Education Research: Use by Neurologists of Microteaching and Microassessment Programs for Teaching, Learning, and Patient Care Needs: A Qualitative Study.

Background And Objectives: Microlearning is the acquisition of knowledge or skills in small units, commonly delivered by digital technology. NeuroBytes (NB) and Question of the Day (QOD) are 2 microinstructional programs in neurology. NB programs are brief, video-based mini-courses on clinical topics (microteaching); QODs are daily multiple-choice questions (microassessment).

Emulation of ARISTOTLE and ROCKET AF trials in real-world atrial fibrillation patients results in similar efficacy and safety as original landmark trials: insights from the GARFIELD-AF registry.

Aims: This study aimed to determine the robustness, reproducibility and representativeness of the landmark Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (AF) (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in AF (ROCKET AF) randomised trials through replication in an observational AF patient registry.

Methods And Results: Patients from the Global Anticoagulant Registry in the FIELD (GARFIELD)-AF registry treated with apixaban, rivaroxaban or vitamin K antagonist (VKA) were assessed for eligibility for the ARISTOTLE and ROCKET AF trials. HRs of apixaban and rivaroxaban versus comparator for stroke/systemic embolism, major bleeding and all-cause mortality within 2 years follow-up were calculated using propensity score overlap-weighted Cox models.

Population pharmacokinetics and exposure-response analysis of durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer.

Purpose: Durvalumab in combination with gemcitabine/cisplatin has shown a favorable benefit-risk profile in the TOPAZ-1 study for advanced biliary tract cancers (BTC). This analysis evaluated the population pharmacokinetics (PopPK) of durvalumab, and exposure-response for efficacy and safety (ERES) of TOPAZ-1.

Methods: The PopPK model for durvalumab was updated using data from 5 previously analysed studies and TOPAZ-1.

Intratumoral Injection of mRNA-2752 and Pembrolizumab for High-Risk Ductal Carcinoma In Situ: A Phase 1 Nonrandomized Clinical Trial.

Importance: Intratumoral immunotherapy that leverages the biological characteristics of high-risk ductal carcinoma in situ (DCIS) may be able to reduce the extent of surgical treatment and provide an alternative approach to improve patient outcomes.

Objective: To determine if combination intratumoral immunotherapy can activate immune cells to shrink or eliminate high-risk DCIS.

Design, Setting, And Participants: This phase 1 open-label nonrandomized clinical trial at a single academic center tested the safety and efficacy of intratumoral immunotherapy in patients with high-risk DCIS, defined as at least 2 of the following present: younger than 45 years, tumor size greater than 5 cm, high-grade, palpable mass, hormone receptor (HR)-negative, or ERBB2-positive.

Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load.

Current understanding of viral dynamics of SARS-CoV-2 and host responses driving the pathogenic mechanisms in COVID-19 is rapidly evolving. Here, we conducted a longitudinal study to investigate gene expression patterns during acute SARS-CoV-2 illness. Cases included SARS-CoV-2 infected individuals with extremely high viral loads early in their illness, individuals having low SARS-CoV-2 viral loads early in their infection, and individuals testing negative for SARS-CoV-2.

An Australian online training and support program for caregivers of children and youth with Fetal Alcohol Spectrum Disorder: Families linking with families.

Background: Australia has limited supports to help families where Fetal Alcohol Spectrum Disorder (FASD) impacts children and young people. National Organisation for Fetal Alcohol Spectrum Disorder Australia (NOFASD), in conjunction with the University of Otago, New Zealand, piloted and established a 7-week online program to assist caregivers to develop strategies and supports to help their families live well in a disabling society.

Method: The online program, Families Linking with Families (FLWF), was delivered to 88 caregivers.

Trait genetic architecture and population structure determine model selection for genomic prediction in natural Arabidopsis thaliana populations.

Genomic prediction applies to any agro- or ecologically relevant traits, with distinct ontologies and genetic architectures. Selecting the most appropriate model for the distribution of genetic effects and their associated allele frequencies in the training population is crucial. Linear regression models are often preferred for genomic prediction.

Highly multiplexed imaging reveals prognostic immune and stromal spatial biomarkers in breast cancer.

Spatial profiling of tissues promises to elucidate tumor-microenvironment interactions and generate prognostic and predictive biomarkers. We analyzed single-cell, spatial data from three multiplex imaging technologies: cyclic immunofluorescence (CycIF) data we generated from 102 breast cancer patients with clinical follow-up, and publicly available imaging mass cytometry and multiplex ion-beam imaging datasets. Similar single-cell phenotyping results across imaging platforms enabled combined analysis of epithelial phenotypes to delineate prognostic subtypes among estrogen-receptor positive (ER+) patients.

Characterization of SARS-CoV-2 Diagnostic Tests and Liver Function Tests Among Patients With COVID-19 Diagnosed in Outpatient Settings Using Administrative Healthcare Data and Data From Commercial Laboratories.

Purpose: To characterize select laboratory tests ordered versus reported for patients diagnosed with COVID-19 in administrative healthcare and commercial laboratory data.

Methods: Among patients with an outpatient COVID-19 diagnosis claim in HealthVerity data (01/01/2021-12/31/2022), this study described baseline characteristics and descriptively compared SARS-CoV-2 diagnostic tests and liver function tests from administrative healthcare (insurance claims and hospital billing data) and commercial laboratories, overall and by code type (e.g.

Video versus Direct Laryngoscopy for Tracheal Intubation Following Cardiac Arrest: a Secondary Analysis of the DEVICE Trial.

Background: Airway management is a critical component of the care of patients experiencing cardiac arrest, but data from randomized trials on the use of video vs direct laryngoscopy for intubation in the setting of cardiac arrest are limited. Current AHA guidelines recommend placement of an endotracheal tube either during CPR or shortly after return of spontaneous circulation but do not provide guidance around intubation methods, including the choice of laryngoscope.

Research Question: Does use of video laryngoscopy improve the incidence of successful intubation on the first attempt, compared to use of direct laryngoscopy, among adults undergoing tracheal intubation after experiencing cardiac arrest?

Study Design And Methods: This secondary analysis of the Direct versus Video Laryngoscope (DEVICE) trial compared video laryngoscopy versus direct laryngoscopy in the subgroup of patients who were intubated following cardiac arrest.

A Critical Appraisal of the Application of Frailty and Sarcopenia in the Spinal Oncology Population.

Study Design: Systematic review and clinimetric analysis.

Objectives: Frailty and sarcopenia predict worse surgical outcomes among spinal degenerative and deformity-related populations; this association is less clear in the context of spinal oncology. Here, we sought to identify frailty and sarcopenia tools applied in spinal oncology and appraise their clinimetric properties.

Characterization of trends in preoperative hemoglobin A1c testing prior to metabolic and bariatric surgery: a retrospective, observational study.

Background: Irrespective of baseline diabetes status, preoperative hemoglobin A1c (A1C) influences perioperative care in patients undergoing metabolic and bariatric surgery (MBS). Accordingly, the American Society of Metabolic and Bariatric Surgery (ASMBS) endorses that patients undergoing MBS should receive a preoperative A1C test. We aimed to assess the proportion of MBS patients who received a preoperative A1C test and determine whether baseline diabetes status influences receipt of a test.

Postpartum Remote Health Coaching Intervention for Individuals With a Hypertensive Disorder of Pregnancy: Proof-of-Concept Study.

Background: Cardiovascular disease (CVD) is the leading cause of death among women in America. Hypertensive disorders of pregnancy (HDP) negatively impact acute and long-term cardiovascular health, with approximately 16% of all pregnancies affected. With CVD 2-4 times more likely after HDP compared to normotensive pregnancies, effective interventions to promote cardiovascular health are imperative.

Structurally and electronically driven uniaxial negative thermal expansion in BaIrO.

Negative thermal expansion is known to exist in a range of structure types but is extremely rare in hexagonal perovskites. Here we demonstrate that BaIrO displays negative linear thermal expansion in the direction of its face-shared IrO trimers, and apparent zero volume thermal expansion below 100 K. We present evidence that this anomalous thermal expansion is driven by an unusual form of rigid body phonon behaviour governed by the effective trimer valence state and therefore has structural and electronic components to the underlying mechanism.

Opening the digital doorway to sexual healthcare: Recommendations from a behaviour change wheel analysis of barriers and facilitators to seeking online sexual health information and support among underserved populations.

Background: The ability to access and navigate online sexual health information and support is increasingly needed in order to engage with wider sexual healthcare. However, people from underserved populations may struggle to pass though this "digital doorway". Therefore, using a behavioural science approach, we first aimed to identify barriers and facilitators to i) seeking online sexual health information and ii) seeking online sexual health support.

Diabetes Mellitus Is Not a Risk Factor for Difficult Intubation Among Critically Ill Adults: A Secondary Analysis of Multicenter Trials.

Objectives: Diabetes mellitus has been associated with greater difficulty of tracheal intubation in the operating room. This relationship has not been examined for tracheal intubation of critically ill adults. We examined whether diabetes mellitus was independently associated with the time from induction of anesthesia to intubation of the trachea among critically ill adults.

Integration of Stromal Cells and Hydrogel Below Epithelium Results in Optimal Barrier Properties of Small Intestine Organoid Models.

: The barrier properties of the human small intestine play a crucial role in regulating digestion, nutrient absorption and drug metabolism. Current in vitro organotypic models consist only of an epithelium, which does not take into account the possible role of stromal cells such as fibroblasts or the extracellular matrix (ECM) which could contribute to epithelial barrier properties. Therefore, the aim of this study was to determine whether these stromal cells or ECM were beneficial or detrimental to barrier function when incorporated into an organotypic human small intestine model.

GREGoR: Accelerating Genomics for Rare Diseases.

Rare diseases are collectively common, affecting approximately one in twenty individuals worldwide. In recent years, rapid progress has been made in rare disease diagnostics due to advances in DNA sequencing, development of new computational and experimental approaches to prioritize genes and genetic variants, and increased global exchange of clinical and genetic data. However, more than half of individuals suspected to have a rare disease lack a genetic diagnosis.

Single-cell analysis of the epigenome and 3D chromatin architecture in the human retina.

Most genetic risk variants linked to ocular diseases are non-protein coding and presumably contribute to disease through dysregulation of gene expression, however, deeper understanding of their mechanisms of action has been impeded by an incomplete annotation of the transcriptional regulatory elements across different retinal cell types. To address this knowledge gap, we carried out single-cell multiomics assays to investigate gene expression, chromatin accessibility, DNA methylome and 3D chromatin architecture in human retina, macula, and retinal pigment epithelium (RPE)/choroid. We identified 420,824 unique candidate regulatory elements and characterized their chromatin states in 23 sub-classes of retinal cells.

Long-read sequencing of hundreds of diverse brains provides insight into the impact of structural variation on gene expression and DNA methylation.

Structural variants (SVs) drive gene expression in the human brain and are causative of many neurological conditions. However, most existing genetic studies have been based on short-read sequencing methods, which capture fewer than half of the SVs present in any one individual. Long-read sequencing (LRS) enhances our ability to detect disease-associated and functionally relevant structural variants (SVs); however, its application in large-scale genomic studies has been limited by challenges in sample preparation and high costs.

Deaminase-mediated chromatin accessibility profiling with single-allele resolution.

Binding of transcription factors (TFs) at gene regulatory elements controls cellular epigenetic state and gene expression. Current genome-wide chromatin profiling approaches have inherently limited resolution, complicating assessment of TF occupancy and co-occupancy, especially at individual alleles. In this work, we introduce Accessible Chromatin by Cytosine Editing Site Sequencing with ATAC-seq (ACCESS-ATAC), which harnesses a double-stranded DNA cytosine deaminase (Ddd) enzyme to stencil TF binding locations within accessible chromatin regions.

Whole genome sequence-based association analysis of African American individuals with bipolar disorder and schizophrenia.

In studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole genome sequencing of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study).

Meta-analyses reveal climate change impacts on an ecologically and economically significant oyster in Australia.

Global oceans are warming and acidifying because of increasing greenhouse gas emissions that are anticipated to have cascading impacts on marine ecosystems and organisms, especially those essential for biodiversity and food security. Despite this concern, there remains some skepticism about the reproducibility and reliability of research done to predict future climate change impacts on marine organisms. Here, we present meta-analyses of over two decades of research on the climate change impacts on an ecologically and economically valuable Sydney rock oyster, .

Efficacy, Indications, and Safety of Intrathecal Baclofen Pump: A Narrative Review.

Purpose Of Review: Baclofen, a muscle relaxant that reduces the release of excitatory neurotransmitters in the pre-synaptic neurons stimulating inhibitory neuronal signals in post-synaptic neurons, has been around for over 5 decades. Baclofen is used primarily for spasticity and since 1982, has had a role as an intrathecal agent. In the present investigation, we review research trends and updates on safety and efficacy of intrathecal baclofen (ITB) pumps.