First-in-human study with SAR445088: A novel selective classical complement pathway inhibitor.

SAR445088 is an anti-C1s humanized monoclonal antibody that inhibits activated C1s in the proximal portion of the classical complement system and has the potential to provide clinical benefit in the treatment of complement-mediated diseases. A phase I, first-in-human, double-blind, randomized, placebo-controlled, dose-escalation trial of single and multiple doses of SAR445088 was conducted in 93 healthy participants to evaluate the safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) profiles. Single (intravenous [i.

Spatial maps of T cell receptors and transcriptomes reveal distinct immune niches and interactions in the adaptive immune response.

T cells mediate antigen-specific immune responses to disease through the specificity and diversity of their clonotypic T cell receptors (TCRs). Determining the spatial distributions of T cell clonotypes in tissues is essential to understanding T cell behavior, but spatial sequencing methods remain unable to profile the TCR repertoire. Here, we developed Slide-TCR-seq, a 10-μm-resolution method, to sequence whole transcriptomes and TCRs within intact tissues.

Association of Adipopenia at Preoperative PET/CT with Mortality in Stage I Non-Small Cell Lung Cancer.

Background Body mass index (BMI) and sarcopenia status are well-established prognostic factors in patients with lung cancer. However, the relationship between the amount of adipose tissue and survival remains unclear. Purpose To investigate the association between baseline adipopenia and outcomes in patients with early-stage non-small cell lung cancer (NSCLC).

Inhibition of HDACs (Histone Deacetylases) Ameliorates High-Fat Diet-Induced Hypertension Through Restoration of the MsrA (Methionine Sulfoxide Reductase A)/Hydrogen Sulfide Axis.

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FKBP5-associated miRNA signature as a putative biomarker for PTSD in recently traumatized individuals.

The epigenetic regulation of microRNA (miRNA) expression related to the FK506-binding protein 5 (FKBP5) gene may contribute to the risk of stress-related disorders such as posttraumatic stress disorder (PTSD). Here, we identified candidate miRNAs derived from FKBP5 knockout mice as a potential diagnostic biomarker of PTSD. Using a translational approach, candidate miRNAs found to alter in expression within the medial prefrontal cortex of FKBP5 knockout mice were selected.

Prognostic Effects of Treatment Strategies for Left Main Versus Non-Left Main Bifurcation Percutaneous Coronary Intervention With Current-Generation Drug-Eluting Stent.

Background: Although 1-stent with provisional approach is the preferred strategy for the treatment of bifurcation lesions, the optimal treatment strategy according to lesion location is still debatable. This study aimed to identify whether clinical outcomes according to treatment strategy differed between left main (LM) and non-LM bifurcation lesions in the second-generation drug-eluting stent era.

Methods: The Coronary Bifurcation Stenting registry III is a retrospective multicenter registry of 2648 patients with bifurcation lesions who underwent percutaneous coronary intervention with second-generation drug-eluting stent.

Competitive α-glucosidase inhibitors, dihydrobenzoxanthones, from the barks of .

This study aimed to search the α-glucosidase inhibitors from the barks part of . The responsible compounds for α-glucosidase inhibition were found out as dihydrobenzoxanthones (-) and alkylated flavones (-). All compounds showed a significant enzyme inhibition toward α-glucosidase with ICs of 7.

Mild behavioral impairment is linked to worse cognition and brain atrophy in Parkinson disease.

Objective: To evaluate the associations of mild behavioral impairment (MBI) with cognitive deficits and patterns of gray matter changes in Parkinson disease (PD).

Methods: Sixty patients with PD without dementia and 29 healthy controls underwent a cognitive neuropsychological evaluation and structural MRI scan. MBI was evaluated with the MBI Checklist (MBI-C), a rating scale designed to elicit emergent neuropsychiatric symptoms in accordance with MBI criteria.

Nondiagnostic Percutaneous Transthoracic Needle Biopsy of Lung Lesions: A Multicenter Study of Malignancy Risk.

Purpose To evaluate the malignancy risk of lung lesions that show nondiagnostic results at transthoracic needle biopsy (PTNB) of the lung and to identify any malignancy-associated risk factors in each nondiagnostic category. Materials and Methods In this retrospective study, 9384 initial PTNBs (9239 patients [mean age, 65 years; age range, 20-99 years] consisting of 5729 men [mean age, 66 years; age range, 20-99 years] and 3510 women [mean age, 63 years; age range, 20-94 years]) were performed in eight institutions between January 2010 and December 2014. PTNB results were categorized as diagnostic (malignant or specifically benign) or nondiagnostic (nonspecific benign pathologic findings, atypical cells, or insufficient specimen), and the proportion of final malignant diagnoses per nondiagnostic category was obtained.

Mechanisms Underlying Epicardial Radiofrequency Ablation to Suppress Arrhythmogenesis in Experimental Models of Brugada Syndrome.

Objectives: This study sought to test the hypothesis that elimination of sites of abnormal repolarization, via epicardial RFA, suppresses the electrocardiographic and arrhythmic manifestations of BrS.

Background: Brugada syndrome (BrS) is associated with ventricular tachycardia and ventricular fibrillation leading to sudden cardiac death. Nademanee et al.

Prognostic Value of Cardiac MR Imaging for Preoperative Assessment of Patients with Severe Functional Tricuspid Regurgitation.

Purpose To explore the prognostic value of cardiac magnetic resonance (MR) imaging in predicting postoperative cardiac death in patients with severe functional tricuspid regurgitation (TR). Materials and Methods This study was approved by the institutional review board, and written informed consent was obtained from all patients. Prospectively collected data included cardiac MR images, New York Heart Association (NYHA) functional class, a comprehensive laboratory test, and clinical events over the follow-up period in 75 consecutive patients (61 women and 14 men; mean age ± standard deviation, 59 years ± 9) undergoing corrective surgery for severe functional TR.

Proangiogenic Properties of Thrombospondin-4.

Objective: Thrombospondin-4 (TSP-4) is 1 of the 5 members of the thrombospondin protein family. TSP-1 and TSP-2 are potent antiangiogenic proteins. However, angiogenic properties of the 3 other TSPs, which do not contain the domains associated with the antiangiogeneic activity of TSP-1 and TSP-2, have not been explored.

Common and rare variants in the exons and regulatory regions of osteoporosis-related genes improve osteoporotic fracture risk prediction.

Context: Osteoporotic fracture risk is highly heritable, but genome-wide association studies have explained only a small proportion of the heritability to date. Genetic data may improve prediction of fracture risk in osteopenic subjects and assist early intervention and management.

Objective: To detect common and rare variants in coding and regulatory regions related to osteoporosis-related traits, and to investigate whether genetic profiling improves the prediction of fracture risk.

Notch pathway targets proangiogenic regulator Sox17 to restrict angiogenesis.

Rationale: The Notch pathway stabilizes sprouting angiogenesis by favoring stalk cells over tip cells at the vascular front. Because tip and stalk cells have different properties in morphology and function, their transcriptional regulation remains to be distinguished. Transcription factor Sox17 is specifically expressed in endothelial cells, but its expression and role at the vascular front remain largely unknown.

Pharmacokinetic interaction between metoprolol and SP-8203 in rats: competitive inhibition for the metabolism of metoprolol by SP-8203 via hepatic CYP2D subfamily.

1. The occurrence of cerebral ischemia is prevalent in patients with hypertension and the combination drug therapy is needed. Thus, the pharmacokinetic interaction between metoprolol (anti-hypertension drug) and SP-8203 (a new drug candidate for cerebral ischemia) with respect to the metabolism via CYP isozymes was evaluated.

Condensation phenomena of a conserved-mass aggregation model on weighted complex networks.

We investigate the condensation phase transitions of the conserved-mass aggregation (CA) model on weighted scale-free networks (WSFNs). In WSFNs, the weight w_{ij} is assigned to the link between the nodes i and j . We consider the symmetric weight given by w_{ij}=(k_{i}k_{j});{alpha} .

Red cell sodium and ionic fluxes in patients with hyper- and hypothyroidism.

To investigate the status of the Na+ concentrations [Na+]i, K+ concentrations [K+]i and ionic fluxes in red cells of human subjects with abnormal thyroid function, we measured the Na(+)-K+ pump activity as well as Na(+)-K+ cotransport (CoT), Na(+)-Li+ countertransport (CTT) and Na+ passive permeability in erythrocytes of 37 normal subjects, 19 untreated hyperthyroid patients, 12 treated hyperthyroid patients and 9 hypothyroid patients with T4 replacement. The mean [Na+]i value in the untreated hyperthyroidism group was significantly higher than that in the normal subjects (p less than .05), but not significantly different from that in the treated hyperthyroidism group.