tbuckley/cabot-search huggingface dataset:
Broadly neutralizing antibodies targeting pandemic GII.4 variants or seven GII genotypes of human norovirus
Authors: Juyeon Park, Lisa C. Lindesmith, Adam S. Olia, Veronica P. Costantini, Paul D. Brewer-Jensen, Michael L. Mallory, Cynthia E. Kelley, Ed Satterwhite, Victoria Longo, Yaroslav Tsybovsky, Tyler Stephens, Jeffrey Marchioni, Christina A. Martins, Yimin Huang, Ridhi Chaudhary, Mark Zweigart, Samantha R. May, Yaoska Reyes, Becca Flitter, Jan Vinjé, Sean N. Tucker, Gregory C. Ippolito, Jason J. Lavinder, Joost Snijder, Peter D. Kwong, George Georgiou, Ralph S. Baric
Journal: Science Translational Medicine (2025)

Human norovirus causes more than 700 million illnesses annually. Extensive genetic diversity and a paucity of information on conserved neutralizing epitopes pose major obstacles to the design of broadly protective norovirus immunogens. Here, we used high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS)-driven proteomics to quantitatively characterize the circulating serum IgG repertoire before and after immunization with an experimental monovalent norovirus GII.4 VP1 capsid-encoding adenoviral vaccine. Two participants were specifically selected on the basis of the breadth of serum neutralization responses either across GII.4 variants (participant A) or across GII genotypes (participant B). In participant A, vaccination back-boosted highly abundant serum antibody clonotypes targeting epitopes conserved among rapidly evolving GII.4 variants spanning from a strain identified in 1987 to a strain identified in 2019. In participant B, we identified a recall response consisting of broadly neutralizing monoclonal antibodies with remarkable cross-GII ligand-binding blockade (blocking ≥ seven GII genotypes) and virus neutralization breadth. The cocrystal structure of one of these antibodies, VX22, in complex with the VP1 capsid protruding (P) domain revealed a highly conserved epitope (residues 479 to 484 and 509 to 513) within two lateral loops of the P1 subdomain. Antibody evolutionary trajectory analysis further revealed that VX22 had originally evolved from an early heterologous infection, likely by a GII.12 strain. Together, our study demonstrates that norovirus human monoclonal antibodies with broad GII.4 potency and cross-GII breadth can be boosted in serum after immunization with an adenoviral vector-based vaccine, findings that may guide the design of immunogens for broadly protective norovirus vaccines.
Re: Angelo Territo, Luca Afferi, Mireia Musquera, et al. Robot-assisted Kidney Transplantation: The 8-year European Experience. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2024.12.005
Authors: Niek F Casteleijn, Robert A Pol, Benjamin H J Doornweerd
Journal: European Urology (2025)
β‐Diketone Functionalized Microspheres Chelate Reactive Iron via Metal Coordination for Cartilage Repair
Authors: Yong Xu, Xin Gu, Xingchen Li, Yicheng Chen, Zhenyuan Wei, Jielin Wang, Yi Liu, Yunhan Ji, Qian Cheng, Shuai Jiang, Jiangming Yu, Xiaoxiao Li, Wenguo Cui, XiaoJian Ye
Journal: Advanced Healthcare Materials (2025)

Excessive intracellular iron accumulation can induce mitochondrial dysfunction, leading to chondrocyte ferroptosis, a key contributor to cartilage damage in osteoarthritis (OA). Here, micelle-microfluidic hydrogel microspheres, featuring keto-enol-thiol bridged nano-sized secondary structures that disintegrate within the intracellular peroxidative environment to reveal β-diketone groups with metal chelation capabilities, are utilized for the in situ removal of reactive iron, thereby facilitating cartilage repair through the restoration of mitochondrial homeostasis. The relevant experiments demonstrate that the microspheres reduce iron influx by downregulating transferrin receptor (TfR1) expression and decrease mitochondrial iron uptake by upregulating mitochondrial outer membrane iron-sulfur cluster protein (CISD1), thus restoring intracellular mitochondrial iron homeostasis. Furthermore, the antioxidant properties of the ketone-thioether segments synergistically mitigate chondrocyte phospholipid peroxidation via Nrf2/SLC7A11/GPX4 axis, inhibiting ferroptosis and slowing OA progression. In summary, this system that in situ sustainably chelates reactive iron via metal coordination exhibits great potential in the minimally invasive treatment of OA and other ferroptosis-mediated diseases.
An Intervertebral Disc (IVD) Regeneration Model Using Human Nucleus Pulposus Cells (iHNPCs) and Annulus Fibrosus Cells (iHAFCs)
Authors: Yi Zhu, Qing Liu, Chao Yu, Hui Zhang, Jiamin Zhong, Yonghui Wang, Ou Mei, Ethan Gerhard, Wulin You, Guowei Shen, Changqi Luo, Xingye Wu, Jingjing Li, Yi Shu, Ya Wen, Usman Zeb, Hue H. Luu, Michael J. Lee, Lewis L. Shi, Yang Bi, Jian Yang, Jiaming Fan, Russell R. Reid, Tong‐Chuan He, Liangyuan Wen
Journal: Advanced Healthcare Materials (2025)

Intervertebral disc (IVD) degeneration (IVDD), primarily caused by nucleus pulposus (NP) dehydration, leads to low back pain. While current treatments focus on symptom management or surgical intervention, tissue engineering using IVD-derived cells, biofactors, and scaffolds offers a promising regenerative approach. Here, human NP cells (NPCs) and annulus fibrosus cells (AFCs) are immortalized with human telomerase reverse transcriptase (hTERT), generating immortalized NPCs (iHNPCs) and AFCs (iHAFCs). These cells express NP and AF-specific markers, are reversible via FLP recombinase, and are non-tumorigenic. iHAFCs exhibit osteogenic potential, while iHNPCs show chondrogenic differentiation. A 3D-printed citrate-based scaffold was employed to develop an IVD regeneration model, with BMP9-stimulated iHAFCs in the peripheral region and BMP2-stimulated iHNPCs in the central region. Histological analysis revealed bone formation in the iHAFC region and cartilage formation in the iHNPC region, mimicking the natural IVD structure. Additionally, an ex vivo spine fusion model demonstrated robust bone formation in iHAFC-treated segments. These findings highlight the potential of iHAFCs and iHNPCs as valuable tools for IVD tissue engineering and regeneration.
Trajectories of Sleep Duration, Sleep Onset Timing, and Continuous Glucose Monitoring in Adults
Authors: Luqi Shen, Bang-yan Li, Wanglong Gou, Xinxiu Liang, Haili Zhong, Congmei Xiao, Ruiqi Shi, Zelei Miao, Yan Yan, Yuanqing Fu, Yu-ming Chen, Ju-Sheng Zheng
Journal: JAMA Network Open (2025)

Understanding the interplay between trajectories of sleep duration, sleep onset timing, and glycemic dynamics is crucial for improving preventive strategies against diabetes and related metabolic diseases. To examine the associations of sleep duration and onset timing trajectories with continuous glucose monitoring (CGM)-derived glycemic metrics in adults. This cohort study analyzed data collected from January 2014 to December 2023 in the Guangzhou Nutrition and Health Study, a prospective cohort in Guangdong province, China, among participants aged 46 to 83. Participants who had repeated sleep assessments at several study visits and were equipped with CGM devices at the last visit were included. Data analyses were conducted between January and June 2024. The trajectories of sleep duration and onset timing were constructed using self-report sleep duration and sleep onset timing, recorded at multiple study visit points. Measurements of glycemic variability and glycemic control were collected using a masked CGM device worn by patients for 14 consecutive days. Huber robust regression models were used to assess the associations between sleep trajectories and CGM-derived metrics. In this study of 1156 participants (mean [SD] age, 63.0 [5.1] years, 816 [70.6%] women), we identified 4 distinct sleep duration trajectory groups: severe inadequate, moderate inadequate, mild inadequate, and adequate. Severe sleep inadequacy was associated with an increment of glycemic variability indicators: 2.87% (95% CI, 1.23%-4.50%) for coefficient of variation and 0.06 (95% CI, 0.02-0.09) mmol/L for mean of daily differences. We found 2 trajectories of sleep onset timing: persistent early and persistent late groups. Late sleep onset was associated with larger coefficient of variation (β = 1.18%; 95% CI, 0.36%-2.01%) and mean of daily differences (β = 0.02 mmol/L; 95% CI, 0.01-0.04 mmol/L). Inappropriate sleep duration and timing trajectories in combination were associated with greater glycemic variability. In this cohort study of middle-aged and older participants, persistent inadequate sleep duration and late sleep onset, whether alone or in combination, were associated with greater glycemic variability. These findings emphasize the importance of considering both sleep duration and timing for optimizing glycemic control in the general population.
Single Cell Analyses Reveal a Functionally Heterogeneous Exhausted CD8+ T Cell Subpopulation that is Correlated with Response to Checkpoint Therapy in Melanoma
Authors: Kelly M. Mahuron, Osmaan Shahid, Prachi Sao, Clinton Wu, Alexandra M. Haugh, Laura A. Huppert, Lauren S. Levine, Margaret M. Lowe, Michael Alvarado, Markee Micu, Katy K. Tsai, Melissa Chow, Meromit Singer, Jason M. Schenkel, Arlene H. Sharpe, Michael D. Rosenblum, Kristen E. Pauken, Adil I. Daud
Journal: Cancer Research (2025)

PD-1 pathway inhibitors have revolutionized cancer therapy. However, most patients do not durably benefit, highlighting the need for biomarkers to stratify patients as responders or nonresponders. Although CD8+ tumor-infiltrating lymphocytes (TIL) have been associated with immune checkpoint therapy response, there is no consensus on which CD8+ TIL subpopulations have the most prognostic value. Preclinical studies have focused on progenitor-like exhausted CD8+ T cells (TPEX) because TPEX proliferate more in response to PD-1 inhibitors than other exhausted T-cell (TEX) subpopulations. However, immune checkpoint inhibitor treatment drives TPEX differentiation into other TEX populations that can mediate antitumor immunity. These data complicate the ability to identify prognostically important T-cell populations in patients that predict immune checkpoint inhibitor treatment response. In this study, we found that patients with advanced melanoma with ≥20% of CD8+ TILs coexpressing PD-1 and CTLA4 (termed CPHi TIL) had better objective response rates and survival following PD-1 monotherapy than those below this threshold. Characterization of the CPHi TIL subset using bulk and single-cell RNA sequencing showed that although TPEX-like cells were present within the CPHi subset, they were in the minority of these cells. Rather, the CPHi population was numerically dominated by other subsets, including cycling, terminally exhausted-like, cytotoxic-like, and/or resident memory-like TEX populations, and a subset enriched for glycolytic genes. Collectively, these data show that CPHi TILs correlate with response in melanoma, but this TIL subset is a heterogeneous mix of different subpopulations that may differentially contribute to antitumor immunity following checkpoint blockade. Significance: The PD-1+ CTLA4+ CD8+ tumor-infiltrating lymphocyte population correlating with immunotherapy response is a heterogeneous mix of subpopulations, which has important implications for optimizing checkpoint-based immunotherapy.
Food Insecurity and Clinical Outcomes in Surgical Trauma Patients
Authors: Anam N. Ehsan, Annabelle Jones, Shivangi Saha, Preet Hathi, Chaun-Chin Huang, Srinivasan Vengadassalapathy, Keerthana Bhat, Praveen Ganesh, Shashank Chauhan, Surya Rao Rao Venkata Mahipathy, Coral Katave, Maneesh Singhal, Seth A. Berkowitz, S. Raja Sabapathy, Kavitha Ranganathan
Journal: JAMA Surgery (2025)

Food insecurity, which is the lack of consistent access to sufficient and nutritious food, impacts over 1.3 billion individuals worldwide. The impact of food insecurity on primary care and medical subspecialties is recognized, but its influence on surgical outcomes remains underexplored. To investigate the association between food insecurity and postoperative clinical outcomes in adult surgical trauma patients. This prospective longitudinal cohort study was conducted from October 2021 to June 2023 and surveyed patients at admission and at 1 and 3 months postoperatively. This multicenter study was conducted across 3 public and private tertiary care centers in India. Adult patients who underwent inpatient operative intervention for traumatic injury were included through consecutive sampling. Food insecurity, which was identified using the validated Hunger Vital Sign tool. This was determined at admission as preoperative food insecurity. Also assessed was a subset of participants who were food secure at admission but then became food insecure during the follow-up period. Postoperative complications and length of stay. These outcomes were tracked during hospitalization and also at 1 month and 3 months after discharge to compare between time points. A total of 848 patients (median [IQR] age, 32 [24-45] years; 692 male [82%]) were included in this analysis. Of the total cohort, 174 participants (21%) reported experiencing food insecurity in the year before admission. Patients with food insecurity had significantly higher rates of postoperative complications compared with those without food insecurity (41.4% [72 of 174] vs 12.5% [84 of 671]; odds ratio [OR], 3.68; 95% CI, 2.24-6.05). Additionally, patients with food insecurity had a longer median (IQR) length of stay (13 [6-28] days vs 5 [3-9] days; incidence rate ratio, 1.51; 95% CI, 1.31-1.74). Furthermore, new-onset food insecurity at 1 month postoperatively was associated with an increased risk of new complications at 3 months postoperatively (OR, 5.06; 95% CI, 2.21-11.13). Results demonstrate that food insecurity was significantly associated with increased postoperative complications and longer hospital stays in surgical trauma patients. Routine screening for food insecurity and targeted interventions like medically tailored meals, food prescription programs, and philanthropic food resources may mitigate the detrimental impact of food insecurity on surgical outcomes.
The Evolving Landscape of Biologics—Biosimilars, Biobetters, and Bioparallels
Authors: Ivo Abraham, Karen MacDonald
Journal: JAMA Dermatology (2025)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2025 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
The Role of <scp>IgE</scp> in Crohn's Disease by Impairing the Capacity of Plasmacytoid Dendritic Cells to Generate <scp>FOXP3</scp><sup>+</sup> Tregs
Authors: Andrés de la Rocha‐Muñoz, Cristina Benito‐Villalvilla, David Olivares, Sofía Sirvent, Miguel A. García‐Brenes, Alba Angelina, Leticia Martín‐Cruz, Javier Cuesta, Paolo Tassinari, Xavier Jaumont, Carlos Taxonera, Oscar Palomares
Journal: Allergy (2025)

A causal relationship between Crohn's disease (CD) and asthma is reported, but the underlying mechanisms are not fully understood. We sought to investigate the role of IgE and IgE-mediated pathways in the pathophysiology of CD. 20 CD patients, 10 allergic patients without inflammatory bowel disease, and 10 healthy donors (HD) were included in the study. Total serum IgE was quantified by ELISA. Circulating IgE+ and FcεRIα+ immune cells, as well as specific CD4+ T cell populations, were determined by flow cytometry. Gene set enrichment signatures from available single-cell (sc)RNAseq datasets of the intestine from CD patients were analyzed. Purified plasmacytoid dendritic cells (pDCs) from CD patients were cocultured with naïve CD4+ T cells to assess Tregs generation. CD patients, similar to allergic non-CD patients, displayed significantly higher numbers of circulating IgE+ or FcεRIα+ immune cells than HD. The percentage of blood IgE+ or FcεRIα+ pDCs was significantly higher in CD than HD and similar to allergic non-CD patients. CD patients showed significantly higher numbers of effector memory CD4+ T cells and lower numbers of FOXP3+ Tregs than HD. scRNAseq data from CD patients confirmed that Tregs imbalance and overactivation of IgE-mediated pathways take place also in gut tissues of children and adults, suggesting IgE could interfere in the pDC-Tregs axis. In vitro functional experiments demonstrated that IgE-crosslinking on pDCs from CD patients impairs Treg generation, which was restored by the anti-IgE mAb omalizumab. IgE might play an unprecedented role in CD by impairing the capacity of pDCs to generate Tregs, which could represent a novel mechanism contributing to CD to be exploited for alternative therapeutic interventions.
Response to: Correspondence on “Hyperleukocytosis in a neuroblastoma patient after treatment with natural killer T cells expressing a GD2-specific chimeric antigen receptor and IL-15” by Ataca Atilla and Atilla
Authors: Gengwen Tian, Amy N Courtney, Andras Heczey, Leonid S Metelitsa
Journal: Journal for ImmunoTherapy of Cancer (2025)
A mobile health application that supports a patient centered approach to cardiovascular risk management
Authors: Ben Li, Kimia Heydari, Elizabeth J. Enichen, Joseph C. Kvedar
Journal: npj Digital Medicine (2025)

Digital health tools have the potential to support patients in managing their chronic diseases. Recently, Ullrich and colleagues (2025) introduced PreventiPlaque, a mobile health application that provides patients with up-to-date ultrasound images of their carotid plaques and tracks their lifestyle habits. Through a randomized controlled trial, the authors provide evidence of PreventiPlaque's efficacy in improving patients' cardiovascular risk profiles. This study highlights the potential for digital health interventions to provide personalized health information to patients and empower them to take actionable steps to improve their cardiovascular health.
Direct-acting antiviral treatment outcomes in people infected with endemic compared to epidemic hepatitis C virus subtypes in England.
Authors: Laura T Phillips, Daniel Bradshaw, Simon Packer, Ruth Simmons, William M Rosenberg, Caroline A Sabin, Jean L Mbisa
Journal: Journal of Infection (2025)

<h2>Abstract</h2><h3>Background</h3> Current evidence suggests reduced efficacy of direct-acting antiviral (DAA) treatment among people with endemic Hepatitis C virus (HCV) subtypes rare to high-income countries. We aimed to determine real-world DAA treatment outcomes of people with endemic HCV subtypes in England. <h3>Methods</h3> Data were collected through a national treatment program. People who had their virus subtyped between 2019-2023, were resident in England and had an outcome recorded for their first DAA treatment episode, were included. Subtypes were divided into epidemic and endemic in England; endemic subtypes were confirmed with whole genome sequencing and resistance associated substitutions (RAS) were determined. Logistic regression was used to determine associations between treatment outcome and exposure variables. <h3>Results</h3> In people with an outcome recorded, 93 with an endemic and 8671 with an epidemic HCV subtype were identified, of whom 49.5% (46/93) and 91.8% (7953/8668) achieved a sustained virological response at 12 weeks post end of DAA treatment (SVR12), respectively. In the multivariable model, people with an endemic subtype had 93% (aOR 0.07 95%CI 0.04-0.12, P=<0.001) reduced odds of achieving SVR12. Treatment with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir was successful for genotypes 1, 2, 4 and 5 (SVR12 100%, n=13) but not 3 (27.3%, n=22) endemic subtypes. Sofosbuvir/velpatasvir/voxilaprevir was successful for GT3 endemic subtypes at retreatment (SVR12 11/12, 91.7%). Treatment failures for genotypes 1, 3 and 4 were likely mediated by naturally occurring baseline NS5A RAS (median n=2). <h3>Discussion</h3> This study provides further evidence that endemic HCV subtypes lead to sub-optimal DAA efficacy, which may impact global HCV elimination.
Clinical and Pathophysiological Characteristics of Non-acute Decompensation of Cirrhosis
Authors: Nipun Verma, Parminder Kaur, Pratibha Garg, Vivek Ranjan, Samonee Ralmilay, Sahaj Rathi, Arka De, Madhumita Premkumar, Sunil Taneja, Akash Roy, Mahesh Goenka, Ajay Duseja, Rajiv Jalan
Journal: Journal of Hepatology (2025)
Mechanistic Insights into Stem Cell Fate Regulation via RNA Methylation
Authors: Yushuang Sun, Jingting Li
Journal: Ageing Research Reviews (2025)

Stem cells possess an extraordinary ability for self-renewal and differentiation, making them essential for tissue repair, regeneration, and anti-aging. RNA methylation is crucial in regulating stem cell fate by modulating gene expression. This review synthesizes current research on RNA methylation modifications, such as m6A, m7G, m5C, and m1A, and their impact on adult stem cell fate. It provides a comprehensive overview of the molecular machinery involved in RNA methylation, emphasizes the critical roles of these modifications in stem cell biology, reviews the latest advancements in sequencing technologies, and discusses potential crosstalk between RNA methylation and epigenetic mechanisms.
High-precision radiotherapy achieves excellent long-term control and preserves function in pediatric craniopharyngioma – Subset analysis of a randomized trial
Authors: Rakesh Jalali, Suman Ghosh, Abhishek Chatterjee, Savita Goswami, Nalini Shah, Debnarayan Dutta, Uday Krishna, Tejpal Gupta, Jayant S Goda
Journal: Neuro-Oncology (2025)

Abstract Background The evolving treatment paradigm in children and adolescents with craniopharyngioma (CP) aims at minimizing late functional sequelae. Advanced radiotherapeutic techniques offer theoretical advantages of preserving neurological functions, however, clinical evidence of such is limited. The current study constitutes a secondary analysis of CP patients in a Randomized Control Trial testing Conventional RT (ConvRT) versus Stereotactic Conformal Radiotherapy (SCRT)(NCT00517959). Methods Eighty-two patients of CP (SCRT: 39, ConvRT: 43, Dose: 54Gy in 30 fractions) were analysed, assessing the clinical impact of dosimetric sparing on neurocognitive function, endocrine function, overall survival (OS) and local control (LC). Patients were longitudinally assessed from baseline through five years post-treatment using the WISC/WAIS scales. Results The median age was 13 years (IQR= 9-17 years). The 10-year OS and LC rates were 86.4% and 92.7%, respectively, with no significant difference between the arms. SCRT patients showed significant improvement in mean full-scale IQ (difference in slope=3.3 points per year, p= 0.01) and performance quotient (difference in slope=3.6, p= 0.04) compared to those treated with ConvRT. Freedom from cognitive decline (a 5-point drop) at 5 years was higher with SCRT (66.6% vs. 38.2%; HR=0.41, p=0.03). Younger age (&amp;lt;15 years) was a significant negative predictor of neurocognitive outcomes (p=0.002). SCRT patients also experienced lower cumulative incidence of new neuroendocrine dysfunction (25.7% vs. 48.8%, p=0.029). Conclusion SCRT offers excellent tumour control and similar survival with superior long-term preservation of neurocognitive and endocrine functions in CP patients compared to conventional RT. High precision RT should constitute the standard of care in CP.