tbuckley/cabot-search huggingface dataset:
Selective BCL-2 inhibitor triggers STING-dependent antitumor immunity via inducing mtDNA release
Authors: Wenxin Zhang, Xiaohui Pan, Longsheng Wang, Wen Li, Xiaoyang Dai, Mingming Zheng, Hongjie Guo, Xi Chen, Yanjun Xu, Honghai Wu, Qiaojun He, Bo Yang, Ling Ding
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background The stimulator of interferon genes (STING) signaling pathway has been demonstrated to propagate the cancer-immunity cycle and remodel the tumor microenvironment and has emerged as an appealing target for cancer immunotherapy. Interest in STING agonist development has increased, and the candidates hold significant promise; however, most are still in the early stages of human clinical trials. We found that ABT-199 activated the STING pathway to enhance the immunotherapeutic effect, and provided a ready-to-use small molecule drug for STING signaling activation. Methods Phosphorylation of STING, TBK1, and IRF3, as well as activation of the interferon-I (IFN-I) signaling pathway, were detected following ABT-199 treatment in various colorectal cancer cells. C57BL/6J and BALB/c mice with subcutaneous tumors were employed to evaluate the in vivo therapeutic effects of the ABT-199 and anti-PD-L1 combination. Flow cytometry and ELISA were employed to analyze the level and activity of tumor-infiltrating T lymphocytes. Immunofluorescence and quantitative real-time PCR were conducted to assess the source and accumulation of double stranded DNA (dsDNA) in the cytoplasm. Chemical cross-linking assay, co-immunoprecipitation, and CRISPR/Cas9-mediated knockout were performed to investigate the molecular mechanism underlying ABT-199-induced voltage-dependent anion channel protein 1 (VDAC1) oligomerization and mitochondrial DNA (mtDNA) release. Results ABT-199 significantly activated the STING signaling pathway in various colorectal cancer cells, which was evidenced by increased phosphorylation of TBK1 and IRF3, and upregulation of C-C motif chemokine ligand 5 (CCL5), C-X-C motif chemokine ligand 10 (CXCL10), and interferon beta transcription. By promoting chemokine expression and cytotoxic T-cell infiltration, ABT-199 promoted antitumor immunity and synergized with anti-PD-L1 therapy to improve antitumor efficacy. ABT-199 induced mtDNA accumulation in the cytoplasm and triggered STING signaling via the canonical pathway. cGAS or STING-KO models significantly abolished both STING signaling activation and the antitumor efficacy of ABT-199. Mechanically, ABT-199 promoted VDAC1 oligomerization by disturbing the binding between BCL-2 and VDAC1, thereby facilitating mtDNA release into the cytoplasm. ABT-199-triggered STING signaling was attenuated when VADC1 was knocked out. Consistently, the antitumor effect of ABT-199 in vivo was abolished in the absence of VDAC1. Conclusions Our results identify a ready-to-use small molecule compound for STING activation, reveal the underlying molecular mechanism through which ABT-199 activates the STING signaling pathway, and provide a theoretical basis for the use of ABT-199 in cancer immunotherapy.
Impact of exercise on health outcomes in people with cancer: an umbrella review of systematic reviews and meta-analyses of randomised controlled trials
Authors: Xue-Li Bai, Yu Li, Zan-Fei Feng, Fan Cao, Dong-Dong Wang, Jing Ma, Dan Yang, Dong-Run Li, Qian Fang, Ying Wang, Xiao-Feng Jiang, Dong-Hui Huang, Xiao-Ying Li, Jia-Kai Guo, Na Zhao, Zhi-Tong Li, Qi-Peng Ma, Lei Wang, Qi-Jun Wu, Ting-Ting Gong
Journal: British Journal of Sports Medicine (2025)

Objective To examine the comprehensive health impacts of exercise on people with cancer by systematically summarising existing evidence and assessing the strength and reliability of the associations. Design Umbrella review of meta-analyses. Data source PubMed, Embase, Cochrane and Web of Science databases were searched from their inception to 23 July 2024. Eligibility criteria for selecting studies Meta-analyses of randomised controlled trials that investigated the associations between exercise and health outcomes among people with cancer. Results This umbrella review identified 485 associations from 80 articles, all evaluated as moderate to high quality using A Measurement Tool to Assess Systematic Reviews (AMSTAR). Two hundred and sixty (53.6%) associations were statistically significant (p&lt;0.05), 81/485 (16.7%) were supported by high-certainty evidence according to the Grading of Recommendations Assessment, Development, and Evaluation criteria. Compared with usual care or no exercise, moderate- to high-certainty evidence supported the view that exercise significantly mitigates adverse events associated with cancer and its treatments (eg, cardiac toxicity, chemotherapy-induced peripheral neuropathy, cognitive impairment and dyspnoea). Exercise also modulates body composition and biomarkers (eg, insulin, insulin-like growth factor-1, insulin-like growth factor-binding protein-1 and C-reactive protein) in people with cancer, and enhances sleep quality, psychological well-being, physiological functioning and social interaction, while improving overall quality of life. Conclusion Exercise reduces adverse events and enhances well-being through a range of health outcomes in people with cancer.
Ferric carboxymaltose assessment of morbidity and mortality in patients with iron deficiency and chronic heart failure (<scp>FAIR</scp>‐<scp>HF2</scp>‐<scp>DZHK05</scp>) trial: Baseline characteristics and comparison to other relevant clinical trials
Authors: Stefan D. Anker, Tim Friede, Javed Butler, Khawaja M. Talha, Marius Placzek, Monika Diek, Anna Nosko, Adriane Stas, Stefan Kluge, Dominik Jarczak, Geraldine Deheer, Meike Rybczynski, Antoni Bayes‐Genis, Frank Edelmann, Gerasimos Filippatos, Gerd Hasenfuß, Wilhelm Haverkamp, Mitja Lainscak, Ulf Landmesser, Iain C. Macdougall, Bela Merkely, Burkert M. Pieske, Fausto J. Pinto, Tienush Rassaf, Maurizio Volterrani, Stephan von Haehling, Markus S. Anker, Wolfram Doehner, Hüseyin Ince, Friedrich Koehler, Gianluigi Savarese, Ursula Rauch‐Kröhnert, Tommaso Gori, Teresa Trenkwalder, Ibrahim Akin, Christina Paitazoglou, Iwona Kobielusz‐Gembala, Witold Zmuda, Luca Kuthi, Norbert Frey, Manuela Licka, Stefan Kääb, Karl‐Ludwig Laugwitz, Piotr Ponikowski, Mahir Karakas
Journal: European Journal of Heart Failure (2025)

Aims Prior randomized trials have reported conflicting evidence regarding the efficacy of intravenous (IV) iron in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency (ID). Methods and results FAIR‐HF2 is a double‐blind, randomized, controlled trial evaluating the efficacy of IV ferric carboxymaltose in patients with HFrEF and ID. We report the baseline characteristics of enrolled patients and compare them with other major trials of IV iron in HFrEF (FAIR‐HF, CONFIRM‐HF, AFFIRM‐AHF, IRONMAN, and HEART‐FID). A total of 1105 patients were randomized between March 2017 and November 2023. Most patients were men (67%) and median age was 72 (interquartile range [IQR] 63–79) years. More than one‐third had a heart failure hospitalization within the preceding 12 months (36%), and 53% were hospitalized at randomization. Common comorbidities included hypertension (79%), coronary artery disease (74%), dyslipidaemia (67%), and diabetes (46%). The median left ventricular ejection fraction was 58% (IQR 42–77) and mean estimated glomerular filtration rate was 58 (IQR 42–77) ml/min/1.73 m 2 . A total of 1064 (96%) patients were on renin–angiotensin system inhibitors (angiotensin receptor–neprilysin inhibitors [ARNI] 38%), 1016 (92%) on beta‐blockers, and 779 (71%) on mineralocorticoid receptor antagonists; and 261 (24%) of patients were on sodium–glucose cotransporter 2 (SGLT2) inhibitors, which is much higher than prior trials. A higher proportion of patients had ischaemic HFrEF (78%) compared to preceding trials. The baseline median haemoglobin (g/dl) was 12.7 (IQR 11.8–13.4), median serum ferritin (μg/dl) was 63 (IQR 36–90), and median transferrin saturation (%) was 16.5 (IQR 11.8–22.9), resembling that of other trials. The mean 6‐min walk distance at enrolment was 314 ± 118 m. Conclusion The FAIR‐HF2 trial represents a contemporary cohort of patients with baseline characteristics mostly similar to prior trial populations. Use of SGLT2 inhibitors and ARNI in FAIR‐HF2 was higher than in prior trials. Clinical Trial Registration: ClinicalTrials.gov ID NCT03036462.
The efficacy of finerenone on hierarchical composite endpoint analysed using win statistics in patients with heart failure and mildly reduced or preserved ejection fraction: A prespecified analysis of <scp>FINEARTS</scp>‐<scp>HF</scp>
Authors: Toru Kondo, Pardeep S. Jhund, Alasdair D. Henderson, Brian L. Claggett, Akshay S. Desai, Meike Brinker, James Lay‐Flurrie, Patrick Schloemer, Prabhakar Viswanathan, Flaviana Amarante, Chern‐En Chiang, Gerasimos Filippatos, Carolyn S.P. Lam, Mark C. Petrie, Michele Senni, Morten Schou, Subodh Verma, Adriaan A. Voors, Dirk von Lewinski, Faiez Zannad, Bertram Pitt, Muthiah Vaduganathan, Scott D. Solomon, John J.V McMurray
Journal: European Journal of Heart Failure (2025)
Fine resolution of the N-terminal IgE-binding epitope of Ara h 2: discovery of variants with enhanced IgE binding
Authors: Joshua S Bernstein, Nicole Canon, Catherine H Schein, Werner Braun, Surendra S Negi, Raffi Tchekmedyian, Marina Pozzoli, Edwin H Kim, Michael D Kulis, Thao Vu, Weimin Liu, Xueni Chen, Stephen C Dreskin
Journal: Journal of Allergy and Clinical Immunology (2025)
Michigan Screening and Intervention for Glaucoma and Eye Health through Telemedicine Program: Impact on Vision, Follow-up, and Costs
Authors: Paula Anne Newman-Casey, Leslie M Niziol, Angela R Elam, Amanda K Bicket, Rithambara Ramachandran, Leroy Johnson, Martha Kershaw, Suzanne Winters, Maria A Woodward
Journal: Ophthalmology (2025)
Optimal timing for lumen-apposing metal stent removal following endoscopic ultrasound-guided drainage of pancreatic fluid collections: a systematic review and meta-analysis
Authors: Marcello Maida, Giacomo Emanuele Maria Rizzo, Mario Traina, John Gásdal Karstensen, Rogier P. Voermans, Joan B. Gornals, Nitin Jagtap, Dario Ligresti, Lucio Carrozza, Gabriele Rancatore, Marco Ventimiglia, Antonio Facciorusso, Carlo Fabbri, Andrea Anderloni, Ilaria Tarantino
Journal: Endoscopy (2025)

Background Lumen-apposing metal stents (LAMSs) are widely used for endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs). Safety is a major concern and the timing of LAMS removal is debated owing to the risk of adverse events (AEs). Previous studies showed early stent removal was associated with a reduced risk of AEs, but data are still conflicting. The aim of this systematic review with meta-analysis was to identify the optimal timing for LAMS removal. Methods Major databases were systematically searched until May 2024. The outcome assessed was the cumulative incidence of AEs related to the early (within 3–4 weeks) versus late (after 3–4 weeks) removal of the LAMS. A random-effects (DerSimonian–Laird) model was used to pool the results. Results Eight studies (1820 patients; mean age 54–61.6 years; 63 % men) were included in the analysis. PFCs included walled-off necrosis (WON; 58.2 %) and pseudocysts (41.8 %). Pooled LAMS-related AEs rate were similar in the late versus early removal groups (risk ratio [RR] 1.03, 95 %CI 0.47–2.28; P = 0.94). Sensitivity analysis, including only studies applying a 4-week cut-off, confirmed a comparable AEs rate (RR 0.80, 95 %CI 0.38–1.65; P = 0.59). The mean (SD) follow-up of the studies was 208 (88) days. Conclusions The results of this meta-analysis showed no difference in the incidence of AEs between early and late removal of LAMSs in the presence of moderate heterogeneity across studies. Removal within 4 weeks is not warranted, and it may instead be planned on a clinical case-by-case basis according on the patient's condition.
Validation and clinical implementation of cerebrospinal fluid C-reactive protein for the diagnosis of bacterial meningitis: a prospective diagnostic accuracy study
Authors: Sabine E. Olie, Steven L. Staal, Nina S. Groeneveld, Hans H.M. Schotman, Jacob Bodilsen, Henrik Nielsen, Merijn W. Bijlsma, Diederik van de Beek, Matthijs C. Brouwer
Journal: The Lancet Regional Health - Europe (2025)
Endoscopic drainage for a thoracic abscess caused by delayed perforation after endoscopic submucosal dissection for gastric tube cancer: a case report
Authors: Aiji Hattori, Yuji Owaki, Atsushi Inaba, Daisuke Kajiyama, Kazuma Sato, Takeo Fujita, Tomonori Yano
Journal: Endoscopy (2025)
Artificial intelligence entering the pathology arena in oncology: current applications and future perspectives
Authors: A Marra, S Morganti, F Pareja, G Campanella, F Bibeau, T Fuchs, M Loda, A Parwani, A Scarpa, J S Reis-Filho, G Curigliano, C Marchiò, J N Kather
Journal: Annals of Oncology (2025)

Artificial intelligence (AI) is rapidly transforming the fields of pathology and oncology, offering novel opportunities for advancing diagnosis, prognosis, and treatment of cancer. Through a systematic review-based approach, the representatives from the European Society for Medical Oncology (ESMO) Precision Oncology Working Group (POWG) and international experts identified studies in pathology and oncology that applied AI-based algorithms for tumour diagnosis, molecular biomarker detection, and cancer prognosis assessment. These findings were synthesised to provide a comprehensive overview of current AI applications and future directions in cancer pathology. The integration of AI tools in digital pathology is markedly improving the accuracy and efficiency of image analysis, allowing for automated tumour detection and classification, identification of prognostic molecular biomarkers, and prediction of treatment response and patient outcomes. Several barriers for the adoption of AI in clinical workflows, such as data availability, explainability, and regulatory considerations, still persist. There are currently no prognostic or predictive AI-based biomarkers supported by level IA or IB evidence. The ongoing advancements in AI algorithms, particularly foundation models, generalist models and transformer-based deep learning, offer immense promise for the future of cancer research and care. AI is also facilitating the integration of multi-omics data, leading to more precise patient stratification and personalised treatment strategies. The application of AI in pathology is poised to not only enhance the accuracy and efficiency of cancer diagnosis and prognosis but also facilitate the development of personalised treatment strategies. Although barriers to implementation remain, ongoing research and development in this field coupled with addressing ethical and regulatory considerations will likely lead to a future where AI plays an integral role in cancer management and precision medicine. The continued evolution and adoption of AI in pathology and oncology are anticipated to reshape the landscape of cancer care, heralding a new era of precision medicine and improved patient outcomes.
The prevalence of parental cancer history and in vitro fertilization utilization
Authors: Abby L Chen, Shufeng Li, Valerie L Baker, Philip J Lupo, Hazel B Nichols, Michael L Eisenberg, Barbara Luke
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Background Advances in cancer treatment have led to an increased number of survivors who may subsequently have children. We aim to describe the prevalence of a parental cancer history with and without the utilization of in vitro fertilization (IVF) in several states in the United States. Methods This study used data from IVF cycles resulting in live births reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System from 2004 to 2018. These were linked to birth certificates and cancer registries in 3 states (New York, Massachusetts, and North Carolina). For each IVF-conceived delivery, the subsequent 10 deliveries were used as the naturally conceived comparison group. A parent’s cancer history was included if the diagnosis preceded the birth of the first child. Results There were 814 658 births (82 544 IVF-conceived and 732 114 naturally conceived births) in our analysis. Among births conceived naturally, 0.5% of mothers and 0.4% of fathers had a cancer history compared with 1.2% of mothers and 1.8% of fathers among IVF-conceived births. The prevalence of cancer history increased over the study period (P ≤.004). The most common cancers among mothers were thyroid or endocrine (28.7%) and breast (12.2%) vs male genital (26.3%) and thyroid or endocrine (9.1%) among fathers. There were higher rates of male and female genital malignancies, female breast, and female lymphoid or hematopoietic cancers among parents who conceived with IVF (P &amp;lt; .001). Conclusions Overall, 1.1% of all births and 3.0% of IVF-conceived births had at least 1 parent with a cancer history with an increasing prevalence over the study period, highlighting the importance of oncofertility programs.
Estimating global direct health-care spending on neurological and mental health between 2000 and 2019: a modelling study
Authors: A J Mitchell, Ian E Cogswell, Jeremy Dalos, Golsum Tsakalos, Jiali Lei, Andrei Oros, Quinn Rafferty, Serena Santoni, Xaviera Steele, Joseph L Dieleman, Angela E Apeagyei
Journal: The Lancet Public Health (2025)
Cigarette taxation and socioeconomic inequalities in under-5 mortality across 94 low-income and middle-income countries: a longitudinal ecological study
Authors: Olivia S Bannon, Jasper V Been, Sam Harper, Anthony A Laverty, Christopher Millett, Frank J van Lenthe, Filippos T Filippidis, Márta K Radó
Journal: The Lancet Public Health (2025)
Isolated perianal Crohn's disease: a systematic review and expert consensus proposing novel diagnostic criteria and management advice
Authors: Luke Nathan Hanna, Liesbeth Jozefien Munster, Shivani Joshi, Jarmila Dagmara Wendelien van der Bilt, Christianne Johanna Buskens, Ailsa Hart, Phil Tozer
Journal: The Lancet. Gastroenterology & hepatology (2025)
Construction of vascularized liver microtissues recapitulates angiocrine-mediated hepatocytes maturation and enhances therapeutic efficacy for acute liver failure
Authors: Liuyang Zhu, Sen Liu, Zhuangzhuang Yang, Long Yang, Yueyue Yang, Pinsheng Han, Yu Miao, Lei Lin, Lilin Xu, Yan Li, Xinyue Li, Libo Wang, Tianyu Zhao, Weiwei Wang, Zilin Cui, Ze Wang, Deling Kong, Zhongyang Shen, Yamin Zhang
Journal: Bioactive Materials (2025)
Impact of the wood-burning <i>Justa</i> cookstove on glycated hemoglobin (HbA1c): a stepped-wedge randomized trial in rural Honduras
Authors: Bonnie N. Young, Jennifer L. Peel, Sarah Rajkumar, Kayleigh P. Keller, Megan L. Benka-Coker, Nicholas Good, Ethan S. Walker, Robert D. Brook, Tracy L. Nelson, John Volckens, Christian L’Orange, Casey Quinn, Sebastian Africano, Anibal B. Osorto Pinel, Maggie L. Clark
Journal: Environmental Health Perspectives (2025)

Type 2 diabetes is a rapidly growing global health challenge in low- and middle-income countries (LMICs), and evidence suggests that air pollution exposure contributes. Household air pollution from burning solid fuels for cooking is a major burden in LMICs but studies demonstrating associations between reductions in household air pollution and improvements in HbA1c, a biomarker of diabetes risk, are lacking. We previously reported substantial reductions in fine particulate matter (PM2.5) and black carbon concentrations following an intervention in rural Honduras with the Justa cookstove, a wood-burning stove with an engineered combustion chamber and chimney. In a stepped-wedge randomized controlled trial among 230 Honduran women using traditional wood-burning stoves at baseline, we evaluated the effect of the Justa intervention on HbA1c and characterized the longitudinal associations between air pollution exposures and HbA1c. At each of 6 visits over 3 years, we measured 24-hour PM2.5 and black carbon concentrations, and finger-stick HbA1c levels. We used linear mixed models in intent-to-treat (condition by assigned stove type), exposure-response (using 24-hour measures and modeled estimates of long-term exposures), and "per protocol" self-reported stove use analyses. HbA1c was reduced for the Justa condition compared to the traditional stove condition, but estimates were small and not statistically significant (-0.03 percentage points, 95% confidence interval [CI]: -0.13, 0.07, n=1,208 observations). A slightly stronger effect was observed when using self-reported stove use in per protocol analyses. Exposure-response analyses demonstrated positive associations between HbA1c and air pollution (e.g., HbA1c was 0.22 percentage points higher (95% CI: 0.13, 0.30) per log-unit higher long-term average personal PM2.5). Our study provides novel evidence of exposure-response associations between household air pollution and HbA1c within a randomized cookstove trial, contributing to the evidence base necessary to support clean cooking policy initiatives. https://doi.org/10.1289/EHP15095.
Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline Rapid Recommendation Update
Authors: Jaishri Blakeley, Nimish A. Mohile, Hans Messersmith, Andrew B. Lassman, David Schiff, Jaishri Blakeley, Na Tosha Gatson, Andreas F. Hottinger, Andrew Lassman, Nimish A. Mohile, Jordan Morton, Douglas Ney, Phioanh Leia Nghiemphu, James Perry, David Schiff, Anne Shannon, Helen A. Shih, Roy Strowd, Martin van den Bent, Mateo Ziu
Journal: Journal of Clinical Oncology (2025)

ASCO Rapid Recommendation Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual . The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information ( Appendix 1 and Appendix 2 , online only).