Time Course for Benefit and Risk of Ticagrelor and Aspirin in Acute Ischemic Stroke or Transient Ischemic Attack.

Background And Objectives: The goal of this work was to investigate the short-term time-course benefit and risk of ticagrelor with aspirin in acute mild-moderate ischemic stroke or high-risk TIA in The Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA for Prevention of Stroke and Death (THALES) trial.

Methods: In an exploratory analysis of the THALES trial, we evaluated the cumulative incidence of irreversible efficacy and safety outcomes at different time points during the 30-day treatment period. The efficacy outcome was major ischemic events defined as a composite of ischemic stroke or nonhemorrhagic death.

The IFNγ-PDL1 Pathway Enhances CD8T-DCT Interaction to Promote Hypertension.

Background: Renal T cells contribute importantly to hypertension, but the underlying mechanism is incompletely understood. We reported that CD8Ts directly stimulate distal convoluted tubule cells (DCTs) to increase NCC (sodium chloride co-transporter) expression and salt reabsorption. However, the mechanistic basis of this pathogenic pathway that promotes hypertension remains to be elucidated.

Mesenchymal and stem-like prostate cancer linked to therapy-induced lineage plasticity and metastasis.

Bioinformatic analysis of 94 patient-derived xenografts (PDXs), cell lines, and organoids (PCOs) identifies three intrinsic transcriptional subtypes of metastatic castration-resistant prostate cancer: androgen receptor (AR) pathway + prostate cancer (PC) (ARPC), mesenchymal and stem-like PC (MSPC), and neuroendocrine PC (NEPC). A sizable proportion of castration-resistant and metastatic stage PC (M-CRPC) cases are admixtures of ARPC and MSPC. Analysis of clinical datasets and mechanistic studies indicates that MSPC arises from ARPC as a consequence of therapy-induced lineage plasticity.

[Dynamic Microbial Shifts and Functional Analysis of Saliva Microbial Communities with Caries Children].

Objective: To observe the dynamic changes in the salivary microbiota of children with dental caries and those who were caries-free and to analyze the functional differences in the oral microecology of the two groups during the course of sugar metabolism and the synthesis and transport of multiple amino acids.

Methods: Ten children with dental caries and 10 caries-free children were enrolled. We employed Illumina metagenomics technology to analyze the composition and function of salivary microbiome in children with and without caries.

Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy.

Cerebral adrenoleukodystrophy (CALD) is a devastating, demyelinating neuroinflammatory manifestation found in up to 40% of young males with an inherited mutation in , the causative gene in adrenoleukodystrophy. The search for biomarkers which correlate to CALD disease burden and respond to intervention has long been sought after. We used the Olink Proximity Extension Assay (Uppsala, Sweden) to explore the cerebral spinal fluid (CSF) of young males with CALD followed by correlative analysis with plasma.

Application of Artificial Intelligence and Deep Learning for Choroid Segmentation in Myopia.

Purpose: To investigate the correlation between choroidal thickness and myopia progression using a deep learning method.

Methods: Two data sets, data set A and data set B, comprising of 123 optical coherence tomography (OCT) volumes, were collected to establish the model and verify its clinical utility. The proposed mask region-based convolutional neural network (R-CNN) model, trained with the pretrained weights from the Common Objects in Context database as well as the manually labeled OCT images from data set A, was used to automatically segment the choroid.

Switchable assembly and function of antibody complexes in vivo using a small molecule.

The antigen specificity and long serum half-life of monoclonal antibodies have made them a critical part of modern therapeutics. These properties have been coopted in a number of synthetic formats, such as antibody-drug conjugates, bispecific antibodies, or Fc-fusion proteins to generate novel biologic drug modalities. Historically, these new therapies have been generated by covalently linking multiple molecular moieties through chemical or genetic methods.

The thalamus and its subnuclei-a gateway to obsessive-compulsive disorder.

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan.

An Investigation of a New Parameter Based on the Plastic Strain Gradient to Characterize Composite Constraint around the Crack Front at a Low Temperature.

Stress corrosion cracking (SCC) is an important destruction form of materials such as stainless steel, nickel-based alloy and their welded components in nuclear reactor pressure vessels and pipes. The existing popular quantitative prediction models of SCC crack growth rate are mainly influenced by fracture toughness values or . In particular, the composite constraint, containing the in-plane constraints and out-of-plane constraints around the crack front, has a significant influence on the fracture toughness of structures in nuclear power plants.

Sex Differences in Short-Term and Long-Term Outcomes Among Patients With Acute Ischemic Stroke in China.

Background: Sex differences in stroke outcomes are crucial to secondary prevention, but previous reports showed inconsistent results. We aimed to explore the sex differences in stroke outcomes in the Third China National Stroke Registry, a prospective multicenter registry study.

Methods: Among the 15 166 patients enrolled between 2015 and 2018, 9038 patients with acute ischemic stroke (AIS) were included.

Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.

Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension.

Pembrolizumab induces HIV latency reversal in people living with HIV and cancer on antiretroviral therapy.

In people living with HIV (PLWH) on antiretroviral therapy (ART), virus persists in a latent form where there is minimal transcription or protein expression. Latently infected cells are a major barrier to curing HIV. Increasing HIV transcription and viral production in latently infected cells could facilitate immune recognition and reduce the pool of infected cells that persist on ART.

Sugar-Based Polymers with Stereochemistry-Dependent Degradability and Mechanical Properties.

Stereochemistry in polymers can be used as an effective tool to control the mechanical and physical properties of the resulting materials. Typically, though, in synthetic polymers, differences among polymer stereoisomers leads to incremental property variation, i.e.

Morphologic Variants of the Hand Motor Cortex in Developing Brains from Neonates through Childhood Assessed by MR Imaging.

Background And Purpose: Knowledge of anatomic markers of the hand motor cortex is essential in the evaluation and treatment of motor neurologic diseases for both adults and developing populations. However, hand motor cortex variants in developing brains remain to be investigated. Our objective was to observe morphologic variants of the hand motor cortex in developing brains from neonates through childhood.

Biodegradability of novel high T poly(isosorbide-co-1,6-hexanediol) oxalate polyester in soil and marine environments.

In order to reduce the plastic accumulation in the environment, biodegradable plastics are attracting interest in the plastics market. However, the low thermal stability of most amorphous biodegradable polymers limits their application. With the aim of combining high glass transition temperature (T), with good (marine) biodegradation a family of novel fully renewable poly(isosorbide-co-diol) oxalate (PISOX-diol) copolyesters was recently developed.

Geographic Atrophy Progression Is Associated With Choriocapillaris Flow Deficits Measured With Optical Coherence Tomographic Angiography.

Purpose: The purpose of this study was to assess the associations between baseline choriocapillaris (CC) flow deficits and geographic atrophy (GA) progression.

Methods: In this prospective cohort study, patients with GA underwent 3 × 3-mm macular spectral-domain optical coherence tomographic angiography (OCTA) at baseline and follow-up visits. Annual GA enlargement rate was defined as change of square root of GA area in 12 months.

Temporal Eating Patterns and Eating Windows among Adults with Overweight or Obesity.

We aim to describe temporal eating patterns in a population of adults with overweight or obesity. In this cross-sectional analysis, data were combined from two separate pilot studies during which participants entered the timing of all eating occasions (>0 kcals) for 10-14 days. Data were aggregated to determine total eating occasions, local time of the first and last eating occasions, eating window, eating midpoint, and within-person variability of eating patterns.

Association Between Fluid Volume in Inner Nuclear Layer and Visual Acuity in Diabetic Macular Edema.

Purpose: In diabetic macular edema (DME), the correlation between visual acuity (VA) and central subfield thickness (CST) is weak. We hypothesize that fluid volume (FV) in the inner nuclear layer (INL) may correlate more strongly with VA.

Design: Retrospective, cross-sectional study.

Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes.

Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples.

Long-acting capsid inhibitor protects macaques from repeat SHIV challenges.

Because no currently available vaccine can prevent HIV infection, pre-exposure prophylaxis (PrEP) with antiretrovirals (ARVs) is an important tool for combating the HIV pandemic. Long-acting ARVs promise to build on the success of current PrEP strategies, which must be taken daily, by reducing the frequency of administration. GS-CA1 is a small-molecule HIV capsid inhibitor with picomolar antiviral potency against a broad array of HIV strains, including variants resistant to existing ARVs, and has shown long-acting therapeutic potential in a mouse model of HIV infection.

Ledipasvir/Sofosbuvir for Patients Coinfected With Chronic Hepatitis C and Hepatitis B in Taiwan: Follow-up at 108 Weeks Posttreatment.

Background: For patients coinfected with hepatitis C virus (HCV) and hepatitis B virus (HBV), HCV treatment with direct-acting antivirals can lead to HBV reactivation. We evaluated HBV reactivation during ledipasvir/sofosbuvir treatment and 108-week follow-up.

Methods: In Taiwan, 111 patients with HCV genotype 1 or 2 and HBV received ledipasvir/sofosbuvir (90mg/400mg) once daily for 12 weeks.