tbuckley/cabot-search huggingface dataset:
Prognostic Models From Transcriptomic Signatures of the Tumor Microenvironment and Cell Cycle in Stage III Colon Cancer From PETACC-8 and IDEA-France Trials
Authors: Claire Gallois, Marine Sroussi, Thierry André, Sophie Mouillet-Richard, Natacha Agueeff, Claire Mulot, Dewi Vernerey, Christophe Louvet, Jean-Baptiste Bachet, Louis-Marie Dourthe, Thibault Mazard, Marine Jary, Clélia Coutzac, Cédric Lecaille, Josep Tabernero, Jean-Luc Van Laethem, Côme Lepage, Jean-François Emile, Aurélien de Reyniès, Julien Taieb, Pierre Laurent-Puig
Journal: Journal of Clinical Oncology (2025)

PURPOSE The objective of this work was to establish prognostic models in stage III colon cancer (CC) on the basis of transcriptomic signatures of the tumor microenvironment (TME) and cell cycle from the PETACC-8 (training set) and IDEA-France (validation set) trials. PATIENTS AND METHODS 3'RNA sequencing was performed in 1,733 patients from the PETACC-8 trial and 1,248 patients from the IDEA-France trial. Four transcriptomic signatures were analyzed: T-cell and macrophage M2 signatures, the expression of CXCL13, and a score on the basis of the Oncotype DX CC Recurrence Score using the same formula from the stromal score and the cell cycle score. The Immune Proliferative Stromal (IPS) score was defined as the number of dichotomized signatures that fall under the category of a dismal prognosis (from 0 to 4). Time to recurrence (TTR) was defined as the time from the date of random assignment to local and/or metastatic relapse and/or death because of CC, whichever occurs first. RESULTS High Oncotype-like and M2 scores and low CXCL13 expression and T-cell score were associated with a shorter TTR. A multivariable model including these signatures and all known prognostic factors applied to the IDEA-France cohort by obtaining a value of this model for each patient showed TTR significantly different depending on the quartile of this value and a 3-year rate of patients without recurrence ranging from 56% for the lowest quartile to 89% for the highest quartile ( P &lt; .0001). The IPS score was significantly associated with TTR in multivariable analysis. CONCLUSION Using transcriptomic data of patients with stage III CC from two large-scale adjuvant trials, a prognostic model on the basis of signatures of the TME and the cell cycle provides important information in addition to known prognostic factors for patient stratification on risk of recurrence.
Nivolumab With or Without Ipilimumab in Patients With Recurrent or Metastatic Merkel Cell Carcinoma: A Nonrandomized, Open-Label, International, Multicenter Phase I/II Study
Authors: Shailender Bhatia, Suzanne L. Topalian, William Sharfman, Tim Meyer, Neil Steven, Christopher D. Lao, Lorena Fariñas-Madrid, Lot A. Devriese, Kathleen Moore, Robert L. Ferris, Yoshitaka Honma, Ileana Elias, Anjaiah Srirangam, Charlie Garnett-Benson, Michelle Lee, Paul Nghiem
Journal: Journal of Clinical Oncology (2025)

PURPOSE Approximately 50% of patients with advanced Merkel cell carcinoma (MCC) have primary or acquired resistance to PD-(L)1 blockade, which may be overcome using combination immune checkpoint inhibition (ICI) with anti–cytotoxic T lymphocyte antigen-4 antibody. We present results from the recurrent/metastatic MCC cohort in CheckMate 358, a nonrandomized, multicohort, phase I/II study of nivolumab (NIVO) with or without ipilimumab (IPI) in virus-associated cancers (ClinicalTrials.gov identifier: NCT02488759 ). METHODS ICI-naïve patients with recurrent/metastatic MCC and 0-2 previous systemic therapies were administered NIVO monotherapy at 240 mg once every 2 weeks or combination therapy with NIVO 3 mg/kg once every 2 weeks + IPI 1 mg/kg once every 6 weeks. The primary end point was objective response. Secondary end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). RESULTS Sixty-eight patients received NIVO (n = 25) or NIVO + IPI (n = 43). The objective response rate (95% CI) and median DOR (95% CI), respectively, were 60% (38.7 to 78.9) and 60.6 months (16.7 to not applicable [NA]) with NIVO and 58% (42.1 to 73) and 25.9 months (10.4 to NA) with NIVO + IPI. The median PFS (95% CI) and OS (95% CI), respectively, were 21.3 (9.2 to 62.5) and 80.7 (23.3 to NA) months with NIVO and 8.4 (3.7 to 24.3) and 29.8 (8.5 to 48.3) months with NIVO + IPI. The incidence of grade 3/4 treatment-related adverse events was 28% with NIVO and 47% with the combination. CONCLUSION This nonrandomized study showed frequent and durable responses with both NIVO and NIVO + IPI in patients with ICI-naïve advanced MCC. However, it did not show improvement in efficacy with the combination, thus contradicting previous study reports that had suggested clinical benefit with combination ICI. A randomized trial of NIVO + IPI versus NIVO monotherapy is warranted.
A molecular basis for milk allergen immune recognition in eosinophilic esophagitis
Authors: Julianna Dilollo, Alex Hu, Huiqi Qu, Karina E Canziani, Rachel L Clement, Sam J McCright, Wayne G Shreffler, Hakon Hakonarson, Jonathan M Spergel, Karen Cerosaletti, David A Hill
Journal: Journal of Allergy and Clinical Immunology (2025)
Rapid validation of NLRP3 gain-of-function variants in cryopyrin-associated periodic syndromes
Authors: Alex Quach, Yunyu Lao, Alexander Troelnikov, Pravin Hissaria, Damien Chan, Amanda Wells, Abhijit Kulkarni, Lesley Rawlings, Nicola Poplawski, Antonio Ferrante
Journal: Journal of Allergy and Clinical Immunology (2025)
Long-term drought and risk of infant mortality in Africa: A cross-sectional study
Authors: Pin Wang, Tormod Rogne, Joshua L. Warren, Ernest O. Asare, Robert A. Akum, N’datchoh E. Toure, Joseph S. Ross, Kai Chen
Journal: PLoS Medicine (2025)

Background As extreme events such as drought and flood are projected to increase in frequency and intensity under climate change, there is still large missing evidence on how drought exposure potentially impacts mortality among young children. This study aimed to investigate the association between drought and risk of infant mortality in Africa, a region highly vulnerable to climate change that bears the heaviest share of the global burden. Methods and findings In this cross-sectional study, we obtained data on infant mortality in 34 African countries during 1992–2019 from the Demographic and Health Surveys program. We measured drought by the standardized precipitation evapotranspiration index at a timescale of 24 months and a spatial resolution of 10 × 10 km, which was further dichotomized into mild and severe drought. The association between drought exposure and infant mortality risk was estimated using Cox regression models allowing time-dependent covariates. We further examined whether the association varied for neonatal and post-neonatal mortality and whether there was a delayed association with drought exposure during pregnancy or infancy. The mean (standard deviation) number of months in which children experienced any drought during pregnancy and survival period (from birth through death before 1 year of age) was 4.6 (5.2) and 7.3 (7.4) among cases and non-cases, respectively. Compared to children who did not experience drought, we did not find evidence that any drought exposure was associated with an increased risk of infant mortality (hazard ratio [HR]: 1.02, 95% confidence interval [CI] [1.00, 1.04], p = 0.072). When stratified by drought severity, we found a statistically significant association with severe drought (HR: 1.04; 95% CI [1.01, 1.07], p = 0.015), but no significant association with mild drought (HR: 1.01; 95% CI [0.99, 1.03], p = 0.353), compared to non-exposure to any drought. However, when excluding drought exposure during pregnancy, the association with severe drought was found to be non-significant. In addition, an increased risk of neonatal mortality was associated with severe drought (HR: 1.05; 95% CI [1.01, 1.10], p = 0.019), but not with mild drought (HR: 0.99; 95% CI [0.96, 1.02], p = 0.657). Conclusions Exposure to long-term severe drought was associated with increased infant mortality risk in Africa. Our findings urge more effective adaptation measures and alleviation strategies against the adverse impact of drought on child health.
Emergency Department Non-Mydriatic Fundus Photography Expedites Care For Patients Referred For “Papilledema”
Authors: Mung Yan Lin, Hetal J Ray, Andrew M Pendley, Étienne Bénard-Séguin, Avital Lily Okrent Smolar, Mariana Rodriguez Duran, Mariam Torres Soto, Nithya Shanmugam, Jessica McHenry, Gabriele Berman, Matthew T Keadey, David W Wright, Beau B Bruce, Nancy J Newman, Valérie Biousse
Journal: Ophthalmology (2025)
Role of plasma and blood-cell co-metagenomic sequencing in precise diagnosis and severity evaluation of sepsis, a prospective cohort study in sepsis patients
Authors: Ying Zhu, Hui Miao, Jingjia Zhang, Zhi Jiang, Xiaobing Chu, Yingchun Xu, Wenjia Tian, Haotian Gao, Yun Zhu, Lifeng Li, Qiwen Yang
Journal: Journal of Infection (2025)
Oral submucous fibrosis: pathogenesis and therapeutic approaches
Authors: Jianfei Tang, Junjie Liu, Zekun Zhou, Xinyan Cui, Hua Tu, Jia Jia, Baike Chen, Xiaohan Dai, Ousheng Liu
Journal: International Journal of Oral Science (2025)

Abstract Oral submucous fibrosis (OSF), characterized by excessive deposition of extracellular matrix (ECM) that causes oral mucosal tissue sclerosis, and even cancer transformation, is a chronic, progressive fibrosis disease. However, despite some advancements in recent years, no targeted antifibrotic strategies for OSF have been approved; likely because the complicated mechanisms that initiate and drive fibrosis remain to be determined. In this review, we briefly introduce the epidemiology and etiology of OSF. Then, we highlight how cell-intrinsic changes in significant structural cells can drive fibrotic response by regulating biological behaviors, secretion function, and activation of ECM-producing myofibroblasts. In addition, we also discuss the role of innate and adaptive immune cells and how they contribute to the pathogenesis of OSF. Finally, we summarize strategies to interrupt key mechanisms that cause OSF, including modulation of the ECM, inhibition of inflammation, improvement of vascular disturbance. This review will provide potential routes for developing novel anti-OSF therapeutics.
Strontium–Alix interaction enhances exosomal miRNA selectively loading in synovial MSCs for temporomandibular joint osteoarthritis treatment
Authors: Wenxiu Yuan, Jiaqi Liu, Zhenzhen Zhang, Chengxinyue Ye, Xueman Zhou, Yating Yi, Yange Wu, Yijun Li, Qinlanhui Zhang, Xin Xiong, Hengyi Xiao, Jin Liu, Jun Wang
Journal: International Journal of Oral Science (2025)

Abstract The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) “difficult-to-treat”. Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix’s crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
Expert consensus on orthodontic treatment of protrusive facial deformities
Authors: Jie Pan, Yun Lu, Anqi Liu, Xuedong Wang, Yu Wang, Shiqiang Gong, Bing Fang, Hong He, Yuxing Bai, Lin Wang, Zuolin Jin, Weiran Li, Lili Chen, Min Hu, Jinlin Song, Yang Cao, Jun Wang, Jin Fang, Jiejun Shi, Yuxia Hou, Xudong Wang, Jing Mao, Chenchen Zhou, Yan Liu, Yuehua Liu
Journal: International Journal of Oral Science (2025)

Abstract Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Treatment of Patients with IgA Nephropathy: A call for a new paradigm
Authors: Jürgen Floege, Amelie Bernier-Jean, Jonathan Barratt, Brad Rovin
Journal: Kidney International (2025)

IgA nephropathy (IgAN), the world's most common primary glomerular disease, carries a significant lifetime risk for kidney failure as well as an enormous socioeconomic burden. In the past, studies in patients with IgAN largely focused on optimizing so-called supportive care, that is, blockade of the renin-angiotensin system, blood pressure control, and lifestyle modifications. The effectiveness of immunosuppressive measures, particularly high-dose corticosteroid therapy, has been reported variably, but there is considerable evidence for an increase in serious adverse effects with such therapies. This disappointing situation has changed dramatically with a better understanding of the pathogenesis of IgAN, and with regulatory agencies accepting changes in proteinuria and the estimated glomerular filtration rate loss or slope over 2 to 3 years as surrogate outcome markers. A multitude of new therapies are now being evaluated in IgAN, and several drugs, such as sodium-glucose transporter-2 inhibitors, sparsentan (a dual endothelin-1 and angiotensin II receptor blocker), nefecon (a targeted release formulation of budesonide), and iptacopan (a complement factor B inhibitor), have been approved, with more to come in the next few years. In this review, we propose a new treatment paradigm that combines therapies with different mechanisms of action to target the immune components and the chronic kidney disease components of IgAN in parallel to preserve long-term kidney survival.
When I use a word . . . Lexicographic anniversaries in 2025: Placebo
Authors: Jeffrey K Aronson
Journal: BMJ (2025)

In 2025, by my count, there are over 650 words with some sort of medical significance that have lexicographic anniversaries. By that I mean that they had a birthday 50, or 100, or 150, or 200, and so on, years ago. I define a word's birthday as the year in which it first appeared in a written text, generally as documented in the <i>Oxford English Dictionary</i> (<i>OED</i>), although in some cases such birthdays can be backdated by finding earlier instances, so-called antedatings. For example, the words "medicine," "remedy," and "remission" all occurred for the first time in written form in a text called <i>The Ancrene Riwle</i>, dated around 1225, and therefore have their 800th anniversary this year. "Placebo" is one of the over 14 000 words of all kinds that have anniversaries in 2025. But its anniversary is not in the medical sense of the word, because the first recorded use of the word, also in around 1225, was a religious one, referring to a Roman Catholic religious service, Vespers in the Office for the Dead. It was called Placebo from the first words in the service, as found in St Jerome's Latin version (the Vulgate) of the Septuagint: "Placebo Domino in regione vivorum ...," "I shall please the Lord in the land of the living." It was not until 1770 that "placebo" was first used in a written text in its modern medical use. It therefore had a lexicographic anniversary five years ago, in 2020, but not this year. For that to be the case, an antedating from at least as early as 1725 would have to be found, and that is highly unlikely.
Methodology for promoting equity-informed research in sport and exercise medicine: recommendations from the AMSSM Collaborative Research Network
Authors: Katherine H Rizzone, Megan Agnew, Stephanie A Kliethermes, Megan Nicole Arthur, Monique Burton, Carly Day, Caitlin Nicholson, Julia Ray, Nicole Stern, Jonathan A Drezner, Emily Kroshus, Cheri Blauwet
Journal: British Journal of Sports Medicine (2025)

Limited guidance exists for conducting research on health disparities within the field of sport and exercise medicine (SEM). This review aimed to identify and summarise existing best practices for conducting equitable, diverse and inclusive research within SEM. A narrative review with evidence synthesis was conducted using electronic databases, reference lists, manual searches and relevant publications from other organisations. Search terms associated with steps of the research process were used in tandem with 'equity', 'inclusion' and 'health disparities'. We developed a research roadmap for SEM researchers with methodological recommendations to develop and conduct equity-informed and equity-focused research. This roadmap serves as a tool for SEM researchers and clinicians to design, execute and disseminate research with a health disparities lens. We recommend SEM researchers should build an equitable, diverse and inclusive research team and include community members; apply a multilevel, intersectional framework; minimise and acknowledge potential biases in the study design and incorporate qualitative or mixed-methods approaches if appropriate; apply multiple inclusive strategies for recruiting and retaining diverse populations; collect accurate and representative data using inclusive data collection methods and tools with validity and reliability in the populations of interest; apply measures with evidence of validity and reliability in the populations of interest; implement a data analysis plan that reflects the conceptual and theoretical frameworks; and promote broad dissemination and interventions that ultimately address and reduce health inequities. SEM researchers should consider these methodological recommendations to conduct equity-informed and equity-focused research to address health disparities in SEM.
Treatment of Androgenetic Alopecia with Low Dose Oral Minoxidil Monotherapy Compared to Combination Therapy with Dutasteride or Finasteride
Authors: Ambika Nohria, Deesha Desai, Michelle Sikora, Akshay Pulavarty, Anna Brinks, Carli Needle, Avrom Caplan, Jerry Shapiro, Kristen Lo Sicco
Journal: Journal of the American Academy of Dermatology (2025)
Temporal profiling of human lymphoid tissues reveals coordinated defense against viral challenge
Authors: Matthew L. Coates, Nathan Richoz, Zewen K. Tuong, Georgina S. Bowyer, Colin Y. C. Lee, John R. Ferdinand, Eleanor Gillman, Mark McClure, Lisa Dratva, Sarah A. Teichmann, David R. Jayne, Rafael Di Marco Barros, Benjamin J. Stewart, Menna R. Clatworthy
Journal: Nature Immunology (2025)
What’s in a name? Memory NK cells for cancer immunotherapy
Authors: Sean J Judge, Megan C Purl, William J Murphy, Robert J Canter
Journal: Journal for ImmunoTherapy of Cancer (2025)

The discovery that natural killer (NK) cells can retain features of “memory” from previous stimulation and pathogen exposure was a landmark advance highlighting one of many ways in which NK cells of the innate immune system resemble T cells of the adaptive immune system. This ability to “remember” prior stimulation to bring about enhanced protection of the host sparked significant excitement regarding potential therapeutic applications. Yet, how closely the features of naïve and memory NK cells recapitulate those of T cells remains unclear. Nonetheless, despite unresolved questions about the immunobiology of naïve and memory NK cells, the application of memory NK cells to the clinic for cancer and other indications has gathered steam to meet the unmet need for novel immunotherapies. Recent work from Arellano-Ballestero et al highlights this evolving field and the current state of the art with memory NK cells. Application of these cells to the clinic is progressing with promising results, but important questions remain about the essential molecular, phenotypic, and functional characteristics that define a memory NK cell.
Genome-Wide Association Study of Plasma Sodium Concentrations with and without Exposure to Thiazide Diuretics
Authors: Niklas Worm Andersson, Xiaoping Wu, Frank Geller, Jan Wohlfahrt, Mads Melbye, Anders Hviid, Michael Schwinn, Christina Mikkelsen, Joseph Dowsett, Mie Topholm Bruun, Bitten Aagaard, Henrik Ullum, Christian Erikstrup, Daniel Fannar Gudbjartsson, Kári Stefánsson, Jonas Ghouse, Ole Birger Pedersen, Erik Sørensen, Sisse Rye Ostrowski, Henning Bundgaard, Marie Lund, Bjarke Feenstra
Journal: Journal of the American Society of Nephrology (2025)

Abnormal plasma sodium concentration represents an imbalance of total body water relative to electrolyte content. Hyponatremia is a common and potentially severe adverse event, and thiazide diuretics constitute a leading cause of drug-induced hyponatremia. We conducted genome-wide association study analyses of plasma sodium concentration, thiazide-induced decrease in sodium concentration, and thiazide-induced hyponatremia in a total of 188,464 individuals of European ancestry . Additionally, we tested for gene-environment interaction between a polygenic score developed for plasma sodium concentration and thiazide exposure on sodium concentration and hyponatremia risk. Meta-analysis yielded 31 independent associated signals at P<5×10-8 with plasma sodium concentrations. Subsequent tissue specificity analysis showed a significantly increased expression of sodium-associated genes in pituitary tissue (P=4.5×10-5). No genome-wide significant loci were found for thiazide-induced sodium concentration decrease or thiazide-induced hyponatremia. A polygenic score for plasma sodium concentration was associated with 0.43 (95% confidence interval (CI) = 0.39-0.46) mmol/L lower plasma sodium per standard deviation lower, and thiazide use was associated with 0.80 (95% CI=0.72-0.88) mmol/L lower plasma sodium, but we observed no gene-environment interaction effect (P=0.71). These results underline the role of genetic variation in regulating plasma sodium concentration and highlight the importance of pathways involving the pituitary gland while finding no evidence of genetic predisposition for the plasma sodium-lowering effect of thiazides.