tbuckley/cabot-search huggingface dataset:
Leveraging implementation science to solve the big problems: a scoping review of health system preparations for the effects of pandemics and climate change
Authors: Georgia Fisher, Carolynn L Smith, Lisa Pagano, Samatha Spanos, Yvonne Zurynski, Jeffrey Braithwaite
Journal: The Lancet Planetary Health (2025)

As the planet warms and pandemics become more common, health systems will face disruptions to both their service delivery and their workforce. To minimise the severity of these impacts, health systems will need to efficiently and rapidly prepare, adapt, and respond. Implementation science will be crucial to the success of these actions. However, the extent to which health systems are using implementation science to address the pressures of pandemics and climate change is not currently known. In this scoping review, we aimed to address this research gap. We reviewed empirical studies that used implementation science to adapt, respond to, or prepare a health-care setting for a pandemic or climate-related event, defining components of implementation science (as proposed by Nilsen [2015]) and implementation evaluation outcomes (as proposed by Proctor and colleagues [2011]). We found a growing evidence base describing the use of implementation science in health system responses to pandemics (n=54 studies), but a dearth of similar evidence for climate change (n=2 studies). Future research could benefit from applying the principles of implementation science in pre-implementation phases and purposefully planning for long-term, ongoing evaluations, which will facilitate tailored and sustainable health system responses to climate-related and pandemic events.
Climate change and child wellbeing: a systematic evidence and gap map on impacts, mitigation, and adaptation
Authors: Malak Mohamed, Saliqa Amin, Edward Lever, Angelina Montini, Komari Machida, Srivatsan Rajagopalan, Anthony Costello, Alice McGushin, Beth Jennings, Laelia Benoit, Naomi Saville, Nicola Walshe, Sarah L Dalglish, Sonja Ayeb-Karlsson, Sarah Sterlini, Audrey Prost
Journal: The Lancet Planetary Health (2025)

We developed a systematic evidence and gap map (2014-24) to assess how climate change impacts, mitigation, and adaptation affect the wellbeing of children aged 0-18 years globally, and discussed findings with the Children in All Policies 2030 Youth Advisory Board. Health was the most researched child wellbeing domain (84%; 948 of 1127 studies), followed by education (15%; n=171), and food security and nutrition (14%; n=160). Research on children's agency and resilience, displacement, socioeconomic distress, and safety received less attention. Health research gaps included limited studies on vector-borne diseases, children's mental health beyond post-traumatic stress disorder, and health outcomes for children aged 5-18 years. Mitigation and adaptation research focused largely on educational (45%; 114 of 252 studies) and behavioural changes (31%; n=79), with gaps in the evaluation of financing, infrastructure, technology, clean energy, and policy actions. Youth advisory board members emphasised the importance of schools, social media, and intergenerational dialogue in driving climate action while protecting children's wellbeing.
Cellular and molecular mechanisms in the pathogenesis of pouchitis: more than just the microbiota
Authors: Manuel B Braga-Neto, Taha Qazi, Clifton Fulmer, Stefan D Holubar, Claudio Fiocchi, Andrei I Ivanov, Florian Rieder
Journal: Gut (2025)

Pouchitis, defined as inflammation of the ileal pouch, is the most common complication following restorative proctocolectomy for refractory ulcerative colitis. Antibiotics remain the first line of therapy for pouchitis, but the majority of patients develop subsequent episodes and some are refractory to antibiotic therapy. This highlights the need for more effective treatment options and points to a more complex pathophysiology beyond the role of th pouch microbiome, similar to what is seen in inflammatory bowel disease. In this review, we outline the putative mechanisms of pouchitis, including genetic predisposition, microbiome alterations, dysfunction of the intestinal barrier and the immune system and review the available animal models of pouchitis. In addition, we introduce the concept of pouchitis as a possible transmural disease and discuss the potential role of non-immune cells, including stromal cells, in perpetuating inflammation and intestinal barrier dysfunction. We discuss future directions, implications for novel therapies and propose novel multicellular disease models that can better capture the complexity of pouchitis pathogenesis.
Anti-tumor immunity mediated by engineered allogeneic stem cells exploiting TRAIL-induced cell death and FLT3L immunomodulation
Authors: Thijs A. van Schaik, Kok-Siong Chen, Nobuhiko Kanaya, Lucia Moreno-Lama, Nicolas W. Freeman, Mian Wang, Wanlu Li, Yu Shrike. Zhang, Vladimir Vrbanac, Raymond Huang, Hiroaki Wakimoto, David Reardon, Khalid Shah
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Death receptor (DR)-targeted therapies offer a promising tumor cell-specific therapeutic strategy for highly malignant brain tumors, such as glioblastoma (GBM). However, whether DR-mediated cell death leads to activation of the adaptive immune system and impacts the tumor immune microenvironment (TIME) remains unknown. In this study we explored the 1) immunomodulatory role of secretable human DR4/5 ligand, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (S-TRAIL); and 2) the therapeutic potential of allogeneic stem cells (SCs) delivered S-TRAIL and myeloid progenitor cell activating cytokine, FMS-like tyrosine kinase 3 ligand (FLT3L). Experimental Design: We created syngeneic murine immune -active and -suppressive mouse GBM tumor models expressing a human-murine chimeric DR5. Next, we created therapeutic SCs that release FLT3L and S-TRAIL and assessed their efficacy in GBM tumor models. To facilitate clinical translation, we tested the mechanism-based efficacy of encapsulated SC-TRAIL/FLT3L in both syngeneic and humanized mouse tumor-models of GBM-resection. Results: We show that S-TRAIL induced apoptosis in GBM cells provokes infiltration and maturation of dendritic cells (DC) within the TIME in vivo. Next, we show that local transplantation of encapsulated bimodal SCs post-surgical GBM-resection improves the survival probability and induces upregulation of conventional DC type 1 (cDC1) and CD8+ T cells. Furthermore, treatment with encapsulated off-the-shelf clinical-grade bimodal human SCs in GBM-bearing humanized mice results in a significant decrease in tumor-volumes. Conclusions: This study uncovers the immunological role of TRAIL-mediated cell death in the TIME and provides evidence for the encapsulated cell-based therapy to kill residual tumor-cells and induce long-term immunity.
A Phase 1 Study of FHD-286, a Dual BRG1/BRM (SMARCA4/SMARCA2) Inhibitor, in Patients With Advanced Myeloid Malignancies
Authors: Courtney D. DiNardo, Amir T. Fathi, Ashwin Kishtagari, Kapil N. Bhalla, Alfonso Quintás-Cardama, Sarah A. Reilly, Caroline Almon, Caitlin Patriquin, Salah Nabhan, Kathleen Healy, Denice Hickman, Michael P. Collins, Alexis Khalil, Dillon Corrigan, Tina Zhao, Jessica Piel, Kelly Lyons, Kim Horrigan, Virna Schuck, Paul Martin, GiNell Elliott, David L. Lahr, Mia Bosinger, Katie D'Aco, Gromoslaw Aleksander. Smolen, Murphy Hentemann, Sanam Loghavi, Samuel Agresta, Michael R. Savona, Eytan M. Stein
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Safety and preliminary clinical activity of FHD-286, a dual BRG1/BRM inhibitor, were evaluated in patients with relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome. Patients and methods: In this multicenter, open-label, phase 1, dose escalation study (NCT04891757), patients received FHD-286 orally once daily (QD) at 2.5, 5, 7.5, and 10 mg. Results: Forty patients (median age 65.5 years; 85% with adverse genetic status; 65% with ≥3 prior therapy lines) received FHD-286 for 28 days (median). FHD-286 was not tolerated at 10 mg QD. Across all doses, treatment-related adverse events (TRAEs) were predominantly Grade 1-2, most commonly dry mouth (27.5%) and increased alanine aminotransferase (20%). Dose-limiting Grade 3 hyperbilirubinemia and Grade 3 muscular weakness occurred at 5 and 10 mg QD, respectively. The most common serious TRAE was differentiation syndrome (DS) (10%). An independent committee retrospectively adjudicated DS in 15% of patients (five Grade 3, one Grade 4). FHD-286 plasma exposure increased with dose and accumulated with continuous dosing. Exposures were typically higher with concomitant CYP3A4 inhibitors. Myeloid differentiation and leukemic burden reduction were observed across cytogenetic and mutational backgrounds, notably in patients with enhancer-driven genotypes. There were no objective responses. Conclusions: DS was the most frequent serious TRAE. While antileukemic activity was observed, no objective responses were achieved and disease progression frequently occurred within 1-2 treatment cycles. Blast reductions were reported across cytogenetic and mutational profiles, coupled with myeloid differentiation via BRG1/BRM inhibition. This novel mechanism warrants further investigation of FHD-286 in combination with other agents in myeloid malignancies.
Variability in sensitivity to inflammation in muscle and lung of patients with COPD may underlie susceptibility to lung function decline
Authors: Paul R Kemp, Mark Griffiths, Michael I Polkey, Amanda Sathyapala
Journal: Thorax (2025)

Background Muscle wasting and weakness (sarcopenia) are commonly associated with COPD causing frailty and reduced quality of life. The contribution of inflammation to muscle loss and the susceptibility to rapid lung function decline is debated. We hypothesised that comparing the muscle transcriptome to circulating inflammatory cytokine profiles in patients would identify any contribution of systemic inflammation to muscle atrophy. Methods Quadriceps differential gene expression was determined between mild-COPD (n=28) and severe-COPD (n=51) using GSE100281. These microarray data were compared by biweight mid-correlation with lung function and plasma cytokine levels from the same patients. Results Patients with severe COPD had reduced fat-free mass index (a measurement of muscle mass) compared with patients with mild COPD despite similar physical activity and inflammatory cytokine levels. Gene sets associated with inflammation and epithelial mesenchymal transition (EMT) were elevated in severe COPD, suggesting that inflammation may contribute to the loss of muscle mass. In patients with severe COPD, EMT and inflammation gene sets were strongly associated with circulating proinflammatory and anti-inflammatory cytokines. However, in patients with mild COPD, anti-inflammatory cytokines showed negative associations with these gene sets and associations with proinflammatory cytokines were weak. In data from lung and blood samples, patients with severe COPD had elevated inflammatory and EMT gene expression compared with patients with mild COPD suggesting that this phenomenon is not muscle-specific. Conclusions In patients at the severe end of the COPD spectrum, the proinflammatory response in muscle predominates, whereas in patients at the mild end of the spectrum, the anti-inflammatory response predominates. This suggestion needs confirming in a longitudinal cohort.
Sarcopenia and Skeletal Muscle Loss after CAR T-cell Therapy in Diffuse Large B cell Lymphoma
Authors: Khushali Jhaveri, Ram Thapa, Dalia Ercan, Aditi Saha, Jerald Noble, Pranit Singh, Johannes Fahrmann, Neeraj Saini, Ranran Wu, Jennifer B. Dennison, Sam Hanash, Robert R. Jenq, Karnav Modi, Nicholas Figura, Julio Chavez, Bijal Shah, Taiga Nishihori, Aleksandr Lazaryan, Farhad Khimani, Christina Bachmeier, Kenneth Gage, Asmita Mishra, Fabiana Perna, Marco L. Davila, Jay Spiegel, Kai Rejeski, Marion Subklewe, Frederick L. Locke, Ciara Freeman, Nathan Parker, Michael D. Jain
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Sarcopenia is a hallmark of cancer cachexia. Chimeric antigen receptor (CAR) T-cell therapy is associated with an inflammatory state that may exacerbate sarcopenia. The relationship between CAR T-cell therapy, sarcopenia, and metabolism is poorly understood. Experimental Design: In 83 large B-cell lymphoma patients, the skeletal muscle index (SMI) was measured from clinical images obtained at baseline and days 30 and 90 post-therapy. Serum metabolomics (n=57 patients) was performed in the first 4 weeks. Results: Baseline sarcopenia was present in over half of patients and associated with shorter median overall survival (OS) than for non-sarcopenic patients (10.5 versus 34.3 months; P=0.006). This reduction was due to increased non-relapse mortality (NRM) with all six NRM events occurring in patients with baseline sarcopenia. In the first 30 days after CAR T-cell therapy, 1/3 of patients experienced skeletal muscle loss greater than 10%. Muscle loss was associated with higher tumor burden and neurotoxicity but was not significantly associated with long term survival. Serum metabolomics revealed an early (weeks 1-2) increase in purine metabolites, followed by a later (weeks 3-4) increase in triglyceride levels. The serum metabolite with the highest fold-increase from baseline was adipic acid, attributed to the inpatient hospital menu of Jello and other tart beverages. Conclusions: Skeletal muscle loss after CAR T-cell therapy is common and is associated with fatty acid catabolism. Patients with baseline sarcopenia have poor tolerance and reduced survival. Future studies of dietary and exercise interventions may improve CAR T-cell therapy outcomes.
Fate reversal: Exosome-driven macrophage rejuvenation and bacterial-responsive drug release for infection immunotherapy in diabetes
Authors: Jiaxuan Zou, Wushi Cui, Niping Deng, Congsun Li, Weinan Yang, Xiaojun Ye, Feng Yao, Tao Zhang, Jian Xiao, Chiyuan Ma, Lingfeng Wu, Dahai Dong, Jing Chen, Chengchen Guo, An Liu, Haobo Wu
Journal: Journal of Controlled Release (2025)
Open versus robotic-assisted partial nephrectomy in patients with intermediate/high-complexity kidney tumours: final results of the randomised, controlled, open-label, multicentre trial OpeRa
Authors: M-O Grimm, J Bedke, J Nyarangi-Dix, W Khoder, S Foller, H-J Sommerfeld, M Giessing, M Heck, W Meißner, A Slee, K Leucht, F von Rundstedt, G Theil, S Buse, S Siemer, P Albers, C Gratzke, M Hohenfellner, A Stenzl
Journal: Annals of Oncology (2025)
European guidelines on treatment and supportive measures in chronic neutropenias: A consensus between the European Hematology Association and the EuNet‐INNOCHRON COST Action based on a systematic evidence review
Authors: Francesca Fioredda, Michail Spanoudakis, Julia Skokowa, Hannah Tamary, Piero Farruggia, Antonio Almeida, Daniela Guardo, Jan Palmblad, Petter Höglund, Ivo P. Touw, Cornelia Zeidler, Alan J. Warren, Mario Csenar, Nicole Skoetz, Elio Castagnola, Erica Ricci, David C. Dale, Peter E. Newburger, Karl Welte, Helen A. Papadaki, Carlo Dufour
Journal: HemaSphere (2025)

Abstract The treatment of chronic neutropenias and control of neutropenia‐related infections remain challenging topics for pediatric and adult hematologists. This article aims to fill the gap in the treatment of neutropenias and, in combination with the previously published European guidelines on diagnosis of neutropenias, gives complete and comprehensive guidance on the whole management of patients with neutropenia. In terms of methodology, an Evidence‐Based Medicine team produced an evidence synthesis of the literature on the treatment of neutropenias. Then, according to the robustness of the evidence, consensus recommendations were elaborated and voted by an expert's panel from the Cooperation in Science and Technology European Network for the Innovative Diagnosis and Treatment of Chronic Neutropenias ( https://eunet-innochron.eu/ ) and the Specialized Working Group on Granulocytes and Constitutional Bone Marrow Failure Syndromes of the European Hematology Association. Whenever evidence was not available, recommendations were based on the expert's panel opinion. Consensus‐based recommendations are related to granulocyte colony‐stimulating factor indications and schedule of administration, indications for hematopoietic stem cell transplantation, supportive treatments and measures, and new treatments that have been evolving over the recent years. These guidelines, rather than a numerical correction of the absolute neutrophil count, suggest a holistic, patient‐centered approach aiming at optimizing the management of chronic neutropenic patients and offering valuable and practical guidance to the hematologists for their daily clinical practice.
Issues in Clinical Trial Design—Lessons From the FDA’s Rejection of MDMA
Authors: Samuel T. Wilkinson, Gerard Sanacora
Journal: JAMA Psychiatry (2025)

This Viewpoint explores potential justifications underlying the US Food and Drug Administration (FDA)’s rejection of methylenedioxymethamphetamine (MDMA) as a treatment for posttraumatic stress disorder, including lack of blinding and issues around the integrity of relevant clinical trials.
Immediate Skin-to-Skin Contact in Very Preterm Neonates and Early Childhood Neurodevelopment
Authors: Laila Kristoffersen, Ragnhild Støen, Håkon Bergseng, Silje Tjøm Flottorp, Grete Magerøy, Kristine Hermansen Grunewaldt, Karoline Aker
Journal: JAMA Network Open (2025)

Importance Preterm neonates are at risk for neurodevelopmental impairments, and there is a need to identify protective factors that can modify the harmful effects of preterm birth on the immature brain. Objective To evaluate whether immediate skin-to-skin contact (SSC) for preterm neonates improves early childhood neurodevelopmental outcomes. Design, Setting, and Participants This open-label randomized clinical trial was conducted in 3 Norwegian neonatal units between February 2014 and October 2020. Participants were preterm neonates born at 28 weeks 0 days’ to 31 weeks 6 days’ gestation with birth weight greater than 1000 g and no major congenital malformations or need for intubation or oxygen supplementation of more than 40%. Intention-to-treat analysis was conducted from July 2023 to July 2024. Intervention Neonates were randomized 1:1 to immediate SSC between mother and neonate in the delivery room for 2 hours or to standard care with direct transport to the neonatal unit in an incubator. Main Outcomes and Measures The primary outcome was cognitive development at 2 to 3 years of age, measured by the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Secondary outcomes were language and motor neurodevelopment measured by the BSID-III, parental questionnaires at 3 and 12 months and 2 to 3 years, and breastfeeding practices up to 12 months. Results Of 108 included neonates (68 [63%] male; mean [SD] gestational age, 30 weeks 3 days [1 week 1 day]), 51 received SSC and 57 received standard care. Eighty-six (80%) had follow-up at 2 to 3 years, and 81 (75%) completed the BSID-III and were analyzed for the primary outcome. The mean difference in BSID-III cognitive composite scores was 0.21 (95% CI, −5.26 to 5.68; P = .94). There was no difference between the groups in the proportion at risk of developmental delay at 2 to 3 years: 21 of 41 (51%) and 22 of 45 (49%) in the SSC and standard care groups, respectively (odds ratio, 1.10 [95% CI, 0.47-2.56]; P = .83). More neonates in the SSC group were breastfed at hospital discharge (42 of 50 [84%] vs 36 of 54 [67%]; P = .04). Conclusions and Relevance In this randomized clinical trial, 2 hours of mother-neonate SSC in the delivery room did not enhance neurodevelopmental outcomes at 2 to 3 years of age. However, the SSC group demonstrated improved breastfeeding practices up to 12 months compared with standard care, suggesting that the feasible and low-cost SSC intervention should be encouraged in clinical practice. Trial Registration ClinicalTrials.gov Identifier: NCT02024854
Finding Rearrangements in the Cell-Free DNA Haystack
Authors: Kurtis D. Davies
Journal: Clinical Cancer Research (2025)

Abstract Circulating tumor DNA (ctDNA) analysis is now a widely used diagnostic approach in the management of patients with solid tumors, including gene fusion-driven lung cancer. However, the accurate detection of genetic rearrangements in ctDNA presents considerable technical challenges. Consequently, studies that assess and compare methodologies for detection are vital.
Automated Deep Learning Phenotyping of Tricuspid Regurgitation in Echocardiography
Authors: Amey Vrudhula, Milos Vukadinovic, Christiane Haeffele, Alan C. Kwan, Daniel Berman, David Liang, Robert Siegel, Susan Cheng, David Ouyang
Journal: JAMA Cardiology (2025)

Importance Accurate assessment of tricuspid regurgitation (TR) is necessary for identification and risk stratification. Objective To design a deep learning computer vision workflow for identifying color Doppler echocardiogram videos and characterizing TR severity. Design, Setting, and Participants An automated deep learning workflow was developed using 47 312 studies (2 079 898 videos) from Cedars-Sinai Medical Center (CSMC) between 2011 and 2021. Data analysis was performed in 2024. The pipeline was tested on a temporally distinct test set of 2462 studies (108 138 videos) obtained in 2022 at CSMC and a geographically distinct cohort of 5549 studies (278 377 videos) from Stanford Healthcare (SHC). Training and validation cohorts contained data from 31 708 patients at CSMC receiving care between 2011 and 2021. Patients were chosen for parity across TR severity classes, with no exclusion criteria based on other clinical or demographic characteristics. The 2022 CSMC test cohort and SHC test cohorts contained studies from 2170 patients and 5014 patients, respectively. Exposure Deep learning computer vision model. Main Outcomes and Measures The main outcomes were area under the receiver operating characteristic curve (AUC), sensitivity, and specificity in identifying apical 4-chamber (A4C) videos with color Doppler across the tricuspid valve and AUC in identifying studies with moderate to severe or severe TR. Results In the CSMC test dataset, the view classifier demonstrated an AUC of 1.000 (95% CI, 0.999-1.000) and identified at least 1 A4C video with color Doppler across the tricuspid valve in 2410 of 2462 studies with a sensitivity of 0.975 (95% CI, 0.968-0.982) and a specificity of 1.000 (95% CI, 1.000-1.000). In the CSMC test cohort, moderate or severe TR was detected with an AUC of 0.928 (95% CI, 0.913-0.943), and severe TR was detected with an AUC of 0.956 (95% CI, 0.940-0.969). In the SHC cohort, the view classifier correctly identified at least 1 TR color Doppler video in 5268 of the 5549 studies, resulting in an AUC of 0.999 (95% CI, 0.998-0.999), a sensitivity of 0.949 (95% CI, 0.944-0.955), and a specificity of 0.999 (95% CI, 0.999-0.999). The artificial intelligence model detected moderate or severe TR with an AUC of 0.951 (95% CI, 0.938-0.962) and severe TR with an AUC of 0.980 (95% CI, 0.966-0.988). Conclusions and Relevance In this study, an automated pipeline was developed to identify clinically significant TR with excellent performance. With open-source code and weights, this project can serve as the foundation for future prospective evaluation of artificial intelligence–assisted workflows in echocardiography.
The Paradox of Acute Myeloid Leukemia Responsiveness to Adoptive T-cell Therapy
Authors: Terry J. Fry
Journal: Blood Cancer Discovery (2025)

Summary: Since the recognition of the allogeneic graft-versus-leukemia effect, acute myeloid leukemia (AML) has been identified as a T cell–targetable malignancy, but success with modern forms of immunotherapy has been slower than anticipated. In this issue, we discuss the biological barriers to the treatment of AML with T-cell therapy revealed by recent reports, including mechanistic insights into AML resistance to T cell–mediated killing by Tin and colleagues. See related article by Tin et al., p. XX