Nup107 contributes to the maternal to zygotic transition by preventing the premature nuclear export of pri-miRNA 427.

Emerging evidence suggests that the nuclear pore complex can have unique compositions and distinct nucleoporin functions in different cells. Here, we show that Nup107, a key component of the NPC scaffold, varies in expression over development: it is expressed at higher levels in the blastula compared to the gastrula suggesting a critical role prior to gastrulation. We find depletion of Nup107 affects the differentiation of the early germ layers leading to an expansion of the ectoderm at the expense of endoderm and mesoderm.

Patient and Healthcare Professional Perspectives on Crohn's Perianal Fistula Treatment: Results From a Discrete Choice Experiment.

Background: Crohn's perianal fistulas (CPF) are difficult to manage and often require multiple interventions. This study aimed to assess the preferences of patients and healthcare professionals (HCPs) for attributes of CPF-related procedures/surgeries to better inform CPF management.

Methods: This US cross-sectional, observational study was conducted via a web-enabled questionnaire (October 2021-January 2022) among patients aged 21-89 years with a self-reported physician diagnosis of CPF (with or without CPF-related surgery experience) and HCPs (gastroenterologists and colorectal surgeons who managed ≥3 patients with CPF in the past 12 months).

Adeno-Associated Virus 8 and 9 Myofibre Type/Size Tropism Profiling Reveals Therapeutic Effect of Microdystrophin in Canines.

Background: Adeno-associated virus (AAV) 8 and 9 are in clinical trials for treating neuromuscular diseases such as Duchenne muscular dystrophy (DMD). Muscle consists of myofibres of different types and sizes. However, little is known about the fibre type and fibre size tropism of AAV in large mammals.

Abaloparatide Enhances Bone Regeneration in Extraction Socket Dental Implant Defects: An Experimental In Vivo Study.

Objective: Abaloparatide (ABL) is a synthetic parathyroid hormone-related protein analog developed as an anabolic drug to treat osteoporosis. ABL increases bone mineral density (BMD) of the long bones and spine; however, the influence of ABL on alveolar bone regeneration remains unknown. This study assessed the effects of systemic ABL administration on tooth extraction socket healing and dental implant osseointegration in a preclinical rodent model.

Neuroactive steroid exposure impacts neurodevelopment: Comparison of human and rodent placental contribution.

The placenta is a fetal endocrine organ that secretes many neuroactive factors, including steroids, that play critical roles in brain development. The study of the placenta-brain axis and the links between placental function and brain development represents an emerging research area dubbed "neuroplacentology." The placenta drives many circulating fetal steroids to very high levels during gestation.

Plasma S100β is a predictor for pathology and cognitive decline in Alzheimer's disease.

Background: Blood-brain barrier dysfunction is one characteristic of Alzheimer's disease (AD) and is recognized as both a cause and consequence of the pathological cascade leading to cognitive decline. The goal of this study was to assess markers for barrier dysfunction in postmortem tissue samples from research participants who were either cognitively normal individuals (CNI) or diagnosed with AD at the time of autopsy and determine to what extent these markers are associated with AD neuropathologic changes (ADNC) and cognitive impairment.

Methods: We used postmortem brain tissue and plasma samples from 19 participants: 9 CNI and 10 AD dementia patients who had come to autopsy from the University of Kentucky AD Research Center (UK-ADRC) community-based cohort; all cases with dementia had confirmed severe ADNC.

Identification of a Subpopulation of Astrocyte Progenitor Cells in the Neonatal Subventricular Zone: Evidence that Migration is Regulated by Glutamate Signaling.

In mice engineered to express enhanced green fluorescent protein (eGFP) under the control of the entire glutamate transporter 1 (GLT1) gene, eGFP is found in all 'adult' cortical astrocytes. However, when 8.3 kilobases of the human GLT1/EAAT2 promoter is used to control expression of tdTomato (tdT), tdT is only found in a subpopulation of these eGFP-expressing astrocytes.

Transcriptome-wide association study identifies genes associated with bladder cancer risk.

Genome-wide association studies (GWAS) have detected several susceptibility variants for urinary bladder cancer, but how gene regulation affects disease development remains unclear. To extend GWAS findings, we conducted a transcriptome-wide association study (TWAS) using PrediXcan to predict gene expression levels in whole blood using genome-wide genotype data for 6180 bladder cancer cases and 5699 controls included in the database of Genotypes and Phenotypes (dbGaP). Logistic regression was used to estimate adjusted gene-level odds ratios (OR) per 1-standard deviation higher expression with 95% confidence intervals (CI) for bladder cancer risk.

Nicotinamide adenine dinucleotide supplementation fails to enhance anesthetic recovery in rodents.

Nicotinamide Adenine Dinucleotide (NAD) is implicated in bioenergetics, DNA repair, and senescence. Depletion of NAD is associated with aging and neurodegenerative disease, prompting a growing interest in NAD supplementation. With rising over-the-counter use of NAD, understanding their impact on anesthetic recovery becomes essential.

A non-covalently bound redox indicator for electrochemical CRISPR-Cas12a and DNase I biosensors.

A rapid and accurate biosensor for detecting disease biomarkers at point-of-care is essential for early disease diagnosis and preventing pandemics. CRISPR-Cas12a is a promising recognition element for DNA biosensors due to its programmability, specificity, and deoxyribonuclease activity initiated in the presence of a biomarker. The current electrochemical CRISPR-Cas12a-based biosensors utilize the single-stranded DNA (ssDNA) self-assembled on an electrode surface and covalently modified with the redox indicator, usually methylene blue (MB).

Selecting genes for analysis using historically contingent progress: from RNA changes to protein-protein interactions.

Progress in biology has generated numerous lists of genes that share some property. But advancing from these lists of genes to understanding their roles is slow and unsystematic. Here we use RNA silencing in Caenorhabditis elegans to illustrate an approach for prioritizing genes for detailed study given limited resources.

Sociodemographic Disparities in the Use of Hospice by U.S. Nursing Home Residents: A Systematic Review.

Hospice can improve end-of-life (EOL) outcomes in U.S. nursing homes (NHs).

Bile acid synthesis impedes tumor-specific T cell responses during liver cancer.

The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid-CoA:amino acid -acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy.

Artificial Intelligence in Health Professions Education assessment: AMEE Guide No. 178.

Health Professions Education (HPE) assessment is being increasingly impacted by Artificial Intelligence (AI), and institutions, educators, and learners are grappling with AI's ever-evolving complexities, dangers, and potential. This AMEE Guide aims to assist all HPE stakeholders by helping them navigate the assessment uncertainty before them. Although the impetus is AI, the Guide grounds its path in pedagogical theory, considers the range of human responses, and then deals with assessment types, challenges, AI roles as tutor and learner, and required competencies.

Children's executive functioning and health behaviors across pediatric life stages and ecological contexts.

Executive functioning (EF) has been linked to chronic disease risk in children. Health behaviors are thought to partially explain this association. The current cross-sectional study evaluated specific domains of EF and varied health behaviors in three pediatric life stages.

Central Nervous System Metastases in Breast Cancer.

Breast cancer metastasizing to the central nervous system (CNS) encompasses two distinct entities: brain metastases involving the cerebral parenchyma and infiltration of the leptomeningeal space, i.e., leptomeningeal disease.

Heterogeneity in Developmental Trajectories of Internalizing and Externalizing Symptomatology: Associations with Risk and Protective Factors.

Among a large sample of youth (9-10 years old at baseline) from the Adolescent Brain Cognitive Development (ABCD) Study® (n = 11,661) we modeled trajectories of psychopathology over three years and associated risk and protective factors. Growth mixture modeling characterized latent classes with distinct psychopathology trajectories. Results indicated four different internalizing trajectories: a high-decreasing class, a moderate-decreasing class, a moderate-increasing class, and a low-stable class.

CAGI6 ID panel challenge: assessment of phenotype and variant predictions in 415 children with neurodevelopmental disorders (NDDs).

The Genetics of Neurodevelopmental Disorders Lab in Padua provided a new intellectual disability (ID) Panel challenge for computational methods to predict patient phenotypes and their causal variants in the context of the Critical Assessment of the Genome Interpretation, 6th edition (CAGI6). Eight research teams submitted a total of 30 models to predict phenotypes based on the sequences of 74 genes (VCF format) in 415 pediatric patients affected by Neurodevelopmental Disorders (NDDs). NDDs are clinically and genetically heterogeneous conditions, with onset in infant age.

Preservation of Cardiac Xenografts in a Model of Infant Human Cardiac Transplantation.

Introduction: There is no standard protocol for management of organ preservation for orthotopic, life-sustaining cardiac xenotransplantation, particularly for hearts from pediatric sized donors. Standard techniques and solutions successful in human allotransplantation are not viable. We theorized that a solution commonly used in reparative cardiac surgery in human children would suffice by exploiting the advantages inherent to xenotransplantation, namely the ability to reduce organ ischemic times by co-locating the donor and recipient.

Differential impacts of ribosomal protein haploinsufficiency on mitochondrial function.

The interplay between ribosomal protein (RP) composition and mitochondrial function is essential for energy homeostasis. Balanced RP production optimizes protein synthesis while minimizing energy costs, but its impact on mitochondrial functionality remains unclear. Here, we investigated haploinsufficiency for RP genes (rps-10, rpl-5, rpl-33, and rps-23) in Caenorhabditis elegans and corresponding reductions in human lymphoblast cells.

α-Catenin force-sensitive binding and sequestration of LZTS2 leads to cytokinesis failure.

Epithelial cells can become polyploid upon tissue injury, but mechanosensitive cues that trigger this state are poorly understood. Using an Madin Darby Canine Kidney (MDCK) cell knock-out/reconstitution system, we show that α-catenin mutants that alter force-sensitive binding to F-actin or middle (M)-domain promote cytokinesis failure and binucleation, particularly near epithelial wound-fronts. We identified Leucine Zipper Tumor Suppressor 2 (LZTS2), a factor previously implicated in abscission, as a conformation sensitive proximity partner of α-catenin.

Public Health.

Background: Most research on cognitive difficulties in the US focus on minoritized groups that are part of the federal minimum reporting guidelines, include White, Black, Hispanic/Latino, Asian, American Indian/Alaskan Native (AI/AN), and Native Hawaiian/Other Pacific Islander (NH/OPI) individuals. Research has begun to describe cognitive difficulties among Middle Eastern and North African (MENA) adults, but it is limited because they are defined as White. In 2023, the Office of Management and Budget (OMB) proposed adding a separate checkbox for MENA individuals.

Trauma-focused evidence-based psychotherapy for post-traumatic stress disorder delivered via video telehealth in the Veterans Health Administration.

Introduction: Trauma-focused evidence-based psychotherapy (EBP) is the recommended treatment for post-traumatic stress disorder (PTSD). During and after the COVID-19 pandemic, veterans began to initiate general mental health services delivered via video telehealth at high rates. Our goal in the current project was to describe the percentage as well as the demographic, military, and clinical characteristics of veterans receiving PTSD EBPs via video telehealth versus in-person.

Developing Topics.

Background: We examined the relationship between nursing home (NH) COVID-19 mortality rates and changes in antidementia and psychotropic medication initiation before and during the pandemic and explored the influence of staffing and resident factors.

Method: Changes in medication initiation were collected through a nationally representative cross-sectional Dementia Treatment Survey (2022) of NH Directors of Nursing. Outcome measures were created by collapsing a 5-point Likert scale contrasting less/about the same vs.

Variability of interobserver interpretation of selected helminth ova in the development of a training image set.

Background: Diagnosis of soil-transmitted helminthiasis and schistosomiasis for surveillance relies on microscopic detection of ova in Kato-Katz (KK) prepared slides. Artificial intelligence (AI)-based platforms for parasitic eggs may be developed using a robust image set with defined labels by reference microscopists. This study aimed to determine interobserver variability among reference microscopists in identifying parasite ova.