tbuckley/cabot-search huggingface dataset:
Dynamic Computed Tomography Findings as Indicators of Uterine Artery Embolization in Postpartum Hemorrhage
Authors: Munekage Yamaguchi, Akihito Sagara, Yasunori Nagayama, Jun Morinaga, Yoshinori Yamanouchi, Shintaro Makino, Shigetaka Matsunaga, Hiroaki Tanaka, Junichi Hasegawa, Tomoaki Ikeda, Takashi Sugiyama, Eiji Kondoh
Journal: JAMA Network Open (2025)

Importance Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality globally. Although traditional management relies on blood loss quantification, identifying cases resistant to conventional treatment remains challenging, potentially delaying crucial interventions. Objective To determine the prevalence and clinical implications of PPH that is resistant to treatment showing arterial contrast extravasation on dynamic computed tomography (CT) (PRACE) and its association with intervention requirements. Design, Setting, and Participants A multicenter retrospective case-control study of PPH cases was conducted at 43 tertiary facilities across Japan, including 30 university hospitals, between January and December 2021. The study included patients with PPH who were either transported to the centers or who delivered there. Data analysis was performed from September 2023 to November 2024. Exposure A diagnosis of PPH, defined as blood loss exceeding 2000 mL or requiring more than 10 units of red blood cell transfusion. Main Outcomes and Measures The primary outcome was the prevalence of PRACE and its association with uterine artery embolization (UAE) requirement. Secondary outcomes included risk factors for severe coagulopathy (fibrinogen &amp;amp;lt;150 mg/dL). Odds ratios (ORs) were estimated using multivariable logistic regression to evaluate the association between types of PPH (atonic uterus, tissue, and PRACE) and PPH severity. Results Among 352 patients (median [IQR] age, 33.0 [30.0-37.0] years; 211 [60.0%] primiparous), 205 (58.2%) underwent CT scans, with PRACE detected in 58 (32.2%) of evaluable cases. Patients with PRACE had significantly higher total blood loss (median [IQR], 3455 [2000-5070] mL vs 2500 [1500-2650] mL) and greater UAE requirement (50 of 58 patients [86.2%] vs 35 of 122 patients [28.7%]) compared with patients without PRACE. PRACE was the primary factor associated with the need for UAE (OR, 27.74; 95% CI, 10.52-83.14). Conclusions and Relevance In this retrospective case-control study of patients with severe PPH undergoing dynamic CT, PRACE represented a distinct and common pathology in severe PPH and was associated with the need for interventional procedures. These findings suggest that dynamic CT imaging should be considered as an essential diagnostic tool in managing treatment-resistant PPH cases.
Priority Health Conditions and Global Life Expectancy Disparities
Authors: Omar Karlsson, Angela Y. Chang, Ole F. Norheim, Wenhui Mao, Sarah Bolongaita, Dean T. Jamison
Journal: JAMA Network Open (2025)

Importance Life expectancy is a composite health measure reflecting acute and life-course exposures. Identifying conditions behind disparities in life expectancy can guide policy, planning, and financing to battle the most urgent health problems. Objective To examine the contribution of 33 causes of death to life expectancy disparities, highlighting 2 sets of priority conditions—8 infectious and maternal and child health conditions (I-8) and 7 noncommunicable diseases and injuries (NCD-7). Design, Setting, and Participants This cross-sectional study examined life expectancy disparities in 7 global regions and 165 countries from 2000 to 2021. Western Europe and Canada (hereafter referred to as the North Atlantic) in 2019 were used as a benchmark for life expectancy achievable with advanced health care and living standards. Life expectancy gaps in locations with life expectancy lower than the benchmark were decomposed by cause of death using the Pollard decomposition on the Global Health Estimates from the World Health Organization. Data were analyzed from February to March 2025. Exposure Geographic location (countries and regions). Main Outcome and Measure Life expectancy at birth. Results In the median country in 2019, the I-8 and NCD-7 together accounted for 80% (IQR, 71%-88%) of the life expectancy gap compared with the North Atlantic. Outside sub-Saharan Africa, the NCD-7 accounted for the largest share of the gap; for example, more than the total life expectancy gap in China, or 5.5 (95% uncertainty bounds [UB], 5.0-6.0) years of a 4.3-year life expectancy gap; and 6.4 (95% UB, 5.9-6.8) years of a 11.5-year gap in India. However, reduced mortality from the I-8 contributed to enormous improvements in sub-Saharan Africa, accounting for 21.4 (95% UB, 20.6-22.2) years of a 31-year gap in 2000 and 11.4 (95% UB, 10.9-11.8) years of a 22-year gap in 2019. India transitioned from having most of the gap accounted for by the I-8 in 2000, or 11.9 (95% UB, 11.0-13.0) years of a 19.6-year life expectancy gap, to having a larger share accounted for by the NCD-7 in 2019. Conclusions and Relevance This cross-sectional study suggests that a limited number of causes account for most life expectancy disparities. Together with current information on risk factors, interventions, and morbidity not yet reflected in life expectancy, the varying contributions of these causes to gaps in life expectancy can help focus health policy and guide interventions to reduce risk factors and treat conditions.
Character of Discharge From the US Military and Suicide Mortality
Authors: Mark A. Reger, Chandru Ravindran, Sybil W. Morley, Andrew Devendorf, Kristen J. Vescera, Brady M. Stephens
Journal: JAMA Network Open (2025)

Importance Suicide risk may be elevated among individuals who separate from military service with a character of discharge or service that was not honorable (ie, dishonorable, bad conduct, other than honorable, general, or uncharacterized), but a comprehensive evaluation of this possibility has not been previously published. Objective To examine suicide mortality by character of discharge compared with individuals who received an honorable discharge and the full veteran population recently separated from service. Design, Setting, and Participants This retrospective cohort study included all individuals who separated from the active component of the US military between January 1, 2002, and December 31, 2021. Data were obtained from the US Department of Veterans Affairs/Department of Defense Mortality Data Repository. Suicide rates for each character of discharge were compared with those among individuals receiving an honorable discharge and the full veteran population recently separated from service. Analyses were conducted between December 21, 2023, and June 1, 2024. Exposure Character of discharge assigned at separation from the active component of military service. Main Outcomes and Measures Crude suicide rates up to 5 years after separation were examined. Age-standardized rate ratios were used for comparisons within the cohort between strata. Age-standardized mortality ratios (SMRs) were used to compare suicide mortality by character of discharge with the full separation cohort and within specific military service branches. Results Among 3 627 653 individuals (mean [SD] age at separation, 28.4 [8.6] years; 83% men), 5599 deaths by suicide occurred during the study period. All character of discharge groups had significantly higher suicide rates than the honorable group, with standardized rate ratios ranging from 1.91 (95% CI, 1.69-2.17) for uncharacterized to 2.77 (95% CI, 2.52-3.05) for general. Veterans who received an honorable discharge were less likely to die by suicide than the overall cohort population (SMR, 0.82 [95% CI, 0.79-0.85]), while veterans with all other characters of discharge were more likely to die by suicide, with SMRs ranging from 1.23 (95% CI, 1.15-1.31) for uncharacterized to 1.84 (95% CI, 1.72-1.97) for general. Common demographic risk factors for suicide (eg, age, race) were replicated within character groups in most cases. Conclusions and Relevance In this cohort study, individuals who did not receive an honorable character of discharge were at significantly higher risk of suicide compared with veterans who received an honorable discharge and the veteran population recently separated from service. These findings suggest that character of discharge may be a helpful risk factor to consider for ongoing suicide prevention efforts.
Efficacy of team‑based collaborative care for distressed patients in secondary prevention of chronic coronary heart disease: Results from the multicenter, randomized controlled TEACH trial
Authors: Monika Sadlonova, Birgit Herbeck Belnap, Ingrid Becker, Kristina Bersch, Franziska Geiser, Viktoria Adenauer, Martin Hellmich, Ingrid Kindermann, Angela Zimmer, Matthias Michal, Jasmin Ghaemi Kerahrodi, Mariel Nöhre, Martina de Zwaan, Astrid Petersmann, Irina Müller-Kozarez, Maja Ehlers, Rolf Wachter, Christian Albus, Christoph Herrmann-Lingen
Journal: Psychotherapy and Psychosomatics (2025)

Introduction: Coronary heart disease (CHD) has serious implications for patients´ quality of life (QoL). Psychological distress affects 15 to 40% of patients with CHD and is robustly associated with poorer prognosis. Blended collaborative care (BCC), a telephone-delivered intervention involving non-physician care managers that address both psychological and medical factors can be applied for secondary prevention of CHD. Methods: We conducted the multicenter, randomized controlled TEACH trial that investigated the efficacy of a BCC intervention (TeamCare) in distressed CHD patients. The primary aim was to examine the treatment response rate of TeamCare defined as ≥ 50% improvements in health-related QoL (HRQoL, assessed by HeartQoL) after 12 months compared to usual care (UC). Secondary endpoints were changes in HRQoL, psychological and medical factors, and satisfaction with care. Results: In total, 457 patients (mean age 62.9 ± 9.5 years, 23% females) were randomized to TeamCare (n=230) or UC (n=227). At 12 months, TeamCare patients showed a significantly higher proportion of treatment response on HeartQoL compared to UC (19% vs. 10%, respectively). TeamCare yielded significantly greater improvements in HeartQoL scores: global (d=0.338), physical (d=0.270), and emotional (d=0.382). Further, TeamCare led to a significantly greater decrease in depression (d=-0.329), anxiety (d=-0.300), perceived stress (d=-0.233), and medical risk score (d=-0.235). Finally, BCC patients showed a higher satisfaction with overall treatment and psychosocial care. Conclusion: The TEACH study is the first ever performed BCC trial in distressed CHD patients in Europe. The BCC intervention has the potential to significantly improve secondary prevention in distressed CHD patients.
Evaluation of a Smartphone App Intervention with Telephone Guidance as Transitional Support from Inpatient Treatment to Continuing Care for Individuals with Alcohol Use Disorder: Results from a Randomized Controlled Trial
Authors: Sebastian Saur, Kiona K. Weisel, Catharina Lang, Lukas M. Fuhrmann, Niklas Meurer, Daniela Reichl, Mathias Zink, Peter Heepe, Thomas Hillemacher, Wolf-Dietrich Braunwarth, Peter Falkai, Gabriele Koller, Yaroslav Kiderman, Thomas Kraus, Johannes Kornhuber, Philipp Spitzer, Dominikus Bönsch, Mark Stemmler, Anja Hildebrand, Sabine Steins-Loeber, Matthias Berking
Journal: Psychotherapy and Psychosomatics (2025)

Introduction: Relapse rates in individuals with alcohol use disorder (AUD) are particularly high following inpatient treatment. Innovative strategies should specifically target the transitional gap between completion of inpatient treatment and uptake of standard continuing care. This study aimed to determine whether Appstinence, a digital approach that combines a smartphone app intervention with adjunct telephone coaching, more markedly reduces the risk of relapse for 6 months after inpatient AUD treatment in comparison to a control group with access to standard continuing care. Methods: In this multicenter clinical trial, 356 participants were randomized to the intervention (n=175) or control group (n=181). Eligibility criteria included diagnosis of AUD, smartphone access, no acute suicidality, and no language or neurocognitive impairments. The primary outcome was risk of relapse within six months after randomization, as assessed with the Timeline-Follow-Back method. Secondary outcomes included uptake of standard continuing care, hazardous alcohol consumption, craving, depression and anxiety symptom severity, and well-being. Results: The intervention reduced the risk of relapse within six months as indicated by a log-rank test (HR 0.72, 95% CI 0.53-0.98, p=0.04) and Cox regression adjusted for baseline characteristics (HR 0.67, 95% CI 0.48-0.92, p=0.01). This effect increased when participants fully adhered to the intervention protocol (log-rank test: HR 0.61, 95% CI 0.39-0.94, p=0.02). No significant differences were observed in secondary outcomes. Conclusion: Our findings provide supportive evidence for digital AUD transition treatment. Specifically, we found that, in comparison with access standard continuing care, the novel intervention more effectively reduced risk of relapse within six months following inpatient treatment.
Targeting SAMD1 enhances the effect of anti-PD-1 plus lenvatinib therapy in hepatocellular carcinoma by increasing ferroptosis sensitivity and immune response
Authors: Guo-Qiang Pan, Yu-Chuan Yan, Rui-Zhe Li, Chen Xiong, Shao-Peng Zhang, Ying Qu, Rui Dong, Yu Zhou, Tuan-Song Zhang, Zhi-Qiang Chen, Xiao-Lu Zhang, Xiao-Feng Dong, Dong-Xu Wang, Zhao-Ru Dong, Tao Li
Journal: Metabolism (2025)
Advancing neurogenetics in Africa: past achievements, current developments and shaping the future
Authors: Guida Landouré, Abdoulaye Yalcouyé, Salimata Diarra, Alassane Dit Baneye Maiga, Mohamed E Dembélé, Cheick A K Cissé, Abdoulaye Bocoum, Lassana Cissé, Salia Bamba, Oumar Samassékou, Kenneth H Fischbeck, Barrington G Burnett
Journal: Nature Reviews Neurology (2025)
Aldehyde metabolism governs resilience of mucociliary clearance to air pollution exposure
Authors: Noriko Shinjyo, Haruna Kimura, Tomomi Yoshihara, Jun Suzuki, Masaya Yamaguchi, Shigetada Kawabata, Yasutaka Okabe
Journal: Journal of Clinical Investigation (2025)

Air pollution is a serious environmental threat to public health; however, the molecular basis underlying its detrimental effects on respiratory fitness remains poorly understood. Here, we show that exposure to particulate matter ≤2.5 µm (PM2.5), a significant fraction of air pollutants, induces the generation of reactive aldehyde species in the airway. We identified aldehyde dehydrogenase 1A1 (ALDH1A1), which is selectively expressed in airway epithelium, as an enzyme responsible for detoxifying these reactive aldehyde species. Loss of ALDH1A1 function results in the accumulation of aldehyde adducts in the airway, which selectively impairs mucociliary clearance (MCC), a critical defense mechanism against respiratory pathogens. Thus, ALDH1A1-deficient mice pre-exposed to PM2.5 exhibited increased susceptibility to pneumonia. Conversely, pharmacological enhancement of ALDH1A1 activity promoted the restoration of MCC function. These findings elucidate the critical role of aldehyde metabolism in protecting against PM2.5 exposure, offering a potential target to mitigate the negative health consequences of air pollution.
A light-regulated circadian timer optimizes neutrophil bactericidal activity to boost daytime immunity
Authors: Lucia Yi Du, Pramuk Keerthisinghe, Leah Rolland, Yih Jian Sung, Hannah Darroch, Tanja Linnerz, Elina Ashimbayeva, Matthew J. Grant, Purvi M. Kakadia, Annasuya Ramachandran, Alexander Tups, Herman P. Spaink, Stefan K. Bohlander, James Cheeseman, Philip S. Crosier, Jonathan W. Astin, Guy Warman, Christopher J. Hall
Journal: Science Immunology (2025)

The immune response exhibits strong circadian rhythmicity, with enhanced bacterial clearance often synchronized with an organism’s active phase. Despite providing the bulk of cellular antibacterial defense, the neutrophil clockwork is poorly understood. Here, we used larval zebrafish to explore the role of clock genes in neutrophils during infection. Per2 was required in neutrophils for reactive oxygen species (ROS) production and bacterial killing by enhancing infection-responsive expression of high-mobility group box 1a ( hmgb1a ). The Cry binding domain of Per2 was required for regulation of neutrophil bactericidal activity, and neutrophils lacking Cry1a had elevated bactericidal activity and infection-responsive hmgb1a expression. A conserved cis-regulatory element with BMAL1 and nuclear factor κB binding motifs gated infection-responsive hmgb1a expression to the light phase. Mutagenesis of the BMAL1 motif in neutrophils blunted the priming effect of light on bactericidal activity and hmgb1a expression. These findings identify a light-responsive cell-intrinsic timer that controls time-of-day variations in antibacterial activity.
An engineered viral protein activates STAT5 to prevent T cell suppression
Authors: Yating Zheng, Zehui Gu, Claire E. Shudde, Taylor L. Piper, Xinyu Wang, Grace A. Aleck, Jiajia Zhou, Dana King, Monica K. Chanda, Lilliana Trinch, Weiping Zou, Adam H. Courtney
Journal: Science Immunology (2025)

T cell therapy efficacy can be compromised if cytokine-induced Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling is dysregulated or insufficient to sustain functionality. Here, we demonstrate that LCK kinase activity can be recruited to noncanonical protein substrates to directly activate targeted STAT proteins in T cells. STAT activation was accomplished by engineering the herpesvirus saimiri tyrosine kinase interacting protein (TIP) to provide a platform for the enforced recruitment of LCK to STAT proteins. We determined that a minimal region of TIP that binds to LCK could be combined with STAT binding sites derived from endogenous cytokine receptors. These constructs activated targeted STAT proteins in a cytokine-independent manner. We identified a STAT5 activator that sustained CD8+ T cell survival and cytotoxic function ex vivo in the absence of interleukin-2. Tumor outgrowth was reduced in vivo because of enhanced T cell persistence and functionality. Single-cell transcriptomics revealed that the STAT5 activator prevented the expression of genes associated with an exhausted T cell fate. Our findings demonstrate that signaling pathways can be rewired in T cells to sustain their function in solid tumors.
Advanced and interpretable corneal staining assessment through fine grained knowledge distillation
Authors: Yuqing Deng, Pujin Cheng, Ruiwen Xu, Lirong Ling, Hongliang Xue, Shiyou Zhou, Yansong Huang, Junyan Lyu, Zhonghua Wang, Kenneth K Y Wong, Yimin Zhang, Kang Yu, Tingting Zhang, Xiaoqing Hu, Xiaoyi Li, Xiaoying Tang, Yan Lou, Jin Yuan
Journal: npj Digital Medicine (2025)

The assessment of corneal fluorescein staining is essential, yet current AI models for Corneal Staining Score (CSS) assessments inadequately identify punctate lesions due to annotation challenges and noise, risk misrepresenting treatment responses through "plateau" effects, and highlight the necessity for real-world evaluations to enhance disease severity assessments. To address these limitations, we developed the Fine-grained Knowledge Distillation Corneal Staining Score (FKD-CSS) model. FKD-CSS integrates fine-grained features into CSS grading, providing continuous and nuanced scores with interpretability. Trained on corneal staining images collected from dry eye (DE) patients across 14 hospitals, FKD-CSS achieved robust accuracy, with a Pearson's r of 0.898 and an AUC of 0.881 in internal validation, matching senior ophthalmologists' performance. External tests on 2376 images from 23 hospitals across China further validated its efficacy (r: 0.844-0.899, AUC: 0.804-0.883). Additionally, FKD-CSS demonstrated generalizability in multi-ocular-surface-disease testing, underscoring its potential in handling different staining patterns.
Off-schedule patient-reported outcomes in adults with asthma may influence research results
Authors: Hami Park, Heather Klusaritz, Tyra Bryant-Stephens, A Russell Localio, Daniel Scharfstein, Kadel La Rose, Lenisha Fergus, Philycia Foote, Knashawn H Morales, Xiaoyan Han, Anna U Morgan, Andrea J Apter
Journal: Journal of Allergy and Clinical Immunology (2025)
Disease characteristics and monitoring of IDH1/IDH2-mutated acute myeloid leukemia
Authors: Mélinda Dantec, Maxime Dufossé, Augustin Boudry, Elise Fournier, Laure Goursaud, Delphine Lebon, Claire Bories, Isabelle Plantier, Sabine Tricot, Adrien Daniel, Alexandre Willaume, Valérie Coiteux, Céline Berthon, Jean-Pierre Marolleau, Claude Preudhomme, Nicolas Duployez, Laurène Fenwarth
Journal: Blood Cancer Journal (2025)
Updated Overall Survival and Long-Term Safety With Ripretinib Versus Sunitinib in Patients With GI Stromal Tumor: Final Overall Survival Analysis From INTRIGUE
Authors: Michael C. Heinrich, Jean-Yves Blay, Hans Gelderblom, Suzanne George, Patrick Schöffski, Margaret von Mehren, John R. Zalcberg, Robin L. Jones, Yoon-Koo Kang, Albiruni Abdul Razak, Jonathan Trent, Steven Attia, Axel Le Cesne, Kjetil Boye, David Goldstein, César Sánchez, Brittany L. Siontis, Paulina Cox, Erika Davis, Matthew L. Sherman, Rodrigo Ruiz-Soto, Sebastian Bauer
Journal: Journal of Clinical Oncology (2025)

In the INTRIGUE phase III trial (ClinicalTrials.gov identifier: NCT03673501 ), adult patients with advanced gastrointestinal stromal tumor previously treated with imatinib were randomly assigned 1:1 to ripretinib 150 mg once daily or sunitinib 50 mg once daily (4 weeks on/2 weeks off). In the primary analysis, overall survival (OS) was immature. In this study, we report the final planned analysis of OS (key secondary end point), progression-free survival (PFS) on third-line therapy (second PFS; prespecified exploratory end point), and long-term safety. Final OS analysis was prespecified to occur with approximately 200 and ≥145 events in the overall and KIT exon 11 intention-to-treat (ITT) populations, respectively. As of March 15, 2023, there were 211 and 151 OS events in the overall ITT and KIT exon 11 ITT populations, respectively. Median OS was similar between second-line ripretinib and sunitinib in both populations (overall, 35.5 v 31.5 months; KIT exon 11, 35.5 v 32.8 months). Median second PFS (on third-line therapy) for the overall ITT population was similar between the ripretinib and sunitinib arms (7.7 v 7.4 months). Safety was consistent with the primary analysis. OS from this analysis was similar between arms, and second PFS suggests that receiving ripretinib did not adversely affect the PFS of third-line therapy.