tbuckley/cabot-search huggingface dataset:
A kidney organoid-based readout to assess disease activity in primary and recurrent focal segmental glomerulosclerosis
Authors: Ashwani Kumar Gupta, Ekta Minocha, Kyle M Koss, Bilal A Naved, Luisa Safar-Boueri, Jason A Wertheim, Lorenzo Gallon
Journal: Kidney International (2025)

Primary Focal Segmental Glomerulosclerosis (pFSGS) is an acquired kidney disorder that frequently leads to kidney failure and confers an elevated risk of recurrence after kidney transplantation, termed recurrent pFSGS. Unfortunately, there is no diagnostic method to foresee recurrence of pFSGS after kidney transplantation. Progress in developing assays to test disease activity is hampered by few preclinical models to replicate disease and inability of in vitro cultured primary podocytes to remain terminally differentiated. In recent years, advancements in kidney organoid biology have led to the development of kidney tissues with glomeruli and major nephron segments including podocytes. To develop a pFSGS model, we studied the effect of plasma from patients diagnosed with pFSGS on kidney organoids differentiated from human pluripotent stem cells. The pFSGS plasma treatment induced podocytopathy, extracellular matrix protein deposition, fibrosis and apoptosis within organoids, whereas non-recurrent plasma did not affect organoid structure. pFSGS plasma also led to loss of normal expression patterns of podocyte specific proteins, nephrin and podocin within podocytes. Further, cytokine array profiling revealed that pFSGS plasma induced secretion of cytokines associated with inflammation and angiogenesis. Additionally, kidney organoids treated with plasma obtained after therapeutic plasma exchange for recurrent pFSGS led to lower cell death in organoids after sequential exchanges with the final exchange showing the least apoptotic cells without morphological abnormality. Overall, our results demonstrate the potential of kidney organoids in advancing kidney disease modeling. These insights could be applied in clinical settings to assist in gauging FSGS recurrence risk prior to kidney transplantation.
Safety and efficacy of repeat ivermectin mass drug administrations for malaria control (RIMDAMAL II): a phase 3, double-blind, placebo-controlled, cluster-randomised, parallel-group trial
Authors: A Fabrice Somé, Anthony Somé, Emmanuel Sougué, Cheick Oumar W Ouédraogo, Ollo Da, S Rodrigue Dah, Frederic Nikièma, Tereza Magalhaes, Lyndsey I Gray, Will Finical, Greg Pugh, Paula Lado, Jenna C Randall, Timothy A Burton, Molly E Ring, Anna-Sophia Leon, McKenzie Colt, Fangyong Li, Kaicheng Wang, Martina Wade, Audun J Lier, Kacey Richards, Hannah Sproch, Elizabeth Zhang, Julia Ellman, Ijeamaka Achebe, Conner L Jackson, Mengli Xiao, Emma J Wu, Teun Bousema, Hannah C Slater, Brian D Foy, Sunil Parikh, Roch K Dabiré
Journal: The Lancet Infectious Diseases (2025)
Acute pulmonary embolism in children and adolescents in the USA (2016 and 2019): a nationwide retrospective cohort study
Authors: Simon Wolf, Luca Valerio, Nils Kucher, Stavros V Konstantinides, Irene L M Klaassen, C Heleen van Ommen, Cihan Ay, Frederikus A Klok, Suzanne C Cannegieter, Stefano Barco
Journal: The Lancet Respiratory Medicine (2025)

SummaryBackgroundEpidemiological data on acute pulmonary embolism among children and adolescents are sparse and only date back to the 2000s. We aimed to establish annual estimates and age-stratified and sex-stratified indicators of acute pulmonary embolism among children and adolescents aged 0–19 years.MethodsWe did a retrospective, nationwide, patient-level analysis of the Kids' Inpatient Database, including 5733 patients with acute pulmonary embolism aged 0–19 years admitted to hospital in the USA in 2016 and 2019. The database includes data of all children admitted to hospital during the 2 years available. We also accessed the US Multiple Cause of Death database and population data from the US Census Bureau for the same 2 years. We estimated the incidence, mortality, case fatality, and proportional mortality rates, provided data on the annual pulmonary embolism burden, and provided data on clinical events recorded during hospitalisation.FindingsIn the years 2016 and 2019, 5733 patients (3353 [58.5%] female and 2380 [41.5%] male) were admitted to hospital with acute pulmonary embolism as the primary diagnosis or a concomitant diagnosis. The annual incidence of acute pulmonary embolism was 3·5 (95% CI 3·4–3·6) per 100 000 people. Two peaks in the incidence rate were observed—one in infants younger than 1 year and one in adolescents aged 15–19 years. The in-hospital case fatality rate was 4·5% (4·0–5·1). The crude odds ratio for in-hospital death among patients with (vs without) acute pulmonary embolism was 9·3 (7·9–10·9). The association between acute pulmonary embolism and death persisted across different multivariable models. Patients with acute pulmonary embolism with high-risk (vs no high-risk) features had the highest risk of death: 25·3% (20·6–30·5) among patients aged 0–9 years and 13·9% (11·9–16·2) among patients aged 10–19 years. In patients without high-risk features, risk of death was 4·9% (3·1–7·6) among patients aged 0–9 years and 0·7% (0·5–1·0) among patients aged 10–19 years. The risk of intracranial bleeding was also highest in the presence of pulmonary embolism with high-risk features: 8·1% (5·5–11·7) among patients aged 0–9 years and 3·6% (2·6–4·9) among patients aged 10–19 years. In patients without high-risk features, the risk of intracranial bleeding was 2·5% (1·3–4·6) among those aged 0–9 years and 0·5% (0·3–0·8) in those aged 10–19 years. Reperfusion treatments beyond systemic thrombolysis were rarely used among children and adolescents with acute pulmonary embolism.InterpretationAcute pulmonary embolism is rare during childhood and adolescence. The high pulmonary embolism-related fatality among specific subgroups of patients can be interpreted in the context of severe comorbidities and pulmonary embolism events with high-risk features.FundingNone.
KP.2-based monovalent mRNA vaccines robustly boost antibody responses to SARS-CoV-2
Authors: Qian Wang, Ian A Mellis, Madeline Wu, Anthony Bowen, Carmen Gherasim, Riccardo Valdez, Jayesh G Shah, Lawrence J Purpura, Michael T Yin, Aubree Gordon, Yicheng Guo, David D Ho
Journal: The Lancet Infectious Diseases (2025)
Costs and outcomes of routine HIV oral pre-exposure prophylaxis implementation across different service delivery models and key populations in South Africa: a retrospective cohort study
Authors: Cheryl Hendrickson, Kamban Hirasen, Constance Mongwenyana, Mariet Benade, Rutendo Bothma, Chantal Smith, Johan Meyer, Brooke E Nichols, Lawrence C Long
Journal: The Lancet HIV (2025)
Haploidentical peripheral blood stem cells combined with bone marrow or unrelated cord blood as grafts for haematological malignancies: an open-label, multicentre, randomised, phase 3 trial
Authors: Sijian Yu, Fen Huang, Na Xu, Zhongming Zhang, Can Liu, Xiaojun Xu, Zhiping Fan, Xiangzong Zeng, Qiong Liu, Guo Qiu, Xu Xi, Ren Lin, Xinquan Liang, Yirong Jiang, Min Dai, Hua Jin, Xiaofang Li, Shunqing Wang, Meiqing Wu, Jing Sun, Li Xuan, Qifa Liu
Journal: The Lancet Haematology (2025)
School phone policies and their association with mental wellbeing, phone use, and social media use (SMART Schools): a cross-sectional observational study
Authors: Victoria A. Goodyear, Amie Randhawa, Péymane Adab, Hareth Al-Janabi, Sally Fenton, Kirsty Jones, Maria Michail, Breanna Morrison, Paul Patterson, Jonathan Quinlan, Alice Sitch, Rebecca Twardochleb, Matthew Wade, Miranda Pallan
Journal: The Lancet Regional Health - Europe (2025)

SummaryBackgroundPoor mental health in adolescents can negatively affect sleep, physical activity and academic performance, and is attributed by some to increasing mobile phone use. Many countries have introduced policies to restrict phone use in schools to improve health and educational outcomes. The SMART Schools study evaluated the impact of school phone policies by comparing outcomes in adolescents who attended schools that restrict and permit phone use.MethodsWe conducted a cross-sectional observational study with adolescents from 30 English secondary schools, comprising 20 with restrictive (recreational phone use is not permitted) and 10 with permissive (recreational phone use is permitted) policies. The primary outcome was mental wellbeing (assessed using Warwick–Edinburgh Mental Well-Being Scale [WEMWBS]). Secondary outcomes included smartphone and social media time. Mixed effects linear regression models were used to explore associations between school phone policy and participant outcomes, and between phone and social media use time and participant outcomes. Study registration: ISRCTN77948572.FindingsWe recruited 1227 participants (age 12–15) across 30 schools. Mean WEMWBS score was 47 (SD = 9) with no evidence of a difference between groups (adjusted mean difference −0.48, 95% CI −2.05 to 1.06, p = 0.62). Adolescents attending schools with restrictive, compared to permissive policies had lower phone (adjusted mean difference −0.67 h, 95% CI −0.92 to −0.43, p = 0.00024) and social media time (adjusted mean difference −0.54 h, 95% CI −0.74 to −0.36, p = 0.00018) during school time, but there was no evidence for differences when comparing usage time on weekdays or weekends.InterpretationThere is no evidence that restrictive school policies are associated with overall phone and social media use or better mental wellbeing in adolescents. The findings do not provide evidence to support the use of school policies that prohibit phone use during the school day in their current form, and indicate that these policies require further development.FundingPublic Health Research Programme, National Institute for Health and Care Research, Department of Health and Social Care, UK.
Author Correction: Artificial intelligence guided screening for cardiomyopathies in an obstetric population: a pragmatic randomized clinical trial
Authors: Demilade A. Adedinsewo, Andrea Carolina Morales-Lara, Bosede B. Afolabi, Oyewole A. Kushimo, Amam C. Mbakwem, Kehinde F. Ibiyemi, James Ayodele Ogunmodede, Hadijat Olaide Raji, Sadiq H. Ringim, Abdullahi A. Habib, Sabiu M. Hamza, Okechukwu S. Ogah, Gbolahan Obajimi, Olugbenga Oluseun Saanu, Olusoji E. Jagun, Francisca O. Inofomoh, Temitope Adeolu, Kamilu M. Karaye, Sule A. Gaya, Isiaka Alfa, Cynthia Yohanna, K. L. Venkatachalam, Jennifer Dugan, Xiaoxi Yao, Hanna J. Sledge, Patrick W. Johnson, Mikolaj A. Wieczorek, Zachi I. Attia, Sabrina D. Phillips, Mohamad H. Yamani, Yvonne Butler Tobah, Carl H. Rose, Emily E. Sharpe, Francisco Lopez-Jimenez, Paul A. Friedman, Peter A. Noseworthy, Rickey E. Carter
Journal: Nature Medicine (2025)
Understanding the molecular bridges between the drugs and immune cell
Authors: Umesh Chandra Dash, Vinayak Nayak, Hiten Shanker Navani, Rashmi Rekha Samal, Palak Agrawal, Anup Kumar Singh, Sanatan Majhi, Devraj Ganpat Mogare, Asim K Duttaroy, Atala Bihari Jena
Journal: Pharmacology & Therapeutics (2025)
Assessment and Management of Patients at Risk for Suicide: Synopsis of the 2024 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guidelines
Authors: Lisa A. Brenner, Vince Capaldi, Joseph Constans, Steven Dobscha, Matthew Fuller, Bridget Matarazzo, Kate McGraw, Kenneth Richter, James Sall, Derek Smolenski, Scott Williams, Sarah Davis-Arnold, Nazanin Bahraini
Journal: Annals of Internal Medicine (2025)

The U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DOD) updated the 2019 joint clinical practice guideline (CPG) for assessing and managing patients who are at risk for suicide. This synopsis provides primary care physicians with a summary of the updated 2024 recommendations regarding evaluation and management of military members and veterans at risk for suicide. In 2023, the VA/DOD Evidence-Based Practice Work Group convened to develop a joint VA/DOD guideline, including clinical stakeholders, which conformed to the National Academy of Medicine's tenets for trustworthy CPGs. The Work Group drafted 12 key questions, reviewed systematically identified literature (1 April 2018 to 15 March 2023), evaluated the evidence, created algorithms, and advanced 24 recommendations in accordance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Despite insufficient evidence to recommend for or against suicide risk screening programs as a means for reducing suicide attempts or deaths, the VA/DOD Work Group identified validated tools that could be used to identify populations at higher risk for suicide-related behaviors. Cognitive behavioral therapy was also recommended for reducing the risk for suicide attempts and decreasing suicidal ideation among those with a history of suicidal behavior or a history of self-directed violence. Periodic communications after previous suicide attempts were also recommended as a prevention strategy. Pharmacologic treatments, such as clozapine or ketamine infusion, also have a role in the management of suicide risk among those with schizophrenia or major depressive disorder, respectively.
JMJD6 Rewires ATF4-Dependent Glutathione Metabolism to Confer Ferroptosis Resistance in SPOP-Mutated Prostate Cancer
Authors: Chuanjie Zhang, Jiawei Ding, Kiat Shenq Lim, Wenjie Zhou, Wenyu Miao, Siqi Wu, Hanqing Liu, Da Huang, Chufeng Chen, Hongchao He, Jun Xiao, Dan-feng Xu, Yan Shen, Hai Huang, Yi Gao
Journal: Cancer Research (2025)

Abstract Ferroptosis inducers have shown therapeutic potential in prostate cancer (PCa), but tumor heterogeneity poses a barrier to their efficacy. Distinguishing the regulators orchestrating metabolic crosstalk between cancer cells could shed light on therapeutic strategies to more robustly activate ferroptosis. Here, we found that aberrant accumulation of jumonji domain containing 6 (JMJD6) proteins correlated with poorer prognosis of PCa patients. Mechanistically, PCa-associated speckle type BTB/POZ protein (SPOP) mutants impaired the proteasomal degradation of JMJD6 proteins. Elevated JMJD6 and ATF4 coordinated enhancer-promoter loop interactions to stimulate the glutathione biosynthesis pathway. Independent of androgen receptor, JMJD6 recruited mediator subunits (Med1/14) to assemble de novo enhancers mapping to pivotal genes associated with glutathione metabolism, including SLC7A11, GCLM, ME1, and others. SPOP mutations thus induced intrinsic resistance to ferroptosis, dependent on enhanced JMJD6-ATF4 activity. Consequently, targeting JMJD6 rendered SPOP-mutated PCa selectively sensitive to ferroptosis. The JMJD6 antagonist SKLB325 synergized with erastin in multiple pre-clinical PCa models. Together, this study identifies JMJD6 as a druggable vulnerability in SPOP-mutated PCa to increase sensitivity to ferroptosis inducers.
Comparison of pharmacological therapies in metabolic dysfunction-associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis
Authors: Matheus Souza, Lubna Al-Sharif, Vanio L J. Antunes, Daniel Q. Huang, Rohit Loomba
Journal: Hepatology (2025)

Background and Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of liver disease. With the advent of multiple therapeutic targets in late-phase clinical drug development for MASH, there is a knowledge gap to better understand the comparative efficacy of various pharmacological agents. We conducted an updated network meta-analysis to evaluate the relative rank-order of the different pharmacological agents for both fibrosis regression and MASH resolution. Methods: We searched PubMed and Embase databases from 2020 to December 1, 2024, for published randomized-controlled trials (RCTs) comparing pharmacological interventions in patients with biopsy-proven MASH. The co-primary endpoints were fibrosis improvement ≥1 stage without MASH worsening and MASH resolution without worsening fibrosis. We conducted surface under the cumulative ranking (SUCRA) curve analysis. Results: A total of 29 RCTs (n=9324) were included. Pegozafermin, cilofexor + firsocostat, denifanstat, survodutide, obeticholic acid, tirzepatide, resmetirom, and semaglutide were significantly better than placebo in achieving fibrosis regression without worsening MASH. Pegozafermin (SUCRA: 79.92), cilofexor + firsocostat (SUCRA: 71.38), and cilofexor + selonsertib (SUCRA: 69.11) were ranked the most effective interventions. Pegozafermin, survodutide, tirzepatide, efruxifermin, liraglutide, vitamin E + pioglitazone, resmetirom, semaglutide, pioglitazone, denifanstat, semaglutide and lanifibranor were significantly better than placebo in achieving MASH resolution without worsening fibrosis. Pegozafermin (SUCRA: 91.75), survodutide (SUCRA: 90.87), and tirzepatide (SUCRA: 84.70) were ranked the most effective interventions for achieving MASH resolution without worsening fibrosis. Conclusion: This study provides updated rank-order efficacy of MASH pharmacological therapies for fibrosis regression and MASH resolution. These data are helpful to inform practice and clinical trial design.
Characterization of an Enhancer RNA Signature Reveals Treatment Strategies for Improving Immunotherapy Efficacy in Cancer
Authors: Chenyang Zhang, Yan-Yan Chen, Shuyu Chen, Yunzhe Wang, Yifan Yuan, Xiwen Yang, Wei Hu, Bo Chen, Zengxin Qi, Jason T. Huse, Yun Liu, Bo Wen, Xiuping Liu, Leng Han, Yuxiang Wang, Zhao Zhang
Journal: Cancer Research (2025)

Abstract Non-coding RNA transcribed from active enhancers, known as enhancer RNA (eRNA), is a critical element in gene regulation with a highly specific expression pattern in the regulatory networks of tumor-infiltrating cells. Therefore, eRNA signatures could potentially be applied to represent anti-tumor immune cells and to improve cancer immunotherapy. Herein, we identified thousands of eRNAs that were significantly correlated with infiltrating immune cell abundance in more than 10,000 patient samples across a variety of cancer types. The expression of these eRNAs was mediated by transcription factors with high expression in anti-tumor immune cells, as identified through single-cell assays. An eRNA immunotherapy signature (eRIS) developed using the anti-tumor eRNAs was highly associated with the objective response rate (ORR) of immunotherapy and was elevated in patients who benefited from immune checkpoint blockade (ICB) treatment. In comparison with a signature based on protein-coding genes, the eRIS was more effective in predicting the response to immunotherapy. Integration of the eRIS with pharmacogenomic data revealed hundreds of anti-cancer drugs that have the potential to enhance immunotherapy efficacy. Finally, treatment of a mouse model of IDH mutant glioma with the histone deacetylase inhibitor vorinostat improved the effects of anti-PD-1 immunotherapy through increased abundance of infiltrating immune cells. Taken together, this study developed an eRIS with demonstrated efficacy in predicting immunotherapy response and used the eRIS to identify a series of effective combination drugs, thus highlighting the clinical utility of the eRIS in immunotherapy enhancement.
Effectiveness of the 2023-to-2024 XBB.1.5 COVID-19 Vaccines Over Long-Term Follow-up
Authors: George N. Ioannou, Kristin Berry, Nallakkandi Rajeevan, Yuli Li, Lei Yan, Yuan Huang, Hung-Mo Lin, David Bui, Denise M. Hynes, Mazhgan Rowneki, Amy Bohnert, Edward J. Boyko, Theodore J. Iwashyna, Matthew L. Maciejewski, Valerie A. Smith, Theodore S.Z. Berkowitz, Ann M. O’Hare, Elizabeth M. Viglianti, Mihaela Aslan, Kristina L. Bajema
Journal: Annals of Internal Medicine (2025)

Monovalent COVID-19 vaccines targeting the XBB.1.5 Omicron variant were introduced in September 2023. In the absence of randomized controlled trials demonstrating their efficacy, information on real-world vaccine effectiveness (VE) is needed. To determine XBB.1.5 COVID-19 VE and the extent to which it declines over time. Target trial emulation. U.S. Veterans Health Administration. Eligible XBB.1.5 vaccine recipients were matched 1:1 to unvaccinated persons in 7 sequential biweekly trials with enrollment from 2 October 2023 through 3 January 2024. XBB.1.5 COVID-19 vaccination versus no XBB.1.5 vaccination. Outcomes were ascertained through 10 May 2024 and included any positive result on a SARS-CoV-2 test from day 10 after the matched index date, subsequent hospitalization within 1 day before or 10 days after the positive result, or death within 30 days after the positive result. Vaccine effectiveness was estimated as 100 × (1 - risk ratio). Participants (91.3% male; mean age, 69.9 years) included 587 137 pairs of vaccinated and matched unvaccinated persons. Over a mean follow-up of 176 days (range, 118 to 211 days), VE was -3.26% (95% CI, -6.78% to -0.22%) against documented SARS-CoV-2 infection, 16.64% (CI, 6.47% to 25.77%) against SARS-CoV-2-associated hospitalization, and 26.61% (CI, 5.53% to 42.32%) against SARS-CoV-2-associated death. When estimated at 60, 90, and 120 days, respectively, VE against documented infection (14.21%, 7.29%, and 3.15%), hospitalization (37.57%, 30.84%, and 25.25%), or death (54.24%, 44.33%, and 30.25%) showed substantial waning. Potential for residual confounding and incomplete capture of COVID-19 vaccination and SARS-CoV-2-related outcomes. COVID-19 vaccines targeting the XBB.1.5 variant of Omicron were not effective in preventing infection and had relatively low VE against hospitalization and death, which declined rapidly over time. U.S. Department of Veterans Affairs.
SGLT2i Therapy Prevents Anthracycline-Induced Cardiotoxicity in a Large Animal Model by Preserving Myocardial Energetics
Authors: Danielle Medina-Hernández, Laura Cádiz, Annalaura Mastrangelo, Andrea Moreno-Arciniegas, Miguel Fernández Tocino, Alejandro A Cueto Becerra, Anabel Díaz-Guerra Priego, Warren A Skoza, María Isabel Higuero-Verdejo, Gonzalo Javier López-Martín, Claudia Pérez-Martínez, Antonio de Molina-Iracheta, María Caballero-Valderrama, Javier Sánchez-González, David Sancho, Valentin Fuster, Carlos Galán-Arriola, Borja Ibáñez
Journal: JACC CardioOncology (2025)
Genomic landscape of clinically acquired resistance alterations in patients treated with KRASG12C inhibitors
Authors: J M Riedl, F Fece de la Cruz, J J Lin, C Parseghian, J E Kim, H Matsubara, H Barnes, B Caughey, B L Norden, A A Morales-Giron, E W Kushner, S Ehnstrom, H Nakamura, P S Patel, H Ellis, L Pappas, A Vakaris, J F Gainor, S Kopetz, S J Klempner, A R Parikh, A N Hata, R S Heist, R B Corcoran
Journal: Annals of Oncology (2025)
Whole genome sequencing powered ctDNA sequencing for breast cancer detection
Authors: I Garcia-Murillas, C W Abbott, R J Cutts, S M Boyle, J Pugh, K C Keough, B Li, R M Pyke, F C P Navarro, R O Chen, K Dunne, C Bunce, S R D Johnston, A Ring, S Russell, A Evans, A Skene, I E Smith, N C Turner
Journal: Annals of Oncology (2025)
Stigmatizing Substance Use Terminology in Grant Abstracts Following High-Level Language Guidance
Authors: Evan L. Eschliman, Haruka Kokaze, Long Jie Huang, Karen Choe, Pia M. Mauro
Journal: JAMA Network Open (2025)

This cross-sectional study examines the use of stigmatizing terms in US grants funded by the National Institute on Drug Abuse following changes to official guidance on the language of substance use disorders in 2017 and 2021.