tbuckley/cabot-search huggingface dataset:
Targeted delivery of TAPI-1 via biomimetic nanoparticles ameliorates post-infarct left ventricle function and remodeling
Authors: Qing Chen, Yang Yu, Lei Tong, Robert M Weiss, Shun-Guang Wei
Journal: Cardiovascular Research (2025)

The potential of nanoparticles as effective drug delivery tools for treating failing hearts in heart failure remains a challenge. Leveraging the rapid infiltration of neutrophils into infarcted hearts after myocardial infarction (MI), we developed a nanoparticle platform engineered with neutrophil-membrane proteins for the targeted delivery of TAPI-1, a TACE/ADAM17 inhibitor, to the inflamed myocardium, aiming to treat cardiac dysfunction and remodeling in rats with MI. Neutrophil-mimic liposomal nanoparticles (Neu-LNPs) were constructed by integrating synthesized liposomal nanoparticles with LPS-stimulated neutrophil membrane fragments and then loaded with TAPI-1. MI rats were treated with TAPI-1 delivered via Neu-LNPs for 4 weeks. Left ventricular function was assessed by echocardiography and cardiac fibrosis was evaluated post-treatment. The novel Neu-LNPs maintained typical nanoparticle features, but with increased biocompatibility. Neu-LNPs demonstrated improved targeting ability and cellular internalization, facilitated by LFA1/Mac1/ICAM-1 interaction. Neu-LNPs displayed higher accumulation and cellular uptake by macrophages and cardiomyocytes in infarcted hearts post-MI, with a sustained duration. Treatments with TAPI-1-Neu-LNPs demonstrated greater protection against myocardial injury and cardiac dysfunction in MI rats compared to untargeted TAPI-1, along with reduced cardiac collagen deposition and expression of fibrosis biomarkers as well as altered immune cell compositions within the hearts. Targeted treatment with TACE/ADAM17 inhibitor delivered via biomimetic nanoparticles exhibited pronounced advantages in improving left ventricle function, mitigating cardiac remodeling, and reducing inflammatory responses within the infarcted hearts. This study underscores the effectiveness of Neu-LNPs as a drug delivery strategy to enhance therapeutic efficacy in clinical settings.
PREVALENCE AND RISK FACTORS FOR STAPHYLOCOCCUS AUREUS COLONISATION AMONG HEALTHY INDIVIDUALS IN LOW- AND MIDDLE-INCOME COUNTRIES: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Thomas E Locke, Alexander J Keeley, Nicholas Laundy, Christopher Keil, Jean Hamilton, Abdullah Pandor, Thushan I de Silva, Thomas C Darton
Journal: Journal of Infection (2025)
The gut microbiota: an emerging modulator of drug resistance in hepatocellular carcinoma
Authors: Jiali Yao, Beifang Ning, Jin Ding
Journal: Gut Microbes (2025)

Liver cancer is usually diagnosed at an advanced stage and is the third most common cause of cancer-related death worldwide. In addition to the lack of effective treatment options, resistance to therapeutic drugs is a major clinical challenge. The gut microbiota has recently been recognized as one of the key factors regulating host health. The microbiota and its metabolites can directly or indirectly regulate gene expression in the liver, leading to gut-liver axis dysregulation, which is closely related to liver cancer occurrence and the treatment response. Gut microbiota disturbance may participate in tumor progression and drug resistance through metabolite production, gene transfer, immune regulation, and other mechanisms. However, systematic reviews on the role of the gut microbiota in drug resistance in liver cancer are lacking. Herein, we review the relationships between the gut microbiota and the occurrence and drug resistance of hepatocellular carcinoma, summarize the emerging mechanisms underlying gut microbiota-mediated drug resistance, and propose new personalized treatment options to overcome this resistance.
Determining safe washout period for immune checkpoint inhibitors prior to liver transplantation: An international retrospective cohort study
Authors: Beat Moeckli, Charles-Henri Wassmer, Sofia El Hajji, Rohan Kumar, Joana Rodrigues Ribeiro, Parissa Tabrizian, Hao Feng, Gabriel Schnickel, Anand V. Kulkarni, Manon Allaire, Sonal Asthana, Constantine J. Karvellas, Glenda Meeberg, Lai Wei, Yasmina Chouik, Pramod Kumar, Robyn Gartrell, Mercedes Martinez, Elise Kang, Miguel Sogbe, Bruno Sangro, Birgit Schwacha-Eipper, Andreas Schmiderer, Felix J. Krendl, Nicolas Goossens, Stephanie Lacotte, Philippe Compagnon, Christian Toso
Journal: Hepatology (2025)

Immune checkpoint inhibitors (ICI) are increasingly used in patients with advanced hepatocellular carcinoma (HCC) patients awaiting liver transplantation (LT). However, concerns about the risk of post-transplant rejection persist. We conducted an international retrospective cohort study including 119 HCC patients who received ICIs prior to LT. We analyzed the incidence of allograft rejection, graft loss, and post-transplant recurrence with particular focus on the washout period between the last ICI dose and LT. In this study, 24 of the 119 (20.2%) patients experienced allograft rejection with a median time to rejection of 9 days (IQR 6-10) post-LT. A linear relationship was observed between shorter washout periods and higher rejection risk. Washout periods less than 30 days (OR 21.3, 95% CI: 5.93-103, p<0.001) and between 30 and 50 days (OR 9.48, CI 2.47-46.8, p=0.002) were significantly associated with higher rejection rates in the univariate analysis compared to the washout period above 50 days. Graft loss as a result of rejection occurred in 6 patients (25%) with rejection. No factors related to grafts were associated with rejection. A longer washout period was not associated with a lower recurrence-free survival post-transplantation at 36 months (71 vs. 67%, p=0.71). Our findings suggest that a washout period longer than 50 days for ICIs before liver transplantation appears to be safe with respect to rejection risk. While these results may help guide clinical decision-making, future prospective studies are essential to establish definitive guidelines.
Mother’s Own Milk Provision During the First 12 Weeks of Life by Gestational Age
Authors: Aloka L. Patel, Joshua Wilson, Melissa Holmes, Tricia J. Johnson
Journal: JAMA Network Open (2025)

Although mother's own milk (MOM) is associated with reduced risk of neonatal complications of prematurity and improved neurodevelopmental outcomes, to our knowledge, there have been no large US studies reporting rates of MOM feeding initiation and sustained MOM feedings by gestational age (GA). To compare rates of MOM feeding initiation and continuation at 12 weeks for infants by GA. This retrospective cross-sectional study used state-level surveillance data for maternal characteristics and behaviors before and after pregnancy. Participants were women who gave birth from January 1 through December 31, 2021, in 36 US jurisdictions (33 states, the District of Columbia, New York City, and Puerto Rico) and completed the Pregnancy Risk Assessment Monitoring System (PRAMS) questionnaire. Data were analyzed from July 2023 to April 2024. Infant GA, including early preterm (EPT; ≤27 weeks' gestation), moderately preterm (MPT; 28-33 weeks' gestation), late preterm (LPT; 34-36 weeks' gestation), and early term to postterm (≥37 weeks' gestation). MOM feeding initiation and continuation at 12 weeks after delivery. Weighted multivariable binary logistic regression models were used to test the association between MOM feeding initiation and continued provision at 12 weeks after delivery by infant GA. Among 29 098 births, there were 0.4% EPT, 1.8% MPT, 6.7% LPT, and 91.1% early-term to postterm infants. Unadjusted MOM feeding initiation was highest for EPT infants (89.7% [95% CI, 85.0%-94.7%]) and lowest for LPT infants (81.8% [95% CI, 79.5%-84.1%]). For infants that initially received MOM, 71.6% (95% CI, 70.7%-72.6%) of early-term to postterm infants still received MOM at 12 weeks followed by 63.1% (95% CI, 52.9%-73.2%) of EPT infants, 61.2% (95% CI, 58.0%-64.3%) of LPT infants, and 58.6% (95% CI, 53.4%-63.8%) of MPT infants. After adjusting for maternal characteristics, LPT infants were 4.4 (95% CI, -6.7 to -2.1) percentage points less likely to initiate MOM feedings and those who received any MOM were 6.7 (95% CI, -9.9 to -3.5) percentage points less likely to receive MOM at 12 weeks compared with early-term to postterm infants. There were no differences in adjusted initiation or continuation rates among EPT (3.1 [95% CI, -1.4 to 7.5] percentage points for initiation and -0.0 [95% CI, -8.6 to 8.6] percentage points for continuation) or MPT (2.4 [95% CI, -0.5 to 5.3] percentage points for initiation and -3.3 [95% CI, -8.0 to 1.5] percentage points for continuation) infants compared with early-term to postterm infants. This cross-sectional study found that MOM feeding initiation and continuation rates at 12 weeks after birth for LPT infants were substantially lower than rates for infants with other GAs. Research is needed to pinpoint barriers to MOM feeding initiation and continuation in this vulnerable population of infants.
Breakthroughs in treatment for hematological malignancies: latest updates on molecular glue, PROTACs and RNA degraders from ASH 2024
Authors: Na Li, Jianpeng Sheng, Hong-Hu Zhu
Journal: Journal of Hematology & Oncology (2025)

Degrader therapies have garnered significant attention for their innovative approach to targeting and eliminating malignancy-associated proteins, holding promise for improving outcomes for patients with relapsed or refractory (R/R) hematological malignancies, especially in cases of leukemia, non-Hodgkin lymphoma, and multiple myeloma. Currently, the main categories developed based on degraders include molecular glue (such as Cemsidomide, NX-5948), PROTACs (such as BGB-16673, AC-676, KT-333 ), and RNA degraders (such as SKY-1214). This correspondence summarizes the preclinical and clinical updates on degrader therapies presented at the ASH 2024 annual meeting.
Interpretable multimodal transformer for prediction of molecular subtypes and grades in adult-type diffuse gliomas
Authors: Yunsu Byeon, Yae Won Park, Soohyun Lee, Doohyun Park, HyungSeob Shin, Kyunghwa Han, Jong Hee Chang, Se Hoon Kim, Seung-Koo Lee, Sung Soo Ahn, Dosik Hwang
Journal: npj Digital Medicine (2025)

Molecular subtyping and grading of adult-type diffuse gliomas are essential for treatment decisions and patient prognosis. We introduce GlioMT, an interpretable multimodal transformer that integrates imaging and clinical data to predict the molecular subtype and grade of adult-type diffuse gliomas according to the 2021 WHO classification. GlioMT is trained on multiparametric MRI data from an institutional set of 1053 patients with adult-type diffuse gliomas to predict the IDH mutation status, 1p/19q codeletion status, and tumor grade. External validation on the TCGA (200 patients) and UCSF (477 patients) shows that GlioMT outperforms conventional CNNs and visual transformers, achieving AUCs of 0.915 (TCGA) and 0.981 (UCSF) for IDH mutation, 0.854 (TCGA) and 0.806 (UCSF) for 1p/19q codeletion, and 0.862 (TCGA) and 0.960 (UCSF) for grade prediction. GlioMT enhances the reliability of clinical decision-making by offering interpretability through attention maps and contributions of imaging and clinical data.
Efficacy of perioperative dexmedetomidine on postoperative pain and neurocognitive functions in orthopaedic surgery: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials
Authors: Xiang Zhang, Yu Leng, Xiurong Yuan, Yaoxin Yang, Cheng Zhou, Hao Liu
Journal: International Journal of Surgery (2025)

With an estimated 2.1 million hip and knee replacements performed annually in developed countries, orthopaedic surgeries can result in complications such as postoperative pain and cognitive dysfunctions. Dexmedetomidine shows potential for reducing pain and opioid use and improving cognitive outcomes, but its efficacy in orthopaedic settings needs further evaluation. A comprehensive literature search was performed across electronic databases (e.g. PubMed) up to 1 June 2024, to identify relevant randomised controlled trials (RCTs) investigating the use of dexmedetomidine for orthopaedic surgeries. The primary outcomes included visual analogue scale (VAS), opioid consumption, incidence of postoperative cognitive dysfunction (POCD) and postoperative delirium (POD). The meta-analysis was conducted via RevMan 5.3 and Stata 16.0, with statistical significance set at p < 0.05. Sensitivity analyses, along with trial sequential analysis (TSA), were used to evaluate the robustness of the findings. The meta-analysis included 59 RCTs with 7,713 participants and demonstrated that dexmedetomidine significantly reduced postoperative VAS score [mean difference (MD) - 0.50, P = 0.0003] and opioid consumption (MD -11.91, P<0.0001) and decreased the incidence of POCD [risk ratio (RR) 0.59, P = 0.006] and POD (RR 0.49, P<0.0001). Dexmedetomidine also prolonged motor (MD: 1.70, P<0.0001), sensory block durations (MD: 1.80, P<0.0001), and delayed the time to first rescue analgesics (MD: 1.51, P<0.0001). TSA and sensitivity analysis confirmed the robustness and reliability of the results, whereas meta-regression revealed no significant effect of variables on primary outcomes. Our study demonstrates that intravenous dexmedetomidine significantly improved postoperative pain and neurocognitive functions in orthopaedic surgery patients.
<i>k</i>-mer-based approaches to bridging pangenomics and population genetics
Authors: Miles D Roberts, Olivia Davis, Emily B Josephs, Robert J Williamson
Journal: Molecular Biology and Evolution (2025)

Many commonly studied species now have more than one chromosome-scale genome assembly, revealing a large amount of genetic diversity previously missed by approaches that map short reads to a single reference. However, many species still lack multiple reference genomes and correctly aligning references to build pangenomes can be challenging for many species, limiting our ability to study this missing genomic variation in population genetics. Here, we argue that k-mers are a very useful but underutilized tool for bridging the reference-focused paradigms of population genetics with the reference-free paradigms of pangenomics. We review current literature on the uses of k-mers for performing three core components of most population genetics analyses: identifying, measuring, and explaining patterns of genetic variation. We also demonstrate how different k-mer-based measures of genetic variation behave in population genetic simulations according to the choice of k, depth of sequencing coverage, and degree of data compression. Overall, we find that k-mer-based measures of genetic diversity scale consistently with pairwise nucleotide diversity (π) up to values of about π = 0.025 (R2 = 0.97) for neutrally evolving populations. For populations with even more variation, using shorter k-mers will maintain the scalability up to at least π = 0.1. Furthermore, in our simulated populations, k-mer dissimilarity values can be reliably approximated from counting bloom filters, highlighting a potential avenue to decreasing the memory burden of k-mer based genomic dissimilarity analyses. For future studies, there is a great opportunity to further develop methods to identifying selected loci using k-mers.
Guideline-Directed Application of Coronary Artery Calcium Scores for Primary Prevention of Atherosclerotic Cardiovascular Disease
Authors: Jelena Pavlović, Daniel Bos, M Kamran Ikram, M Arfan Ikram, Maryam Kavousi, Maarten J G Leening
Journal: JACC. Cardiovascular imaging (2025)

The 2018 ACC (American College of Cardiology)/AHA (American Heart Association) and 2021 ESC (European Society of Cardiology)/EAS (European Atherosclerosis Society) guidelines recommend coronary artery calcium (CAC) score for risk refinement in primary prevention of atherosclerotic cardiovascular disease (ASCVD). The study sought to compare CAC utility as a risk-refining tool following the ACC/AHA guideline using pooled cohort equations (PCE) or PREVENT (Predicting Risk of cardiovascular disease EVENTs) equations and ESC/EAS guideline using SCORE2 (Systematic COronary Risk Evaluation 2). A total of 1,903 statin-naive participants 55 to 75 years of age, free of ASCVD and diabetes, with low-density lipoprotein cholesterol <190 mg/dL from the prospective population-based Rotterdam Study were included. Per the guidelines, we determined proportions of CAC scan-eligible and reclassified men and women, ASCVD incidence rates, and numbers needed to treat for 10 years (NNT10y). By the ACC/AHA (PCE), 18.3% of men and 11.9% of women, and by ACC/AHA (PREVENT), 13.4% of men and 3.4% of women were eligible for a CAC scan. By the ESC/EAS, 46.6% of men and 44.9% of women were CAC eligible. Proportions of uprisked and derisked individuals varied per guideline. Among ACC/AHA and ESC/EAS CAC-eligible individuals, incidence rates ranged from 9.3 to 23.8 per 1,000 person-years, and the estimated NNT10y to prevent 1 ASCVD event, based on high-intensity statin use, varied from 11 to 26. The ACC/AHA and ESC/EAS guidelines differ in the selection and application of the CAC score for primary prevention of ASCVD. Guideline-directed application of CAC score in a middle-aged apparently healthy population improved risk stratification at an acceptable NNT10y for both guidelines.
Clinical relevance of engineered cartilage maturation in a randomized multicenter trial for articular cartilage repair
Authors: Marcus Mumme, Anke Wixmerten, Alan Ivkovic, Giuseppe M. Peretti, Tayfun Yilmaz, Stephan Reppenhagen, Oliver Pullig, Sylvie Miot, Kaywan Izadpanah, Marcel Jakob, Laura Mangiavini, Corrado Sosio, Filip Vuletić, Oliver Bieri, Stefano Biguzzi, Brigitta Gahl, Gyözö Lehoczky, Rudolf Vukojevic, Sebastian Häusner, Anna Gryadunova, Martin Haug, Andrea Barbero, Ivan Martin
Journal: Science Translational Medicine (2025)

Cartilage lesions do not heal spontaneously and predispose to osteoarthritis. Functional cartilage tissues, engineered using autologous chondrocytes, have a therapeutic advantage over conventional cellular therapies in preclinical studies. Here, we tested whether ex vivo maturation of engineered grafts for cartilage repair leads to improved patient benefit. Using autologous nasal chondrocytes (NCs), we tested whether implantation of in vitro-matured NC-tissue-engineered cartilage (N-TEC) versus undifferentiated NC-cell-activated matrices (N-CAM) in focal cartilage lesions would result in a superior clinical outcome. The prospective, randomized, parallel, open-label phase-2 trial (ClinicalTrials.gov, NCT02673905) enrolled 108 patients in five hospitals from four countries. Patients ranging in age from 30 to 46 years with full-thickness knee cartilage defects (size, 2.7 to 6.0 square centimeters) were equally randomized and treated with N-TEC or N-CAM. The primary preregistered outcome was the overall Knee Injury Osteoarthritis Outcome Score (KOOS) at 24 months. N-TEC, which underwent a longer NC culture time, was phenotypically, structurally, and functionally more like hyaline cartilage than N-CAM. The overall KOOS increased with clinical relevance in both groups compared with preoperative values. KOOS was higher at 24 months for N-TEC [85; interquartile range (IQR), 74 to 91] than for N-CAM (79; IQR, 65 to 85). N-TEC, but not N-CAM, was similarly effective in patients with larger defects or revision surgery. Radiologically, N-TEC resulted in a superior composition of both repair tissue and surrounding cartilage, whereas structural scores were similar. This trial validates the clinical efficacy of NC-based grafts for articular cartilage repair and supports the clinical relevance of engineering mature tissues, even for patients with more challenging cartilage defects.
Models for T-large granular lymphocytic leukemia: how to mimic the cellular interplays in malignant autoimmunity
Authors: Hanna Klepzig, Marco Herling, Natali Pflug, Till Braun
Journal: Leukemia (2025)

Abstract T-large granular lymphocytic leukemia (T-LGLL) is a chronic lymphoproliferative disorder characterized by clonal expansions of cytotoxic T-cells. It presents with cytopenias that are not explained by the typically low leukemic burden. Notably, T-LGLL is frequently accompanied by autoimmune disorders, particularly rheumatoid arthritis (RA). As clonal T-cell expansions are also increasingly identified in autoimmune-driven conditions, better models of T-LGLL’s pathogenesis as a spectrum of (auto)antigen-driven oligoclonal hierarchies towards overt leukemic escape with associated immune dysregulations would provide details to a valuable prototype for determinants of T-cell fitness and transformation as well as T-cell instructed dysfunctions of other immune cells. Such insights would advance our concepts of cancer biology and immunology. Common molecular links between T-LGLL and autoimmune diseases include activation of JAK/STAT signaling, proinflammatory cytokine environments, and antigen-driven immune responses. Current murine models address these mechanisms rather individually: JAK/STAT based systems replicate pathway activation, cytokine-driven models simulate inflammatory conditions, and RA models often mimic antigen stimulation. However, none of these fully captures the duality of clonal T-cell expansion and the complex immune dysregulations, inherent to T-LGLL. This review examines criteria for autochthonous in-vivo T-LGLL models and evaluates existing systems, identifying their strengths, limitations, and specific representations of clinico-pathologic aspects of LGLL. Prominent transgenic models, for example, not only manipulate the T-cell compartment but also indiscriminately alter the tumor microenvironment, impeding research on the specific role of elements of the LGLL micromilieu. We propose strategies to overcome such insufficiencies of present models. Overall, our critical appraisal emphasizes the need for novel comprehensive models that more faithfully integrate the key features of T-LGLL or for models that, by featuring specific pathogenetic aspects of the disease, would supplement existing incomplete systems. We expect such new model systems to aid in better understanding the cancer-immunity interface and in assessing novel therapeutic approaches for T-LGLL.