73,341 results match your criteria: "b Clinical R&D[Affiliation]"

Background: Increased attention has been focused on the association of periodontal disease with cardio-metabolic syndrome. Although the associations are multi-factorial, very few studies have explored the role of lipoprotein Apo A1 and Apo B100 with chronic periodontitis. Additionally, obstructive sleep apnea (OSA), a chronic multi-factorial respiratory disease, consists of a temporary decrease or cessation of breath for ≥ 10 seconds and leads to a reduction in blood oxygen saturation of more than 3% to 4% and/or neurological arousal.

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Multi-Omics Analysis for Identifying Cell-Type-Specific Druggable Targets in Alzheimer's Disease.

medRxiv

January 2025

Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 550 N. University Blvd. Indianapolis, IN, 46202, USA.

Background: Analyzing disease-linked genetic variants via expression quantitative trait loci (eQTLs) is important for identifying potential disease-causing genes. Previous research prioritized genes by integrating Genome-Wide Association Study (GWAS) results with tissue-level eQTLs. Recent studies have explored brain cell type-specific eQTLs, but they lack a systematic analysis across various Alzheimer's disease (AD) GWAS datasets, nor did they compare effects between tissue and cell type levels or across different cell type-specific eQTL datasets.

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Background: Early antifungal initiation in invasive aspergillosis (IA) is recommended. Changing antifungals occurs for a myriad of reasons but associated costs are unclear.

Methods: US claims data for adults admitted for IA were identified from 10/1/2015 to 11/30/2022.

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Relaxin mimetic in pulmonary hypertension associated with left heart disease: Design and rationale of Re-PHIRE.

ESC Heart Fail

January 2025

Department of Cardiology, Pulmonology, and Intensive Care Medicine, Center for Molecular Medicine Cologne (CMMC), Cologne Cardiovascular Research Center (CCRC), Medical Faculty, University of Cologne, Cologne, Germany.

Aims: Despite receiving guideline-directed medical heart failure (HF) therapy, patients with pulmonary hypertension associated with left heart disease (PH-LHD) experience higher mortality and hospitalization rates than the general HF population. AZD3427 is a functionally selective, long-acting mimetic of relaxin, a hormone that has the potential to induce vasodilation and prevent fibrosis. In a phase 1b study conducted in patients with HF, AZD3427 demonstrated a favourable safety and pharmacokinetic profile.

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Traditional natural polysaccharide-based hydrogels, when used as drug carriers, often struggle to maintain long-term stability in the extremely harsh gastric environment. This results in unstable drug release and significant challenges in bioavailability. To address this issue, this study utilized inexpensive and safe natural polysaccharides-chitosan (CS) and high methoxyl pectin (HM)-as raw materials.

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Objectives: To assess different tear film parameters in female patients with thyroid eye disease and diabetes using a single portable device.

Methods: The observational study was conducted at the College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia, from January 12 to April 28, 2022, and comprised women patients with thyroid eye disease in group A, women patients with diabetes in group B, and healthy controls in group C. The sample size was determined with a confidence level of 80% and a significance of 0.

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Background: We previously reported the safety and immunogenicity data from a randomized trial comparing the booster responses of vaccinees who received monovalent (MV) recombinant protein Beta-variant (MVB.1.351) and MV ancestral protein (MVD614) vaccines with AS03 adjuvant (Sanofi/GSK) to booster response of vaccinees who received mRNA MV ancestral strain BNT162b2 vaccine (Pfizer-BioNTech).

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As next-generation sequencing technologies produce deeper genome coverages at lower costs, there is a critical need for reliable computational host DNA removal in metagenomic data. We find that insufficient host filtration using prior human genome references can introduce false sex biases and inadvertently permit flow-through of host-specific DNA during bioinformatic analyses, which could be exploited for individual identification. To address these issues, we introduce and benchmark three host filtration methods of varying throughput, with concomitant applications across low biomass samples such as skin and high microbial biomass datasets including fecal samples.

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Advances in the structural understanding of opioid allostery.

Trends Pharmacol Sci

January 2025

Department of Anesthesiology and Washington University Pain Center, Washington University School of Medicine, St Louis, MO, USA; Center for Clinical Pharmacology, Washington University School of Medicine, St Louis, MO, USA. Electronic address:

Activation of the μ opioid receptor (MOR) can give analgesia, but also has dangerous side effects. Drugs that target MOR through an allosteric site, meaning they bind outside of the usual pocket, present a novel mode of receptor activation with different pharmacology relative to orthosteric drugs. Recent structural studies give valuable new information on how allosteric modulators interact with MOR.

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Functional capacity at rehabilitation discharge predicts physical activity characteristics twenty-four weeks later for people with total knee arthroplasty: a secondary analysis of a randomized controlled trial.

Arch Phys Med Rehabil

January 2025

Geriatric, Research, Education, and Clinical Center, VA Eastern Colorado Healthcare System, Aurora, CO, USA; Department of Physical Medicine and Rehabilitation, University of Colorado, Aurora, CO, USA. Electronic address:

Objective: To determine the association between performance-based and patient-reported functional capacity at the conclusion of 12-week rehabilitation with average daily step counts and peak walking cadence 38 weeks following total knee arthroplasty (TKA).

Design: Secondary analysis of an RCT.

Setting: Veterans Affairs Medical Center.

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Background: Preeclampsia is a key cause of prematurity in the U.S. and incurs significant healthcare costs.

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Background: Celiac disease (CeD) has shown an association with autoimmune disorders including vitiligo and alopecia areata (AA). Ritlecitinib, a JAK3 and TEC kinase family inhibitor, has been approved for treatment of patients with AA and is in late-stage development for vitiligo. Ritlecitinib inhibits cytotoxic T cells, NK cells, and B cells which play a role in the pathogenesis of CeD.

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Background: Spinal cord (SC) atrophy is a key imaging biomarker of progressive multiple sclerosis (MS). Progressive MS is more common in men and postmenopausal women.

Objective: Investigate the impact of sex and menopause on SC measurements in persons with MS (pwMS).

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Chinese Registry of Rheumatoid Arthritis (CREDIT) VI: Temporal Trends in Patients With Early Rheumatoid Arthritis and Moderate-To-Severe Disease Activity - A Multicenter Cohort Study of Treatment Strategies and Outcomes.

Int J Rheum Dis

January 2025

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences and Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science and Technology; State Key Laboratory of Complex Severe and Rare Diseases; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Aim: The continuous update of international guidelines and enhanced availability of biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) have made a significant impact on the diagnosis and treatment of early rheumatoid arthritis (ERA). This study aims to systematically evaluate the current treatment strategies and outcomes within a large-scale cohort of patients with ERA.

Methods: Data from the Chinese Registry of Rheumatoid Arthritis (CREDIT), a large multicenter Chinese registry of RA, were collected to analyze temporal trends in clinical profiles, therapeutic strategies, and treatment outcomes among patients with ERA.

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Anti-CD19 chimeric antigen receptor T cells (CAR) are a well-established treatment option for children and young adults suffering from relapsed/refractory B-lineage acute lymphoblastic leukemia. Bridging therapy is used to control disease prior to start of lymphodepletion before CAR infusion and thereby improve efficacy of CAR therapy. However, the effect of different bridging strategies on outcome, side effects and response to CAR therapy is still poorly understood.

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Myoelectric pattern recognition with virtual reality and serious gaming improves upper limb function in chronic stroke: a single case experimental design study.

J Neuroeng Rehabil

January 2025

Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Vita Stråket 12, Floor 4, 41346, Gothenburg, Sweden.

Background: Myoelectric pattern recognition (MPR) combines multiple surface electromyography channels with a machine learning algorithm to decode motor intention with an aim to enhance upper limb function after stroke. This study aims to determine the feasibility and preliminary effectiveness of a novel intervention combining MPR, virtual reality (VR), and serious gaming to improve upper limb function in people with chronic stroke.

Methods: In this single case experimental A-B-A design study, six individuals with chronic stroke and moderate to severe upper limb impairment completed 18, 2 h sessions, 3 times a week.

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Background: Helicobacter pylori (H. pylori), a specific bacterium capable of surviving in the acidic environment of the stomach, has been recognized as a group of causative agents of gastric cancer. Therefore, the development of mucosal vaccines against H.

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Background: Low-grade glioma (LGG) is a primary brain tumor with relatively low malignancy. NCOA4 is a key regulator of ferritinophagy-related processes and is involved in the occurrence and development of many cancers. However, the role of NCOA4 in LGG remains poorly understood.

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Background: Huntington disease (HD) is a progressive neurodegenerative disease that causes psychiatric and neurological symptoms, including involuntary and irregular muscle movements (chorea). Chorea can disrupt activities of daily living, pose safety issues, and may lead to social withdrawal. The vesicular monoamine transporter 2 inhibitors tetrabenazine, deutetrabenazine, and valbenazine are approved treatments that can reduce chorea.

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Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

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Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.

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Digital twins in precision medicine provide tailored health recommendations by simulating patient-specific trajectories and interventions. We examine the critical role of Verification, Validation, and Uncertainty Quantification (VVUQ) for digital twins in ensuring safety and efficacy, with examples in cardiology and oncology. We highlight challenges and opportunities for developing personalized trial methodologies, validation metrics, and standardizing VVUQ processes.

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Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide in all age groups and cause significant disease and economic burden globally. To date, no approved vaccines or antiviral therapies are available to treat or prevent HuNoV illness. Several candidate vaccines are in clinical trials, although potential barriers to successful development must be overcome.

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Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost.

Nat Commun

January 2025

Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.

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