Physician documentation requirements are a known contributor to clinician burnout, with the manual creation of brief hospital course (BHC) summaries being particularly time-consuming. Automating BHC summarization may mitigate this workload and reduce documentation errors. However, current natural language processing (NLP) methods are often limited to single-document inputs, and large language models (LLMs) face privacy and deployment challenges. Furthermore, existing methods often require manual information extraction and struggle to maintain temporal accuracy.

We developed and evaluated LiteMedDoc, a lightweight, locally deployable LLM-based framework to automatically generate BHC summaries without model fine-tuning. Our objective was to determine whether clinically useful clinical summaries could be generated under strict privacy and resource constraints, making automated summarization feasible in real-world hospital environments.

LiteMedDoc is a modular pipeline built upon an 8-billion-parameter open-source LLM (Llama 3.1). It features 3 specialized modules: a static dynamic information hierarchy module to condense multisource inputs and structure clinical events chronologically; a similar document retrieval-augmented generation module that retrieves contextually relevant prior case summaries; and a self-adaptive feedback optimization module used offline for prompt optimization. All processing was performed locally without any model fine-tuning. We evaluated the framework on a retrospective cohort of 4538 coronary artery bypass grafting (CABG) surgery cases from the Medical Information Mart for Intensive Care (MIMIC)-IV database. A held-out test set of 403 cases was used to generate BHC summaries. The model-generated summaries were compared to reference BHCs using 8 standard NLP metrics covering lexical overlap (BLEU-4 [Bilingual Evaluation Understudy-4 gram] and ROUGE [Recall-Oriented Understudy for Gisting Evaluation]), semantic similarity (BERTScore and METEOR [Metric for Evaluation of Translation With Explicit Ordering]), and clinical relevance (AlignScore [Alignment Score] and MEDCON [Medical Concept Overlap]). Additionally, 15 cardiac surgeons conducted a clinical evaluation of a sample of model-generated summaries, rating them on completeness, correctness, readability, conciseness, and global quality using a 5-point Likert scale.

Without any model training, LiteMedDoc achieved strong performance across individual automated metrics, nearly matching a fine-tuned model and exceeding a 70-billion-parameter model on all metrics. Additionally, in a within-database cross-domain evaluation on lobectomy cases, the framework maintained encouraging performance after prompt adaptation and outperformed both the base model and the CABG-fine-tuned model. Surgeons rated the AI-generated summaries above the prespecified acceptability threshold across all domains (mean scores ≥3.0), specifically praising their structure and conciseness.

By integrating 3 specialized modules, the proposed framework offers a practical, locally deployable solution for clinician-in-the-loop BHC draft generation under privacy and resource constraints, and holds promise for improving documentation efficiency and enhancing information continuity during care transitions.

Although periodontal ligament stem cells (PDLSCs) are pivotal for periodontal tissue regeneration, their regenerative capacity diminishes with the PDL maturity. To elucidate the mechanisms underlying this phenomenon, we performed single-cell RNA sequencing (scRNA-seq) on immature and mature human PDL tissues to characterize the heterogeneity and predict critical regulators affecting osteogenic capacity of PDLSCs. Subsequently, the predicted role of RELB was experimentally validated both in vitro and in vivo using small interfering RNA. The scRNA-seq analysis revealed significant heterogeneity within the PDLSC population. Notably, PDLSC-5 subtype, which exhibited osteogenic potential and positioned at the terminus of the pseudotime trajectory, was markedly reduced in mature PDL tissues. RELB was specifically overexpressed in PDLSC-5 and identified as a key transcription factor (TF) for this subcluster. Knockdown of RELB significantly inhibited the osteogenic differentiation capacity of PDLSCs in vitro and bone formation potential in vivo at both developmental stages. This inhibitory effect appears to be mediated, at least in part, through the downregulation of its target gene, superoxide dismutase 2 (SOD2). Our findings demonstrate that the proportion of PDLSCs with osteogenic ability significantly declines with maturity, accounting for the diminished regeneration capacity of mature periodontal tissue. Furthermore, RELB was identified as a crucial TF for maintaining the osteogenic potential of PDLSCs. These results provide a theoretical basis for strategies aimed at optimizing the bone regeneration capacity of PDLSCs.

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, and myocardial infarction (MI) frequently progresses to heart failure despite advances in contemporary therapies. A major barrier to the clinical translation of cardioprotective biologics is the lack of noninvasive, organ-targeted delivery systems suitable for repeated administration. Although inhalation is an attractive route for systemic delivery, strategies that efficiently direct inhaled nanocarriers from the lung to the injured heart remain limited. In a murine MI model, inhaled PPL showed greater accumulation in infarcted myocardium than unmodified liposomes after pulmonary administration. Repeated administration of IGF@PPL significantly improved cardiac function, attenuated adverse ventricular remodeling and fibrosis, and enhanced angiogenesis, without inducing detectable pulmonary or systemic toxicity. Collectively, these findings support the feasibility of pulmonary-to-systemic delivery followed by preferential cardiac accumulation and provides a broadly applicable framework for inhalable nanomedicine-based treatment of myocardial injury.

Carotid free-floating thrombus (CFFT) is an uncommon vascular condition involving an elongated thrombus that extends in the direction of distal blood flow, remaining only partially attached to the artery wall. Risk factors include atherosclerosis, hypercoagulable states, and vascular trauma. Symptoms of CFFT can include sudden unilateral weakness or numbness, slurred speech, visual disturbances, dizziness, and headaches, which may indicate a transient ischemic attack or stroke. However, due to its rarity, the optimal treatment strategies remain under investigation. Here, we present a unique case of a patient with Marfan syndrome who developed CFFT while on long-term warfarin therapy, effectively managed with enoxaparin. This case illustrates the role of arterial tortuosity and aneurysmal dilatation in thrombus formation as a manifestation of Marfan syndrome. It also emphasizes the complexities of managing CFFT, presenting a therapeutic dilemma due to the uncertainty surrounding optimal treatment strategies and shedding light on the need for further research to inform clinical decision-making.

Cardiac fibrosis independently predicts adverse outcomes in heart failure (HF), yet no Food and Drug Administration-approved therapy directly targets fibrotic remodeling in the heart. To address this unmet clinical need, we used a multidimensional drug discovery pipeline centered on a human induced pluripotent stem cell (iPSC)-based platform. Through high-throughput screening, we identified CGS15943 (CGS) as the lead antifibrotic compound and validated its activity in human cardiac fibroblasts, three-dimensional engineered heart tissues, and animal models of HF. Mechanistic studies revealed an atypical adenosine receptor (AR)-dependent signaling pathway in which AR subtypes converge on Gβγ (the βγ subunits of heterotrimeric GTP-binding proteins) to activate phosphoinositide 3-kinase (PI3K)-AKT and yes-associated protein (YAP). CGS suppressed this signaling axis, thereby reducing fibrotic gene expression and fibroblast activation. These findings establish AR-driven Gβγ signaling as a potential therapeutic target for cardiac fibrosis.

Hypertrophic cardiomyopathy (HCM) patients exhibit heightened susceptibility to atrial fibrillation (AF), yet the underlying genetic nexus remains poorly defined. This study aimed to identify genes common to HCM and AF, thereby revealing the underlying pathogenesis of susceptibility to AF in HCM patients.

Genes associated with HCM and AF were sourced from the Gene Expression Omnibus (GEO), Online Mendelian Inheritance in Man (OMIM), Comparative Toxicogenomics Database (CTD), GeneCards, and DisGeNET databases. We conducted a comparative analysis to identify overlapping genes between HCM and AF for further investigation, which included functional enrichment analysis, protein-protein interaction networks, and immune infiltration assessment. Key hub genes were determined using cytoHubba, a Cytoscape plugin, and their validation was performed using independent datasets GSE36961 and GSE115574. The genes corroborated by these datasets were additionally validated in clinical samples.

A total of 11 overlapping genes were identified between HCM and AF. Functional enrichment and immune infiltration analyses revealed their involvement in immune regulation and inflammatory processes. Three hub genes NPPA, ACE, and POMC were recognized as key molecular links between HCM and AF. Validation using the GSE36961 dataset confirmed the upregulation of NPPA in HCM, supporting its potential as a central gene connecting the two conditions. Consistent with the bioinformatics findings, exploratory clinical verification findings of serum levels of N-terminal fragment of A-type natriuretic peptide (NT-proANP), encoded by NPPA, were markedly elevated in both the HCM and HCM with AF groups compared with healthy controls (P < 0.01). Moreover, NT-proANP concentrations were significantly higher in the HCM + AF group than in the HCM-only group (P < 0.01).

This study identifies a shared genetic link between HCM and AF. The findings strongly associate elevated NT-proANP levels, encoded by the NPPA gene, with AF in HCM patients. We propose NT-proANP as a promising circulating biomarker for stratifying AF risk in this patient population.

Atherosclerosis is driven by interacting lipid and inflammatory pathways. There remains a pressing clinical need for drugs that exert both lipid-lowering and vascular anti-inflammatory effects. Studies have suggested that thyroid hormone receptor β (THR-β) agonists can alleviate atherosclerosis while avoiding the cardiotoxic adverse effects associated with thyroid hormone. Resmetirom is an oral, once-daily, liver-targeted selective THR-β agonist. It has attracted attention for improving lipid metabolism, yet its effects on vascular inflammatory phenotypes remain poorly clarified. We investigated the effects of resmetirom on atherosclerosis-associated dyslipidemia, plaque burden and vascular inflammatory phenotypes.

Apolipoprotein E-deficient (ApoE-/-) mice fed a high-fat diet (HFD) for 8 weeks were randomized to vehicle, low-dose (3 mg/kg/day), or high-dose (10 mg/kg/day) resmetirom for eight weeks (n = 10 per group). Serum lipids, inflammatory cytokines, aortic plaque morphology, NLRP3 inflammasome signaling, NF-κB activation, oxidative stress, and macrophage polarization were analyzed by one-way ANOVA with Tukey post hoc testing; dose-response regression was performed across disease-bearing groups.

Resmetirom treatment reduced aortic plaque burden, corrected atherogenic dyslipidemia, and suppressed aortic NLRP3 and caspase-1 expression in a dose-dependent manner. High-dose resmetirom lowered low-density lipoprotein cholesterol (LDL-C) by 39.48%, and reduced aortic lipid accumulation on Oil Red O staining compared to model controls. Additionally, it suppressed interleukin-1β (IL-1β) by 59.28%; Western blotting showed lower p-p65/total p65 ratio and higher IκBα/GAPDH abundance. Flow-cytometric ROS intensity decreased by 35.56%, and the M1/M2 macrophage ratio decreased by 72.81%. Exploratory cross-assay analyses showed coherent associations among systemic cytokines and aortic NF-κB/ROS/macrophage readouts.

Resmetirom attenuated atherosclerosis-associated dyslipidemia, plaque burden and vascular inflammation in HFD ApoE-/- mice. The data support an association between resmetirom treatment and suppression of the NF-κB/ROS-NLRP3 inflammatory phenotype, warranting mechanistic validation in models with direct pathway perturbation. These findings support its translational potential in atherosclerotic cardiovascular disease.

Methicillin-resistant Staphylococcus aureus (MRSA) poses challenges in healthcare settings, contributing to antimicrobial resistance and complicating treatment of staphylococcal infections. In resource-limited settings such as Zambia, staphylococcal infections are treated empirically with clindamycin or co-trimoxazole due to limited susceptibility testing. However, MRSA and multidrug resistance are reducing treatment effectiveness. This study aimed to determine the prevalence and antimicrobial susceptibility of MRSA at Mansa General Hospital, Zambia. A retrospective cross-sectional study was conducted on 266 clinical S. aureus isolates from 2020-2024. Bacterial identification was performed using microbiological methods (Mannitol Salt Agar, catalase, coagulase, DNase tests). MRSA detection and antimicrobial susceptibility testing (AST) using the Kirby-Bauer disk diffusion- method with cefoxitin (30 µg) as a surrogate marker, interpreted according to CLSI M100 34th Edition guidelines. Multivariable logistic regression identified factors associated with MRSA. Among 266 S. aureus isolates, the overall MRSA prevalence was 31.6% (84/266). MRSA demonstrated significantly lower susceptibility than MSSA to non-beta-lactam antibiotics: clindamycin (46.2% vs. 67.7%), erythromycin (50.0% vs. 79.5%), ciprofloxacin (58.2% vs. 91.4%), and tetracycline (58.3% vs. 81.9%). Chloramphenicol (86.5% vs. 100%) and linezolid (81.8% vs. 97.9%) retained activity. MDR prevalence was 28.6% (76/266), with higher MDR (57.1%, 48/84) than MSSA (15.4%, 28/182). Older age was independently associated with MRSA: adults aged 45-59 years (AOR 2.77; 95% CI 1.09-7.01; p = 0.032) and ≥60 years (AOR 4.53; 95% CI 1.45-14.1; p = 0.009) had higher odds compared to children. Sex, patient type and specimen source were not significant predictors. This study highlights the high prevalence of MRSA at Mansa General Hospital, reduced susceptibility to used oral antibiotics and a burden of multidrug resistance. Empirical use of clindamycin and erythromycin for suspected staphylococcal skin and soft tissue infections should be reconsidered and guided by local antimicrobial susceptibility whenever available. Continued local surveillance and multicenter studies are needed to inform empirical treatment guidelines across Zambia.

Primary aortic mural thrombus (PAMT) is defined by an aortic thrombus in the absence of underlying aortic disease. Management relies on anticoagulation, with or without surgery, but optimal treatment duration remains uncertain. We evaluated clinical and radiological outcomes of symptomatic PAMT after 6 months of oral anticoagulation.

We performed a retrospective cohort study (2011-2022) reviewing all consecutive cases of aortic thrombosis. Inclusion criteria were symptomatic PAMT without prior anticoagulation. Patients treated surgically, without imaging follow-up, or lost to follow-up were excluded. Clinical, biological, and imaging data were collected. Radiological evolution was independently assessed by four physicians.

Of 101 screened cases, 29 were included. Median age was 57 years (IQR 49-67), 66% were men, and cardiovascular risk factors were frequent (current and former smokers 86%, hypertension 55%, dyslipidemia 41%). Thrombi were mainly infrarenal (55%), followed by thoracic descending (21%), suprarenal abdominal (14%), and aortic arch (10%). Presentations included acute limb ischemia (76%) and organ infarction (21%). After a median of 180 days (IQR 167-208) of anticoagulation, thrombus evolution showed complete resolution in 17%, partial improvement in 48%, stability in 31%, and progression in 3%. Two embolic recurrences (7%) occurred, including one requiring thrombectomy. At extended follow-up (median 268 days), one major and three clinically relevant nonmajor bleeding events occurred; three deaths were unrelated to PAMT.

Six months of anticoagulation in symptomatic PAMT achieves low recurrence and thrombus regression in most patients with acceptable safety. Prolonging anticoagulation beyond 6 months did not improve outcomes.

Metabolic dysfunction-associated steatohepatitis (MASH) is rising globally despite recent therapeutic advances, highlighting the need to identify new targetable pathways. While dysregulated lipid and amino acid metabolism are established features of MASH, the interplay between these two metabolic pathways remains unexplored. Here, metabolomics of livers from humans and mice with MASH uncovered depletion of lipidated amino acids, where these two distinctive pathways converge. Notably, hepatic levels of N-oleoyl-leucine (C18:1-Leu) were inversely correlated with the severity of MASH-fibrosis. The C18:1-Leu-regulating enzyme, peptidase M20 domain containing 1 (PM20D1), was suppressed in MASH due to attenuated de novo transcription, and stable-isotope tracing confirmed impaired hepatic biosynthesis of C18:1-Leu in MASH. Hepatocyte-specific PM20D1 ablation lowered hepatic C18:1-Leu and exacerbated MASH, whereas hepatocyte-specific PM20D1 overexpression restored C18:1-Leu and ameliorated both MASH progression and established disease. Exogenous administration of C18:1-Leu similarly ameliorated MASH-fibrosis. In silico modeling, transcriptomics, metabolic flux analyses and hepatocyte-specific in vivo manipulations revealed that C18:1-Leu binds and activates peroxisome proliferator-activated receptor alpha to suppress C-C motif chemokine ligand 2, concurrently enhancing fatty acid β-oxidation and attenuating monocyte recruitment to reduce MASH-fibrosis. These findings highlight C18:1-Leu deficiency as a driver and a therapeutic target in MASH-fibrosis, warranting further clinical evaluation.