Quantitative Structural and Compositional Elucidation of Real-World Pharmaceutical Tablet Using Large Field-of-View, Correlative Microscopy-Tomography Techniques and AI-Enabled Image Analysis.

Purpose: The purpose of this study is to present a correlative microscopy-tomography approach in conjunction with machine learning-based image segmentation techniques, with the goal of enabling quantitative structural and compositional elucidation of real-world pharmaceutical tablets.

Methods: Specifically, the approach involves three sequential steps: 1) user-oriented tablet constituent identification and characterization using correlative mosaic field-of-view SEM and energy dispersive X-ray spectroscopy techniques, 2) phase contrast synchrotron X-ray micro-computed tomography (SyncCT) characterization of a large, representative volume of the tablet, and 3) constituent segmentation and quantification of the imaging data through user-guided, iterative supervised machine learning and deep learning.

Results: This approach was implemented on a real-world tablet containing 15% API and multiple common excipients.

The association between neighbourhood marginalization and SARS-CoV-2 outcomes in patients presenting to emergency departments.

Objective: Social and economic marginalizations have been associated with inferior health outcomes in Canada. Our objective was to describe the relationship between neighbourhood marginalization and COVID-19 outcomes among patients presenting to Canadian emergency departments (ED).

Methods: We conducted an observational study among consecutive COVID-19 patients recruited from 47 hospitals participating in the Canadian COVID-19 ED Rapid Response Network (CCEDRRN) between March 3, 2020, and July 24, 2022.

Structure of subcortico-cortical tracts in middle-aged and older adults with autism spectrum disorder.

Middle-aged and older adults with autism spectrum disorder may be susceptible to accelerated neurobiological changes in striato- and thalamo-cortical tracts due to combined effects of typical aging and existing disparities present from early neurodevelopment. Using magnetic resonance imaging, we employed diffusion-weighted imaging and automated tract-segmentation to explore striato- and thalamo-cortical tract microstructure and volume differences between autistic (n = 29) and typical comparison (n = 33) adults (40 to 70 years old). Fractional anisotropy, mean diffusivity, and tract volumes were measured for 14 striato-cortical and 12 thalamo-cortical tract bundles.

Investigation of the State of Hydration of a Non-Stoichiometric Hydrate in a Low Dose Formulation Using F Solid-State NMR.

A variable or non-stoichiometric hydrate of GDC-4379 was developed into a formulated capsule with a 1% drug loading. The water content of this hydrate varied from 0-0.7 moles over the relative humidity (RH) range of 0-98% (25°C).

Comparative functional analysis reveals differential nucleotide sensitivity between human and mouse UCP1.

Aim: Mitochondrial uncoupling protein 1 (UCP1) is a unique protein of brown adipose tissue. Upon activation by free fatty acids, UCP1 facilitates a thermogenic net proton flux across the mitochondrial inner membrane. Non-complexed purine nucleotides inhibit this fatty acid-induced activity of UCP1.

Leveraging a clinical emergency department dataset to estimate two-dose COVID-19 vaccine effectiveness and duration of protection in Canada.

Background: During the COVID-19 pandemic, clinical care shifted toward virtual and Emergency Department care. We explored the feasibility of mRNA vaccine effectiveness (VE) estimation against SARS-CoV-2-related Emergency Department visits and hospitalizations using prospectively collected Emergency Department data.

Methods: We estimated two-dose VE using a test-negative design and data from 10 participating sites of the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN).

Associations between atypical intracortical myelin content and neuropsychological functions in middle to older aged adults with ASD.

Introduction: In vivo myeloarchitectonic mapping based on Magnetic Resonance Imaging (MRI) provides a unique view of gray matter myelin content and offers information complementary to other morphological indices commonly employed in studies of autism spectrum disorder (ASD). The current study sought to determine if intracortical myelin content (MC) and its age-related trajectories differ between middle aged to older adults with ASD and age-matched typical comparison participants.

Methods: Data from 30 individuals with ASD and 36 age-matched typical comparison participants aged 40-70 years were analyzed.

Crossing the digital divide: The workload of manual data entry for integration between mobile health applications and eHealth infrastructure.

Background: Many digital health interventions (DHIs), including mobile health (mHealth) apps, aim to improve both client outcomes and efficiency like electronic medical record systems (EMRS). Although interoperability is the gold standard, it is also complex and costly, requiring technical expertise, stakeholder permissions, and sustained funding. processes are commonly used to "integrate" across systems and allow for assessment of DHI impact, a best practice, before further investment.

Administrative data ICD-10 diagnostic codes identifies most lab-confirmed SARS-CoV-2 admissions but misses many discharged from the Emergency Department.

We estimated the operating characteristics of ICD-10 code U07.1, introduced by the World Health Organization in 2020, to identify lab-confirmed SARS-CoV-2. CCEDRRN is a national research registry of adults (March 2020-August 2021) with suspected/confirmed SARS-CoV-2 identified in Canadian emergency departments (EDs) using chart review (symptoms, clinical information, and lab test results including SARS-CoV-2 polymerase chain reaction, PCR results).

Removal of Incidental Skin Cancer During Mohs Micrographic Surgery Indicated for a Different Primary Tumor.

Background: Mohs surgery is a tissue-sparing, microscopically controlled procedure used to treat biopsy-proven skin cancers. Because Mohs surgery allows for examination of the complete margin of each tissue layer removed, separate cancers can be treated concomitantly when identified. As early detection of skin cancer is beneficial for reducing morbidity, incidental tumors discovered during Mohs surgery are of significant interest.

Heatstroke presentations to urban hospitals during BC's extreme heat event: lessons for the future.

Background: Climate change is leading to more extreme heat events in temperate climates that typically have low levels of preparedness. Our objective was to describe the characteristics, treatments, and outcomes of adults presenting to hospitals with heatstroke during BC's 2021 heat dome.

Methods: We conducted a review of consecutive adults presenting to 7 hospitals in BC's Lower Mainland.

Functionality of the Na-translocating NADH:quinone oxidoreductase and quinol:fumarate reductase from Prevotella bryantii inferred from homology modeling.

Members of the family Prevotellaceae are Gram-negative, obligate anaerobic bacteria found in animal and human microbiota. In Prevotella bryantii, the Na-translocating NADH:quinone oxidoreductase (NQR) and quinol:fumarate reductase (QFR) interact using menaquinone as electron carrier, catalyzing NADH:fumarate oxidoreduction. P.

Functional dysregulation of the auditory cortex in bilateral perisylvian polymicrogyria: Multiparametric case analysis of the absent speech phenotype.

The absence of speech is a clinical phenotype seen across neurodevelopmental syndromes, offering insights for neural language models. We present a case of bilateral perisylvian polymicrogyria (BPP) and complete absence of speech with considerable language comprehension and production difficulties. We extensively characterized the auditory speech perception and production circuitry by employing a multimodal neuroimaging approach.

The low mutational flexibility of the EPSP synthase in Bacillus subtilis is due to a higher demand for shikimate pathway intermediates.

Glyphosate (GS) inhibits the 5-enolpyruvyl-shikimate-3-phosphate (EPSP) synthase that is required for aromatic amino acid, folate and quinone biosynthesis in Bacillus subtilis and Escherichia coli. The inhibition of the EPSP synthase by GS depletes the cell of these metabolites, resulting in cell death. Here, we show that like the laboratory B.

Comparing methods to classify admitted patients with SARS-CoV-2 as admitted for COVID-19 versus with incidental SARS-CoV-2: A cohort study.

Introduction: Not all patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection develop symptomatic coronavirus disease 2019 (COVID-19), making it challenging to assess the burden of COVID-19-related hospitalizations and mortality. We aimed to determine the proportion, resource utilization, and outcomes of SARS-CoV-2 positive patients admitted for COVID-19, and assess the impact of using the Center for Disease Control's (CDC) discharge diagnosis-based algorithm and the Massachusetts state department's drug administration-based classification system on identifying admissions for COVID-19.

Methods: In this retrospective cohort study, we enrolled consecutive SARS-CoV-2 positive patients admitted to one of five hospitals in British Columbia between December 19, 2021 and May 31,2022.

Comparing United States and European Union academic animal programs: Finances.

The Yale Animal Resource Cost and Benchmarking survey, conducted in United States (US) academic animal research/resource centres (ARC), was modified to capture similar information in European Union (EU) (including the non-EU countries Switzerland and the United Kingdom) academic ARCs, who are members of the League of European Research Universities (LERU). Participating institutions came from Denmark, England, Finland, France, Germany, Ireland, Italy, Netherlands, Scotland, Spain and Switzerland. Survey data analysis suggests that (a) per diem rates have similar compositions in LERU and US programs, with >50% of the rates dedicated to recovering salary and fringe, followed by supplies (∼25%), facility costs (∼10%) and other expenses (∼15%); (b)  ∼60% of US and LERU programs under-recover mouse care costs; (c) on average, LERU programs have a small positive net-operating balance, while US programs average a large deficit; (d) in LERU programs <50% of institutions fund the animal program deficit, while in US programs almost 100% of such deficits are covered by the institution; and (e) when setting per diem rates, both US and LERU programs rank cost accounting as the most influential factor.

Comparing United States and European Union academic animal programs: Organization, operation, and services offered.

The Yale Animal Resource Cost and Benchmarking survey, conducted in US academic Animal Research/Resource Centers (ARC), was modified to capture similar thematic information in European Union (EU; including the non-EU countries Switzerland and the UK) academic ARCs, which are members of the League of European Research Universities (LERU). Participating institutions came from Denmark, England, Finland, France, Germany, Ireland, Italy, Netherlands, Scotland, Spain, and Switzerland. Survey data analysis suggests that: (a) in LERU programs, it is common to have more than one ARC under the umbrella of a single institution with organizational "lumping" of the financial, regulatory, and/or operational tasks under one administrative unit; (b) accreditation by an outside agency (e.

Conformational coupling of redox-driven Na-translocation in Vibrio cholerae NADH:quinone oxidoreductase.

In the respiratory chain, NADH oxidation is coupled to ion translocation across the membrane to build up an electrochemical gradient. In the human pathogen Vibrio cholerae, the sodium-pumping NADH:quinone oxidoreductase (Na-NQR) generates a sodium gradient by a so far unknown mechanism. Here we show that ion pumping in Na-NQR is driven by large conformational changes coupling electron transfer to ion translocation.

Rapid ammonia build-up in small individually ventilated mouse cages cannot be overcome by adjusting the amount of bedding.

We sought to investigate if varying levels of bedding had an effect on intra-cage ammonia levels in individually ventilated mouse cages (Euro Standard Types II and III). Employing a routine 2 week cage-changing interval, our goal is to keep ammonia levels under 50 ppm. In smaller cages used for breeding or for housing more than four mice, we measured problematic levels of intra-cage ammonia, and a considerable proportion of these cages had ammonia levels at more than 50 ppm toward the end of the cage-change cycle.

Propensities of Fatty Acid-Modified ASOs: Self-Assembly vs Albumin Binding.

We conducted a biophysical study to investigate the self-assembling and albumin-binding propensities of a series of fatty acid-modified locked nucleic acid (LNA) antisense oligonucleotide (ASO) gapmers specific to the MALAT1 gene. To this end, a series of biophysical techniques were applied using label-free ASOs that were covalently modified with saturated fatty acids (FAs) of varying length, branching, and 5'/3' attachment. Using analytical ultracentrifugation (AUC), we demonstrate that ASOs conjugated with fatty acids longer than C16 exhibit an increasing tendency to form self-assembled vesicular structures.

The burden of incidental SARS-CoV-2 infections in hospitalized patients across pandemic waves in Canada.

Many health authorities differentiate hospitalizations in patients infected with SARS-CoV-2 as being "for COVID-19" (due to direct manifestations of SARS-CoV-2 infection) versus being an "incidental" finding in someone admitted for an unrelated condition. We conducted a retrospective cohort study of all SARS-CoV-2 infected patients hospitalized via 47 Canadian emergency departments, March 2020-July 2022 to determine whether hospitalizations with "incidental" SARS-CoV-2 infection are less of a burden to patients and the healthcare system. Using a priori standardized definitions applied to hospital discharge diagnoses in 14,290 patients, we characterized COVID-19 as (i) the "Direct" cause for the hospitalization (70%), (ii) a potential "Contributing" factor for the hospitalization (4%), or (iii) an "Incidental" finding that did not influence the need for admission (26%).

Fast IMAC purification of non-tagged S100A8/A9 (calprotectin) from Homo sapiens and Sus scrofa.

S100A8/A9 (calprotectin) is a damage-associated molecular pattern molecule (DAMP) that plays a key role in the innate immune response of mammalia. S100A8/A9 is therefore widely used as a biomarker in human and veterinary medicine, but diagnostic tools for the detection of S100A8/A9 are rarely optimised for the specific organism, since the corresponding S100A8/A9 is often not available. There is need for an easy, reliable protocol for the production of recombinant, highly pure S100A8/A9 from various mammalia.

Intubation practices and outcomes for patients with suspected or confirmed COVID-19: a national observational study by the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN).

Objective: Intubation practices changed during the COVID-19 pandemic to protect healthcare workers from transmission of disease. Our objectives were to describe intubation characteristics and outcomes for patients tested for SARS CoV-2 infection. We compared outcomes between patients testing SARS COV-2 positive with those testing negative.