Three-Year Follow-up After Antiviral Treatment in New-Onset Type 1 Diabetes: Results From the Diabetes Virus Detection and Intervention Trial.

Objective: In the Diabetes Virus Detection and Intervention trial, antiviral treatment with pleconaril and ribavirin decreased the decline, compared with placebo, in endogenous C-peptide 1 year after diagnosis of type 1 diabetes (T1D) in children and adolescents. This article reports the results 2 and 3 years after diagnosis.

Research Design And Methods: This was a multicenter, randomized, placebo-controlled (1:1) trial of 96 children and adolescents aged 6-15.

Cell integrity limits ploidy in budding yeast.

Evidence suggests that increases in ploidy have occurred frequently in the evolutionary history of organisms and can serve adaptive functions to specialized somatic cells in multicellular organisms. However, the sudden multiplication of all chromosome content may present physiological challenges to the cells in which it occurs. Experimental studies have associated increases in ploidy with reduced cell survival and proliferation.

Five-Year Results With Patisiran for Hereditary Transthyretin Amyloidosis With Polyneuropathy: A Randomized Clinical Trial With Open-Label Extension.

Importance: There is a lack of long-term efficacy and safety data on hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) and on RNA interference (RNAi) therapeutics in general. This study presents the longest-term data to date on patisiran for hATTR-PN.

Objective: To present the long-term efficacy and safety of patisiran in adults with hATTR-PN.

Artificial Liver Support Systems in Acute Liver Failure and Acute-on-Chronic Liver Failure: Systematic Review and Meta-Analysis.

Objectives: To systematically review the safety and efficacy of nonbiological (NBAL) or biological artificial liver support systems (BAL) and whole-organ extracorporeal liver perfusion (W-ECLP) systems, in adults with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF).

Data Sources: Eligible NBAL/BAL studies from PubMed/Embase searches were randomized controlled trials (RCTs) in adult patients with ALF/ACLF, greater than or equal to ten patients per group, reporting outcomes related to survival, adverse events, transplantation rate, and hepatic encephalopathy, and published in English from January 2000 to July 2023. Separately, we searched for studies evaluating W-ECLP in adult patients with ALF or ACLF published between January1990 and July 2023.

NephroCheck as a Predictor of Acute Kidney Injury Following Coronary Artery Bypass Graft Surgery.

Background Cardiac surgery-associated acute kidney injury (CSA-AKI) remains a significant complication following coronary artery bypass grafting (CABG), affecting 22%-30% of patients. This study evaluates the efficacy of NephroCheck, a biomarker-based test measuring insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP2), in predicting postoperative AKI. Methods In this retrospective observational cohort study, 21 patients undergoing isolated CABG were analyzed.

A multimodal neural signature of face processing in autism within the fusiform gyrus.

Atypical face processing is commonly reported in autism. Its neural correlates have been explored extensively across single neuroimaging modalities within key regions of the face processing network, such as the fusiform gyrus (FFG). Nonetheless, it is poorly understood how variation in brain anatomy and function jointly impacts face processing and social functioning.

Global, regional, and national trends in drug use disorder mortality rates across 73 countries from 1990 to 2021, with projections up to 2040: a global time-series analysis and modelling study.

Background: Drug use disorder (DUD) poses a major public health crisis globally, necessitating immediate attention to global trends and future projections to develop effective health policies and interventions. Thus, we aimed to estimate the global trends in DUD mortality rates from 1990 to 2021 and future projections of DUD deaths until 2040 across 73 countries.

Methods: In this time-series analysis and modelling study, we investigated the global trends in DUD mortality rates from 1990 to 2021 using the WHO Mortality Database and forecasted future trends through 2040.

Maternal and neonatal complications of pregnant women with bipolar disorder: a systematic review and meta-analysis.

Background: Confidence in pregnancy outcome data for women with bipolar disorder is compromised by small cohort sizes. However, comprehensive national data have been published over the last decade, but no quantitative synthesis has been established to determine the factors associated with complications in these women. Our goal is to summarise the evidence of population-based data on obstetric complications and neonatal outcomes in women with bipolar disorder compared to women without bipolar disorder.

Identifying biomarker-driven subphenotypes of cardiogenic shock: analysis of prospective cohorts and randomized controlled trials.

Background: Cardiogenic shock (CS) is a heterogeneous clinical syndrome, making it challenging to predict patient trajectory and response to treatment. This study aims to identify biological/molecular CS subphenotypes, evaluate their association with outcome, and explore their impact on heterogeneity of treatment effect (ShockCO-OP, NCT06376318).

Methods: We used unsupervised clustering to integrate plasma biomarker data from two prospective cohorts of CS patients: CardShock (N = 205 [2010-2012, NCT01374867]) and the French and European Outcome reGistry in Intensive Care Units (FROG-ICU) (N = 228 [2011-2013, NCT01367093]) to determine the optimal number of classes.

Health indicators in the management of diabetes in Primary health care: Iran-package of Essential Non-communicable diseases (IraPEN) program.

Objectives: This study evaluated the effectiveness of the IraPEN program, an adapted version of the WHO Package of Essential Non-communicable Disease (PEN) intervention, in managing diabetes from September 2020 to September 2021 using the Input-Process-Output-Outcome framework.

Methods: In this Cross-sectional/Ecological study, aggregated data was collected from IraPEN facilities by medical universities using the electronic health system. The data was presented as numbers and proportions, for urban and rural healthcare facilities separately.

Implementing Mutational Epidemiology on a Global Scale: Lessons from Mutographs.

The Mutographs Cancer Grand Challenge team aimed to discover unknown causes of cancer through mutational epidemiology, an alliance of cancer epidemiology and somatic genomics. By generating whole-genome sequences from thousands of cancers and normal tissues from more than 30 countries on five continents, it discovered unsuspected mutagenic exposures affecting millions of people, raised the possibility that some carcinogens act by altering forces of selection in tissue microenvironments rather than by mutagenesis, and demonstrated changes to the direction of somatic evolution in normal cells of the human body in response to exogenous exposures and noncancer diseases. See related article by Bressan et al.

Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation.

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas.

Effects of periodontal disease on the proteomic profile of the periodontal ligament.

Periodontal disease affects over 1 billion people globally. This study investigated how periodontitis affects the protein profile of the periodontal ligament (PDL) in rats. Eight Holtzman rats were divided into the control and experimental periodontitis groups.

Artificial enforcement of the unfolded protein response (UPR) reduces disease features in multiple preclinical models of ALS/FTD.

Amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) are part of a spectrum of diseases that share several causative genes, resulting in a combinatory of motor and cognitive symptoms and abnormal protein aggregation. Multiple unbiased studies have revealed that proteostasis impairment at the level of the endoplasmic reticulum (ER) is a transversal pathogenic feature of ALS/FTD. The transcription factor XBP1s is a master regulator of the unfolded protein response (UPR), the main adaptive pathway to cope with ER stress.

Unsupervised deep learning of electrocardiograms enables scalable human disease profiling.

The 12-lead electrocardiogram (ECG) is inexpensive and widely available. Whether conditions across the human disease landscape can be detected using the ECG is unclear. We developed a deep learning denoising autoencoder and systematically evaluated associations between ECG encodings and ~1,600 Phecode-based diseases in three datasets separate from model development, and meta-analyzed the results.

Efficacy, safety, and target engagement of dazukibart, an IFNβ specific monoclonal antibody, in adults with dermatomyositis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.

Background: Dermatomyositis is a chronic autoimmune disease with distinctive cutaneous eruptions and muscle weakness, and the pathophysiology is characterised by type I interferon (IFN) dysregulation. This study aims to assess the efficacy, safety, and target engagement of dazukibart, a potent, selective, humanised IgG1 neutralising monoclonal antibody directed against IFNβ, in adults with moderate-to-severe dermatomyositis.

Methods: This multicentre, double-blind, randomised, placebo-controlled, phase 2 trial was conducted at 25 university-based hospitals and outpatient sites in Germany, Hungary, Poland, Spain, and the USA.

Accuracy of Survey-Based Assessment of Eligibility for Medication Abortion Compared to Clinician Assessment.

Background: With increasingly restricted access to facility-based abortion in the United States, pregnant people are increasingly relying on models of care that utilize history-based or no-test approaches to eligibility assessment. Minimal research has examined the accuracy of abortion patients' self-assessment of eligibility for medication abortion using their health history, a necessary step towards ensuring optimal access to history-based or no-test models, as well as potential over-the-counter access.

Objective: To examine the accuracy of pregnant people's eligibility for medication abortion determined using their self-reported health history as compared to clinician assessment with ultrasound and other tests.

Default mode network functional connectivity as a transdiagnostic biomarker of cognitive function.

The default mode network (DMN) is intricately linked with processes such as self-referential thinking, episodic memory recall, goal-directed cognition, self-projection, and theory of mind. Over recent years, there has been a surge in examining its functional connectivity, particularly its relationship with frontoparietal networks (FPN) involved in top-down attention, executive function, and cognitive control. The fluidity in switching between these internal and external modes of processing-highlighted by anti-correlated functional connectivity-has been proposed as an indicator of cognitive health.

AZD2693, a PNPLA3 antisense oligonucleotide, for the treatment of MASH in 148M homozygous participants: two randomized phase I trials.

Background & Aims: A common genetic variant (rs738409) encoding isoleucine to methionine at position 148 in the PNPLA3 protein is a determinant of hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver-related mortality. AZD2693 is a liver-targeted antisense oligonucleotide against PNPLA3 mRNA. We evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics in single ascending dose (SAD) and multiple ascending dose (MAD) studies.

The relationship between nonalcoholic fatty liver disease and frailty: A systematic review and meta-analysis.

Background And Aim: Frailty is frequently observed in end-stage liver disease of various etiologies, but its role in nonalcoholic fatty liver disease (NAFLD) remains incompletely understood. We aimed to conduct a systematic review and meta-analysis to assess the association and prevalence of frailty in NAFLD.

Methods: A systematic review of PubMed/MEDLINE, EMBASE, Web of Science, and Scopus was performed.

Physical and neurophysiological maturation associated with ADHD among previously institutionalized children: a randomized controlled trial.

Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental outcome among children with a history of early institutional care. Prior research on institutionalized children suggested that accelerated physical growth in childhood is a risk factor for ADHD outcomes.

Methods: The current study examined physical and neurophysiological growth trajectories among institutionalized children randomized to foster care treatment (n = 59) or care as usual (n = 54), and never institutionalized children (n = 64) enrolled in the Bucharest Early Intervention Project (NCT00747396, clinicaltrials.