tbuckley/cabot-search huggingface dataset:
The AI-enhanced surgeon – integrating black-box artificial intelligence in the operating room
Authors: Ronan A. Cahill, Mindy Duffourc, Sara Gerke
Journal: International Journal of Surgery (2025)

New artificial intelligence (AI)/machine learning (ML) technology offers great potential to assist surgeons with real-time intraoperative decision-making. While currently, AI/ML-driven tools for surgeons focus primarily on technical assistance and postoperative insights, AI/ML cognitive support in surgery can add further capability. However, these AI/ML models usually conceal their underlying algorithmic reasoning process. As a result, such “black box” AI/ML models have important clinical and legal implications for patient’s safety and surgeon’s liability. This article provides an overview of surgeons’ current practice and the potential for AI enhancement in surgical decision-making. It suggests a path toward a safe and effective integration of black-box AI/ML models into the operating room. We argue that future surgeons who rely on AI for cognitive assistance do not necessarily need to fully understand, interpret, and explain the algorithmic basis of an AI’s real-time recommendation in the midst of surgery, but rather, they need to know that these tools work as promised. Assuming new black-box AI/ML models demonstrate clear benefits for surgical patients, their use will likely be incorporated into the legal standard of care and affect the liability landscape for surgeons.
Elastance May Determine the Neuromuscular Blockade Effect on Mortality in Acute Respiratory Distress Syndrome
Authors: Ann A. Zalucky, Jose Dianti, Lucile P. A. Neyton, Pratik Sinha, Kathleen D Liu, Michael A. Matthay, B. Taylor Thompson, Ewan C. Goligher, Carolyn S Calfee
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Patients with acute respiratory distress syndrome (ARDS) have a reduction in functional lung volume resulting in increased respiratory system elastance (Ers); however, the extent of this increase varies by patient. Patients with high Ers are at risk of excess lung-distending pressures and may derive greater clinical benefit from neuromuscular blockade (NMB). To evaluate whether the effect of early NMB administration on mortality varies according to baseline physiological and biological biomarkers of lung injury, including Ers. We conducted a secondary analysis of the ROSE trial. Bayesian logistic regression modelling was employed to estimate the posterior probability of NMB effect moderation by baseline Ers, ventilatory ratio, and select ARDS plasma biomarkers on 90-day mortality. The probability of mortality benefit with NMB increased substantially with higher baseline Ers (posterior probability of interaction, 92%; interaction odds ratio 0.76, 90% credible interval (CrI) 0.59-0.99). In patients with Ers ≥2cm H2O/(mL/kg), the posterior probability of benefit was 96% (median absolute risk reduction 9%, 90% CrI 0.5-17.9%). The effect of NMB did not vary meaningfully according to ventilatory ratio (posterior probability of interaction, 62%) or baseline plasma levels of receptor for advanced glycation end-products, tumor necrosis factor receptor-1, interleukin-6 or -8 (posterior probabilities of interaction: 12%, 18%, 44% and 22% respectively). These findings suggest that the mortality benefit of NMB varies with baseline Ers. High Ers may represent a physiological phenotype of ARDS. Future prospective testing to confirm benefit in this potentially treatment-responsive group is needed.
Clinical and Biological Features of a Thickened Basement Membrane Zone in Asthma
Authors: Clarus Leung, Monica Tang, Walter E. Finkbeiner, Mats W. Johansson, Loren C. Denlinger, Nizar N Jarjour, Mario Castro, Kaharu Sumino, Serpil C Erzurum, Suzy A Comhair, Wendy C. Moore, Annette T. Hastie, Bruce D. Levy, Elliot Israel, Brenda R. Phillips, David T Mauger, Sally E. Wenzel, Stephanie Christenson, Max A Seibold, Nathan Jackson, Prescott G. Woodruff, John V Fahy
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

A subset of asthma patients have airway pathology characterized by a thickened subepithelial basement membrane zone ("BMZ-thick asthma"). To characterize the clinical features of BMZ-thick asthma and to determine if BMZ thickness accompanies specific patterns of inflammation in the airway epithelium. Design-based stereology was used to quantify BMZ thickness in endobronchial biopsy tissue sections from 109 asthma patients and 41 healthy controls from the Severe Asthma Research Program-3 whose participants had undergone spirometry and gene expression profiling in airway epithelial brushings. The upper 90th percentile value for BMZ thickness in the healthy cohort was 2.9 µM, and 35% of the asthma cohort had values above this upper limit. Compared to BMZ-thin asthma patients, BMZ-thick asthma patients were younger and had higher blood eosinophil numbers and serum immunoglobulin E levels that were specific to animal proteins. Mean pre-bronchodilator FEV1 was significantly lower in BMZ-thick than in BMZ-thin patients, but post-bronchodilator FEV1 was not. Upregulation of genes signifying interleukin-13 activation and presence of mast cells were evident in epithelial brushings in BMZ-thick patients, but gene signatures for activation by interferon gamma or interleukin-17 were not. A thickened BMZ marks a subset of younger asthma patients characterized by higher IgE levels to animal aeroallergens and by increased bronchomotor tone occurring in the context of airway epithelial cells activated by interleukin-13 and infiltrated by mast cells.
Shining a Light on Cardiopulmonary Fitness in Pediatric Inherited Cardiac Disease
Authors: William W. Russell, Jonathan B. Edelson
Journal: JAMA Network Open (2025)

Luc Souilla, PhD; Oscar Werner, MD; Helena Huguet, MSc; Arthur Gavotto, MD, PhD; Marie Vincenti, MD; Jean-Luc Pasquie, MD, PhD; Gregoire De La Villeon, MD; Sophie Guillaumont, MD; Victor Pommier, MD; Stefan Matecki, MD, PhD; Alban-Elouen Baruteau, MD, PhD; Constance Beyler, MD; Christophe Delclaux, MD, PhD; Isabelle Denjoy, MD; Philippe Charron, MD, PhD; Philippe Chevalier, MD, PhD; Antoine Delinière, MD; Mathieu Andrianoely, BSc; Lauriane Cornuault, PharmD, PhD; Caroline Besnard-Neyraud, MD, PhD; Frederic Sacher, MD, PhD; Patricia Reant, MD, PhD; Denis Mottet, MD, PhD; Marie-Christine Picot, MD, PhD; Pascal Amedro, MD, PhD; Quality of Life in Children With Inherited Cardiomyopathy or Arrhythmia (QUALIMYORYTHM) Study Group; Hamouda Abassi; Aymeric Boisson; Anne Requirand; Annie Auer; Vincent Probst; Solène Prigent; Quentin Hauet; Christelle Haddad; Claire Bertail-Galoin; Xavier Iriart; Julie Thomas-Chabaneix; Pierre-Marie Duboue; Amandine Ruissel; Jean-Bernard Selly
GPR65 inactivation in tumor cells drives antigen-independent CAR-T cell resistance via macrophage remodeling
Authors: Jayadev Mavuluri, Yogesh Dhungana, Lindsay L. Jones, Sheetal Bhatara, Hao Shi, Xu Yang, Song-Eun Lim, Noemi Reyes, Hongbo Chi, Jiyang Yu, Terrence L. Geiger
Journal: Cancer Discovery (2025)

Abstract Chimeric antigen receptor (CAR)-T cell therapies, while promising for CD19+ hematological malignancies, often face setbacks due to relapses. Our research identifies GPR65 as a tumor-specific determinant affecting the efficacy of CAR-T cell therapy. In human patients and an immune-competent mouse model of B-cell acute lymphoblastic leukemia (B-ALL), low GPR65 expression correlates with resistance to CD19+ CAR-T treatment. GPR65 knockout (GPR65 KO) tumors in mice similarly exhibit resistance. Through single-cell network analyses, we discovered that GPR65 deficiency reshapes tumor interactions with host macrophages by increasing tumor VEGFA levels, leading to macrophage expansion and preferential M2 polarization. Depleting host macrophages or by deletion of VEGFA in GPR65 KO tumors, restores CAR-T cell therapy responsiveness. Moreover, combining anti-VEGFA therapy with CAR-T cell treatment significantly prolongs the survival of mice bearing GPR65 KO tumors. These findings emphasize the profound impact of tumor gene expression on the tumor microenvironment and subsequent CAR-T cell therapy outcomes.
Neuronal autophagy in the control of synapse function
Authors: Anna Karpova, P Robin Hiesinger, Marijn Kuijpers, Anne Albrecht, Janine Kirstein, Maria Andres-Alonso, Alexander Biermeier, Britta J Eickholt, Marina Mikhaylova, Marta Maglione, Carolina Montenegro-Venegas, Stephan J Sigrist, Eckart D Gundelfinger, Volker Haucke, Michael R Kreutz
Journal: Neuron (2025)

Neurons are long-lived postmitotic cells that capitalize on autophagy to remove toxic or defective proteins and organelles to maintain neurotransmission and the integrity of their functional proteome. Mutations in autophagy genes cause congenital diseases, sharing prominent brain dysfunctions including epilepsy, intellectual disability, and neurodegeneration. Ablation of core autophagy genes in neurons or glia disrupts normal behavior, leading to motor deficits, memory impairment, altered sociability, and epilepsy, which are associated with defects in synapse maturation, plasticity, and neurotransmitter release. In spite of the importance of autophagy for brain physiology, the substrates of neuronal autophagy and the mechanisms by which defects in autophagy affect synaptic function in health and disease remain controversial. Here, we summarize the current state of knowledge on neuronal autophagy, address the existing controversies and inconsistencies in the field, and provide a roadmap for future research on the role of autophagy in the control of synaptic function.
Perioperative lung expansion and pulmonary outcomes after open abdominal surgery versus usual care in the USA (PRIME-AIR): a multicentre, randomised, controlled, phase 3 trial
Authors: Ana Fernandez-Bustamante, Robert A Parker, Gyorgy Frendl, Jae Woo Lee, Alexander Nagrebetsky, Loreta Grecu, David Amar, Pedro Tanaka, Juraj Sprung, Ravindra A Gupta, Balachundhar Subramanian, Jadelis Giquel, Matthias Eikermann, Guido Musch, Jacob W Nadler, Marcelo Gama de Abreu, Karsten Bartels, Meera Grover, Lee-Lynn Chen, Jamie Sparling, David J Douin, Toby Weingarten, Gebhard Wagener, B Taylor Thompson, Marcos F Vidal Melo
Journal: The Lancet Respiratory Medicine (2025)
Defining brain fog across medical conditions
Authors: Peter Denno, Sijia Zhao, Masud Husain, Adam Hampshire
Journal: Trends in Neurosciences (2025)

'Brain fog' is commonly reported in more than a dozen chronic diseases, but what is it? We review research across conditions which has characterised brain fog and evaluate its definitions and objective correlates. Brain fog has been used to refer to a variable set of overlapping symptoms implicating cognition, fatigue, and affect. It has been defined as a distinct symptom, a syndrome, or a nonspecific term. We consider the evidence that brain fog is a transdiagnostic entity with a common phenomenology and profile of objective cognitive deficits. We discuss where these commonalities arise and argue that linguistic ambiguity, shared cognitive impairments, and noncognitive factors are more likely than shared neurobiology. We suggest how future research might apply existing tools to disambiguate the phenomena that brain fog conflates.
Batch correcting single-cell spatial transcriptomics count data with Crescendo improves visualization and detection of spatial gene patterns
Authors: Nghia Millard, Jonathan H. Chen, Mukta G. Palshikar, Karin Pelka, Maxwell Spurrell, Colles Price, Jiang He, Nir Hacohen, Soumya Raychaudhuri, Ilya Korsunsky
Journal: Genome biology (2025)

Spatial transcriptomics facilitates gene expression analysis of cells in their spatial anatomical context. Batch effects hinder visualization of gene spatial patterns across samples. We present the Crescendo algorithm to correct for batch effects at the gene expression level and enable accurate visualization of gene expression patterns across multiple samples. We show Crescendo's utility and scalability across three datasets ranging from 170,000 to 7 million single cells across spatial and single-cell RNA sequencing technologies. By correcting for batch effects, Crescendo enhances spatial transcriptomics analyses to detect gene colocalization and ligand-receptor interactions and enables cross-technology information transfer.
“I bet being trans in The Netherlands is like living in the future”: Could The Netherlands serve as an imperfect “gold standard” comparator for transgender youth research in the United States?
Authors: Anna I. R. van der Miesen, Sharanya Rao, Abigail L. Fischbach, Alex C. Bakker, Marjolein van den Brink, Renata A. Sanders, Caitlin Ryan, Stephen M. Rosenthal, Joep Roeffen, Asaf Orr Esq, Heather Newby, Kathie Moehlig, Richard Mocarski, Kim Horsnell, Thijs de Greeff, Annelou L. C. de Vries, Aisa Burgwal, Owen Wilson, Annika Kooke, Ellen Kahn, Peggy T. Cohen-Kettenis, Lisa van Ginneken, Scott F. Leibowitz, Minneh Song, Bodi Huisman, Elodie Carel, Jamie M. Joseph, Baudewijntje P. C. Kreukels, John B. F. de Wit, John F. Strang
Journal: International Journal of Transgender Health (2025)

Background In available comparative studies, Dutch transgender youth have consistently shown better psychosocial well-being compared to those in other countries. Therefore, the Netherlands (N.L.) could be considered a gold-standard—though imperfect—comparator for transgender youth research. The United States (U.S.) is heterogeneous in its policies and practices impacting transgender youth, and policies are in flux. This study examines similarities and differences between U.S. and Dutch policies, practices, and contexts relevant to the well-being of transgender adolescents.
Genomic alterations and transcriptional phenotypes in circulating free DNA and matched metastatic tumor
Authors: Nobuyuki Takahashi, Lorinc Pongor, Shivam P. Agrawal, Mariya Shtumpf, Ankita Gurjar, Vinodh N. Rajapakse, Ahmad Shafiei, Christopher W. Schultz, Sehyun Kim, Diana Roame, Paula Carter, Rasa Vilimas, Samantha Nichols, Parth Desai, William Douglas Figg, Mohammad Bagheri, Vladimir B. Teif, Anish Thomas
Journal: Genome Medicine (2025)

Abstract Background Profiling circulating cell-free DNA (cfDNA) has become a fundamental practice in cancer medicine, but the effectiveness of cfDNA at elucidating tumor-derived molecular features has not been systematically compared to standard single-lesion tumor biopsies in prospective cohorts of patients. The use of plasma instead of tissue to guide therapy is particularly attractive for patients with small cell lung cancer (SCLC), due to the aggressive clinical course of this cancer, which makes obtaining tumor biopsies exceedingly challenging. Methods In this study, we analyzed a prospective cohort of 49 plasma samples obtained before, during, and after treatment from 20 patients with recurrent SCLC. We conducted cfDNA low-pass whole genome sequencing (0.1X coverage), comparing it with time-point matched tumor characterized using whole-exome (130X) and transcriptome sequencing. Results A direct comparison of cfDNA and tumor biopsy revealed that cfDNA not only mirrors the mutation and copy number landscape of the corresponding tumor but also identifies clinically relevant resistance mechanisms and cancer driver alterations not detected in matched tumor biopsies. Longitudinal cfDNA analysis reliably tracks tumor response, progression, and clonal evolution. Sequencing coverage of plasma DNA fragments around transcription start sites showed distinct treatment-related changes and captured the expression of key transcription factors such as NEUROD1 and REST in the corresponding SCLC tumors. This allowed for the prediction of SCLC neuroendocrine phenotypes and treatment responses. Conclusions cfDNA captures a comprehensive view of tumor heterogeneity and evolution. These findings have significant implications for the non-invasive stratification of SCLC, a disease currently treated as a single entity.
A Roadmap to Precision Immunotherapy for Early-Stage Non–Small Cell Lung Cancer
Authors: Alessandra Vaccaro, Zahraa Rahal, Humam Kadara, Tina Cascone
Journal: Cancer Discovery (2025)

Summary: Immunotherapy has revolutionized the treatment of early-stage non–small cell lung cancer; yet many patients fail to achieve long-lasting benefit, partially because of incomplete or inconsistent biomarker predictions. Integrative multiomics, combining tumor-intrinsic, immune microenvironment, and systemic factors, offer a more comprehensive framework for precision immunotherapy, enabling improved patient stratification, treatment selection and outcomes.
Circadian disruption by simulated shift work aggravates periodontitis via orchestrating BMAL1 and GSDMD-mediated pyroptosis
Authors: Yazheng Wang, Rui Li, Qingyuan Ye, Dongdong Fei, Xige Zhang, Junling Huang, Tingjie Liu, Jinjin Wang, Qintao Wang
Journal: International Journal of Oral Science (2025)

Abstract Approximately 20% to 30% of the global workforce is engaged in shift work. As a significant cause of circadian disruption, shift work is closely associated with an increased risk for periodontitis. Nevertheless, how shift work-related circadian disruption functions in periodontitis remains unknown. Herein, we employed a simulated shift work model constructed by controlling the environmental light-dark cycles and revealed that shift work-related circadian disruption exacerbated the progression of experimental periodontitis. RNA sequencing and in vitro experiments indicated that downregulation of the core circadian protein brain and muscle ARNT-like protein 1 (BMAL1) and activation of the Gasdermin D (GSDMD)-mediated pyroptosis were involved in the pathogenesis of that. Mechanically, BMAL1 regulated GSDMD-mediated pyroptosis by suppressing NOD-like receptor protein 3 (NLRP3) inflammasome signaling through modulating nuclear receptor subfamily 1 group D member 1 (NR1D1), and inhibiting Gsdmd transcription via directly binding to the E-box elements in its promoter. GSDMD-mediated pyroptosis accelerated periodontitis progression, whereas downregulated BMAL1 under circadian disruption further aggravated periodontal destruction by increasing GSDMD activity. And restoring the level of BMAL1 by circadian recovery and SR8278 injection alleviated simulated shift work-exacerbated periodontitis via lessening GSDMD-mediated pyroptosis. These findings provide new evidence and potential interventional targets for circadian disruption-accelerated periodontitis.
Mendelian randomisation studies for causal inference in chronic obstructive pulmonary disease: A narrative review
Authors: Zizheng Chen, Yuqiong Yang, Chusheng Peng, Zifei Zhou, Fengyan Wang, Chengyu Miao, Xueping Li, Mingdie Wang, Shengchuan Feng, Tingnan Chen, Rongchang Chen, Zhenyu Liang
Journal: Pulmonology (2025)

Background and objective Most non-randomised controlled trials are unable to establish clear causal relationships in chronic obstructive pulmonary disease (COPD) due to the presence of confounding factors. This review summarises the evidence that the Mendelian randomisation method can be a powerful tool for performing causal inferences in COPD.
Haploinsufficiency of miR-143 and miR-145 reveal targetable dependencies in resistant del(5q) myelodysplastic neoplasm
Authors: Nadia Gharaee, Joanna Wegrzyn-Woltosz, Jihong Jiang, Vijay Suresh Akhade, Joshua Bridgers, Ryan J. Stubbins, Devendra Hiwase, Monika M. Kutyna, Onyee Chan, Rami Komrokji, Eric Padron, Yu Deng, Gary Cole, Patricia Umlandt, Megan Fuller, Ada Kim, Aly Karsan
Journal: Leukemia (2025)

Myelodysplastic neoplasms (MDS) are stem cell disorders characterized by ineffective hematopoiesis and risk of transformation to acute myeloid leukemia (AML). Chromosomal alterations are frequent in MDS, with interstitial deletion of chromosome 5q (del(5q)) being the most common. Lenalidomide is the current first-line treatment for del(5q) MDS and its efficacy relies on degradation of CK1α which is encoded by the CSNK1A1 gene located in the commonly deleted region (CDR) of chromosome 5q. However, lenalidomide-resistance is common, often secondary to loss-of-function mutations in TP53 or RUNX1. The CDR in del(5q) harbors several genes, including noncoding miRNAs, the loss of which contribute to disease phenotypes. miR-143 and miR-145 are located within the del(5q) CDR, but precise understanding of their role in human hematopoiesis and in the pathogenesis of del(5q) MDS is lacking. Here we provide evidence that deficiency of miR-143 and miR-145 plays a role in clonal expansion of del(5q) MDS. We show that insulin-like growth factor 1 receptor (IGF-1R) is a direct target of both miR-143 and miR-145. Our data demonstrate that IGF-1R inhibition reduces proliferation and viability of del(5q) cells in vitro and in vivo, and that lenalidomide-resistant del(5q) MDS cells depleted of either TP53 or RUNX1 are sensitive to IGF-1R inhibition. Resistant del(5q) MDS-L cells, as well as primary MDS marrow cells, are also sensitive to targeting of IGF-1R-related dependencies in del(5q) MDS, which include the Abl and MAPK signaling pathways. This work thus provides potential new therapeutic avenues for lenalidomide-resistant del(5q) MDS.
Could transparent model cards with layered accessible information drive trust and safety in health AI?
Authors: Stephen Gilbert, Rasmus Adler, Taras Holoyad, Eva Weicken
Journal: npj Digital Medicine (2025)

We place 'Model Cards' and graphical 'nutrition labels' for health AI in context with the information needs of patients, health care providers and deployers. We discuss the applicability of Model Cards for General Purpose AI (GPAI) models. If these approaches are to be useful and safe they need to be integrated with regulatory approaches and linked to deeper layers of open and detailed model information and optimized through user testing.
Comparison of recognition of symptom burden in MPN between patient- and physician-reported assessment – an intraindividual analysis by the German Study Group for MPN (GSG-MPN)
Authors: Kirsi Manz, Florian H. Heidel, Steffen Koschmieder, Rudolf Schlag, Jörg Lipke, Frank Stegelmann, Martin Griesshammer, Martine Klausmann, Carl Crodel, Andreas Hochhaus, Holger Schulz, Joachim R. Göthert, Haifa Al-Ali, Heiko Becker, Andreas Reiter, Gernot Beutel, Kim Kricheldorf, Tim H. Brümmendorf, Wolfgang Hoffmann, Konstanze Döhner, Susanne Isfort
Journal: Leukemia (2025)

Abstract Myeloproliferative neoplasms (MPN) are associated with a variety of symptoms that severely impact patients’ quality of life and ability to perform daily activities. Recent studies showed differences in the perception of physician- versus patient-reported symptom burden. However, studies directly comparing patient- and physician-reported ratings are lacking. Here, a retrospective analysis on symptom burden of 3979 MPN patients of the Bioregistry of the German Study Group for MPN was conducted to intra-individually compare physician and patient reports collected at the same time. Cohen’s kappa was calculated to assess the degree of agreement between patient and physician reports. Factors influencing baseline symptom severity were identified using linear regression and adjusted Cox models were calculated to investigate the effect of symptom burden on survival. MPN patients had a high symptom burden, which neither decreased over time nor upon cytoreductive therapy. All symptoms were more frequently reported by patients compared to physicians. Agreement remained low and only slightly improved when considering a higher threshold for patient symptom severity. Patients with severe symptom burden had inferior survival compared to patients with less severe symptoms. Assessment of symptom burden in MPN is therefore insufficient and patient-reported outcome tools need to be implemented into clinical routine.
Pathogen aetiology and risk factors for death among neonates with bloodstream infections at lower-tier South African hospitals: a cross-sectional study
Authors: Susan Meiring, Vanessa Quan, Rudzani Mashau, Olga Perovic, Rindidzani Magobo, Marshagne Smith, Ruth Mpembe, Anne von Gottberg, Linda de Gouveia, Sibongile Walaza, Cheryl Cohen, Constance Kapongo, Cheryl Mackay, Mphekwa Thomas Mailula, Omphile Mekgoe, Lerato Motjale, Rose Phayane, Angela Dramowski, Nelesh P Govender
Journal: The Lancet Microbe (2025)