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Embryonic development is dictated by tight regulation of DNA replication, cell division and differentiation. Mutations in DNA repair and replication genes disrupt this equilibrium, giving rise to neurodevelopmental disease characterized by microcephaly, short stature and chromosomal breakage. Here, we identify biallelic variants in two components of the RAD18-SLF1/2-SMC5/6 genome stability pathway, SLF2 and SMC5 , in 11 patients with microcephaly, short stature, cardiac abnormalities and anemia. Patient-derived cells exhibit a unique chromosomal instability phenotype consisting of segmented and dicentric chromosomes with mosaic variegated hyperploidy. To signify the importance of these segmented chromosomes, we have named this disorder Atelís (meaning - incomplete) Syndrome. Analysis of Atelís Syndrome cells reveals elevated levels of replication stress, partly due to a reduced ability to replicate through G-quadruplex DNA structures, and also loss of sister chromatid cohesion. Together, these data strengthen the functional link between SLF2 and the SMC5/6 complex, highlighting a distinct role for this pathway in maintaining genome stability. The SMC5/6 complex is critical for genome stability. Here, the authors identify mutations in SLF2 and SMC5 as cause of Atelís Syndrome characterized by microcephaly, short stature, anemia, segmented chromosomes and mosaic variegated hyperploidy.

ObjectiveMetabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health concern, with increasing mortality rates driven by the obesity pandemic. Weight loss has been shown to improve MASLD outcomes, yet the effectiveness of eHealth interventions in MASLD management remains uncertain. We aimed to evaluate the effectiveness of eHealth interventions compared with standard care in improving health outcomes among patients with MASLD.DesignA systematic review and meta-analysis were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data sourcesRelevant studies were retrieved from PubMed, Cochrane Central and Embase databases from inception to 26 April 2024.Eligibility criteriaOnly double-arm clinical trials involving human participants diagnosed with MASLD were included. Eligible studies were limited to those published in English.Data extraction and synthesiseHealth interventions—including internet-based platforms, smartwatches, telephone follow-ups and mobile applications for dietary and exercise modifications—were compared against traditional intervention methods. The primary outcomes assessed were changes in body weight, abdominal/waist circumference, aspartate aminotransferase (AST) and alanine transaminase (ALT). Secondary outcomes were changes in body mass index (BMI), diastolic blood pressure, systolic blood pressure, MASLD fibrosis score, high-density lipoprotein, gamma-glutamyl transferase and triglycerides.Results11 studies met the inclusion criteria, of which 10 provided relevant outcomes and were included. The mean age of participants across the studies ranged from 39.3 to 57.9 years, with intervention durations spanning 3 to 24 months. Our results indicate significant improvements with eHealth interventions compared with control comparators, including reductions in AST (standardised mean difference (SMD): −0.35 (95% CI –0.61, –0.10); p<0.05), ALT (SMD: −0.38 (95% CI –0.65, –0.11); p<0.05), weight loss (SMD: −0.38 (95% CI –0.60, –0.17); p<0.05) and BMI (SMD: −0.37 (95% CI –0.54, –0.21); p<0.05).ConclusionsThe utilisation of eHealth interventions showed significant improvements in outcomes related to AST, ALT, abdominal circumference, weight loss and BMI. However, future studies with larger sample sizes and longer follow-ups are warranted to assess the sustainability of these outcomes.