tbuckley/cabot-search huggingface dataset:
State Earned Income Tax Credits and Firearm Suicides
Authors: Nicole Asa, Alice Ellyson, Ali Rowhani-Rahbar
Journal: JAMA Network Open (2025)

Importance Firearm suicides are an increasing public health crisis and disproportionately impact low-income communities. The earned income tax credit (EITC) is the largest poverty alleviation program for working families with low income in the US. Objective To evaluate the association of presence and generosity of state EITC policies with state-level firearm suicide rates. Design, Setting, and Participants This ecological cohort study analyzed EITC data and suicide rates from 46 US states and Washington, DC, from 1981 to 2019. Data analysis was conducted from June 2022 to August 2024. Exposure The exposure was the presence and generosity of state refundable EITCs (ie, amount of a refundable tax credit that exceeds income tax liability is refunded to taxpayers). The EITC generosity was measured as a continuous exposure quantified by percentage of the federal EITC offered by a state each year. Main Outcomes and Measures The outcome was state-level annual firearm suicide rates. The association of state EITC implementation with firearm suicide rates was estimated using heterogeneity-robust 2-stage difference-in-difference (DID). All regression models used ordinary least squares, included state and year fixed effects with standard errors clustered at the state level, and adjusted for time-varying state-level covariates. Results Individual-level data were not available in this study of state-level firearm suicide rates. During the study period, 20 states implemented a refundable EITC (generosity range, 3.4%-85%). In 2019, the final year of the study, the nationwide rate of firearm suicide was 7.29 per 100 000 persons. A statistically significant negative association was found between refundable EITCs and firearm suicide rates. Every 10% increase in refundable EITC generosity was associated with a decrease in the mean firearm suicide rate by 0.28 (95% CI, −0.48 to −0.08) cases per 100 000 person-years (relative decline, 4.3%; 95% CI, 1.5% to 7.0%). The mean firearm suicide rate was 0.49 (95% CI, −0.91 to −0.07) cases per 100 000 person-years fewer comparing postimplementation and preimplementation years among states that implemented a refundable EITC contrasting with the change during that time in states without a refundable EITC (relative decline, 7.9%; 95% CI, 2.7% to 12.9%). Conclusion In this cohort study, the presence and generosity of state refundable EITCs were associated with a decrease in firearm suicide rates, supporting the growing body of literature highlighting the importance of antipoverty policies for reducing firearm suicide.
Seven vs Fourteen Days of Antibiotics for Gram-Negative Bloodstream Infection
Authors: Todd C. Lee, Connor J. Prosty, Michael Fralick, Angela Huttner, Emily G. McDonald, José Molina, Mical Paul, Ruxandra Pinto, Asgar Rishu, Elodie von Dach, Dafna Yahav, Rob Fowler, Nick Daneman
Journal: JAMA Network Open (2025)

Importance Gram-negative bloodstream infections are a common cause of hospitalization. A 2-week duration of antibiotic therapy has been commonly used, but shorter durations may have similar outcomes. Objectives To assess whether 7 days of antibiotic therapy was noninferior to 14 days. Data Sources Starting with a 2022 individual patient data meta-analysis, PubMed, Cochrane Central Register of Controlled Trials, and Web of Science were searched to identify additional eligible randomized clinical trials (RCTs) conducted from May 1, 2022, until November 30, 2024. Study Selection RCTs involving primarily adults who were hospitalized at the time of Gram-negative bloodstream infection and were allocated to 7 or 14 days of antibiotic therapy. Studies were independently reviewed by 2 investigators. Data Extraction and Synthesis PRISMA guidelines were followed. Data were extracted by 2 investigators. Any unpublished data were obtained directly from study authors. Risk of bias and certainty of the evidence were assessed in duplicate using the Cochrane Risk of Bias Tool, version 2, and the Grading of Recommendations Assessment, Development and Evaluation approach. Data were pooled by separate random-effects meta-analyses for the intention-to-treat (ITT) and per-protocol (PP) populations. A noninformative prior probability was used for the effect, and an evidence-based weakly informative prior probability was used for heterogeneity. Risk ratios (RRs), 95% credible intervals (CrIs), and probability of noninferiority were calculated using a prespecified upper bound of 1.25 or less. Main Outcomes and Measures Ninety-day all-cause mortality. Results Four eligible RCTs contributed 3729 patients in the ITT population (1912 women [51.3%]; median age range, 67-79 years) and 3126 in the PP population. In the ITT analysis, within 90 days, 226 patients (12.8%) receiving 7 days of antibiotics died compared with 253 (13.7%) receiving 14 days, corresponding to an RR for 90-day mortality of 0.91 (95% CrI, 0.69-1.22) and a 97.8% probability of noninferiority. In the PP analysis, the RR was 0.93 (95% CrI, 0.68-1.32), corresponding to a 95.1% probability of noninferiority. Conclusions and Relevance In this systematic review and meta-analysis of patients with Gram-negative bloodstream infections and adequate source control, 7 days of antibiotic therapy had a high probability of being noninferior to 14 days. These findings support a shorter duration of antibiotic therapy for appropriately selected patients like those in the included RCTs.
External Validation of the Phoenix Sepsis Score in Children With Suspected Community-Acquired Sepsis
Authors: Elliot Long, Meredith L. Borland, Shane George, Shefali Jani, Eunicia Tan, Natalie Phillips, Amit Kochar, Simon Craig, Anna Lithgow, Arjun Rao, Stuart Dalziel, Ed Oakley, Stephen Hearps, Ben Gelbart, Sarah McNab, Fran Balamuth, Scott L. Weiss, Nathan Kuppermann, Charlotte Brad, Amanda Williams, Franz E. Babl, Catherine L Wilson
Journal: JAMA Network Open (2025)

Importance The novel Phoenix Sepsis Score and sepsis criteria were derived and validated using a multicountry dataset and proposed as a new definition for sepsis in children. Objective To externally validate the Phoenix Sepsis Score and sepsis criteria in a cohort of children hospitalized with suspected community-acquired sepsis. Design, Setting, and Participants This diagnostic study used data from the multicenter, multicountry Sepsis Epidemiology in Australian and New Zealand Emergency Departments (SENTINEL) study, collected from 2021 to 2023 and including 90-day follow-up. Children admitted to the hospital through 11 emergency departments in Australia and New Zealand and treated with parenteral antibiotics with either (1) a provisional diagnosis of sepsis or (2) treatment for sepsis (intravenous fluid bolus to treat poor perfusion) were included. Exposure Development of organ dysfunction over the first 24 hours of hospitalization. Main Outcomes and Measures The main outcomes were (1) in-hospital mortality and (2) death or requirement for extracorporeal life support (ECLS) within 72 hours of hospitalization. Results A total of 6232 children were included in the analysis, with a median (IQR) age of 2.1 (0.3-7.1) years, 3386 (54.1%) male, in-hospital mortality of 60 (1.0%), and death or ECLS within 72 hours in 36 (0.6%). In this population, the worst Phoenix Sepsis Score calculated over the first 24 hours of hospitalization had an area under the precision recall curve of 0.17 (95% CI, 0.07-0.28) for predicting in-hospital mortality and 0.23 (95% CI, 0.11-0.36) for predicting death or ECLS within 72 hours. Overall, 306 children (4.9%) met the Phoenix sepsis criteria, of whom 33 (10.8%) died in the hospital (nearly half of the total number who died) and 28 (9.2%) died or required ECLS within 72 hours. The Phoenix sepsis criteria had a sensitivity of 55.0% (95% CI, 41.6%-67.9%) and positive predictive value (PPV) of 10.8% (95% CI, 7.6%-14.9%) for in-hospital mortality and sensitivity of 77.8% (95% CI, 60.8%-89.9%) and PPV of 9.2% (95% CI, 6.2%-13.0%) for death or ECLS within 72 hours. Coagulation data for the calculation of the Phoenix Sepsis Score were missing in more than 85% of children. Conclusions and Relevance In this multicenter diagnostic study of children hospitalized with suspected sepsis, the Phoenix Sepsis Score and sepsis criteria had similar performance to the original derivation and validation cohorts. The small proportion of children meeting Phoenix sepsis criteria, missingness of data, timing of application, and lack of sensitivity for in-hospital mortality limit the clinical utility of the criteria.
Telacebec, A Potent Agent in the Fight Against Tuberculosis: Findings from A Randomized, Phase 2 Clinical Trial and Beyond
Authors: Saskia Janssen, Caryn Upton, Veronique R. de Jager, Christo van Niekerk, Rodney Dawson, Jane Hutchings, Jeongjun Kim, Jinho Choi, Kiyean Nam, Eugene Sun, Andreas H. Diacon
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Antibiotic-resistant mycobacterial infections are a major threat to health care. Telacebec is a novel, first-in-class agent targeting mycobacterial cellular energy production in a range of pathogenic mycobacteria including M. tuberculosis, M. leprae and M. ulcerans. To explore telacebec's early bactericidal activity, tolerability, safety and pharmacokinetics in patients with pulmonary tuberculosis (TB) and to summarize its current state of development for other diseases. We randomly assigned 64 patients with smear-positive, drug-sensitive TB to daily telacebec 100mg, 200mg, or 300mg, or standard 4-drug treatment as control, for 14 days. Sputum collected overnight was cultured in liquid and on solid media to determine the change of viable mycobacteria over time. Safety and tolerability were assessed daily. A full pharmacokinetic profile was obtained on Day 14. We found a dose-dependent reduction of the sputum mycobacterial load with a mean daily change (±standard deviation) for telacebec 300mg and control, respectively, of 0.097 (±0.050) and 0.200 (±0.073) log colony forming units, and 3.738 (±2.747) and 6.853 (±1.194) hours to culture positivity over the first 14 days of treatment. Pharmacokinetics were dose-proportional. Telacebec was well tolerated and safe with low adverse events rates across all doses. The results confirm telacebec's clinical activity against M. tuberculosis. Longer trials, in combination with other agents, are required to validate these results and to investigate telacebec's full potential. These results encourage exploring telacebec for more effective, shorter treatment regimens for leprosy and Buruli ulcer. A clinical trial for Buruli ulcer is underway.
Racial and Ethnic Inequalities in Actual vs Nearest Delivery Hospitals
Authors: Nansi S. Boghossian, Lucy T. Greenberg, Jeffrey S. Buzas, Joshua Radack, Molly Passarella, Jeannette Rogowski, George R. Saade, Ciaran S. Phibbs, Scott A. Lorch
Journal: JAMA Network Open (2025)

Importance Minoritized racial and ethnic groups, such as American Indian and Black individuals, often receive lower quality health care compared with White individuals. There is limited understanding of how these disparities extend to obstetric care, particularly when comparing the quality of care at the actual delivery hospital vs the nearest obstetric hospital based on the birthing individual’s residence. Objective To examine inequality in care based on the actual delivery hospital and the closest delivery hospital to the birthing individual’s residential zip code centroid. Design, Setting, and Participants This population-based retrospective cohort study used data from 5 states (2008 to 2020 for Michigan, Oregon, and South Carolina; 2008 to 2018 for Pennsylvania; and 2008 to 2012 for California). Individuals delivering a fetal death or a live birth with gestational age between 22 to 44 weeks were included. Analysis was conducted between February and August 2024. Exposure Race and ethnicity. Main Outcomes and Measures The obstetric inequality index was calculated using Gini coefficients from Lorenz curves for American Indian, Asian, Black, and Hispanic birthing individuals compared with White individuals, with hospitals ranked by their standardized morbidity ratio for nontransfusion severe maternal morbidity. Results There were 6 418 635 birthing individuals across 549 hospitals (23 050 American Indian individuals [0.4%], 463 342 Asian individuals [7.2%], 807 738 Black individuals [12.6%], 1 645 922 Hispanic individuals [25.6%], and 3 279 315 White individuals [51.1%]). Compared with White individuals, American Indian and Black individuals delivered at lower-quality hospitals, while there was no significant difference for Asian and Hispanic individuals (delivery hospital inequality index: American Indian, 0.07 [95% CI, 0.03 to 0.11]; Asian, −0.02 [95% CI, −0.08 to 0.04]; Black, 0.15 [95% CI, 0.12 to 0.19]; Hispanic −0.04 [95% CI, −0.09 to 0.01]). Black individuals lived closer to lower-quality hospitals than White individuals (closest hospital inequality index for Black individuals: 0.11 [95% CI, 0.07 to 0.14]). Asian and Hispanic individuals had similar closest hospital inequality indices to White individuals. The inequality index for Black individuals would have been lower if individuals had delivered at their nearest hospital. Conclusions and Relevance This cohort study found that American Indian and Black individuals delivered at lower-quality hospitals than White individuals. The disparity in care between Black and White birthing individuals would have been reduced if individuals had delivered at their nearest hospital.
Author Correction: Transcriptional function of E2A, Ebf1, Pax5, Ikaros and Aiolos analyzed by in vivo acute protein degradation in early B cell development
Authors: Anna S. Fedl, Hiromi Tagoh, Sarah Gruenbacher, Qiong Sun, Robyn L. Schenk, Kimon Froussios, Markus Jaritz, Meinrad Busslinger, Tanja A. Schwickert
Journal: Nature Immunology (2025)
Integrating DCPR-R and DSM-5 into clinical psychosomatic practice in Taiwan: Their relationship with psychopathologies and quality of life
Authors: Wei-Lieh Huang, Yi-Ting Chiu, Chi-Shin Wu, Bernd Löwe, Shih-Cheng Liao
Journal: Psychotherapy and Psychosomatics (2025)

Introduction: This study aimed to assess the benefit of integrating the Diagnostic Criteria for Psychosomatic Research-Revised (DCPR-R) into the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5). Specifically, it examined whether this integration enhances the understanding of psychopathologies and quality of life (QOL) in psychosomatic medicine. Methods: In this cross-sectional study conducted in Taiwan, 277 patients from psychosomatic clinics and 225 community participants were included. Standardized interview tools based on DCPR-R and DSM-5 were used to assess the presence of various diagnoses. Participants also completed several scales related to persistent somatic symptoms, negative emotions, and QOL. Latent class analysis was used to explore the clustering of diagnoses, and multiple linear regression analysis was employed to investigate the relationship between diagnoses, psychopathologies, and QOL under conditions of possible comorbidity. Results: Three classes were identified via latent class analysis: somatic symptoms, demoralization and stress, and insomnia. In the multivariate analysis considering multiple diagnoses simultaneously, the number of diagnoses significantly associated with psychopathologies and QOL was greatly reduced compared to the univariate analysis. Persistent somatization was more strongly associated with somatic distress than somatic symptom disorder. Several DCPR-R constructs showed significant associations with illness-related anxiety. The DCPR-R diagnoses with broader influences on QOL were demoralization, demoralization with hopelessness, and irritable mood. Conclusions: The results suggest the potential clinical significance of integrating DCPR-R and DSM-5 in Eastern societies. The DCPR-R diagnoses with significant findings mentioned above may contribute to the personalized treatment plans for patients in psychosomatic medicine.
Telephone-guided sleep restriction for insomnia: A randomized sleep diary-controlled trial
Authors: Mathilde I. Looman, Tessa F. Blanken, Tim M. Schoenmakers, Joyce E. Reesen, Marieke Effting, Floris E. Linnebank, Annemieke van Straten, Jan H. Kamphuis, Jaap Lancee
Journal: Psychotherapy and Psychosomatics (2025)

Introduction: Insomnia is common, but access to its first-line treatment, Cognitive Behavioral Therapy for Insomnia (CBT-I), is limited. To explore a scalable alternative, we investigated the efficacy of Sleep Restriction Therapy (SRT), a core component of CBT-I, delivered via telephone. Methods: In a randomized controlled trial, 147 adults with insomnia were allocated to 6 weeks of telephone-guided SRT (n = 76) or a sleep diary control group (n = 71). The SRT group received weekly supporting phone calls lasting 10 to 15 minutes. At baseline and post-test, we measured insomnia severity (primary outcome), sleep diary measures, anxiety symptoms, depressive symptoms, pre-sleep arousal, sleep-safety behaviors, daytime sleepiness, and dysfunctional sleep-related cognitions (secondary outcomes). The SRT group repeated these measures at 3- and 6-month follow-up. Results: Telephone-guided SRT showed large between-group effects on insomnia severity at post-test relative to the sleep diary control group (d = 1.52; p &lt; .001). Based on intention-to-treat, 36 (47%) participants randomized to SRT achieved clinical improvement, and 23 (30%) achieved insomnia remission. We found medium-to-large between-group effects at post-test (d = 0.53 to 1.18) for all secondary outcomes except daytime sleepiness and total sleep time. At 3- and 6-month follow-up, the primary and all secondary outcomes, including daytime sleepiness and total sleep time, improved relative to baseline within the SRT group (d = 0.50 to 1.93). Conclusion: This trial shows that telephone-guided SRT is an effective insomnia treatment requiring minimal therapist guidance. If direct comparisons with CBT-I corroborate these findings, SRT could be an interesting scalable alternative to CBT-I as a first-line insomnia treatment. Trial registry: NCT05548907
How to use directed acyclic graphs: guide for clinical researchers
Authors: Timothy Feeney, Fernando Pires Hartwig, Neil M Davies
Journal: BMJ (2025)

Directed acyclic graphs are commonly used to illustrate and assess the hypothesised causal mechanisms in health and social research. These graphs can illuminate investigators' assumptions and help clearly describe each possible explanation for associations observed in data given researchers' assumptions, ranging from causal effects to confounding and selection bias, and thereby help identify variables that can be used to reduce or overcome bias. This article explains how to construct, interpret, and present directed acyclic graphs as part of clinical research studies and how they can help communicate a study's strengths or limitations.
Urinary problems in men: self-management advice is helpful
Authors: Helen Saul, Brendan Deeney, Laura Swaithes, Marcus Drake
Journal: BMJ (2025)

The study Worthington J, Frost J, Sanderson E, et al. Lower urinary tract symptoms in men: the TRIUMPH cluster RCT. Health Technology Assessment 2024;28:1-162. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/urinary-problems-in-men-self-management-advice-is-helpful/
GM-CSF–mediated epithelial-immune cell cross-talk orchestrates pulmonary immunity to <i>Aspergillus fumigatus</i>
Authors: Kathleen A. M. Mills, Frederike Westermann, Vanessa Espinosa, Eric Rosiek, Jigar V. Desai, Mariano A. Aufiero, Yahui Guo, Fitty L. Liu, Kennedy A. Mitchell, Selma Tuzlak, Donatella De Feo, Michail S. Lionakis, Amariliz Rivera, Burkhard Becher, Tobias M. Hohl
Journal: Science Immunology (2025)

Aspergillus fumigatus causes life-threatening mold pneumonia in immunocompromised patients, particularly in those with quantitative or qualitative defects in neutrophils. Whereas innate immune cell cross-talk licenses neutrophil antifungal activity in the lung, the role of epithelial cells in this process is unknown. Here, we find that surfactant protein C (SPC)–expressing lung epithelial cells integrate infection-induced interleukin-1 and type III interferon signaling to produce granulocyte-macrophage colony-stimulating factor (GM-CSF) preferentially at local sites of fungal infection and neutrophil influx. Using in vivo models that distinguish the role of GM-CSF during acute infection from its homeostatic function in alveolar macrophage survival and surfactant catabolism, we demonstrate that epithelial-derived GM-CSF increases the accumulation and fungicidal activity of GM-CSF–responsive neutrophils, which is essential for host survival. Our findings establish SPC + epithelial cells as a central player in regulating the quality and strength of neutrophil-dependent immunity against inhaled mold pathogens.
Dysregulation of γδ intraepithelial lymphocytes precedes Crohn’s disease–like ileitis
Authors: Weili Xu, Natasha B. Golovchenko, Irving U. Martínez-Vargas, Andrew Fong, Prateeksha Rout, Sajan Achi, Edie B. Bucar, Jonathan J. Hsieh, Kaylynn J. Vidmar, Lanjing Zhang, Alexandros D. Polydorides, Immo Prinz, George Kollias, Mark R. Frey, Theresa T. Pizarro, Michael P. Verzi, Karen L. Edelblum
Journal: Science Immunology (2025)

Intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IELs) provide immunosurveillance of the intestinal barrier but are reduced in patients with active Crohn’s disease (CD). Here, we report an underappreciated role for γδ IELs in maintaining immunological tolerance during the onset and progression of CD-like ileitis using TNF ΔARE/+ mice. We found that TNF-induced down-regulation of epithelial hepatocyte nuclear factor 4-gamma/butyrophilin is followed by a loss of ileal Vγ7 IELs and impaired barrier surveillance before the histological onset of disease. A reduction of immunoregulatory CD39 + γδ IELs coincided with the influx of immature, peripheral CD39 neg γδ T cells into the epithelium, leading to an expansion of induced IELs, whereas an earlier depletion of γδ IELs correlated with accelerated onset of ileal inflammation. Our findings identify multiple layers of γδ IEL dysregulation before ileitis development, indicating that the loss of steady-state immunoregulatory γδ IELs may contribute to the initiation of ileal CD.
DNMT1 inhibition reprograms T cells to NK-like cells with potent antitumor activity
Authors: Yao Li, Jiongliang Wang, Linfu Zhou, Wenbin Gu, Le Qin, Dongdong Peng, Shanglin Li, Diwei Zheng, Qiting Wu, Youguo Long, Yao Yao, Shouheng Lin, Mingwei Sun, Xiaofei Zhang, Jie Wang, Pentao Liu, Xiangqian Kong, Peng Li
Journal: Science Immunology (2025)

Inactivation of the transcription factor BCL11B reprograms T cells into induced-T-to-NK cells (ITNKs). However, it remains unclear how BCL11B suppresses natural killer (NK) cell transcriptional programs. Here, we identified that the DNA methyltransferase DNMT1 physically interacts with BCL11B, increasing BCL11B stability and the fidelity of DNA methylation maintenance for NK cell–related genes, thereby repressing their expression. Moreover, DNMT1 maintains the epigenetic silencing of a distinct subset of NK cell–related genes independent of BCL11B. DNMT1 inhibition or depletion reprograms T cells and chimeric antigen receptor (CAR)–T cells into NK-like cells that exhibit more robust antitumor effects than BCL11B-deficient ITNKs and parental CAR-T cells. Moreover, H3K27me3 (trimethylation of histone 3 lysine 27) synergizes with DNA methylation to repress NK cell–related pathways, and combined EZH2 (enhancer of zeste homolog 2) and DNMT1 inhibition potentiates both the reprogramming and cytotoxicity of NK-like cells. Our findings uncover the molecular mechanisms that safeguard T cell identity and provide a rationale for deriving NK-like cells with epigenetic inhibitors for cancer immunotherapy.