tbuckley/cabot-search huggingface dataset:
Projections of heat-related mortality in Chinese cities: The roles of climate change, urbanization, socioeconomic adaptation, and landscape level strategies
Authors: Xue Liu, Ming Hao, Yuyu Zhou, Yue Zhang, Ziheng Xu, Xiaojuan Liu, Yukun Gao, Rui Li, Han Zhang, Xia Li, Xiaoping Liu, Yuanzhi Yao
Journal: Environmental Health Perspectives (2025)

Physiological heat strain induced by extreme temperature in cities has led to significant heat-related deaths. Although socioeconomic adaptation is suggested to mitigate this issue, its effectiveness is limited. Conversely, there is a lack of comprehensive evaluation on the effectiveness of landscape level strategies for mitigating heat-related deaths. We developed a comprehensive modeling framework to estimate the impacts of environmental stresses and mitigating strategies on heat-related deaths in China's cities from 2016 to 2055. The framework assesses future heat-related deaths through five experiments considering the influences of climate change, urbanization, socioeconomic adaptation, and landscape level strategies. We used extrapolated region-specific exposure-response functions (ERF) and recent advancement of geo-statistics for public health to generate urban patch level ERF curves. We used these curves, temperature and population data to generate future heat-related deaths with 1 km resolution and conducted 5,000 Monte Carlo simulations for uncertainty analysis. Our analyses estimated that heat-related mortality will increase from 136.5±16.5 deaths per million in 2016 to 175.7±27.5 deaths per million in 2055 under SSP2-RCP4.5 (shared socioeconomic pathways-representative concentration pathways) scenario and from 140.0±21.4 deaths per million to 230.2±38.7 deaths per million under SSP5-RCP8.5 scenario, despite socioeconomic adaptation and landscape level strategies. Socioeconomic adaptation (reducing deaths by 18.4-64.1 per million) and landscape level strategies (reducing deaths by 45.6-51.3 per million) significantly mitigate heat-related deaths with varying effectiveness across different income levels. Specifically, in high-income cities with dense populations, landscape level strategies are 2.2-4.3 times more effective than socioeconomic adaptation. Within these cities, implementing the same landscape level strategies in the high-density urban centers lead to an additional reduction up to 4.9-6.8 death•km-2 compared to surrounding areas. Our framework helps to systematically understand the effectiveness of landscape level strategies in reducing heat-related mortality. Future sustainable city management should prioritize landscape level strategies along with socioeconomic adaptation to support healthy and comfortable communities. https://doi.org/10.1289/EHP15010.
Correlation of Natriuretic Peptides with Invasively Measured Intracardiac Filling Pressures in Patients With Cancer
Authors: Mariya M Fatakdawala, Hyeon-Ju Ryoo Ali, Juhee Song, Jorge A Irizarry-Caro, Saadia A Faiz, Salil Kumar, Syed Wamique Yusuf, Jean-Bernard Durand, Cezar Iliescu, Nicolas Palaskas, Anita Deswal, Efstratios Koutroumpakis
Journal: JACC CardioOncology (2025)
Mitigation of Doxorubicin Cardiotoxicity With Synergistic miRNA Combinations Identified Using Combinatorial Genetics en masse (CombiGEM)
Authors: Yasutomi Higashikuni, Colin Platt, Margaret H Hastings, William C W Chen, Justin R B Guerra, Takeshi Tokuyama, Fuad Gandhi Torizal, Wenhao Liu, Takumi Obana, Abraham L Bayer, Hannah Whipple, Alexandra Kuznetsov, Ashish Yeri, Cole Turissini, Robert R Kitchen, Kota Shibayama, Takayoshi Matsumura, Norihiko Takeda, Hideki Uosaki, Aarti H Asnani, Timothy K Lu, Anthony Rosenzweig
Journal: JACC CardioOncology (2025)

Cardiomyocyte loss occurs in acute and chronic cardiac injury, including cardiotoxicity due to chemotherapeutics like doxorubicin, and contributes to heart failure development. There is a pressing need for cardiac-specific therapeutics that target cardiomyocyte loss, preventing chemotherapy complications without compromising chemotherapeutic efficacy. The authors employed massively parallel combinatorial genetic screening to find microRNA (miRNA) combinations that promote cardiomyocyte survival. CombiGEM (combinatorial genetics en masse) screening in a cardiomyocyte cell line was followed by validation in the original cell type and screening in primary cardiomyocytes. The top combination was tested in mouse and developing zebrafish models of doxorubicin cardiotoxicity. RNA sequencing provided insight into possible mechanisms. Multiple miRNA combinations protected cardiomyocytes from doxorubicin in vitro. The most effective (miR-222+miR-455) appeared to act synergistically, and mitigated doxorubicin cardiotoxicity phenotypes in murine and zebrafish in vivo models. RNA sequencing revealed overlapping and synergistic regulation of relevant genes and biological processes in cardiomyocytes, including mitochondrial homeostasis, oxidative stress, muscle contraction, and others. We identified miR-222 and miR-455 as a combination with potential therapeutic applications for cardioprotection. This study furthers our knowledge of the cardiac effects of miRNAs and their combinations and demonstrates the potential of CombiGEM for cardioprotective combinatorial therapeutic discovery.
Blood Pressure Lowering and Risk of Cancer
Authors: Milad Nazarzadeh, Emma Copland, Karl Smith Byrne, Dexter Canoy, Zeinab Bidel, Mark Woodward, Qianqian Yang, James McKay, Anders Mälarstig, Åsa K Hedman, John Chalmers, Koon K Teo, Carl J Pepine, Barry R Davis, Sverre E Kjeldsen, Johan Sundström, Kazem Rahimi
Journal: JACC CardioOncology (2025)

Pharmacologic blood pressure (BP) lowering is typically a lifelong treatment, and both clinicians and patients may have concerns about the long-term use of antihypertensive agents and the risk for cancer. However, evidence from randomized controlled trials (RCTs) regarding the effect of long-term pharmacologic BP lowering on the risk for new-onset cancer is limited, with most knowledge derived from observational studies. The aim of this study was to assess whether long-term BP lowering affects the risk for new-onset cancer, cause-specific cancer death, and selected site-specific cancers. Individual-level data from 42 RCTs were pooled using a one-stage individual participant data meta-analysis. The primary outcome was incident cancer of all types, and secondary outcomes were cause-specific cancer death and selected site-specific cancers. Prespecified subgroup analyses were conducted to assess the heterogeneity of the BP-lowering effect by baseline variables and over follow-up time. Cox proportional hazards regression, stratified by trial, was used for the statistical analysis. For site-specific cancers, analyses were complemented with Mendelian randomization, using naturally randomized genetic variants associated with BP lowering to mimic the design of a long-term RCT. Data from 314,016 randomly allocated participants without known cancer at baseline were analyzed. Over a median follow-up of 4 years (Q1-Q3: 3-5 years), 17,954 participants (5.7%) developed cancer, and 4,878 (1.5%) died of cancer. In the individual participant data meta-analysis, no associations were found between reductions in systolic or diastolic BP and cancer risk (HR per 5 mm Hg reduction in systolic BP: 1.03 [95% CI: 0.99-1.06]; HR per 3 mm Hg reduction in diastolic BP: 1.03 [95% CI: 0.98-1.07]). No changes in relative risk for incident cancer were observed over follow-up time, nor was there evidence of heterogeneity in treatment effects across baseline subgroups. No effect on cause-specific cancer death was found. For site-specific cancers, no evidence of an effect was observed, except a possible link with lung cancer risk (HR for systolic BP reduction: 1.17; 99.5% CI: 1.02-1.32). Mendelian randomization studies showed no association between systolic or diastolic BP reduction and site-specific cancers, including overall lung cancer and its subtypes. Randomized data analysis provided no evidence to indicate that pharmacologic BP lowering has a substantial impact, either increasing or decreasing, on the risk for incident cancer, cause-specific cancer death, or selected site-specific cancers.
Effects of Bisphenol A and Retinoic Acid Exposure on Neuron and Brain Formation: a Study in Human Induced Pluripotent Stem Cells and Zebrafish Embryos
Authors: Tomomi Nishie, Tomoki Taya, Shunichi Omori, Kenya Ueno, Yoshinori Okamoto, Shogo Higaki, Marina Oka, Yachiyo Mitsuishi, Taiga Tanaka, Mana Nakamoto, Hideaki Kawahara, Natsuki Teraguchi, Tomoyuki Kotaka, Misaki Sawabe, Miu Takahashi, Shoko Kitaike, Minori Wada, Keiko Iida, Akihiro Yamashita, Hideto Jinno, Atsuhiko Ichimura, Ikuo Tooyama, Noriyoshi Sakai, Masahiko Hibi, Akira Hirasawa, Tatsuyuki Takada
Journal: Environmental Health Perspectives (2025)

Developing human fetuses may be exposed to the chemical compound bisphenol A (BPA), and retinoic acid (RA) has been detected at low levels in water sources. RA signaling regulates key developmental genes and is essential for organ development, including the brain. We previously reported that RA/BPA co-exposure of mouse embryonic stem cells potentiates RA signaling, which warrants further investigation. This study was undertaken in human induced pluripotent stem cells (iPSCs) and zebrafish embryos to investigate whether co-exposure to BPA and exogenous RA could potentiate HOX gene expression and exert pleiotropic effects on RA signaling. Human iPSCs and zebrafish embryos were exposed to exogenous RA (0, 7.5, 10, or 12.5 nM) or BPA (20 µM) alone or co-exposed to BPA (2 nM-20 µM) and exogenous RA (7.5-100 nM). Post-exposure changes in HOX genes were assessed by quantitative polymerase chain reaction and/or transcriptome analyses. RA receptor antagonists were used to identify the receptor responsible for signaling. In zebrafish, spacial expression of fgf8a and hoxb1a was evaluated by whole-mount in situ hybridization. Mauthner cell and craniofacial cartilage anomalies were studied by immunostaining and Alcian blue staining, respectively. Transcriptome was compared between iPSCs and zebrafish to identify alterations of common biologic processes. Gradient curves of RA signal were calculated to simulate the effects of exogenous RA and BPA in zebrafish. In both iPSCs and zebrafish, RA/BPA co-exposure had higher expression of 3' HOX genes compared to RA alone; BPA alone had no effect. Addition of RA receptor antagonists abolished these changes. In zebrafish, RA/BPA co-exposure, compared to RA alone, resulted in a significant rostral shift in hoxb1a expression and increased rate of anomalies in Mauthner cells and craniofacial cartilage. Transcriptome comparison and correlations between the experimental results and gradient curve simulations strengthened these observations. Our findings suggested a mechanistic link between chemical exposure and neurodevelopmental impairments, and demonstrated involvement of exogenous RA signaling in endocrine disruption. Further investigation is needed to explore why BPA alone did not affect endogenous RA signaling, whereas exogenous RA signaling was potentiated with RA/BPA co-exposure. https://doi.org/10.1289/EHP15574.
Patient perceptions of empathy in physician and artificial intelligence chatbot responses to patient questions about cancer
Authors: David Chen, Kabir Chauhan, Rod Parsa, Zhihui Amy Liu, Fei-Fei Liu, Ernie Mak, Lawson Eng, Breffni Louise Hannon, Jennifer Croke, Andrew Hope, Nazanin Fallah-Rad, Phillip Wong, Srinivas Raman
Journal: npj Digital Medicine (2025)
A framework to assess clinical safety and hallucination rates of LLMs for medical text summarisation
Authors: Elham Asgari, Nina Montaña-Brown, Magda Dubois, Saleh Khalil, Jasmine Balloch, Joshua Au Yeung, Dominic Pimenta
Journal: npj Digital Medicine (2025)

Integrating large language models (LLMs) into healthcare can enhance workflow efficiency and patient care by automating tasks such as summarising consultations. However, the fidelity between LLM outputs and ground truth information is vital to prevent miscommunication that could lead to compromise in patient safety. We propose a framework comprising (1) an error taxonomy for classifying LLM outputs, (2) an experimental structure for iterative comparisons in our LLM document generation pipeline, (3) a clinical safety framework to evaluate the harms of errors, and (4) a graphical user interface, CREOLA, to facilitate these processes. Our clinical error metrics were derived from 18 experimental configurations involving LLMs for clinical note generation, consisting of 12,999 clinician-annotated sentences. We observed a 1.47% hallucination rate and a 3.45% omission rate. By refining prompts and workflows, we successfully reduced major errors below previously reported human note-taking rates, highlighting the framework's potential for safer clinical documentation.
Can transperineal ultrasound replace endoscopic ultrasound in staging distal ulcerative colitis?
Authors: Partha Pal, Mohammad Abdul Mateen, Anuradha Sekaran, Kanapuram Pooja, Arzeena Kaleemuddin, Thanmayee Rangineni, Jahangeer Basha, Rajesh Gupta, Manu Tandan, Sundeep Lakhtakia, D Nageshwar Reddy
Journal: Gut (2025)
Severe community-acquired pneumonia (sCAP): advances in management and future directions
Authors: Ignacio Martin-Loeches, Luis Felipe Reyes, Alejandro Rodriguez
Journal: Thorax (2025)

Severe community-acquired pneumonia (sCAP) is a major global health challenge, with high morbidity and mortality, especially among patients requiring intensive care. Despite advancements in antimicrobial therapies and supportive care, sCAP remains a significant threat, particularly for those needing invasive mechanical ventilation or vasopressor support. Recent progress in diagnostics, therapeutics and management strategies offers hope for improved outcomes. Pathogen-specific management is now central to sCAP care, with molecular diagnostics enhancing pathogen detection accuracy and enabling tailored antimicrobial therapy. These tools help combat antimicrobial resistance by reducing unnecessary broad-spectrum antibiotic use. Host immune responses in sCAP vary widely and significantly impact outcomes. Some patients face an overwhelming pathogen burden, while others experience excessive immune responses, such as acute respiratory distress syndrome. This distinction is vital for guiding immunomodulatory therapies, as immunosuppression may benefit hyperinflammatory states but harm those overwhelmed by infection. Corticosteroids, though controversial, show potential benefits in select populations but carry risks like secondary infections and hyperglycaemia, requiring a nuanced approach. Non-invasive respiratory support strategies, such as high-flow nasal oxygen, have transformed care by improving oxygenation and reducing the need for invasive ventilation. However, their efficacy depends on timing, patient tolerance and disease severity, necessitating careful monitoring. Global disparities in sCAP management, particularly in low-income and middle-income countries, highlight the need for region-specific guidelines and scalable solutions. Limited access to advanced diagnostics and critical care resources exacerbates poor outcomes, underscoring the importance of investments in affordable diagnostics, infection control and multidisciplinary training. Emerging technologies, such as artificial intelligence and advanced imaging, promise to revolutionise sCAP management by enabling precision medicine and real-time insights into disease severity. A holistic, multidisciplinary approach integrating these advancements is essential to improving outcomes and advancing personalised care for this life-threatening condition.
Serotype 3 associated invasive pneumococcal disease in children: analysis of 15 years of Australian national surveillance data
Authors: Nusrat Homaira, Jahidur Rahman Khan, Adam Jaffé
Journal: Thorax (2025)

The 13-valent conjugate pneumococcal vaccine (13vPCV) replaced the 7vPCV in the Australian Immunisation Program in 2011 as a 3+0 schedule, updated to 2+1 schedule in 2018. We analysed national surveillance data to investigate the change in the incidence of pneumococcal serotype 3 (ST3) invasive pneumococcal disease (IPD) in preschool children. During 2009–2023 the incidence/100 000 children of ST3 IPD increased from 0.42 in 2009 to 3.65 in 2023. Compared with 2009–2011 (7vPCv), ST3 IPD incidence in 2012–2018 (13vPCV 3+0 dose) was almost four times higher and two times higher in 2019–2023 (13vPCV 2+1 dose) compared with 2012–2018 suggesting limited protection against ST3.
Prevention of rebleeding after primary haemostasis using haemostatic powder in non-variceal upper gastrointestinal bleeding: a multicentre randomised controlled trial
Authors: Jongbeom Shin, Boram Cha, Jitaek Hong, Kye Sook Kwon, Eunhye Lee, Jin Hee Maeng, Jun-Won Chung, Dong Kyun Park, Yoon Jae Kim, Kwang An Kwon, Jung Ho Kim, Kwang-Suk Seo, Su Jin Hong, Kyoung Oh Kim
Journal: Gut (2025)

Background Non-variceal upper gastrointestinal bleeding (NVUGIB) remains a major cause of morbidity and mortality. Rebleeding rates following endoscopic treatment can reach up to 25% within 72 hours in patients with high-risk lesions. Objective To evaluate the efficacy of a haemostatic powder (Nexpowder) in reducing rebleeding rates after conventional endoscopic treatment in patients with NVUGIB. Design This was a prospective, multicentre, randomised controlled trial involving patients with acute NVUGIB from high-risk lesions who achieved initial endoscopic haemostasis. Participants were randomised 1:1 to receive either the haemostatic powder or no further therapy (control group). The primary outcome was the rebleeding rate within 72 hours post-treatment. Secondary outcomes included the 30-day rebleeding rate and the safety profile. Results A total of 341 patients (72.1% male; mean age 64.8 years) were included, with 173 in the powder group and 168 in the control group. Baseline characteristics were similar between groups. Ulcer bleeding was the predominant aetiology (n=317), with Forrest type I bleeding observed in two-thirds of cases. The 72-hour rebleeding rate was significantly lower in the powder group (2.9%, 95% CI 0.9 to 6.6%) compared with the control group (11.3%, 95% CI 6.9 to 17.1%; p =0.005). A significant reduction was also observed in the 30-day cumulative rebleeding rate (7.0% vs 18.8%), with similar findings in the ulcer subgroup for the 3-day rebleeding rate (3.0% vs 12.0%; p =0.004). No adverse events related to the powder application were reported. Conclusion The application of Nexpowder following endoscopic haemostasis significantly reduced both early (3 days) and late (30 days) rebleeding rates in patients with NVUGIB, particularly in cases of ulcer-related bleeding. Trial registration number NCT04124588 .
Effect of viloxazine and trazodone in obstructive sleep apnoea: a randomised, placebo-controlled, cross-over study
Authors: Atqiya Aishah, Molly Kim, Laura Gell, Daniel Vena, Ali Azarbarzin, Huy Pho, Daniel Norman, Joseph Ojile, Neda Esmaeili, Luigi Taranto-Montemurro, Andrew Wellman, Scott Sands, Ludovico Messineo
Journal: Thorax (2025)

Introduction Combination of the noradrenergic atomoxetine with either the antimuscarinic aroxybutynin or trazodone has been shown to improve obstructive sleep apnoea (OSA) severity. However, atomoxetine may contribute to apnoea-cycling and reduced drug tolerability due to wake-promoting, especially in a subgroup (poor cytochrome 2D6 metabolisers leading to higher blood concentration of medication). We investigated the effect of a potentially more manageable noradrenergic, viloxazine, with and without trazodone, on OSA severity. Methods In this double-blind, placebo-controlled, cross-over study, 24 patients with OSA (18–75 years) were analysed and randomised to 500 mg viloxazine, 500/75 mg viloxazine-trazodone (vilo-trazo) or placebo; taken before bed for 2 weeks with 1-week washout between treatments. In-laboratory polysomnography was performed at the end of each cross-over period. Mixed-model analyses compared the effect of vilo-trazo versus placebo on AHI 4 (apnoea-hypopnoea index with 4% desaturations; primary outcome) and hypoxic burden (secondary outcome). Additional outcomes examined the effects of vilo-trazo versus viloxazine on total sleep time (TST) and wake-after-sleep-onset (WASO). Safety endpoints (patient-reported outcomes, heart rate and adverse events) were also assessed. Results Vilo-trazo reduced AHI 4 (mean difference (95% CI): 10.5 (6.6, 13.6) events/hour, p&lt;0.001) and hypoxic burden (16.7 (9.6, 21.8) %min/hr, p&lt;0.001) versus placebo. Compared with viloxazine, TST tended to be longer on vilo-trazo (22.3 (−1.4, 46.0) min, p&lt;0.065), while WASO was unchanged. TST and WASO remained significantly reduced on vilo-trazo versus placebo. Both interventions worsened patient-reported outcomes, although to a lesser extent on vilo-trazo, and increased heart rate versus placebo. Commonly reported adverse events were insomnia, constipation, headache and xerostomia. Conclusions Viloxazine-trazodone reduced OSA severity. Potential deleterious effects of viloxazine on sleep quality appeared partly attenuated by trazodone. Trial registration number NCT05793684 .
Hepatocyte-specific C-C motif chemokine ligand 9 signaling promotes liver fibrosis progression in mice
Authors: Chaomin Wang, Dong Dong, Na Zhao, Shuya Zhao, Jialei Hua, Changsen Bai, Ranliang Cui, Ting Zhao, Ning Ji, Huikai Li, Yang Liu, Yueguo Li
Journal: Hepatology (2025)

Background and Aims: Liver fibrosis involves the activation of hepatic stellate cells (HSCs) and persistent inflammatory responses. Ccl9, a CC chemokine implicated in inflammation, has an undefined role in liver homeostasis. Our study investigates this murine homolog of human CCL15 to elucidate its role in the development of liver fibrosis. Approach and Results: We investigated the expression of Ccl9 and its upstream regulatory elements in liver fibrosis using mouse models induced by carbon tetrachloride (CCl 4 ), bile-duct ligation, and a high-fat, methionine- and choline-deficient diet. A significant increase in Ccl9 expression was observed in fibrotic liver tissues, predominantly in damaged hepatocytes, with Myc identified as a key driver of this upregulation. The role of Ccl9 was further elucidated through hepatocyte-specific knockout mice, neutralizing antibodies, and in vitro analyses of hepatic stellate cells (HSCs) and macrophages. Targeted deletion of Ccl9 in hepatocytes mitigated liver fibrosis and injury across multiple models, characterized by reduced inflammation and decreased monocyte/macrophage and neutrophil infiltration. Additionally, neutralizing Ccl9 in CCl 4 -induced models reduced both fibrosis and liver damage. Mechanistically, Ccl9 modulated macrophage infiltration, promoted M1 polarization, and regulated inflammatory cytokine responses through the Ccr1 receptor in models of hepatic injury induced by CCl 4 and bile-duct ligation. Furthermore, Ccl9 directly activated HSCs by recruiting Myh9 via Ccr1, thereby enhancing the Wnt signaling pathway through Myh9-mediated Gsk3β ubiquitination. Conclusions: Ccl9 is a significant contributor to liver fibrosis, influencing macrophage behavior and directly activating HSCs. Targeting Ccl9 offers a potential therapeutic approach for treating liver fibrosis.
Pleuropulmonary Blastoma on FDG PET/CT in a Pediatric Patient Before and After Treatment
Authors: Pensiree Attaseth, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2025)

A 5-year-old boy with right-sided chest pain and fever was diagnosed with pleuropulmonary blastoma, confirmed by thoracoscopic biopsy. Initial imaging showed a large hypermetabolic mass in the right lower lobe. After 2 cycles of chemotherapy, FDG PET/CT demonstrated significant solid component shrinkage and increased cystic airspaces with decreased hypermetabolic activity. After surgery, pathology confirmed type II pleuropulmonary blastoma. Nine months later, recurrent disease was detected on follow-up FDG PET/CT. Patient underwent further tumor resection, followed by radiation and chemotherapy. This case illustrates the evolving FDG PET/CT findings, and recurrence of pleuropulmonary blastoma after treatment.