tbuckley/cabot-search huggingface dataset:
NLRP3 inflammasome in neuroinflammation and central nervous system diseases
Authors: Wen Xu, Yi Huang, Rongbin Zhou
Journal: Cellular and Molecular Immunology (2025)

Abstract Neuroinflammation plays an important role in the pathogenesis of various central nervous system (CNS) diseases. The NLRP3 inflammasome is an important intracellular multiprotein complex composed of the innate immune receptor NLRP3, the adaptor protein ASC, and the protease caspase-1. The activation of the NLRP3 inflammasome can induce pyroptosis and the release of the proinflammatory cytokines IL-1β and IL-18, thus playing a central role in immune and inflammatory responses. Recent studies have revealed that the NLRP3 inflammasome is activated in the brain to induce neuroinflammation, leading to further neuronal damage and functional impairment, and contributes to the pathological process of various neurological diseases, such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and stroke. In this review, we summarize the important role of the NLRP3 inflammasome in the pathogenesis of neuroinflammation and the pathological course of CNS diseases and discuss potential approaches to target the NLRP3 inflammasome for the treatment of CNS diseases.
Revised Perspective on the AJCC Staging System for Medullary Thyroid Cancer: A Study of Two Nationwide Cohorts
Authors: Cenkai Shen, Yuxin Du, Shiyu Xiang, Zimeng Li, Chuqiao Liu, Zhiyan Liu, Yijun Wu, Liang Guo, Yan Zhang, Hao Zhang, Chuang Chen, Min Yin, Haitao Tang, Qinghai Ji, Wenjun Wei, Xiao Shi, Yu Wang
Journal: Journal of the National Comprehensive Cancer Network (2025)

Background: The current AJCC TNM staging system for medullary thyroid cancer (MTC) is largely adapted from criteria for differentiated thyroid cancer, which may not fully capture MTC-specific prognostic factors. This study aimed to evaluate the prognostic significance of upper mediastinal lymph node metastasis (LNM) and propose corresponding modifications to the N category and staging system to improve their applicability for MTC. Methods: We conducted a population-based, retrospective study enrolling patients with MTC from 19 Chinese referral centers. Demographics and pathologic characteristics were collected, and patients were categorized into 4 LNM subgroups: no LNM, central cervical LNM, lateral cervical LNM, and upper mediastinal (level VII) LNM. We assessed their prognostic significance using Kaplan-Meier survival curves and Cox regression analysis. Recursive partitioning analysis was then applied to regroup patients with similar overall survival (OS). To validate our findings, we analyzed an independent cohort from the SEER database. Results: Our multicenter cohort included 827 patients with initially treated MTC, of whom 438 (53.0%) were female, with a median age of 50 years (IQR, 40–59). Upper mediastinal (level VII) LNM was present in 12.6% of patients and was significantly associated with worse OS, structural recurrence-free survival, and biochemical response compared with other LNM sites (all P &lt;.05). Based on these findings, we proposed up-classifying level VII metastases from N1a to a new category, N1c, while keeping the T and M definitions unchanged. We then regrouped 4 TNM stages: stage I (T1–2N0–1aM0), stage II (T1–3N1bM0, T3N0–1aM0), stage III (T4N0–1bM0, T1–3N1cM0), and stage IV (T4N1cM0, T1–4N0–1cM1). Our modified staging system demonstrated superior prognostic discrimination and predictive power compared with the current AJCC TNM system, both in our multicenter cohort and the SEER validation cohort. Conclusions: For the first time, we identified the upper mediastinum as the most critical site for regional LNM in MTC. Our proposed adjustments to the N category and TNM staging system could provide better risk stratification for patients with MTC, potentially guiding improved clinical management and treatment strategies.
Locoregional Radiotherapy Candidates in de Novo Metastatic Nasopharyngeal Carcinoma: Real-World Insights in the Immunotherapy Era
Authors: Dongxiang Wen, Jing Jin, Jieyi Lin, Meijuan Luo, Rongping Liu, Siqi Liu, Longbin Xiong, Liting Liu, Linquan Tang, Haiqiang Mai, Shanshan Guo, Yujing Liang, Qiuyan Chen
Journal: Journal of the National Comprehensive Cancer Network (2025)

Background: Chemotherapy combined with immunotherapy (CT-IO) has become the first-line treatment for de novo metastatic nasopharyngeal carcinoma (dmNPC). Locoregional radiotherapy (LRRT) following chemotherapy has been shown to significantly improve survival outcomes in patients with dmNPC. However, it remains unclear whether LRRT provides additional benefits in the context of CT-IO. Furthermore, there is no consensus on how to identify the optimal patient population for LRRT after first-line CT-IO. Methods: This study included patients with dmNPC who received platinum-based palliative chemotherapy and anti–PD-1 immunotherapy, with or without LRRT. Progression-free survival (PFS) was assessed in LRRT and non-LRRT groups using inverse probability of treatment weighting (IPTW) to mitigate selection bias. Median PFS (mPFS) at the 6-month landmark was estimated using Kaplan-Meier analyses. A novel prognostic nomogram was developed and validated to predict PFS and stratify patients by risk. Using prognostic scores from the nomogram, a model-based tree approach was employed to assess stratified treatment outcomes and identify the ideal candidates for LRRT. Results: A total of 500 patients were included, with 367 receiving LRRT and 133 not receiving it. At the 6-month conditional landmark, IPTW-adjusted Kaplan-Meier curves demonstrated significantly improved survival in the LRRT group compared with the non-LRRT group (mPFS, not reached vs 21.5 months; P &lt;.001). Patients were randomized into training and validation cohorts in a 7:3 ratio. A prognostic model integrating serum lactate dehydrogenase (LDH) level, posttreatment Epstein-Barr virus DNA level, number of metastatic lesions, and liver metastases status was developed from the training cohort and graphically represented as a nomogram. The model demonstrated favorable discrimination (C-index, 0.721; 95% CI, 0.681–0.761) and predictive accuracy (1-year time-dependent area under the curve [tAUC]), 0.788), and its performance was validated in the internal cohort (C-index, 0.752; 95% CI, 0.698–0.806; 1-year tAUC, 0.778). A tree-based risk stratification derived from the model classified patients into 2 prognostic subgroups. Low-risk patients benefited from additional LRRT (mPFS, not reached vs 23.6 months; P &lt;.001), whereas high-risk patients did not (mPFS, 18.3 vs 16.5 months; P =.210). Conclusions: In patients with dmNPC, additional LRRT following first-line CT-IO was associated with improved PFS, particularly among low-risk patients identified using a novel prognostic model.
Cutting‐Edge Therapy and Immune Escape Mechanisms in EBV‐Associated Tumors
Authors: Jie Wang, Rong Wang, Meifeng Wang, Junshang Ge, Yian Wang, Yanhan Li, Changan Chen, Jiale He, Boshu Zheng, Meifang Xu, Xianjie Jiang, Yuhang Liu, Mingfen Chen, Jun Long
Journal: Medicinal Research Reviews (2025)

Epstein-Barr virus (EBV), the first identified human tumor virus, significantly influences the immune microenvironment of associated cancers. EBV-induced expression of viral antigens by tumor cells triggers immune recognition and elicits a pro-inflammatory response. While mild inflammation may help eliminate malignant cells, intense inflammation can accelerate tumor progression. Moreover, EBV can establish lifelong latency in human hosts, characterized by low immunogenicity of its proteins and noncoding RNAs. This enables tumor cells to evade immune detection and impair immune cell function, disrupting immune homeostasis. Consequently, EBV-associated malignancies pose a considerable public health challenge globally, often complicating the prognosis of cancer patients under conventional treatment. With deeper research into the oncogenic expressions and mechanisms of EBV, novel targeted therapies against EBV are gaining prominence. This review discusses recent advancements in understanding how EBV helps tumor cells evade immune surveillance and induce immune dysfunction. It also examines the clinical potential of targeting EBV-associated tumors, providing fresh perspectives on the mechanisms and therapeutic strategies for these cancers.
Opportunities and challenges for the use of human samples in translational cardiovascular research: a scientific statement of the ESC Working Group on Cellular Biology of the Heart, the ESC Working Group on Cardiovascular Surgery, the ESC Council on Basic Cardiovascular Science, the ESC Scientists of Tomorrow, the European Association of Percutaneous Cardiovascular Interventions of the ESC, and the Heart Failure Association of the ESC
Authors: Sean M Davidson, Ioanna Andreadou, Charalambos Antoniades, Jozef Bartunek, Cristina Basso, Bianca J J M Brundel, Robert A Byrne, Gemma Chiva-Blanch, Paula da Costa Martins, Paul C Evans, Henrique Girão, Zoltan Giricz, Can Gollmann-Tepeköylü, Tomasz Guzik, Mariann Gyöngyösi, Norbert Hübner, Michael Joner, Petra Kleinbongard, Thomas Krieg, Elisa Liehn, Rosalinda Madonna, Ange Maguy, Melanie Paillard, Maurizio Pesce, Steffen E Petersen, Gabriele G Schiattarella, Joost P G Sluijter, Sabine Steffens, Katrin Streckfuss-Bömeke, Matthias Thielmann, Art Tucker, Sophie Van Linthout, William Wijns, Johann Wojta, Joseph C Wu, Cinzia Perrino
Journal: Cardiovascular Research (2025)

Animal models offer invaluable insights into disease mechanisms but cannot entirely mimic the variability and heterogeneity of human populations, nor the increasing prevalence of multi-morbidity. Consequently, employing human samples-such as whole blood or fractions, valvular and vascular tissues, myocardium, pericardium, or human-derived cells-is essential for enhancing the translational relevance of cardiovascular research. For instance, myocardial tissue slices, which preserve crucial structural and functional characteristics of the human heart, can be used in vitro to examine drug responses. Human blood serves as a rich source of biomarkers, including extracellular vesicles, various types of RNA (miRNA, lncRNA, and circRNAs), circulating inflammatory cells, and endothelial colony-forming cells, facilitating detailed studies of cardiovascular diseases. Primary cardiomyocytes and vascular cells isolated from human tissues are invaluable for mechanistic investigations in vitro. In cases where these are unavailable, human induced pluripotent stem cells serve as effective substitutes, albeit with specific limitations. However, the use of human samples presents challenges such as ethical approvals, tissue procurement and storage, variability in patient genetics and treatment regimens, and the selection of appropriate control samples. Biobanks are central to the efficient use of these scarce and valuable resources. This scientific statement discusses opportunities to implement the use of human samples for cardiovascular research within specific clinical contexts, offers a practical framework for acquiring and utilizing different human materials, and presents examples of human sample applications for specific cardiovascular diseases, providing a valuable resource for clinicians, translational and basic scientists engaged in cardiovascular research.
Updated Systematic Review and Meta-analysis of Extracorporeal Shock Wave Lithotripsy, Flexible Ureterorenoscopy, and Percutaneous Nephrolithotomy for Lower Pole Renal Stones
Authors: Steven MacLennan, Oliver Wiseman, Daron Smith, Kathryn Starr, Lorna Aucott, Rodolfo Hernández, Paul Manson, Ruth Thomas, Charles Terry Clark, Graeme MacLennan, Dawn McRae, Victoria Bell, Seonaidh Cotton, Zara Gall, Ben Turney, Sam McClinton
Journal: European Urology (2025)
Therapy Dogs for Anxiety in Children in the Emergency Department
Authors: Heather P. Kelker, Huma K. Siddiqui, Alan M. Beck, Jeffrey A. Kline
Journal: JAMA Network Open (2025)

Importance Prior evidence suggests that the use of therapy dogs in emergency care reduces anxiety in adults, but no trial has tested the use of therapy dogs in emergency care of children. Objective To examine whether adjunctive use of therapy dogs in standard child-life therapy reduces child-reported and parent-reported child anxiety in a pediatric emergency department (ED). Design, Setting, and Participants This randomized clinical trial was conducted from February 1, 2023, to June 30, 2024, at an academic pediatric ED. Children (aged 5-17 years) with suspected moderate to high anxiety were included. Intervention All participants received standard child-life therapy, and the intervention group was randomly assigned to have exposure to a therapy dog and handler for approximately 10 minutes. Main Outcomes and Measures Anxiety was measured using the 0- to 10-point FACES scale (with 0 indicating no anxiety and 10 indicating very severe anxiety) and salivary cortisol concentrations. Measurements were obtained at baseline (T0), 45 minutes (T1), and 120 minutes (T2) for both child and parents. Results A total of 80 patients (mean [SD] age, 10.9 [3.8] years; 45 [56%] female) were enrolled (40 in the control group and 40 in the intervention group). At T0, the mean (SD) FACES scores were 5.4 (2.8) for child report and 6.4 (2.4) for parent report; the means were not different between groups. From T0 to T1, child-reported anxiety changed by a mean (SD) of −1.5 (3.4) points in the control group vs −2.7 (2.5) points in the intervention group ( P = .02, Mann-Whitney U test); similarly, mean (SD) parent-estimated child anxiety changed by −1.8 (2.7) points in the control group vs −3.2 (2.3) points in the intervention group ( P = .008). A total of 9 children (23%) in the control group had a greater than 2.5-point decrease in FACES score vs 18 (46%) in intervention group ( P = .04, Fisher test). At T2, mean (SD) child-reported FACES scores decreased to 3.6 (3.4) points in the control group and 3.0 (2.7) points in the intervention group ( P = .70). A total of 14 control participants (35%) received ketamine, midazolam, lorazepam, or droperidol vs 7 (18%) in the intervention group ( P = .08, Fisher test). Child and parent salivary cortisol decreased from T0 to T1 in both groups but was not different between groups. Parental salivary cortisol was significantly consistently higher than their children’s salivary cortisol ( P &amp;amp;lt; .001, unpaired t test, for comparisons of child vs parent at T0 and T1 in both groups). Conclusions and Relevance This study of adjunctive use of therapy dogs in standard child-life therapy found a modest but significantly greater reduction in both child-reported and parental-reported child anxiety in the pediatric ED for the intervention vs control group. These findings support the use of therapy dogs to help reduce pain and anxiety without the use of chemical or physical constraint. Trial Registration ClinicalTrials.gov Identifier: NCT03784573
Health Concerns of Youths From Historically Marginalized Communities During the Postacute Phase of COVID-19
Authors: Melissa A. Jones, Margaux Jones, Kathleen M. Mazor, Benjamin P. Linas
Journal: JAMA Network Open (2025)

This survey study uses text message surveys to explore the behaviors, perspectives, and health concerns of youths from historically marginalized racial and ethnic groups in Boston, Massachusetts, during the postacute phase of the COVID-19 pandemic.
IRF2BP2 Deficiency: An important form of common variable immunodeficiency with inflammation
Authors: Chioma Udemgba, Bethany Pillay, Samantha Shafer, Angelika Alberstadt, Michael Abers, Olivier Gilliaux, Karin Chen, William Rae, Leif Hanitsch, Horst Von Bernuth, Joao Farela Neves, Nikita Raje, Leen Moens, P Martin van Hagen, Jenna Bergerson, Nicholas Hartog, Tim Niehues, Gregor Dückers, Emilia Falcone, Michael Keller, Amy Hsu, Isabelle Meyts, Steven M Holland
Journal: Journal of Allergy and Clinical Immunology (2025)
ATF4 drives regulatory T cell functional specification in homeostasis and obesity
Authors: Ke Wang, Andrea Farrell, Enchen Zhou, Houji Qin, Zixuan Zeng, Kailun Zhou, Karina Cunha e Rocha, Dinghong Zhang, Gaowei Wang, Amha Atakilit, Dean Sheppard, Li-Fan Lu, Chunyu Jin, Wei Ying
Journal: Science Immunology (2025)

Regulatory T cells (T regs ) have diverse functional specification in homeostasis and disease. However, how liver T regs function and are transcriptionally regulated in obesity is not well understood. Here, we identified that effector T regs expressing activating transcription factor 4 (ATF4) were enriched in the livers of obese mice. ATF4 was critical for driving an effector T reg transcriptional program, and ATF4-expressing T regs promoted the development of obesity-induced liver fibrosis by enhancing transforming growth factor–β activation via integrin αvβ8. T reg -specific deletion of Atf4 resulted in reduced liver T regs and attenuation of obesity-induced liver abnormalities. Furthermore, ATF4 was required to promote the differentiation of nonlymphoid tissue T reg precursors under steady state. These findings demonstrate that ATF4 is important for regulating T reg functional specification in homeostasis and obesity.
QRICH1 mediates an intracellular checkpoint for CD8 <sup>+</sup> T cell activation via the CARD11 signalosome
Authors: Nicole M. Carter, Wihib D. Hankore, Yong-Kang Yang, Chao Yang, Shelby M. Hutcherson, Wyatt Fales, Anushka Ghosh, Piyusha Mongia, Sophie Mackinnon, Anna Brennan, Robert D. Leone, Joel L. Pomerantz
Journal: Science Immunology (2025)

Antigen receptor signaling pathways that control lymphocyte activation depend on signaling hubs and negative regulatory proteins to fine-tune signaling outputs to ensure host defense and avoid pathogenic responses. Caspase recruitment domain–containing protein 11 (CARD11) is a critical signaling scaffold that translates T cell receptor (TCR) triggering into the activation of nuclear factor κB (NF-κB), c-Jun N-terminal kinase (JNK), mechanistic target of rapamycin (mTOR), and Akt. Here, we identify glutamine-rich protein 1 (QRICH1) as a regulator of CARD11 signaling that mediates an intracellular checkpoint for CD8 + T cell activation. QRICH1 associates with CARD11 after TCR engagement and negatively regulates CARD11 signaling to NF-κB. QRICH1 binding to CARD11 is controlled by an autoregulatory intramolecular interaction between QRICH1 domains of previously uncharacterized function. QRICH1 controls the antigen-induced activation, proliferation, and effector status of CD8 + T cells by regulating numerous genes critical for CD8 + T cell function. Our results define a component of antigen receptor signaling circuitry that fine-tunes effector output in response to antigen recognition.
Sequential construction of vascularized and mineralized bone organoids using engineered ECM-DNA-CPO-based bionic matrix for efficient bone regeneration
Authors: Tingting Gai, Hao Zhang, Yan Hu, Ruiyang Li, Jian Wang, Xiao Chen, Jianhua Wang, Zhenhua Chen, Yingying Jing, Chenglong Wang, Long Bai, Xiuhui Wang, Jiacan Su
Journal: Bioactive Materials (2025)
Exploring the frontiers: a panoramic analysis of global multi-specific antibody clinical trials
Authors: Simeng Gao, Yan Zhang, Jingru Han, Jianfu Zhao
Journal: International Journal of Surgery (2025)

aResearch Center of Cancer Diagnosis and Therapy, Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou, China *Corresponding author. Address: Research Center of Cancer Diagnosis and Therapy, Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China. E-mail: [email protected] (J. Zhao). Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website,www.journalsurgery.net. This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms.
Lactated Ringer’s solution versus saline fluid resuscitation for reducing PROGRESSION TO moderate-to-severe acute pancreatitis: a systematic review and meta-analysis
Authors: Tang Zhao, Zhiqiang Kang, Qiu Zhang, Feng Pu, Yun Zhang, Wen Qing Yin, Hong Ji Yang, Yu Zhou, Shi Kai Zhu
Journal: International Journal of Surgery (2025)

Background: Fluid resuscitation represents a pivotal early therapeutic intervention in the management of acute pancreatitis (AP), yet a consensus on the optimal fluid type remains elusive. The present study endeavors to elucidate the differential effects of lactated Ringer’s solution (LR) and normal saline (NS) in the initial treatment of AP. Methods: A comprehensive literature search was conducted through the PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases, spanning from inception until July 2024. The primary outcome of interest was the likelihood of developing moderate-to-severe AP. Results: This meta-analysis synthesized evidence from six randomized controlled trials (RCTs) and four observational studies, involving a total of 1500 AP patients. Patients were stratified into two groups based on the administered fluid: LR (n = 689) and NS (n = 811). Our findings revealed that, compared to the NS group, patients in the LR group demonstrated a significantly lower risk of moderate-to-severe acute pancreatitis (OR 0.48; 95%Cl 0.34 to 0.67; P &lt; 0.001; I 2 = 0%), a shorter hospital stay (MD = − 0.74, 95% CI −1.20 to −0.28, P = 0.001; I 2 = 0%), and a reduced ICU admission rate (RR = 0.42, 95% CI 0.20–0.89, P = 0.02; I 2 = 0%). Moreover, the LR group also showed a lower incidence of local complications (RR = 0.58, 95% CI 0.34–0.98, P = 0.04). Conversely, no statistically significant differences were observed between the two groups in terms of mortality, organ failure rates, Fluid administered 24 h, systemic inflammatory response syndrome (SIRS). Conclusions: Our analysis underscores the superior efficacy of Lactated Ringer’s (LR) solution in comparison to Normal Saline (NS). It provides compelling evidence of LR’s ability to significantly mitigate the onset of moderate to severe pancreatitis. Additionally, our findings reveal that LR is associated with a reduced need for Intensive Care Unit (ICU) admissions, a lower incidence of local complications, and a shorter overall hospital stay, thereby offering a more favorable clinical outcome. However, no notable differences were discerned in other complications. Subgroup analyses further suggest LR’s potential to curb pancreatic necrosis and other indices, albeit these findings necessitate corroboration through extensive experimentation.