Semblans: Automated assembly and processing of RNA-Seq data.

Motivation: Recent advancements in parallel sequencing methods have precipitated a surge in publicly available short-read sequence data. This has encouraged the development of novel computational tools for the de novo assembly of transcriptomes from RNA-seq data. Despite the availability of these tools, performing an end-to-end transcriptome assembly remains a programmatically involved task necessitating familiarity with best practices.

Trends in Ethnic Disparities in Stroke Care and Long-Term Outcomes.

Importance: Reducing the burden of stroke is a public health priority. While higher stroke incidence among ethnic minority populations (defined in the context of this study as individuals who are not White) is well established, reports on ethnic inequalities in care or outcomes are conflicting and often limited to hospital-admitted patients and short-term outcomes.

Objective: To investigate ethnic differences in stroke care and outcomes up to 5 years after stroke and describe temporal trends and contributory factors.

Utility of Candidate Genes From an Algorithm Designed to Predict Genetic Risk for Opioid Use Disorder.

Importance: Recently, the US Food and Drug Administration gave premarketing approval to an algorithm based on its purported ability to identify individuals at genetic risk for opioid use disorder (OUD). However, the clinical utility of the candidate genetic variants included in the algorithm has not been independently demonstrated.

Objective: To assess the utility of 15 genetic variants from an algorithm intended to predict OUD risk.

Adaptive Lambda Scheduling: A Method for Computational Efficiency in Free Energy Perturbation Simulations.

Recent increases in the availability of computational power have improved the accessibility of ligand-protein relative binding free energy (RBFE) calculations; however, these calculations remain resource-intensive, which can limit their practical application. RBFE calculations typically use a set of thermodynamic intermediates mediated by the transformation coordinate λ. Optimizing λ offers a way to tune the computational efforts required for a given RBFE calculation.

Performance of Noninvasive Tests for Metabolic Dysfunction-Associated Steatohepatitis and Liver Fibrosis Resolution after Bariatric Surgery.

Background: Noninvasive tests (NITs) to monitor metabolic dysfunction-associated steatohepatitis (MASH) progression and response to interventions are needed because of the risks of liver biopsy. A monocytes-based diagnostic test using perilipin-2 (PLIN2) and Ras-related protein-14 (RAB14) predict the severity of MASH and fibrosis. Here we compared the performances of PLIN2 and RAB14 with cytokeratin-18 (CK18) assessed by Ella™ or M65 ELISA in predicting MASH and fibrosis resolution following bariatric surgery in a longitudinal and histologically characterized cohort of individuals with obesity.

Physician Engagement in Addressing Health-Related Social Needs and Burnout.

Importance: Previous research suggests that a greater capacity of health care organizations to address patients' health-related social needs (HRSNs) is associated with lower physician burnout. However, individual physician-level engagement in addressing HRSNs has not been fully characterized, and its association with physician burnout remains understudied.

Objective: To characterize physicians' engagement in addressing HRSNs and examine its association with burnout.

Breast Cancer Susceptibility Gene Sequence Variations and Development of Contralateral Breast Cancer.

Importance: Heterogeneity in development of estrogen receptor (ER)-specific first primary breast cancer exists due to deleterious germline variants in moderate- to high-penetrance breast cancer susceptibility genes, but it is unknown if these associations occur in ER-specific CBC.

Objective: To determine the association of deleterious germline variants in breast cancer susceptibility genes with ER-specific CBC development and whether ER status of the first primary breast cancer modifies these associations.

Design, Setting, And Participants: This case-control study included CBC cases and matched unilateral breast cancer controls from The Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study, a population-based case-control study.

Hydrogen-Borrowing-Based Methods for the Construction of Quaternary Stereocentres.

Compounds containing quaternary stereocentres are a valuable motif in biologically active compounds. Herein we present our strategy to utilise the hydrogen borrowing manifold to access α-quaternary ketones via a tandem acceptorless dehydrogenation-cyclisation cascade. This new application of the methodology results in the formation of five- and six-membered carbocycles with a high degree of diastereoselectivity.

Predictive Methods and Probabilistic Mapping of Subcortical Brain Components in Fossil Carnivora.

Paleoneurology reconstructs the evolutionary history of nervous systems through direct observations from the fossil record and comparative data from extant species. Although this approach can provide direct evidence of phylogenetic links among species, it is constrained by the availability and quality of data that can be gleaned from the fossil record. Here, we sought to translate brain component relationships in a sample of extant Carnivora to make inferences about brain structure in fossil species.

CO Cryo-sorption as a Surface-sensitive Spectroscopic Probe of the Active Site Density of Single-atom Catalysts.

Quantifying the number of active sites is a crucial aspect in the performance evaluation of single metal-atom electrocatalysts. A possible realization is using adsorbing gas molecules that selectively bind to the single-atom transition metal and then probing their surface density using spectroscopic tools. Herein, using in situ X-ray photoelectron (XPS) and near edge X-ray absorption fine structure (NEXAFS) spectroscopy, we detect adsorbed CO gas molecules on a FeNC oxygen reduction single atom catalyst.

Biomarkers.

Background: Alzheimer's Disease (AD) is associated with sleep disturbances. Moreover, individuals with sleep disturbances have been reported to have a higher risk for developing AD. The measurement of sleep behavior therefore opens the opportunity for a potential digital biomarker of AD.

Biomarkers.

Background: Growth/differentiation factor-15 (GDF15) has been associated with dementia risk, yet its predictive value across cohorts and sub-population, as well as its relationship with endophenotypes relevant to dementia, remains unknown.

Methods: Using the Atherosclerosis Risk in Communities (ARIC) study as the discovery cohort, we examined the relationship between plasma GDF15 levels (SomaScan) and risk for incident all-cause dementia (ACD) in late-life (N=4,287, 7-year follow-up, M=75±5) and in midlife (N=11,595, 20-year follow-up, M=57±6). Utilizing the UK Biobank (UKB; replication cohort), we related plasma GDF15 (Olink) to incident ACD (N=35,673, 14-year follow-up, M=61±5), vascular dementia (VaD) and Alzheimer's disease dementia (AD).

Biomarkers.

Background: With the approval of several anti-amyloid antibodies and a robust pipeline of new amyloid-based therapies, attention turns towards questions related to real-world clinical practice. Here we explore the impact of several biological pathways on the amyloid biomarker response of AD patients using a Quantitative Systems Pharmacology (QSP) approach with the ultimate objective to find measurable biomarkers for responder identification.

Method: Using a well-validated QSP biophysically realistic model of amyloid aggregation, we performed sensitivity analysis to identify key drivers of amyloid biomarkers both in a longitudinal observational context and after treatment with specific amyloid antibodies.

Biomarkers.

Background: Type 2 diabetes (T2D) is a prevalent health condition associated with cognitive impairment and dementia. T2D induces adverse effects not only on the pancreas but also on the liver, kidneys, muscles, fat cells, and, notably, the brain. Both T2D and Alzheimer's disease (AD) exhibit associations with neurodegeneration, yet the extent of their shared patterns of brain atrophy remains poorly understood, potentially indicating common pathways.

Biomarkers.

Background: Alzheimer's disease (AD) impacts over 50 million individuals and imposes a substantial burden on patients, caregivers, and society at large. Recent research suggests that AD is a continuum comprising preclinical, prodromal, and dementia stages, with underlying pathology manifesting well before symptoms appear. Early and accurate diagnosis is therefore crucial for optimal clinical outcomes; yet current diagnostic methods, such as neuroimaging and cerebrospinal fluid lumbar puncture, are expensive and invasive.

Socioeconomic Deprivation and Risk of Operative Mortality After Emergency Laparotomy: A Systematic Review and Meta-Analysis.

Aims: The aim was to determine the effect of socioeconomic deprivation on operative mortality after emergency laparotomy.

Methods: A PRISMA-compliant systematic review and meta-analysis (random-effects modeling) was performed searching for studies comparing operative mortality between the least and the most socioeconomically deprived patients undergoing emergency laparotomy. Both unadjusted and adjusted odds ratio (OR) were calculated as summary measure.

Biomarkers.

Background: The exact mechanism underlying amyloid-related imaging abnormalities (ARIA) is unknown. Several factors explain ARIA risk, including the presence of microbleeds, APOE4 carriership, and very low Aβ42 levels. The cerebrospinal fluid (CSF) proteome reflects ongoing mechanisms and, thereby, provides an accessible fluid to refine risk of ARIA development.

Biomarkers.

Background: In the context of Alzheimer's disease (AD), blood-based biomarkers have become increasingly important for various clinical purposes, such as screening patients and tracking the progression of the disease. Tau is a protein that stabilizes microtubules in nerve cells. In AD, different isoforms of tau become hyperphosphorylated, leading to the formation of neurofibrillary tangles, which are a key pathological feature of the AD.

Biomarkers.

Background: Alzheimer's disease (AD) blood biomarkers alone can detect amyloid-β (Aβ) pathology in cognitively unimpaired (CU) individuals. We assessed whether combining different plasma biomarkers improves the detection of Aβ-positivity and identifies rapid amyloid deposition in CU individuals.

Method: CU participants from the ALFA+ cohort were included.

Biomarkers.

Background: Alzheimer disease (AD) plasma biomarkers change in the preclinical stage of AD. However, the robustness of the discrimination performance of these biomarkers, as well as their association with longitudinal primary pathology (amyloid and tau) changes, is less understood. We aimed to determine the ability of baseline and longitudinal plasma amyloid-β (Aβ)42/40, p-tau181, GFAP and NfL to detect primary pathology in CU individuals at risk of AD.

Biomarkers.

Background: Emerging evidence underscores the importance of neuroinflammation in the progression of Alzheimer's disease (AD) pathophysiology. Recent studies indicate the involvement of the inflammatory mechanisms both in amyloid- β (Aβ) and tau deposition in the brain. Nevertheless, due to the complexity of the immune responses and the intricate interplay between the peripheral and the central nervous systems, identifying biomarkers that reflect the brain´s inflammatory state in AD has been a challenge.

Biomarkers.

Background: Single molecule array (Simoa) technology enables the detection of Alzheimer's disease (AD) neuropathology in blood. This study compared cross-sectional biomarker profiles for participants from the New Zealand-Dementia Prevention Research Clinics (NZ-DPRCs) who spanned the continuum from healthy older adults to a clinical diagnosis of AD.

Method: NZ-DPRC participants were clinically classified as cognitively unimpaired adults (CU, n=34), subjective cognitive decline (SCD, n=65), non-amnestic mild cognitive impairment (single and multi-domain, non-aMCI, n= 23), amnestic MCI (single and multi-domain, aMCI, n=104), and AD (n=27).

Biomarkers.

Background: Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease (AD) patients, are prevalent and clinically meaningful in this group of older adults.

Method: To uncover atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to structural MRI data from 813 participants (mean ± SD age = 70.

Biomarkers.

Background: Plasma biomarkers have emerged as a promising tool to detect the presence of Alzheimer's disease (AD) when cognitive symptoms have not yet emerged. However, there is also a pressing need to detect and track subtle cognitive change at the preclinical stage of AD for population screening purposes and to monitor disease progression at scale. A potential solution is remote cognitive assessment, yet it is still not extensively employed.