tbuckley/cabot-search huggingface dataset:
Visualizing GSH‐ONOO<sup>−</sup> Redox and Tracking Lesion‐Remedy of Acute Kidney Oxidative Injury Based on a Dual‐Site Chemosensor
Authors: Meili Yang, Zuzhe Kang, Xinpei Zhong, Sirui Bai, Dong‐En Wang, Qin Tu, Sheng Chen, Jinyi Wang, Mao‐Sen Yuan
Journal: Advanced Healthcare Materials (2025)

Abstract Drug‐induced acute kidney injury (DIAKI) is strongly associated with the accumulation of peroxynitrite (ONOO − ) and the depletion of glutathione (GSH), both of which contribute to increased morbidity and mortality. Owing to the lack of an effective method for the real‐time monitoring of nephrotoxicity, it remains a diagnostic and therapeutic challenge and is considered a significant issue in clinical practice. Herein, a dual‐site fluorescent chemosensor, BPS is developed , which enables the simultaneous real‐time monitoring of ONOO − and GSH through distinct channels (ONOO − : λ ex = 410 nm, λ em = 548 nm; GSH: λ ex = 490 nm, λ em = 660 nm) without spectral crosstalk. The sensor displays remarkable sensitivity toward ONOO − and GSH, with low detection limits (181 n m and 2.42 µ m , respectively), exceptional specificity, and anti‐interference effects. BPS is used to monitor ONOO − /GSH in real time to track the lesion of cisplatin‐stimulated DIAKI and the following remedy process in mice and HK‐2 cells for the first time. BPS provides a feasible tool for investigating oxidative stress‐related DIAKI disease processes and further exploring some physiological mechanisms. Moreover, this study also offers a strategy for visualizing, modulating, and controlling the intracellular GSH/ONOO − redox.
Brief Report: Successful Pregnancy and Healthy Baby Outcome in a TKI-refractory ALK+ NSCLC Patient with CNS Metastasis Treated with Lorlatinib with Maternal-fetal Pharmacokinetics and Child Milestone Development Correlations
Authors: Zhuoran Yao, Min Tang, Ying Jin, Jie Ruan, Yong Hu, Hua Xie, Zhenlei Wang, Lisha Fu, Xing Huang, Xiaojuan Zhou, Bingwen Zou, Geofrrey Liu, Li Zheng, You Lu
Journal: Journal of Thoracic Oncology (2025)
Splicing of erythroid transcription factor is associated with therapeutic response in myelodysplastic syndromes
Authors: Srinivas Aluri, Te Ling, Ellen Fraint, Samarpana Chakraborty, Kevin Zhang, Aarif Ahsan, Leah Kravets, Gowri Poigaialwar, Rongbao Zhao, Kith Pradhan, Anitria Cotton, Kimo Bachiashvili, Jung-In Yang, Anjali Budhathoki, Beamon Agarwal, Shanisha Gordon-Mitchell, Milagros Carbajal, Srabani Sahu, Jacqueline Boultwood, Andrea Pellagatti, Ulrich Steidl, Amittha Wickrema, Satish Nandakumar, Aditi Shastri, Rajasekhar Nvs Suragani, Teresa V Bowman, John D Crispino, Sadanand Vodala, Amit Verma
Journal: Journal of Clinical Investigation (2025)

Anemia is the primary clinical manifestation of myelodysplastic syndromes (MDS), but the molecular pathogenesis of ineffective erythropoiesis remains incompletely understood. Luspatercept, an activin receptor 2B (ACVRIIB-Fc) ligand trap, has been approved to treat anemia, however its molecular mechanism of action is unclear. We found that the ACVR2B, its ligand GDF11, and effector, SMAD2, are upregulated in MDS patient samples. GDF11 inhibited human erythropoiesis in vitro and caused anemia in zebrafish, effects that were abrogated by luspatercept. Upon GDF11 stimulation of human erythroid progenitors, SMAD2 binding occurred in the erythroid regulatory regions, including at GATA1 intron. Intronic SMAD2 binding led to skipping of exon 2 of GATA1, resulting in a shorter, hypomorphic isoform (GATA1s). CRISPR deletion of the SMAD2 binding intronic region decreased GATA1s production upon GDF11 stimulation. Expression of gata1s in a mouse model led to anemia, rescued by a murine ActRIIB-Fc (RAP-536). Finally, RNA-seq analysis of samples from the Phase 3 MEDALIST trial revealed that responders to Luspatercept had a higher proportion of GATA1s compared to non-responders. Moreover, the increase RBCs post-treatment was linked to a relative decrease in GATA1s isoform. Our study indicates that GDF11-mediated SMAD2 activation results in an increase in functionally impaired GATA1 isoforms, consequently contributing to anemia and influencing responses to Luspatercept in MDS.
Efficacy and safety of dupilumab in pediatric patients aged 6 months to 11 years with erythrodermic atopic dermatitis: A post-hoc analysis of three clinical trials
Authors: Amy S. Paller, Elaine C. Siegfried, Michael J. Cork, Kenji Kabashima, Peter D. Arkwright, Edyta Gębska, Zhen Chen, Joseph Zahn, Ana B. Rossi
Journal: Journal of the American Academy of Dermatology (2025)
A novel cationic liposome-formulated toll like receptor (TLR)7/8 agonist enhances the efficacy of a vaccine against fentanyl toxicity
Authors: Fatima A. Hamid, Nguyet-Minh Nguyen Le, Daihyun Song, Hardik Amin, Linda Hicks, Sophia Bird, Karthik Siram, Brooke Hoppe, Borries Demeler, Jay T. Evans, David Burkhart, Marco Pravetoni
Journal: Journal of Controlled Release (2025)
β-Cell Function Derived From Routine Clinical Measures Reports and Predicts Treatment Response to Immunotherapy in Recent-Onset Type 1 Diabetes
Authors: Michelle So, Sara Vogrin, Michaela Waibel, Thomas W.H. Kay, John M. Wentworth
Journal: Diabetes Care (2025)

OBJECTIVE Baricitinib preserves β-cell function in people with recently diagnosed type 1 diabetes. We aimed to determine whether simple routine clinical measures could be used to assess β-cell preservation and predict treatment response. RESEARCH DESIGNS AND METHOD Measures of β-cell function derived from clinical and biochemical measures were calculated using data from the BAricitinib in Newly DIagnosed Type 1 diabetes (BANDIT) randomized trial of baricitinib in recent-onset type 1 diabetes. Measures that reported and predicted treatment efficacy were determined using linear regression and receiver operator characteristic analysis, respectively. Therapeutic predictors were validated using data from trials of rituximab, abatacept, and antithymocyte globulin. RESULTS Quantitative response score (QRS), fasting C-peptide, and model-estimated C-peptide (CPest) most reliably differentiated placebo-treated from baricitinib-treated participants at 24 and 48 weeks. The Beta2 score, derived from fasting glucose, C-peptide, HbA1c, and insulin dose at 12 weeks, was optimal for predicting QRS &amp;gt;0 following 1 year of treatment with baricitinib and the other immunotherapies (areas under receiver operator curve 0.864 and 0.765, respectively). A 6.2% decrease in the Beta2 score at week 12 predicted significant improvement in HbA1c (−0.6% or −6 mmol/mol) and insulin use (−0.26 units/kg/day) in combined data from the rituximab, abatacept, and antithymocyte globulin trials. CONCLUSIONS QRS, fasting C-peptide, and CPest could be used as more efficient, less burdensome primary outcome measures for future immunotherapy trials. The ability of the Beta2 score to predict treatment responses could facilitate adaptive trial designs and help guide treatment decisions in the clinic.
Characterization of Pro‐Drug Metabolism and Drug Permeability Kinetics in a Microphysiological In Vitro Model of the Human Small Intestinal Barrier Incorporating Mucus‐Generating Cells Coupled with LC‐MS/MS Analysis
Authors: Sultan K. AlShmmari, Roa S. Fardous, Mohammed A. ALHamamah, Dana Cialla‐May, Jürgen Popp, Qasem Ramadan, Mohammed Zourob
Journal: Advanced Healthcare Materials (2025)

Abstract A micro‐physiological model of the human small intestinal barrier incorporating mucus‐generating cells has been developed. The established barrier was utilized to assess the absorption kinetics of three selected therapeutic compounds: Doxycycline, Ganciclovir, and its prodrug Valganciclovir, following the implementation of a thorough LC‐MS/MS validation protocol. The co‐culture of Caco‐2 cells, representing absorptive enterocytes, and HT‐29 MTX cells, modeling goblet cells, enabled the in‐situ generation of a sufficiently thick mucus layer covering the entire cell monolayer. The presence of HT‐29 MTX cells, which exhibit weaker tight junctions than enterocytes, contributed to the observed lower transepithelial electrical resistance (TEER) and higher FITC‐dextran flux. The permeability of all the compounds was higher when tested in the co‐culture system containing mucus‐generating cells, compared to the Caco‐2 monoculture, demonstrating the impact of mucus on intestinal drug transport kinetics. The permeability of ganciclovir following its generation from the prodrug valganciclovir was significantly higher than the permeability of ganciclovir itself, as the active metabolite ganciclovir exhibited an enhanced transport rate compared to when administered without metabolic activation. The developed microfluidic‐based intestinal barrier model has demonstrated the capability to reliably simulate drug absorption and prodrug metabolism, and its impact on drug permeation kinetics across the small intestine.
A village doctor-led mobile health intervention for cardiovascular risk reduction in rural China: cluster randomised controlled trial
Authors: Xingyi Zhang, Siming Wang, Xingyu Zhou, Yajie Tang, Liying Xing, Shaoning Ma, Yan Xu, Chaoqun Wu, Jianlan Cui, Yang Yang, Chunying Lin, Yi Wu, Haibo Zhang, Lei Fan, Chunxiao Xu, Xi Li
Journal: BMJ (2025)

Abstract Objective To assess the effectiveness of a village doctor-led mobile health intervention on cardiovascular risk reduction among residents in rural China. Design Cluster randomised controlled trial. Setting 127 villages from five provinces and autonomous regions in China. Participants 4533 participants from 127 villages: 2297 (64 villages) were randomly assigned to the intervention group and 2236 (63 villages) to the control group. Participants were aged ≥35 years, had no established atherosclerotic cardiovascular disease (ASCVD) but a predicted 10 year risk of ≥10%, had contracted a family doctor service with the local village doctor, and owned a smart phone. Interventions In addition to usual clinical care and basic public health services provided for the control group, the intervention led by village doctors included five components: assessing risk factors to identify individualised intervention targets, setting gradual goals based on doctor-participant communication, providing targeted short videos on health education, conducting health monitoring with periodic feedback, and providing motivation to reduce risk based on gamification. Main outcome measure Mean change in predicted 10 year risk of ASCVD from baseline to 12 months. Results Enrolment took place between March 2023 and May 2023. During the 12 month follow-up (completion rate 99.4%), the 10 year risk of ASCVD decreased from 18.0% to 11.7% in the intervention group and from 17.8% to 13.6% in the control group (absolute difference −1.88% (95% confidence interval (CI) −2.57% to −1.19%; P&lt;0.001). Compared with the control group, the intervention group showed larger reductions in lifetime ASCVD risk (−15.9% v −11.0%; difference −4.59%; Plt;0.001), systolic blood pressure (−23.2 mm Hg v −15.2 mm Hg; difference −7.64 mm Hg; Plt;0.001), diastolic blood pressure (−10.9 mm Hg v −6.9 mm Hg; difference: −3.59 mm Hg; Plt;0.001), fasting blood glucose (−0.9 mmol/L v −0.5 mmol/L; difference −0.30 mmol/L; P=0.008), proportion of daily smokers (−3.1% v −0.6%; odds ratio 0.60, 95% CI 0.43 to 0.84; P=0.003), and insufficient physical activity (−3.0% v 1.3%; odds ratio 0.63, 0.42 to 0.95; P=0.03). No significant differences were observed for change in non-high density lipoprotein cholesterol or proportion of participants with obesity. Conclusions The village doctor-led mobile health intervention was effective at reducing cardiovascular risk and improving control of behavioural and metabolic risk factors. This feasible approach could be scaled up in rural China and other under-resourced settings to improve health management based on the local primary healthcare system. Trial registration ClinicalTrials.gov NCT05645640 .
Current management of hypertrophic cardiomyopathy
Authors: Nikhil Sikand, John Stendahl, Sounok Sen, Rachel Lampert, Sharlene Day
Journal: BMJ (2025)

ABSTRACT Hypertrophic cardiomyopathy is a common yet under-recognized genetic structural heart condition characterized by left ventricular hypertrophy. Patients may present with obstructive disease characterized by an elevated left ventricular outflow tract gradient or non-obstructive disease. Long established medical and surgical treatment options for patients with obstructive hypertrophic cardiomyopathy and refractory symptoms can be effective in eliminating outflow tract gradients and improving symptoms. Cardiac myosin inhibitors have emerged as a new class of evidence based medical therapy for patients with obstructive hypertrophic cardiomyopathy and an alternative to septal reduction therapies. However, effective treatments for patients with non-obstructive hypertrophic cardiomyopathy remain limited, with several clinical trials ongoing. Variants in cardiac sarcomeric genes are the primary genetic cause of hypertrophic cardiomyopathy and are being investigated as targets for gene based therapies. Stratification of the risk of sudden death is an important component of caring for patients with hypertrophic cardiomyopathy. Recommendations for implantable cardioverter-defibrillator implantation are based on well validated risk factors in combination with shared decision making. Atrial fibrillation is common in patients with hypertrophic cardiomyopathy, and anticoagulation is strongly recommended for stroke prevention. Rhythm control is essential for patients with symptomatic atrial fibrillation. Historically, vigorous exercise has been restricted; however, newer data suggest that the arrhythmic risk is less than previously thought and emphasize an individualized approach. Advanced heart failure is an uncommon but important cause of morbidity and mortality. Early identification is key to improving outcomes with advanced therapies including cardiac transplantation. The management of hypertrophic cardiomyopathy is rapidly evolving toward a more personalized approach, based on genotype and phenotype, to alter disease progression and improve patients’ outcomes.
Intraperitoneal Infusion of NKG2D CAR-NK cells Induces Endogenous CD8+ T Cell Activation in Patients with Advanced Colorectal Cancer
Authors: Bin Li, Xudong Zhu, Jingyu Ge, Hangyu Zhang, Yang Gao, Xuanwen Bao, Xiaomeng Dai, Zhicheng Du, Xiaoxuan Tu, Zhou Tong, Qihan Fu, Dongxue Hu, Weihong Tian, Yi Zheng, Lulu Liu, Peng Zhao, Weijia Fang, Shu Wang, Dongrui Wang
Journal: Molecular Therapy (2025)
Reprogramming the neuroblastoma tumor immune microenvironment to enhance GPC2 CAR T cells
Authors: Anna Maria Giudice, Sydney L. Roth, Stephanie Matlaga, Evan Cresswell-clay, Pamela Mishra, Patrick M. Schürch, Kwame Attah M. Boateng-Antwi, Minu Samanta, Guillem Pascual-Pasto, Vincent Zecchino, Timothy T. Spear, Brendan McIntyre, Neil Chada, Tingting Wang, Lingling Liu, Ruoning Wang, John T. Wilson, Adam J. Wolpaw, Kristopher R. Bosse
Journal: Molecular Therapy (2025)
Adverse Event Costs and Cost-Effectiveness Analyses of Anticancer Drugs
Authors: Mingye Zhao, Taihang Shao, Yue Yin, Hongshu Fang, Hanqiao Shao, Wenxi Tang
Journal: JAMA Network Open (2025)

Importance Accurately quantifying adverse event (AE) costs is essential for cost-effectiveness analyses (CEAs) of anticancer drugs. Misestimates in AE costs may significantly affect cost-effectiveness conclusions. Objective To assess whether AE cost quantification in anticancer drug CEAs accurately reflects the true cost of AEs and to evaluate whether replacing AE costs with actual values affects cost-effectiveness conclusions. Evidence Review A systematic search of PubMed, Web of Science, and Tufts CEA databases was conducted from October 24 to December 1, 2023, with an additional search from November 4 to 10, 2024, for English-language CEAs and claims-based studies examining AE costs for anticancer drugs published between January 2003 and December 2023. Claims-based AE costs were considered to represent actual values. AE costs were compared in absolute terms and as a proportion of total medical costs. Impact of replacing CEA AE cost estimates with actual values for incremental cost-effectiveness ratios (ICERs) was examined at thresholds of $100 000 and $150 000 per quality-adjusted life year (QALY). AE cost differences between CEA estimates and actual values and their impact on ICERs were the main outcomes. Findings The sample included 11 claims-based US studies with 34 022 patients and 102 US payer-perspective CEAs. AE cost estimates in CEAs were consistently lower than actual values, with a median difference of 9.73% (IQR, 5.15%-27.22%; P = .002) in proportion of total medical costs and of $17 201 (IQR, $13 365-$48 970; P = .03) in absolute costs. Adjusting AE costs led to an ICER change of $42 656 per QALY, altering cost-effectiveness conclusions in 8 of 17 cases (47.1%). Among the 102 CEAs, 41 (40.2%) did not report AE types; of the remaining 61 (59.8%), 48 (78.7%) focused on treatment-related AEs instead of all-cause AEs. Of all CEAs, 79 (77.5%) considered grade 3 or higher AEs, ignoring grades 1 and 2. Only 13 studies (12.7%) accounted for AE-related dose reductions or interruptions, 87 (85.3%) did not consider postprogression AE costs, and 77 (82.8%) assumed AEs occurred only in the first treatment cycle. Substantial variability was observed in both drug AE and unit AE costs across studies. Conclusions and Relevance In this systematic review of AE costs in oncology CEAs, AE costs were frequently underestimated, potentially altering cost-effectiveness conclusions. Key problems included incomplete AE inclusion, inaccurate AE cost estimates, overlooked long-term AEs, and unaccounted dose modifications. Best practices and standardized guidelines should be established to improve AE cost quantification in oncology CEAs.
Trends and Disparities in Maternal Self-Reported Mental and Physical Health
Authors: Jamie R. Daw, Colleen L. MacCallum-Bridges, Lindsay K. Admon
Journal: JAMA Internal Medicine (2025)

Importance While rising maternal morbidity and mortality have been well documented in the US, national data on general maternal physical and mental health beyond the perinatal period are lacking. Objective To examine recent trends and disparities in self-reported maternal physical and mental health. Design, Setting, and Participants In this pooled, cross-sectional study, the nationally representative National Survey of Children’s Health was used to assess self-reported mental and physical health of female biological or adoptive parents of children aged 0 to 17 years (hereafter, mothers) from 2016 to 2023. Main Outcomes and Measures The main outcomes were self-reported maternal physical and mental health, measured on a 4-point Likert scale (excellent, very good, good, fair/poor). Regression models were used to estimate trends and sociodemographic disparities in self-reported physical and mental health. Results A total of 198 417 mothers (mean [SD] age, 39.0 [0.04] years) were included in the sample, representing 42 130 370 individuals nationally in the weighted sample. Among mothers in the study, 89.8% were 30 years and older; 57.9% of mothers had a privately insured child, 35.7% had a publicly insured child, and 6.4% had an uninsured child. The unadjusted prevalence of excellent physical health declined from 28.0% to 23.9%, while good physical health rose from 24.3% to 28.1%, and fair/poor physical health did not significantly change. The unadjusted prevalence of excellent mental health declined from 38.4% to 25.8%, while good mental health rose from 18.8% to 26.1%, and fair/poor mental health rose from 5.5% to 8.5%. After adjusting for secular changes in the sociodemographic characteristics of mothers, excellent physical health decreased by 4.2 percentage points (pp) (95% CI, −5.7 to −2.8 pp), excellent mental health decreased by 12.4 pp (95% CI, −14.0 to −10.7 pp), and fair/poor mental health increased by 3.5 pp (95% CI, 2.6-4.4 pp) over the 8-year study period. Mental health declines occurred broadly across socioeconomic subgroups. However, self-reported physical and mental health status was significantly lower among mothers who were US born, single parents, less educated, and those with publicly insured or uninsured children. Conclusions and Relevance In this cross-sectional study, self-reported mental health was found to have significantly declined for female parents. Investments are needed to investigate and address the underlying causes of mental health decline among US mothers, especially those of low socioeconomic status.
Implementation of Delirium Screening at Scale in Older Patients With Emergency Hospital Admission
Authors: Emily Louise Boucher, Jasmine Ming Gan, Nicola G. Lovett, Sarah C. Smith, Sasha Shepperd, Sarah Tamsin Pendlebury
Journal: JAMA Internal Medicine (2025)

This cohort study assesses the frequency of screen completion and the prevalence and outcomes of delirium diagnosis for older patients with unplanned admission to acute general (internal) medicine.
Policies for Infection Prevention and Control in Home Health Care, 2019 vs 2023
Authors: Jingjing Shang, Ji Won Lee, Andrew W. Dick, Ashley M. Chastain, U. Gayani E. Perera, Laurent G. Glance, Patricia W. Stone
Journal: JAMA Network Open (2025)

This cross-sectional study examines how policies for infection prevention and control have evolved among US home health care agencies after the COVID-19 pandemic.