Shorter weeknight sleep duration mediates the relationship between earlier adrenarche and depressed mood in adolescents.

Background: Shorter weeknight sleep duration has not been assessed as a mediating mechanism linking earlier pubertal timing to a greater burden of adolescent depression symptoms.

Methods: Among 1138 participants (48.6 % female) from Project Viva, a pre-birth longitudinal cohort, we examined relationships among pubertal timing measures, actigraphy-captured and self-reported weeknight sleep duration across mid-adolescence, and depression symptoms in late adolescence.

Generalizability of Randomized Controlled Trials to Routine Clinical Care in Ulcerative Colitis.

Background: Historically, randomized controlled trials (RCTs) have been criticized for being poorly generalizable to patients with ulcerative colitis (UC) evaluated in routine care. We aimed to evaluate the proportion of patients with UC starting an advanced therapy who would be eligible to participate in phase 3 registrational UC RCTs.

Methods: We conducted a retrospective cohort analysis of UC patients starting vedolizumab, ustekinumab, or tofacitinib at 2 IBD clinics at the University of Calgary.

Characterization of LTBP2 mutation causing mitral valve prolapse.

Aims: Mitral valve prolapse (MVP) is a common valvular disorder associated with significant morbidity and mortality, with a strong genetic basis. This study aimed to identify a mutation in a family with MVP and to characterize the valve phenotype in LTBP2 knockout (KO) mice.

Methods And Results: Exome sequencing and segregation analysis were performed on a large family with MVP.

Systematic empirical evaluation of individual base editing targets: validating therapeutic targets in USH2A and comparison of methods.

Base editing shows promise for the correction of human mutations at a higher efficiency than other repair methods and is especially attractive for mutations in large genes that are not amenable to gene augmentation therapy. Here, we demonstrate a comprehensive workflow for in vitro screening of potential therapeutic base editing targets for the USH2A gene and empirically validate the efficiency of adenine and cytosine base editor/guide combinations for correcting 35 USH2A mutations. Editing efficiency and bystander edits are compared between different target templates (plasmids versus transgenes) and assays (Next generation sequencing versus Sanger), as well as comparisons between unbiased empirical results and computational predictions.

Ultrasound-guided intraoperative liver ablation - retrospective review of indications and outcomes.

Aim: To define the indications and outcomes of intraoperative ablation of hepatic malignancies.

Materials And Methods: This retrospective study comprises 27 patients (male/female: 19/8; mean age: 56 ± 13) undergoing intraoperative ablation (IOA) of liver tumours between July 2001 and August 2021 for 42 tumours, including colorectal liver metastasis (CRLM) (n = 27), hepatocellular carcinoma (HCC)(n = 14), and ovarian cancer metastasis (n = 1). The mean tumour diameter was 2.

Predicting falls with ultrasound, physical parameters or fall-risk questions among older adults: A prospective cohort study.

Background: Falls are a significant issue among older adults, leading to morbidity and mortality. Screening for fall risk in the ED is crucial but challenging due to time limitations and patient conditions. Sarcopenia, characterized by muscle loss, is associated with increased fall risk, and ultrasound has been proposed as a non-invasive tool to measure muscle mass in this context.

Pharmacotherapy for Tourette Syndrome.

Tourette syndrome (TS) is associated with dysregulated cortico-striatal-thalamo-cortical neural circuitry, of which the primary implicated neurotransmitters include dopamine, glutamate, and gamma-aminobutyric acid. Pharmacologic intervention for tics should be considered when tics are causing psychological, functional, or physical impairment, and behavioral treatment is either inaccessible or ineffective. Only 3 medications have Food and Drug Administration approval for TS, including 2 typical antipsychotics (pimozide and haloperidol) and 1 atypical antipsychotic (aripiprazole).

Organ-specific microenvironments drive divergent T cell evolution in acute graft-versus-host disease.

Tissue-specific T cell immune responses play a critical role in maintaining organ health but can also drive immune pathology during both autoimmunity and alloimmunity. The mechanisms controlling intratissue T cell programming remain unclear. Here, we leveraged a nonhuman primate model of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation to probe the biological underpinnings of tissue-specific alloimmune disease using a comprehensive systems immunology approach including multiparameter flow cytometry, population-based transcriptional profiling, and multiplexed single-cell RNA sequencing and TCR sequencing.

Association between changes in genital immune markers and vaginal microbiome transitions in bacterial vaginosis.

Bacterial vaginosis (BV), characterized by an imbalance in the vaginal microbiota, is a prevalent condition among women of reproductive age and a risk factor for human immunodeficiency virus, sexually transmitted infections, and preterm birth. BV is generally considered to induce mucosal inflammation, but the specific pathways and cell types involved are not well characterized. This prospective study aimed to assess associations between microbial changes and mucosal immune responses in BV patients.

AMH protects the ovary from doxorubicin by regulating cell fate and the response to DNA damage.

Anti-Müllerian hormone (AMH) protects the ovarian reserve from chemotherapy, and this effect is most pronounced with Doxorubicin (DOX). However, DOX toxicity and AMH rescue mechanisms in the ovary have remained unclear. Herein, we characterize the consequences of these treatments in ovarian cell types using scRNAseq.

Trigeminal nerve microstructure is linked with neuroinflammation and brainstem activity in migraine.

Although the pathophysiology of migraine involves a complex ensemble of peripheral and central nervous system changes that remain incompletely understood, the activation and sensitization of the trigeminovascular system is believed to play a major role. However, non-invasive, in vivo neuroimaging studies investigating the underlying neural mechanisms of trigeminal system abnormalities in human migraine patients are limited. Here, we studied 60 patients with migraine (55 females, mean age ± SD: 36.

Rethinking the residual approach: leveraging statistical learning to operationalize cognitive resilience in Alzheimer's disease.

Cognitive resilience (CR) describes the phenomenon of individuals evading cognitive decline despite prominent Alzheimer's disease neuropathology. Operationalization and measurement of this latent construct is non-trivial as it cannot be directly observed. The residual approach has been widely applied to estimate CR, where the degree of resilience is estimated through a linear model's residuals.

White matter connections within the central sulcus subserving the somato-cognitive action network.

The somato-cognitive action network (SCAN) consists of three nodes interspersed within Penfield's motor effector regions. The configuration of the somato-cognitive action network nodes resembles the one of the 'plis de passage' of the central sulcus: small gyri bridging the precentral and postcentral gyri. Thus, we hypothesize that these may provide a structural substrate of the somato-cognitive action network.

Investigating the potential of diffusion tensor atlases to generate anisotropic clinical tumor volumes in glioblastoma patients.

Background And Purpose: Diffusion tensor imaging (DTI) has been proposed to guide the anisotropic expansion from gross tumor volume to clinical target volume (CTV), aiming to integrate known tumor spread patterns into the CTV. This study investigate the potential of using a DTI atlas as an alternative to patient-specific DTI for generating anisotropic CTVs.

Materials And Methods: The dataset consisted of twenty-eight newly diagnosed glioblastoma patients from a Danish national DTI protocol with post-operative T1-contrast and DTI imaging.

Mitochondrial Dysfunction in HFpEF: Potential Interventions Through Exercise.

HFpEF is a prevalent and complex type of heart failure. The concurrent presence of conditions such as obesity, hypertension, hyperglycemia, and hyperlipidemia significantly increase the risk of developing HFpEF. Mitochondria, often referred to as the powerhouses of the cell, are crucial in maintaining cellular functions, including ATP production, intracellular Ca regulation, reactive oxygen species generation and clearance, and the regulation of apoptosis.

Use of the Adaptive Behaviour Dementia Questionnaire in a Down Syndrome Specialty Clinic.

Objective: To study the use of a dementia screening tool in our clinic cohort of adults with Down syndrome.

Study Design: A retrospective chart review of patients with Down syndrome was conducted to follow the use of the Adaptive Behaviour Dementia Questionnaire (ABDQ) in a dementia screening protocol. The ABDQ results for patients aged 40 years and older at a Down syndrome specialty clinic program were assessed.

Viral Transcript and Tumor Immune Microenvironment-Based Transcriptomic Profiling of HPV-Associated Head and Neck Squamous Cell Carcinoma Identifies Subtypes Associated with Prognosis.

Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HPV-positive HNSCC) has distinct biological characteristics from HPV-negative HNSCC. Using an AI-based analytical platform on meta cohorts, we profiled expression patterns of viral transcripts and HPV viral genome integration, and classified the tumor microenvironment (TME). Unsupervised clustering analysis revealed five distinct and novel TME subtypes across patients (immune-enriched, highly immune and B-cell enriched, fibrotic, immune-desert, and immune-enriched luminal).

Adherence to the Mediterranean Diet and the Risk of Head and Neck Cancer: A Systematic Review and Meta-Analysis of Case-Control Studies.

Background/objectives: Head and neck cancer (HNC) is the seventh most common cancer worldwide, with rising incidence rates and significant mortality. While tobacco use, alcohol consumption, and viral infections are established risk factors, the role of dietary patterns, particularly adherence to the Mediterranean diet (MD), in HNC prevention has gained increasing attention. The aim of the current systematic review and meta-analysis is to investigate the association between adherence to the MD and the risk of HNC.

Non-Celiac Gluten/Wheat Sensitivity-State of the Art: A Five-Year Narrative Review.

Non-celiac gluten/wheat sensitivity (NCGWS) is a syndrome for which pathogenesis and management remain debated. It is described as a condition characterized by gastrointestinal and extra-intestinal symptoms rapidly occurring after gluten ingestion in subjects who have had celiac disease or wheat allergy excluded. To date, the diagnosis of NCGWS is challenging as no universally recognized biomarkers have been yet identified, nor has a predisposing genetic profile been described.

Hepatitis C Virus-Pediatric and Adult Perspectives in the Current Decade.

Hepatitis C virus (HCV) infects both pediatric and adult populations and is an important cause of chronic liver disease worldwide. There are differences in the screening and management of HCV between pediatric and adult patients, which have been highlighted in this review. Direct-acting antiviral agents (DAA) have made the cure of HCV possible, and fortunately, these medications are approved down to three years of age.

Utilization Trends of Glucose-Lowering Medications Among Adult Kidney Transplant Recipients with Type 2 Diabetes in the United States.

To date, there are limited studies describing the use of glucose-lowering medications (GLMs) in adult kidney transplant recipients (KTRs), and the uptake of sodium glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP1RAs). Thus, we aimed to evaluate the use of GLMs, including SGLT2i and GLP1RA, among adult KTRs with type 2 diabetes (T2D). This is an ecologic study of adult KTR with T2D.

Restoration of Genuine Sensation and Proprioception of Individual Fingers Following Transradial Amputation with Targeted Sensory Reinnervation as a Mechanoneural Interface.

: Tactile gnosis derives from the interplay between the hand's tactile input and the memory systems of the brain. It is the prerequisite for complex hand functions. Impaired sensation leads to profound disability.

Acral Melanoma: A Review of Its Pathogenesis, Progression, and Management.

Acral melanoma is a distinct subtype of cutaneous malignant melanoma that uniquely occurs on ultraviolet (UV)-shielded, glabrous skin of the palms, soles, and nail beds. While acral melanoma only accounts for 2-3% of all melanomas, it represents the most common subtype among darker-skinned, non-Caucasian individuals. Unlike other cutaneous melanomas, acral melanoma does not arise from UV radiation exposure and is accordingly associated with a relatively low tumor mutational burden.

Urinary Proteome and Exosome Analysis Protocol for the Discovery of Respiratory Diseases Biomarkers.

This study aims to develop a protocol for respiratory disease-associated biomarker discovery by combining urine proteome studies with urinary exosome components analysis (i.e., miRNAs).