Genome sequencing reveals the impact of pseudoexons in rare genetic disease.

Purpose: Advancements in sequencing technologies have significantly improved clinical genetic testing, yet the diagnostic yield remains around 30-40%. Emerging technologies are now being deployed to address the remaining diagnostic gap.

Methods: We tested whether short-read genome sequencing could increase the diagnostic yield in individuals enrolled into the UCI-GREGoR research study, who had suspected Mendelian conditions and prior inconclusive testing.

Toward Health Equity: A Workshop Report on the State of the Science of Obesity Interventions for Adults.

Objective: From October 18-20, 2022, the National Institutes of Health held a workshop to examine the state of the science concerning obesity interventions in adults to promote health equity. The workshop had three objectives: (1) Convene experts from key institutions and the community to identify gaps in knowledge and opportunities to address obesity, (2) generate recommendations for obesity prevention and treatment to achieve health equity, and (3) identify challenges and needs to address obesity prevalence and disparities, and develop a diverse workforce.

Methods: A three-day virtual convening.

Age-related amyloid beta dynamics modeled with the generalized additive model for location, scale, and shape (GAMLSS) across diverse populations: Cross-sectional trajectories and longitudinal validation.

Introduction: We developed and validated age-related amyloid beta (Aβ) positron emission tomography (PET) trajectories using a statistical model in cognitively unimpaired (CU) individuals.

Methods: We analyzed 849 CU Korean and 521 CU non-Hispanic White (NHW) participants after propensity score matching. Aβ PET trajectories were modeled using the generalized additive model for location, scale, and shape (GAMLSS) based on baseline data and validated with longitudinal data.

Maximizing theoretical and practical storage capacity in single-layer feedforward neural networks.

Artificial neural networks are limited in the number of patterns that they can store and accurately recall, with capacity constraints arising from factors such as network size, architectural structure, pattern sparsity, and pattern dissimilarity. Exceeding these limits leads to recall errors, eventually leading to catastrophic forgetting, which is a major challenge in continual learning. In this study, we characterize the theoretical maximum memory capacity of single-layer feedforward networks as a function of these parameters.

The Case for Limiting "Sequences of Concern" to Those with Demonstrated Pathogenic Function.

Screening synthetic nucleic acid orders for sequences of concern is a necessary part of a healthy biosecurity regime, but it exacts costs for nucleic acid providers. Taxonomy is and will remain a critical part of the decision-making process for screening, especially for viral sequences. But, moving forward, the function of a sequence will also be determinative of its level of concern, or lack thereof.

Retinal progenitor cells (jCell) for retinitis pigmentosa.

Objective: To assess the safety and tolerability of intravitreal injection of human retinal progenitor cells (RPCs) at multiple dose levels in adults with non-syndromic retinitis pigmentosa (RP).

Design: A prospective, multicenter, open-label, single-arm, Phase I/IIa safety study of RPCs in adults with RP ( = 28). Two patient cohorts were studied: Cohort 1: BCVA no better than 20/200 and no worse than Hand Motions, and Cohort 2: BCVA no better than 20/40 and no worse than 20/200).

Improving Communication and Management Following a Positive Home HPV Self-Sampling Result: Comparing Intervention Strategies Between the HOME and STEP Trials.

Background: Mailed human papillomavirus (HPV) self-sampling kits improve cervical cancer screening adherence. The HOME trial found information needs and anxiety among HPV-positive patients. We designed a STEP trial to test optimized intervention strategies with bolstered educational materials and a centralized nurse communicating positive results.

Open-source models for development of data and metadata standards.

Machine learning and artificial intelligence promise to accelerate research and understanding across many scientific disciplines. Harnessing the power of these techniques requires aggregating scientific data. In tandem, the importance of open data for reproducibility and scientific transparency is gaining recognition, and data are increasingly available through digital repositories.

A view of the sustainable computing landscape.

This article presents a holistic research agenda to address the significant environmental impact of information and communication technology (ICT), which accounts for 2.1%-3.9% of global greenhouse gas emissions.

Single-Cell and Plasma Proteomics Do Not Differentiate Patients With and Without SARS-CoV-2 Antigenemia in Convalescence in a Cohort of 100 Patients.

Plasma samples obtained approximately 3 ( = 100) and 12 months ( = 78) after acute SARS-CoV-2 infection were tested for S1, spike, and N antigens. There were no significant differences in plasma proteins or single-cell protein expression levels on immune cells between those with and without plasma antigen detected.

Systematic review of prospective hazard analysis in radiation therapy.

Introduction: Prospective hazard analysis (PHA) was introduced to the wider medical physics community by the initiation of American association of physicists in medicine task group 100 in 2003. Since then, there has been increasing interest in the applicability of PHA to radiotherapy for the purpose of keeping patients safe and assessing the risks within the whole practice of radiotherapy. The purpose of this research was to review the PHA literature focusing on which techniques and technologies have been assessed, how they have been assessed, and what can be learnt.

Soil Carbon Availability Drives Depth-Dependent Responses of Microbial Nitrogen Use Efficiency to Warming.

Microbial nitrogen use efficiency (NUE) describes the partitioning of organic N between microbial growth and N mineralization, which is crucial for assessing soil N retention. However, how warming affects NUE along soil depth remains unclear. Based on a whole-soil-profile warming experiment (0 to 100 cm, +4°C) on the Qinghai-Tibetan Plateau, combined with O and N isotope labeling techniques, we determined soil carbon (C) composition, edaphic properties, and microbial parameters.

The systematic assessment of completeness of public metadata accompanying omics studies in the Gene Expression Omnibus data repository.

Background: Recent advances in high-throughput sequencing technologies have enabled the collection and sharing of a massive amount of omics data, along with its associated metadata-descriptive information that contextualizes the data, including phenotypic traits and experimental design. Enhancing metadata availability is critical to ensure data reusability and reproducibility and to facilitate novel biomedical discoveries through effective data reuse. Yet, incomplete metadata accompanying public omics data may hinder reproducibility and reusability and limit secondary analyses.

Structure, function and assembly of nuclear pore complexes.

The defining property of eukaryotic cells is the storage of heritable genetic material in a nuclear compartment. For eukaryotic cells to carry out the myriad biochemical processes necessary for their function, macromolecules must be efficiently exchanged between the nucleus and cytoplasm. The nuclear pore complex (NPC) - which is a massive assembly of ~35 different proteins present in multiple copies totalling ~1,000 protein subunits and architecturally conserved across eukaryotes - establishes a size-selective channel for regulated bidirectional transport of folded macromolecules and macromolecular assemblies across the nuclear envelope.

Durotaxis is a driver and potential therapeutic target in lung fibrosis and metastatic pancreatic cancer.

Durotaxis, cell migration along stiffness gradients, is linked to embryonic development, tissue repair and disease. Despite solid in vitro evidence, its role in vivo remains largely speculative. Here we demonstrate that durotaxis actively drives disease progression in vivo in mouse models of lung fibrosis and metastatic pancreatic cancer.

Using American Sign Language-Fluent Community Health Navigators to Advance Cancer Screening Adherence through Videoconferencing With Deaf, Deafblind, and Hard of Hearing Adults: Protocol for a Randomized Controlled Trial.

Background: Cancer screening nonadherence persists among adults who are deaf, deafblind, and hard of hearing (DDBHH). These barriers span individual, clinician, and health care system levels, contributing to difficulties understanding cancer information, accessing screening services, and following treatment directives. Critical communication barriers include ineffective patient-physician communication, limited access to American Sign Language (ASL) cancer information, misconceptions about medical procedures, insurance navigation difficulties, and intersectional barriers for multiply marginalized individuals.

"Just Being Connected, It's Like a Way of Resisting": Latinx Youth Strengthening Cultural Ties as Resilience and Resistance in the Deep South.

Over the last decade, a range of research has demonstrated the detrimental impacts of policies criminalizing migration ("crimmigration") on Latinx mental health. In this study, we seek to examine youth perspectives on how crimmigration policies affect Latinx adolescents' connections to Latinx identity, culture, and communities and the implications for Latinx youth mental health. We explored how immigration enforcement policies affect Latinx youths' mental health using photovoice with ten youth in a high-deportation county in Atlanta in 2022.

Adherence thresholds for emtricitabine-tenofovir disoproxil fumarate preexposure prophylaxis against HIV acquisition in cisgender women: A randomized directly observed dosing study.

Background: Oral emtricitabine/tenofovir disoproxil fumarate (F/TDF) preexposure prophylaxis (PrEP) effectiveness against HIV acquisition highly depends on adherence. For men who have sex with men, a dosing study in the United States (US) population defined clinically meaningful tenofovir diphosphate (TFV-DP) thresholds in dried blood spots (DBS) based on the rounded 25th percentile for 2, 4, and 7 doses/week as 350, 700, and 1,250 fmol/punch. However, divergent efficacy results in the first generation randomized clinical trials of F/TDF PrEP among African women led to several hypotheses to question whether the pharmacology and adherence requirement for oral F/TDF PrEP may be different in cisgender women compared to what is already established for men.

The effects of brines relevant to Mars and the ocean worlds on bacterial growth reflect salt-specific responses across water activity.

Freezing point depression due to high salt concentration is crucial for liquid water to exist on cold worlds, expanding special regions where habitats are plausible. Determination of the growth tolerances of terrestrial microbes in analog systems impacts planetary protection protocols aimed at preventing interference with life detection missions or potential native ecosystems on celestial bodies. We measured the salinity tolerances of 18 salinotolerant bacteria (Bacillus, Halomonas, Marinococcus, Nesterenkonia, Planococcus, Salibacillus, and Terribacillus).

Enhanced Versus Standard Dermatologic Management With Amivantamab-Lazertinib in EGFR-Mutated Advanced NSCLC: The COCOON Global Randomized Controlled Trial.

Introduction: Amivantamab plus lazertinib significantly improved progression-free and overall survival versus osimertinib in patients with previously untreated, EGFR-mutant advanced NSCLC. EGFR-targeted therapies are associated with dermatologic adverse events (AEs), which can affect quality of life (QoL). COCOON was conducted to assess prophylactic management and improve treatment experience.

Deep Learning Estimation of 24-2 Visual Field Map from Optic Nerve Head Optical Coherence Tomography Angiography.

Precis: Artificial intelligence applied to OCTA images demonstrated high accuracy in estimating 24-2 visual field maps by leveraging information from pararpapillary area.

Purpose: To develop deep learning (DL) models estimating 24-2 visual field (VF) maps from optical coherence tomography angiography (OCTA) optic nerve head (ONH) en face images.

Methods: A total of 3148 VF OCTA pairs were collected from 994 participants (1684 eyes).

Bayesian estimation of HIV acquisition dates for prevention trials.

Accurate timing estimates of when participants acquire HIV in HIV prevention trials are necessary for determining antibody levels at acquisition. The Antibody-Mediated Prevention (AMP) Studies showed that a passively administered broadly neutralizing antibody can prevent the acquisition of HIV from a neutralization-sensitive virus. We developed a pipeline for estimating the date of detectable HIV acquisition (DDA) in AMP Study participants using diagnostic and viral sequence data.

Migratory Strategy is a Key Factor Driving Interactions at Wind Energy Facilities in At-Risk North American Bats.

Animal migration remains poorly understood for many organisms, impeding understanding of movement dynamics and limiting conservation actions. We develop a framework that scales from movements of individuals to the dynamics of continental migration using data synthesis of endogenous markers, which we apply to three North American bat species with unexplained high rates of fatalities at wind energy facilities. The two species experiencing the highest fatality rates exhibit a "pell-mell" migration strategy in which individuals move from summer habitats in multiple directions, both to higher and lower latitudes, during autumn.

A bibliometric analysis of the study of health equity of migrants.

Background: Research on migrants has grown significantly over the past 20 years. However, systematic reviews and summaries of the health equity of migrants are lacking.

Objective: This bibliometric analysis aims to reveal the knowledge structure, cooperation networks, and research frontiers in immigrant health equity for the first time, providing a framework and guidance for future studies.