A genome-first approach to characterize DICER1 pathogenic variant prevalence, penetrance and cancer, thyroid, and other phenotypes in 2 population-scale cohorts.

Purpose: Population-scale, exome-sequenced cohorts with linked electronic health records (EHR) permit genome-first exploration of phenotype. Phenotype and cancer risk are well-characterized in children with a pathogenic (HGNC ID:17098) variant. Here, the prevalence, penetrance and phenotype of pathogenic germline variants in adults was investigated in two population-scale cohorts.

Impact of a new state law and electronic health record prompt on naloxone prescribing in an academic medical center.

Purpose: To evaluate the impact of a best-practice advisory (BPA) and South Carolina legislation on naloxone prescribing patterns. The primary objective was to assess the change in naloxone prescription rates following BPA implementation. The secondary objective was to analyze the performance of the BPA.

High-Resolution Depth-Discrete Analysis of PFAS Distribution and Leaching for a Vadose-Zone Source at an AFFF-Impacted Site.

The long-term leaching of polyfluoroalkyl substances (PFAS) within the vadose zone of an AFFF application site for which the depth to groundwater is approximately 100 m was investigated by characterizing the vertical distribution of PFAS in a high spatial resolution. The great majority (99%) of PFAS mass resides in the upper 3 m of the vadose zone. The depths to which each PFAS migrated, quantified by moment analysis, is an inverse function of molar volume, demonstrating chromatographic separation.

Delivering a sleep intervention across a youth mental health service using non-expert practitioners: A service evaluation.

Aims: Poor sleep is highly prevalent in young people and increases risk of mental health difficulties, yet access to sleep interventions remains limited. This paper evaluates the use of a sleep intervention delivered by non-expert practitioners in a secondary care youth mental health service.

Method: Assistant psychologists were trained to deliver a six-session 1:1 cognitive-behavioural sleep intervention adapted for use with young people with mental health difficulties.

Proposed Diagnostic Reference Levels in the Missouri/Southern Illinois Region Associated with Cone-beam Computed Tomography Use in Endodontics.

Introduction: Diagnostic reference levels (DRLs) are intended to improve patient safety and ensure that patient ionizing radiation doses are as low as reasonably achievable. The purpose of this dosimetry study was to establish regional DRL levels for cone-beam computed tomography (CBCT) imaging for specialty endodontics. Another aim was to compare phantom-measured ionizing radiation dose index 1 (DI1) index doses to the manufacturer-provided dose area product (DAP) radiation output values for each of the CBCT machines studied, to ascertain their degree of correlation.

How are cell and tissue structure and function influenced by gravity and what are the gravity perception mechanisms?

Progress in mechanobiology allowed us to better understand the important role of mechanical forces in the regulation of biological processes. Space research in the field of life sciences clearly showed that gravity plays a crucial role in biological processes. The space environment offers the unique opportunity to carry out experiments without gravity, helping us not only to understand the effects of gravitational alterations on biological systems but also the mechanisms underlying mechanoperception and cell/tissue response to mechanical and gravitational stresses.

Specifications of the ACMG/AMP Variant Classification Guidelines for Germline Variant Curation.

Germline pathogenic variants in predispose individuals to develop a variety of benign and malignant tumors. Accurate variant curation and classification is essential for reliable diagnosis of -related tumor predisposition and identification of individuals who may benefit from surveillance. Since 2015, most labs have followed the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) sequence variant classification guidelines for germline variant curation.

Intronic Germline Variants in Patients With Sertoli-Leydig Cell Tumor.

Germline pathogenic loss-of-function (pLOF) variants in are associated with a predisposition for a variety of solid neoplasms, including pleuropulmonary blastoma and Sertoli-Leydig cell tumor (SLCT). The most common pLOF variants include small insertions or deletions leading to frameshifts, and base substitutions leading to nonsense codons or altered splice sites. Larger deletions and pathogenic missense variants occur less frequently.

Genome-first approach of the prevalence and cancer phenotypes of pathogenic or likely pathogenic germline TP53 variants.

Pathogenic or likely pathogenic (P/LP) germline TP53 variants are the primary cause of Li-Fraumeni syndrome (LFS), a hereditary cancer predisposition disorder characterized by early-onset cancers. The population prevalence of P/LP germline TP53 variants is estimated to be approximately one in every 3,500 to 20,000 individuals. However, these estimates are likely impacted by ascertainment biases and lack of clinical and genetic data to account for potential confounding factors, such as clonal hematopoiesis.

Spectrum and Excess Risk of Gastrointestinal Tumors in Li-Fraumeni Syndrome.

Li-Fraumeni syndrome (LFS), linked to heterozygous germline pathogenic/likely pathogenic variants in TP53, confers exceptionally high cancer risk, including core cancers (sarcoma, breast, adrenocortical, and brain cancer) among many other cancer types. Colorectal cancer (CRC) is most common after the core and hematologic cancers, accounting for ∼2.8% of diagnoses.

Deductive automated pollen classification in environmental samples via exploratory deep learning and imaging flow cytometry.

Pollen and tracheophyte spores are ubiquitous environmental indicators at local and global scales. Palynology is typically performed manually by microscopic analysis; a specialised and time-consuming task limited in taxonomical precision and sampling frequency, therefore restricting data quality used to inform climate change and pollen forecasting models. We build on the growing work using AI (artificial intelligence) for automated pollen classification to design a flexible network that can deal with the uncertainty of broad-scale environmental applications.

Estimated Prevalence, Tumor Spectrum, and Neurofibromatosis Type 1-Like Phenotype of CDKN2A-Related Melanoma-Astrocytoma Syndrome.

Importance: Knowledge about the prevalence and tumor types of CDKN2A-related melanoma-astrocytoma syndrome (MAS) is limited and could improve disease recognition.

Objective: To estimate the prevalence and describe the tumor types of MAS.

Design, Setting, And Participants: This retrospective cohort study analyzed all available MAS cases from medical centers in the US (2 sites) and Europe (2 sites) and from biomedical population genomic databases (UK Biobank [United Kingdom], Geisinger MyCode [US]) between January 1, 1976, and December 31, 2020.

Predicting dry matter intake in beef cattle.

Technology that facilitates estimations of individual animal dry matter intake (DMI) rates in group-housed settings will improve production and management efficiencies. Estimating DMI in pasture settings or facilities where feed intake cannot be monitored may benefit from predictive algorithms that use other variables as proxies. This study examined the relationships between DMI, animal performance, and environmental variables.

Impact of Transcript (p16/p14ARF) Alteration on Cancer Risk in CDKN2A Germline Pathogenic Variant Carriers.

Background: Few studies have evaluated the relationship between CDKN2A germline pathogenic variants (GPV), transcript (p16/p14ARF) alteration, and cancer risk.

Methods: Standardized incidence ratios (SIRs) comparing cancer risk with the general population were calculated for 385 CDKN2A GPV carriers from 2 large cohorts (259 United States and 126 Swedish individuals) using Poisson regression; statistical significance was defined as P less than .002 (Bonferroni correction).

Moving nursing innovation to prime time through the use of creative partnerships.

Nurses are well-positioned to solve many problems in healthcare through engagement in innovation. Support from healthcare organizations to facilitate creative partnerships may accelerate nurses' ability to innovate and improve job satisfaction. The value of creative partnerships is rooted in the diversity of experiences and skillsets of each project team member.

The Kaiser Permanente Northern California Advance Alert Monitor Program: An Automated Early Warning System for Adults at Risk for In-Hospital Clinical Deterioration.

Background: In-hospital deterioration among ward patients is associated with substantially increased adverse outcome rates. In 2013 Kaiser Permanente Northern California (KPNC) developed and implemented a predictive analytics-driven program, Advance Alert Monitor (AAM), to improve early detection and intervention for in-hospital deterioration. The AAM predictive model is designed to give clinicians 12 hours of lead time before clinical deterioration, permitting early detection and a patient goals-concordant response to prevent worsening.

New complementary perspectives for inpatient physical function assessment: matched clinician-report and patient-report short form measures from the PROMIS adult physical function item bank.

Purpose: To develop two item content-matched, precise, score-level targeted inpatient physical function (PF) short form (SF) measures: one clinician-reported, one patient-reported. Items were derived from PROMIS PF bank content; scores are reported on the PROMIS PF T-score metric.

Methods: The PROMIS PF item bank was reviewed for content measuring lower-level PF status (T-scores 10-50) with high item set score-level reliability (≥ 0.