Comprehensive evaluation of AlphaMissense predictions by evidence quantification for variants of uncertain significance.

Accurate variant classification is critical for genetic diagnosis. Variants without clear classification, known as "variants of uncertain significance" (VUS), pose a significant diagnostic challenge. This study examines AlphaMissense performance in variant classification, specifically for VUS.

Prequalification of genome-based newborn screening for severe childhood genetic diseases through federated training based on purifying hyperselection.

Genome-sequence-based newborn screening (gNBS) has substantial potential to improve outcomes in hundreds of severe childhood genetic disorders (SCGDs). However, a major impediment to gNBS is imprecision due to variants classified as pathogenic (P) or likely pathogenic (LP) that are not SCGD causal. gNBS with 53,855 P/LP variants, 342 genes, 412 SCGDs, and 1,603 therapies was positive in 74% of UK Biobank (UKB470K) adults, suggesting 97% false positives.

Model of superior semicircular canal dehiscence: asymmetrical vestibular dysfunction induces reversible balance impairment.

Background: Superior semicircular canal dehiscence (SSCD) is a vestibular-cochlear disorder in humans in which a pathological third mobile window of the otic capsule creates changes to the flow of sound pressure energy through the perilymph/endolymph. The primary symptoms include sound-induced dizziness/vertigo, inner ear conductive hearing loss, autophony, headaches, and visual problems. We have developed an animal model of this human condition in the Mongolian Gerbil that uses surgically created SSCD to induce the condition.

Physical Activity and the Health of a Nation: A National Challenge and Collective Response.

Historic recruitment and retention challenges confront the U.S. military.

A case report of superior vena cava/right coronary artery fistula secondary to chronic endocarditis.

Background: Coronary arteriovenous fistulas present an abnormal connection between the coronary arteries and an adjacent systemic or pulmonary vessel. They are rare, representing 0.002% of the general population.

Low indoleamine 2, 3 dioxygenase (IDO) activity is associated with psycho-obstetric risk.

Objectives: Preeclampsia and depression in pregnancy are among the most prevalent obstetric disorders with no known cures. While depression and preeclampsia each increase risk for the other, shared mechansisms are unclear. One possibility is low levels of Indoleamine 2,3 dioxygenase (IDO), which links immune dysregulation and oxidative arterial damage resulting in poor vascular function in both preeclampsia and depression.

TFAP2 paralogs regulate midfacial development in part through a conserved ALX genetic pathway.

Cranial neural crest development is governed by positional gene regulatory networks (GRNs). Fine-tuning of the GRN components underlies facial shape variation, yet how those networks in the midface are connected and activated remain poorly understood. Here, we show that concerted inactivation of Tfap2a and Tfap2b in the murine neural crest, even during the late migratory phase, results in a midfacial cleft and skeletal abnormalities.

MEMO1 Is Required for Ameloblast Maturation and Functional Enamel Formation.

Coordinated mineralization of soft tissue is central to organismal form and function, while dysregulated mineralization underlies several human pathologies. Oral epithelial-derived ameloblasts are polarized, secretory cells responsible for generating enamel, the most mineralized substance in the human body. Defects in ameloblast development result in enamel anomalies, including amelogenesis imperfecta.

TFAP2 paralogs regulate midfacial development in part through a conserved genetic pathway.

Cranial neural crest development is governed by positional gene regulatory networks (GRNs). Fine-tuning of the GRN components underly facial shape variation, yet how those in the midface are connected and activated remain poorly understood. Here, we show that concerted inactivation of and in the murine neural crest even during the late migratory phase results in a midfacial cleft and skeletal abnormalities.

Increased Prevalence of Overweight and Obesity and Incidence of Prediabetes and Type 2 Diabetes During the COVID-19 Pandemic, Active Component Service Members, U.S. Armed Forces, 2018 to 2021.

This study evaluated trends in the prevalence of overweight, obesity, and diabetes among active component service members between 2018 and 2021, before and after the start of the COVID-19 pandemic. This study also investigated the incidence of prediabetes and type 2 diabetes mellitus (T2DM) diagnoses during the same period. Between 2018 and 2021, the prevalence of obesity among active component service members who completed a Periodic Health Assessment (PHA) increased from 16.

Hospital Admission and Discharge: Lessons Learned from a Large Programme in Southwest Germany.

Introduction: In the context of a GP-based care programme, we implemented an admission, discharge and follow-up programme.

Description: The VESPEERA programme consists of three sets of components: pre-admission interventions, in-hospital interventions and post-discharge interventions. It was aimed at all patients with a hospital stay participating in the GP-based care programme and was implemented in 7 hospitals and 72 general practices in southwest Germany using a range of strategies.

Estimation of ENPP1 deficiency genetic prevalence using a comprehensive literature review and population databases.

Background: ENPP1 Deficiency-caused by biallelic variants in ENPP1-leads to widespread arterial calcification in early life (Generalized Arterial Calcification of Infancy, GACI) or hypophosphatemic rickets in later life (Autosomal Recessive Hypophosphatemic Rickets type 2, ARHR2). A prior study using the Exome Aggregation Consortium (ExAC)-a database of exomes obtained from approximately 60,000 individuals-estimated the genetic prevalence at approximately 1 in 200,000 pregnancies.

Methods: We estimated the genetic prevalence of ENPP1 Deficiency by evaluating allele frequencies from a population database, assuming Hardy-Weinberg equilibrium.

ENPP1 deficiency: A clinical update on the relevance of individual variants using a locus-specific patient database.

Loss-of-function variants in the ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1) cause ENPP1 Deficiency, a rare disorder characterized by pathological calcification, neointimal proliferation, and impaired bone mineralization. The consequence of ENPP1 Deficiency is a broad range of age dependent symptoms and morbidities including cardiovascular complications and 50% mortality in infants, autosomal recessive hypophosphatemic rickets type 2 (ARHR2) in children, and joint pain, osteomalacia and enthesopathies in adults. Recent research continues to add to the growing clinical presentation profile as well as expanding the role of ENPP1 itself.

Distribution of Pupil Size and Associated Factors: Results from the Population-Based Gutenberg Health Study.

Results: 18,335 eyes of 9,559 participants aged 40 to 80 years were included in the analysis. Median pupil diameter was 4.19 mm in right eyes and 4.

A genome sequencing system for universal newborn screening, diagnosis, and precision medicine for severe genetic diseases.

Newborn screening (NBS) dramatically improves outcomes in severe childhood disorders by treatment before symptom onset. In many genetic diseases, however, outcomes remain poor because NBS has lagged behind drug development. Rapid whole-genome sequencing (rWGS) is attractive for comprehensive NBS because it concomitantly examines almost all genetic diseases and is gaining acceptance for genetic disease diagnosis in ill newborns.

Novel PHEX gene locus-specific database: Comprehensive characterization of vast number of variants associated with X-linked hypophosphatemia (XLH).

X-linked hypophosphatemia (XLH), the most common form of hereditary hypophosphatemia, is caused by disrupting variants in the PHEX gene, located on the X chromosome. XLH is inherited in an X-linked pattern with complete penetrance observed for both males and females. Patients experience lifelong symptoms resulting from chronic hypophosphatemia, including impaired bone mineralization, skeletal deformities, growth retardation, and diminished quality of life.

Comparison of DMEK and DSAEK in Eyes With Endothelial Decompensation After Previous Penetrating Keratoplasty.

Purpose: Posterior lamellar keratoplasty is increasingly applied in patients with endothelial decompensation after penetrating keratoplasty (PK). The aim of this study was to compare the results of Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) after PK.

Methods: In this retrospective study, clinical data of 30 patients who received DMEK (n = 19) or DSAEK (n = 11) for endothelial decompensation after PK were evaluated.

Mastermind: A Comprehensive Genomic Association Search Engine for Empirical Evidence Curation and Genetic Variant Interpretation.

Design and interpretation of genome sequencing assays in clinical diagnostics and research labs is complicated by an inability to identify information from the medical literature and related databases quickly, comprehensively and reproducibly. This challenge is compounded by the complexity and heterogeneity of nomenclatures used to describe diseases, genes and genetic variants. Mastermind is a widely-used bioinformatic platform of genomic associations that has indexed more than 7.

Genome Sequence of the Fish Brain Bacterium Clostridium tarantellae.

was originally cultivated from the brain of fish affected by twirling movements. Here, we present the draft genome sequence of DSM 3997, which consists of 3,982,316 bp. Most protein-coding genes in this strain are similar to genes of bacteria, supporting the renaming of as .

Correction: Care management intervention to strengthen self-care of multimorbid patients with type 2 diabetes in a German primary care network: A randomized controlled trial.

[This corrects the article DOI: 10.1371/journal.pone.

Phenotypic and Genotypic Characterization of Causing Urinary Tract Infections in Kidney-Transplanted Patients.

Urinary tract infection (UTI), frequently caused by uropathogenic Escherichia coli (UPEC), is the most common infection after kidney transplantation (KTx). Untreated, it can lead to urosepsis and impairment of the graft function. We questioned whether the UPEC isolated from KTx patients differed from the UPEC of non-KTx patients.