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We aimed to compare the associations of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with coronary artery calcification (CAC). Patients who simultaneously underwent ultrasonography to diagnose hepatic steatosis and cardiac computed tomography to detect CAC were included. The presence and severity of CAC were defined with CAC-score thresholds of > 0 and > 300, respectively, and patients were divided into the following groups: no MASLD or MAFLD (reference), MASLD-only, MAFLD-only, and overlapping groups. Overall, 1,060/2,773 (38.2%) patients had CAC, of which 196 (18.5%) had severe CAC. The MASLD and MAFLD prevalence rates were 32.6% and 45.2%, respectively, with an overlap of 30.7%. In an ASCVD risk score-adjusted model, both MASLD (adjusted odd ratios [aOR], 1.21; 95% confidence interval [CI], 1.02-1.44; p = 0.033) and MAFLD (aOR 1.20; 95% CI 1.01-1.42, p = 0.034) were associated with CAC, whereas only MASLD (aOR 1.38; 95% CI 1.01-1.89, p = 0.041) was associated with severe CAC. Compared to the reference group, the overlapping group showed an association with CAC (aOR 1.22; 95% CI 1.01-1.47; p = 0.038); however, the MASLD and MAFLD subgroups did not differ in their association with CAC. MASLD may predict a higher risk of ASCVD more effectively than MAFLD.

Federated learning (FL) is a method used for training artificial intelligence models with data from multiple sources while maintaining data anonymity, thus removing many barriers to data sharing. Here we used data from 20 institutes across the globe to train a FL model, called EXAM (electronic medical record (EMR) chest X-ray AI model), that predicts the future oxygen requirements of symptomatic patients with COVID-19 using inputs of vital signs, laboratory data and chest X-rays. EXAM achieved an average area under the curve (AUC) >0.92 for predicting outcomes at 24 and 72 h from the time of initial presentation to the emergency room, and it provided 16% improvement in average AUC measured across all participating sites and an average increase in generalizability of 38% when compared with models trained at a single site using that site's data. For prediction of mechanical ventilation treatment or death at 24 h at the largest independent test site, EXAM achieved a sensitivity of 0.950 and specificity of 0.882. In this study, FL facilitated rapid data science collaboration without data exchange and generated a model that generalized across heterogeneous, unharmonized datasets for prediction of clinical outcomes in patients with COVID-19, setting the stage for the broader use of FL in healthcare.

The RNA-directed DNA methylation (RdDM) pathway in plants controls gene expression via cytosine DNA methylation. The ability to manipulate RdDM would shed light on the mechanisms and applications of DNA methylation to control gene expression. Here, we identified diverse RdDM proteins that are capable of targeting methylation and silencing in Arabidopsis when tethered to an artificial zinc finger (ZF-RdDM). We studied their order of action within the RdDM pathway by testing their ability to target methylation in different mutants. We also evaluated ectopic siRNA biogenesis, RNA polymerase V (Pol V) recruitment, targeted DNA methylation, and gene-expression changes at thousands of ZF-RdDM targets. We found that co-targeting both arms of the RdDM pathway, siRNA biogenesis and Pol V recruitment, dramatically enhanced targeted methylation. This work defines how RdDM components establish DNA methylation and enables new strategies for epigenetic gene regulation via targeted DNA methylation.

Aim: This post-marketing surveillance study evaluated the safety and effectiveness of lenvatinib as first-line treatment for unresectable hepatocellular carcinoma in Korea. Materials & methods: Adverse drug reactions (ADRs) and other safety and effectiveness end points were assessed in patients who initiated lenvatinib according to the approved label in republic of Korea. Results: Among 658 lenvatinib-treated patients, ADRs were reported in 57.8%; ADRs grade ≥3 in 13.5%. The most common grade ≥3 ADRs were asthenia (1.2%) and hepatic encephalopathy (1.2%). Physician-reported tumor responses (n = 511) were complete (1.0%) or partial (12.9%) response and stable (45.2%) or progressive disease (40.9%); objective response rates were higher with longer lenvatinib treatment duration (p < 0.001). Conclusion: Lenvatinib was generally well tolerated and effective in real-world clinical practice in Korea. Clinical trial registration:ClinicalTrials.govNCT05225207 Article highlights Since 2018, lenvatinib has been available in several countries as first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC). This was a prospective, multicenter, observational, post-marketing surveillance of the safety and effectiveness of lenvatinib as first-line treatment for uHCC in routine clinical practice in republic of Korea. Among 700 case report forms of patients who initiated lenvatinib according to the approved label in republic of Korea at 29 institutions, 658 were included in the safety analysis and 511 in the effectiveness analysis. None of the safety population (median age 64 years, 85% male) had received prior chemotherapy, 64.1% had received non-chemotherapy treatment, and 42.1% had a history of hypertension treatment. Among 658 lenvatinib-treated patients, the incidence of adverse drug reactions (ADRs) was 57.8% and the incidence of ADRs grade ≥3 was 13.5%. The most common ADRs were hypertension (14.4%) diarrhea (10.5%), palmar-plantar erythrodysesthesia syndrome (10.0%) and decreased appetite (7.6%); the most common grade ≥3 ADRs were asthenia (1.2%) and hepatic encephalopathy (1.2%). Factors significantly associated with adverse events were history of non-chemotherapy treatment, hypertension treatment; and the average daily dose of lenvatinib (12 mg/day compared with <8 mg/day and 8 – <10 mg/day). Physician-reported tumor responses evaluated by RECIST v1.1 or mRECIST criteria were: complete response (1.0%); partial response (12.9%); stable disease (45.2%); and progressive disease (40.9%). Objective response rates were significantly higher with longer (≥3 months to >9 months) lenvatinib treatment duration compared with <3 months. This PMS study shows that lenvatinib has a manageable tolerability profile and provides clinically meaningful effectiveness as first-line treatment for patients with uHCC in the real-world clinical setting in Korea. [ABSTRACT FROM AUTHOR]

Background/Objectives: The role of body composition parameters in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) with presence and severity of coronary artery calcification (CAC) is still not fully elucidated. We aimed to evaluate the impact of computed tomography (CT)-based body composition parameters in patients with MASLD with CAC severity. Methods: In this multicenter study, 1870 individuals underwent cardiac CT for the detection of CAC as well as ultrasonography for the diagnosis of hepatic steatosis. The presence of CAC was defined by a CAC score threshold of >0, while severe CAC was defined by a threshold of >300. Using the abdominal cross-sectional CT images at the L3 vertebra level, we analyzed the skeletal muscle index, visceral to subcutaneous adipose tissue ratio, and muscle density using the Hounsfield unit. Results: Of 648 patients with MASLD, the proportions of presence of CAC and severe CAC were 45.2% and 9.9%, respectively. Visceral obesity was not associated with the presence of CAC after adjustment for age, sex, smoking, statin therapy, type 2 diabetes, and advanced fibrosis (adjusted odds ratio (aOR), 1.38; 95% confidence interval (CI), 0.86–2.23; p = 0.180). However, visceral obesity was independently associated with severe CAC after adjustment for several metabolic risk factors (aOR, 3.54; 95% CI, 1.25–14.90; p = 0.039), and adjustment for atherosclerotic cardiovascular disease risk scores (aOR, 3.74; 95% CI, 1.31–15.79; p = 0.032). Conclusions: Visceral obesity may serve as a novel prognostic CT-based radiological biomarker for patients with MASLD with severe CAC. [ABSTRACT FROM AUTHOR]