Autism spectrum disorders (ASDs) are genetically and phenotypically heterogeneous and the majority of cases still remain genetically unresolved. To better understand large-effect pathogenic variation, we generated long-read sequencing data to construct phased and near-complete genome assemblies (average contig N50=43 Mbp, QV=56) for 189 individuals from 51 families with unsolved cases of autism. We applied read- and assembly-based strategies to facilitate comprehensive characterization of de ...| medRxiv
Long-read whole genome sequencing (LR-WGS) technologies enhance the discovery of structural variants (SVs) and tandem repeats (TRs). Application of LR-WGS has potential to identify novel risk factors that contribute to autism spectrum disorder (ASD). We performed LR-WGS on 243 individuals from 63 ASD families and generated an integrated call set combining long- and short-read data. LR-WGS increased detection of gene-disrupting SVs and TRs by 29% and 38%, respectively, and enabled identificati...| medRxiv
Importance Antidepressant use is rising globally, with increasing duration of real-world prescribing. While the FDA considers 6-8 week trials adequate for regulatory approval, guidelines recommend prolonged treatment. This raises questions about the evidence supporting long-term prescribing practices. Objective To systematically compare the duration of placebo-controlled randomized trials of commonly prescribed antidepressants with real-world usage patterns. Design, Setting, and Participants:...| medRxiv
Importance Light at night causes circadian disruption, which is a known risk factor for adverse cardiovascular outcomes. However, it is not well understood whether personal light exposure patterns predicts and individual’s risk of cardiovascular diseases. Objective To assess whether day and night light exposure predicts incidence of cardiovascular diseases, and whether relationships of light with cardiovascular diseases differ according to genetic susceptibility, sex, and age. Design Prospe...| medRxiv
Background The clinical trials used to approve COVID-19 vaccines excluded pregnant women, and existing safety assessments of COVID-19 vaccination, particularly during early stages of pregnancy, are limited to observational studies prone to various types of potential bias, including healthy vaccinee bias. Methods The study includes pregnancies in Israel with last menstruation period (LMP) between March 1, 2016 and February 28, 2022. The main analysis presents observed-to-expected comparisons o...| medRxiv
Background Children and adolescents in England were offered BNT162b2 as part of the national COVID-19 vaccine roll out from September 2021. We assessed the safety and effectiveness of first and second dose BNT162b2 COVID-19 vaccination in children and adolescents in England. Methods With the approval of NHS England, we conducted an observational study in the OpenSAFELY-TPP database, including a) adolescents aged 12-15 years, and b) children aged 5-11 years and comparing individuals receiving ...| medRxiv
Systematic reviews (SRs) inform evidence-based decision making. Yet, they take over a year to complete, are prone to human error, and face challenges with reproducibility; limiting access to timely and reliable information. We developed otto-SR, an end-to-end agentic workflow using large language models (LLMs) to support and automate the SR workflow from initial search to analysis. We found that otto-SR outperformed traditional dual human workflows in SR screening (otto-SR: 96.7% sensitivity,...| medRxiv
COVID-19 vaccines have prevented millions of COVID-19 deaths. Yet, a small fraction of the population reports a chronic debilitating condition after COVID-19 vaccination, often referred to as post-vaccination syndrome (PVS). To explore potential pathobiological features associated with PVS, we conducted a decentralized, cross-sectional study involving 42 PVS participants and 22 healthy controls enrolled in the Yale LISTEN study. Compared with controls, PVS participants exhibited differences i...| medRxiv
The mRNA-based BNT162b2 vaccine from Pfizer/BioNTech was the first registered COVID-19 vaccine and has been shown to be up to 95% effective in preventing SARS-CoV-2 infections. Little is known about the broad effects of the new class of mRNA vaccines, especially whether they have combined effects on innate and adaptive immune responses. Here we confirmed that BNT162b2 vaccination of healthy individuals induced effective humoral and cellular immunity against several SARS-CoV-2 variants. Intere...| medRxiv
Acute SARS-CoV-2 infection triggers the generation of diverse and functional autoantibodies (AABs), even after mild cases. Persistently elevated autoantibodies have been found in some individuals with long COVID (LC). Using a >21,000 human protein array, we identified diverse AAB targets in LC patients that correlated with their symptoms. Elevated AABs to proteins in the nervous system were found in LC patients with neurocognitive and neurological symptoms. Purified Immunoglobulin G (IgG) sam...| medRxiv
The etiologic mechanisms of post-acute medical morbidities and unexplained symptoms (Long COVID) following SARS-CoV-2 infection are incompletely understood. There is growing evidence that viral persistence and immune dysregulation may play a major role. We performed whole-body positron emission tomography (PET) imaging in a cohort of 24 participants at time points ranging from 27 to 910 days following acute SARS-CoV-2 infection using a novel radiopharmaceutical agent, [18F]F-AraG, a highly se...| medRxiv
Introduction A chronic post-vaccination syndrome (PVS) after covid-19 vaccination has been reported but has yet to be well characterized. Methods We included 241 individuals aged 18 and older who self-reported PVS after covid-19 vaccination and who joined the online Yale Listen to Immune, Symptom and Treatment Experiences Now (LISTEN) Study from May 2022 to July 2023. We summarized their demographics, health status, symptoms, treatments tried, and overall experience. Results The median age of...| medRxiv
