tbuckley/cabot-search huggingface dataset:
Cefazolin versus Antistaphylococcal Penicillins for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Systematic Review and Meta-Analysis
Authors: Connor Prosty, Dean Noutsios, Todd C Lee, Nick Daneman, Joshua S Davis, Nynke G L Jager, Nesrin Ghanem-Zoubi, Anna L Goodman, Achim J Kaasch, Ilse Kouijzer, Brendan J McMullan, Emily G McDonald, Steven Y C Tong, Sean W X Ong
Journal: Clinical Microbiology and Infection (2025)

There is debate on whether cefazolin or antistaphylococcal penicillins should be the first-line treatment for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Ongoing trials are investigating whether cefazolin is non-inferior to (flu)cloxacillin, but it remains uncertain whether these findings apply to other antistaphylococcal penicillins. We conducted a systematic review and meta-analysis comparing cefazolin to each of the individual antistaphylococcal penicillins for MSSA bacteremia. Data SourcesWe updated a 2019 systematic review but specifically focused on evaluating outcomes by individual antistaphylococcal penicillins.Study Eligibility CriteriaComparative observational studies.ParticipantsPatients with MSSA bacteremia.InterventionsCefazolin versus the antistaphylococcal penicillins.Assessment of Risk of BiasThe risk of bias in non-randomized studies of interventions tool.Methods of Data SynthesisThe primary outcome was 30-day all-cause mortality and we assessed for non-inferiority of cefazolin using a prespecified non-inferiority margin of a pooled odds ratio (OR) <1.2 using raw unadjusted data. Secondary outcomes were 90-day mortality, treatment-related adverse events (TRAEs), discontinuation due to toxicity, and nephrotoxicity. No randomized data have been published. 30 observational studies at moderate or high risk of bias were included, which comprised 3869 patients who received cefazolin and 11644 patients who received antistaphylococcal penicillins (flucloxacillin=6721, unspecified=2440, nafcillin=1305, cloxacillin=1258, and oxacillin=120). Cefazolin was associated with a reduced odds of 30-day all-cause mortality (OR=0.73, 95%CI=0.62-0.85) compared to antistaphylococcal penicillins, meeting pre-specified non-inferiority. This effect was consistent versus flucloxacillin (OR=0.92, 95%CI=0.73-1.16), nafcillin (OR=0.58, 95%CI=0.28-1.17), cloxacillin (OR=0.42, 95%CI=0.11-1.58), and oxacillin (OR=0.31, 95%CI=0.03-2.75). Point estimates favored cefazolin for 90-day mortality, TRAEs, nephrotoxicity, and discontinuation due to toxicity overall and in each comparison with individual antistaphylococcal penicillins, except for TRAEs versus cloxacillin. In moderate to low quality observational data, cefazolin was non-inferior for mortality and potentially superior for safety as compared to antistaphylococcal penicillins overall and across most individual comparisons.
Effectiveness of the live zoster vaccine in patients with type 2 diabetes: A nationwide emulated target trial
Authors: Tae Hyeon Kim, Kyeongmin Lee, Sooji Lee, Jiyeon Oh, Jaeyu Park, Hyesu Jo, Yejun Son, Soeun Kim, Sang Youl Rhee, Lee Smith, Hanseul Cho, Junyang Jung, Seung Geun Yeo, Hayeon Lee, Dong Keon Yon
Journal: Clinical Microbiology and Infection (2025)
Restoration of intestinal secondary bile acid synthesis: A potential approach to improve pancreatic β cell function in type 1 diabetes
Authors: Qing Liu, Yifei Hua, Rongbo He, Liqian Xiang, Shaoqing Li, Ying Zhang, Rourou Chen, Li Qian, Xiaomeng Jiang, Congyi Wang, Yangyang Li, Hao Wu, Yu Liu
Journal: Cell Reports Medicine (2025)

This study investigates the roles of gut microbiome and secondary bile acid dysfunctions in type 1 diabetes (T1D) and explores targeted interventions to address them. It finds that T1D is associated with reduced gut microbial diversity and imbalance favoring harmful bacteria over beneficial ones. Additionally, patients with T1D exhibited impaired secondary bile acid metabolism. Interventions aimed at modulating the gut microbiome and metabolites are safe and improve glycemic control, reduce daily insulin dose, and reduce inflammation. These interventions reshape the gut microbiome toward a healthier state and enhance secondary bile acid production. Responders to the interventions show increased levels of beneficial bacteria and secondary bile acids, along with improved C-peptide responses. Overall, these findings suggest that targeted modulation of the gut microbiome and secondary bile acid metabolism could be a promising therapeutic approach for T1D management. The trial is registered at Chinese Clinical Trial Registry (ChiCTR-ONN-17011279).
Ribociblib in Sequential Combination with Doxorubicin in Anthracycline-Naive Advanced Soft Tissue Sarcomas: Results of a Dose-Finding Phase 1B Study
Authors: Lara E. Davis, Limin Zhu, Emile Latour, Nathan McMahon, Go Nishikawa, Florence Choo, Kevin D. Nusser, Janét Pittsenbarger, Reid Burch, Byung Park, Gordon B. Mills, Jessica L. Davis, Monika Davare, Christopher W. Ryan
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Doxorubicin is first-line treatment for metastatic soft tissue sarcomas (STS). Ribociclib, a CDK 4/6 inhibitor, targets the retinoblastoma pathway to induce cell cycle arrest at the G1/S cell cycle checkpoint. We hypothesized that administering ribociclib prior to doxorubicin to synchronize cell cycle progression among tumor cells may enhance the efficacy of doxorubicin. Patients and Methods: Doxorubicin-naive patients with metastatic STS were enrolled in this phase 1b study. Every 21d, subjects received ribociclib daily for 7d followed by 3d of no treatment before administration of doxorubicin. The primary objective was to establish the recommended phase 2 dose (RP2D) of the sequenced drug combination. Secondary objectives included progression-free survival and objective response rate (ORR). Exploratory correlative studies assessed pharmacokinetic (PK) and pharmacodynamic measures. Results: Of 38 screened patients, 16 were enrolled and 15 were evaluable for dose determination. The most common reason for exclusion was lack of normal retinoblastoma protein (pRb) expression. At dose level 0 (ribociclib 400 mg, doxorubicin 75 mg/m2), 4 of 7 patients experience febrile neutropenia as a dose limiting toxicity (DLT). Of the 8 patients treated at dose level -1 (ribociclib 400 mg, doxorubicin 60 mg/m2), 1 had a DLT of grade 4 anemia. Three patients achieved partial response (ORR 20.0%). Ribociclib PK levels were lower than predicted. Phospho-pRb levels in on-treatment tumor biopsy tissue were variable and did not correlate with ribociclib plasma levels. Conclusions: The RP2D is ribociclib 400 mg followed by doxorubicin 60 mg/m2, which demonstrated an acceptable toxicity profile.
Endoscopic Submucosal Dissection for Previously Attempted Colorectal Lesions: An International Multicenter Experience
Authors: Suchapa Arayakarnkul, Hiroyuki Aihara, Alessandro Repici, Roberta Maselli, Antonio Capogreco, Leonardo Da Rio, Fabio Shiguehissa Kawaguti, Fauze Maluf-Filho, Makato Nishimura, Sera Satoi, Sayaka Nagao, Shai Friedland, Robert Bechara, Norio Fukami, Sonmoon Mohapatra, Amit Bhatt, Abel Joseph, Alex Schlachterman, Anand Kumar, Andrew Y Wang, Ross C D Buerlein, Louis M Wong Kee Song, Fnu Deepali, Dennis Yang, Muhammad K Hasan, Nikhil A Kumta, David L Diehl, Edward J Despott, Alberto Murino, Alessandro Rimondi, Laura Lucaciu, Neil R Sharma, Christina M Zelt, Ashley Rumple, David Leslie Carr-Locke, Reem Z Sharaiha, Srihari Mahadev, Kamal M Hassan, Mohamad-Noor Abu-Hammour, Carlos Robles-Medranda, Martha Arevalo-Mora, Juan Alcivar-Vasquez, Vivek Kumbhari, Jongkyu Park, Salmaan Jawaid, Mai A Khalaf, Kasenee Tiankanon, Sarah S Al Ghamdi, Mohamed O Othman, Saowanee Ngamruengphong
Journal: Clinical Gastroenterology and Hepatology (2025)
Marine n-3 polyunsaturated fatty acids slow sleep impairment progression by regulating central circadian rhythms in type 2 diabetes
Authors: Pan Zhuang, Yuqi Wu, Jianxin Yao, Xiaohui Liu, Haoyin Liu, Xuzhi Wan, Wei Jia, Tao Wang, Yu Zhang, Jingjing Jiao
Journal: Cell Reports Medicine (2025)

The role of marine n-3 polyunsaturated fatty acids (PUFAs) in promoting sleep has been proposed, yet their benefits for patients with type 2 diabetes (T2D) and the underlying molecular mechanisms remain poorly understood. In this study, we identify a significant association between habitual fish oil use and improved sleep quality in a cohort of 27,549 patients with T2D. A subsequent randomized controlled trial demonstrates that fish oil supplementation enhances sleep parameters in patients with T2D, accompanied by the upregulation of core circadian clock genes, including Clock, Bmal1, and Per2. In vitro, DHA and EPA restore the rhythmic oscillations of key clock genes in hypothalamic neurons disrupted by palmitic acid. Notably, n-3 PUFAs target RORα to regulate circadian clock oscillations and facilitate BMAL1 nuclear translocation. Collectively, our findings highlight the potential of marine n-3 PUFAs as a dietary intervention to improve sleep health in patients with T2D. This study was registered at ClinicalTrials.gov (NCT03708887).
Safety of Stimulants Across Patient Populations
Authors: Henrique Nunes Pereira Oliva, Tiago Paiva Prudente, Talia F. Mayerson, Marcella M. Mignosa, Isabela Oliveira Oliva, Marc N. Potenza, Oluwole O. Jegede, Gustavo A. Angarita
Journal: JAMA Network Open (2025)

Importance The use of stimulant medications has expanded substantially beyond the traditional treatment of attention-deficit/hyperactivity disorder (ADHD) to encompass a variety of other clinical conditions. Understanding the safety of these medications is important as their use increases across diverse patient populations. Objective To assess the safety of stimulant medications as reported in randomized clinical trials (RCTs) investigating methylphenidate, lisdexamfetamine, and other amphetamines. Data Sources A comprehensive literature search was conducted from July 1, 2024, through February 28, 2025, using CINAHL, Embase, PubMed or MEDLINE, ScienceDirect, and Web of Science for studies published since 2000. Keywords included safety, adverse event, side effect, amphetamine, dextroamphetamine, stimulant, lisdexamfetamine, and methylphenidate . Study Selection RCTs published between January 1, 2000, and December 13, 2024, were included. These trials investigated the safety of stimulants in various clinical conditions, including ADHD, depression, binge eating disorder, schizophrenia, Alzheimer disease, and stimulant use disorders as well as in healthy individuals. Trials not focused on safety or adverse events (AEs) of stimulants, nonoriginal research, nonhuman research, trials with concomitant prescriptions other than stimulants, and trials without a placebo group were excluded. Data Extraction and Synthesis Data extraction followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Independent reviewers extracted study data, and a random-effects model was used to pool results. Heterogeneity was assessed using the I 2 statistic. Main Outcomes and Measures The primary outcome was the risk ratio (RR) of developing any AE in participants taking stimulants vs placebo. Results A total of 93 RCTs were included after exclusions. The methodological quality assessment of the included trials showed overall low or unclear risk of bias. Trials with a duration of up to 52 weeks showed that stimulant medications were associated with an increased risk of overall AEs compared with placebo (RR, 1.34; 90% CI, 1.27-1.41), with high heterogeneity ( I 2 = 67%). Statistical significance of this finding was maintained when subgroups (ie, methylphenidate, lisdexamfetamine, and other amphetamines) were separately analyzed. Conclusions and Relevance This meta-analysis found an increased risk of overall AEs associated with stimulants compared with placebo. Future research could provide more standardized and consistent assessments of this outcome and may improve understanding about misuse risk.
Multitrait GWAS of non-suicidal self-injury and the polygenetic effects on child psychopathology and brain structures
Authors: Yaoyao Sun, Guorui Zhao, Yuyanan Zhang, Zhe Lu, Zhewei Kang, Junyuan Sun, Xiaoyang Feng, Jing Guo, Yundan Liao, Liangkun Guo, Yang Yang, Dai Zhang, Wenjian Bi, Runsen Chen, Weihua Yue
Journal: Cell Reports Medicine (2025)

Non-suicidal self-injury (NSSI) is highly prevalent in recent years, but the genetic architecture remains unknown. We perform a multitrait analysis of genome-wide association study on NSSI, incorporating self-harm and suicide attempt. Common genetic variants account for 6.03% of NSSI variance. Three risk loci are associated with NSSI at 7q31.2 (rs62474683), DCC (rs4372758), and LCA5L/GET1/GET1-SH3BGR (rs2837022). Increased expression levels of GET1/SH3BGR in hippocampus relates to NSSI risk. Fine-mapping identifies seven likely causal variants, and colocalization with rs4281987 and rs2837022 evidences SH3BGR/GET1 expression in hippocampus to NSSI. In an independent sample, polygenic risk score for NSSI is associated with children's NSSI behavior, suicidal ideation, and suicide attempt (odds ratios [ORs]: 1.14-1.37). Reduction in right temporal pole volume mediates NSSI genetic liability for children's NSSI behavior. Walking for pleasure and exercises like swimming and bowling reduces NSSI risk, whereas smoking increases it. This study elucidates the NSSI genetic basis and its impact on children's emotions, behavior, and brain structure.
68Ga-NK224 PET/CT for Non-Invasive Evaluation of PD-L1 Expression and Inter-Tumor Heterogeneity: A Translational Exploratory Study
Authors: Liang Zhao, Yizhen Pang, Yi Ding, Jianhao Chen, Jianyang Fang, Lingyu Yu, Dan Ruan, Yaqing Dai, Hui Zhou, Hao Fu, Wei Guo, Long Sun, Hua Wu, Shan Zhong, Qin Lin, Haojun Chen
Journal: Clinical Cancer Research (2025)

Abstract Background: This study developed 68Ga-NK224, a novel peptide-based radiotracer targeting human PD-L1, to evaluate the feasibility of 68Ga-NK224 PET/CT for assessing PD-L1 expression and tumor heterogeneity in a prospective investigator-initiated trial. Methods: In preclinical studies, NK224 was labeled with 68Ga. Small-animal PET, biodistribution, and blocking studies were performed using tumor models with varying PD-L1 expression levels to assess the targeting ability and specificity of 68Ga-NK224 in vivo. Serial 68Ga-NK224 PET assessed target occupancy following PD-L1 antibody administration. In the clinical study, 37 patients with non-small cell lung cancer (NSCLC) who underwent 68Ga-NK224 PET/CT were prospectively recruited, with PD-L1 expression assessed via immunohistochemistry and analyzed for correlation with 68Ga-NK224 uptake. Results: Preclinical studies demonstrated that 68Ga-NK224 exhibited high tumor uptake and rapid clearance, producing favorable tumor-to-background contrast. In human CD34+ humanized mice, immunotherapy guided by 68Ga-NK224 PET/CT (once weekly) yielded similar antitumor effects as conventional dosing (three times weekly). Clinically, 68Ga-NK224 PET/CT was well-tolerated, with no adverse events reported. Among the 31 patients who underwent paired 68Ga-NK224 and 18F-FDG PET/CT, tumor uptake of 68Ga-NK224 significantly correlated with PD-L1 expression, whereas no correlation was found with 18F-FDG PET/CT. Additionally, 68Ga-NK224 demonstrated high heterogeneity across intrapatient lesions, with a median SUVmax coefficient of variation of 27.5% (range, 5.7%–53.2%). Conclusion: 68Ga-NK224 provides a straightforward radiolabeling approach with high tumor-to-background contrast, enabling accurate assessment of PD-L1 expression and visualization of heterogeneity across intrapatient lesions. Its ability to dynamically monitor PD-L1 occupancy in tumors offers a novel method for optimizing immunotherapy dosing regimens.
Diet, Gut Microbiota, and Histidine Metabolism Toward Imidazole Propionate Production in Relation to Type 2 Diabetes
Authors: Hongbo Yang, Kai Luo, Brandilyn A. Peters, Yi Wang, Yanbo Zhang, Martha Daviglus, Amber Pirzada, Christina Cordero, Bing Yu, Robert D. Burk, Robert Kaplan, Qibin Qi
Journal: Diabetes Care (2025)

OBJECTIVE To examine associations of serum imidazole propionate (ImP), histidine, and their ratio with incident type 2 diabetes (T2D) and related dietary and gut microbial factors in U.S. Hispanic/Latino people. RESEARCH DESIGN AND METHODS In the Hispanic Community Health Study/Study of Latinos, we evaluated serum ImP, histidine, and ImP-to-histidine ratio at baseline (2008–2011) and their cross-sectional associations with dietary intake and prospective associations with incident T2D over ∼12 years (n = 4,632). In a subsample with gut microbiota data during a follow-up visit (2016–2018), we examined gut microbial species associated with serum ImP and their potential interactions with dietary intake. RESULTS Serum ImP and ImP-to-histidine ratio were positively associated with incident T2D (hazard ratio [95% CI] = 1.17 [1.00–1.36] and 1.33 [1.14–1.55], respectively, comparing highest and lowest tertiles), whereas histidine was inversely associated with incident T2D (hazard ratio = 0.75 [95% CI 0.64–0.86]). A higher amount of fiber intake was associated with lower serum ImP level and ImP-to-histidine ratio, whereas histidine intake was not associated with serum ImP level in the overall sample. Fifty-three bacterial species, including 19 putative ImP producers, were associated with serum ImP. Histidine intake was positively associated with serum ImP and ImP-to-histidine ratio only in participants with a high ImP-associated gut microbiota score (P = 0.03 and 0.02, respectively, for interaction). The associations of fiber intake with serum ImP and ImP-to-histidine ratio were partly mediated by ImP-associated gut microbiota (proportion mediated = 31.4% and 19.8%, respectively). CONCLUSIONS This study suggested an unfavorable relationship between histidine metabolism toward ImP production, potentially regulated by dietary intake and gut microbiota, and risk of T2D in U.S. Hispanics/Latino people.
Low-Density Lipoprotein Cholesterol Levels and Bleeding Risk in Venous Thromboembolism
Authors: Carmine Siniscalchi, Tiziana Meschi, Pierpaolo Di Micco, Egidio Imbalzano, Luis Hernández-Blasco, Isabelle Mahé, José Luis Fernández-Reyes, Alberto García-Ortega, Peter Verhamme, Joaquín Alfonso-Megido, Manuel Monreal
Journal: JAMA Network Open (2025)

This case-control study evaluates low-density lipoprotein cholesterol levels and bleeding risk during anticoagulation in patients with acute venous thromboembolism.
Tumor-draining lymph nodes – friend or foe during immune checkpoint therapy?
Authors: Janusz von Renesse, Mei-Chun Lin, Ping-Chih Ho
Journal: Trends in cancer (2025)

The pivotal role of tumor-draining lymph nodes (TDLNs) in supporting antitumor immunity and serving as sites for cancer metastasis presents a clinical challenge: eliminate tumors while preserving antitumor immune responses. In this article, we explore the initiation of tumor-specific immune responses within lymph nodes (LNs), the immunocompromised microenvironment induced by tumors within LNs, and the crucial involvement of TDLNs in immunotherapy. Additionally, we examine the clinical prospects of modifying surgical procedures or therapy sequences to enhance the efficacy of cancer treatment.
Epitopes targeted by autoantibodies in presymptomatic individuals predict early rheumatoid arthritis
Authors: Yibo He, Outi Sareila, Linda Johansson, Monica Leu Agelii, Lei Cheng, Anders Lundquist, Erik Lönnblom, Gerdur Gröndal, Bjorn Gudbjornsson, Kim Hørslev-Petersen, Jon Lampa, Kristina Lend, Merete Lund Hetland, Dan Nordström, Michael Nurmohamed, Anna Rudin, Till Uhlig, Mikkel Østergaard, Inger Gjertsson, Solbritt Rantapää-Dahlqvist, Rikard Holmdahl
Journal: Annals of the Rheumatic Diseases (2025)

To determine anticitrullinated protein antibody (ACPA) responses to novel peptides predicting the clinical outcomes of treatment-naïve early rheumatoid arthritis (RA) in the presymptomatic stage. We analysed monoclonal ACPAs derived from RA patients, including a characterised protective ACPA (clone E4), along with plasma samples collected from 520 presymptomatic individuals, of whom 244 were also sampled at diagnosis of RA, and 530 population controls in Sweden. The validation cohort (The Nordic Rheumatic Diseases Strategy Trials and Registries, NORD-STAR) consisted of 690 treatment-naïve early RA patients. Responses to citrullinated or native alpha-enolase (ENO1) or peptidylarginine deiminase 4 (PAD4) peptides were analysed by bead-based multiplex flow immunoassay. Clinical outcomes included C-reactive protein (CRP) and the 28-joint disease activity score (DAS28) with its components: tender joint count (TJC), swollen joint count (SJC), and erythrocyte sedimentation rate (ESR). Monoclonal ACPAs displayed distinct binding patterns to ENO1 and PAD4 peptides. A time-dependent increase of ACPA response to citrullinated peptides was observed in the presymptomatic stage towards onset. In the presymptomatic (0.2-5 years before onset) and early RA stage, ACPA responses to several ENO1 and PAD4 peptides were associated with less severe RA, assessed as lower levels of CRP and DAS28 and its components. In early RA, the association was more pronounced in rheumatoid factor (RF)-negative patients based on lower SJC. In presymptomatic individuals, ACPA responses widely predicted lower disease activity in early RA and were more pronounced in 5 selected peptides. Antibody responses to certain citrullinated epitopes are associated with lower disease activity in treatment-naïve early RA and appear years before symptom onset of RA.
Evaluating large language model workflows in clinical decision support for triage and referral and diagnosis
Authors: Farieda Gaber, Maqsood Shaik, Fabio Allega, Agnes Julia Bilecz, Felix Busch, Kelsey Goon, Vedran Franke, Altuna Akalin
Journal: npj Digital Medicine (2025)

Abstract Accurate medical decision-making is critical for both patients and clinicians. Patients often struggle to interpret their symptoms, determine their severity, and select the right specialist. Simultaneously, clinicians face challenges in integrating complex patient data to make timely, accurate diagnoses. Recent advances in large language models (LLMs) offer the potential to bridge this gap by supporting decision-making for both patients and healthcare providers. In this study, we benchmark multiple LLM versions and an LLM-based workflow incorporating retrieval-augmented generation (RAG) on a curated dataset of 2000 medical cases derived from the Medical Information Mart for Intensive Care database. Our findings show that these LLMs are capable of providing personalized insights into likely diagnoses, suggesting appropriate specialists, and assessing urgent care needs. These models may also support clinicians in refining diagnoses and decision-making, offering a promising approach to improving patient outcomes and streamlining healthcare delivery.