Discovery of a MET-driven monogenic cause of steatotic liver disease.

Background Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects about a third of adults worldwide and is projected soon to be the leading cause of cirrhosis. It occurs when fat accumulates in hepatocytes and can progress to metabolic dysfunction-associated steatohepatitis (MASH), liver cirrhosis, and hepatocellular carcinoma. MASLD pathogenesis is believed to involve a combination of genetic and environmental risk factors.

Creating a family health history interview protocol for use with undergraduate health professional students: A scoping review.

Background: Family health history can be used as a health promotion tool to assess health risk, improve data collection and disease prevention, initiate interventions, and motivate behavioral change, but its utility as a public health tool has not been fully explored. Collecting information for a family health history can be a challenging task. However, it is an important skill for undergraduate students to learn, particularly those in pre-health majors.

A Prototype "Smart" 3-Dimensionally Printed Model Showcasing Interactivity: Implementing Voice Command for the Ventricular and Cisternal Systems.

The next step in the evolution of static 3-dimensionally (3D) printed models may be the creation of "smart" models, where subcomponents can be seamlessly interacted with through a feedback mechanism, with potential applications in trainee education and patient counseling. Considering the complexity of the ventricular and cisternal systems, they were chosen for segmentation, using Materialize InPrint with outward hollowing using 2.5-mm wall thickness.

Species- and strain-specific microbial modulation of interferon, innate immunity, and epithelial barrier in 2D air-liquid interface respiratory epithelial cultures.

Background: The microbiome regulates the respiratory epithelium's immunomodulatory functions. To explore how the microbiome's biodiversity affects microbe-epithelial interactions, we screened 58 phylogenetically diverse microbes for their transcriptomic effect on human primary bronchial air-liquid interface (ALI) cell cultures.

Results: We found distinct species- and strain-level differences in host innate immunity and epithelial barrier response.

Ketamine Versus Midazolam as the First-Line Continuous Infusion for Status Epilepticus in Children with Cardiac Disease.

Background: The treatment of status epilepticus (SE) in children with cardiac disease is challenging given their often-tenuous hemodynamic state. We aim to determine whether ketamine is safe and effective in children with cardiac disease as the first-line continuous infusion for the treatment of refractory SE (RSE) and to compare ketamine to midazolam for the treatment of RSE in this population.

Methods: This is a single-center retrospective cohort study of pediatric patients with cardiac disease and RSE admitted to the cardiac intensive care unit at a tertiary children's hospital between January 1, 2017 and June 30, 2023.

Evaluating pathogenicity of variants of unknown significance in APP, PSEN1, and PSEN2.

Autosomal dominant Alzheimer's disease (ADAD) is driven by rare variants in APP, PSEN1, and PSEN2. Although more than 200 pathogenic variants in these genes are known to cause ADAD, other variants are benign, may act as risk factors, or may even reduce Alzheimer's disease risk (e.g.

Exploring the neuroprotective potential of immunosuppressants in Parkinson's disease.

Introduction: Neuroprotective therapy to slow Parkinson's disease (PD) progression is a critical unmet need. Neuroinflammation likely represents an important pathophysiologic mechanism for disease progression. Medications that target this inflammation, such as immunosuppressants, represent potential disease-modifying therapies for PD.

Retinoic acid antagonizes estrogen signaling to maintain adult uterine cell fate.

Classical tissue recombination experiments demonstrate that cell-fate determination along the anterior-posterior axis of the Müllerian duct occurs prior to postnatal day 7 in mice. However, little is known about how these cell types are maintained in adults. In this study, we provide genetic evidence that a balance between antagonistic retinoic acid (RA) and estrogen signaling activity is required to maintain simple columnar cell fate in adult uterine epithelium.

Surgical Management of Meniscus Tears: Update on Indications and Techniques for Repair.

Because of the crucial role of the menisci in maintaining cartilage and joint health, meniscal tears affect the long-term health of the knee. Although partial meniscectomy has a role in the treatment of complex degenerative tears and tears with low healing capacity, advances in the concepts and understanding of meniscal repair, along with improvements in repair techniques and instrumentation, have expanded the indications for meniscal repair. With appropriate patient selection and preoperative planning, repair of meniscal tears can lower the rate of degenerative changes when compared with meniscectomy.

Nebulized aminoglycosides for ventilator-associated pneumonia: Methodological considerations and lessons from experimental studies.

Aminoglycosides are concentration-dependent antibiotics exerting a bactericidal effect when concentrations at the site of infection are equal to or greater than 5 times the minimum inhibitory concentrations (MIC). When administered intravenously, they exhibit poor lung penetration and high systemic renal and ototoxicity, imposing to restrict their administration to 5 days. Experimental studies conducted in anesthetized and mechanically ventilated sheep and pigs provide evidence that high doses of nebulized aminoglycosides induce a rapid and potent bacterial killing in the infected lung parenchyma.

Environment scan of generative AI infrastructure for clinical and translational science.

This study reports a comprehensive environmental scan of the generative AI (GenAI) infrastructure in the national network for clinical and translational science across 36 institutions supported by the CTSA Program led by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) at the United States. Key findings indicate a diverse range of institutional strategies, with most organizations in the experimental phase of GenAI deployment. The results underscore the need for a more coordinated approach to GenAI governance, emphasizing collaboration among senior leaders, clinicians, information technology staff, and researchers.

Rome Foundation Working Team Report on overlap in disorders of gut-brain interaction.

In patients with disorders of gut-brain interaction (DGBI), overlapping non-gastrointestinal conditions such as fibromyalgia, headaches, gynaecological and urological conditions, sleep disturbances and fatigue are common, as is overlap among DGBI in different regions of the gastrointestinal tract. These overlaps strongly influence patient management and outcome. Shared pathophysiology could explain this scenario, but details are not fully understood.

NAD World 3.0: the importance of the NMN transporter and eNAMPT in mammalian aging and longevity control.

Over the past five years, systemic NAD (nicotinamide adenine dinucleotide) decline has been accepted to be a key driving force of aging in the field of aging research. The original version of the NAD World concept was proposed in 2009, providing an integrated view of the NAD-centric, systemic regulatory network for mammalian aging and longevity control. The reformulated version of the concept, the NAD World 2.

An Artificial Intelligence Model Using Diffusion Basis Spectrum Imaging Metrics Accurately Predicts Clinically Significant Prostate Cancer.

Purpose: Conventional prostate magnetic resonance imaging has limited accuracy for clinically significant prostate cancer (csPCa). We performed diffusion basis spectrum imaging (DBSI) prior to biopsy and applied artificial intelligence models to these DBSI metrics to predict csPCa.

Materials And Methods: Between February 2020 and March 2024, 241 patients underwent prostate MRI that included conventional and DBSI-specific sequences prior to prostate biopsy.

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.

Association of rapid eye movement sleep latency with multimodal biomarkers of Alzheimer's disease.

Introduction: Sleep disturbances are associated with Alzheimer's disease (AD) and Alzheimer's disease and related dementias (ADRD), but the relationship between sleep architecture, particularly rapid eye movement (REM) sleep, and AD/ADRD biomarkers remains unclear.

Methods: We enrolled 128 adults (64 with Alzheimer's disease, 41 with mild cognitive impairment [MCI], and 23 with normal cognition [NC]), mean age 70.8 ± 9.

Intestinal Bacteroides drives glioma progression by regulating CD8+ T cell tumor infiltration.

Background: The intestinal microbiota regulates normal brain physiology and the pathogenesis of several neurological disorders. While prior studies suggested that this regulation operates through immune cells, the underlying mechanisms remain unclear. Leveraging two well characterized murine models of low-grade glioma (LGG) occurring in the setting of the neurofibromatosis type 1 (NF1) cancer predisposition syndrome, we sought to determine the impact of the gut microbiome on optic glioma progression.

Frontline Voice: AO Spine Member Survey Regarding Spine Oncology Knowledge Generation and Translation Needs.

Study Design: cross-sectional survey.

Objectives: To evaluate AO Spine members' practices and comfort in managing metastatic and primary spine tumors, explore the use of decision-support and patient assessment tools, and identify knowledge gaps and future needs in spine oncology.

Methods: An online survey was distributed to AO Spine members to query comfort levels with key decisions in spinal oncology management, utilization of decision frameworks and spine oncology-specific instruments, and educational material preferences.

methylGrapher: genome-graph-based processing of DNA methylation data from whole genome bisulfite sequencing.

Genome graphs, including the recently released draft human pangenome graph, can represent the breadth of genetic diversity and thus transcend the limits of traditional linear reference genomes. However, there are no genome-graph-compatible tools for analyzing whole genome bisulfite sequencing (WGBS) data. To close this gap, we introduce methylGrapher, a tool tailored for accurate DNA methylation analysis by mapping WGBS data to a genome graph.

ATG-3 limits Orsay virus infection in through regulation of collagen pathways.

Autophagy is an essential cellular process which functions to maintain homeostasis in response to stressors such as starvation or infection. Here, we report that a subset of autophagy factors including ATG-3 play an antiviral role in Orsay virus infection of . Orsay virus infection does not modulate autophagic flux, and re-feeding after starvation limits Orsay virus infection and blocks autophagic flux, suggesting that the role of ATG-3 in Orsay virus susceptibility is independent of its role in maintaining autophagic flux.