Newborn screening for common genetic variants associated with permanent hearing loss: Implementation in Ontario and a review of the first 3 years.

Purpose: Universal newborn hearing screening (UNHS) programs using audiometric techniques alone are limited in ability to detect non-congenital childhood permanent hearing loss (PHL). In 2019, Ontario launched universal newborn screening (NBS) for PHL risk factors: congenital cytomegalovirus (cCMV) and 22 common variants in GJB2 and SLC26A4. Here we describe our experience with genetic risk factor screening.

Synthesis, HS releasing properties, antiviral and antioxidant activities and acute cardiac effects of nucleoside 5'-dithioacetates.

Hydrogen sulfide (HS) is an endogenous gasotransmitter with cardioprotective and antiviral effects. In this work, new cysteine-selective nucleoside-HS-donor hybrid molecules were prepared by conjugating nucleoside biomolecules with a thiol-activatable dithioacetyl group. 5'-Dithioacetate derivatives were synthesized from the canonical nucleosides (uridine, adenosine, cytidine, guanosine and thymidine), and the putative 5'-thio metabolites were also produced from uridine and adenosine.

Patient-derived xenografts from circulating cancer stem cells as a preclinical model for personalized pancreatic cancer research.

Patient-derived xenografts (PDXs) provide biologically relevant models and potential platforms for the development of treatment strategies for precision medicine in pancreatic cancer. Furthermore, circulating epithelial tumor cells (CETCs/CTCs) are released into the bloodstream by solid tumors and a rare subpopulation-circulating cancer stem cells (cCSCs) - is considered to be responsible for recurrence and plays a key role in metastasis. For the identification of cCSCs, an innovative in vitro assay to generate tumorspheres was established in this study.

WHO guidelines on waist circumference and physical activity and their joint association with cancer risk.

Objective: Low body fat and high physical activity levels are key lifestyle factors in cancer prevention, but the interplay of abdominal obesity and physical activity on cancer risk remains unknown. We explored individual and joint associations of waist circumference and physical activity with cancer risk.

Methods: Using UK Biobank data (n=315 457), we categorised individuals according to WHO guideline thresholds for waist circumference and self-reported physical activity levels.

Healthy Aging and the Gut Microbiome in People With and Without HIV.

Background: Aging-related comorbidities are more common in people with human immunodeficiency virus (HIV) compared to people without HIV. The gut microbiome may play a role in healthy aging; however, this relationship remains unexplored in the context of HIV.

Methods: 16S rRNA gene sequencing was conducted on stool from 1409 women (69% with HIV; 2304 samples) and 990 men (54% with HIV; 1008 samples) in the MACS/WIHS Combined Cohort Study.

Aprocitentan for Blood Pressure Reduction in Black Patients.

Background: Black individuals frequently present with resistant hypertension and disproportionately increased cardiovascular risk. We investigated the blood pressure (BP)-lowering effect of the dual endothelin receptor antagonist aprocitentan in Black individuals enrolled in the PRECISION study (Parallel-Group, Phase 3 Study with Aprocitentan in Subjects with Resistant Hypertension).

Methods: Patients with confirmed resistant hypertension were randomized to aprocitentan 12.

Recommendations for reporting and evaluating proton therapy beyond dose and constant relative biological effectiveness.

Background And Purpose: In proton therapy, a relative biological effectiveness (RBE) of 1.1 is used to convert proton dose into an equivalent photon dose. However, RBE varies with tissue type, fraction dose, and beam quality parameters beyond dose such as linear energy transfer (LET) raising concerns about increased local effectiveness and potential toxicity.

Multi-target gene therapy AUP1602-C to improve healing and quality of life for diabetic foot ulcer patients: a phase I, open-label, dose-finding study.

Background: Diabetic foot ulcer (DFU) is a common and highly morbid complication of diabetes with high unmet medical needs. AUP1602-C, a topical four-in-one gene therapy medicinal product (GTMP), consisting of a strain that produces fibroblast growth factor-2, interleukin-4, and colony-stimulating factor-1, is a promising novel treatment for DFU.

Objectives: The aim of this first-in-human study was to investigate whether AUP1602-C is safe and effective in improving wound healing and quality of life (QoL) in patients with non-healing DFU (nhDFU), and to determine the recommended phase II dose.

A comparative analysis in monitoring 24-hour urinary copper in wilson disease: sampling on or off treatment?

Background & Aim: Twenty-four-hour urinary copper excretion (24 h-UCE) is the standard diagnostic tool for dose adjustments in maintenance therapy in Wilson disease (WD) patients. Guidelines lack data if both variants of 24 h-UCE measurement (with or without 48 h of treatment interruption) are equally interpretable.

Methods: Eighty-four patients with a confirmed diagnosis of WD treated with chelators (50% of patients with D-Penicillamine and 50% with trientine) and with pairwise 24-h-UCE values on-therapy and off-therapy were included in the analysis.

Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients.

Total proctocolectomy with ileal pouch anal anastomosis is the standard of care for patients with severe ulcerative colitis. We generated a cell-type-resolved transcriptional and epigenetic atlas of ileal pouches using scRNA-seq and scATAC-seq data from paired biopsy samples of the ileal pouch and the ileal segment above the pouch (pre-pouch) from patients (male=4, female=2), and paired biopsies of the terminal ileum and ascending colon from healthy individuals (male=3, female=3) serving as reference. Our study finds an additional population of absorptive and secretory epithelial cells within the pouch but not the pre-pouch.

More than a token photo: humanizing scientists enhances student engagement.

Despite broad consensus that highlighting counter-stereotypical scientist role models in educational materials promotes equity and success, the specific elements that make these materials effective remain untested. Are pictures of counter-stereotypical scientists enough to communicate to students that scientists come from a variety of backgrounds, or is additional information required? To parse the effects of including visual depictions and humanizing information about scientists featured in biology course materials, we distributed three randomized versions of assignments over several academic terms across 36 undergraduate institutions ( > 3700 students). We found that including humanizing information about scientists was key to increasing student engagement with the biology course materials.

Smoking and Risks Contributing to COVID-19 Hospitalization in Washoe County, Nevada, 2020-2021.

Objectives: To investigate the association between smoking behavior and COVID-19 hospitalization, integrating individual and regional factors such as community resilience and social determinants of health (SDOH), addressing gaps in existing research.

Design: Retrospective cohort study utilizing multilevel analytical methods to evaluate the effects of individual smoking status and regional SDOH on COVID-19 hospitalization.

Setting: Washoe County, Nevada, during the first year of the COVID-19 pandemic (March 5, 2020, to April 30, 2021).

Cardiovascular Complications During Delivery Hospitalization in Patients With Psoriasis.

Background: Psoriasis in pregnancy is associated with adverse maternal outcomes. However, there are limited data on this subject.

Objectives: The purpose of our study was to investigate the association between psoriasis and related cardiovascular complications during delivery.

Assessing bnAb potency in the context of HIV-1 envelope conformational plasticity.

For use in prevention and treatment, HIV-1 broadly neutralizing antibodies (bnAbs) have to overcome Env conformational heterogeneity of viral quasispecies and neutralize with constant high potency. Comparative analysis of neutralization data from the CATNAP database revealed a nuanced relationship between bnAb activity and Env conformational flexibility, with substantial epitope-specific variation of bnAb potency ranging from increased to decreased activity against open, neutralization-sensitive Env. To systematically investigate the impact of variability in Env conformation on bnAb potency we screened 126 JR-CSF point mutants for generalized neutralization sensitivity to weakly neutralizing antibodies (weak-nAbs) depending on trimer opening and plasma from people with chronic HIV-1 infection.

Outcomes of a Population-Based Congenital Cytomegalovirus Screening Program.

Importance: Detection of congenital cytomegalovirus (cCMV) infection has previously relied on targeted screening programs or clinical recognition; however, these approaches miss most cCMV-infected newborns and fail to identify those infants who are asymptomatic at birth but at risk for late-onset sensorineural hearing loss.

Objective: To determine the feasibility of using routinely collected newborn dried blood spots (DBS) in a population-based cCMV screen to identify infants at risk for hearing loss and describe outcomes of infants screened.

Design, Setting, And Participants: This diagnostic study of a population-based screening program in Ontario, Canada, took place from July 29, 2019, to July 31, 2023.

Orthopedic Patients Are Highly Amenable to Cannabis-Based Products for the Treatment of Musculoskeletal Pain.

Background: Tetrahydrocannabinol (THC)-based and cannabidiol (CBD)-based products are increasing in popularity for the management of pain. Cannabis-based products may serve as a valuable alternative to traditional analgesics such as opioids for pain management among orthopedic patients. The purpose of this study was to investigate the perspective of orthopedic sports medicine patients regarding the use of THC- and CBD-based products for the management of musculoskeletal pain.

Physical fitness assessment tools for children with developmental coordination disorder and their feasibility for low-income settings: A systematic review.

Background: This study systematically reviewed the literature on physical fitness assessment tools for children with developmental coordination disorder compared with typically developing children aged 7 to 10 and analyzed the feasibility of these tools for use in low-income settings.

Methods: Searches were conducted in the PubMed, Scopus, Web of Science, and EBSCO/RIC databases. The Newcastle - Ottawa Quality Assessment Scale assessed the methodological quality of the studies, and a checklist adapted from COSMIN assessed the feasibility of the instruments.

"Where There's a Will There's a Way": The Impact of State Variations in the Implementation of Continuous Coverage on Access to Postpartum Care During the Pandemic Emergency.

Objectives: To explore how the Medicaid continuous coverage requirement and unwinding process was implemented in three states with diverse existing policy environments and implications for the implementation of post-emergency 12-month postpartum extensions.

Data Sources: State data on unwinding performance and qualitative in-depth interviews with 48 stakeholders and patient-facing healthcare workers in Texas, New York and New Jersey.

Study Design: State Medicaid stakeholders and patient-facing healthcare workers in each state were interviewed with the goal of gaining insights into: (1) How the continuous coverage requirement was implemented; (2) What effects continuous coverage had on access to care for postpartum mothers; (3) How states are implementing the pandemic unwinding and postpartum extensions.

Trust in scientists and their role in society across 68 countries.

Science is crucial for evidence-based decision-making. Public trust in scientists can help decision makers act on the basis of the best available evidence, especially during crises. However, in recent years the epistemic authority of science has been challenged, causing concerns about low public trust in scientists.

[Diagnosis and treatment of perioperative anaemia in elective primary hip and knee arthroplasty : Consensus statement of the "Committee for Perioperative Management" of the Working Group for Endoprosthetics].

Background: Hip and knee arthroplasty remain risk procedures for bleeding complications. The prevalence of preoperative anaemia prior to elective joint replacement is high. There are no standardized guidelines in Germany for the diagnosis and treatment of perioperative anaemia in elective hip and knee arthroplasty.

[Perioperative management of obese patients undergoing elective hip and knee arthroplasty].

Introduction: Obesity is a worldwide growing health crisis, affecting younger and younger age groups and posing new challenges for arthroplasty. Due to increased complication rates in this population, many authors are of the opinion that in patients with a body mass index (BMI) of over 40, the problems outweigh the benefits of surgery and that surgery should be postponed until significant weight reduction has been achieved.

Materials And Methods: A systematic review of electronic databases (PubMed, Embase, Web of Science and the Cochrane Library) was performed.

Perceptions of science, science communication, and climate change attitudes in 68 countries - the TISP dataset.

Science is integral to society because it can inform individual, government, corporate, and civil society decision-making on issues such as public health, new technologies or climate change. Yet, public distrust and populist sentiment challenge the relationship between science and society. To help researchers analyse the science-society nexus across different geographical and cultural contexts, we undertook a cross-sectional population survey resulting in a dataset of 71,922 participants in 68 countries.

Sustainability of Enzymatic Monomer Synthesis: Evaluation via Comparison of Petrochemical and Enzymatic Alkene Epoxidation by Life Cycle Assessment.

Life cycle assessment (LCA) was used, next to green chemistry concepts, to compare the full environmental impacts of the epoxidation of a bio-based monomer, which can be used for the synthesis of vitrimers. On a laboratory scale, the synthesis of the monomer can either be done via a petrochemical route or via an enzymatic reaction pathway. Both reaction pathways were initially optimized to minimize the impact of suboptimal routes on the sustainability evaluation.

Multi-Institutional Analysis of Pancreatoduodenectomy for Nonfamilial Periampullary Adenoma: A Novel Risk Score to Guide Shared Decision-Making.

Introduction: Pancreatoduodenectomy (PD) may occasionally be indicated for complete removal of periampullary (duodenal and ampullary) adenomas (PAs). As compared with malignant indications, PD for benign or pre-malignant disease is often associated with increased morbidity. While the Spigelman classification assesses malignancy risk for familial adenomatous polyposis (FAP)-related duodenal adenomas, no malignancy risk score (MRS) exists for non-FAP related PAs.