Amphetamine-like stimulants are the most used psychostimulants in the world; methamphetamine use is the most prevalent in people with HIV. Prolonged methamphetamine use can cause lasting damage to the heart, gut, and brain, as well as auditory hallucinations and paranoid thinking. However, relatively little is known about methamphetamine use and its genetic contributors.

METHODS: Using genetic information from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort, we conducted a multi-ancestry genome-wide association study (GWAS) of methamphetamine use among people with HIV (n = 1,196 reported ever use, n = 4,750 reported never use).

RESULTS: No single nucleotide polymorphism was statistically associated with methamphetamine use at the genome-wide level (p < 5 * 10[-8]) in our study. Further, we did not replicate previously suggested genetic variants from other studies (all p > 0.05 in our analysis).

DISCUSSION: Our study suggests that there is no single strong genetic contributor to lifetime use of methamphetamine in people with HIV enrolled in CNICS. Larger studies with more refined outcome assessment are warranted to further understand the contribution of genetics to methamphetamine use and use disorder. Investigation into social and environmental contributors to methamphetamine use are similarly necessary.},
}

Humans
*Methamphetamine/adverse effects
*Genome-Wide Association Study
*HIV Infections/genetics
*Polymorphism, Single Nucleotide
Male
Female
Adult
Amphetamine-Related Disorders/genetics
Middle Aged
Cohort Studies

@article {pmid40064621,
year = {2025},
author = {Salerno, S and Yang, E and Dahlerus, C and Hirth, RA and Han, P and Xu, T and Eckard, A and Agbenyikey, W and Horton, GM and Clark, S and Messana, JM and Li, Y},
title = {Adding New Components to a Composite Quality Metric: How Good Is Good Enough?.},
journal = {Medical care},
volume = {63},
number = {4},
pages = {293-299},
doi = {10.1097/MLR.0000000000002116},
pmid = {40064621},
issn = {1537-1948},
mesh = {Humans ; Reproducibility of Results ; *Quality Indicators, Health Care ; Renal Dialysis/standards ; Quality of Health Care/standards ; United States ; },
abstract = {OBJECTIVES: This study illustrates how the statistical reliability of an individual measure relates to the overall reliability of a composite metric, as understanding this relationship provides additional information when evaluating measures for endorsement.

BACKGROUND: National quality measure endorsement processes typically evaluate individual metrics on criteria such as importance and scientific acceptability (eg, reliability). In practice, quality measures may be used in composite rating systems, which aid in the interpretation of overall quality differences.

METHODS: We define an individual measure's reliability by its intraclass correlation and analytically establish the relationship between a composite's reliability and the reliability of its components. We use real data to confirm this relationship under various scenarios. We are motivated by 8 quality measures, which comprise the Quality of Patient Care Star Ratings on Dialysis Facility Care Compare. These measure 4 primary outcomes (mortality, hospitalizations, readmissions, and blood transfusions), vascular access (2 measures), and facility processes (2 measures).

RESULTS: Depending on the reliability of the individual measures, their respective weights in the composite, and their pairwise correlations, there are circumstances when adding a new measure, even if it is less reliable, increases the composite's reliability. For the dialysis facility Star Ratings, we find that the combined reliability of measures grouped within certain domains of care exceeded the reliability of the individual measures within those domains.

CONCLUSIONS: New quality measures may add utility to a composite rating system under certain circumstances-a consideration that should, in part, factor into quality measure endorsement processes.},
}

Humans
Reproducibility of Results
*Quality Indicators, Health Care
Renal Dialysis/standards
Quality of Health Care/standards
United States