Separating direct, indirect and parent-of-origin genetic effects in the human population.

Here, we present a novel approach to estimate the degree to which the phenotypic effect of a DNA locus is attributable to four components: alleles in the child (direct genetic effects), alleles in the mother and the father (indirect genetic effects), or is dependent upon the parent from which it is inherited (parent-of-origin, PofO effects). Applying our model, JODIE, to 30,000 child-mother-father trios with phased DNA information from the Estonian Biobank (EstBB) and the Norwegian Mother, Father, Child Cohort (MoBa), we jointly estimate the phenotypic variance attributable to these four effects unbiased of assortative mating (AM) for height, body mass index (BMI) and childhood educational test score (EA). For all three traits, direct effects make the largest contribution to the genetic effect variance.

Influenza and respiratory syncytial virus dynamics in Lao PDR during the COVID-19 pandemic: a hospital-based surveillance study.

Objectives: Globally, the circulation of influenza and other seasonal respiratory viruses changed dramatically during the COVID-19 pandemic. This study aims to determine the trends of acute respiratory infections (ARIs) caused by SARS-CoV-2, influenza A, influenza B and respiratory syncytial viruses (RSVs) in patients presenting to hospitals in the Lao People's Democratic Republic (PDR) (Laos).

Design: Prospective surveillance study.

Screening for visceral leishmaniasis in humans and animals in Laos.

Background: Visceral leishmaniasis (VL) is a vector-borne protozoan disease with a global distribution, with higher rates of infection associated with HIV. Zoonotic species of Leishmania have also been reported infecting domestic animals. Reports of VL are increasing in Southeast Asia, with over 200 cases reported in Thailand since the first autochthonous case in 1999, and recently the first patients have been reported from Vietnam and Cambodia.

Dissociative Photoionization of 2-Thiouracil and 4-Thiouracil: A Molecular Dynamics Study.

Thionated nucleobases have drawn considerable attention due to their role in medical treatment and biology, which triggered studies of their photophysics and photochemistry using various experimental and theoretical techniques. In particular, vacuum ultraviolet (VUV)-induced dissociative photoionization of 2-thiouracil (2-TU) has been recently studied using synchrotron radiation [Robinson et al., , 28, 2354].

Estimating scrub typhus and murine typhus incidence among adolescents and adults in Yangon, Myanmar.

Objectives: Rickettsioses are frequent causes of treatable febrile illness in Southeast Asia, including Myanmar. Accurate estimates of the incidence of rickettsioses are needed to inform investments in disease prevention and control. We sought to estimate the incidence of rickettsioses among adults and adolescents by combining sentinel hospital surveillance with a healthcare utilisation survey in Yangon, Myanmar.

Prevalence and risk factors for murine typhus, scrub typhus and spotted fever group rickettsioses among adolescent and adult patients presenting to Yangon General Hospital, Yangon, Myanmar.

Objectives: To inform patient management and disease prevention, we sought to estimate the prevalence of, and identify risk factors for, scrub typhus, murine typhus, and spotted fever group rickettsioses (SFGR) among febrile patients presenting to hospital in Myanmar.

Methods: We recruited patients ≥12 years old with fever ≥38°C among those seeking care at Yangon General Hospital from 5 October 2015 through 4 October 2016. Standardised clinical and risk factor assessments were conducted.

Open-science discovery of DNDI-6510, a compound that addresses genotoxic and metabolic liabilities of the COVID Moonshot SARS-CoV-2 Mpro lead inhibitor.

The 2020 SARS-CoV-2 coronavirus pandemic highlighted the urgent need for novel small molecule antiviral drugs. (S)- DNDI-6510 is a non-covalent SARS-CoV-2 main protease inhibitor developed by the open science collaboration COVID Moonshot. Here, we report on the metabolic and toxicologic optimization of the lead series previously disclosed by the COVID Moonshot Initiative, leading up to the selection of (S)- DNDI-6510 as the preclinical candidate.

Discovery of orally bioavailable Zika and West Nile Virus antiviral compounds targeting the NS2B-NS3 protease.

Flaviviruses are a class of pathogenic viruses with pandemic potential which are typically transmitted via infected arthropods. In particular, Zika virus is sexually transmissible and causes congenital malformations if infection occurs during pregnancy. Although over 1.

Aerobic and resistance exercise-regulated phosphoproteome and acetylproteome modifications in human skeletal muscle.

Despite indisputable benefits of different exercise modes, the molecular underpinnings of their divergent responses remain unclear. We investigate post-translational modifications in human skeletal muscle following 12 weeks of high-intensity aerobic interval or resistance exercise training. High-intensity aerobic training induces acetylproteome modifications including several mitochondrial proteins, indicating post-translational regulation of energetics machinery, whereas resistance exercise training regulates phosphoproteomic modifications of contractile/cytoskeletal machinery, consistent with greater strength.

Identification of Long-Term Care Facility Residence From Admission Notes Using Large Language Models.

Importance: An estimated half of all long-term care facility (LTCF) residents are colonized with antimicrobial-resistant organisms, and early identification of these patients on admission to acute care hospitals is a core strategy for preventing intrahospital spread. However, because LTCF exposure is not reliably captured in structured electronic health record data, LTCF-exposed patients routinely go undetected. Large language models (LLMs) offer a promising, but untested, opportunity for extracting this information from patient admission histories.

Wrangling Real-World Data: Optimizing Clinical Research Through Factor Selection with LASSO Regression.

Data-driven approaches to clinical research are necessary for understanding and effectively treating infectious diseases. However, challenges such as issues with data validity, lack of collaboration, and difficult-to-treat infectious diseases (e.g.

Direct Observation of the to Transition in 2-Thiouracil via Time-Resolved NEXAFS Spectroscopy.

The photophysics of nucleobases has been the subject of both theoretical and experimental studies over the past decades due to the challenges posed by resolving the steps of their radiationless relaxation dynamics, which cannot be described in the framework of the Born-Oppenheimer approximation (BOA). In this context, the ultrafast dynamics of 2-thiouracil has been investigated with a time-resolved NEXAFS study at the Free Electron Laser FLASH. Near Edge X-ray Absorption Fine Structure spectroscopy (NEXAFS) can be used to observe electronic transitions in ultrafast molecular relaxation.

Risk Factors for Health Care-Associated Bloodstream Infections in NICUs.

Importance: Neonates requiring intensive care are at high risk of health care-associated infections. In neonatal intensive care units (NICUs) in low-resource settings, the identification of modifiable risk factors can inform targeted prevention strategies to reduce the global burden of neonatal morbidity and mortality.

Objective: To describe the incidence of and the risk factors associated with health care-associated bloodstream infections (BSIs) in NICUs in Pune, India.

Effect of antecedent B-cell depletion therapy for patients hospitalized with COVID-19 within a single health system: a propensity score analysis.

B-cell depletion therapy is employed in a variety of clinical contexts from auto-immune diseases to malignancy. Prior research on patients with prior B-cell depletion treatment has suggested a mortality risk in patients hospitalized with COVID-19 however previous case-control studies have differed in their methods of patient comparison. Patients previously treated with B-cell-depletion hospitalized with COVID-19 were compared to matched controls in the Johns Hopkins Health System between March 1, 2020 and November 30, 2021.

Clinical patterns in a neuroimaging-based predictive model of self-reported dissociation.

Objective: Assessment of trauma-related dissociation has been historically challenging given its subjective nature and the lack of provider education around this topic. Recent work identified a promising neural biomarker of trauma-related dissociation, representing a significant step toward improved assessment and identification of dissociation. However, it is necessary to better understand clinical factors that may be associated with this biomarker.

Blood-based epigenome-wide association study and prediction of alcohol consumption.

Alcohol consumption is an important risk factor for multiple diseases. It is typically assessed via self-report, which is open to measurement error through recall bias. Instead, molecular data such as blood-based DNA methylation (DNAm) could be used to derive a more objective measure of alcohol consumption by incorporating information from cytosine-phosphate-guanine (CpG) sites known to be linked to the trait.

Leptospirosis, melioidosis, and rickettsioses in the vicious circle of neglect.

The global priorities in the field of infectious diseases are constantly changing. While emerging viral infections have regularly dominated public health attention, which has only intensified after the COVID-19 pandemic, numerous bacterial diseases have previously caused, and continue to cause, significant morbidity and mortality-deserving equal attention. Three potentially life-threatening endemic bacterial diseases (leptospirosis, melioidosis, and rickettsioses) are a huge public health concern especially in low- and middle-income countries.

DNA methylation-based predictors of metabolic traits in Scottish and Singaporean cohorts.

Exploring the molecular correlates of metabolic health measures may identify their shared and unique biological processes and pathways. Molecular proxies of these traits may also provide a more objective approach to their measurement. Here, DNA methylation (DNAm) data were used in epigenome-wide association studies (EWASs) and for training epigenetic scores (EpiScores) of six metabolic traits: body mass index (BMI), body fat percentage, waist-hip ratio, and blood-based measures of glucose, high-density lipoprotein cholesterol, and total cholesterol in >17,000 volunteers from the Generation Scotland (GS) cohort.

Hospital-Level Variation in COVID-19 Treatment Among Hospitalized Adults in the United States: A Retrospective Cohort Study.

Study Design: Retrospective cohort study.

Objective: To characterize variation in dexamethasone and remdesivir use over time among hospitals.

Background: Little is known about hospital-level variation in COVID-19 drug treatments in a large and diverse network in the United States.

Application of center for disease control and prevention standardized antimicrobial administration ratio to an Indian hospital.

Background: Rigorous antibiotic stewardship is advised by international societies to combat rising antibiotic resistance. A major component of these programs is the metric used for antibiotic consumption measurement. A method for standardized antimicrobial administration ratio (SAAR) is suggested by the Centre for Disease Control & Prevention-National Healthcare Safety Network (NHSN).

Pathogen genomic surveillance status among lower resource settings in Asia.

Asia remains vulnerable to new and emerging infectious diseases. Understanding how to improve next generation sequencing (NGS) use in pathogen surveillance is an urgent priority for regional health security. Here we developed a pathogen genomic surveillance assessment framework to assess capacity in low-resource settings in South and Southeast Asia.