@article {pmid40347455,
year = {2025},
author = {Schenk, JM and Gulati, R and Beatty, SJ and Plymate, S and Lin, DW and Dash, A and Porter, MP and Vandoren, M and Wright, JL and Neuhouser, ML},
title = {Reduced adipose tissue with limited loss of lean mass after weight loss: results from the Prostate Active Lifestyle Study.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf113},
pmid = {40347455},
issn = {1460-2105},
abstract = {Adiposity reduction has both cancer-specific and overall health benefits for patients with overweight or obesity. However, the indiscriminate loss of lean mass accompanying weight loss remains a concern for older cancer patients. Body composition was evaluated in the Prostate Active Lifestyle Study, a randomized controlled weight loss trial targeting caloric restriction and increased physical activity among patients with prostate cancer (PCa) and overweight or obesity on active surveillance. Compared to control, the intervention statistically significantly decreased total fat (-3.4%; 95%CI: -5.3%, -1.5%), android fat (-2.0%; 95%CI: -3.6%, -0.4%), and visceral adipose tissue mass (-613 g; 95%CI: -894 g, -331 g) (all 2-sided p < .001) with no difference in lean mass (p = .70) and a statistically significant increase in lean-to-fat ratio (0.40; 95%CI: 0.06, 0.73; 2-sided p = .02). Weight loss interventions incorporating diet and physical activity among patients with PCa and overweight or obesity can yield statistically significant reductions in adiposity while limiting lean mass loss.},
}

@article {pmid40346049,
year = {2025},
author = {Pasvolsky, O and Dima, D and Feng, L and Dong, W and Richards, T and Davis, JA and Afrough, A and Vazquez-Martinez, M and Sannareddy, A and Goel, U and Banerjee, R and Khouri, J and Cervoni, F and Gaballa, MR and Lieberman-Cribbin, A and Rana, MS and Julian, K and Ferreri, CJ and Shune, L and DeJarnette, S and Bhurtel, E and Susanibar Adaniya, S and Portuguese, A and Hosoya, H and Mikkilineni, L and Kaur, G and Rossi, A and Herr, MM and Schrum, D and Lin, C and Raza, S and Lin, Y and Midha, S and Omar, N and Atarsh, S and McGuirk, J and Sborov, D and Voorhees, P and Anwer, F and Alsina, M and Freeman, C and Garfall, AL and Razzo, BM and Sidana, S and Cowan, AJ and Anderson, LD and Hansen, DK and Richard, S and Patel, KK and Lee, HC and Grajales-Cruz, A},
title = {Outcomes of elderly patients with relapsed refractory multiple myeloma (RRMM) treated with teclistamab: a multicenter study from the U.S. Multiple Myeloma Immunotherapy Consortium.},
journal = {Blood cancer journal},
volume = {15},
number = {1},
pages = {92},
pmid = {40346049},
issn = {2044-5385},
support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA281756/CA/NCI NIH HHS/United States ; NCI Grant P30 CA016672//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; NCI (R01CA281756-01A1)//U.S. Department of Health & Human Services | NIH | NIH Clinical Center (Clinical Center)/ ; },
mesh = {Humans ; *Multiple Myeloma/drug therapy/mortality/pathology ; Aged ; Male ; Female ; Aged, 80 and over ; Middle Aged ; Retrospective Studies ; *Antibodies, Bispecific/therapeutic use/adverse effects/administration & dosage ; Treatment Outcome ; United States ; Adult ; *Antineoplastic Agents, Immunological/therapeutic use/adverse effects ; Age Factors ; },
abstract = {Teclistamab, a BCMA-directed bispecific antibody, received regulatory approval for relapsed/refractory multiple myeloma (RRMM) based on the MajesTEC-1 study. Despite the fact that myeloma is primarily a cancer of elderly adults, only 15% of MajesTEC-1 participants (n = 24) were ≥75 years old. In this multicenter retrospective study, we report real-world outcomes of a large cohort of older RRMM patients treated with teclistamab. Of 385 analyzed patients, 83 (22%) were in the older group (age ≥75) and 302 (78%) in the younger group (age <75). Compared to the younger group, the older group had less adverse baseline disease characteristics, including a lower incidence of high-risk cytogenetics (44.6% vs. 57.9%, p = 0.03) and extramedullary disease (22% vs. 40%, p = 0.02). There were no significant differences in rates of any-grade CRS (52% vs. 59%, p = 0.27), any-grade ICANS (19% vs. 13%, p = 0.12), and overall response rate (62% vs. 53%, p = 0.17) between the older and younger groups. In multivariable analysis, age was not significantly associated with survival outcomes. Our findings suggest that teclistamab is safe and efficacious in well-selected patients ≥75 years old, and advanced age alone should not preclude teclistamab administration.},
}

Humans
*Multiple Myeloma/drug therapy/mortality/pathology
Aged
Male
Female
Aged, 80 and over
Middle Aged
Retrospective Studies
*Antibodies, Bispecific/therapeutic use/adverse effects/administration & dosage
Treatment Outcome
United States
Adult
*Antineoplastic Agents, Immunological/therapeutic use/adverse effects
Age Factors

@article {pmid40346033,
year = {2025},
author = {Mihalas, AB and Arora, S and O'Connor, SA and Feldman, HM and Cucinotta, CE and Mitchell, K and Bassett, J and Kim, D and Jin, K and Hoellerbauer, P and Delegard, J and Ling, M and Jenkins, W and Kufeld, M and Corrin, P and Carter, L and Tsukiyama, T and Aronow, B and Plaisier, CL and Patel, AP and Paddison, PJ},
title = {KAT5 regulates neurodevelopmental states associated with G0-like populations in glioblastoma.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {4327},
pmid = {40346033},
issn = {2041-1723},
support = {R01 CA295090/CA/NCI NIH HHS/United States ; R01 CA190957/CA/NCI NIH HHS/United States ; S10 OD026919/OD/NIH HHS/United States ; R01CA190957//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P30 CA015704/CA/NCI NIH HHS/United States ; R01NS119650//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R35 GM139429/GM/NIGMS NIH HHS/United States ; T32CA080416//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R21 CA232244/CA/NCI NIH HHS/United States ; R01 NS119650/NS/NINDS NIH HHS/United States ; P30CA15704//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; T32 CA080416/CA/NCI NIH HHS/United States ; },
mesh = {*Glioblastoma/pathology/genetics/metabolism ; Humans ; *Histone Acetyltransferases/metabolism/genetics ; *Brain Neoplasms/pathology/genetics/metabolism ; Cell Line, Tumor ; Neoplastic Stem Cells/metabolism/pathology ; Animals ; Gene Expression Regulation, Neoplastic ; Neural Stem Cells/metabolism ; Mice ; Cell Proliferation ; Proto-Oncogene Proteins c-myc/metabolism/genetics ; },
abstract = {Quiescence cancer stem-like cells may play key roles in promoting tumor cell heterogeneity and recurrence for many tumors, including glioblastoma (GBM). Here we show that the protein acetyltransferase KAT5 is a key regulator of transcriptional, epigenetic, and proliferative heterogeneity impacting transitions into G0-like states in GBM. KAT5 activity suppresses the emergence of quiescent subpopulations with neurodevelopmental progenitor characteristics, while promoting GBM stem-like cell (GSC) self-renewal through coordinately regulating E2F- and MYC- transcriptional networks with protein translation. KAT5 inactivation significantly decreases tumor progression and invasive behavior while increasing survival after standard of care. Further, increasing MYC expression in human neural stem cells stimulates KAT5 activity and protein translation, as well as confers sensitivity to homoharringtonine, to similar levels to those found in GSCs and high-grade gliomas. These results suggest that the dynamic behavior of KAT5 plays key roles in G0 ingress/egress, adoption of quasi-neurodevelopmental states, and aggressive tumor growth in gliomas.},
}

*Glioblastoma/pathology/genetics/metabolism
Humans
*Histone Acetyltransferases/metabolism/genetics
*Brain Neoplasms/pathology/genetics/metabolism
Cell Line, Tumor
Neoplastic Stem Cells/metabolism/pathology
Animals
Gene Expression Regulation, Neoplastic
Neural Stem Cells/metabolism
Mice
Cell Proliferation
Proto-Oncogene Proteins c-myc/metabolism/genetics

@article {pmid40344957,
year = {2025},
author = {Rugo, HS and Bardia, A and Gradishar, WJ and Hamilton, EP and Hurvitz, SA and Jhaveri, K and Mahtani, R and Tolaney, SM},
title = {Expert consensus on treating HR+/HER2- metastatic breast cancer based on real-world practice patterns observed in the RETRACT survey of US oncologists.},
journal = {Breast (Edinburgh, Scotland)},
volume = {82},
number = {},
pages = {104485},
doi = {10.1016/j.breast.2025.104485},
pmid = {40344957},
issn = {1532-3080},
abstract = {Hormone receptor-positive, HER2-negative metastatic breast cancer (HR+/HER2-mBC) is incurable, but recent progress has been made in developing new treatment options and the treatment landscape is rapidly shifting. There are published recommendations for treatment choices and sequencing to help guide oncologists in treating HR+/HER2-mBC, but little evidence has been published regarding real-world practice patterns. The REal-world TReatment patterns And Considerations of Toxicity in HR+/HER2-mBC (RETRACT) survey was designed to evaluate real-world practice patterns in the testing and management of this disease by US oncologists. The survey questions were answered via an online platform and the data were anonymized before analysis. A total of 150 oncologists practicing at academic and community centers completed the survey. The results showed this sample of oncologists largely followed recommended best practices for testing biomarkers, selecting treatments, and managing adverse events. However, several items did show substantial minorities of oncologists not in alignment with recommendations in areas including the definition and treatment of visceral crisis, ideal treatment for patients with endocrine resistance, the routine use of next-generation sequencing for biomarker testing, and the use of prophylactic measures for treatment-related adverse events in patients receiving alpelisib.},
}

@article {pmid40344546,
year = {2025},
author = {Check, DK and Li, Z and Shibeika, S and Sloan, CE and Sitlinger, A and Zullig, LL and Graf, SA and Blalock, DV},
title = {Receipt of Alcohol Screening, Brief Intervention, and Treatment Among US Adults With and Without a History of Cancer.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2401030},
doi = {10.1200/OP-24-01030},
pmid = {40344546},
issn = {2688-1535},
abstract = {PURPOSE: Many cancer survivors consume alcohol above recommended limits, increasing their risk of recurrence, second cancers, and cancer-related mortality. Alcohol screening, brief intervention, and referral to treatment (SBIRT) is a guideline-recommended strategy for reducing unhealthy alcohol consumption among adult primary care patients. To our knowledge, no prior studies have evaluated SBIRT's reach among cancer survivors.

METHODS: We conducted a cross-sectional study of adults who completed the National Survey on Drug Use and Health from 2015 to 2022. We examined past-year receipt of alcohol screening and-among respondents who endorsed unhealthy alcohol use-brief intervention and treatment. All outcomes were examined among cancer survivors and those with no cancer history. We used modified Poisson regression to assess the associations of cancer history with each outcome, adjusting for sociodemographic characteristics.

RESULTS: The cohort included 86,410 respondents with no history of cancer and 9,963 cancer survivors. The percentages of respondents endorsing past-year receipt of alcohol screening (approximately 40%), brief intervention (approximately 8%), and treatment (approximately 2%) were similarly low in both groups. After adjustment, there was a small but statistically significant difference in alcohol screening, with cancer survivors more likely than people without a history of cancer to receive alcohol screening (adjusted risk ratio [aRR], 1.07; 95% CI, 1.02 to 1.13). Among those with unhealthy alcohol use, cancer survivors were no more or less likely than people without a history of cancer to receive brief alcohol intervention (aRR, 1.00; 95% CI, 0.93 to 1.07) or alcohol treatment (aRR, 0.92; 95% CI, 0.47 to 1.69).

CONCLUSION: Results reveal an important opportunity to improve SBIRT uptake across the board and especially for cancer survivors, who are at increased risk of alcohol-related adverse health effects and, potentially, more motivated to change cancer-related health behaviors.},
}

@article {pmid40343485,
year = {2025},
author = {Yang, H and Luo, K and Peters, BA and Wang, Y and Zhang, Y and Daviglus, M and Pirzada, A and Cordero, C and Yu, B and Burk, RD and Kaplan, R and Qi, Q},
title = {Diet, Gut Microbiota, and Histidine Metabolism Toward Imidazole Propionate Production in Relation to Type 2 Diabetes.},
journal = {Diabetes care},
volume = {},
number = {},
pages = {},
doi = {10.2337/dc24-2816},
pmid = {40343485},
issn = {1935-5548},
support = {R01DK119268/DK/NIDDK NIH HHS/United States ; R01HL140976/HL/NHLBI NIH HHS/United States ; },
abstract = {OBJECTIVE: To examine associations of serum imidazole propionate (ImP), histidine, and their ratio with incident type 2 diabetes (T2D) and related dietary and gut microbial factors in U.S. Hispanic/Latino people.

RESEARCH DESIGN AND METHODS: In the Hispanic Community Health Study/Study of Latinos, we evaluated serum ImP, histidine, and ImP-to-histidine ratio at baseline (2008-2011) and their cross-sectional associations with dietary intake and prospective associations with incident T2D over ∼12 years (n = 4,632). In a subsample with gut microbiota data during a follow-up visit (2016-2018), we examined gut microbial species associated with serum ImP and their potential interactions with dietary intake.

RESULTS: Serum ImP and ImP-to-histidine ratio were positively associated with incident T2D (hazard ratio [95% CI] = 1.17 [1.00-1.36] and 1.33 [1.14-1.55], respectively, comparing highest and lowest tertiles), whereas histidine was inversely associated with incident T2D (hazard ratio = 0.75 [95% CI 0.64-0.86]). A higher amount of fiber intake was associated with lower serum ImP level and ImP-to-histidine ratio, whereas histidine intake was not associated with serum ImP level in the overall sample. Fifty-three bacterial species, including 19 putative ImP producers, were associated with serum ImP. Histidine intake was positively associated with serum ImP and ImP-to-histidine ratio only in participants with a high ImP-associated gut microbiota score (P = 0.03 and 0.02, respectively, for interaction). The associations of fiber intake with serum ImP and ImP-to-histidine ratio were partly mediated by ImP-associated gut microbiota (proportion mediated = 31.4% and 19.8%, respectively).

CONCLUSIONS: This study suggested an unfavorable relationship between histidine metabolism toward ImP production, potentially regulated by dietary intake and gut microbiota, and risk of T2D in U.S. Hispanics/Latino people.},
}

@article {pmid40342410,
year = {2025},
author = {Zhang, T and Gentry, CA and Kuderer, NM and Lyman, GH and Ng, B and Michailidou, D},
title = {Association of SSRI and SNRI use with incidence of cardiovascular events in veterans with giant cell arteritis and polymyalgia rheumatica.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1509941},
pmid = {40342410},
issn = {1664-3224},
mesh = {Humans ; *Polymyalgia Rheumatica/drug therapy/epidemiology/complications ; Male ; Female ; Aged ; *Giant Cell Arteritis/drug therapy/epidemiology/complications ; *Selective Serotonin Reuptake Inhibitors/therapeutic use/adverse effects ; Incidence ; Veterans ; *Serotonin and Noradrenaline Reuptake Inhibitors/therapeutic use/adverse effects ; *Cardiovascular Diseases/epidemiology/etiology ; Aged, 80 and over ; Middle Aged ; United States/epidemiology ; },
abstract = {The leading cause of death in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) is cardiovascular disease. The objective of this study was to determine whether the use of selective serotonin reuptake inhibitors (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRI) in veterans with GCA and PMR could have a cardio-modulatory effect as compared to nonuse. Patients with GCA and PMR were identified through the Veterans Affairs Informatics and Computing Infrastructure. After a 2:1 propensity score matching for SSRI or SNRI users, we identified nonusers with similar covariates. We then applied a multivariate logistic regression (MLR), to calculate the odds ratio (OR) for cardiovascular event (CVE) outcomes within 5 years after the index date. Related hazard ratios (HR) were also calculated to validate the discovery of our findings. We identified 2249 patients with GCA and 3906 patients with PMR. Among patients with GCA, 174 (27%) SSRI users had incident cardiovascular disease as compared to 47 (28%) SNRI users and 277 (19%) nonusers; in the PMR cohort, 108 (13%) were SSRI users compared to 71 (15%) SNRI users and 255 (11%) nonusers. The adjusted ORs of the CVE outcome associated with venlafaxine (2.44, p=0.01) and sertraline (1.45, p=0.04) were significantly greater than 1 in GCA, with similar results observed in the PMR cohort (2.01, p=0.02, and 1.45, p=0.04, respectively). Cox-regression analysis was also conducted, and the hazard ratios were qualitatively consistent with the MLR analysis. In conclusion, the adjusted risk of CVE in patients with GCA or PMR using either venlafaxine or sertraline was higher than that in the non-exposed groups.},
}

Humans
*Polymyalgia Rheumatica/drug therapy/epidemiology/complications
Male
Female
Aged
*Giant Cell Arteritis/drug therapy/epidemiology/complications
*Selective Serotonin Reuptake Inhibitors/therapeutic use/adverse effects
Incidence
Veterans
*Serotonin and Noradrenaline Reuptake Inhibitors/therapeutic use/adverse effects
*Cardiovascular Diseases/epidemiology/etiology
Aged, 80 and over
Middle Aged
United States/epidemiology

@article {pmid40341939,
year = {2025},
author = {Byun, J and Han, Y and Choi, J and Sun, R and Shaw, VR and Zhu, C and Xiao, X and Lusk, C and Badr, H and Lee, HS and Jang, HJ and Li, Y and Lim, H and Long, E and Liu, Y and Kachuri, L and Walsh, KM and Wiencke, JK and Albanes, D and Lam, S and Tardon, A and Neuhouser, ML and Barnett, MJ and Chen, C and Bojesen, S and Brenner, H and Landi, MT and Johansson, M and Risch, A and Wichmann, HE and Bickeböller, H and Christiani, DC and Rennert, G and Arnold, S and Field, JK and Shete, S and Le Marchand, L and Liu, G and Andrew, AS and Zienolddiny, S and Grankvist, K and Johansson, M and Caporaso, N and Taylor, F and Lazarus, P and Schabath, MB and Aldrich, MC and Patel, A and Lin, X and Zanetti, KA and Harris, CC and Chanock, S and McKay, J and Schwartz, AG and Hung, RJ and Amos, CI and , },
title = {Genome-wide association study for lung cancer in 6531 African Americans reveals new susceptibility loci.},
journal = {Human molecular genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/hmg/ddaf059},
pmid = {40341939},
issn = {1460-2083},
support = {U19CA203654//the National Institutes of Health (NIH)/ ; RR170048//Cancer Prevention Research Interest of Texas (CPRIT)/ ; },
abstract = {Despite lung cancer affecting all races and ethnicities, disparities are observed in incidence and mortality rates among different ethnic groups in the United States. Non-Hispanic African Americans had a high incidence rate of lung cancer at 55.8 per 100 000 people, as well as the highest death rate at 37.2 per 100 000 people from 2016 to 2020. While previous genome-wide association studies (GWAS) have identified over 45 susceptibility risk loci that influence lung cancer development, few GWAS have investigated the etiology of lung cancer in African Americans. To address this gap in knowledge, we conducted GWAS of lung cancer focused on studying African Americans, comprising 2267 lung cancer cases and 4264 controls. We identified three loci associated with lung cancer, one with lung adenocarcinoma, and four with lung squamous cell carcinoma in this population at the genomic-wide significance level. Among them, three novel loci were identified near VWF at 12p13.31 for overall lung cancer and GACAT3 at 2p24.3 and LMAN1L at 15q24.1 for lung squamous cell carcinoma. In addition, we confirmed previously reported risk loci with known or new lead variants near CHRNA5 at 15q25.1 and CYP2A6 at 19q13.2 associated with lung cancer and TRIP13 at 5p15.33 and ERC1 at 12p13.33 associated with lung squamous cell carcinoma. Further multi-step functional analyses shed light on biological mechanisms underlying these associations of lung cancer in this population. Our study highlights the importance of ancestry-specific studies for the potential alleviation of lung cancer burden in African Americans.},
}

@article {pmid40341199,
year = {2025},
author = {Ajani, JA and D'Amico, TA and Bentrem, DJ and Corvera, CU and Das, P and Enzinger, PC and Enzler, T and Gerdes, H and Gibson, MK and Grierson, P and Gupta, G and Hofstetter, WL and Ilson, DH and Jalal, S and Kim, S and Kleinberg, LR and Klempner, S and Lacy, J and Lee, B and Licciardi, F and Lloyd, S and Ly, QP and Matsukuma, K and McNamara, M and Merkow, RP and Miller, AM and Mukherjee, S and Mulcahy, MF and Perry, KA and Pimiento, JM and Reddi, DM and Reznik, S and Roses, RE and Strong, VE and Su, S and Uboha, N and Wainberg, ZA and Willett, CG and Woo, Y and Yoon, HH and McMillian, NR and Stein, M},
title = {Gastric Cancer, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {23},
number = {5},
pages = {169-191},
doi = {10.6004/jnccn.2025.0022},
pmid = {40341199},
issn = {1540-1413},
mesh = {Humans ; *Stomach Neoplasms/therapy/diagnosis/pathology/mortality ; *Medical Oncology/standards/methods ; Biomarkers, Tumor/analysis ; Prognosis ; Neoplasm Staging ; },
abstract = {Gastric cancer is the fifth leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improve survival, and enhance the quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing has had a significant impact on clinical practice and patient care. Targeted therapies have demonstrated encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. This selection from the NCCN Clinical Practice Guidelines in Oncology for Gastric Cancer highlights recommendations for biomarker testing and discusses updates for the treatment of advanced disease, including peritoneal carcinoma as only disease and unresectable locally advanced, recurrent, or metastatic disease.},
}

Humans
*Stomach Neoplasms/therapy/diagnosis/pathology/mortality
*Medical Oncology/standards/methods
Biomarkers, Tumor/analysis
Prognosis
Neoplasm Staging

@article {pmid40341193,
year = {2025},
author = {Tsang, TK and Rojas, DP and Xu, F and Xu, Y and Zhu, X and Halloran, ME and Longini, IM and Yang, Y},
title = {Estimating transmissibility of Zika virus in Colombia in the presence of surveillance bias.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {4299},
pmid = {40341193},
issn = {2041-1723},
mesh = {Humans ; *Zika Virus Infection/transmission/epidemiology/virology ; Colombia/epidemiology ; Female ; Adolescent ; Male ; Adult ; *Zika Virus/physiology ; Young Adult ; Bayes Theorem ; Disease Outbreaks ; Middle Aged ; Child ; Population Surveillance ; Bias ; Microcephaly/epidemiology/virology ; },
abstract = {The 2015-2016 Zika virus outbreak in the Americas presented significant challenges in understanding the transmission dynamics due to substantial reporting biases, as women of reproductive age (15-39 years) were disproportionately represented in the surveillance data when public awareness of relationship between Zika and microcephaly increased. Using national surveillance data from Colombia during July 27, 2015-November 21, 2016, we developed a Bayesian hierarchical modeling framework to reconstruct the true numbers of symptomatic cases and estimate transmission parameters while accounting for differential reporting across age-sex groups. Our model revealed that the detection rate of symptomatic cases among women of reproductive age was 99% (95% CI: 98.7-100), compared to 85.4% (95% CI: 84.7-86.1) in other demographic groups. After correcting for these biases, our results showed that females aged 15-39 years remained 82.8% (95% CI: 80.2-85.2%) more susceptible to Zika symptomatic infection than males of the same age, independent of differential reporting areas. Departments with medium-high altitude, medium-high population density, low coverage of forest, or high dengue incidence from 2011-2015 exhibited greater Zika risk. This study underscores the importance of accounting for surveillance biases in epidemiological studies to better understand factors influencing Zika transmission and to inform disease control and prevention.},
}

Humans
*Zika Virus Infection/transmission/epidemiology/virology
Colombia/epidemiology
Female
Adolescent
Male
Adult
*Zika Virus/physiology
Young Adult
Bayes Theorem
Disease Outbreaks
Middle Aged
Child
Population Surveillance
Bias
Microcephaly/epidemiology/virology

@article {pmid40340857,
year = {2025},
author = {Kumar, SK and Callander, NS and Adekola, K and Anderson, LD and Baljevic, M and Baz, R and Campagnaro, E and Costello, C and D'Angelo, C and Derman, B and Devarakonda, S and Elsedawy, N and Godara, A and Godby, K and Hillengass, J and Holmberg, L and Htut, M and Huff, CA and Hultcrantz, M and Kang, Y and Larson, S and Lee, HC and Liedtke, M and Martin, T and Omel, J and Robinson, T and Rosenberg, A and Schroeder, MA and Sherbenou, D and Suvannasankha, A and Valent, J and Varshavsky-Yanovsky, AN and Vogl, D and Kovach, E and Kumar, R},
title = {NCCN Guidelines® Insights: Multiple Myeloma, Version 1.2025.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {23},
number = {5},
pages = {132-140},
doi = {10.6004/jnccn.2025.0023},
pmid = {40340857},
issn = {1540-1413},
mesh = {Humans ; *Multiple Myeloma/diagnosis/therapy ; *Medical Oncology/standards ; },
abstract = {The NCCN Guidelines for Multiple Myeloma (MM) provide recommendations for diagnosis, initial workup, treatment, follow-up, and supportive care for patients with MM. These NCCN Guidelines Insights highlight the important updates and changes specific to systemic therapy for patients with newly diagnosed as well as previously treated MM included in Version 1.2025 of the NCCN Guidelines for MM.},
}

Humans
*Multiple Myeloma/diagnosis/therapy
*Medical Oncology/standards

@article {pmid40340130,
year = {2025},
author = {Ujjani, C and Wang, H and Broome, C and Gopal, AK and Smith, SD and Lai, C and Shadman, M and Leslie, L and Warren, EH and Lynch, R and Swanson, N and Grossfeld, T and Cheson, BD and Dunleavy, K},
title = {Ibrutinib and Venetoclax in Relapsed and Refractory Follicular Lymphoma.},
journal = {Clinical lymphoma, myeloma & leukemia},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.clml.2025.04.004},
pmid = {40340130},
issn = {2152-2669},
abstract = {BACKGROUND: Bruton tyrosine kinase (BTK) inhibitors are approved in several B-cell malignancies, including the recent authorization of zanubrutinib for relapsed or refractory follicular lymphoma (FL).

METHODS: Based on preclinical studies demonstrating synergy with ibrutinib and the B-cell lymphoma (BCL)-2 inhibitor, venetoclax, in FL cell lines, we conducted a multicenter phase Ib/II study evaluating this combination in relapsed or refractory FL.

RESULTS: The recommended phase 2 dose was ibrutinib 560 mg and venetoclax 600 mg. There was no evidence of clinical tumor lysis syndrome, despite the omission of a venetoclax ramp up. At a median duration of therapy of 6 months, the most common adverse events were low grade diarrhea (83%), infection (75%), and rash (58%). Amongst the 24 patients enrolled, the overall and complete response (CR) rates were 63% and 21%. At a median follow up of 6.9 months, the median progression-free survival was 8.2 months, and the median duration of CR (n = 5) was 38 months.

CONCLUSION: The combination of a BTK and BCL2 inhibitor is efficacious in relapsed/refractory FL and represents a unique dual-targeted approach warranting further investigation.},
}

@article {pmid40339592,
year = {2025},
author = {Escrivá-de-Romani, S and Cejalvo, JM and Alba, E and Friedmann, J and Rodríguez-Lescure, Á and Savard, MF and Pezo, RC and Gion, M and Ruiz-Borrego, M and Hamilton, E and Pluard, T and Webster, M and Beeram, M and Linden, H and Saura, C and Shpektor, D and Salim, B and Harvey, P and Hurvitz, SA},
title = {Zanidatamab plus palbociclib and fulvestrant in previously treated patients with hormone receptor-positive, HER2-positive metastatic breast cancer: primary results from a two-part, multicentre, single-arm, phase 2a study.},
journal = {The Lancet. Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1470-2045(25)00140-8},
pmid = {40339592},
issn = {1474-5488},
abstract = {BACKGROUND: New HER2-targeted regimens, including chemotherapy-free options, are needed for metastatic breast cancer. In an ongoing, two-part, phase 2a study, we assessed the safety and antitumour activity of zanidatamab, a HER2-targeted bispecific antibody, plus palbociclib and fulvestrant, in heavily pretreated patients with hormone receptor-positive, HER2-positive advanced or metastatic breast cancer.

METHODS: This multicentre, single-arm, two-part, phase 2a study is being conducted at 13 university hospitals, cancer centres, or research institutes in Spain, Canada, and the USA. Eligible patients were adults (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1, and with pathologically confirmed unresectable or metastatic breast cancer, assessed locally to be hormone receptor-positive and HER2-positive, with disease progression during or after previous HER2-targeted therapies. Patients were enrolled in part 1, part 2, or part 1 followed by part 2. In part 1, patients received starting doses of zanidatamab (20 mg/kg intravenously once every 2 weeks on days 1 and 15 of a 28-day cycle) with palbociclib (125 mg orally once a day on days 1-21 of each cycle) and fulvestrant (500 mg intramuscular injection once every 2 weeks for the first three doses [cycle 1: days 1 and 15, cycle 2: day 1], then once every 4 weeks [all subsequent cycles: day 1]). In part 1, primary endpoints were safety of the triplet combination and confirmation of recommended doses for part 2. In part 2, patients received the recommended doses confirmed in part 1, and the primary endpoint was progression-free survival at 6 months. Safety and progression-free survival were assessed in all enrolled patients who received any dose of zanidatamab, palbociclib, or fulvestrant. Patients in part 1 who were treated at the recommended doses were analysed together with the patients in part 2. This study is registered with ClinicalTrials.gov, NCT04224272, and is active with recruitment completed.

FINDINGS: Overall, 51 patients (49 [96%] female and two [4%] male; median age 54·0 [46·0-62·0] years; 42 [82%] White) were enrolled: eight in part 1 (June 10, 2020-Feb 7, 2021) and 43 in part 2 (Feb 8, 2021-Oct 31, 2022). All 51 patients had received study treatment at the data cutoff (Aug 3, 2023); median follow-up was 16·1 months (IQR 9·9-23·4) and the median duration of triplet regimen treatment was 7·4 months (3·4-14·8). The median number of previous HER2-targeted therapies was 4 (IQR 3-4). 12 (24%) of 51 patients had previously received trastuzumab deruxtecan. The planned starting drug doses administered in part 1 of the study were confirmed as the recommended doses for part 2. All 51 patients were treated at the recommended doses. All 51 patients had at least one treatment-related adverse event of any grade, with diarrhoea being the most common (41 [80%] patients, with 34 [67%] having grade 1-2 events). Grade 3 or 4 treatment-related adverse events occurred in 34 (67%) patients, with neutropenia being the most common (26 [51%] patients). One (2%) patient had a serious grade 3 treatment-related adverse event of increased transaminases. No treatment-related deaths occurred. In the overall sample (N=51), progression-free survival at 6 months was 66·7% (95% CI 52·1-79·2).

INTERPRETATION: Zanidatamab plus palbociclib and fulvestrant was generally safe and showed promising antitumour activity, supporting further evaluation of this chemotherapy-free triplet regimen.

FUNDING: Zymeworks, Jazz Pharmaceuticals, and Pfizer.},
}

@article {pmid40339051,
year = {2025},
author = {Burger, R and Bell-Mandla, N and Harper, A and Richardson, S and Kanema, S and Thomas, R and Mwenge, L and Wilson, E and Floyd, S and Bock, P and Ayles, H and Fidler, S and Hayes, R and Hauck, K and , },
title = {Does enhanced HIV prevention, diagnosis, and linkage to care reduce hospitalisation in high HIV-burden communities in Zambia and South Africa? findings from the HPTN 071 (PopART) randomised trial.},
journal = {PLOS global public health},
volume = {5},
number = {5},
pages = {e0004373},
pmid = {40339051},
issn = {2767-3375},
abstract = {ClinicalTrials.gov NCT01900977.},
}

@article {pmid40339010,
year = {2025},
author = {Ely, ZA and Kulstad, ZJ and Gunaydin, G and Addepalli, S and Verzani, EK and Casarrubios, M and Clauser, KR and Wang, X and Lippincott, IE and Louvet, C and Schmitt, T and Kapner, KS and Agus, MP and Hennessey, CJ and Cleary, JM and Hadrup, SR and Klaeger, S and Su, J and Jaeger, AM and Wolpin, BM and Raghavan, S and Smith, EL and Greenberg, PD and Aguirre, AJ and Abelin, JG and Carr, SA and Jacks, T and Freed-Pastor, WA},
title = {Pancreatic cancer-restricted cryptic antigens are targets for T cell recognition.},
journal = {Science (New York, N.Y.)},
volume = {388},
number = {6747},
pages = {eadk3487},
doi = {10.1126/science.adk3487},
pmid = {40339010},
issn = {1095-9203},
mesh = {*Pancreatic Neoplasms/immunology/therapy/genetics ; Humans ; *Antigens, Neoplasm/immunology/genetics ; *Histocompatibility Antigens Class I/immunology ; *T-Lymphocytes, Cytotoxic/immunology ; *Peptides/immunology ; Organoids/immunology ; Receptors, Antigen, T-Cell/immunology ; Antigen Presentation ; Cell Line, Tumor ; },
abstract = {Translation of the noncoding genome in cancer can generate cryptic (noncanonical) peptides capable of presentation by human leukocyte antigen class I (HLA-I); however, the cancer specificity and immunogenicity of noncanonical HLA-I-bound peptides (ncHLAp) are incompletely understood. Using high-resolution immunopeptidomics, we discovered that cryptic peptides are abundant in the pancreatic cancer immunopeptidome. Approximately 30% of ncHLAp exhibited cancer-restricted translation, and a substantial subset were shared among patients. Cancer-restricted ncHLAp displayed robust immunogenic potential in a sensitive ex vivo T cell priming platform. ncHLAp-reactive, T cell receptor-redirected T cells exhibited tumoricidal activity against patient-derived pancreatic cancer organoids. These findings demonstrate that pancreatic cancer harbors cancer-restricted ncHLAp that can be recognized by cytotoxic T cells. Future therapeutic strategies for pancreatic cancer, and potentially other solid tumors, may include targeting cryptic antigens.},
}

*Pancreatic Neoplasms/immunology/therapy/genetics
Humans
*Antigens, Neoplasm/immunology/genetics
*Histocompatibility Antigens Class I/immunology
*T-Lymphocytes, Cytotoxic/immunology
*Peptides/immunology
Organoids/immunology
Receptors, Antigen, T-Cell/immunology
Antigen Presentation
Cell Line, Tumor

@article {pmid40338545,
year = {2025},
author = {Schoen, MW and Doherty, J and Eaton, D and Khan, S and Candelieri, D and Fedele, N and Baxi, P and Wynveen, M and Pickett, C and Wilson, RJ and Stackable, K and Ingram, K and Karunanandaa, K and Agarwal, R and Rajasekhar, A and Riekhof, F and Govindan, S and Cheranda, N and Knoche, EM and Etzioni, RD and Montgomery, RB},
title = {Treatment Patterns and Survival Among Veterans With De Novo Metastatic Hormone-Sensitive Prostate Cancer.},
journal = {JAMA network open},
volume = {8},
number = {5},
pages = {e259433},
pmid = {40338545},
issn = {2574-3805},
mesh = {Humans ; Male ; Aged ; Retrospective Studies ; Cross-Sectional Studies ; *Veterans/statistics & numerical data ; *Prostatic Neoplasms/mortality/drug therapy/pathology ; Docetaxel/therapeutic use ; *Androgen Antagonists/therapeutic use ; Middle Aged ; United States/epidemiology ; Aged, 80 and over ; *Androgen Receptor Antagonists/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; },
abstract = {IMPORTANCE: Combination therapy for metastatic hormone-sensitive prostate cancer (mHSPC) has been widely adopted, yet clinical use and outcomes are unknown. Furthermore, optimal therapy is uncertain due to lack of direct comparison of androgen receptor pathway inhibitors (ARPIs) and docetaxel in high-volume disease.

OBJECTIVE: To evaluate the use of combination therapy and its association with overall survival among patients with mHSPC and to compare ARPIs vs docetaxel doublet therapy by volume of disease.

This retrospective cross-sectional study was conducted in the US Veterans Health Administration among 6216 US veterans with de novo mHSPC from January 1, 2013, to December 31, 2022, treated with androgen deprivation therapy (ADT) within 3 months of diagnosis. Treatments for mHSPC were collected within 4 months of ADT. Volume of disease was assessed from radiology report review. Data were analyzed from July 2023 to October 2024.

MAIN OUTCOMES AND MEASURES: Overall survival (OS) and clinical progression-free survival (PFS), indicated by time to castration resistance or death.

RESULTS: Among 6216 male veterans with mHSPC (mean [SD] age, 73.9 [9.7] years), use of combination therapy increased from 344 of 637 veterans (54.0%) in 2020 to 465 of 737 veterans (63.1%) in 2022. Among 4106 veterans treated from 2017 to 2022, combination therapy was associated with longer OS (40.3 [95% CI, 38.0-42.1] months vs 33.0 [95% CI, 31.2-35.1] months; hazard ratio [HR], 0.80 [95% CI, 0.74-0.87]) and was used more frequently among younger veterans with fewer comorbidities. Among 1174 veterans with high-volume mHSPC, there was no difference in OS between ARPIs and docetaxel (32.3 [95% CI, 29.5-35.3] months vs 34.7 [95% CI, 31.7-37.1] months; HR, 1.06 [95% CI, 0.91-1.23]); however, ARPIs were associated with longer PFS (18.7 [95% CI, 17.1-20.9] months vs 16.0 [95% CI, 14.0-17.7] months; HR, 0.80 [95% CI, 0.70-0.91]; P = .001). In a multivariable model of high-volume mHSPC, there was no difference in OS between ARPIs and docetaxel (adjusted HR, 0.89 [95% CI, 0.76-1.05]). Among 366 veterans with low-volume mHSPC, there was no difference in OS between ARPIs and docetaxel (68.4 [95% CI, 52.6 months to not reached] months vs 55.3 [95% CI, 41.7-78.9] months; HR, 0.81 [95% CI, 0.58-1.13]), but ARPIs were associated with longer PFS (39.7 [95% CI, 34.3-52.9] months vs 24.0 [95% CI, 20.3-32.9] months; HR, 0.57 [95% CI, 0.43-0.76]).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of veterans with de novo mHSPC, use of combination therapies increased over time and were associated with longer survival compared with ADT monotherapy. In both high- and low-volume mHSPC, no differences in OS were observed between ARPI and docetaxel combinations; however, ARPIs had longer PFS. Future research into the role of docetaxel is needed to elucidate the benefit of chemotherapy in mHSPC.},
}

Humans
Male
Aged
Retrospective Studies
Cross-Sectional Studies
*Veterans/statistics & numerical data
*Prostatic Neoplasms/mortality/drug therapy/pathology
Docetaxel/therapeutic use
*Androgen Antagonists/therapeutic use
Middle Aged
United States/epidemiology
Aged, 80 and over
*Androgen Receptor Antagonists/therapeutic use
Antineoplastic Combined Chemotherapy Protocols/therapeutic use

@article {pmid40337764,
year = {2025},
author = {Damle, SR and Pillarisetty, VG and Safyan, RA and Chiorean, EG},
title = {A new dawn in cancer immunotherapy: the promise of mutant KRAS-specific vaccines.},
journal = {Translational gastroenterology and hepatology},
volume = {10},
number = {},
pages = {20},
pmid = {40337764},
issn = {2415-1289},
}

@article {pmid40337301,
year = {2025},
author = {Eckardt, JN and Hahn, W and Ries, RE and Chrost, SD and Winter, S and Stasik, S and Röllig, C and Platzbecker, U and Müller-Tidow, C and Serve, H and Baldus, CD and Schliemann, C and Schäfer-Eckart, K and Hanoun, M and Kaufmann, M and Burchert, A and Schetelig, J and Bornhäuser, M and Wolfien, M and Meshinchi, S and Thiede, C and Middeke, JM},
title = {Age-stratified machine learning identifies divergent prognostic significance of molecular alterations in AML.},
journal = {HemaSphere},
volume = {9},
number = {5},
pages = {e70132},
pmid = {40337301},
issn = {2572-9241},
abstract = {Risk stratification in acute myeloid leukemia (AML) is driven by genetics, yet patient age substantially influences therapeutic decisions. To evaluate how age alters the prognostic impact of genetic mutations, we pooled data from 3062 pediatric and adult AML patients from multiple cohorts. Signaling pathway mutations dominated in younger patients, while mutations in epigenetic regulators, spliceosome genes, and TP53 alterations became more frequent with increasing age. Machine learning models were trained to identify prognostic variables and predict complete remission and 2-year overall survival, achieving area-under-the-curve scores of 0.801 and 0.791, respectively. Using Shapley (SHAP) values, we quantified the contribution of each variable to model decisions and traced their impact across six age groups: infants, children, adolescents/young adults, adults, seniors, and elderly. The highest contributions to model decisions among genetic variables were found for alterations of NPM1, CEBPA, inv(16), and t(8;21) conferring favorable risk and alterations of TP53, RUNX1, ASXL1, del(5q), -7, and -17 conferring adverse risk, while FLT3-ITD had an ambiguous role conferring favorable treatment responses yet poor overall survival. Age significantly modified the prognostic value of genetic alterations, with no single alteration consistently predicting outcomes across all age groups. Specific alterations associated with aging such as TP53, ASXL1, or del(5q) posed a disproportionately higher risk in younger patients. These results challenge uniform risk stratification models and highlight the need for context-sensitive AML treatment strategies.},
}

@article {pmid40335656,
year = {2025},
author = {Harris, K},
title = {An uneasy truce between population health and the gene pools within our bodies.},
journal = {Nature reviews. Genetics},
volume = {},
number = {},
pages = {},
pmid = {40335656},
issn = {1471-0064},
}

@article {pmid40334068,
year = {2025},
author = {Muhsen, IN and Roloff, GW and Faramand, RG and Othman, T and Valtis, YK and Kopmar, NE and Dekker, SE and Connor, M and Mercadal, S and O'Connor, TE and Dykes, KC and Ahmed, M and Jeyakumar, N and Zhang, A and Miller, K and Sutherland, KC and Guzowski, C and Gupta, VK and Majhail, NS and Battiwalla, M and Solh, MM and Malik, SA and Mathews, J and Oliai, C and Shaughnessy, PJ and Mountjoy, L and Lee, CJ and Logan, AC and Tsai, SB and Leonard, JT and Schwartz, MS and Sasine, JP and Kumaran, M and Frey, NV and Park, JH and Koura, D and Cassaday, RD and Shah, BD and Aldoss, I and Muffly, LS and Hill, LC},
title = {Outcomes of Brexucabtagene Autoleucel in Relapsed/Refractory Acute Lymphoblastic Leukemia Patients with CNS Involvement.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024015779},
pmid = {40334068},
issn = {2473-9537},
abstract = {Relapsed/Refractory (r/r) B-cell acute lymphoblastic leukemia patients with central nervous system involvement (CNS B-ALL) have poor outcomes and were frequently excluded from CD19-targeting chimeric antigen receptor T-cell (CAR T-cell) clinical trials. The efficacy and safety of brexucabtagene autoleucel (brexu-cel) in adults with r/r B-ALL was established by the ZUMA-3 trial, which excluded patients with advanced or symptomatic CNS involvement. In this retrospective multicenter analysis, we investigated the safety and efficacy of brexu-cel in CNS B-ALL patients utilizing data from the Real-World Outcomes Collaborative for CAR T in ALL (ROCCA) consortium. Of 189 patients infused, 31 had CNS-2 (presence of blasts in CSF with < 5 WBC/uL) or CNS-3 (presence of blasts with >5 WBC/uL and/or clinical signs/symptoms) disease pre-apheresis and are the focus of this report. The median age was 46.5 years (range, 24-76), and 58.1% were males. Most (87.1%) received bridging therapy. Following brexu-cel, 21 of 24 with CNS restaging (87.5%) achieved CNS-1. Additionally, 28 of 30 evaluable patients achieved marrow complete remission (CR); 25 were MRD-negative. No statistically significant differences were seen in progression-free survival (PFS) or overall survival (OS) following brexu-cel among patients with or without CNS involvement. Similarly, grade 3-4 immune effector cell associated neurotoxicity syndrome (ICANS) occurred similarly in patients with (35.5%) and without CNS disease (30%). In conclusion, our data suggest that brexu-cel results in high response rates in CNS B-ALL patients with toxicity comparable to patients without CNS involvement.},
}

@article {pmid40334067,
year = {2025},
author = {Shadman, M and Burke, JM and Cultrera, J and Yimer, HA and Zafar, SF and Misleh, J and Rao, SS and Farber, CM and Cohen, AC and Yao, H and Idoine, A and An, Q and Flinn, IW and Sharman, JP},
title = {Zanubrutinib is well tolerated and effective in CLL/SLL patients intolerant of ibrutinib/acalabrutinib: Updated results.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024015493},
pmid = {40334067},
issn = {2473-9537},
abstract = {Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib revolutionized chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) treatment, although treatment-related toxicities limit the use of some BTK inhibitors. Zanubrutinib, a potent next-generation BTK inhibitor, has higher selectivity than ibrutinib or acalabrutinib. The ongoing phase 2, single-arm BGB-3111-215 study investigates the safety and efficacy of zanubrutinib in patients with B-cell malignancies who are intolerant of ibrutinib and/or acalabrutinib. Here, results in patients with CLL/SLL are presented. Patients received zanubrutinib 160 mg BID or 320 mg QD. With a 34.5-month median follow-up, 71 patients (ibrutinib intolerant only, n=44; acalabrutinib intolerant only, n=17; ibrutinib and acalabrutinib intolerant, n=10) received ≥1 zanubrutinib dose. On zanubrutinib, 54% (28/52) of ibrutinib-intolerant patients and 70% (19/27) of acalabrutinib-intolerant patients experienced no recurrence of intolerance AEs; 60% and 72% of intolerance AEs did not recur, respectively. Of recurrent ibrutinib-intolerance AEs, 64% were lower grade; 44% of acalabrutinib-intolerance AEs were lower grade. No intolerance AEs recurred at a higher grade with zanubrutinib. The most common recurrent ibrutinib-intolerance and acalabrutinib-intolerance AEs were fatigue and diarrhea, respectively. The most common TEAEs with zanubrutinib were fatigue (32%), COVID-19 (28%), and diarrhea and contusion (each 24%). Grade ≥3 TEAEs occurred in 61%, serious TEAEs in 32%, and TEAEs leading to discontinuation in 11%. Of 67 efficacy-evaluable patients, 94% experienced disease control: 30% had a best response of stable disease and 64% had a partial or complete response. These data demonstrate that patients intolerant of ibrutinib/acalabrutinib may benefit from switching to zanubrutinib therapy. ClinicalTrials.gov: NCT04116437.},
}

@article {pmid40333962,
year = {2025},
author = {Zheng, D and van den Heuvel, A and Balog, J and Willemsen, IM and Kloet, S and Tapscott, SJ and Mahfouz, A and van der Maarel, SM},
title = {DUX4 activates common and context-specific intergenic transcripts and isoforms.},
journal = {Science advances},
volume = {11},
number = {19},
pages = {eadt5356},
pmid = {40333962},
issn = {2375-2548},
mesh = {*Homeodomain Proteins/genetics/metabolism ; Muscular Dystrophy, Facioscapulohumeral/genetics/metabolism/pathology ; Animals ; Protein Isoforms/genetics/metabolism ; Mice ; *DNA, Intergenic/genetics ; Transcriptome ; Humans ; Myoblasts/metabolism ; Gene Expression Regulation, Developmental ; Muscle, Skeletal/metabolism ; },
abstract = {DUX4 regulates the expression of genic and nongenic elements and modulates chromatin accessibility during zygotic genome activation in cleavage stage embryos. Its misexpression in skeletal muscle causes facioscapulohumeral dystrophy (FSHD). By leveraging full-length RNA isoform sequencing with short-read RNA sequencing of DUX4-inducible myoblasts, we elucidate an isoform-resolved transcriptome featuring numerous unannotated isoforms from known loci and novel intergenic loci. While DUX4 activates similar programs in early embryos and FSHD muscle, the isoform usage of known DUX4 targets is notably distinct between the two contexts. DUX4 also activates hundreds of previously unannotated intergenic loci dominated by repetitive elements. The transcriptional and epigenetic profiles of these loci in myogenic and embryonic contexts indicate that the usage of DUX4-binding sites at these intergenic loci is influenced by the cellular environment. These findings demonstrate that DUX4 induces context-specific transcriptomic programs, enriching our understanding of DUX4-induced muscle pathology.},
}

*Homeodomain Proteins/genetics/metabolism
Muscular Dystrophy, Facioscapulohumeral/genetics/metabolism/pathology
Animals
Protein Isoforms/genetics/metabolism
Mice
*DNA, Intergenic/genetics
Transcriptome
Humans
Myoblasts/metabolism
Gene Expression Regulation, Developmental
Muscle, Skeletal/metabolism

@article {pmid40333666,
year = {2025},
author = {Olivieri, DJ and Eastment, MC and Mugisha, N and Menon, MP},
title = {Correlates of cervical cancer awareness among women aged 30-49 in five sub-Saharan African nations: Evidence from the Demographic and Health Survey (DHS)-2017-2023.},
journal = {PLOS global public health},
volume = {5},
number = {5},
pages = {e0003344},
pmid = {40333666},
issn = {2767-3375},
abstract = {Cervical cancer is the leading cause of cancer-related mortality in low- and middle-income countries (LMICs). Prior studies associate high cervical cancer awareness with reductions in cervical cancer incidence. In this study, we utilize nationally representative Demographic and Health Surveys Program (DHS) to analyze correlates of cervical cancer awareness to inform global strategies. All DHS surveys between 2017-2023 were queried for questions on cervical cancer awareness. Socio-demographic variables (e.g., age, marital status), socioeconomic variables (e.g., education, wealth, literacy) and variables pertaining to healthcare decision making, distance traveled, intimate partner violence (IPV), and female genital mutilation/circumcision (FGC/M)) were extracted. Sample weights were applied, and logistic regressions were performed. Variables with p < 0.20 were included in multivariate analysis. Data was obtained from 30,214 women aged 30-49 years old living in Benin, Cameroon, Madagascar, Mauritania, and Mozambique, 19,403 of whom were asked questions on cervical cancer awareness. Cervical cancer awareness varied from 53% in Cameroon to 12% in Benin. Literacy, frequency of watching television, mobile telephone ownership, visiting a local healthcare facility and hormonal contraceptive use were associated with increased cervical cancer awareness, while lack of healthcare decision making independence was associated with decreased awareness after multivariate adjustment. Women who experienced emotional IPV were associated with increased awareness in Cameroon. Less than 4% of all women were screened for cervical cancer. Given the known association between awareness and screening, targeted efforts to increase awareness among women without communication modalities has the potential to reduce global cervical cancer disparities. Potential strategies include co-locating cervical cancer awareness programs with public health programs and implementing large-scale telecommunication outreach programs to improve awareness.},
}

@article {pmid40329475,
year = {2025},
author = {Sullivan, SD and Grueger, J and Sullivan, AP and Ramsey, SD},
title = {The consequences of pharmaceutical tariffs in the United States.},
journal = {Journal of managed care & specialty pharmacy},
volume = {},
number = {},
pages = {1-4},
doi = {10.18553/jmcp.2025.25090},
pmid = {40329475},
issn = {2376-1032},
abstract = {The Trump Administration has threatened to impose tariffs on imported branded, generic, and biosimilar pharmaceutical products. Although specific details regarding the exact rates and implementation timeline remain unclear, the administration has indicated that these tariffs will be substantial. Tariffs can create supply chain disruptions, increase costs, limit patient access to essential medications, and negatively impact research and innovation. Rather than punitive tariffs, industrial policy options and collaborative international treaties may better serve US economic and public health interests and lead to a more secure and consistent domestic supply of critical medicines.},
}

@article {pmid40329098,
year = {2025},
author = {Bulteel, AJB and Barnum, K and Datta, S and Dodge, LE and Lake, L and Elavalakanar, P and Lam, BD and Patell, R},
title = {Clinician characteristics associated with use of risk assessment models for venous thromboembolism and bleeding in hospitalized patients.},
journal = {Annals of hematology},
volume = {},
number = {},
pages = {},
pmid = {40329098},
issn = {1432-0584},
support = {DD20-2002/CC/CDC HHS/United States ; },
}

@article {pmid40328984,
year = {2025},
author = {Abernethy, NF and McCloskey, K and Trahey, M and Rinn, L and Broder, G and Andrasik, M and Laborde, R and McGhan, D and Spendolini, S and Marimuthu, S and Kanzmeier, A and Hanes, J and Kublin, JG},
title = {Rapid development of a registry to accelerate COVID-19 vaccine clinical trials.},
journal = {NPJ digital medicine},
volume = {8},
number = {1},
pages = {251},
pmid = {40328984},
issn = {2398-6352},
support = {UM1AI068614//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UM1AI068635//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
abstract = {Response to the SARS-Cov-2 pandemic required the unprecedented, rapid activation of the COVID-19 Prevention Network (CoVPN) representing hundreds of sites conducting vaccine clinical trials. The CoVPN Volunteer Screening Registry (VSR) collected participant information, distributed qualified candidates across sites, and monitored enrollment progress. The system consisted of three web-based interfaces. The Volunteer Questionnaire flowed into a secure database. The Site Portal supported volunteer selection, analytics, and enrollment. The Administrative Portal enabled dynamic analytic reports by geography, clinical trial, and site, including volunteering rates over time. The VSR collected over 650,000 volunteers, serving a key role in the recruitment of diverse participants for multiple Phase 3 clinical trials. Over 47% of the 166,729 volunteers selected for screening represented prioritized groups. The success of the VSR demonstrates how digital tools can be rapidly yet safely integrated into an accelerated clinical trial setting. We summarize the development of the system and lessons learned for pandemic preparedness.},
}

@article {pmid40328898,
year = {2025},
author = {Zamora, D and Xie, H and Wong, E and Santiano, C and Vivas-Jimenez, A and Sadowska-Klasa, A and Kampouri, E and Stevens-Ayers, T and Ueda Oshima, M and Leisenring, WM and Hill, JA and Boeckh, M},
title = {ELISPOT as a predictor of clinically significant cytomegalovirus infection after hematopoietic cell transplantation in letermovir recipients.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {40328898},
issn = {1476-5365},
support = {T32 AI118690/AI/NIAID NIH HHS/United States ; K23AI163343//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; K23AI163343//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; K23AI163343//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
abstract = {We examined cytomegalovirus-specific cell-mediated immunity (CMV-CMI) to pp65 and IE-1 at 100 days after hematopoietic cell transplantation (HCT) following discontinuation of letermovir prophylaxis using ELISPOT (T-SPOT®.CMV, Oxford-Immunotec, Abingdon, UK). We compared ELISPOT results to a laboratory-developed intracellular cytokine staining (ICS) assay and characterized thresholds for the prediction of late clinically significant (cs)CMV infection using receiver operating characteristic analysis. We identified factors associated with high (i.e., at or above threshold) CMV-CMI to both antigens. ELISPOT correlated well with polyfunctional CMV-specific T-cell immunity by ICS. We defined thresholds of 67 and 4 spots per 250,000 cells for pp65 and IE-1, respectively, for predicting late csCMV infection. PBSC graft source, CMV seropositive donor, and/or CMV reactivation in the first 100 days post-HCT were associated with high CMV-CMI to pp65 and/or IE-1. Patients with high CMV-CMI to both antigens at day 100 had a lower incidence of late csCMV infection, however, late changes in immunosuppression affected risk prediction. Clinical risk factors (e.g., early CMV infection, acute graft-versus-host disease) predicted late csCMV and improved the predictive value of CMV-CMI testing. Thus, standardized CMV-CMI, after HCT, combined with clinical factors can be used to accurately stratify the risk of late csCMV infection after letermovir prophylaxis.},
}

@article {pmid40328734,
year = {2025},
author = {Chehayeb, RJ and Odzer, N and Albany, RA and Ferrucci, L and Sarpong, D and Perez-Escamilla, R and Lewis, JB and Phipps, AI and Meisner, A and Pusztai, L},
title = {Breastfeeding attributable fraction of triple negative breast cancer in the US.},
journal = {NPJ breast cancer},
volume = {11},
number = {1},
pages = {40},
pmid = {40328734},
issn = {2374-4677},
abstract = {Rates of triple negative breast cancer (TNBC) are higher in Black women than in non-Hispanic White women. Breastfeeding duration and younger age at first birth are known risk factors for TNBC and vary by race. To quantify the contribution of these risk factors to disparities in TNBC, we calculated the population-attributable fraction (PAF). A PubMed search was performed to identify relevant studies and pooled odds ratios for breastfeeding for < 6 months and age at first birth < 25 years were calculated. PAF was calculated using the Levin formula. PAF of breastfeeding for < 6 months was 12% (95% confidence interval (CI) 5-20%) among White women and 15% (95%CI 3-26%) among Black women. We estimate that up to 15% of annual new TNBC in Black women and 12% in White women might be avoided by supporting breastfeeding. Policies supporting breastfeeding could hence reduce TNBC incidence and lessen racial disparities.},
}

@article {pmid40328293,
year = {2025},
author = {Davis, CP and Fest, S and Cushing-Haugen, K and Kensler, TW and Chavarro, JE and Harris, HR},
title = {Dietary patterns and age at menarche in a prospective study of girls in the USA.},
journal = {Human reproduction (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/humrep/deaf072},
pmid = {40328293},
issn = {1460-2350},
support = {//Breast Cancer Research Foundation/ ; U01 HL145386/NH/NIH HHS/United States ; T32 CA094880/NH/NIH HHS/United States ; //Breast Cancer Research Foundation/ ; U01 HL145386/NH/NIH HHS/United States ; T32 CA094880/NH/NIH HHS/United States ; },
abstract = {STUDY QUESTION: Are dietary patterns associated with age at menarche after accounting for BMI-for-age (BMIz) and height?

SUMMARY ANSWER: We observed associations between both the Alternative Healthy Eating Index (AHEI) and the Empirical Dietary Inflammatory Pattern (EDIP) and age at menarche.

WHAT IS KNOWN ALREADY: Dietary patterns have been sparsely examined in relation to age at menarche and no studies have examined the association between the AHEI, a healthier diet, and EDIP, a pro-inflammatory diet, and menarche.

STUDY DESIGN, SIZE, DURATION: The Growing Up Today Study (GUTS) is a prospective cohort of children ages 9-14 years at study enrollment. GUTS enrolled in two waves with enrollment beginning in 1996 (GUTS1) and 2004 (GUTS2). For this analysis, GUTS1 and GUTS2 participants were followed through 2001 and 2008, respectively.

We included 7530 participants who completed food frequency questionnaire(s) (FFQ) prior to menarche who then self-reported age at menarche during study follow-up. Cox proportional hazard models were used to calculate multivariable hazard ratios (HRs) and 95% CIs for the associations between two dietary patterns, the AHEI and EDIP, and age at menarche, with and without adjustment for time-varying BMIz and height.

Six thousand nine hundred ninety-two participants (93%) reported menarche during the study period. On average, participants completed the baseline FFQ 1.75 years prior to menarche. Participants in the highest quintile of AHEI diet score (indicating a healthier diet) were 8% less likely to attain menarche within the next month compared to those in the lowest quintile (95% CI = 0.85-0.99; Ptrend = 0.03). This association remained after adjustment for BMIz and height (corresponding HR = 0.93; 95% CI = 0.86-1.00; Ptrend = 0.04). Participants in the highest quintile of the EDIP score (i.e. most inflammatory diet), were 15% more likely to attain menarche in the next month relative to those in the lowest quintile (95% CI = 1.06-1.25; Ptrend = 0.0004), and the association remained following adjustment for BMIz and height (corresponding HR = 1.15; 95% CI = 1.06-1.25; Ptrend = 0.0004).

Self-reported questionnaires are subject to some error; however, given our prospective study design it is likely this error is non-differential with respect to the outcome.

Our findings of an association between both the AHEI and EDIP and age at menarche indicate that diet quality may play a role in age at menarche independent of BMI or height.

This work was supported by the Breast Cancer Research Foundation. The GUTS is supported by the National Institutes of Health U01 HL145386. C.P.D. was supported by National Institutes of Health T32 CA094880. The authors have no conflicts of interest to disclose.

TRIAL REGISTRATION NUMBER: N/A.},
}

@article {pmid40327712,
year = {2025},
author = {Jia, C and Peters, BA and Usyk, M and Wang, Z and Hanna, DB and Sharma, A and Anastos, K and Kaplan, R and Burk, R and Qi, Q},
title = {Associations of fecal and blood microbiota-related metabolites with gut microbiota and type 2 diabetes in HIV infection.},
journal = {AIDS (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1097/QAD.0000000000004231},
pmid = {40327712},
issn = {1473-5571},
abstract = {OBJECTIVES: Assess the relationships of gut microbiota (GMB)-related metabolites in feces and blood with GMB and type 2 diabetes (T2D) in the context of HIV infection, the presence of which could disrupt host metabolism.

DESIGN: We conducted a cross-sectional study among 111 women with HIV (WWH) and 56 women without HIV (WWOH) in the MACS/WIHS Combined Cohort Study.

METHODS: We measured 62 targeted metabolites in both feces and plasma and examined their associations with GMB composition (243 species) and prevalent T2D.

RESULTS: We observed 44 metabolites with detection rates ≥25% in both feces and plasma. Correlations between fecal and plasma metabolites were stronger in WWOH than in WWH (median r: 0.13 vs. 0.04). Fecal metabolites showed stronger correlations with GMB than plasma metabolites among all participants (median r [IQR] of measured vs. GMB-predicted metabolites: 0.24 [0.11, 0.33] vs. 0.08 [-0.03, 0.24]; P = 0.002), and the difference in this comparison was more pronounced in WWOH compared to WWH. We found a moderate consistency for the associations of fecal and plasma metabolites with T2D in WWH (r for effect sizes of fecal and plasma metabolites on T2D = 0.36; P = 0.03), but not in WWOH (r = 0.13; P = 0.45). Fecal and plasma kynurenate, a tryptophan catabolism metabolite, showed opposite associations with T2D, with a positive association for plasma (OR: 2.54, 95% CI: [1.28-5.76]; P = 0.01) and an inverse association for feces (0.59 [0.27-1.23]; P = 0.18) in WWH.

CONCLUSIONS: Fecal metabolites are more strongly associated with GMB than plasma metabolites, especially among WWOH. HIV infection might also influence associations of fecal and plasma metabolites with T2D.},
}

@article {pmid40327300,
year = {2025},
author = {Hamilton, EP and Jeselsohn, RM and Vahdat, LT and Hurvitz, SA},
title = {PROteolysis TArgeting Chimera (PROTAC) Estrogen Receptor Degraders for Treatment of Estrogen Receptor-Positive Advanced Breast Cancer.},
journal = {Targeted oncology},
volume = {},
number = {},
pages = {},
pmid = {40327300},
issn = {1776-260X},
abstract = {The estrogen receptor (ER) signaling pathway is a key driver of breast cancer, primarily through the activation of genes that promote tumor cell survival and growth. The recommended first-line treatment for ER-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer is endocrine therapy plus a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. However, most patients experience disease progression, and there is no clear standard of care in the second-line setting. Thus, novel treatments in the advanced setting are needed. In this narrative review, we describe the unique mechanisms of action of a new class of drugs called PROteolysis TArgeting Chimera (PROTAC) ER degraders. Unlike other ER-targeted therapies, these small molecules harness the body's primary intracellular natural protein disposal machinery, the ubiquitin-proteasome system, to directly induce ER degradation. Vepdegestrant (ARV-471) is the furthest advanced PROTAC ER degrader currently in clinical development. Preclinical data demonstrate increased tumor growth inhibition with vepdegestrant alone or in combination with CDK4/6 inhibitors compared with the selective ER degrader fulvestrant. In a first-in-human phase 1/2 clinical study, vepdegestrant administered orally as monotherapy or in combination with palbociclib showed promising clinical activity and a favorable safety profile in patients with heavily pretreated ER+/HER2- advanced breast cancer. Several other PROTAC ER degraders (AC699, ERD-3111, ERD-4001, and HP568) are in early development and have demonstrated activity in preclinical breast cancer models, with some recently entering clinical trials. The data highlight the potential for PROTAC ER degraders to be a new backbone therapy in breast cancer.},
}

@article {pmid40325041,
year = {2025},
author = {Langowski, MD and Francica, JR and Roederer, AL and Hurlburt, NK and Rodarte, JV and Da Silva Pereira, L and Flynn, BJ and Bonilla, B and Dillon, M and Kiyuka, P and Ravichandran, R and Weidle, C and Carter, L and Rao, M and Matyas, GR and Pepper, M and Idris, AH and Seder, RA and Pancera, M and King, NP},
title = {Elicitation of liver-stage immunity by nanoparticle immunogens displaying P. falciparum CSP-derived antigens.},
journal = {NPJ vaccines},
volume = {10},
number = {1},
pages = {87},
pmid = {40325041},
issn = {2059-0105},
support = {INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; DGE-1762114//National Science Foundation/ ; },
abstract = {A vaccine that provides robust, durable protection against malaria remains a global health priority. Although a breakthrough in the fight against malaria has recently been achieved by the licensure of two vaccines based on the circumsporozoite protein (CSP), the effectiveness and durability of protection can still be improved. Both vaccines contain a portion of CSP that does not include epitopes targeted by recently identified, potently protective monoclonal antibodies, suggesting that newer immunogens can expand the breadth of immunity and potentially increase protection. Here we explored >100 alternative CSP-based immunogens and evaluated the immunogenicity and protection of a large number of candidates, comparing several to the licensed R21 vaccine. The data highlight several general features that improve the stability and immunogenicity of CSP-based vaccines, such as inclusion of the C-terminal domain and high-density display on protein nanoparticle scaffolds. We also identify antigen design strategies that do not warrant further exploration, such as synthetic repeat regions that include non-native repeat cadences. The benchmark R21 vaccine outperformed our best immunogen for immunogenicity and protection. Overall, our data provide valuable insights on the inclusion of junctional region epitopes that will guide the development of potent and durable vaccines against malaria.},
}

@article {pmid40323670,
year = {2025},
author = {Rodríguez-Díaz, CE and Zangeneh, SZ and Chen, YO and Guo, X and Tsuyuki, K and Ransome, Y and Friedman, RK and Srithanaviboonchai, K and Roberts, ST and Mimiaga, MJ and Mayer, KH and Safren, SA},
title = {The Longitudinal Impact of Psychosocial Syndemic Variables on Adherence to Antiretroviral Therapy Among People With HIV in Brazil, Thailand, and Zambia: An Analysis by HIV Transmission Groups in HPTN 063.},
journal = {AIDS education and prevention : official publication of the International Society for AIDS Education},
volume = {37},
number = {2},
pages = {89-106},
doi = {10.1521/aeap.2025.37.2.89},
pmid = {40323670},
issn = {1943-2755},
mesh = {Humans ; Male ; *HIV Infections/drug therapy/psychology/epidemiology/transmission ; Thailand/epidemiology ; Zambia/epidemiology ; Female ; Adult ; Longitudinal Studies ; Brazil/epidemiology ; *Medication Adherence/psychology ; *Syndemic ; *Anti-HIV Agents/therapeutic use ; Homosexuality, Male/psychology/statistics & numerical data ; Middle Aged ; Substance-Related Disorders/psychology/epidemiology ; Heterosexuality/psychology/statistics & numerical data ; Cross-Sectional Studies ; Young Adult ; },
abstract = {In the field of HIV prevention and care, most studies of HIV syndemic problems are cross-sectional, few differentiate by HIV transmission groups, and few focus on people living with HIV (PWH). We analyzed one-year longitudinal data of 692 sexually active PWH (heterosexual men [HM], heterosexual women [HW], and men who have sex with men [MSM]) in care from Brazil, Thailand, and Zambia. Syndemic scores (0-3+) included stimulant use, polydrug use, depression, alcohol use, and fear of discrimination. Overall, syndemic scores were associated with lower ART adherence over time, but this differed across sexual transmission categories. For HM and HW, those with 2 or 3+ syndemic problems had lower odds of ART adherence than those with none. However, for MSM, the association between syndemic scores and ART adherence was not significant. While syndemic problems generally predicted suboptimal ART adherence among PWH, the association appears nuanced across subgroups.},
}

Humans
Male
*HIV Infections/drug therapy/psychology/epidemiology/transmission
Thailand/epidemiology
Zambia/epidemiology
Female
Adult
Longitudinal Studies
Brazil/epidemiology
*Medication Adherence/psychology
*Syndemic
*Anti-HIV Agents/therapeutic use
Homosexuality, Male/psychology/statistics & numerical data
Middle Aged
Substance-Related Disorders/psychology/epidemiology
Heterosexuality/psychology/statistics & numerical data
Cross-Sectional Studies
Young Adult

@article {pmid40323243,
year = {2025},
author = {Yu, JB and Grew, D and Sculley, E and Siva, S and Hardcastle, N and Tang, C and Yang, J and Kim, M and Lo, SS},
title = {Practical Considerations for the Treatment of Primary Renal Cell Carcinoma With SABR.},
journal = {Practical radiation oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.prro.2025.03.007},
pmid = {40323243},
issn = {1879-8519},
}

@article {pmid40321251,
year = {2025},
author = {Deslandes, B and Wu, X and Lee, MA and Goudswaard, LJ and Jones, GW and Gsur, A and Lindblom, A and Ogino, S and Vymetalkova, V and Wolk, A and Wu, AH and Huyghe, JR and Peters, U and Phipps, AI and Thomas, CE and Pai, RK and Grant, RC and Buchanan, DD and Yarmolinsky, J and Gunter, MJ and Zheng, J and Hazelwood, E and Vincent, EE},
title = {Transcriptome-wide Mendelian randomisation exploring dynamic CD4+ T cell gene expression in colorectal cancer development.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40321251},
support = {HHSN268201200008C/HL/NHLBI NIH HHS/United States ; U01 CA167551/CA/NCI NIH HHS/United States ; R01 CA081488/CA/NCI NIH HHS/United States ; U01 CA122839/CA/NCI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; HHSN268201200008I/HL/NHLBI NIH HHS/United States ; U19 CA148107/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Recent research has identified a potential protective effect of higher numbers of circulating lymphocytes on colorectal cancer (CRC) development. However, the importance of different lymphocyte subtypes and activation states in CRC development and the biological pathways driving this relationship remain poorly understood and warrant further investigation. Specifically, CD4+ T cells - a highly dynamic lymphocyte subtype - undergo remodelling upon activation to induce the expression of genes critical for their effector function. Previous studies investigating their role in CRC risk have used bulk tissue, limiting our current understanding of the role of these cells to static, non-dynamic relationships only.

METHODS: Here, we combined two genetic epidemiological methods - Mendelian randomisation (MR) and genetic colocalisation - to evaluate evidence for causal relationships of gene expression on CRC risk across multiple CD4+ T cell subtypes and activation stage. Genetic proxies were obtained from single-cell transcriptomic data, allowing us to investigate the causal effect of expression of 1,805 genes across five CD4+ T cell activation states on CRC risk (78,473 cases; 107,143 controls). We repeated analyses stratified by CRC anatomical subsites and sex, and performed a sensitivity analysis to evaluate whether the observed effect estimates were likely to be CD4+ T cell-specific.

RESULTS: We identified six genes with evidence (FDR-P<0.05 in MR analyses and H4>0.8 in genetic colocalisation analyses) for a causal role of CD4+ T cell expression in CRC development - FADS2, FHL3, HLA-DRB1, HLA-DRB5, RPL28, and TMEM258. We observed differences in causal estimates of gene expression on CRC risk across different CD4+ T cell subtypes and activation timepoints, as well as CRC anatomical subsites and sex. However, our sensitivity analysis revealed that the genetic proxies used to instrument gene expression in CD4+ T cells also act as eQTLs in other tissues, highlighting the challenges of using genetic proxies to instrument tissue-specific expression changes.

CONCLUSIONS: Our study demonstrates the importance of capturing the dynamic nature of CD4+ T cells in understanding disease risk, and prioritises genes for further investigation in cancer prevention research.},
}

@article {pmid40313741,
year = {2025},
author = {Barrero, DJ and Hedouin, S and Mao, Y and Asbury, CL and Stergachis, A and O'Toole, E and Biggins, S},
title = {Centromeres in the thermotolerant yeast K. marxianus mediate attachment to a single microtubule.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {40313741},
issn = {2693-5015},
support = {DP5 OD029630/OD/NIH HHS/United States ; R35 GM134842/GM/NIGMS NIH HHS/United States ; R35 GM149357/GM/NIGMS NIH HHS/United States ; },
abstract = {Eukaryotic chromosome segregation requires spindle microtubules to attach to chromosomes through kinetochores. The chromosomal locus that mediates kinetochore assembly is the centromere and is epigenetically specified in most organisms by a centromeric histone H3 variant called CENP-A. An exception to this is budding yeast which have short, sequenced-defined point centromeres. In S. cerevisiae, a single CENP-A nucleosome is formed at the centromere and is sufficient for kinetochore assembly. The thermophilic budding yeast Kluyveromyces marxianus also has a point centromere but its length is nearly double the S. cerevisiae centromere and the number of centromeric nucleosomes and kinetochore attachment sites is unknown. Purification of native kinetochores from K. marxianus yielded a mixed population, with one subpopulation that appeared to consist of doublets, making it unclear whether K. marxianus shares the same attachment architecture as S. cerevisiae. Here, we demonstrate that though the doublet kinetochores have a functional impact on kinetochore strength, kinetochore localization throughout the cell cycle appears conserved between these two yeasts. In addition, whole spindle electron tomography demonstrates that a single microtubule binds to each chromosome. Single-molecule nucleosome mapping analysis suggests the presence of a single centromeric nucleosome. Taken together, we propose that the K. marxianus point centromere assembles a single centromeric nucleosome that mediates attachment to one microtubule.},
}

@article {pmid40323013,
year = {2025},
author = {Garcia, NMG and Becerra, JN and Srinivasan, S and McKinney, BJ and DiMarco, AV and Wu, F and Fitzgibbon, M and Alvarez, JV},
title = {APOBEC3 activity promotes the survival and evolution of drug-tolerant persister cells during EGFR inhibitor resistance in lung cancer.},
journal = {Cancer research communications},
volume = {},
number = {},
pages = {},
doi = {10.1158/2767-9764.CRC-24-0442},
pmid = {40323013},
issn = {2767-9764},
abstract = {APOBEC mutagenesis is one of the most common endogenous sources of mutations in human cancer and is a major source of genetic intratumor heterogeneity. High levels of APOBEC mutagenesis are associated with poor prognosis and aggressive disease across diverse cancers, but the mechanistic and functional impacts of APOBEC mutagenesis on tumor evolution and therapy resistance remain relatively unexplored. To address this, we investigated the contribution of APOBEC mutagenesis to acquired therapy resistance in a model of EGFR-mutant non-small cell lung cancer. We find that inhibition of EGFR in lung cancer cells leads to a rapid and pronounced induction of APOBEC3 expression and activity. Functionally, APOBEC expression promotes the survival of drug-tolerant persister cells (DTPs) following EGFR inhibition. Constitutive expression of APOBEC3B alters the evolutionary trajectory of acquired resistance to the EGFR inhibitor gefitinib, making it more likely that resistance arises through de novo acquisition of the T790M gatekeeper mutation and squamous transdifferentiation during the DTP state. APOBEC3B expression is associated with increased expression of the squamous cell transcription factor deltaNp63 and squamous cell transdifferentiation in gefitinib-resistant cells. Knockout of p63 in gefitinib-resistant cells reduces the expression of the deltaNp63 target genes IL1alpha/beta and sensitizes these cells to the third-generation EGFR inhibitor osimertinib. These results suggest that APOBEC activity promotes acquired resistance by facilitating evolution and transdifferentiation in DTPs, and suggest that approaches to target deltaNp63 in gefitinib-resistant lung cancers may have therapeutic benefit.},
}

@article {pmid40321654,
year = {2025},
author = {Alvarez, CS and Kaplan, RC and Camargo, MC and Avilés-Santa, ML and Daviglus, M and Garcia-Bedoya, O and Isasi, CR and Pattany, MS and Thyagarajan, B and Talavera, GA and Graubard, BI and McGlynn, KA},
title = {Associations of Helicobacter pylori with metabolic dysfunction-associated steatotic liver disease and related conditions: cross-sectional results from the Hispanic Community Health Study/Study of Latinos.},
journal = {Lancet regional health. Americas},
volume = {41},
number = {},
pages = {100953},
pmid = {40321654},
issn = {2667-193X},
abstract = {BACKGROUND: Hispanic/Latino populations have been reported to have high rates of both metabolic dysfunction-associated steatotic liver disease (MASLD) and Helicobacter pylori infection. Several observational studies, predominantly from Asian populations, have suggested a link between these conditions. Thus, the primary objective of the current study was to examine the association between H. pylori and MASLD and secondarily, to assess its association with related conditions in the Hispanic Community Health Study/Study of Latinos.

METHODS: In this cross-sectional study, a total of 16,144 participants with baseline data on H. pylori serology were included. Based on weighted statistics, the median age was 40 years [interquartile range (IQR): 28, 52]; 52.2% women (n = 9661) and 47.8% men (n = 6483). Participants' Hispanic/Latino heritage included 37.6% Mexicans (n = 6397), 20.1% Cubans (n = 2307), 15.8% Puerto Ricans (n = 2663), 10.0% Dominicans (n = 1447), 7.4% Central Americans (n = 1710), 4.9% South Americans (1052). MASLD was estimated using the Fatty Liver Index (FLI) and the Hepatic Steatosis Index (HSI). Other conditions examined were obesity, central obesity, diabetes and metabolic syndrome. Multivariable logistic regression models were used to calculate the ratios of (adjusted) prevalences (RP) and 95% confidence intervals (CI) for the overall association of H. pylori seropositivity with MASLD and related conditions. Analyses were also stratified by Hispanic/Latino heritage.

FINDINGS: The overall prevalence of MASLD ranged from 47% (FLI) to 65% (HSI). After accounting for age, sex, education, and other key variables, the analysis found a modest association between H. pylori seropositivity and MASLD as determined by HSI (RP: 1.06, 95% CI: 1.02-1.10) overall, and among individuals of Puerto Rican and Mexican heritages. Furthermore, an overall association between H. pylori seropositivity and obesity was observed (RP: 1.09, 95% CI: 1.02-1.16).

INTERPRETATION: This study provides support for a positive association of H. pylori seropositivity with MASLD and obesity among Hispanic/Latino populations. However, given the exploratory nature of these findings, caution is warranted in their interpretation. Further research is necessary to establish causality and examine potential mechanisms of these associations.

FUNDING: The Hispanic Community Health Study/Study of Latinos was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), San Diego State University (N01-HC65237), and University of Illinois at Chicago (HHSN268201300003I). The following Institutes/Centers/Offices contribute to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, United States, the National Institute of Deafness and Other Communications Disorders, the National Institute of Dental and Craniofacial Research, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the Office of Dietary Supplements. This study was also funded in part by the Intramural Research Program of the National Cancer Institute.},
}

@article {pmid40321290,
year = {2025},
author = {Samandari, T and Achola, M and Hutter, JN and Mboya, G and Otieno, W and Kee, JJ and Huang, Y and Aponte, JJ and Ockenhouse, CF and Lee, CK and Polakowski, L and Yacovone, M and Tapley, A and Dadabhai, S and Mkhize, NN and Kaldine, H and Bhebhe, S and Moore, PL and Hural, J and Garrett, N and Kublin, JG},
title = {Neutralizing Antibody Responses After mRNA COVID-19 Booster Vaccination are Unaffected by Parasitemia in a Malaria-Endemic Setting.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40321290},
support = {T32 AI007044/AI/NIAID NIH HHS/United States ; UM1 AI068614/AI/NIAID NIH HHS/United States ; UM1 AI068618/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; },
abstract = {Subclinical malaria may reduce the immunogenicity of mRNA vaccines. We evaluated neutralizing antibody responses in adults with (n=87) and without (n=221) PCR-confirmed Plasmodium falciparum who received a COVID-19 booster. Similar boosted ID50 geometric mean titers >22,000 in parasitemic and non-parasitemic participants suggests that COVID-19 mRNA vaccine responses are not impaired.},
}

@article {pmid40321081,
year = {2025},
author = {Lottermoser, JA and Liu, H and Bai, J and Hu, Z and Dittman, JS},
title = {Complexin gains effective access to the assembling SNAREs via its membrane-binding C-terminal domain.},
journal = {The Journal of physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/JP286500},
pmid = {40321081},
issn = {1469-7793},
support = {NS116747/NS/NINDS NIH HHS/United States ; NS127534/NS/NINDS NIH HHS/United States ; R56NS128048//National Science Foundation/ ; },
abstract = {The conserved presynaptic SNARE-binding protein complexin (Cpx) promotes Ca[2+]-triggered synaptic vesicle (SV) fusion and inhibits spontaneous fusion at some synapses. A membrane-binding motif in the C-terminal domain (CTD) of Cpx plays a critical role in Cpx function, but it remains unclear whether the CTD participates in Cpx regulation of synaptic transmission beyond targeting Cpx to membranes. We examined the impact of the Caenorhabditis elegans CPX-1 CTD in vivo and found that this domain profoundly boosted the efficiency of CPX-1-mediated inhibition of spontaneous SV fusion as a function of protein abundance at the synapse. Removing the C-terminal half of CPX-1 and substituting it with the SV protein RAB-3 was able to fully restore both the fusogenic and inhibitory functions of CPX-1 whereas other SV proteins failed to restore CPX-1 function with the same efficiency regardless of abundance. These results indicate that regulation of spontaneous SV fusion requires a specific interaction of CPX-1 with the SV membrane. We propose that Cpx cannot efficiently access assembling SNAREs from the cytoplasm and that interactions of its CTD with the SV membrane guide Cpx to these sites of SNARE assembly. KEY POINTS: Complexin (Cpx) regulates presynaptic SNARE assembly to control synaptic transmission. A membrane curvature-sensing motif within the Cpx C-terminal domain (CTD) recruits Cpx to vesicles. Replacement of the CTD with the synaptic vesicle protein Rab3 can restore full Cpx function whereas other vesicle proteins fail to substitute regardless of abundance. The efficiency of Cpx-mediated inhibition of synaptic vesicle fusion is profoundly enhanced by the specific localization supplied by its CTD. These results suggest that Cpx reaches the assembling SNARE complexes via its specific CTD-membrane interactions and these SNAREs are inaccessible from the cytoplasmic compartment.},
}

@article {pmid40320146,
year = {2025},
author = {Su, CT and Saber, W and Bansal, A and Li, L and Nakamura, R and Cutler, C and Roth, JA and Wright, W and Steuten, L and Ramsey, SD},
title = {Out-of-Pocket Expenditures and Financial Hardship Among Patients with Myelodysplastic Syndrome Undergoing Allogeneic Transplant or Hypomethylating Agent / Supportive Care (BMT CTN 1102).},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.04.015},
pmid = {40320146},
issn = {2666-6367},
abstract = {INTRODUCTION: The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1102 trial demonstrated that allogeneic hematopoietic cell transplantation (HCT) was associated with superior overall survival compared to non-HCT approaches among elderly patients with higher-risk myelodysplastic syndrome (MDS). The trial included an ancillary cost diary component to assess the out-of-pocket (OOP) expenditures and financial hardship in the post-HCT period through three phased surveys for up to 19 months after enrollment.

OBJECTIVE: The purpose of the study is to assess the OOP costs and financial hardship experienced by participants of BMT CTN 1102.

STUDY DESIGN: BMT CTN 1102 assigned participants to Donor and No-Donor arms based on donor availability. Participants could additionally enroll in the ancillary cost diary component, with a total of 138 participants returning 267 surveys across three survey waves at 1-, 7-, and 19-months after enrollment. As participants who underwent HCT returned 78% (207/267) of the total surveys, we report on the collected data descriptively.

RESULTS: Participants who underwent HCT had high levels of monthly OOP expenditure ($1126, $812, $442) and financial hardship (47%, 53%, 57%) across the three survey waves. For reference, participants who did not undergo HCT generally reported lower levels of OOP expenditure ($478, $845, $256) and financial hardship (37%, 55%, 46%).

CONCLUSION: Among BMT CTN 1102 participants, those who underwent HCT reported high levels of OOP expenditures and financial hardship for up to 19 months after enrollment. Ongoing routine assessment of patient-level OOP expenditures and financial burden may be helpful in the post-HCT survivorship period.},
}

@article {pmid40319195,
year = {2025},
author = {Merkel, EC and Meyer, CL and Yusuf, RA and Morrison, CF and Kelly, DL and Levine, DR and LeBlanc, TW and Ullrich, CK and El-Jawahri, A},
title = {What do pediatric transplant physicians think about palliative care? Results from a national survey study.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {40319195},
issn = {1476-5365},
abstract = {The benefits of palliative care (PC) for hematopoietic cell transplant (HCT) patients are well established, however, uptake in pediatric HCT remains limited. To understand pediatric transplant physicians' attitudes towards PC, we conducted a cross-sectional study with a 28-question survey. A composite score and regression model identified factors associated with positive attitudes towards subspecialty PC. Ninety-eight participants reported caring for pediatric patients. Most (81%) trust PC clinicians to care for their patients, yet 33% feel PC clinicians lack enough HCT knowledge to counsel patients. Nearly half (46%) see the name "PC" as a barrier to referral. Multivariable analysis showed that spiritual practice (β = 1.53, p = 0.029), <10 years of clinical practice (β = 2.23, p = 0.007), and perceived PC quality (β = 0.73, p < 0.001) were associated with a more positive attitude towards PC. More training in PC (β = -2.70, p = 0.003) and a higher sense of ownership over PC issues (β = -0.51, p = 0.001) were associated with a more negative attitude towards subspecialty PC. These findings highlight barriers to pediatric HCT and PC collaboration, including concerns about PC team knowledge of HCT and patient perceptions. While most pediatric transplant physicians trust PC to enhance patient care, interventions are needed to improve collaboration.},
}

@article {pmid40319052,
year = {2025},
author = {Olivieri, DJ and Berridge-Green, A and Othus, M and Radich, JP and Advani, AS and Erba, HP and Walter, RB},
title = {Biobanking and consent to future biospecimen use among adults enrolled in SWOG trials from 2000 to 2024.},
journal = {Blood cancer journal},
volume = {15},
number = {1},
pages = {85},
pmid = {40319052},
issn = {2044-5385},
support = {U10 CA180819/CA/NCI NIH HHS/United States ; U10 CA180888/CA/NCI NIH HHS/United States ; ASH HONORS Award (DJO)//American Society of Hematology (ASH)/ ; U10-CA180888, U10-CA180819//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
}

@article {pmid40318950,
year = {2025},
author = {Grivas, P and Aragon-Ching, JB and Bellmunt, J and Loriot, Y and Climent Duran, MA and Sridhar, SS and Su, PJ and Park, SH and Kopyltsov, E and Yamamoto, Y and Jacob, N and Hoffman, J and Tyroller, K and Manitz, J and Kearney, M and Schlichting, M and Powles, T},
title = {Avelumab First-line Maintenance for Advanced Urothelial Carcinoma: Long-term Analyses of Patient-reported Outcomes and Quality-adjusted Time Without Symptoms or Toxicity from the JAVELIN Bladder 100 Trial.},
journal = {European urology oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.euo.2025.04.004},
pmid = {40318950},
issn = {2588-9311},
abstract = {BACKGROUND AND OBJECTIVE: In JAVELIN Bladder 100, avelumab first-line maintenance plus best supportive care (BSC) significantly prolonged overall survival versus BSC alone, with no detrimental impact on quality of life (QOL), in patients with advanced urothelial carcinoma without progression following first-line platinum-based chemotherapy. We report long-term analyses of patient-reported outcomes (PROs) in patients treated with avelumab (any duration or ≥12 mo) and a post hoc analysis comparing quality-adjusted time without symptoms or toxicity (Q-TWiST) between arms.

METHODS: PROs were assessed using National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Bladder Symptom Index-18 (FBlSI-18) and EuroQol 5-level EQ-5D (EQ-5D-5L). Q-TWiST was calculated as the utility-weighted sum of mean time in three health states: time with all-cause grade 3/4 toxicity prior to progression, time without grade 3/4 toxicity or symptoms of progression, and time after progression.

KEY FINDINGS AND LIMITATIONS: In the overall avelumab plus BSC arm (n = 350) and the subgroup treated for ≥12 mo (n = 118), completion rates for PRO assessments during treatment were >80%. FBlSI-18 total and EQ-5D-5L index scores remained stable throughout 24 mo of treatment, with no clinically important changes from baseline. The mean Q-TWiST was 18.46 mo with avelumab plus BSC versus 15.13 mo with BSC alone (22% relative improvement). Limitations include open-label trial design and small patient numbers at later cycles.

Patients receiving avelumab had preserved health-related QOL and control of cancer-related symptoms with manageable toxicity, further supporting avelumab first-line maintenance as the recommended treatment for advanced urothelial carcinoma not progressed after platinum-based chemotherapy.},
}

@article {pmid40318860,
year = {2025},
author = {Tembhare, P and Chen, X and Chan, JKC and Wood, B and Naresh, KN},
title = {Fifth edition WHO classification: precursor lymphoid neoplasms, acute leukaemias of mixed or ambiguous lineage, myeloid/lymphoid neoplasms, and histiocytic and dendritic cell neoplasms, including strategies for application in resource-limited settings.},
journal = {Journal of clinical pathology},
volume = {},
number = {},
pages = {},
doi = {10.1136/jcp-2025-210135},
pmid = {40318860},
issn = {1472-4146},
abstract = {The fifth edition of the WHO classification of haematolymphoid tumours (WHO-HEM5) introduces significant updates to the classification of acute lymphoblastic leukaemia, ALAL (including mixed phenotype acute leukaemia (MPAL)), myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK), and histiocytic and dendritic cell neoplasms, reflecting the advances in the understanding of the genetic basis of these diseases. This review provides an overview of these changes, highlighting a shift to a more refined molecular-genetic approach. The incorporation of newly recognised genetic subtypes into the classification scheme underscores the evolving landscape of these entities. Challenges in diagnosing ALAL/MPAL and MLN-TK are discussed, along with recent insights into histiocytic and dendritic cell neoplasms, including newly defined entities such as ALK-positive histiocytosis.The review also explores the practical implications of WHO-HEM5, particularly in resource-limited settings, where comprehensive molecular testing may be unavailable. While morphology and immunohistochemistry remain essential diagnostic tools, strategic use of flow cytometry and targeted fluorescence in situ hybridisation can facilitate risk-adapted classification and improve survival in regions with limited resources and therapeutic options. Future large-scale studies are necessary to establish the diagnostic and prognostic value of these newly genetically defined entities for diverse healthcare environments, and to standardise guidelines in refining disease classification and optimising patient outcomes.},
}

@article {pmid40318736,
year = {2025},
author = {Lee, SJ and Pavletic, S and Blazar, BR and Yao, Y and Ji, R and Marshall, K and Cutler, C and , },
title = {Belumosudil for Chronic Graft-Versus-Host Disease: Analysis of Long-Term Results From the KD025-208 and ROCKstar Studies.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.04.020},
pmid = {40318736},
issn = {2666-6367},
abstract = {BACKGROUND: Belumosudil is an oral selective rho-associated coiled-coil-containing protein kinase-2 (ROCK2) inhibitor approved for the treatment of chronic graft-versus-host disease (cGVHD) following an allogeneic hematopoietic cell transplant (alloHCT) in patients aged ≥12 years after failure of ≥2 prior systemic lines of therapy (LOTs). The KD025-208 (NCT02841995) and KD025-213 (ROCKstar; NCT03640481) studies demonstrated that belumosudil was well tolerated, with clinically meaningful responses in patients with cGVHD. KD025-217 (NCT05305989) is a follow-up study that evaluated extended treatment with belumosudil in patients enrolled in the parent studies, KD025-208 and ROCKstar.

OBJECTIVE: This pooled analysis reports the long-term follow-up (overall median follow-up duration of 31.4 months) results from these studies in patients with cGVHD.

STUDY DESIGN: The study included a total of 208 patients across 3 cohorts. Cohort 1 (n=95) received belumosudil 200 mg once daily, cohort 2 (n=92) received belumosudil 200 mg twice daily and cohort 3 (n=21) received belumosudil 400 mg once daily. The primary end point was best overall response rate (ORR). Duration of response (DOR), failure-free survival (FFS) and time to next treatment (TTNT) were also evaluated in this analysis.

RESULTS: The best ORR in the modified intent-to-treat (mITT) population was 72%. The median DOR for the responder population was 62.3 weeks (range, 36.1-82.6 weeks). The median FFS in the mITT population was 15.1 months (range, 11.3-20.6 months). The 1- and 2-year FFS rates were 56% and 40%, respectively. The median TTNT was 22.1 months (range, 15.2-40.3 months), where 47% of patients received a new systemic therapy for cGVHD by 36 months.

CONCLUSION: When compared with the published data, the long-term results from this pooled analysis of these two phase 2 studies demonstrated belumosudil was associated with durable responses, and it remained well tolerated with no new safety concerns.},
}

@article {pmid40313749,
year = {2025},
author = {Chanda, A and Song, Y and Nazir, J and Lin, C and Cheng, A and Sargent, J and Sikora, AE},
title = {Bridging Gaps in Antibody Responses and Animal Welfare: Assessing Blood Collection Methods and Vaginal Immunity in Mice Immunized with Intranasal Gonococcal Vaccines.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {40313749},
issn = {2693-5015},
support = {R01 AI117235/AI/NIAID NIH HHS/United States ; },
abstract = {Assessing antibody titers and functional responses is essential for evaluating vaccine efficacy, yet the impact of blood collection methods on these immunological assessments remains unclear. Retro-orbital (RO) blood collection is commonly used but significant complications can occur. Increasingly, investigators have adopted alternative blood collection approaches, such as saphenous vein (SV) sampling to improve laboratory animal welfare. This study compared RO and SV sampling in the development of a Neisseria gonorrhoeae (Ng) vaccine, evaluating Adhesin Complex Protein (ACP) and multiple transferable resistance (Mtr) E protein (MtrE) as antigen candidates. Epitope mapping revealed that ACP and MtrE possess multiple, highly accessible B-cell and T-cell epitope clusters, reinforcing their immunological potential. Following intranasal immunization with rACP, rACP+CpG, and rMtrE+CpG, we assessed the specificity, magnitude, kinetics, and functional quality of immune responses elicited by the immunization regimens. Out of 45 comparisons, only eight significant differences were detected in antibody titers, while the human serum bactericidal assays revealed no differences between RO and SV in antigen-immunized groups. However, antibodies elicited by rACP alone or ACP+CpG in SV samples restored 30.05% and 75.2% of human lysozyme hydrolytic activity compared to 19.3 and 59.9 % in RO, respectively suggesting that SV sampling may be more reliable for assessing functional antibody responses. Beyond its immunological advantages, SV sampling reduces stress, minimizes ocular trauma, and improves animal welfare, making it a viable alternative to RO collection. Given its widespread use in vaccine research, standardizing SV sampling could improve data reliability, ethical compliance, and translational relevance in preclinical studies.},
}

@article {pmid40317503,
year = {2025},
author = {Christie, JR and Romine, P and Eddy, K and Chen, DL and Daher, O and Abdelrazek, M and Malthaner, RA and Qiabi, M and Nayak, R and Kinahan, P and Nair, VS and Mattonen, SA},
title = {Thorax-encompassing multi-modality PET/CT deep learning model for resected lung cancer prognostication: A retrospective, multicenter study.},
journal = {Medical physics},
volume = {},
number = {},
pages = {},
doi = {10.1002/mp.17862},
pmid = {40317503},
issn = {2473-4209},
support = {//Gerald C. Baines Foundation/ ; //London Health Sciences Foundation/ ; 152218//Cancer Research Society/ ; //Natural Sciences and Engineering Research Council of Canada/ ; 2020-06498//Discovery Grants program/ ; //Lawson Health Research Institute's Internal Research Fund (IRF)/ ; T32CA009515/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Patients with early-stage non-small cell lung cancer (NSCLC) typically receive surgery as their primary form of treatment. However, studies have shown that a high proportion of these patients will experience a recurrence after their resection, leading to an increased risk of death. Cancer staging is currently the gold standard for establishing a patient's prognosis and can help clinicians determine patients who may benefit from additional therapy. However, medical images which are used to help determine the cancer stage, have been shown to hold unutilized prognostic information that can augment clinical data and better identify high-risk NSCLC patients. There remains an unmet need for models to incorporate clinical, pathological, surgical, and imaging information, and extend beyond the current staging system to assist clinicians in identifying patients who could benefit from additional therapy immediately after surgery.

PURPOSE: We aimed to determine whether a deep learning model (DLM) integrating FDG PET and CT imaging from the thoracic cavity along with clinical, surgical, and pathological information can predict NSCLC recurrence-free survival (RFS) and stratify patients into risk groups better than conventional staging.

MATERIALS AND METHODS: Surgically resected NSCLC patients enrolled between 2009 and 2018 were retrospectively analyzed from two academic institutions (local institution: 305 patients; external validation: 195 patients). The thoracic cavity (including the lungs, mediastinum, pleural interfaces, and thoracic vertebrae) was delineated on the preoperative FDG PET and CT images and combined with each patient's clinical, surgical, and pathological information. Using the local cohort of patients, a multi-modal DLM using these features was built in a training cohort (n = 225), tuned on a validation cohort (n = 45), and evaluated on testing (n = 35) and external validation (n = 195) cohorts to predict RFS and stratify patients into risk groups. The area under the curve (AUC), Kaplan-Meier curves, and log-rank test were used to assess the prognostic value of the model. The DLM's stratification performance was compared to the conventional staging stratification.

RESULTS: The multi-modal DLM incorporating imaging, pathological, surgical, and clinical data predicted RFS in the testing cohort (AUC = 0.78 [95% CI:0.63-0.94]) and external validation cohort (AUC = 0.66 [95% CI:0.58-0.73]). The DLM significantly stratified patients into high, medium, and low-risk groups of RFS in both the testing and external validation cohorts (multivariable log-rank p < 0.001) and outperformed conventional staging. Conventional staging was unable to stratify patients into three distinct risk groups of RFS (testing: p = 0.94; external validation: p = 0.38). Lastly, the DLM displayed the ability to further stratify patients significantly into sub-risk groups within each stage in the testing (stage I: p = 0.02, stage II: p = 0.03) and external validation (stage I: p = 0.05, stage II: p = 0.03) cohorts.

CONCLUSION: This is the first study to use multi-modality imaging along with clinical, surgical, and pathological data to predict RFS of NSCLC patients after surgery. The multi-modal DLM better stratified patients into risk groups of poor outcomes when compared to conventional staging and further stratified patients within each staging classification. This model has the potential to assist clinicians in better identifying patients that may benefit from additional therapy.},
}

@article {pmid40316478,
year = {2025},
author = {Cavanaugh, D and Holt, SK and Dwyer, E and Petersen, E and Gore, JL and Schade, GR and Grivas, P and Hsieh, AC and Lee, JK and Montgomery, B and Schweizer, MT and Yezefski, T and Yu, EY and Chen, JJ and Liao, JJ and Weg, E and Zeng, J and Jannat, S and Berry, DL and Master, VA and Garcia, JM and Reed, MJ and Bentov, I and Wright, JL and Psutka, SP},
title = {Prospective evaluation of comprehensive geriatric assessments in multidisciplinary bladder cancer care and implications for personalized vulnerability phenotyping.},
journal = {Urologic oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.urolonc.2025.03.025},
pmid = {40316478},
issn = {1873-2496},
abstract = {PURPOSE: Frailty predicts adverse outcomes in bladder cancer (BC). Current guidelines endorse completion of Comprehensive Geriatric Assessments (CGAs) in older adults prior to treatment election to objectively measure frailty, however, these are rarely performed in urologic practice due to inadequate resources. We hypothesized CGA implementation would be feasible and identify multifaceted vulnerabilities beyond standard risk assessments in a multidisciplinary BC clinic and developed a novel method to visualize "vulnerability phenotypes" to guide supportive interventions.

METHODS: Adults with BC were prospectively enrolled (June, 2020-July, 2021). Initially, patients underwent standard of care (SOC) risk assessment (N = 27). Subsequently, patients completed CGAs augmented with body composition assessments (N = 67). CGA completion time, rates, and patient-reported burden were assessed. Interdependence of CGA domains were quantified using Spearman correlation coefficients and compared decisional conflict and regret between arms. Vulnerability phenotypes were visualized using Spider Plots, generated in R. Clinical and survival associations with CGAs were evaluated using Cox proportional hazards models.

RESULTS: 94 patients were enrolled with a median age of 72 years. Instrument completion in the CGA cohort was 79% to 100%. 91% of patients reported CGA completion was at most minimally burdensome. CGAs identified vulnerabilities including 31% vulnerable-to-moderately frail, 21% with mild-to-severe depression, 3% with mild-moderate dementia, and 40% at risk for malnutrition-malnourished. Frailty measures across instruments were weakly correlated (rho <0.4). In this heterogeneous cohort, vulnerability domains were not significantly associated with decisional conflict/regret, survival, nor complication rates after treatment. A novel Spider Plot tool is proposed to facilitate communication of the dominant vulnerability-driving individual risks.

CONCLUSIONS: CGAs can be successfully incorporated into uro-oncology practice with low perceived burden, identifying key vulnerabilities with implications for clinical care. Weak correlations across instruments support the value of gathering information across discrete domains. We present a novel approach to visually characterize personalized vulnerability phenotypes.},
}

@article {pmid40315850,
year = {2025},
author = {Wu, W and Ahmad, K and Henikoff, S},
title = {Chromatin-bound U2AF2 splicing factor ensures exon inclusion.},
journal = {Molecular cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.molcel.2025.04.013},
pmid = {40315850},
issn = {1097-4164},
abstract = {Most mRNA splicing occurs co-transcriptionally, but it is unclear how splicing factors accurately select exons for inclusion. Using CUT&RUN profiling in K562 cells, we demonstrate that three splicing factors-SF3B1, U2AF1, and U2AF2-bind near active promoters of intron-containing and intronless genes, implying their association with the general transcriptional machinery. RNase A treatment reduces factor binding at promoters, indicating that these proteins interact with nascent transcripts. Strikingly, the U2AF2 protein also accumulates throughout intron-containing gene bodies and requires histone H3-lysine36 trimethylation but not nascent transcripts or persistent RNA polymerase II. Chromatin-bound U2AF2 preferentially binds to exons of highly expressed, exon-dense genes, with greater occupancy at exons skipped after U2AF2 knockdown, suggesting that U2AF2 enhances exon selection accuracy. U2AF2-targeted genes include those encoding splicing factors, where it improves splicing accuracy and efficiency. Our findings provide a mechanistic basis for the homeostatic regulation of efficient co-transcriptional splicing by chromatin-bound U2AF2.},
}

@article {pmid40315406,
year = {2025},
author = {Chen, W and Chang, TC and Rabin, KR and Raetz, EA and Devidas, M and Hunger, SP and Ramirez, NC and Mullighan, CG and Loh, ML and Wu, G},
title = {Performance of Two-Phase Designs for the Time-to-Event Outcome and a Case Study Assessing the Relapse Risk Associated With B-ALL Subtypes.},
journal = {JCO clinical cancer informatics},
volume = {9},
number = {},
pages = {e2400223},
pmid = {40315406},
issn = {2473-4276},
mesh = {Humans ; Case-Control Studies ; *Research Design ; Computer Simulation ; *Neoplasm Recurrence, Local ; },
abstract = {PURPOSE: To reduce costs in genomic studies of time-to-event phenotypes like survival, researchers often sequence a subset of samples from a larger cohort. This process usually involves two phases: first, collecting inexpensive variables from all samples, and second, selecting a subset for expensive measurements, for example, sequencing-based biomarkers. Common two-phase designs include nested case-control and case-cohort designs. Additional designs include sampling subjects based on follow-up time, like extreme case-control designs. Recently an optimal two-phase design using a maximum likelihood-based method was proposed, which could accommodate arbitrary sample selection in the second phase. However, direct comparisons of this optimal design with others in terms of power and computational cost is lacking.

METHODS: This study performs a direct evaluation of typical two-phase designs, including Tao's optimal design, on type I error, power, effect size estimation, and computational time, using both simulated and real data sets.

RESULTS: Results show that the optimal design had the highest power and accurate effect size estimation under the Cox regression model. Surprisingly, logistic regression achieved similar power with much lower computational cost than a more sophisticated method. The study further applied these methods to the MP2PRT study, reporting hazard ratios of cancer subtypes on relapse risk.

CONCLUSION: Recommendations for selecting two-phase designs and analysis methods are regarding power, bias of estimated effect size, and computational time.},
}

Humans
Case-Control Studies
*Research Design
Computer Simulation
*Neoplasm Recurrence, Local

@article {pmid40315399,
year = {2025},
author = {Carlsson, SV and Barata, PC and Bryce, AH and George, DJ and Gillessen, S and Loeb, S and Montgomery, B and Morris, D and Riaz, IB and Palapattu, G and Schoen, MW and Washington Iii, SL and Cornell, B and Levine, R and Aggarwal, P and McGowan, T and Cotter, M and Thompson, B and Devgan, G and Russell, D and Kuperman, G and Lenero, E and Iwata, K and Miyahira, AK and Soule, HR and Carithers, G and Oh, WK and Agarwal, N},
title = {Prostate Cancer Foundation White Paper on Combination Therapy for Metastatic Hormone-Sensitive Prostate Cancer.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2500050},
doi = {10.1200/OP-25-00050},
pmid = {40315399},
issn = {2688-1535},
abstract = {Despite several randomized controlled trials demonstrating the benefits of combination therapies for metastatic hormone-sensitive prostate cancer (mHSPC), a significant treatment gap persists. This initiative by the Prostate Cancer Foundation (PCF) convened stakeholders from academia, community practices, industry, and patient advocacy groups to address critical challenges in mHSPC care. Expert discussions and a review of real-world evidence and meta-analyses informed the development of strategies to improve care delivery. Evaluation of the data from global registries, such as IRONMAN, and large community databases was used to assess treatment utilization patterns and disparities. Combination therapies with two agents-androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI)-or three agents-ADT + ARPI + docetaxel-demonstrate significant survival improvements while preserving quality of life for patients with mHSPC, yet adoption remains inconsistent. Of the eligible patients, 20%-60% remain undertreated, with geographic, financial, and systemic barriers contributing to inconsistencies in care. Younger, White, urban-dwelling patients with fewer comorbidities are more likely to receive combination treatment, highlighting disparities across populations. Meta-analyses identified a lack of standardization due to varying inclusion criteria and comparators across trials. Real-world evidence underscored disparities influenced by geographic location, practice type, and access to specialty care. Initiatives such as the PANTHER study highlight improved outcomes in Black patients treated with combination therapies, emphasizing the importance of including diverse populations in clinical trials. To bridge gaps in care, this initiative prioritizes awareness, standardization, and equitable access to evidence-based therapies. Proposed solutions include targeted knowledge dissemination strategies, development of educational resources, and advocacy for policy changes to promote guideline-concordant care. By leveraging collaborative efforts, organizations, including PCF, can contribute to enhancing survival outcomes and quality of life for all patients with mHSPC.},
}

@article {pmid40315333,
year = {2025},
author = {Geiger, RA and Khera, D and Tenthorey, JL and Kochs, G and Graf, L and Emerman, M and Malik, HS},
title = {Heterozygous and generalist MxA super-restrictors overcome breadth-specificity trade-offs in antiviral restriction.},
journal = {Science advances},
volume = {11},
number = {18},
pages = {eadu0062},
pmid = {40315333},
issn = {2375-2548},
mesh = {*Myxovirus Resistance Proteins/genetics/metabolism/chemistry ; Humans ; Influenza A Virus, H5N1 Subtype ; *Antiviral Agents/pharmacology ; Thogotovirus ; },
abstract = {Antiviral restriction factors such as MxA (myxovirus resistance protein A) inhibit many viruses. Viral escape drives restriction factors to evolve rapidly at virus-binding interfaces to regain defense. Here, we explore how antiviral proteins balance restricting many viruses with evolving specificity against individual viruses. Human MxA uses its rapidly evolving loop L4 as the specificity determinant for orthomyxoviruses such as thogotovirus (THOV) and influenza (IAV). Previous combinatorial mutagenesis of rapidly evolving residues in human MxA loop L4 identified THOV "super-restrictors" and suggested an antiviral breadth-specificity trade-off. Using a modified combinatorial mutagenesis strategy, we find super-restrictor MxA variants specific to H5N1 IAV. A single L4 residue underlies the MxA breadth-specificity trade-off. However, rare "generalist" super-restrictors or a heterozygous combination of more common "specialist" super-restrictors can overcome the breadth-specificity trade-off. Our findings suggest that at least two strategies enable restriction factors such as MxA to increase their restriction of diverse viruses to overcome breadth-specificity trade-offs, which might be pervasive in host-virus conflicts.},
}

*Myxovirus Resistance Proteins/genetics/metabolism/chemistry
Humans
Influenza A Virus, H5N1 Subtype
*Antiviral Agents/pharmacology
Thogotovirus

@article {pmid40314975,
year = {2025},
author = {Zheng, Y and Ahmad, K and Henikoff, S},
title = {Total whole-arm chromosome losses predict malignancy in human cancer.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {18},
pages = {e2505385122},
doi = {10.1073/pnas.2505385122},
pmid = {40314975},
issn = {1091-6490},
support = {Henikoff//Howard Hughes Medical Institute (HHMI)/ ; HG012797//HHS | National Institutes of Health (NIH)/ ; },
mesh = {Humans ; *Neoplasms/genetics/pathology ; *Aneuploidy ; Centromere/genetics/metabolism ; Histones/genetics/metabolism ; },
abstract = {Aneuploidy is observed as gains or losses of whole chromosomes or chromosome arms and is a common hallmark of cancer. Whereas models for the generation of aneuploidy in cancer invoke mitotic chromosome segregation errors, whole-arm losses might occur simply as a result of centromere breakage. We recently showed that elevated RNA Polymerase II level over the S-phase-dependent histone genes predicts rapid recurrence of human meningioma and is correlated with total whole-arm losses relative to gains. To explain this imbalance in arm losses over gains, we have proposed that histone overexpression at S-phase competes with the histone H3 variant CENP-A, resulting in centromere breaks and whole-arm losses. To test whether centromere breaks alone can drive aneuploidy, we ask whether total whole-arm aneuploids can predict outcomes across different cancer types in large RNA and whole-genome sequencing databanks. We find that total whole-arm losses generally predict outcome, suggesting that centromere breakage is a major initiating factor leading to aneuploidy and the resulting changes in the selective landscape that drive most cancers. We also present evidence that centromere breakage alone is sufficient to account for whole-arm losses and gains, contrary to mitotic spindle error models for the generation of aneuploidy. Our results suggest that therapeutic intervention targeting histone overexpression has the potential to reduce aneuploidy and slow cancer progression.},
}

Humans
*Neoplasms/genetics/pathology
*Aneuploidy
Centromere/genetics/metabolism
Histones/genetics/metabolism

@article {pmid40311704,
year = {2025},
author = {Alfaifi, SA and Louie, AV and Siva, S and Guckenberger, M and Videtic, GMM and Higgins, KA and Alshafa, F and AlGhamdi, H and Gillespie, EF and Stephans, K and Mula-Hussain, L and Harrow, S and Palma, DA},
title = {International Patterns of Practice for Stereotactic Ablative Radiotherapy for Early-Stage Non-Small Cell Lung Cancer: Are We All in Sync?: Global patterns of practice for SABR for early-stage NSCLC.},
journal = {International journal of radiation oncology, biology, physics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ijrobp.2025.04.022},
pmid = {40311704},
issn = {1879-355X},
abstract = {PURPOSE: To generate an understanding of the similarities and variations in international practice patterns for stereotactic ablative radiotherapy (SABR) in early-stage non-small cell lung cancer (NSCLC).

METHODS: An online survey was conducted from October to December 2023, addressing general clinical and technical considerations for lung SABR, and for 5 specific anatomical NSCLC locations (peripheral, abutting chest wall, near brachial plexus, central, and ultra-central). Invitations to participate were extended through email and were distributed on social media.

RESULTS: The survey was completed by 255 radiation oncologists, each representing a single institution across 51 countries. Respondents reported treating a median of 20 cases annually. A total of 38% of participants reported using single-fraction SABR, and 54% applied an upper limit on the maximum dose (Dmax). Among those who applied a Dmax limit, 58% reported a Dmax threshold at ≥130% of the prescription, though this limit varied by region and national economy status. Respondents from low- and middle-income countries were less likely to set a Dmax limit at ≥130% (30% vs. 66%, p < 0.01) and less likely to use single-fraction SABR (14% vs. 44%, p < 0.01). Higher annual SABR patient volumes were associated with higher Dmax adoption (г = 0.23, p < 0.01). Across the 5 clinical scenarios presented; 57 distinct dose regimens were recommended. The most common regimen in each scenario was: 54 Gy in 3 fractions for peripheral tumors, 50 Gy in 5 fractions for apical, central, and abutment of chest wall, and 60 Gy in 8 fractions for ultra-central tumors. Approximately two-thirds of practices recommend a biologically effective dose (BED10) <100 Gy for one or more anatomical sites.

CONCLUSION: The findings reveal considerable variation in global SABR practice. These differences highlight the need for further data to guide prescription practices, and an international experts' consensus may be beneficial to standardize practice.},
}

@article {pmid40311075,
year = {2025},
author = {Sharma, R and Holtzman, NG and Pusic, I and Cutler, CS and Treister, N and Mehta, RS and Alousi, AS and Vigneswaran, N and Javaid, A and Boksa, FA and Mody, DP and Costa-da-Silva, AC and Schueller, O and Macé, S and Yao, Y and Ji, R and Hu, B and Marshall, K and Blazar, BR and Lee, SJ and Pavletic, SZ and Mays, JW},
title = {Belumosudil reduces oral chronic graft-versus-host disease tissue inflammation and fibrosis: a ROCKstar companion study.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025016170},
pmid = {40311075},
issn = {2473-9537},
abstract = {Belumosudil (KD025), an oral, selective, Rho-associated, coiled-coil containing protein kinase 2 (ROCK2) inhibitor, is approved for third-line treatment of chronic graft-versus-host disease (cGVHD). Previous studies demonstrated that ROCK2 inhibition reduces blood interleukin (IL)-17 activity and promotes regulatory T-cell (Treg) recovery. However, these studies did not evaluate immune responses within cGVHD-affected tissues. This study assessed tissue-level immune dynamics in 20 subjects with oral cGVHD from the phase 2 ROCKstar trial, before and after 6 months of belumosudil treatment, focusing on key effector sites (oral mucosa [OM], minor salivary glands [MSG], and skin) and peripheral blood. Following belumosudil treatment, reduction in collagen was observed in OM in parallel with decreased IL-17+ cell frequency in both OM (n = 14 pairs) and MSG (n = 11 pairs). IL-17 was primarily produced by non-T cells in the oral tissues. Immune cell frequencies in the OM decreased following treatment, while CD4 Tregs increased in both MSG and blood. Per overall or mouth-specific clinical response criteria, responders to belumosudil exhibited a reduction in collagen type I and IL-17 in OM. Additionally, salivary transforming growth factor β1 (TGF)-β1, a critical driver of fibrosis, decreased significantly, with a strong correlation observed between TGF-β1 and IL-17 levels. These findings illustrate the tissue-level response to belumosudil therapy and suggest that there is a reduction in tissue fibrosis and inflammation, thereby highlighting the therapeutic impact of ROCK2 inhibition in mitigating cGVHD. The ROCKstar study was registered at www.clinicaltrials.gov as NCT03640481.},
}

@article {pmid40309186,
year = {2025},
author = {Andrews, SS and Brent, R},
title = {Individual yeast cells signal at different levels but each with good precision.},
journal = {Royal Society open science},
volume = {12},
number = {4},
pages = {241025},
pmid = {40309186},
issn = {2054-5703},
abstract = {Different isogenic cells exhibit different responses to the same extracellular signals. Several authors assumed that this variation arose from stochastic signalling noise with the implication that single eukaryotic cells could not detect their surroundings accurately, but work by us and others has shown that the variation is dominated instead by persistent cell-to-cell differences. Here, we analysed previously published data to quantify the sources of variation in pheromone-induced gene expression in Saccharomyces cerevisiae. We found that 91% of response variation was due to stable cell-to-cell differences, 8% from experimental measurement error, and 1% from signalling noise and expression noise. Low noise enabled precise signalling; individual cells could transmit over 3 bits of information through the pheromone response system and so respond differently to eight different pheromone concentrations. Additionally, if individual cells could reference their responses against constitutively expressed proteins, then cells could determine absolute pheromone concentrations with 2 bits of accuracy. These results help explain how individual yeast cells can accurately sense and respond to different extracellular pheromone concentrations.},
}

@article {pmid40308027,
year = {2025},
author = {Gomez, RA and Hou, J and Gersuk, VH and Chow, IT and Farrington, ML and Robinson, D and Kwok, WW},
title = {Ara h 2105-124-Specific TH2A Cells Drive Peanut Allergy in DRB1*15:01 Individuals: A Detailed Epitope Analysis.},
journal = {Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology},
volume = {},
number = {},
pages = {},
doi = {10.1111/cea.70072},
pmid = {40308027},
issn = {1365-2222},
support = {U19 AI135817/NH/NIH HHS/United States ; },
abstract = {BACKGROUND: The IgE-mediated CD4 T-cell response to peanut (Arachis hypogaea) is heterogeneous, yet TH2 cells remain central drivers of pathology. This study aimed to dissect this complexity at the epitope level by focusing on the HLA-DRB1*15:01-DRB5*01:01 haplotype. Specifically, we examined how distinct epitope-specific T-cell subsets shape the immunological landscape of peanut allergy in peanut-allergic (PA) versus non-peanut-allergic (NPA) individuals.

METHODS: Using in vitro and ex vivo MHC-II tetramer approaches, the phenotype, frequency, function, and transcriptome of CD4 T-cell responses to novel Ara h epitopes were assessed. Bulk RNA sequencing further characterised these T cells, allowing identification of subsets associated with TH2 polarisation in PA individuals.

RESULTS: Eleven HLA-DRB1*15:01 and DRB5*01:01-restricted epitopes were identified in Ara h 1, 2, 3, 6, 7, and 8 using tetramer-guided epitope mapping on cell lines, followed by ex vivo validation in peripheral blood. T-cell phenotype was epitope-dependent, with a distinct TH2A population specific to the epitope Ara h 2105-124 (Ara h 2 p14) detected only in PA donors. These TH2A cells were phenotypically and transcriptionally distinct, marked by high CRTH2/CD161, low CD27, IL-5 production, and gene enrichment in cytokine signalling and lipid metabolism. Other epitope-specific T-cell subsets displayed more heterogeneous gene profiles related to immune activation, differentiation, and antigen presentation, underscoring the complexity of peanut-specific responses even within a single HLA haplotype.

CONCLUSION: These findings reveal that the strong TH2 bias in DRB1*15:01-DRB5*01:01 PA individuals arises from a distinct subset of Ara h 2 p14-specific TH2A cells characterised by a specialised metabolic and cytokine signalling program. At the same time, the functional diversity observed in non-Ara h 2 p14 subsets highlights the potential for leveraging these populations in tolerance-promoting therapies. Understanding the epitope-level heterogeneity of peanut-specific T-cells provides insight into the epitope-specific mechanisms driving peanut allergy and has potential implications for therapeutic interventions.},
}

@article {pmid40307656,
year = {2025},
author = {Keiser, E and Corbett, AM and Chido-Amajuoyi, O and Antoine, A and Stehman, C and Dorn, I and Goines, D and LoConte, NK},
title = {Acceptability of Stool-Based DNA Colorectal Cancer Screening among Black/African-American Patients Served by Federally Qualified Health Centers.},
journal = {Journal of cancer education : the official journal of the American Association for Cancer Education},
volume = {},
number = {},
pages = {},
pmid = {40307656},
issn = {1543-0154},
support = {UWCCC: University of Wisconsin Carbone Cancer Center Support Grant P30 CA014520/CA/NCI NIH HHS/United States ; },
abstract = {Colorectal cancer (CRC) has an increased burden among Black/African-American populations. Following the COVID-19 pandemic, home-based CRC screening options are being used more frequently. We conducted focus groups to understand the acceptability of stool-based DNA testing for CRC screening in this population. Ten focus groups about the acceptability of various CRC screening modalities were held with Black/African-American participants at two federally qualified health centers (FQHCs) in Milwaukee, Wisconsin. Participants were separated into focus groups based on age and gender. Thematic analysis was carried out using NVivo. Across the groups, there were a total of 79 participants, of which 40.5% were aged 40-50 years ("younger participants"), 59.5% aged > 50 years ("older participants"), 53.2% male, and 46.8% female. Overall, knowledge was low regarding perceived risk of CRC. There was limited awareness of CRC screening options among younger patients and widespread lack of knowledge about stool-based DNA testing. Most respondents preferred colonoscopy as their first-choice screening test but were open to other screening tests. Stool-based DNA tests were more preferred among younger participants but was felt to be acceptable across all groups. Given the low awareness/knowledge of screening modalities identified in our study, educational interventions and shared decision making by primary care providers are needed.},
}

@article {pmid40307080,
year = {2025},
author = {Melão, BVLA and Assel, M and Pere, M and Nalavenkata, S and Touijer, KA and Laudone, VP and Lin, DW and Rivas, JG and Bjartell, A and Carlsson, SV},
title = {Assessment of postoperative practices and discharge recommendations after radical prostatectomy.},
journal = {Urologic oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.urolonc.2025.03.027},
pmid = {40307080},
issn = {1873-2496},
abstract = {PURPOSE: Consistent, accurate postoperative guidance is crucial for early recovery and patient satisfaction in urology, especially for radical prostatectomy (RP) patients. However, patients often receive inconsistent information, highlighting the need for standardized, evidence-based postoperative care guidelines.

MATERIALS AND METHODS: We conducted a comprehensive review and evaluation of current postoperative practices for RP. This involved (1) reviewing existing discharge information at Josie Robertson Surgery Center, Memorial Sloan Kettering Cancer Center to identify areas of improvement; (2) systematically evaluating inconsistencies in discharge instructions and their impact on patient care; (3) distributing an anonymous survey to urologists in the US and Europe via REDCap to gather insights into global postoperative care practices. The survey included questions on various aspects of postoperative care, such as catheter use, medication regimens, dietary restrictions, and physical activity guidelines.

RESULTS: We received 247 survey responses. Despite some consensus on certain postoperative practices and recommendations, significant variability existed, underscoring the lack of standardized guidelines. Notable differences were observed between US and European cohorts, particularly in postoperative length of stay and discharge practices. Only 1.4% of US responders discharged patients 3 or more days postsurgery compared to 46% in Europe. Variability was also noted in recommendations for erectile function medications and postoperative activity restrictions.

CONCLUSION: This study underscores the significant variability in postoperative care recommendations for RP and the urgent need for standardized, evidence-based guidelines. Implementing such guidelines will enhance patient recovery, satisfaction, and overall outcomes, improving postoperative care across various surgical procedures.},
}

@article {pmid40306967,
year = {2025},
author = {Parihar, AS and Pant, N and Heidari, P and Fong, L and Iravani, A},
title = {Approaches to Imaging Immune Activation Using PET.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.124.268289},
pmid = {40306967},
issn = {1535-5667},
abstract = {This review explores the role of PET in imaging immune activation, particularly in oncology. [18]F-FDG is widely used for assessing treatment response to immunotherapies and can demonstrate unique response patterns as well as immune-related adverse events. However, because of the limited specificity of [18]F-FDG, newer PET radiopharmaceuticals targeting specific cellular or subcellular components of the immune system have been developed that can provide more precise information. The development of immune-specific PET radiopharmaceuticals offers significant potential for improving immune monitoring in both clinical practice and research.},
}

@article {pmid40305682,
year = {2025},
author = {Chappidi, MR and Newcomb, LF and Zheng, Y and Liu, M and Schenk, JM and Zhu, K and de la Calle, CM and Brooks, JD and Carroll, PR and Dash, A and Filson, CP and Gleave, ME and Liss, MA and Martin, F and McKenney, JK and Morgan, TM and Wagner, AA and Nelson, PS and Lin, DW},
title = {Magnetic Resonance Imaging at second surveillance biopsy after diagnosis in patients with Grade Group 1 prostate cancer in the Canary Prostate Active Surveillance Study.},
journal = {The Journal of urology},
volume = {},
number = {},
pages = {101097JU0000000000004592},
doi = {10.1097/JU.0000000000004592},
pmid = {40305682},
issn = {1527-3792},
abstract = {PURPOSE: No clear guidelines exist regarding MRI use after confirmatory biopsy during active surveillance (AS). Our objective was to evaluate MRI performance after confirmatory biopsy in patients with vs. without prior MRI-informed biopsy.

METHODS: Patients in Canary PASS with Gleason grade group (GG) 1 disease undergoing MRI-informed Biopsy 2, defined as second surveillance biopsy after diagnosis, were separated into prior vs. no prior MRI-informed biopsy groups. Primary outcome was reclassification (≥GG2) at MRI-informed Biopsy 2. Reclassification rates and location (systematic cores, targeted cores, both) were compared between groups. Univariable and multivariable logistic regression identified predictors of reclassification.

RESULTS: Patients with (n=101) vs. without (n=103) prior MRI-informed biopsy had lower reclassification rates at Biopsy 2 (21% vs. 36%, p=0.017) and lower GG at reclassification (95% vs. 73% of reclassifications to GG2, p=0.039). In multivariable modeling, PI-RADS 4-5 at MRI-informed Biopsy 2 was associated with increased odds of reclassification (OR=2.04 95%CI [1.04-4.05]). The negative predictive value of MRI at Biopsy 2 was 87% (95%CI[78-96]) and 73% (95%CI[61-85]) in with vs. without prior MRI groups, respectively. Reclassification location was identified by targeted cores only in 36% vs. 19% of patients with vs. without prior MRI, respectively (p=0.4). Reclassification location was identified by systematic cores only in 36% vs. 58% of patients with vs. without prior MRI, respectively (p=0.4).

CONCLUSIONS: These results support MRI use at Biopsy 2 and suggest negative surveillance MRI should not replace Biopsy 2. Both targeted and systematic cores should be taken at Biopsy 2 in patients with and without prior MRI on AS.},
}

@article {pmid40305509,
year = {2025},
author = {Gabel, AM and Crosse, EI and Belleville, AE and Hogg, SJ and McKellar, SA and Abdel-Wahab, O and Thomas, JD and Bradley, RK},
title = {Muscleblind-like proteins are novel modulators of the tumor-immune microenvironment.},
journal = {PloS one},
volume = {20},
number = {4},
pages = {e0321148},
pmid = {40305509},
issn = {1932-6203},
mesh = {*Tumor Microenvironment/immunology/genetics ; Animals ; Humans ; Mice ; *RNA-Binding Proteins/genetics/metabolism/immunology ; Cell Line, Tumor ; CD8-Positive T-Lymphocytes/immunology ; Female ; Interferon-gamma/pharmacology ; *Neoplasms/immunology/genetics/pathology ; Gene Expression Regulation, Neoplastic ; Mice, Inbred C57BL ; Antigen Presentation ; },
abstract = {Exploiting the immune system to eradicate cancer cells is an area of intense clinical study. However, the mechanisms that shape the tumor-immune microenvironment are incompletely understood. Here, we identify Muscleblind-like (MBNL) proteins as novel modulators of the tumor-immune microenvironment across diverse cancers. We demonstrate that loss of tumor MBNL expression results in an attenuated response to interferon gamma and reduced tumor antigen presentation in melanoma, breast cancer, and colorectal cancer cells. Parallel experiments in a syngeneic mouse melanoma model revealed that MBNL loss reduces tumor cell killing by CD8 + T cells in vitro and facilitates tumor escape from cytotoxic CD8 + T cell infiltration in vivo. Finally, we extended these studies to 29 human cancer types to find that MBNL expression levels are strongly associated with gene expression signatures of T cell tumor infiltration. These insights suggest that MBNL proteins play important roles in shaping the immune landscape across diverse malignancies.},
}

*Tumor Microenvironment/immunology/genetics
Animals
Humans
Mice
*RNA-Binding Proteins/genetics/metabolism/immunology
Cell Line, Tumor
CD8-Positive T-Lymphocytes/immunology
Female
Interferon-gamma/pharmacology
*Neoplasms/immunology/genetics/pathology
Gene Expression Regulation, Neoplastic
Mice, Inbred C57BL
Antigen Presentation

@article {pmid40305026,
year = {2025},
author = {Montano-Campos, JF and Hahn, EE and Haupt, EC and Radich, J and Bansal, A},
title = {Oncologist-Patient Concordance and Treatment Adherence in Chronic Myeloid Leukemia.},
journal = {JAMA network open},
volume = {8},
number = {4},
pages = {e258039},
pmid = {40305026},
issn = {2574-3805},
}

@article {pmid40304602,
year = {2025},
author = {Kopyeva, I and Bretherton, RC and Ayers, JL and Yu, M and Grady, WM and DeForest, CA},
title = {Matrix Stiffness and Biochemistry Govern Colorectal Cancer Cell Growth and Signaling in User-Programmable Synthetic Hydrogels.},
journal = {ACS biomaterials science & engineering},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsbiomaterials.4c01632},
pmid = {40304602},
issn = {2373-9878},
abstract = {Colorectal cancer (CRC) studies in vitro have been conducted almost exclusively on 2D cell monolayers or suspension spheroid cultures. Though these platforms have shed light on many important aspects of CRC biology, they fail to recapitulate essential cell-matrix interactions that often define in vivo function. Toward filling this knowledge gap, synthetic hydrogel biomaterials with user-programmable matrix mechanics and biochemistry have gained popularity for culturing cells in a more physiologically relevant 3D context. Here, using a poly(ethylene glycol)-based hydrogel model, we systematically assess the role of matrix stiffness and fibronectin-derived RGDS adhesive peptide presentation on CRC colony morphology and proliferation. Highlighting platform generalizability, we demonstrate that these hydrogels can support the viability and promote spontaneous spheroid or multicellular aggregate formation of six CRC cell lines that are commonly utilized in biomedical research. These gels are engineered to be fully degradable via a "biologically invisible" sortase-mediated reaction, enabling the triggered recovery of single cells and spheroids for downstream analysis. Using these platforms, we establish that substrate mechanics play a significant role in colony growth: soft conditions (∼300 Pa) encourage robust colony formation, whereas stiffer (∼2 kPa) gels severely restrict growth. Tuning the RGDS concentration did not affect the colony morphology. Additionally, we observe that epidermal growth factor receptor (EGFR) signaling in Caco-2 cells is influenced by adhesion ligand identity─whether the adhesion peptide was derived from collagen type I (DGEA) or fibronectin (RGDS)─with DGEA yielding a marked decrease in the level of downstream protein kinase phosphorylation. Taken together, this study introduces a versatile method to culture and probe CRC cell-matrix interactions within engineered 3D biomaterials.},
}

@article {pmid40304595,
year = {2025},
author = {Abrams, HR and Saifee, NH and Miller, WS and Cortez, A and Hasan, RA and Panch, SR and Fertrin, KY},
title = {Alloimmunization as a barrier to gene therapy in sickle cell disease.},
journal = {Transfusion},
volume = {},
number = {},
pages = {},
doi = {10.1111/trf.18266},
pmid = {40304595},
issn = {1537-2995},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; },
abstract = {Alloimmunization is prevalent in patients with sickle cell disease (SCD) and can be a barrier to gene therapy (GT) due to the necessary transfusion support for successful stem cell collection and infusion. We estimate that standard-of-care GT for an adult with SCD will require an average of 35-45 units of red blood cells over a 6-month period. Institutions should actively plan for these transfusion needs and share information to inform national consensus policies on the management of alloimmunization during GT.},
}

@article {pmid40304490,
year = {2025},
author = {Owen, MC and Zhou, Y and Dudley, H and Feehley, T and Hahn, A and Yokoyama, CC and Axelrod, ML and Lin, C-Y and Wang, D and Janowski, AB},
title = {Novel murine model of human astrovirus infection reveals cardiovascular tropism .},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0024025},
doi = {10.1128/jvi.00240-25},
pmid = {40304490},
issn = {1098-5514},
abstract = {UNLABELLED: Astroviruses are a common cause of gastrointestinal disease in humans and have been linked to fatal cases of encephalitis. A major barrier to the study of human-infecting astroviruses is the lack of an in vivo model as previous attempts failed to identify a host that supports viral replication. We describe a novel murine model of infection using astrovirus VA1/HMO-C (VA1), an astrovirus with high seroprevalence in humans. VA1 is cardiotropic, and viral RNA levels peak in the heart tissue 7 days post-inoculation in multiple different murine genetic backgrounds. Infectious VA1 particles could be recovered from heart tissue 3 and 5 days post-inoculation. Viral capsid was detected intracellularly in the heart tissue by immunostaining, and viral RNA was detected in cardiac myocytes, endocardium, and endothelial cells based on fluorescent in situ hybridization and confocal microscopy. Histologically, we identified inflammatory infiltrates consistent with myocarditis in some mice, with viral RNA colocalizing with the infiltrates. These foci contained CD3 +T cells and CD68 +macrophages. Viral RNA levels increased by >10 fold in the heart tissue or serum samples from Rag1 or Stat1 knockout mice, demonstrating the role of both adaptive and innate immunity in the response to VA1 infection. Based on the in vivo tropisms, we tested cardiac-derived primary cells and determined that VA1 can replicate in primary human cardiac endothelial cells, suggesting a novel cardiovascular tropism in human cells. This novel in vivo model of a human-infecting astrovirus enables further characterization of the host immune response and reveals a new cardiovascular tropism of astroviruses.

IMPORTANCE: Astroviruses routinely cause infections in humans; however, few methods were available to study these viruses. Here, we describe the first animal system to study human-infecting astroviruses by using mice. We demonstrate that mice are susceptible to astrovirus VA1, a strain that commonly infects humans and has been linked to fatal brain infections. The virus infects the heart tissue and is associated with inflammation. When mice with impaired immune systems were infected with VA1, they were found to have higher amounts of the virus in their hearts and blood. We found that VA1 can infect cells from human blood vessels of the heart, which is associated with human health. This model will enable us to better understand how astroviruses cause disease and how the immune system responds to infection. Our findings also suggest that astroviruses could be linked to cardiovascular diseases, including in humans.},
}

@article {pmid40303999,
year = {2025},
author = {Seber, A and Arcuri, LJ and Colturato, VR and Souza, MP and Zogbi, YAN and Funke, V and Lerner, D and Macedo, MC and Daudt, L and Kerbauy, MN and Zecchin, VG and Duarte, FB and Rabello Chiattone, R and Soares, RDA and Bettarello, G and Vaz de Macedo, A and Paton, E and Monteiro, TDM and Schmidt Filho, J and Astigarraga, CC and Scheinberg, P and Vigorito, AC and Vergueiro, CSV and Simione, A and Hashmi, S and Saber, W and Patel, J and Bonfim, CMS and Pasquini, M and Flowers, ME and Hamerschlak, N},
title = {Haploidentical, matched-related, and matched-unrelated hematopoietic cell transplant for acute leukemias in the early years of haploidentical transplant implementation in a developing country with a large unrelated donor registry.},
journal = {Frontiers in oncology},
volume = {15},
number = {},
pages = {1584631},
pmid = {40303999},
issn = {2234-943X},
abstract = {INTRODUCTION: Over the last decades, the donor network for hematopoietic cell transplantation (HCT) has grown exponentially, including unrelated and haploidentical (Haplo) donors. This study aimed to describe HCT outcomes with MSD, Haplo, and matched unrelated donors (MUD) in an early period of Haplo with posttransplant cyclophosphamide in a developing country with a large unrelated donor registry.

METHODS: This study was conducted in collaboration with the CIBMTR. We included patients with acute leukemias undergoing HCT between 2014-2018.

RESULTS: With 595 patients, 2-year overall survival (OS) was 69% for the MSD, 65% for the Haplo, and 71% for MUD (p=0.24) in CR1, confirmed in multivariable analysis. Relapse rate was lower for MUD (HR=0.35, p=0.0005) than MSD in patients with CR2+, leading to higher OS. Relapse was also higher with Haplo compared with MUD (HR=2.06, p=0.03).

DISCUSSION: Only survival bias can explain these findings in CR2+, suggesting some high-risk MUD patients, in which HCT timing is crucial, may not achieve HCT. Alternative donors were associated with higher non-relapse mortality, while PTCy-based Haplo offered the best protection against chronic graft-versus-host disease. Our study suggests Haplo and MUD are acceptable options for patients lacking MSD in developing countries like ours.},
}

@article {pmid40302927,
year = {2025},
author = {Dharamshi, A and Neufeld, A and Motwani, K and Gao, LL and Witten, D and Bien, J},
title = {Generalized data thinning using sufficient statistics.},
journal = {Journal of the American Statistical Association},
volume = {120},
number = {549},
pages = {511-523},
pmid = {40302927},
issn = {0162-1459},
support = {P30 DA048736/DA/NIDA NIH HHS/United States ; R01 DA047869/DA/NIDA NIH HHS/United States ; R01 EB026908/EB/NIBIB NIH HHS/United States ; R01 GM123993/GM/NIGMS NIH HHS/United States ; },
abstract = {Our goal is to develop a general strategy to decompose a random variable X into multiple independent random variables, without sacrificing any information about unknown parameters. A recent paper showed that for some well-known natural exponential families, X can be thinned into independent random variables X (1) , … , X (K) , such that X = ∑ k = 1 K X (k) . These independent random variables can then be used for various model validation and inference tasks, including in contexts where traditional sample splitting fails. In this paper, we generalize their procedure by relaxing this summation requirement and simply asking that some known function of the independent random variables exactly reconstruct X . This generalization of the procedure serves two purposes. First, it greatly expands the families of distributions for which thinning can be performed. Second, it unifies sample splitting and data thinning, which on the surface seem to be very different, as applications of the same principle. This shared principle is sufficiency. We use this insight to perform generalized thinning operations for a diverse set of families.},
}

@article {pmid40302197,
year = {2025},
author = {Nascimento de Lima, P and Maerzluft, C and Ozik, J and Collier, N and Rutter, CM},
title = {Stress-testing US colorectal cancer screening guidelines: Decennial colonoscopy from age 45 is robust to natural history uncertainty and colonoscopy sensitivity assumptions.},
journal = {Medical decision making : an international journal of the Society for Medical Decision Making},
volume = {},
number = {},
pages = {272989X251334373},
doi = {10.1177/0272989X251334373},
pmid = {40302197},
issn = {1552-681X},
abstract = {PurposeThe 2023 American College of Physicians (ACP) guidelines for colorectal cancer (CRC) screening are at odds with the United States Preventive Task Force (USPSTF) guidelines, with the former recommending screening starting at age 50 y and the latter at age 45 y. This article "stress tests" CRC colonoscopy screening strategies to investigate their robustness to uncertainties stemming from the natural history of disease and sensitivity of colonoscopy.MethodsThis study uses the CRC-SPIN microsimulation model to project the life-years gained (LYG) under several colonoscopy CRC screening strategies. The model was extended to include birth cohort effects on adenoma risk. We estimated natural history parameters under 2 different assumptions about the youngest age of adenoma initiation. For each, we generated 500 parameter sets to reflect uncertainty in the natural history parameters. We simulated 26 colonoscopy screening strategies and examined 4 different colonoscopy sensitivity assumptions, encompassing the range of sensitivities consistent with prior tandem colonoscopy studies. Across this set of scenarios, we identify efficient screening strategies and report posterior credible intervals for benefits of screening (LYG), burden (number of colonoscopies), and incremental burden-effectiveness ratios.ResultsProjected absolute screening benefits varied widely based on assumptions, but strategies starting at age 45 y were consistently in the efficiency frontier. Strategies in which screening starts at age 50 y with 10-y intervals were never efficient, saving fewer life-years than starting screening at age 45 y and performing colonoscopies every 15 y while requiring more colonoscopies per person.ConclusionsDecennial colonoscopy screening initiation at age 45 y remained a robust recommendation. Colonoscopy screening with a 10-y interval starting at age 50 y did not result in an efficient use of colonoscopies in any of the scenarios evaluated.HighlightsColorectal cancer colonoscopy screening strategies initiated at age 45 y were projected to yield more life-years gained while requiring the least number of colonoscopies across different model assumptions about disease natural history and colonoscopy sensitivity.Colonoscopy screening starting at age 50 y with a 10-y interval consistently underperformed strategies that started at age 45 y.},
}

@article {pmid40301663,
year = {2025},
author = {Goel, U and Dima, D and Davis, JA and Rashid, A and Wesson, W and Williams, L and Mazzoni, S and Bhurtel, E and Ullah, F and Rudoni, J and Rice, M and Tiger, YKR and Sauter, CS and Anwer, F and Raza, S and Shune, L and Khouri, J},
title = {Development of an Endothelial Activation and Stress Index (EASIX)-based predictive model for cytokine release syndrome and neurotoxicity after B-cell maturation antigen directed chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {40301663},
issn = {1476-5365},
}

@article {pmid40299982,
year = {2025},
author = {Kubinski, HC and Despres, HW and Johnson, BA and Schmidt, MM and Jaffrani, SA and Turner, AH and Fanuele, CD and Mills, MG and Lokugamage, KG and Dumas, CM and Shirley, DJ and Estes, LK and Pekosz, A and Crothers, JW and Roychoudhury, P and Greninger, AL and Jerome, KR and Di Genova, BM and Walker, DH and Ballif, BA and Ladinsky, MS and Bjorkman, PJ and Menachery, VD and Bruce, EA},
title = {Variant mutation G215C in SARS-CoV-2 nucleocapsid enhances viral infection via altered genomic encapsidation.},
journal = {PLoS biology},
volume = {23},
number = {4},
pages = {e3003115},
pmid = {40299982},
issn = {1545-7885},
mesh = {*SARS-CoV-2/genetics/physiology ; Humans ; Animals ; Mutation ; *COVID-19/virology ; *Coronavirus Nucleocapsid Proteins/genetics/metabolism ; Genome, Viral ; *Nucleocapsid/genetics/metabolism ; Chlorocebus aethiops ; Vero Cells ; *Viral Genome Packaging/genetics ; Virus Assembly/genetics ; Virion/genetics ; Phosphoproteins ; },
abstract = {The evolution of SARS-CoV-2 variants and their respective phenotypes represents an important set of tools to understand basic coronavirus biology as well as the public health implications of individual mutations in variants of concern. While mutations outside of spike are not well studied, the entire viral genome is undergoing evolutionary selection, with several variants containing mutations in the central disordered linker region of the nucleocapsid (N) protein. Here, we identify a mutation (G215C), characteristic of the Delta variant, that introduces a novel cysteine into this linker domain, which results in the formation of a more stable N-N dimer. Using reverse genetics, we determined that this cysteine residue is necessary and sufficient for stable dimer formation in a WA1 SARS-CoV-2 background, where it results in significantly increased viral growth both in vitro and in vivo. Mechanistically, we show that the N:G215C mutant has more encapsidation as measured by increased RNA binding to N, N incorporation into virions, and electron microscopy showing that individual virions are larger, with elongated morphologies.},
}

*SARS-CoV-2/genetics/physiology
Humans
Animals
Mutation
*COVID-19/virology
*Coronavirus Nucleocapsid Proteins/genetics/metabolism
Genome, Viral
*Nucleocapsid/genetics/metabolism
Chlorocebus aethiops
Vero Cells
*Viral Genome Packaging/genetics
Virus Assembly/genetics
Virion/genetics
Phosphoproteins

@article {pmid40298902,
year = {2025},
author = {Haack, AJ and Brown, LG and Goldstein, AJ and Mulimani, P and Berthier, J and Viswanathan, AR and Kopyeva, I and Whitten, JM and Lin, A and Nguyen, SH and Leahy, TP and Bouker, EE and Padgett, RM and Mazzawi, NA and Tokihiro, JC and Bretherton, RC and Wu, A and Tapscott, SJ and DeForest, CA and Popowics, TE and Berthier, E and Sniadecki, NJ and Theberge, AB},
title = {Suspended Tissue Open Microfluidic Patterning (STOMP).},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e2501148},
doi = {10.1002/advs.202501148},
pmid = {40298902},
issn = {2198-3844},
support = {R35GM128648/NH/NIH HHS/United States ; R35GM138036/NH/NIH HHS/United States ; R01HL149734/NH/NIH HHS/United States ; R03DE029827/NH/NIH HHS/United States ; T32CA080416/NH/NIH HHS/United States ; F30HL158030/NH/NIH HHS/United States ; R90DE023059/NH/NIH HHS/United States ; 5TL1TR002318-08/NH/NIH HHS/United States ; P50AR065139//Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center - Seattle/ ; },
abstract = {Free-standing tissue structures tethered between pillars are powerful mechanobiology tools for studying cell contraction. To model interfaces ubiquitous in natural tissues and upgrade existing single-region suspended constructs, we developed Suspended Tissue Open Microfluidic Patterning (STOMP), a method to create multi-regional suspended tissues. STOMP uses open microfluidics and capillary pinning to pattern subregions within free-standing tissues, facilitating the study of complex tissue interfaces, such as diseased-healthy boundaries (e.g., fibrotic-healthy) and tissue-type interfaces (e.g., bone-ligament). We observed altered contractile dynamics in fibrotic-healthy engineered heart tissues compared to single-region tissues and differing contractility in bone-ligament enthesis constructs compared to single-tissue periodontal ligament models. STOMP is a versatile platform - surface tension-driven patterning removes material requirements common with other patterning methods (e.g., shear-thinning, photopolymerizable) allowing tissue generation in multiple geometries with native extracellular matrices and advanced four-dimensional (4D)- materials. STOMP combines the contractile functionality of suspended tissues with precise patterning, enabling dynamic and spatially controlled studies.},
}

@article {pmid40298430,
year = {2025},
author = {Cai, L and Wu, F and Zhou, Q and Gao, Y and Yao, B and DeBerardinis, RJ and Acquaah-Mensah, GK and Aidinis, V and Beane, JE and Biswal, S and Chen, T and Concepcion-Crisol, CP and Grüner, BM and Jia, D and Jones, RA and Kurie, JM and Lee, MG and Lindahl, P and Lissanu, Y and Lorz, C and MacPherson, D and Martinelli, R and Mazur, PK and Mazzilli, SA and Mii, S and Moll, HP and Moorehead, RA and Morrisey, EE and Ng, SR and Oser, MG and Pandiri, AR and Powell, CA and Ramadori, G and Santos, M and Snyder, EL and Sotillo, R and Su, KY and Taki, T and Taparra, K and Tran, PT and Xia, Y and van Veen, JE and Winslow, MM and Xiao, G and Rudin, CM and Oliver, TG and Xie, Y and Minna, JD},
title = {The Lung Cancer Autochthonous Model Gene Expression Database Enables Cross-Study Comparisons of the Transcriptomic Landscapes Across Mouse Models.},
journal = {Cancer research},
volume = {},
number = {},
pages = {OF1-OF15},
doi = {10.1158/0008-5472.CAN-24-1607},
pmid = {40298430},
issn = {1538-7445},
support = {R01CA285336//National Cancer Institute (NCI)/ ; IRG-21-142-16//American Cancer Society (ACS)/ ; U24CA213274//National Cancer Institute (NCI)/ ; P50CA070907//National Cancer Institute (NCI)/ ; R01GM140012//National Institute of General Medical Sciences (NIGMS)/ ; R01DE030656//National Institute of Dental and Craniofacial Research (NIDR)/ ; //Howard Hughes Medical Institute (HHMI)/ ; R35CA220449//National Cancer Institute (NCI)/ ; R35CA263816//National Cancer Institute (NCI)/ ; R01CA271540//National Cancer Institute (NCI)/ ; R01CA244841//National Cancer Institute (NCI)/ ; U01CA249245//National Cancer Institute (NCI)/ ; U01AI156189//National Institute of Allergy and Infectious Diseases (NIAID)/ ; U01CA213338//National Cancer Institute (NCI)/ ; R35GM136375//National Institute of General Medical Sciences (NIGMS)/ ; R01CA212415//National Cancer Institute (NCI)/ ; R01CA272945//National Cancer Institute (NCI)/ ; P50CA228944//National Cancer Institute (NCI)/ ; GR4575/1-2//Deutsche Forschungsgemeinschaft (DFG)/ ; PI21/00764//Instituto de Salud Carlos III (ISCIII)/ ; },
abstract = {Lung cancer, the leading cause of cancer mortality, exhibits diverse histologic subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. In this study, we established the Lung Cancer Autochthonous Model Gene Expression Database (LCAMGDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMM), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model. Meticulous curation and collaboration with data depositors produced a robust and comprehensive database, enhancing the fidelity of the genetic landscape it depicts. The LCAMGDB aligned 859 tumors from GEMMs with human lung cancer mutations, enabling comparative analysis and revealing a pressing need to broaden the diversity of genetic aberrations modeled in the GEMMs. To accompany this resource, a web application was developed that offers researchers intuitive tools for in-depth gene expression analysis. With standardized reprocessing of gene expression data, the LCAMGDB serves as a powerful platform for cross-study comparison and lays the groundwork for future research, aiming to bridge the gap between mouse models and human lung cancer for improved translational relevance. Significance: The Lung Cancer Autochthonous Model Gene Expression Database (LCAMGDB) provides a comprehensive and accessible resource for the research community to investigate lung cancer biology in mouse models.},
}

@article {pmid40298376,
year = {2025},
author = {Atmar, RL and Lyke, KE and Posavad, CM and Deming, ME and Brady, RC and Dobrzynski, D and Edupuganti, S and Mulligan, MJ and Rupp, RE and Rostad, CA and Jackson, LA and Martin, JM and Shriver, MC and Rajakumar, K and Coler, RN and El Sahly, HM and Kottkamp, AC and Branche, AR and Frenck, RW and Johnston, C and Babu, TM and Bäcker, M and Archer, JI and Crandon, S and Nakamura, A and Nayak, SU and Szydlo, D and Dominguez Islas, CP and Brown, ER and O'Connell, SE and Montefiori, DC and Eaton, A and Neuzil, KM and Stephens, DS and Beigel, JH and Pasetti, M and Roberts, PC},
title = {Mucosal and Systemic Antibody Responses After Boosting With a Bivalent Messenger RNA Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf176},
pmid = {40298376},
issn = {1537-6613},
support = {//Infectious Diseases Clinical Research Consortium/ ; //National Institute of Allergy and Infectious Diseases/ ; UM1AI48372/NH/NIH HHS/United States ; 75N93019C00050)//NIAID Collaborative Influenza Vaccine Innovation Centers/ ; //Vaccine Research Center/ ; },
abstract = {BACKGROUND: Mucosal immunity plays a critical role in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and replication. Understanding the capacity of coronavirus disease 2019 (COVID-19) vaccines to elicit both mucosal and systemic antibodies could help optimize vaccination strategies.

METHODS: We conducted an open-label, phase 1/2 adaptive-design clinical trial to evaluate the safety and immunogenicity of COVID-19 immunizations. Healthy adults received 2 priming doses of mRNA-1273, a booster dose of mRNA-1273, and a second booster of bivalent (WA-1 and BA.4/BA.5) mRNA-1273.222. Adverse event data were collected. Serum and mucosal immunity were evaluated.

RESULTS: One hundred six persons were enrolled. Thirty received all 4 study-related vaccine doses. All vaccines were well tolerated, with injection site pain, malaise, myalgias, and headache being the most frequently reported symptoms. Among those who received a second booster, 24 of 30 (80%) had serological evidence of SARS-CoV-2 infection. Following the second booster, increases in geometric mean binding and pseudovirus neutralization antibody titers to the ancestral strain and BA.1 and BA.5 variants were observed. Increases in mucosal immunoglobulin G and immunoglobulin A (IgA) antibodies in nasal and salivary samples were observed in both previously infected and infection-naive participants, although prior infection markedly boosted virus-specific mucosal IgA responses.

CONCLUSIONS: The mRNA-1273.222 booster vaccine was safe and immunogenic and induced mucosal antibody responses in previously infected and infection-naive persons.

CLINICAL TRIALS REGISTRATION: NCT04889209.},
}

@article {pmid40297938,
year = {2025},
author = {Richardson, BD and Blette, BS and Gilbert, PB and Hudgens, MG},
title = {Addressing confounding and continuous exposure measurement error using corrected score functions.},
journal = {Biometrics},
volume = {81},
number = {2},
pages = {},
pmid = {40297938},
issn = {1541-0420},
support = {AI068635//U.S. Public Health Service/ ; R37 AI054165/AI/NIAID NIH HHS/United States ; T32 ES007018/ES/NIEHS NIH HHS/United States ; R37AI029168/GF/NIH HHS/United States ; },
mesh = {Humans ; HIV Infections/prevention & control/epidemiology/immunology ; Bias ; Computer Simulation ; Confounding Factors, Epidemiologic ; *Models, Statistical ; Biomarkers ; Data Interpretation, Statistical ; *Biometry/methods ; },
abstract = {Confounding and exposure measurement error can introduce bias when drawing inference about the marginal effect of an exposure on an outcome of interest. While there are broad methodologies for addressing each source of bias individually, confounding and exposure measurement error frequently co-occur, and there is a need for methods that address them simultaneously. In this paper, corrected score methods are derived under classical additive measurement error to draw inference about marginal exposure effects using only measured variables. Three estimators are proposed based on g-formula, inverse probability weighting, and doubly-robust estimation techniques. The estimators are shown to be consistent and asymptotically normal, and the doubly-robust estimator is shown to exhibit its namesake property. The methods, which are implemented in the R package mismex, perform well in finite samples under both confounding and measurement error as demonstrated by simulation studies. The proposed doubly-robust estimator is applied to study the effects of two biomarkers on HIV-1 infection using data from the HVTN 505 preventative vaccine trial.},
}

Humans
HIV Infections/prevention & control/epidemiology/immunology
Bias
Computer Simulation
Confounding Factors, Epidemiologic
*Models, Statistical
Biomarkers
Data Interpretation, Statistical
*Biometry/methods

@article {pmid40296864,
year = {2025},
author = {Long, KJ and Silvestri, GA and Kammer, MN and Gibbs, S and Wu, W and Johal, M and Pipavath, S and Pitcher, T and Jett, J and Nair, VS},
title = {Validation of a High-Specificity Blood Autoantibody Test to Detect Lung Cancer in Pulmonary Nodules.},
journal = {CHEST pulmonary},
volume = {3},
number = {1},
pages = {},
pmid = {40296864},
issn = {2949-7892},
support = {T32 HL144470/HL/NHLBI NIH HHS/United States ; },
abstract = {BACKGROUND: Pulmonary nodules (PNs) are frequently detected by chest CT scan, which is increasingly used in clinical practice. Accurately identifying malignant nodules can pose a diagnostic challenge; therefore, a high-specificity biomarker could help clinicians identify malignant nodules and ideally lead to the earlier diagnosis of lung cancer.

RESEARCH QUESTION: What are the performance characteristics of a blood-based biomarker for identifying malignancy in patients with a CT-detected PN?

STUDY DESIGN AND METHODS: Banked plasma samples from 2 independent prospective observational cohorts of patients presenting with benign or malignant PNs 8 to 30 mm in size were tested using a 7-autoantibody panel. Sensitivity, specificity, and positive predictive value of the autoantibody test (AAT) to identify cancer were calculated for the individual and combined cohorts.

RESULTS: Overall, 447 patients (263 and 184 from each cohort) were included in the analysis with a prevalence of malignancy of 55%. The performance of the AAT between the 2 cohorts was similar. The AAT demonstrated a specificity of 90% (95% CI, 85%-93%), a positive predictive value of 66% (95% CI, 52%-77%), sensitivity of 16% (95% CI, 12%-22%), and false-positive rate of 10% in the combined cohort. Using a pretest probability of cancer cutoff of 20% improved the positive predictive value to 76% (95% CI, 61%-88%) and resulted in a 52% decrease in the number of false-positive test results. In the subset of patients who had 18F-fluorodeoxyglucose PET imaging performed for clinical purposes (n = 222), specificity of the AAT was higher (93% vs 58%, P < .001), but the sensitivity was lower than 18F-fluorodeoxyglucose PET scan (17% vs 75%, P < .001).

INTERPRETATION: This study validates the specificity of a blood-based autoantibody biomarker for identifying malignancy in patients with indeterminate PNs. This rule-in biomarker may help to expedite workup of malignant nodules.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT01752114; URL: www.clinicaltrials.gov CHEST Pulmonary 2025; 3(1):100130.},
}

@article {pmid40295790,
year = {2024},
author = {Jelley, L and Aminisani, N and O'Neill, M and Jennings, T and Douglas, J and Utekar, S and Johnston, H and Welch, D and Hadfield, J and , and de Ligt, J and Winter, D and French, N and Thomas, PG and Webby, RJ and Huang, S and Geoghegan, JL},
title = {Tracing household transmission of SARS-CoV-2 in New Zealand using genomics.},
journal = {Npj viruses},
volume = {2},
number = {1},
pages = {21},
pmid = {40295790},
issn = {2948-1767},
support = {22/138//New Zealand Health Research Council Grant/ ; 22/138//New Zealand Health Research Council Grant/ ; 22/138//New Zealand Health Research Council Grant/ ; 22/138//New Zealand Health Research Council Grant/ ; 22/138//New Zealand Health Research Council Grant/ ; 22/138//New Zealand Health Research Council Grant/ ; U01 AI 144616//US-NIAID/ ; 75N93021C00016/AI/NIAID NIH HHS/United States ; U01 AI 144616//US-NIAID/ ; },
abstract = {By early 2022, the highly transmissible Omicron variant of SARS-CoV-2 had spread across most of the world. For the first time since the pandemic began, New Zealand was experiencing high levels of community transmission of SARS-CoV-2. We enroled a cohort of households to better understand differences in transmission dynamics among subvariants of Omicron. We enroled 71 households, comprising 289 participants, and aimed to use viral genomes to gain a clearer understanding of variant-specific differences in epidemiological parameters affecting transmission dynamics. Approximately 80% of the households enroled experienced transmission of BA.2, while most of the remaining households had infections with BA.1 or BA.5. Using a logistic regression generalised linear mixed model, we found no difference in household secondary infection rate between Omicron subvariants BA.1, BA.2 and BA.5. Of the households recruited, the vast majority (92%) experienced a single chain of transmission with one inferred introduction. Further, we found that in 48% of the households studied, all household participants became infected following an index case. Most household participants tested positive within a week following an introduction, supporting the seven-day isolation requirement for household contacts that was in place in New Zealand at the time. By integrating genomic and epidemiological data, we show that viral transmission dynamics can be investigated with a higher level of granularity than with epidemiological data alone. Overall, households are a high risk setting for viral transmission in New Zealand.},
}

@article {pmid40294415,
year = {2025},
author = {Riddler, SA and Moodie, Z and Clark, J and Yen, C and Allen, M and Furch, BD and Lu, H and Grant, S and Mondal, K and Anderson, M and Maenza, J and Lemos, MP and Woodward Davis, AS and Walsh, SR and Sobieszczyk, ME and Frank, I and Goepfert, P and Stephenson, KE and Baden, LR and Tieu, HV and Keefer, MC and McElrath, MJ and Kublin, JG and Corey, L},
title = {High Frequency of Chronic Urticaria Following an Investigational HIV-1 BG505 MD39.3 Trimer mRNA Vaccine in a Phase 1, Randomized, Open-Label Clinical Trial (HVTN 302).},
journal = {Annals of internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.7326/ANNALS-24-02701},
pmid = {40294415},
issn = {1539-3704},
abstract = {BACKGROUND: The mRNA platform is under investigation for many vaccines, including HIV-1 vaccines.

OBJECTIVE: To evaluate the safety and tolerability of 3 investigational HIV-1 trimer mRNA vaccines.

DESIGN: Safety analysis of mRNA vaccination in a phase 1, randomized, open-label trial. (ClinicalTrials.gov: NCT05217641).

SETTING: Ten research sites in the United States.

PARTICIPANTS: 108 volunteers aged 18 to 55 years without HIV-1.

INTERVENTION: Investigational HIV-1 BG505 MD39.3 trimer mRNA vaccines (gp140 soluble trimer, gp151 membrane-bound trimer, and gp151 CD4KO membrane-bound trimer) at doses of 100 and 250 mcg at 0, 2, and 6 months.

MEASUREMENTS: Solicited and unsolicited adverse reactions and events reported during the 12 months after the first vaccination.

RESULTS: Participants (n = 108) were randomly assigned to 6 vaccine groups. Mild to moderate local and systemic solicited events were common. Eighty participants reported 190 unsolicited adverse events (AEs); 30 were considered to be related to a study product. Most (73%) related AEs were mild, and the rest were moderate. Among related AEs, urticaria was reported by 7 of 108 participants (7% [95% CI, 3% to 13%]), 4 of whom had unresolved, intermittent urticaria at 12 months. In post hoc analyses, demographic characteristics, history of allergy or medication use, and COVID-19 were not associated with urticaria. In a comparison of participants with versus without urticaria, 100% (7 of 7; CI, 65% to 100%) versus 37% (37 of 101; CI, 28% to 46%) reported previous Moderna COVID-19 vaccination, 29% (2 of 7; CI, 8% to 64%) versus 76% (77 of 101; CI, 67% to 84%) reported previous Pfizer-BioNTech COVID-19 vaccination, and 0% (0 of 7; CI, 0% to 35%) versus 5% (5 of 101; CI, 2% to 11%) reported no previous mRNA COVID-19 vaccination.

LIMITATIONS: Lack of a placebo group, open-label study, and post hoc evaluation of urticarial risk.

CONCLUSION: Urticarial reactions associated with experimental HIV-1 mRNA vaccines were observed in this trial. Studies to investigate the mechanism and approaches to mitigate these reactions are underway to further advance HIV-1 vaccine research.

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

@article {pmid40294366,
year = {2025},
author = {Huang, BJ and Meyer, LK and Alonzo, TA and Wang, YC and Lamble, AJ and Ries, RE and Wang, W and Hirsch, B and Raca, G and Ma, X and Gamis, AS and Aplenc, R and Kolb, EA and Cooper, TM and Tarlock, K and Loken, MR and Meshinchi, S and Chewning, JH and Woods, WG and Horan, JT},
title = {Hematopoietic Stem Cell Transplantation Outcomes for High-Risk AML: A Report From the Children's Oncology Group.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2401841},
doi = {10.1200/JCO-24-01841},
pmid = {40294366},
issn = {1527-7755},
abstract = {PURPOSE: Hematopoietic stem cell transplantation (HSCT) is used as consolidation for pediatric patients with high-risk AML in first complete remission (CR1). The definition of high-risk AML has evolved considerably over the past two decades with the successive identification of new unfavorable risk factors. We conducted a cross-study analysis to determine whether HSCT improves the outcomes of patients with contemporarily defined high-risk AML.

METHODS: We combined data from AAML0531 and AAML1031, the last two phase III clinical trials completed by the Children's Oncology Group (COG). These two trials established the prognostic importance of measurable residual disease (MRD) and several high-risk cryptic cytogenetic/molecular (CM) alterations, which were applied to reclassify patients in the current COG phase III clinical trial, AAML1831. We compared the outcomes after HSCT in CR1 with those after chemotherapy alone in CR1 in the redefined high-risk group.

RESULTS: Our study cohort comprised 463 patients with high-risk CM alterations and 72 patients with standard-risk (SR) CM results with positive MRD at end of induction I. In all, 33.9% and 45.8% of these groups underwent HSCT in CR1, respectively. HSCT was associated with decreased relapse and improved disease-free survival (DFS) in both groups. In the high-risk CM group, 5-year DFS was 26.0% (95% CI, 20.6 to 31.6) and 49.8% (95% CI, 41.7 to 57.4; P < .001) in patients receiving chemotherapy alone and HSCT, respectively. In the SR CM and MRD+ groups, DFS was 16.9% (95% CI, 4.3 to 36.7) compared with 50.9% (95% CI, 32.7 to 66.5; P = .032). HSCT was also associated with improvement in outcomes based on multivariable analysis and across subgroups defined by clinical trial and by high-risk CM subtype, with the exception of chromosome 7 or 5 loss.

CONCLUSION: HSCT was associated with improved outcomes in pediatric patients with contemporarily defined high-risk AML.},
}

@article {pmid40294356,
year = {2025},
author = {Rosenberg, AR and Fladeboe, KM and Zhou, C and Bradford, MC and Kang, T and Maurer, S and Freyer, DR and Baker, KS and Comiskey, L and Junkins, CC and Taylor, MR and Yi-Frazier, JP},
title = {Promoting Resilience in Stress Management: A Randomized Controlled Trial of a Novel Psychosocial Intervention for Adolescents and Young Adults With Advanced Cancer.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2500161},
doi = {10.1200/OP-25-00161},
pmid = {40294356},
issn = {2688-1535},
abstract = {PURPOSE: Adolescents and young adults (AYAs) with advanced cancer (AC) report poor quality of life (QOL), high psychological distress, and minimal engagement in health care discussions. We assessed the effect of a novel resilience coaching program (Promoting Resilience in Stress Management [PRISM]-AC) on AYA outcomes.

METHODS: We conducted a multisite randomized trial of PRISM-AC versus usual care (UC) among AYAs age 12-24 years, diagnosed with AC within 2 weeks before enrollment. PRISM-AC consists of four sessions targeting AYA-endorsed resilience resources (stress management, goal-setting, cognitive reframing, and meaning-making) plus a session integrating elements of advance care planning. Participants completed surveys at baseline, and 3, 6, 9, and 12 months. The primary outcome was Pediatric QOL at 3 months; secondary/exploratory outcomes included 3-month changes in resilience (10-item Connor-Davidson Resilience Scale) and hope (Snyder Hope Scale), and trajectories of QOL, anxiety, and depression (Hospital Anxiety and Depression Scale) over 12 months. We examined associations with linear mixed effects regression models. We also explored PRISM-AC's impact on AYA participation in critical health care discussions, as documented in the electronic health record.

RESULTS: Between April 2019 and January 2024, we enrolled 239 AYAs (56% of 426 approached) and randomly assigned 195 (82% of enrolled; 96 UC, 99 PRISM). They were of mean age 16.5 years (standard deviation, 3.9), mostly White (63%), non-Hispanic (59%), and publicly insured (53%). At 3 months, we detected no significant differences between groups with respect to QOL, anxiety, or depression; PRISM-AYAs demonstrated greater improvements in resilience (+1.3 [5.9] v -1.4 (7.5); P = .038) and hope (+2.4 [10.4] v -2.8 [11.2]; P = .001) than UC-AYAs. Over the 12-month study period, PRISM-AYAs reported more improvements in QOL and anxiety, with significant differences at later time points (PRISM-QOL improvements, 6 months: +3.4 [95% CI, 0.1 to 6.6]; P = .043; 12 months: +6.8 [95% CI, 3.3 to 10.3]; P < .001). Although participation in key health care discussions was similar between groups from baseline to 6 months, 67% (95% CI, 35 to 88) and 50% (95% CI, 22 to 78) of PRISM-AYAs participated at 9 and 12 months, respectively, compared with 39% (95% CI, 20 to 61) and 38% (95% CI, 21 to 59) of UC-AYAs.

CONCLUSION: Among AYAs with AC, PRISM-AC did not immediately improve QOL. Rather, it improved resilience and hope, potentially enabling longer-term improvements in QOL.},
}

@article {pmid40293383,
year = {2025},
author = {Colbert, CM and Melancon, D and Kang, J and Ford, EC and Smith, WP},
title = {A Comparative Risk Analysis of Cone Beam Computed Tomography-based Daily Adaptive Radiation Therapy and Cone Beam Computed Tomography-based Radiation Therapy Alone.},
journal = {International journal of radiation oncology, biology, physics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ijrobp.2025.04.009},
pmid = {40293383},
issn = {1879-355X},
abstract = {PURPOSE: When adopting a new therapeutic technology, a comparison to a standard of care is needed. We aim to directly compare the specific safety implications of adaptive radiation therapy (ART) to those of traditional image guided radiation therapy (IGRT), as implemented on a ring gantry linear accelerator with kilovoltage cone beam computed tomography-based online ART capability.

METHODS AND MATERIALS: An interdisciplinary committee performed a failure modes and effects analysis based on the American Association of Physicists in Medicine (AAPM) Task Group 100 method addressing initial treatment planning, quality assurance, and treatment delivery for both IGRT-alone and IGRT with ART on the Varian Ethos. Failure modes were categorized by process step and associated clinical roles, scored by severity, occurrence, and detectability, and ranked by risk priority number (RPN). Failure modes shared by IGRT and ART were scored and analyzed comparatively.

RESULTS: We identified 33 unique system failure modes as part of the IGRT-alone workflow, and 9 additional failure modes specific to ART. Most high-risk IGRT-alone system failure modes were associated with initial treatment planning errors. High-risk ART failure modes also included errors related to adaptive replanning. Reanalysis of 33 IGRT-alone failure modes in the ART setting found an overall decrease in median RPN from 96 (IQR, 56-144) to 72 (IQR, 32-120; P = .035). RPN decreased for 12 failure modes, with the greatest change observed among the highest-ranked failure modes for IGRT-alone.

CONCLUSIONS: Although online ART introduces new avenues for error in the adaptive replanning process, the enhanced staffing and iterative plan review reduce the risk associated with systematic errors originating in initial treatment planning. The finding that the RPN decreased in the adaptive setting provides a unique motivation for the adoption of ART from a patient safety perspective, beyond the well-documented dosimetric benefit of ART.},
}

@article {pmid40293363,
year = {2025},
author = {Minalga, B and Siskind, R and Campbell, R and Adamson, T and Cermak, MA and Davis, A and Givens, ED and Dyer, M and McCarthy, K and Montañez, NA and White, R and , },
title = {The Representative Studies Rubric: A Tool for Diversity in Clinical Trials.},
journal = {AJOB empirical bioethics},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/23294515.2025.2497753},
pmid = {40293363},
issn = {2329-4523},
abstract = {When clinical trials fail to enroll diverse study populations, a multitude of consequences can occur, including compromised validity and generalizability, safety and efficacy uncertainties, regulatory limitations, widened disparities, distrust in science and medicine, and undermined efforts to address urgent health needs. We developed the Representative Studies Rubric (RSR), a questionnaire that evaluates the extent to which clinical trials are designed to enroll representative study populations with a focus on age, ethnicity, drug use, gender, pregnancy, race, and sex assigned at birth. We used the RSR to conduct an analysis of all active studies in the NIH-funded HIV/AIDS Clinical Trials Networks (Networks) and identified patterns of research practices that may limit the participation of underrepresented populations, with ethical implications. The Networks subsequently formalized the RSR as a required protocol development tool for all future studies to correct exclusionary research practices with the goal to achieve more representative study populations.},
}

@article {pmid40288610,
year = {2025},
author = {Shouval, R and Strouse, C and Kim, S and Oloyede, T and Ahmed, S and Awan, FT and Luan, D and Bachanova, V and Badar, T and Bar, M and Barba, P and Beitinjaneh, AM and Cashen, A and Dholaria, B and Elsawy, M and Ganguly, S and Geethakumari, PR and Greenbaum, U and Hashmi, H and Hill, LC and Jain, MD and Jain, T and Kebriaei, P and Kittai, AS and Locke, FL and Lulla, PD and Mead, E and McGuirk, JP and Mussetti, A and Nishihori, T and Olson, AL and Pennisi, M and Perales, MA and Riedell, PA and Saber, W and Mirza, AS and Magalhaes-Silverman, M and Shpall, EJ and Sorror, M and Wudhikarn, K and Turtle, CJ and Moskop, A and Pasquini, MC},
title = {Cytokine release syndrome and neurotoxicity following CD19 CAR-T in B-cell lymphoma.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.03.011},
pmid = {40288610},
issn = {2666-6367},
abstract = {BACKGROUND: Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for relapsed-refractory large B-cell lymphoma (LBCL). However, toxicities, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), remain significant concerns.

OBJECTIVE: Analyze temporal trends, risk factors and associations between these toxicities and their severity.

STUDY DESIGN: In this registry study by the Center for International Blood and Marrow Transplant Research (CIBMTR), we studied CRS and ICANS in 1,916 LBCL patients treated with commercial CAR-T therapies (axicabtagene ciloleucel 74.9%, tisagenlecleucel 25.1%) between 2018 and 2020. Outcomes include development of CRS/ICANS, timing and severity according to ASTC grading, overall survival. Risk factors were assessed using Cox proportional hazards model.

RESULTS: Among patients developing CRS (75.2%), 11.3% had grade ≥ 3 CRS. Among patients developing ICANS (43.5%) 47.7% had grade ≥ 3 ICANS. Among patients developing CRS, severe CRS rates decreased from 14.0% in 2018 to 9.2% in 2020 (P< .01). However, the proportion of severe ICANS in patients who developed ICANS remained statistically unchanged (41.5% in 2018 to 53.7% in 2020, P= .10). CRS and ICANS were correlated: 57.1% of patients with CRS also experienced ICANS, and CRS was reported in 97.5% of ICANS cases, suggesting a potential continuum between toxicities. Axicabtagene ciloleucel was associated with higher risk of any grade CRS (OR, 4.6; 95% CI, 3.65-5.81) and ICANS (OR, 5.85; 95% CI, 4.48-7.64) as well as early and severe forms of both complications. Older age, lower performance status, and elevated lactate dehydrogenase (LDH) levels prior to infusion also variably predicted these toxicities. In a landmark analysis starting 30 days post-infusion, patients with severe CRS or severe ICANS had shorter overall survival compared to those without these toxicities.

CONCLUSION: High grades of CRS improved over time likely related to earlier intervention, development of ICANS is intrinsically related with CRS. These findings underscore the need for effective strategies to mitigate these toxicities and improve CAR-T safety.},
}

@article {pmid40287589,
year = {2025},
author = {Vo, P and Ng, K and Schoch, G and Cooper, J and Vupalanchi, A and Flowers, M and Sandmaier, BM and Gooley, T and Storb, R},
title = {Subsequent cancers following non-myeloablative conditioning for allogeneic hematopoietic cell transplantation.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {40287589},
issn = {1476-5365},
support = {CA 078902//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA 078902//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P30 CA 015704//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {We examined the risk of subsequent malignant neoplasms (SMNs) in 1720 patients with hematologic cancers given allogeneic hematopoietic grafts from 03/1998 to 08/2023 after nonmyeloablative conditioning regimens. With a median follow-up of 12 years, the cumulative incidence of SMNs was 17% (95% CI, [15%, 19%]). Most SMNs (n = 543) were non-melanoma skin cancers seen in 208 patients; unfortunately, information on these cancers was not available in the Surveillance, Epidemiology, and End Results (SEER) database for comparison with such tumors in the general population. However, developing non-melanoma skin cancers was statistically significantly associated with chronic GVHD and, thus, unlikely to be conditioning regimen related. Eighty-six patients (5%) developed 93 other SMNs. This number (93 SNMs) significantly exceeded the expected 73.4 cases in the comparison group (p = 0.03). This increase was driven exclusively by increases in uterine adenocarcinoma (n = 2), squamous lip cancer (n = 5), and squamous penile cancer (n = 2); the latter two cancers were, again, associated with chronic GVHD. Apart from these three tumor types, there were no observed increases in the risk of other tumors compared to those in the general population.},
}

@article {pmid40281324,
year = {2025},
author = {Posluszny, DM and Nezu, AM and Bovbjerg, DH and Syrjala, KL and Dew, MA},
title = {Intervention Development to Promote Medical Adherence After Stem Cell Transplant.},
journal = {Journal of clinical psychology in medical settings},
volume = {},
number = {},
pages = {},
pmid = {40281324},
issn = {1573-3572},
support = {K23CA149082 and P30CA047904/CA/NCI NIH HHS/United States ; },
abstract = {Allogeneic hematopoietic cell transplantation (HCT) can be a lifesaving treatment for patients with hematologic disease. However, adherence to the post-HCT clinical regimen has many challenges that patients and their family caregivers must manage after hospital discharge. To address their needs, we developed a Dyadic Problem-Solving Therapy (DPST) intervention, then examined its feasibility and acceptability to patients and their family caregivers. Twelve patient-family caregiver dyads participated. Four dyads received DPST in person, four received it via online video conferencing. Another four received an enhanced usual care (EUC) intervention of the same length. Feasibility was assessed using completion rates, while acceptability was assessed using satisfaction ratings on the Client Satisfaction Questionnaire. DPST and EUC were both feasible (100% of dyads who started the intervention completed it) and acceptable with satisfaction ratings ranging from 3.6 to 4 for patients and 3.6-3.9 for family caregivers on a 1-4 scale for both DPST groups and ranging from 3.3 to 3.8 for EUC patients and 3.5-4 for EUC family caregivers. There were no evident differences by mode of intervention delivery. DPST, both in person and via video, appears feasible and acceptable for training patient-family caregiver dyads to manage challenges to adherence to the post-HCT regimen.},
}

@article {pmid40280707,
year = {2025},
author = {Wang, M and Guo, Y and Hippe, DS and Zhao, X and Yuan, C and Saba, L and Zhang, B and Mossa-Basha, M},
title = {Plaque RADS Related to Cerebrovascular Event Risk with Mild/moderate Stenosis: a CARE II study.},
journal = {AJNR. American journal of neuroradiology},
volume = {},
number = {},
pages = {},
doi = {10.3174/ajnr.A8819},
pmid = {40280707},
issn = {1936-959X},
abstract = {BACKGROUND AND PURPOSE: Carotid Plaque-Reporting And Data System (Plaque-RADS) provides a standardized approach for evaluating carotid plaque morphology and composition. The aim of this study was to evaluate carotid Plaque-RADS, and its relationship with clinical risk factors and ipsilateral cerebrovascular symptoms, in a prospectively-acquired multi-center, vessel-wall MRI dataset.

MATERIALS AND METHODS: Symptomatic patients were recruited from the CARE-II (Chinese Atherosclerosis Risk Evaluation, NCT02017756) study. This cross-sectional study included patients with recent stroke or transient ischemia attack and atherosclerotic plaques in at least one carotid artery. Lipid-rich necrotic core, ulceration, intraplaque hemorrhage, thick or thin fibrous cap, fibrous cap rupture and intraluminal thrombi were identified from multiple contrast vessel wall imaging and used to determine carotid Plaque-RADS. In addition, ancillary features including calcification and plaque burden via maximum normalized wall index (max_NWI) were collected. Degree of stenosis was classified as mild (<30%), moderate (30-69%), and severe (70-99%). Generalized Estimating Equation-based logistic regression was performed to assess the relationship between the Plaque-RADS score and cerebrovascular events.

RESULTS: A total of 433 patients (62 years ± 9.97, 302 males (69.7%)) with 866 carotid arteries were included in this study. Symptomatic carotid arteries had higher stenosis degree (11.8%±24.7 vs 8.6%±18.8, p=0.01), plaque-RADS score (≥3: 33.9% vs 28.4%, p=0.02) and max_NWI (0.53±0.14 vs 0.51±0.13, p=0.002) compared to the asymptomatic side. Plaque RADS was significantly associated with cerebrovascular events (OR=1.11 per 1-level increase, 95%CI=1.01-1.24; p=0.04). In patients with mild/moderate bilateral carotid artery stenosis, plaque RADS≥3 was significantly associated with symptomatic events (OR=1.30, 95%CI=1.01-1.68; p=0.04). Higher plaque-RADS on the symptomatic side was related to advanced age (OR=1.27 per 10-year increase, 95%CI=1.03-1.56; p=0.03), male sex (OR=1.90, 95%CI=1.05-3.43; p=0.03), and smoking history (OR=1.99, 95%CI=1.20-3.31; p=0.007).

CONCLUSIONS: Male patients of advanced age and with a smoking history were associated with an increased risk of higher plaque-RADS scores. Plaque-RADS demonstrated the ability to stratify patients experiencing cerebrovascular events, even in cases with mildto-moderate stenosis. However, this association did not retain statistical significance after adjusting for stenosis or max_NWI.

ABBREVIATIONS: IPH = intraplaque hemorrhage; Max-NWI = maximum normalized wall index; MWT = maximum wall thickness; RADS = Reporting And Data System; VWI = vessel wall imaging.},
}

@article {pmid40280142,
year = {2025},
author = {Luetkemeyer, AF and Donnell, D and Celum, C},
title = {Doxy-PEP could select for ceftriaxone resistance in Neisseria gonorrhoeae - Authors' reply.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(25)00235-X},
pmid = {40280142},
issn = {1474-4457},
}

@article {pmid40279415,
year = {2025},
author = {Freie, B and Ibrahim, AH and Carroll, PA and Bronson, RT and Augert, A and MacPherson, D and Eisenman, RN},
title = {MAX inactivation deregulates the MYC network and induces neuroendocrine neoplasia in multiple tissues.},
journal = {Science advances},
volume = {11},
number = {17},
pages = {eadt3177},
pmid = {40279415},
issn = {2375-2548},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R01 CA248762/CA/NCI NIH HHS/United States ; R35 CA231989/CA/NCI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; },
mesh = {Animals ; *Proto-Oncogene Proteins c-myc/genetics/metabolism ; Mice ; *Neuroendocrine Tumors/genetics/pathology/metabolism ; *Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; Humans ; *Gene Regulatory Networks ; Carcinoma, Neuroendocrine/genetics/pathology ; Tumor Suppressor Protein p53/genetics ; Cell Proliferation ; },
abstract = {The MYC transcription factor requires MAX for DNA binding and widespread activation of gene expression in both normal and neoplastic cells. Inactivating mutations in MAX are associated with a subset of neuroendocrine cancers including pheochromocytoma, pituitary adenoma, and small cell lung cancer. Neither the extent nor the mechanisms of MAX tumor suppression are well understood. Deleting Max across multiple mouse neuroendocrine tissues, we find that Max inactivation alone produces pituitary adenomas, while Max inactivation cooperates with Rb1/Trp53 loss to accelerate medullary thyroid C cell and pituitary adenoma development. In the thyroid tumor cell lines, MAX loss triggers a marked shift in genomic occupancy by other members of the MYC network (MNT, MLX, MondoA) supporting metabolism, survival, and proliferation of neoplastic neuroendocrine cells. Our work reveals MAX as a broad suppressor of neuroendocrine tumorigenesis through its ability to maintain a balance of genomic occupancies among the diverse transcription factors in the MYC network.},
}

Animals
*Proto-Oncogene Proteins c-myc/genetics/metabolism
Mice
*Neuroendocrine Tumors/genetics/pathology/metabolism
*Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics/metabolism
Gene Expression Regulation, Neoplastic
Cell Line, Tumor
Humans
*Gene Regulatory Networks
Carcinoma, Neuroendocrine/genetics/pathology
Tumor Suppressor Protein p53/genetics
Cell Proliferation

@article {pmid40277348,
year = {2025},
author = {Chung, Y and Cai, T and Newcomb, L and Lin, DW and Zheng, Y},
title = {Improving Efficiency and Robustness of the Prognostic Accuracy of Biomarkers With Partial Incomplete Failure-Time Data and Auxiliary Outcome: Application to Prostate Cancer Active Surveillance Study.},
journal = {Statistics in medicine},
volume = {44},
number = {8-9},
pages = {e70072},
doi = {10.1002/sim.70072},
pmid = {40277348},
issn = {1097-0258},
support = {R01 CA236558/NH/NIH HHS/United States ; U01 CA86368/NH/NIH HHS/United States ; UH3CA234196/NH/NIH HHS/United States ; R01 HL089778/NH/NIH HHS/United States ; },
mesh = {Humans ; *Prostatic Neoplasms/diagnosis/therapy ; Male ; Prognosis ; Computer Simulation ; *Biomarkers, Tumor ; Disease Progression ; Models, Statistical ; *Watchful Waiting ; Prostate-Specific Antigen/blood ; },
abstract = {When novel biomarkers are developed for the clinical management of patients diagnosed with cancer, it is critical to quantify the accuracy of a biomarker-based decision tool. The evaluation can be challenging when the definite outcome T $$ T $$ , such as time to disease progression, is only partially ascertained on a limited set of study patients. Under settings where T $$ T $$ is only observed on a subset but an auxiliary outcome correlated with T $$ T $$ is available on all subjects, we propose an augmented estimation procedure for commonly used time-dependent accuracy measures. The augmented estimators are easy to implement without imposing modeling assumptions between the two types of time-to-event outcomes and are more efficient than the complete-case estimator. When the ascertainment of the outcome is non-random and subject to informative censoring, we further augment our proposed method with inverse probability weighting to improve robustness. Results from simulation studies confirm the robustness and efficiency properties of the proposed estimators. The method is illustrated with data from the Canary Prostate Active Surveillance Study.},
}

Humans
*Prostatic Neoplasms/diagnosis/therapy
Male
Prognosis
Computer Simulation
*Biomarkers, Tumor
Disease Progression
Models, Statistical
*Watchful Waiting
Prostate-Specific Antigen/blood

@article {pmid40276374,
year = {2025},
author = {Raskin, S and de Blank, P and Billups, CA and Li, Y and Olson, JM and Leary, SES},
title = {Isotretinoin has no effect on event-free survival across high-risk medulloblastoma molecular groups when added to maintenance: A secondary analysis of the Children's Oncology Group ACNS0332 data.},
journal = {Neuro-oncology advances},
volume = {7},
number = {1},
pages = {vdaf054},
pmid = {40276374},
issn = {2632-2498},
abstract = {BACKGROUND: The Children's Oncology Group (COG) study ACNS0332 examined the effect of adding carboplatin and isotretinoin to high-risk medulloblastoma therapy. Isotretinoin arms were closed early due to futility, but the effect of carboplatin was shown to vary by individual medulloblastoma subgroups. Because isotretinoin arms were closed before subgroup classification was available, a differential effect of isotretinoin among various subgroups was not examined. Here, we conduct a secondary analysis of ACNS0332 data examining the effect of isotretinoin on event-free survival (EFS) among individual medulloblastoma subgroups.

METHODS: Among 261 patients enrolled in ACNS0332, a subgroup was evaluable in 231 patients. Fisher's exact tests and chi-square tests were used to compare distributions of categorical variables among patients with and without exposure to isotretinoin. EFS for subgroups was estimated, and the log-rank test was used to examine differences in outcome distributions among patient groups.

RESULTS: Among 231 evaluable patients, 85 were randomized to isotretinoin, 85 were randomized to no isotretinoin, and 61 received no isotretinoin without randomization. All 4 medulloblastoma groups were identified: Randomization to isotretinoin was not associated with any difference in EFS in patients with group 3 (n = 79, P = .87), group 4 (n = 101, P = .53), SHH (n = 37, P = .69) or WNT (n = 14, P = 1) medulloblastoma.

CONCLUSIONS: This study confirms that isotretinoin in addition to radiation and chemotherapy did not improve EFS in pediatric high-risk medulloblastoma regardless of molecular subgroup.},
}

@article {pmid40275643,
year = {2025},
author = {Rodriguez, CP and Wu, QV and Ng, K and Voutsinas, J and Fromm, JR and Dumenigo-Jimenez, A and Martins, RG and Eaton, KD and Santana-Davila, R and Baik, C and Lee, SM and Tseng, D and Futran, N and Barber, B and Marchiano, E and Laramore, G and Lo, SS and Liao, JJ and Parvathaneni, U},
title = {Dual PD-1 and CTLA4 Immune Checkpoint Blockade and Hypofractionated Radiation in Patients With Advanced Salivary Gland Cancers.},
journal = {Head & neck},
volume = {},
number = {},
pages = {},
doi = {10.1002/hed.28169},
pmid = {40275643},
issn = {1097-0347},
support = {//Bristol-Myers Squibb/ ; },
abstract = {BACKGROUND: No standard systemic therapy exists for recurrent/metastatic salivary gland cancer (R/M SGC). We explored the safety and activity of nivolumab and ipilimumab with palliative hypofractionated radiation (XRT) in this population.

METHODS: This Phase I/II Trial enrolled R/M SGCs with evidence of progression, ECOG 0-1, no prior anti-PD-1 or CTLA4 therapy, measurable disease excluding the XRT site. Nivolumab 3 mg/kg iv Q2 weeks × 12 doses followed by 480 mg iv Q4 weeks × 8 doses and ipilimumab 1 mg/kg iv Q6 weeks × 4 doses was given. Twenty four gray XRT was given over three fractions, 2 weeks after the first dose of nivolumab. The primary endpoint was safety; secondary endpoints included RECIST 1.1 response (non-radiated lesions), progression free, and overall survival.

RESULTS: Between April 2019 and May 2022, 20 pts. were enrolled, the median age was 58 (range 27-77 years), 10 (50%) were male, and 12 (60%) had ECOG 0. Five (20%) Grade 3 AEs were observed in three pts.; no Grade 4 or 5 toxicities were observed. Among 19 response-evaluable patients, RECIST 1.1 PRs were observed in 4 (21%), in 2 pts. with salivary duct, 1 acinic cell, and 1 adenoid cystic, SD in 6 (31.5%) and PD in 9 (47.5%). With a median follow-up of 16 months, median OS was 25 months (95% CI: [18.7, 31]) and median PFS was 7.3 months (95% CI [2.5, 18.7]).

CONCLUSION: Nivolumab/ipilimumab and palliative XRT result in low rates of severe toxicities and modest response rates for SGC; further work is necessary to explore predictors for response.},
}

@article {pmid40274741,
year = {2025},
author = {Juels, M and Larson, JC and Ensrud, KE and Stefanick, ML and Shadyab, AH and Garcia, L and Nassir, R and Schnatz, PF and Nelson, R and Crandall, CJ},
title = {Race, Ethnicity, and Mortality Following Major Osteoporotic Fracture: Results from the Women's Health Initiative Study.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
pmid = {40274741},
issn = {1525-1497},
abstract = {BACKGROUND: Major osteoporotic fracture (MOF) is associated with increased mortality; however, few studies in postmenopausal women have examined racial and ethnic differences in 1-year and 5-year mortality following MOF.

OBJECTIVE: To assess 1-year and 5-year mortality following MOF by race and ethnicity.

DESIGN: This prospective cohort study included postmenopausal women enrolled in the Women's Health Initiative (WHI), a population-based, multisite US study. Participants were followed from September 1994 to February 2023. Data were analyzed between August 2023 and November 2023.

PARTICIPANTS: Postmenopausal women aged 50 to 79 years old who experienced a MOF (N = 32,675 in 1 year and 29,506 in 5 years following MOF).

MAIN MEASURES: Self-reported race and ethnicity. All-cause mortality was determined by death certificates, reports of surrogates, and the National Death Index Search.

KEY RESULTS: The baseline mean age of participants was 77.0 [SD = 8.5] years with 31,223 [95.6%] White participants in the 1-year mortality analysis, and 76.3 [SD = 8.5] years with 28,212 [95.6%] White participants in the 5-year mortality analysis. In fully adjusted models, compared to White women, Black women had a higher risk of mortality (adjusted odds ratio (aOR) = 1.42, 95% CI [1.06, 1.90], while Asian women had a lower risk of mortality (aOR = 0.48 95% CI [0.27, 0.88]), within 1 year following MOF. Compared to White women, the mortality risk within 5 years after MOF was significantly higher among American Indian/Alaska Native (aOR = 3.30, 95% CI [1.65, 6.60]) and lower among Asian (aOR = 0.58, 95% CI [0.42,0.80]) women. While there were no mortality differences by ethnicity 1 year following MOF, Hispanic/Latina women were less likely to die 5 years following MOF (aOR = 0.74, [95% CI 0.57-0.96]) compared to Non-Hispanic/Latina women.

CONCLUSIONS: In this large prospective study, mortality following MOF differed by race. Future research is needed to delineate the mechanism behind these associations.},
}

@article {pmid40274389,
year = {2025},
author = {Chan, M and Zhu, S and Nukaya, M and Ferreira, LT and Ronnekleiv-Kelly, SM and Riehle, KJ and Scott, JD and Yeung, RS and Gujral, TS},
title = {DNAJ-PKAc fusion heightens PLK1 inhibitor sensitivity in fibrolamellar carcinoma.},
journal = {Gut},
volume = {},
number = {},
pages = {},
doi = {10.1136/gutjnl-2024-334274},
pmid = {40274389},
issn = {1468-3288},
abstract = {BACKGROUND: Fibrolamellar carcinoma (FLC), a rare and fatal liver cancer lacking effective drug therapy, is driven by the DNAJ-PKAc fusion oncoprotein. However, the underlying mechanism of DNAJ-PKAc's role in FLC tumour growth remains enigmatic.

OBJECTIVE: We sought to determine the protein kinase-mediated signalling networks that drive growth and proliferation in FLC.

DESIGN: We integrated a combination of newly established preclinical models of FLC and an unbiased polypharmacology-based approach to identify downstream kinases involved in DNAJ-PKAc-mediated FLC cell growth. We validated our findings in multiple patient-derived mouse models and patient tumours.

RESULTS: Functional screening, coupled with computational analysis, highlighted Polo-like kinase 1 (PLK1) as vital for FLC cell viability. Genetic and pharmacological PLK1 inhibition significantly reduced FLC cell growth, inducing apoptosis. Further studies showed DNAJ-PKAc's centrosomal presence and direct interaction with PLK1, revealing a novel mechanism that promotes PLK1 activation and mitotic progression. Clinical-grade PLK1 inhibitors effectively suppressed FLC tumour growth across multiple preclinical models, including patient-derived xenograft and an orthotopic model of FLC, suggesting promising therapeutic avenues.

CONCLUSION: Our findings underscore the role of DNAJ-PKAc in rewiring signalling networks and highlight valuable clinical implications for PLK1-targeted therapies for FLC.},
}

@article {pmid40274340,
year = {2025},
author = {Patel, D and Reese Koç, J and Otegbeye, F},
title = {Creating a GMP cell processing program: A focus on quality and regulation.},
journal = {Best practice & research. Clinical haematology},
volume = {38},
number = {1},
pages = {101614},
doi = {10.1016/j.beha.2025.101614},
pmid = {40274340},
issn = {1532-1924},
mesh = {Humans ; United States ; *Cell- and Tissue-Based Therapy/standards ; Quality Control ; United States Food and Drug Administration ; },
abstract = {Implementing current Good Manufacturing Practice (GMP) regulations and principles even in early phases of cell-based therapy studies is crucial for ensuring safety and reproducible quality of these products. This paper outlines the comprehensive steps necessary to establish a robust GMP-compliant cell processing program in academic programs with emphases on adherence to regulatory and quality standards. While there are different regulatory agencies governing practice across the globe, the prevailing quality principles described here incorporate common requirements and guidelines from agencies such as the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The goal of this review is to provide guidance for developing a quality management program (QMP) that addresses all critical factors impacting each step in the cell therapy product lifecycle: from procurement and receipt of starter material, through manufacturing, testing, storage, distribution, and administration. The QMP should be designed to assure quality outcomes by maintaining qualified and trained staff at all levels as applicable to their job functions; establishing clear policies and procedures; ensuring the qualification of facilities and equipment; using qualified materials for human use; and providing a framework for detection of trends and implementing process improvement.},
}

Humans
United States
*Cell- and Tissue-Based Therapy/standards
Quality Control
United States Food and Drug Administration

@article {pmid40273911,
year = {2025},
author = {Kim, WJ and Crosse, EI and De Neef, E and Etxeberria, I and Sabio, EY and Wang, E and Bewersdorf, JP and Lin, KT and Lu, SX and Belleville, A and Fox, N and Castro, C and Zhang, P and Fujino, T and Lewis, J and Rahman, J and Zhang, B and Winick, JH and Lewis, AM and Stanley, RF and DeWolf, S and Urben, BM and Takizawa, M and Krause, T and Molina, H and Chaligne, R and Koppikar, P and Molldrem, J and Gigoux, M and Merghoub, T and Daniyan, A and Chandran, SS and Greenbaum, BD and Klebanoff, CA and Bradley, RK and Abdel-Wahab, O},
title = {Mis-splicing-derived neoantigens and cognate TCRs in splicing factor mutant leukemias.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2025.03.047},
pmid = {40273911},
issn = {1097-4172},
abstract = {Mutations in RNA splicing factors are prevalent across cancers and generate recurrently mis-spliced mRNA isoforms. Here, we identified a series of bona fide neoantigens translated from highly stereotyped splicing alterations promoted by neomorphic, leukemia-associated somatic splicing machinery mutations. We utilized feature-barcoded peptide-major histocompatibility complex (MHC) dextramers to isolate neoantigen-reactive T cell receptors (TCRs) from healthy donors, patients with active myeloid malignancy, and following curative allogeneic stem cell transplant. Neoantigen-reactive CD8[+] T cells were present in the blood of patients with active cancer and had a distinct phenotype from virus-reactive T cells with evidence of impaired cytotoxic function. T cells engineered with TCRs recognizing SRSF2 mutant-induced neoantigens arising from mis-splicing events in CLK3 and RHOT2 resulted in specific recognition and cytotoxicity of SRSF2-mutant leukemia. These data identify recurrent RNA mis-splicing events as sources of actionable public neoantigens in myeloid leukemias and provide proof of concept for genetically redirecting T cells to recognize these targets.},
}

@article {pmid40272942,
year = {2025},
author = {Karvonen, KA and Vu, A and Lin, K and Gibbons, J and Mendoza, JA and Chow, EJ and Winestone, LE and Gomez, SL},
title = {Historical redlining and mortality in children, adolescents, and young adults with cancer in California, 2000-2019.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf105},
pmid = {40272942},
issn = {1460-2105},
abstract = {BACKGROUND: Historical redlining, or the Home Owners Loan Corporation (HOLC) program's racially biased mortgage risk monitoring maps in the 1930s, is implicated in shaping modern neighborhoods and health outcomes. This retrospective cohort study evaluates the association between redlining and mortality in young cancer patients.

METHODS: Using the California Cancer Registry, we identified patients <25 years old diagnosed with malignant cancer between 2000-2019. HOLC maps were spatially joined with patient address at diagnosis to determine redlining status (A "Best", B "Still Desirable", C "Declining", D "Hazardous"). Census tract-level U.S. Census and American Community Survey data were appended to determine modern neighborhood characteristics. The Kaplan-Meier method was used to evaluate overall survival and multivariable Cox proportional hazards models to estimate the associations between HOLC grade and mortality, adjusting for clinical and multilevel social drivers of health.

RESULTS: In total 8,108 patients resided in HOLC-graded neighborhoods among 51,084 patients statewide. Overall survival at 5 years was inferior for patients who resided in D graded neighborhoods at diagnosis vs A graded neighborhoods (80.3%, 95% CI: 78.6-81.8 vs 88.5%, 95% CI: 84.3-91.6). Adjusting for clinical characteristics, patients in D graded neighborhoods experienced greater mortality (HR 1.32, 95% CI: 1.12-1.56) compared with those in A and B graded neighborhoods. Additional adjustment for insurance attenuated the effect (HR 1.17, 95%CI: 1.00-1.36) and for neighborhood socioeconomic status marginally attenuated the effect (HR 0.96, 95% CI: 0.81-1.13).

CONCLUSION: Findings suggest enduring legacy effects of historical redlining on young individuals with cancer, potentially mediated social factors including health insurance.},
}

@article {pmid40272674,
year = {2025},
author = {Fest, SN and Farland, LV and Doody, DR and Eliassen, AH and Rosner, BA and Fung, TT and Hankinson, SE and Kensler, TW and Willett, WC and Harris, HR},
title = {Correction: Hormone-associated dietary patterns and premenopausal breast cancer risk.},
journal = {Breast cancer research and treatment},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10549-025-07706-6},
pmid = {40272674},
issn = {1573-7217},
}

@article {pmid40272393,
year = {2025},
author = {Prada, D and Kalia, V and Gao, F and Rexrode, K and Kooperberg, C and Reiner, A and Balasubramanian, R and Wu, HC and Crandall, CJ and Horowitz, C and Cantu-de-Leon, D and Garcia-Cuellar, C and Ramirez, A and González-Ruiz, J and Liao, D and Yanosky, J and Stewart, JD and Whitsel, EA and Baccarelli, AA},
title = {Metabolomic Evaluation of Air Pollution-related Bone Damage and Potential Mediation in Women's Health Initiative Participants.},
journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research},
volume = {},
number = {},
pages = {},
doi = {10.1093/jbmr/zjaf059},
pmid = {40272393},
issn = {1523-4681},
abstract = {Ambient air pollution has been associated with bone damage. However, no studies have evaluated the metabolomic response to air pollutants and its potential influence on bone health in postmenopausal women. We analyzed data from WHI participants with plasma samples. Whole-body, total hip, femoral neck, and spine BMD were determined using dual-energy X-ray absorptiometry (DXA) at enrollment and follow-up visits (Years 1, 3, 6, and 9 visits; Y1, Y3, Y6, Y9, respectively). Geocoded, participant address-specific, daily particulate matter nitrogen oxide (NO), nitrogen dioxide (NO2), particulate matter ≤10 μm (PM10), and sulfur dioxide (SO2) concentrations were averaged over 1-, 3-, and 5-yr periods before plasma sampling for metabolomic assessments. (at baseline and Y1 visit). The averages were then integrated using masked WHI participant identifiers. Statistical analyses included multivariable-adjusted linear mixed models, pathways analyses, and mediation modeling. At all averaging periods, NO, NO2, and SO2, but not PM10, were associated with taurine, inosine, and C38:4 phosphatidylethanolamine (PE). We found a partial potential mediation of C38:4 PE in the association between 1-yr average NO and lumbar spine BMD (p-value: 0.032). This is the first study suggesting phospholipids may partially mediate air pollution-related bone damage in postmenopausal women.},
}

@article {pmid40269324,
year = {2025},
author = {Bajunaid, R and Niu, C and Hambly, C and Liu, Z and Yamada, Y and Aleman-Mateo, H and Anderson, LJ and Arab, L and Baddou, I and Bandini, L and Bedu-Addo, K and Blaak, EE and Bouten, CVC and Brage, S and Buchowski, MS and Butte, NF and Camps, SGJA and Casper, R and Close, GL and Cooper, JA and Cooper, R and Das, SK and Davies, PSW and Dabare, P and Dugas, LR and Eaton, S and Ekelund, U and Entringer, S and Forrester, T and Fudge, BW and Gillingham, M and Goris, AH and Gurven, M and El Hamdouchi, A and Haisma, HH and Hoffman, D and Hoos, MB and Hu, S and Joonas, N and Joosen, AM and Katzmarzyk, P and Kimura, M and Kraus, WE and Kriengsinyos, W and Kuriyan, R and Kushner, RF and Lambert, EV and Lanerolle, P and Larsson, CL and Leonard, WR and Lessan, N and Löf, M and Martin, CK and Matsiko, E and Medin, AC and Morehen, JC and Morton, JP and Must, A and Neuhouser, ML and Nicklas, TA and Nyström, CD and Ojiambo, RM and Pietiläinen, KH and Pitsiladis, YP and Plange-Rhule, J and Plasqui, G and Prentice, RL and Racette, SB and Raichlen, DA and Ravussin, E and Redman, LM and Reilly, JJ and Reynolds, R and Roberts, SB and Samaranayakem, D and Sardinha, LB and Silva, AM and Sjödin, AM and Stamatiou, M and Stice, E and Urlacher, SS and Van Etten, LM and van Mil, EGAH and Wilson, G and Yanovski, JA and Yoshida, T and Zhang, X and Murphy-Alford, AJ and Sinha, S and Loechl, CU and Luke, AH and Pontzer, H and Rood, J and Sagayama, H and Schoeller, DA and Westerterp, KR and Wong, WW and Speakman, JR},
title = {Author Correction: Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake.},
journal = {Nature food},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43016-025-01175-2},
pmid = {40269324},
issn = {2662-1355},
}