Epigenetics and individuality: from concepts to causality across timescales.

Traditionally, differences among individuals have been divided into genetic and environmental causes. However, both types of variation can underlie regulatory changes in gene expression - that is, epigenetic changes - that persist across cell divisions (developmental differentiation) and even across generations (transgenerational inheritance). Increasingly, epigenetic variation among individuals is recognized as an important factor in human diseases and ageing.

Predictors of Cryptococcus gattii clinical presentation and outcome: An international study.

Background: Infection by Cryptococcus gattii can lead to pulmonary or central nervous system (CNS) disease, or both. Whether site of infection and disease severity are associated with C. gattii species and lineages or with certain underlying medical conditions, or both is unclear.

Disentangling Sources of Momentum Fluctuations in Xe+Xe and Pb+Pb Collisions with the ATLAS Detector.

High-energy nuclear collisions create a quark-gluon plasma, whose initial condition and subsequent expansion vary from event to event, impacting the distribution of the eventwise average transverse momentum [P([p_{T}])]. Disentangling the contributions from fluctuations in the nuclear overlap size (geometrical component) and other sources at a fixed size (intrinsic component) remains a challenge. This problem is addressed by measuring the mean, variance, and skewness of P([p_{T}]) in ^{208}Pb+^{208}Pb and ^{129}Xe+^{129}Xe collisions at sqrt[s_{NN}]=5.

Analysis of Time-to-Positivity Data in Tuberculosis Treatment Studies: Identifying a New Limit of Quantification.

Background: The BACTEC Mycobacteria Growth Indicator Tube (MGIT) machine is the standard globally for detecting viable mycobacteria in patients' sputum. Samples are observed for no longer than 42 days, at which point the sample is declared 'negative' for tuberculosis (TB). This time to detection of bacterial growth, referred to as time-to-positivity (TTP), is increasingly of interest, not solely as a diagnostic tool but also as a continuous biomarker wherein change in TTP can be used for comparing the bactericidal activity of different TB treatments.

Perceptual Expertise of Forensic Examiners and Reviewers on Tests of Cross-Race and Disguised Face Identification and Face Memory.

Forensic facial professionals have been shown in previous studies to identify people from frontal face images more accurately than untrained participants when given 30 s per face pair. We tested whether this superiority holds in more challenging conditions. Two groups of forensic facial professionals (examiners, reviewers) and untrained participants were tested in three lab-based tasks: other-race face identification, disguised face identification, and face memory.

C-reactive Protein-based Screening of People with Tuberculosis Symptoms: A Diagnostic Accuracy Study.

: C-reactive protein (CRP)-based tuberculosis (TB) screening is recommended for people with HIV (PWH). However, its performance among people without HIV and in diverse settings is unknown. : In a multi-country study, we aimed to determine whether CRP meets the minimum accuracy targets (sensitivity ≥90%, specificity ≥70%) for an effective TB screening test.

From invasion to outbreak: tick introductions and disease.

Introductions of tick disease vectors are inevitable in our changing world. While recent attention to tick invasions has increased following prominent invasion events worldwide, our understanding of how tick community ecology drives infection dynamics is lacking. Interactions between invasive and resident ticks can have profound impacts on human diseases.

Representativeness and adverse event reporting in late-phase clinical trials for rifampin-susceptible tuberculosis: a systematic review.

We did a systematic review and meta-analysis of trials of treatment for rifampicin-susceptible tuberculosis to evaluate the representativeness of participants compared with characteristics of the global population of people with tuberculosis, and the adequacy of adverse event reporting. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from Jan 1, 2000, to Dec 10, 2023, for trials that had greater than or equal to 50 participants per arm and had follow-up to at least treatment completion. Studies were excluded if they compared different formulations of standard drugs (eg, fixed-dose combination tablets); aimed to primarily enrol participants with isoniazid-resistant or rifampicin-resistant tuberculosis; evaluated treatment to prevent tuberculosis infection; tested dietary or vitamin supplementation; tested vaccines or other immune-based interventions; tested adherence support or system-related mechanisms; or enrolled participants with tuberculosis, but tuberculosis treatment itself was not randomised (ie, trials of the timing of antiretroviral therapy initiation).

Adverse Events Reported During Weekly Isoniazid-Rifapentine (3HP) Tuberculosis Preventive Treatment Among People With Human Immunodeficiency Virus in Uganda.

Background: Short-course tuberculosis (TB) prevention regimens, including 12 weeks of isoniazid and rifapentine (3HP), are increasingly used in high-TB-burden countries. Despite established safety and tolerability in efficacy trials, 3HP-related adverse events (AEs) could differ in routine settings. Real-world data on AE type, frequency, and timing are crucial for health systems considering 3HP programmatic scale-up.

Precise Lineage Tracking Using Molecular Barcodes Demonstrates Fitness Trade-offs for Ivermectin Resistance in Nematodes.

A fundamental tenet of evolutionary genetics is that the direction and strength of selection on individual loci varies with the environment. Barcoded evolutionary lineage tracking is a powerful approach for high-throughput measurement of selection within experimental evolution that to date has largely been restricted to studies within microbial systems, largely because the random integration of barcodes within animals is limited by physical and molecular protection of the germline. Here, we use the recently developed TARDIS barcoding system in (Stevenson et al.

Transcriptomic Sexual Conflict at Two Evolutionary Timescales Revealed by Experimental Evolution in Caenorhabditis elegans.

Sex-specific regulation of gene expression is the most plausible way for generating sexually differentiated phenotypes from an essentially shared genome. However, since genetic material is shared, sex-specific selection in one sex can have an indirect response in the other sex. From a gene expression perspective, this tethered response can move one sex away from their wild-type expression state and potentially impact many gene regulatory networks.

Self-reported history of childhood vision impairment among older adults screened for dementia.

We investigated the relationship between self-reported history of visual impairment in youth and the development of dementia in later life using data from the Panel Study of Income Dynamics (PSID) household survey, which included the Eight-item Informant Interview to Differentiate Aging and Dementia (AD-8) screen. Adults with a reported history of childhood visual impairment were found to have significantly higher odds of positive dementia screening. After adjusting for confounders, we found a twofold increase in those reporting early visual impairment compared with those who did not report early visual impairment.

Temporal concentrations of Quaternary ammonium compounds in wastewater treatment effluents during the COVID-19 pandemic, 2020-2021.

Quaternary ammonium compounds (QAC) are high production chemicals used in many commercial and household disinfection products. During the SARS-CoV-2 (COVID-19) pandemic, QACs were included on lists of COVID-19 disinfectants. Increased QAC use could lead to higher levels of QACs in wastewater treatment plant (WWTP) effluents, which could subsequently be released into the environment.

Using Real-World Data to Assess the Association of Retinal Detachment With Topical Pilocarpine Use.

Purpose: To examine the association between topical pilocarpine and the risk of new-onset rhegmatogenous retinal detachment (RRD).

Design: Retrospective clinical cohort study.

Methods: We used an aggregated electronic health records research network, TriNetX, to examine the risk of RRD (ICD-10: H33.

Search for the Exclusive W Boson Hadronic Decays W^{±}→π^{±}γ, W^{±}→K^{±}γ and W^{±}→ρ^{±}γ with the ATLAS Detector.

A search for the exclusive hadronic decays W^{±}→π^{±}γ, W^{±}→K^{±}γ, and W^{±}→ρ^{±}γ is performed using up to 140  fb^{-1} of proton-proton collisions recorded with the ATLAS detector at a center-of-mass energy of sqrt[s]=13  TeV. If observed, these rare processes would provide a unique test bench for the quantum chromodynamics factorization formalism used to calculate cross sections at colliders. Additionally, at future colliders, these decays could offer a new way to measure the W boson mass through fully reconstructed decay products.

Risk-stratified treatment for drug-susceptible pulmonary tuberculosis.

The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events.

Evaluating the implementation of weekly rifapentine-isoniazid (3HP) for tuberculosis prevention among people living with HIV in Uganda: A qualitative evaluation of the 3HP Options Trial.

Three months of isoniazid-rifapentine (3HP) is being scaled up for tuberculosis (TB) preventive treatment (TPT) among people living with HIV (PLHIV) in high-burden settings. More evidence is needed to identify factors influencing successful 3HP delivery. We conducted a qualitative assessment of 3HP delivery nested within the 3HP Options Trial, which compared three optimized strategies for delivering 3HP: facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), and patient choice between facilitated DOT and facilitated SAT at the Mulago HIV/AIDS clinic in Kampala, Uganda.

Advancing Patient Education in Idiopathic Intracranial Hypertension: The Promise of Large Language Models.

Background And Objectives: We evaluated the performance of 3 large language models (LLMs) in generating patient education materials (PEMs) and enhancing the readability of prewritten PEMs on idiopathic intracranial hypertension (IIH).

Methods: This cross-sectional comparative study compared 3 LLMs, ChatGPT-3.5, ChatGPT-4, and Google Bard, for their ability to generate PEMs on IIH using 3 prompts.

Evaluating the implementation of weekly rifapentine-isoniazid (3HP) for tuberculosis prevention among people living with HIV in Uganda: A qualitative evaluation of the 3HP Options Trial.

Three months of isoniazid-rifapentine (3HP) is being scaled up for tuberculosis (TB) preventive treatment (TPT) among people living with HIV (PLHIV) in high-burden settings. More evidence is needed to identify factors influencing successful 3HP delivery. We conducted a qualitative assessment of 3HP delivery nested within the 3HP Options Trial, which compared three optimized strategies for delivering 3HP: facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), and patient choice between facilitated DOT and facilitated SAT at the Mulago HIV/AIDS clinic in Kampala, Uganda.

Combination of Searches for Higgs Boson Pair Production in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

This Letter presents results from a combination of searches for Higgs boson pair production using 126-140  fb^{-1} of proton-proton collision data at sqrt[s]=13  TeV recorded with the ATLAS detector. At 95% confidence level (CL), the upper limit on the production rate is 2.9 times the standard model (SM) prediction, with an expected limit of 2.

Studies of the Energy Dependence of Diboson Polarization Fractions and the Radiation-Amplitude-Zero Effect in WZ Production with the ATLAS Detector.

This Letter presents the first study of the energy dependence of diboson polarization fractions in WZ→ℓνℓ^{'}ℓ^{'}(ℓ,ℓ^{'}=e,μ) production. The dataset used corresponds to an integrated luminosity of 140  fb^{-1} of proton-proton collisions at a center-of-mass energy of 13 TeV recorded by the ATLAS detector. Two fiducial regions with an enhanced presence of events featuring two longitudinally polarized bosons are defined.