Fibroblast transcriptomics uncovers pathogenic genomic variants in individuals with exome-negative childhood onset epilepsy.

Objective: This study aims to improve genetic diagnosis in childhood onset epilepsy with neurodevelopmental problems by utilizing RNA sequencing of fibroblasts to identify pathogenic variants that may be missed by exome sequencing and copy number variation analysis.

Methods: We enrolled 41 individuals with childhood onset epilepsy and neurodevelopmental problems who previously had inconclusive genetic testing. Fibroblast samples were cultured and analyzed using RNA sequencing to detect aberrant expression, aberrant splicing, and monoallelic expression using the Detection of RNA Outlier Pipeline (DROP) pipeline.

Trends in the incidence and mutational landscape of advanced uterine cancer.

Objective: The aim of this study was to examine disparities in 20-year incidence trends and mutations in advanced-stage uterine cancer in the United States, given poor survival rates.

Methods: Data were obtained from the United States Cancer Statistics for patients from 2001 to 2019 with International Federation of Gynecology and Obstetrics 2009 stage IVA and IVB uterine cancer. SEER∗Stat 8.

Central Nervous System Response Against Ionizing Radiation Exposure: Cellular, Biochemical, and Molecular Perspectives.

Gamma radiation is known to induce several detrimental effects on the nervous system. The hippocampus region, specifically the dentate gyrus (DG) and subventricular zone (SVZ), have been identified as a radiation-sensitive neurogenic niche. Radiation alters the endogenous redox status of neural stem cells (NSCs) and other proliferative cells, especially in the hippocampus region, leading to oxidative stress, neuroinflammation, and cell death.

Screening a 681-membered yeast collection for the secretion of proteins with antifungal activity.

Fungal pathogens pose a threat to human health and food security. Few antifungals are available and resistance to all has been reported. Novel strategies to control plant and human pathogens as well as food spoilers are urgently required.

Association of Obesity and Skeletal Muscle with Postoperative Survival in Non-Small Cell Lung Cancer.

Background A comprehensive assessment of skeletal muscle health is crucial to understanding the association between improved clinical outcomes and obesity as defined by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) in lung cancer, but limited studies have been conducted on this topic. Purpose To investigate the association between BMI-defined obesity and survival in patients with non-small cell lung cancer who underwent curative resection, with a specific focus on the status of skeletal muscle assessed at CT. Materials and Methods This retrospective study investigated Korean patients with non-small cell lung cancer who underwent curative resection between January 2008 and December 2019.

Large-Scale Validation of the Feasibility of GPT-4 as a Proofreading Tool for Head CT Reports.

Background The increasing workload of radiologists can lead to burnout and errors in radiology reports. Large language models, such as OpenAI's GPT-4, hold promise as error revision tools for radiology. Purpose To test the feasibility of GPT-4 use by determining its error detection, reasoning, and revision performance on head CT reports with varying error types and to validate its clinical utility by comparison with human readers.

A Cross-Species Atlas of the Dorsal Vagal Complex Reveals Neural Mediators of Cagrilintide's Effects on Energy Balance.

Amylin analogs, including potential anti-obesity therapies like cagrilintide, act on neurons in the brainstem dorsal vagal complex (DVC) that express calcitonin receptors (CALCR). These receptors, often combined with receptor activity-modifying proteins (RAMPs), mediate the suppression of food intake and body weight. To understand the molecular and neural mechanisms of cagrilintide action, we used single-nucleus RNA sequencing to define 89 cell populations across the rat, mouse, and non-human primate caudal brainstem.

Lower incidence of hepatocellular carcinoma with tenofovir alafenamide in chronic hepatitis B: Evidence from a large-scale cohort.

Background & Aims: Tenofovir alafenamide (TAF) lacks extensive research regarding its impact on hepatocellular carcinoma (HCC). This study evaluated and compared the effects of TAF, tenofovir disoproxil fumarate (TDF), and entecavir (ETV) on HCC incidence using nationwide claim data.

Methods: In total, 75,816 patients with treatment-naïve HBV were included in the study and divided into TAF (n = 25,680), TDF (n = 26,954), and ETV (n = 23,182) groups after exclusions.

Genome-wide profiling of tRNA modifications by Induro-tRNAseq reveals coordinated changes.

While all native tRNAs undergo extensive post-transcriptional modifications as a mechanism to regulate gene expression, mapping these modifications remains challenging. The critical barrier is the difficulty of readthrough of modifications by reverse transcriptases (RTs). Here we use Induro-a new group-II intron-encoded RT-to map and quantify genome-wide tRNA modifications in Induro-tRNAseq.

Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial.

Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC.

Explainable vision transformer for automatic visual sleep staging on multimodal PSG signals.

Polysomnography (PSG) is crucial for diagnosing sleep disorders, but manual scoring of PSG is time-consuming and subjective, leading to high variability. While machine-learning models have improved PSG scoring, their clinical use is hindered by the 'black-box' nature. In this study, we present SleepXViT, an automatic sleep staging system using Vision Transformer (ViT) that provides intuitive, consistent explanations by mimicking human 'visual scoring'.

Comparison of Interportal and Periportal Capsulotomies and Axial Distraction Resistance During Hip Arthroscopy: An In Vivo Propensity-Matched Cohort Study.

Background: Intraoperative hip capsule management is increasingly recognized as an important component of hip arthroscopy for the prevention of capsular-related instability. The periportal capsulotomy, relative to the interportal capsulotomy, has been proposed as a minimally invasive technique for decreasing postarthroscopy hip instability; however, the biomechanical effects of this technique are not well established.

Purpose/hypothesis: This study aimed to provide a biomechanical characterization of interportal and periportal capsulotomies, helping inform surgeon choice of capsulotomy type and repair, potentially guiding clinical practice in hip arthroscopy.

Visual Acuity Outcomes and Influencing Factors in a Cohort of UK Real-World Diabetic Macular Oedema Patients During the First Two Years of Anti-VEGF Treatment.

Background/objectives: The visual acuity (VA) outcomes after the first and second years of anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with diabetic macular oedema (DMO) were evaluated, and the factors associated with treatment success were investigated.

Methods: Using Medisoft electronic medical records (UK), this retrospective cohort study analysed VA outcomes, changes, and determinants in DMO patients at year 1 and year 2 after initial anti-VEGF injection. Descriptive analysis examined baseline demographics and clinical characteristics, while regression models were used to assess associations between these factors and changes in VA.

Harnessing the AI/ML in Drug and Biological Products Discovery and Development: The Regulatory Perspective.

Artificial Intelligence (AI) has the disruptive potential to transform patients' lives via innovations in pharmaceutical sciences, drug development, clinical trials, and manufacturing. However, it presents significant challenges, ethical concerns, and risks across sectors and societies. AI's rapid advancement has revealed regulatory gaps as existing public policies struggle to keep pace with the challenges posed by these emerging technologies.

The Role of microRNA-22 in Metabolism.

microRNA-22 (miR-22) plays a pivotal role in the regulation of metabolic processes and has emerged as a therapeutic target in metabolic disorders, including obesity, type 2 diabetes, and metabolic-associated liver diseases. While miR-22 exhibits context-dependent effects, promoting or inhibiting metabolic pathways depending on tissue and condition, current research highlights its therapeutic potential, particularly through inhibition strategies using chemically modified antisense oligonucleotides. This review examines the dual regulatory functions of miR-22 across key metabolic pathways, offering perspectives on its integration into next-generation diagnostic and therapeutic approaches while acknowledging the complexities of its roles in metabolic homeostasis.

Order in Chaos: Lesser-Conserved and Repeat Structures in Dehydrins.

Dehydrins (Dhns) are a group of intrinsically disordered land plant proteins that are closely associated with tolerance of dehydrative stress. Dhns are recognized and classified by the presence and sequence of five different conserved segments, varying in length from 8 to 15 residues, separated by highly variable disordered regions. In addition to one or more copies of the diagnostic, fifteen-residue K segment, most Dhns can be classified into one of three major groups based on the mutually exclusive presence of three other conserved segments (H, Y, or F), with all three groups typically incorporating multi-serine S segments.

Evolving Trends and Patterns of Utilization of Magnetic Resonance-Guided Radiotherapy at a Single Institution, 2018-2024.

: Over the past decade, significant advances have been made in image-guided radiotherapy (RT) particularly with the introduction of magnetic resonance (MR)-guided radiotherapy (MRgRT). However, the optimal clinical applications of MRgRT are still evolving. The intent of this analysis was to describe our institutional MRgRT utilization patterns and evolution therein, specifically as an early adopter within a center endowed with multiple other technology platforms.

Affordable mRNA Novel Proteins, Recombinant Protein Conversions, and Biosimilars-Advice to Developers and Regulatory Agencies.

mRNA technology can replace the expensive recombinant technology for every type of protein, making biological drugs more affordable. It can also expedite the entry of new biological drugs, and copies of approved mRNA products can be treated as generic or biosimilar products due to their chemical nature. The introduction of hundreds of new protein drugs have been blocked due to the high cost of recombinant development.

Pediatric COVID-19 severity by SARS-CoV-2 lineage and vaccine status in Canada: an IMPACT study.

Background: Interpretations of pediatric COVID-19 severity are complicated by novel lineages and COVID-19 vaccine introduction. We estimated the risk of severe COVID-19 by SARS-CoV-2 lineage and vaccination status among hospitalized Canadian children.

Methods: Data were collected through the Canadian Paediatric Surveillance Program (April 2020-May 2021) and Canadian Immunization Monitoring Program, ACTive (June 2021-December 2022).

The Long-Term Immunity of a Microneedle Array Patch of a SARS-CoV-2 S1 Protein Subunit Vaccine Irradiated by Gamma Rays in Mice.

Background/objectives: COVID-19 vaccines effectively prevent severe disease, but unequal distribution, especially in low- and middle-income countries, has led to vaccine-resistant strains. This highlights the urgent need for alternative vaccine platforms that are safe, thermostable, and easy to distribute. This study evaluates the immunogenicity, stability, and scalability of a dissolved microneedle array patch (MAP) delivering the rS1RS09 subunit vaccine, comprising the SARS-CoV-2 S1 monomer and RS09, a TLR-4 agonist peptide.

Exploring the Pharmacokinetics and Gut Microbiota Modulation of Hesperidin and Nobiletin from Mandarin Orange Peel in Experimental Dogs: A Pilot Study.

Mandarin orange peel (MOP) is recognized for its traditional medicinal properties due to its high flavonoid content. This study aimed to analyze MOP harvested in Japan for specific bioactive compounds and to explore its health applications in dogs, including effects on gut microbiota and cognitive symptoms. Flavonoid content (particularly hesperidin and nobiletin) of MOP was measured.

Comparative Investigation of Vortex and Direct Plasma Discharge for Treating Titanium Surface.

Numerous studies have investigated the surface treatment of implants using various types of plasma, including atmospheric pressure plasma and vacuum plasma, to remove impurities and increase surface energy, thereby enhancing osseointegration. Most previous studies have focused on generating plasma directly on the implant surface by using the implant as an electrode for plasma discharge. However, plasmas generated under atmospheric and moderate vacuum conditions often have a limited plasma volume, meaning the shape of the electrodes significantly influences the local electric field characteristics, which in turn affects plasma behavior.

Constraint of Different Knee Implant Designs Under Anterior-Posterior Shear Forces and Internal-External Rotation Moments in Human Cadaveric Knees.

Instability remains one of the most common indications for revision after total knee arthroplasty. To gain a better understanding of how an implant will perform in vivo and support surgeons in selecting the most appropriate implant design for an individual patient, it is crucial to evaluate the implant constraint within clinically relevant ligament and boundary conditions. Therefore, this study investigated the constraint of three different implant designs (symmetrical implants with and without a post-cam mechanism and an asymmetrical medial-stabilized implant) under anterior-posterior shear forces and internal-external rotation moments at different flexion angles in human cadaveric knees using a six-degrees-of-freedom joint motion simulator.

Effect of Ripasudil on the Change Rates of the Circumpapillary Retinal Nerve Fiber Layer Thickness in Patients With Primary Open-Angle Glaucoma.

The effect of the Rho-kinase inhibitor ripasudil on the retinal optic nerve fiber layer (RNFL) remains unclear. We aimed to determine this effect in patients with primary open-angle glaucoma (POAG) using optical coherence tomography (OCT) measurements and linear mixed analysis. This study prospectively included outpatients from a single center with POAG without a history of vitreoretinal or glaucoma surgery from December 2014 to June 2020, in whom the circumpapillary RNFL thickness (cpRNFLT) was measured more than three times before and after ripasudil initiation, without additional medication or surgery during the period.

Neurochemical Alterations Linked to Persistent COVID-19-Induced Anosmia: Probing Into Orbitofrontal Cortex by Magnetic Resonance Spectroscopy.

Background: While many COVID-19-induced anosmia patients recover their sense of smell within a few months, a substantial number of them continue to experience olfactory impairment. In our primary study, the metabolic patterns in orbitofrontal cortex (OFC) were observed to exhibit more alterations than other regions. Hence, this study specifically probes into alterations within OFC region in subjects with persistent COVID-19-induced anosmia.