Values of Baseline Posterior Circulation Acute Stroke Prognosis Early Computed Tomography Score for Treatment Decision of Acute Basilar Artery Occlusion.

Background And Purpose: This study aimed to analyze the impact of baseline posterior circulation Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS) on the efficacy and safety of endovascular therapy (EVT) for patients with acute basilar artery occlusion.

Methods: The BASILAR was a nationwide prospective registry of consecutive patients with a symptomatic and radiologically confirmed acute basilar artery occlusion within 24 hours of symptom onset. We estimated the effect of standard medical therapy alone (SMT group) versus SMT plus EVT (EVT group) for patients with documented pc-ASPECTS on noncontrast CT, both as a categorical (0-4 versus 5-7 versus 8-10) and as a continuous variable.

Frequency of interruptions to prolonged sitting and postprandial metabolic responses in young, obese, Chinese men.

This study aimed to examine the effects of 3-min light-intensity walking every 30 min (3-min) and 6-min light-intensity walking every 60 min (6-min) compared with prolonged sitting (SIT) on the postprandial metabolic responses in young, centrally obese, Chinese men. Twenty-one Chinese men with central obesity (age, 23 ± 4 years; body mass index, 29.8 ± 3.

Clinical, Imaging, and Lab Correlates of Severe COVID-19 Leukoencephalopathy.

Background And Purpose: Patients infected with the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) can develop a spectrum of neurological disorders, including a leukoencephalopathy of variable severity. Our aim was to characterize imaging, lab, and clinical correlates of severe coronavirus disease 2019 (COVID-19) leukoencephalopathy, which may provide insight into the SARS-CoV-2 pathophysiology.

Materials And Methods: Twenty-seven consecutive patients positive for SARS-CoV-2 who had brain MR imaging following intensive care unit admission were included.

CXCR4-Binding Positron Emission Tomography Tracers Link Monocyte Recruitment and Endothelial Injury in Murine Atherosclerosis.

Objective: vMIP-II (viral macrophage inflammatory protein 2)/vCCL2 (viral chemotactic cytokine ligand 2) binds to multiple chemokine receptors, and vMIP-II-based positron emission tomography tracer (Cu-DOTA-vMIP-II: vMIP-II tracer) accumulates at atherosclerotic lesions in mice. Given that it would be expected to react with multiple chemokine receptors on monocytes and macrophages, we wondered if its accumulation in atherosclerosis lesion-bearing mice might correlate with overall macrophage burden or, alternatively, the pace of monocyte recruitment. Approach and Results: We employed a mouse model of atherosclerosis regression involving adenoassociated virus 8 vector encoding murine Apoe (AAV-mApoE) treatment of mice where the pace of monocyte recruitment slows before macrophage burden subsequently declines.

Toward allele-specific targeting therapy and pharmacodynamic marker for spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3), caused by a CAG repeat expansion in the ataxin-3 gene (), is characterized by neuronal polyglutamine (polyQ) ATXN3 protein aggregates. Although there is no cure for SCA3, gene-silencing approaches to reduce toxic polyQ ATXN3 showed promise in preclinical models. However, a major limitation in translating putative treatments for this rare disease to the clinic is the lack of pharmacodynamic markers for use in clinical trials.

A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer.

Neoantigens arise from mutations in cancer cells and are important targets of T cell-mediated anti-tumor immunity. Here, we report the first open-label, phase Ib clinical trial of a personalized neoantigen-based vaccine, NEO-PV-01, in combination with PD-1 blockade in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. This analysis of 82 patients demonstrated that the regimen was safe, with no treatment-related serious adverse events observed.

Analysis of 70 patients with hydrocephalus due to cobalamin C deficiency.

Objective: To analyze the clinical characteristics of patients with hydrocephalus secondary to cobalamin C (cblC) deficiency and to discuss the optimal strategies for assessing and treating such patients by performing clinical and laboratory studies in 70 patients.

Methods: A total of 1,211 patients were clinically diagnosed with methylmalonic acidemia (MMA) from 1998 to 2019. Among them, cblC deficiency was confirmed in 70 patients with hydrocephalus by brain imaging and biochemical and genetic analysis.

Presence of Subclinical Hypercortisolism in Clinical Aldosterone-Producing Adenomas Predicts Lower Clinical Success.

The clinical characteristics and outcomes in patients with clinical aldosterone-producing adenomas harboring mutations with or without subclinical hypercortisolism remain unclear. This prospective study is aimed at determining factors associated with subclinical hypercortisolism in patients with clinical aldosterone-producing adenomas. Totally, 82 patients were recruited from November 2016 to March 2018 and underwent unilateral laparoscopic adrenalectomy with at least a 12-month follow-up postoperatively.

A simplified cell-based assay to identify coronavirus 3CL protease inhibitors.

We describe a mammalian cell-based assay capable of identifying coronavirus 3CL protease (3CLpro) inhibitors without requiring the use of live virus. By enabling the facile testing of compounds across a range of coronavirus 3CLpro enzymes, including the one from SARS-CoV-2, we are able to quickly identify compounds with broad or narrow spectra of activity. We further demonstrate the utility of our approach by performing a curated compound screen along with structure-activity profiling of a series of small molecules to identify compounds with antiviral activity.

Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation.

Background: The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD.

Lead compounds for the development of SARS-CoV-2 3CL protease inhibitors.

We report the identification of three structurally diverse compounds - compound 4, GC376, and MAC-5576 - as inhibitors of the SARS-CoV-2 3CL protease. Structures of each of these compounds in complex with the protease revealed strategies for further development, as well as general principles for designing SARS-CoV-2 3CL protease inhibitors. These compounds may therefore serve as leads for the basis of building effective SARS-CoV-2 3CL protease inhibitors.

Contact Settings and Risk for Transmission in 3410 Close Contacts of Patients With COVID-19 in Guangzhou, China : A Prospective Cohort Study.

Background: Risk for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to close contacts of infected persons has not been well estimated.

Objective: To evaluate the risk for transmission of SARS-CoV-2 to close contacts in different settings.

Design: Prospective cohort study.

Clinical and Analytical Validation of a Novel Urine-Based Test for the Detection of Allograft Rejection in Renal Transplant Patients.

In this clinical validation study, we developed and validated a urinary Q-Score generated from the quantitative test QSant, formerly known as QiSant, for the detection of biopsy-confirmed acute rejection in kidney transplants. Using a cohort of 223 distinct urine samples collected from three independent sites and from both adult and pediatric renal transplant patients, we examined the diagnostic utility of the urinary Q-Score for detection of acute rejection in renal allografts. Statistical models based upon the measurements of the six QSant biomarkers (cell-free DNA, methylated-cell-free DNA, clusterin, CXCL10, creatinine, and total protein) generated a renal transplant Q-Score that reliably differentiated stable allografts from acute rejections in both adult and pediatric renal transplant patients.

Bivalent binding of a fully human IgG to the SARS-CoV-2 spike proteins reveals mechanisms of potent neutralization.

antibody selection against pathogens from naïve combinatorial libraries can yield various classes of antigen-specific binders that are distinct from those evolved from natural infection. Also, rapid neutralizing antibody discovery can be made possible by a strategy that selects for those interfering with pathogen and host interaction. Here we report the discovery of antibodies that neutralize SARS-CoV-2, the virus responsible for the COVID-19 pandemic, from a highly diverse naïve human Fab library.

Redefining Cardiac Biomarkers in Predicting Mortality of Inpatients With COVID-19.

The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019 to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effects Cox model, after adjusting for age, sex, and comorbidities, the adjusted hazard ratio of 28-day mortality for hs-cTnI (high-sensitivity cardiac troponin I) was 7.

A nomogram to predict symptomatic epilepsy in patients with radiation-induced brain necrosis.

Objective: To develop and validate a nomogram to predict epilepsy in patients with radiation-induced brain necrosis (RN).

Methods: The nomogram was based on a retrospective analysis of 302 patients who were diagnosed with symptomatic RN from January 2005 to January 2016 in Sun Yat-sen Memorial Hospital using the Cox proportional hazards model. Discrimination of the nomogram was assessed by the concordance index ( index) and the calibration curve.

Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion.

Fat mass and obesity-associated protein (FTO), an RNA N-methyladenosine (mA) demethylase, plays oncogenic roles in various cancers, presenting an opportunity for the development of effective targeted therapeutics. Here, we report two potent small-molecule FTO inhibitors that exhibit strong anti-tumor effects in multiple types of cancers. We show that genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especially LILRB4.

Disseminated Coccidioidomycosis Treated with Interferon-γ and Dupilumab.

We describe a case of life-threatening disseminated coccidioidomycosis in a previously healthy child. Like most patients with disseminated coccidioidomycosis, this child had no genomic evidence of any known, rare immune disease. However, comprehensive immunologic testing showed exaggerated production of interleukin-4 and reduced production of interferon-γ.

Genotype-Guided Dosing of Warfarin in Chinese Adults: A Multicenter Randomized Clinical Trial.

Background: Warfarin is an effective treatment for thromboembolic disease but has a narrow therapeutic index; optimal anticoagulation dosage can differ tremendously among individuals. We aimed to evaluate whether genotype-guided warfarin dosing is superior to routine clinical dosing for the outcomes of interest in Chinese patients.

Methods: We conducted a multicenter, randomized, single-blind, parallel-controlled trial from September 2014 to April 2017 in 15 hospitals in China.

Universal mechanical exfoliation of large-area 2D crystals.

Two-dimensional materials provide extraordinary opportunities for exploring phenomena arising in atomically thin crystals. Beginning with the first isolation of graphene, mechanical exfoliation has been a key to provide high-quality two-dimensional materials, but despite improvements it is still limited in yield, lateral size and contamination. Here we introduce a contamination-free, one-step and universal Au-assisted mechanical exfoliation method and demonstrate its effectiveness by isolating 40 types of single-crystalline monolayers, including elemental two-dimensional crystals, metal-dichalcogenides, magnets and superconductors.

Template-assisted loading of FeO nanoparticles inside hollow carbon "rooms" to achieve high volumetric lithium storage.

The design of electrodes with simultaneously high compaction density, developed porosity, and structural stability has always been a challenge so as to meet the demand of high volumetric performance lithium ion storage devices. In this paper, we demonstrate a new compositing method for hollow carbon "room" loading of FeO nanoparticles (HCR@FeO) with the assistance of NaCO salt crystal templates. The as-obtained HCR@FeO composites have a massive compaction density (1.

Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke.

Background: In acute ischemic stroke, there is uncertainty regarding the benefit and risk of administering intravenous alteplase before endovascular thrombectomy.

Methods: We conducted a trial at 41 academic tertiary care centers in China to evaluate endovascular thrombectomy with or without intravenous alteplase in patients with acute ischemic stroke. Patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation were randomly assigned in a 1:1 ratio to undergo endovascular thrombectomy alone (thrombectomy-alone group) or endovascular thrombectomy preceded by intravenous alteplase, at a dose of 0.

Artificial Intelligence Augmentation of Radiologist Performance in Distinguishing COVID-19 from Pneumonia of Other Origin at Chest CT.

Background Coronavirus disease 2019 (COVID-19) and pneumonia of other diseases share similar CT characteristics, which contributes to the challenges in differentiating them with high accuracy. Purpose To establish and evaluate an artificial intelligence (AI) system for differentiating COVID-19 and other pneumonia at chest CT and assessing radiologist performance without and with AI assistance. Materials and Methods A total of 521 patients with positive reverse transcription polymerase chain reaction results for COVID-19 and abnormal chest CT findings were retrospectively identified from 10 hospitals from January 2020 to April 2020.