Combination Antithrombotic Therapy for Reduction of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease.

Background: Stroke secondary to intracranial atherosclerotic disease (ICAD) is associated with high recurrence risk despite currently available secondary prevention strategies. In patients with systemic atherosclerosis, a significant reduction of stroke risk with no increase in intracranial or fatal hemorrhage was seen when rivaroxaban 2.5 mg twice daily was added to aspirin.

Prevalence and Clinical Outcomes of Discordant Lesions Between Fractional Flow Reserve and Nonhyperemic Pressure Ratios in Clinical Practice: The J-PRIDE Registry.

Background: Limited large-scale, real-world data exist on the prevalence and clinical impact of discordance between fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs).

Methods: The J-PRIDE registry (Clinical Outcomes of Japanese Patients With Coronary Artery Disease Assessed by Resting Indices and Fractional Flow Reserve: A Prospective Multicenter Registry) prospectively enrolled 4304 lesions in 3200 patients from 20 Japanese centers. The lesions were classified into FFR+/NHPR-, FFR-/NHPR+, FFR+/NHPR+, or FFR-/NHPR groups according to cutoff values of 0.

Artificial removal of the zona pellucida at the pronuclear stage: an exploratory study to improve embryo fragmentation.

Objective: To investigate whether artificial removal of zona pellucida (ZP) at the pronuclear stage improves good-quality embryos and blastocyst development in patients with difficulty conceiving because of severe fragmentation in early-cleavage stage.

Design: Exploratory investigation.

Setting: Reproductive center.

Exosomes: Historical Evolution and Emerging Roles in Dermatology.

Background: Exosomes are a nanoscale extracellular vesicles derived from different cell types that have been investigated for various clinical applications, including functioning as biomarkers and use as direct therapeutics. Given the role of exosomes in multiple pathophysiologic pathways and potential practical applications, they have garnered significant interest in the scientific community but much is still unknown about their development and use.

Aims: This literature review covers the background, mechanisms of action, use as biomarkers, methods of application, and direct therapeutic applications of exosomes.

Transcript-specific enrichment enables profiling of rare cell states via single-cell RNA sequencing.

Single-cell genomics technologies have accelerated our understanding of cell-state heterogeneity in diverse contexts. Although single-cell RNA sequencing identifies rare populations that express specific marker transcript combinations, traditional flow sorting requires cell surface markers with high-fidelity antibodies, limiting our ability to interrogate these populations. In addition, many single-cell studies require the isolation of nuclei from tissue, eliminating the ability to enrich learned rare cell states based on extranuclear protein markers.

Toward expert-level medical question answering with large language models.

Large language models (LLMs) have shown promise in medical question answering, with Med-PaLM being the first to exceed a 'passing' score in United States Medical Licensing Examination style questions. However, challenges remain in long-form medical question answering and handling real-world workflows. Here, we present Med-PaLM 2, which bridges these gaps with a combination of base LLM improvements, medical domain fine-tuning and new strategies for improving reasoning and grounding through ensemble refinement and chain of retrieval.

Multimodal cell-free DNA whole-genome TAPS is sensitive and reveals specific cancer signals.

The analysis of circulating tumour DNA (ctDNA) through minimally invasive liquid biopsies is promising for early multi-cancer detection and monitoring minimal residual disease. Most existing methods focus on targeted deep sequencing, but few integrate multiple data modalities. Here, we develop a methodology for ctDNA detection using deep (80x) whole-genome TET-Assisted Pyridine Borane Sequencing (TAPS), a less destructive approach than bisulphite sequencing, which permits the simultaneous analysis of genomic and methylomic data.

Load-bearing capacity of screw-retained fixed dental prostheses made of monolithic zirconia on different abutment designs and abutment-free implant connection.

Objectives: A new abutment-free implant connection allows for direct screwing of FDPs on implants to avoid complications caused by cement rests or screw loosening, which may affect to screw torque and load distribution. The objective of this study was to test the initial (Fi) and final failure (Ff) loads and torque changes of abutment-free monolithic zirconia CAD-CAM fixed dental prostheses (FDPs) compared to titanium FDPs on different abutment designs.

Methods: Three-unit screw-retained FDPs (n = 50) on two implants (n = 100) were divided into groups (n = 10) based on the implant-abutment connection and material of the supra-structure: (1) abutment-free monolithic CAD-CAM zirconia FDP (Abut-free-Zr), (2) abutment-free veneered titanium FDPs (Abut-free-Ti), (3) monolithic zirconia FDPs with titanium base abutments (Zr-Ti-Base), (4) monolithic zirconia FDPs on multi-unit abutments (Zr-MU), (5) veneered titanium FDP on multi-unit abutments (Ti-MU).

Patients With Shoulder Labral Tears Search the Internet to Understand Their Diagnoses and Treatment Options.

Purpose: To analyze the most frequently searched questions associated with shoulder labral pathology and to evaluate the source-type availability and quality.

Methods: Common shoulder labral pathology-related search terms were entered into Google, and the suggested frequently asked questions were compiled and categorized. In addition, suggested sources were recorded, categorized, and scored for quality of information using JAMA benchmark criteria.

All Suture Biceps Tenodesis Has Greater Biomechanical Strength Than Metal Button Fixation.

Purpose: To evaluate the maximal load to failure, cyclic displacement, stiffness, and modes of failure of onlay subpectoral biceps tenodesis with an intramedullary unicortical metal button (MB) versus an inlay, all-suture Caspari-Weber (CW) technique.

Methods: Sixteen matched paired human cadaveric proximal humeri were randomly allocated for subpectoral BT with either CW or MB using a high-strength suture (N = 16; 8 male, 8 female, mean age = 82.5 years, range 62-99 years).

Auxillary aids for pain and anxiety reduction during dental local anesthesia in pediatric patients: a systematic review.

Aims/objectives: This systematic review aimed to evaluate the effectiveness of auxiliary aids-Transcutaneous Electrical Nerve Stimulation (TENS), vibrotactile devices, and Low-Level Laser Therapy (LLLT) in reducing pain and anxiety during dental local anesthesia in pediatric patients.

Methods: The review followed PRISMA guidelines, employing a comprehensive search strategy across multiple databases (PubMed, Cochrane, EBSCO, LILACS, Google Scholar, and Embase) from 2014 to July 2024. Eligibility criteria were based on the PICOS framework, focusing on randomized clinical trials and clinical studies involving pediatric patients undergoing dental procedures with local anesthesia.

Computed tomography-guided microwave ablation therapy for pediatric adrenal neuroblastoma with lung nodule a case report.

Background: Solid lung lesions are common in clinical practice, and percutaneous thermal ablation has been shown to be an effective treatment for these lesions. While computed tomography (CT)-guided microwave ablation (MWA) therapy is frequently used for adult solid lesions, it is rarely considered for pediatric cases.

Case Presentation: A case of an 8-year-old child with adrenal neuroblastoma and a left upper lung mass.

Characterization of Hepatitis B Virus Transcripts in Chronically HBV-Infected Chimpanzees and Patients Treated with ARC-520 siRNA Demonstrates Transcriptional Silencing of cccDNA.

Full-length hepatitis B virus (HBV) transcripts of chimpanzees and patients treated with multidose (MD) HBV siRNA ARC-520 and entecavir (ETV) were characterized by single-molecule real-time (SMRT) sequencing, identifying multiple types of transcripts with the potential to encode HBx, HBsAg, HBeAg, core, and polymerase, as well as transcripts likely to be derived from dimers of dslDNA, and these differed between HBeAg-positive (HBeAg+) and HBeAg-negative (HBeAg-) individuals. HBV transcripts from the last follow-up ~30 months post-ARC-520 treatment were categorized from one HBeAg+ (one of two previously highly viremic patients that became HBeAg- upon treatment and had greatly reduced cccDNA products) and four HBeAg- patients. The previously HBeAg+ patient received a biopsy that revealed that he had 3.

Distributed Consensus Control for Discrete-Time T-S Fuzzy Multiple-Agent Systems Based on an Unknown Input Observer.

This paper investigates a consensus problem for a class of T-S fuzzy multiple-agent systems (MASs) with unknown input (UI). To begin with, an unknown input observer (UIO) is able to asymptotically estimate the system state and the UI is designed for each agent. In order to construct the UIO, the state interval estimation is obtained by first using zonotope theory.

Microstructure and Bioactivity of Ca- and Mg-Modified Silicon Oxycarbide-Based Amorphous Ceramics.

Silicon oxycarbide (SiOC), Ca- and Mg-modified silicon oxycarbide (SiCaOC and SiMgOC) were synthesized via sol-gel processing with subsequent pyrolysis in an inert gas atmosphere. The physicochemical structures of the materials were characterized by XRD, SEM, FTIR, and Si MAS NMR. Biocompatibility and in vitro bioactivity were detected by MTT, cell adhesion assay, and simulated body fluid (SBF) immersion test.

Untargeted Mutation Triggered by Ribonucleoside Embedded in DNA.

DNA polymerases frequently misincorporate ribonucleoside 5'-triphosphates into nascent DNA strands. This study examined the effects of an incorporated ribonucleoside on untargeted mutations in human cells. Riboguanosine (rG) was introduced into the downstream region of the gene to preferentially detect the untargeted mutations.

Bovine Lactoferrin Enhances Toll-like Receptor 7 Response in Plasmacytoid Dendritic Cells and Modulates Cellular Immunity.

Plasmacytoid dendritic cells (pDCs) express Toll-like receptor 7 (TLR7) in the endosomes, recognize viral single-stranded RNA (ssRNA), and produce significant amounts of interferon (IFN)-α. Bovine lactoferrin (LF) enhances the response of IFN regulatory factors followed by the activation of IFN-sensitive response elements located in the promoter regions of the gene and IFN-stimulated genes in the TLR7 reporter THP-1 cells in the presence of R-848, a TLR7 agonist. In ex vivo experiments using human peripheral blood mononuclear cells, LF enhances IFN-α levels in the supernatant in the presence of R-848.

P2 Receptor Antagonists Rescue Defective Heme Content in an In Vitro SLC25A38-Associated Congenital Sideroblastic Anemia Cell Model.

Mutations in the SLC25A38 gene are responsible for the second most common form of congenital sideroblastic anemia (CSA), a severe condition for which no effective treatment exists. We developed and characterized a K562 erythroleukemia cell line with markedly reduced expression of the SLC25A38 protein (A38-low cells). This model successfully recapitulated the main features of CSA, including reduced heme content and mitochondrial respiration, increase in mitochondrial iron, ROS levels and sensitivity to oxidative stress.

Management of Hereditary Transthyretin Amyloidosis (ATTRv) Patients and Asymptomatic Carriers in Spain: The EMPATIa Study.

Hereditary transthyretin amyloidosis (ATTRv) is an autosomal-dominant systemic disease, where amyloid fibrils accumulate especially in the peripheral and autonomic nervous systems and in the heart. The aim of the present work was to outline the follow-up and type of management received by asymptomatic carriers (ACs) and stage 1 ATTRv patients in Spain. A cross-sectional, non-interventional study was conducted throughout seven experienced hospitals in Spain.

Transcutaneous Kilohertz High-Frequency Alternating Current at 10 kHz for Upper-Limb Tremor in People with Parkinson's Disease: A Double-Blind, Randomized, Crossover Study.

Preclinical studies have evidenced a peripheral nerve blockade with kilohertz high-frequency alternating current (KHFAC) stimulation. It could have a potential effect on aberrant nerve hyperactivity, such as tremor in people with Parkinson's disease (PwPD). The objective was to investigate the effects of transcutaneous KHFAC at 10 kHz compared with sham intervention on tremor modulation, upper limb motor function, and adverse events in PwPD.

Pemafibrate Induces a Low Level of PPARα Agonist-Stimulated mRNA Expression of ANGPTL4 in ARPE19 Cell.

To elucidate the unidentified roles of a selective peroxisome proliferator-activated receptor α (PPARα) agonist, pemafibrate (Pema), on the pathogenesis of retinal ischemic diseases (RID)s, the pharmacological effects of Pema on the retinal pigment epithelium (RPE), which is involved in the pathogenesis of RID, were compared with the pharmacological effects of the non-fibrate PPARα agonist GW7647 (GW). For this purpose, the human RPE cell line ARPE19 that was untreated (NT) or treated with Pema or GW was subjected to Seahorse cellular metabolic analysis and RNA sequencing analysis. Real-time cellular metabolic function analysis revealed that pharmacological effects of the PPARα agonist actions on essential metabolic functions in RPE cells were substantially different between Pema-treated cells and GW-treated cells.

Nutrition-Focused Quality Improvement Programs in Pediatric Care.

Nutrition is fundamental to a child's growth and development. However, nutritional health is often compromised by acute and chronic conditions and treatments that can commonly result in malnutrition. Malnutrition encompasses undernutrition and overnutrition and may be exacerbated by food insecurity.

"I Prefer High-Intensity Exercise"-A Qualitative Study of Men's Experiences with a Nature-Based Exercise Program for People with Arthritis.

Arthritis significantly reduces health-related quality of life, causing pain, fatigue, and decreased physical activity. To address this, exercise is highly recommended. However, men are less likely to participate in rehabilitation compared to women.

Sex Differences in Sleep Profiles and the Effect of Elexacaftor/Tezacaftor/Ivacaftor on Sleep Quality in Adult People with Cystic Fibrosis: A Prospective Observational Study.

Background/objectives: Recent studies indicate that sleep and sleep disorders differ between men and women, but corresponding data in people with chronic lung diseases are lacking. This study aims to answer the question of what the sex-specific differences in sleep profiles and responses to elexacaftor/tezacaftor/ivacaftor (ETI) therapy in people with cystic fibrosis (pwCF) are.

Methods: Adult pwCF and a matched control group (adults with suspected sleep-disordered breathing undergoing in-laboratory polysomnography (PSG)) were included.