Risk Factors for Severe Residual Headache in Cerebral Venous Thrombosis.

Background And Purpose: Which factors will influence the presence of severe residual headache after cerebral venous thrombosis (CVT) is unclear. The purpose of this study was to identify risk factors for severe residual headache in a large single-center cohort of patients with CVT.

Methods: We consecutively included eligible patients with CVT from a prospective stroke registry.

Targeting Thymidine Phosphorylase With Tipiracil Hydrochloride Attenuates Thrombosis Without Increasing Risk of Bleeding in Mice.

Objective: Current antiplatelet medications increase the risk of bleeding, which leads to a clear clinical need in developing novel mechanism-based antiplatelet drugs. TYMP (Thymidine phosphorylase), a cytoplasm protein that is highly expressed in platelets, facilitates multiple agonist-induced platelet activation, and enhances thrombosis. Tipiracil hydrochloride (TPI), a selective TYMP inhibitor, has been approved by the Food and Drug Administration for clinical use.

Application of liver acquisition with volume acceleration enhanced sequence in improving the accuracy of reassessing organ-invasive rectal mucinous adenocarcinoma after chemoradiation.

Objectives: To explore the ability of liver acquisition with volume acceleration contrast-enhanced sequence (LAVA-ce) to improve the accuracy of reassessing adjacent organ involvement by rectal mucinous adenocarcinoma (MC) after neoadjuvant therapy (NAT).

Methods: This study retrospectively enrolled twenty-five patients with MC who underwent pre- and post-NAT MRI, were staged as T4b using pre-NAT T weighted imaging, received NAT and underwent radical resection. All MR images were divided into two schemes, T weighted plus diffusion weighted imaging (TD protocol) and plus LAVA-ce (TDL protocol).

Myocardial Tissue Reverse Remodeling After Guideline-Directed Medical Therapy in Idiopathic Dilated Cardiomyopathy.

Background: The prognosis of patients with idiopathic dilated cardiomyopathy (DCM) has improved remarkably in recent decades with guideline-directed medical therapy. Left ventricular (LV) reverse remodeling (LVRR) is one of the major therapeutic goals. Whether myocardial fibrosis or inflammation would reverse associated with LVRR remains unknown.

Whole blood transcriptome biomarkers of unruptured intracranial aneurysm.

Background: The rupture of an intracranial aneurysm (IA) causes devastating subarachnoid hemorrhages, yet most IAs remain undiscovered until they rupture. Recently, we found an IA RNA expression signature of circulating neutrophils, and used transcriptome data to build predictive models for unruptured IAs. In this study, we evaluate the feasibility of using whole blood transcriptomes to predict the presence of unruptured IAs.

Rapid identification of a human antibody with high prophylactic and therapeutic efficacy in three animal models of SARS-CoV-2 infection.

Effective therapies are urgently needed for the SARS-CoV-2/COVID-19 pandemic. We identified panels of fully human monoclonal antibodies (mAbs) from large phage-displayed Fab, scFv, and VH libraries by panning against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. A high-affinity Fab was selected from one of the libraries and converted to a full-size antibody, IgG1 ab1, which competed with human ACE2 for binding to RBD.

An Herbal Formulation of Jiawei Xiaoyao for the Treatment of Functional Dyspepsia: A Multicenter, Randomized, Placebo-Controlled, Clinical Trial.

Introduction: To investigate the efficacy and safety of an herbal formulation of Jiawei Xiaoyao (JX) on gastrointestinal symptoms in patients with functional dyspepsia (FD) who had previously rejected standard therapies of proton pump inhibitors, H2 blockers, or Helicobacter pylori eradication.

Methods: A total of 144 adult men and women with FD according to the Rome III criteria were recruited at 9 sites in China from August 2017 to April 2019. Participants were randomized to receive either a JX pill or placebo (12 g/d, 6 g twice a day) for 4 weeks.

Skin-interfaced soft microfluidic systems with modular and reusable electronics for capacitive sensing of sweat loss, rate and conductivity.

Important insights into human health can be obtained through the non-invasive collection and detailed analysis of sweat, a biofluid that contains a wide range of essential biomarkers. Skin-interfaced microfluidic platforms, characterized by soft materials and thin geometries, offer a collection of capabilities for in situ capture, storage, and analysis of sweat and its constituents. In ambulatory uses cases, the ability to provide real-time feedback on sweat loss, rate and content, without visual inspection of the device, can be important.

Optimization of Peptide Inhibitors of β-Klotho as Antagonists of Fibroblast Growth Factors 19 and 21.

Fibroblast growth factors 19 and 21 (FGF19 and FGF21) have biological actions that render them promising clinical candidates for treatment of metabolic diseases, particularly dyslipidemia and nonalcoholic steatohepatitis (NASH). These two atypical endocrine FGFs employ an accessory receptor β-klotho (KLB) to signal through classical FGF receptors (FGFRs). FGF19 and FGF21 bind to KLB via their C-terminus, to orient the N-terminus for productive interaction with FGFRs.

A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model.

The emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from 10 COVID-19 patients, we identified 40 strongly neutralizing mAbs.

Three-Dimensional Late Gadolinium Enhancement Cardiovascular Magnetic Resonance Predicts Inducibility of Ventricular Tachycardia in Adults With Repaired Tetralogy of Fallot.

Background: Adults with repaired tetralogy of Fallot die prematurely from ventricular tachycardia (VT) and sudden cardiac death. Inducible VT predicts mortality. Ventricular scar, the key substrate for VT, can be noninvasively defined with late gadolinium enhancement (LGE) cardiovascular magnetic resonance but whether this relates to inducible VT is unknown.

Single-Cell Transcriptome Analysis Reveals Dynamic Cell Populations and Differential Gene Expression Patterns in Control and Aneurysmal Human Aortic Tissue.

Background: Ascending thoracic aortic aneurysm (ATAA) is caused by the progressive weakening and dilatation of the aortic wall and can lead to aortic dissection, rupture, and other life-threatening complications. To improve our understanding of ATAA pathogenesis, we aimed to comprehensively characterize the cellular composition of the ascending aortic wall and to identify molecular alterations in each cell population of human ATAA tissues.

Methods: We performed single-cell RNA sequencing analysis of ascending aortic tissues from 11 study participants, including 8 patients with ATAA (4 women and 4 men) and 3 control subjects (2 women and 1 man).

Microfluidics-enabled 96-well perfusion system for high-throughput tissue engineering and long-term all-optical electrophysiology.

This work demonstrates a novel high-throughput (HT) microfluidics-enabled uninterrupted perfusion system (HT-μUPS) and validates its use with chronic all-optical electrophysiology in human excitable cells. HT-μUPS consists of a soft multichannel microfluidic plate cover which could button on a commercial HT 96-well plate. Herein, we demonstrate the manufacturing process of the system and its usages in acute and chronic all-optical electrophysiological studies of human induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CM) and engineered excitable (spiking HEK) cells.

Identification of GGC repeat expansion in the gene in amyotrophic lateral sclerosis.

Objective: To determine whether the GGC repeats in the gene contribute to amyotrophic lateral sclerosis (ALS).

Methods: In this study, 545 patients with ALS and 1,305 healthy controls from mainland China were recruited. Several pathogenic mutations in known ALS-causative genes (including and ) and polynucleotide repeat expansions in and genes were excluded.

Single-Cell Genomics Reveals a Novel Cell State During Smooth Muscle Cell Phenotypic Switching and Potential Therapeutic Targets for Atherosclerosis in Mouse and Human.

Background: Smooth muscle cells (SMCs) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC dedifferentiation, migration, and transdifferentiation into other cell types. Yet how SMCs contribute to the pathophysiology of atherosclerosis remains elusive.

Methods: To reveal the trajectories of SMC transdifferentiation during atherosclerosis and to identify molecular targets for disease therapy, we combined SMC fate mapping and single-cell RNA sequencing of both mouse and human atherosclerotic plaques.

Orally available tubulin inhibitor VERU-111 enhances antitumor efficacy in paclitaxel-resistant lung cancer.

Lung cancer is the most common cause of cancer associated mortality. Chemotherapeutic agents, such as paclitaxel, are important treatment options but drug resistance often develops upon prolonged use. We report here the preclinical evaluation of a new orally available tubulin inhibitor, VERU-111, which can overcome several ABC-transporters mediated multi-drug resistance associated with taxane treatment.

First Report of Anthracnose Caused by Colletotrichum gloeosporioides on Akebia trifoliata in China.

Akebia trifoliata (Thunberg) Koidzumi (three-leaf akebia), a climbing deciduous woody plant, grows wild in mountains of China and Japan. It has long been prized for its delicious sweet taste and medicinal value (Lu et al., 2019).

Aspirin and Growth of Small Unruptured Intracranial Aneurysm: Results of a Prospective Cohort Study.

Background And Purpose: The role of aspirin in unruptured intracranial aneurysm (UIA) growth remains largely unknown. We aim to identify whether aspirin is associated with a lower rate of UIA growth in patients with UIA <7 mm.

Methods: This prospective cohort study consecutively enrolled patients with UIAs <7 mm with ischemic cerebrovascular disease between January 2016 and December 2019.

Gut Microbiota-Associated Activation of TLR5 Induces Apolipoprotein A1 Production in the Liver.

Rationale: Dysbiosis of gut microbiota plays an important role in cardiovascular diseases but the molecular mechanisms are complex. An association between gut microbiome and the variance in HDL-C (high-density lipoprotein-cholesterol) level was suggested in a human study. Besides, dietary fat was shown to increase both HDL-C and LDL-C (low-density lipoprotein-cholesterol) levels.

Association of serum neurofilament light and disease severity in patients with spinocerebellar ataxia type 3.

Objective: To investigate serum neurofilament light protein (sNfL) levels in patients with spinocerebellar ataxia type 3 (SCA3) and to determine whether they are associated with disease severity.

Methods: This cross-sectional study enrolled 185 healthy controls and 235 mutation carriers (17 asymptomatic stage, 20 preclinical stage, and 198 ataxic stage). We measured sNfL levels with the single molecule array (Simoa) platform.

High-Mobility Group Box-1 Is Associated With Obesity, Inflammation, and Subclinical Cardiovascular Risk Among Young Adults: A Longitudinal Cohort Study.

Objective: We aimed to characterize circulating HMGB1 (high-mobility group box-1) levels, one of the better-characterized damage-associated molecular patterns, with respect to age, sex, and race in the general population, and investigate the longitudinal associations of HMGB1 with inflammatory markers, obesity, and preclinical markers of cardiovascular disease. Approach and Results: The analyses included 489 participants (50% Blacks, aged 24.6±3.