Development of a framework to structure decision-making in environmental and occupational health: A systematic review and Delphi study.

Background: Environmental and occupational health (EOH) assessments increasingly utilize systematic review methods and structured frameworks for evaluating evidence about the human health effects of exposures. However, there is no prevailing approach for how to integrate this evidence into decisions or recommendations. Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence-to-decision (EtD) frameworks provide a structure to support standardized and transparent consideration of relevant criteria to inform health decisions.

Spiritual Well-Being in Appalachian Family Caregivers.

Introduction: Dementia and heart failure (HF) are the most common co-existing end-of-life conditions among rural older adults requiring extensive caregiving. Studies conducted in Appalachia have found that caregivers report a lack of information about palliative care and managing complex care at home. They also indicate the need for spiritual support.

Mutational signature analyses in multi-child families reveal sources of age-related increases in human germline mutations.

Whole-genome sequencing studies of parent-offspring trios have provided valuable insights into the potential impact of de novo mutations (DNMs) on human health and disease. However, the molecular mechanisms that drive DNMs are unclear. Studies with multi-child families can provide important insight into the causes of inter-family variability in DNM rates but they are highly limited.

Bi- and Monoallelic Variants and Chronic Kidney Disease in West Africans.

Background: Apolipoprotein L1 gene () variants are risk factors for chronic kidney disease (CKD) among Black Americans. Data are sparse on the genetic epidemiology of CKD and the clinical association of variants with CKD in West Africans, a major group in the Black population.

Methods: We conducted a case-control study involving participants from Ghana and Nigeria who had CKD stages 2 through 5, biopsy-proven glomerular disease, or no kidney disease.

Holy grail or convenient excuse? Stakeholder perspectives on the role of health system strengthening evaluation in global health resource allocation.

Background: The role of evaluation evidence in guiding health systems strengthening (HSS) investments at the global-level remains contested. A lack of rigorous impact evaluations is viewed by some as an obstacle to scaling resources. However, others suggest that power dynamics and knowledge hierarchies continue to shape perceptions of rigor and acceptability in HSS evaluations.

Identifying, quantifying, and mitigating background with the time-resolved x-ray diffraction platform at the National Ignition Facility.

The time-resolved x-ray diffraction platform at the National Ignition Facility (NIF) fields electronic sensors closer to the exploding laser-driven target than any other NIF diagnostic in order to directly detect diffracted x rays from highly compressed materials. We document strategies to characterize and mitigate the unacceptably high background signals observed in this geometry. We specifically assess the possible effects of electromagnetic pulse, x-ray fluorescence, hot electrons, and sensor-specific non-x-ray artifacts.

Modifying x-ray streak cameras for operation on igniting fusion experiments.

The National Ignition Facility produced the first nuclear fusion experiment demonstrating net positive energy gain on December 5, 2022. The x-ray streak camera that measures the bang time and burn-width from this landmark experiment had an electronic failure and did not record data. The CCD sensor was replaced with a radiation hardened CMOS sensor that has since demonstrated successful operation on repeat ignition shots.

Time resolved x-ray diffraction using the flexible imaging diffraction diagnostic for laser experiments (FIDDLE) at the National Ignition Facility (NIF): Preliminary assessment of diffraction precision.

The Flexible Imaging Diffraction Diagnostic for Laser Experiments (FIDDLE) is a new diagnostic at the National Ignition Facility (NIF) designed to observe in situ solid-solid phase changes at high pressures using time resolved x-ray diffraction. FIDDLE currently incorporates five Icarus ultrafast x-ray imager sensors that take 2 ns snapshots and can be tuned to collect X-rays for tens of ns. The platform utilizes the laser power at NIF for both the laser drive and the generation of 10 keV X-rays for ∼10 ns using a Ge backlighter foil.

Developing time-resolved x-ray diffraction diagnostics at the National Ignition Facility (invited).

As part of a program to measure phase transition timescales in materials under dynamic compression, we have designed new x-ray imaging diagnostics to record multiple x-ray diffraction measurements during a single laser-driven experiment. Our design places several ns-gated hybrid CMOS (hCMOS) sensors within a few cm of a laser-driven target. The sensors must be protected from an extremely harsh environment, including debris, electromagnetic pulses, and unconverted laser light.

Robust genome and cell engineering via in vitro and in situ circularized RNAs.

Circularization can improve RNA persistence, yet simple and scalable approaches to achieve this are lacking. Here we report two methods that facilitate the pursuit of circular RNAs (cRNAs): cRNAs developed via in vitro circularization using group II introns, and cRNAs developed via in-cell circularization by the ubiquitously expressed RtcB protein. We also report simple purification protocols that enable high cRNA yields (40-75%) while maintaining low immune responses.

Building a Client Resource and Communication Platform for Community-Based Organizations to Address Health and Social Needs: Co-Design Study.

Background: Connecting individuals to existing community resources is critical to addressing social needs and improving population health. While there is much ongoing informatics work embedding social needs screening and referrals into health care systems and their electronic health records, there has been less focus on the digital ecosystem and needs of community-based organizations (CBOs) providing or connecting individuals to these resources.

Objective: We used human-centered design to develop a digital platform for CBOs, focused on identification of health and social resources and communication with their clients.

A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes.

Association of with Coronary Artery Calcium Differs by Sex and Cigarette Smoking.

Coronary artery calcium (CAC) is a marker of subclinical atherosclerosis and is a complex heritable trait with both genetic and environmental risk factors, including sex and smoking. We performed genome-wide association (GWA) analyses for CAC among all participants and stratified by sex in the COPDGene study ( = 6144 participants of European ancestry and = 2589 participants of African ancestry) with replication in the Diabetes Heart Study (DHS). We adjusted for age, sex, current smoking status, BMI, diabetes, self-reported high blood pressure, self-reported high cholesterol, and genetic ancestry (as summarized by principal components computed within each racial group).

The prevalence of gestational diabetes among underweight and normal weight women worldwide: a scoping review.

Background: Gestational diabetes (GDM) affects nearly 15% of pregnancies worldwide and is increasing globally. While this growth is thought to be primarily from overweight and obesity, normal and underweight women are affected as well, particularly in low and middle-income countries. However, GDM in non-overweight women remains understudied.

Electrical design of the flexible imaging diffraction diagnostic for laser experiments (FIDDLE) at the National Ignition Facility (NIF)-Requirements, design, and performance.

The Flexible Imaging Diffraction Diagnostic for Laser Experiments (FIDDLE) is a newly developed diagnostic for imaging time resolved diffraction in experiments at the National Ignition Facility (NIF). It builds on the successes of its predecessor, the Gated Diffraction Development Diagnostic (G3D). The FIDDLE was designed to support eight Daedalus version 2 sensors (six more hCMOS sensors than any other hCMOS-based diagnostic in NIF to date) and an integrated streak camera.

Fragment-Based Discovery of a Series of Allosteric-Binding Site Modulators of β-Glucocerebrosidase.

β-Glucocerebrosidase (GBA/GCase) mutations leading to misfolded protein cause Gaucher's disease and are a major genetic risk factor for Parkinson's disease and dementia with Lewy bodies. The identification of small molecule pharmacological chaperones that can stabilize the misfolded protein and increase delivery of degradation-prone mutant GCase to the lysosome is a strategy under active investigation. Here, we describe the first use of fragment-based drug discovery (FBDD) to identify pharmacological chaperones of GCase.

Integrated multi-omic analyses uncover the effects of aging on cell-type regulation in glucose-responsive tissues.

Aging significantly influences cellular activity and metabolism in glucose-responsive tissues, yet a comprehensive evaluation of the impacts of aging and associated cell-type responses has been lacking. This study integrates transcriptomic, methylomic, single-cell RNA sequencing, and metabolomic data to investigate aging-related regulations in adipose and muscle tissues. Through coexpression network analysis of the adipose tissue, we identified aging-associated network modules specific to certain cell types, including adipocytes and immune cells.

Structural and Interactional Analysis of the Flavonoid Pathway Proteins: Chalcone Synthase, Chalcone Isomerase and Chalcone Isomerase-like Protein.

Chalcone synthase (CHS) and chalcone isomerase (CHI) catalyze the first two committed steps of the flavonoid pathway that plays a pivotal role in the growth and reproduction of land plants, including UV protection, pigmentation, symbiotic nitrogen fixation, and pathogen resistance. Based on the obtained X-ray crystal structures of CHS, CHI, and chalcone isomerase-like protein (CHIL) from the same monocotyledon, , along with the results of the steady-state kinetics, spectroscopic/thermodynamic analyses, intermolecular interactions, and their effect on each catalytic step are proposed. In addition, PvCHI's unique activity for both naringenin chalcone and isoliquiritigenin was analyzed, and the observed hierarchical activity for those type-I and -II substrates was explained with the intrinsic characteristics of the enzyme and two substrates.

Mechanisms of actin filament severing and elongation by formins.

Humans express 15 formins that play crucial roles in actin-based processes, including cytokinesis, cell motility and mechanotransduction. However, the lack of structures bound to the actin filament (F-actin) has been a major impediment to understanding formin function. Whereas formins are known for their ability to nucleate and elongate F-actin, some formins can additionally depolymerize, sever or bundle F-actin.

Evaluation of deep-learning TSE images in clinical musculoskeletal imaging.

In this study, we compared the fat-saturated (FS) and non-FS turbo spin echo (TSE) magnetic resonance imaging knee sequences reconstructed conventionally (conventional-TSE) against a deep learning-based reconstruction of accelerated TSE (DL-TSE) scans. A total of 232 conventional-TSE and DL-TSE image pairs were acquired for comparison. For each consenting patient, one of the clinically acquired conventional-TSE proton density-weighted sequences in the sagittal or coronal planes (FS and non-FS), or in the axial plane (non-FS), was repeated using a research DL-TSE sequence.