Effect of Anti-CD4 Antibody UB-421 on HIV-1 Rebound after Treatment Interruption.

Background: Administration of a single broadly neutralizing human immunodeficiency virus (HIV)-specific antibody to HIV-infected persons leads to the development of antibody-resistant virus in the absence of antiretroviral therapy (ART). It is possible that monotherapy with UB-421, an antibody that blocks the virus-binding site on human CD4+ T cells, could induce sustained virologic suppression without induction of resistance in HIV-infected persons after analytic treatment interruption.

Methods: We conducted a nonrandomized, open-label, phase 2 clinical study evaluating the safety, pharmacokinetics, and antiviral activity of UB-421 monotherapy in HIV-infected persons undergoing analytic treatment interruption.

Comprehensive genomic and immunological characterization of Chinese non-small cell lung cancer patients.

Deep understanding of the genomic and immunological differences between Chinese and Western lung cancer patients is of great importance for target therapy selection and development for Chinese patients. Here we report an extensive molecular and immune profiling study of 245 Chinese patients with non-small cell lung cancer. Tumor-infiltrating lymphocyte estimated using immune cell signatures is found to be significantly higher in adenocarcinoma (ADC, 72.

Learning Curve Analysis of Transvaginal Natural Orifice Adnexal Surgery.

Study Objective: This study was designed to evaluate the learning curve of transvaginal natural orifice surgery (NOS) for adnexal tumors based on the type of procedure (adnexectomy or cystectomy).

Design: Retrospective cohort study.

Setting: Tertiary-care university hospital.

Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.

Background: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.

Methods: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries.

Author Correction: Sculpting nanoparticle dynamics for single-bacteria-level screening and direct binding-efficiency measurement.

The original version of this Article omitted the author Kuan Wang, who is from the 'College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan' and 'Nanyang Environment & Water Research Institute, Nanyang Technological University, Singapore 637141, Singapore.'Also, the author S.H.

Characteristics of High Cardiovascular Risk in 1.7 Million Chinese Adults.

Background: As cardiovascular risk increases in China, interest in strategies to mitigate it is growing. However, national information about the prevalence and treatment of high cardiovascular disease (CVD) risk is limited.

Objective: To assess the prevalence and treatment of high CVD risk as well as variations in risk across population subgroups.

Standardized MR Perfusion Scoring System for Evaluation of Sequential Perfusion Changes and Surgical Outcome of Moyamoya Disease.

Background And Purpose: Simple-but-precise evaluation of cerebral perfusion is crucial for the treatment of Moyamoya disease. We aimed to develop a standardized scoring system for MR perfusion suitable for Moyamoya disease evaluation and investigate the postoperative serial changes and outcome predictors.

Materials And Methods: From January 2013 to December 2016, patients diagnosed with Moyamoya disease and receiving indirect revascularization were recruited prospectively.

A Premature Termination Codon Mutation in MYBPC3 Causes Hypertrophic Cardiomyopathy via Chronic Activation of Nonsense-Mediated Decay.

Background: Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in myosin-binding protein C3 ( MYBPC3) resulting in a premature termination codon (PTC). The underlying mechanisms of how PTC mutations in MYBPC3 lead to the onset and progression of HCM are poorly understood. This study's aim was to investigate the molecular mechanisms underlying the pathogenesis of HCM associated with MYBPC3 PTC mutations by utilizing human isogenic induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs).

Murine exposure to gold nanoparticles during early pregnancy promotes abortion by inhibiting ectodermal differentiation.

Background: Gold nanoparticles (AuNPs) have been widely studied for biomedical applications, although their safety and potential toxicity in pregnancy remains unknown. The aim of this study is to explore the effect of AuNPs maternal exposure at different gestational ages on fetal survival and development, as well as the potential mechanism of AuNPs affecting embryos and fetuses.

Methods: Thirty nm polyethylene glycol (PEG)-coated AuNPs (A30) were administered to pregnant mice via intravenous injection (5 μg Au/g body weight) over three days at either early or late pregnancy.

Clinical relevance of single nucleotide polymorphisms in the CXCL1 and CXCL12 genes in patients with major trauma.

Background: Genetic backgrounds have been recognized as significant determinants of susceptibility to sepsis. CXC chemokines play a significant role in innate immunity against infectious diseases. Genetic polymorphisms of CXC chemokine genes have been widely studied in inflammatory and infectious diseases but not in sepsis.

Mechanical loading mitigates osteoarthritis symptoms by regulating endoplasmic reticulum stress and autophagy.

Osteoarthritis (OA) is a disease characterized by cartilage damage and abnormal remodeling of subchondral bone. Our previous study showed that in the early stage of OA, knee loading exerts protective effects by suppressing osteoclastogenesis through Wnt signaling, but little is known about loading effects at the late OA stage. Endoplasmic reticulum (ER) stress and autophagy are known to be involved in the late OA stage.

Clinical features of 2041 human brucellosis cases in China.

Background: Human brucellosis has become a major public health problem in China. However, the available clinical data on brucellosis cases are limited.

Methods: We retrospectively reviewed medical charts of 2041 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview.

Leveraging the genetic basis of Rett syndrome to ascertain pathophysiology.

Mutations in the methyl-CpG binding protein 2 (MECP2) gene cause Rett syndrome (RTT), a progressive X-linked neurological disorder characterized by loss of developmental milestones, intellectual disability and breathing abnormality. Despite being a monogenic disorder, the pathogenic mechanisms by which mutations in MeCP2 impair neuronal function and underlie the RTT symptoms have been challenging to elucidate. The seemingly simple genetic root and the availability of genetic data from RTT patients have led to the generation and characterization of a series of mouse models recapitulating RTT-associated genetic mutations.

Quantitative Assessment of Liver Function by Using Gadoxetic Acid-enhanced MRI: Hepatocyte Uptake Ratio.

Purpose To determine whether hepatocyte uptake ratios derived at gadoxetic acid-enhanced MRI correlate with quantitative measures of liver function and can help to identify contraindication to major hepatectomy. Materials and Methods Between August 2016 and October 2016, 50 study participants with chronic liver disease or cirrhosis underwent liver MRI at 3.0 T including T1 mapping and elastography.

Consensus report of the 8 and 9th Weinman Symposia on Gene x Environment Interaction in carcinogenesis: novel opportunities for precision medicine.

The relative contribution of intrinsic genetic factors and extrinsic environmental ones to cancer aetiology and natural history is a lengthy and debated issue. Gene-environment interactions (G x E) arise when the combined presence of both a germline genetic variant and a known environmental factor modulates the risk of disease more than either one alone. A panel of experts discussed our current understanding of cancer aetiology, known examples of G × E interactions in cancer, and the expanded concept of G × E interactions to include somatic cancer mutations and iatrogenic environmental factors such as anti-cancer treatment.

Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer.

Background: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, has robust efficacy in patients with ALK-positive non-small-cell lung cancer (NSCLC) that is refractory to crizotinib. The efficacy of brigatinib, as compared with crizotinib, in patients with advanced ALK-positive NSCLC who have not previously received an ALK inhibitor is unclear.

Methods: In an open-label, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced ALK-positive NSCLC who had not previously received ALK inhibitors to receive brigatinib at a dose of 180 mg once daily (with a 7-day lead-in period at 90 mg) or crizotinib at a dose of 250 mg twice daily.

Clinical Value of Hybrid TOF-PET/MR Imaging-Based Multiparametric Imaging in Localizing Seizure Focus in Patients with MRI-Negative Temporal Lobe Epilepsy.

Background And Purpose: Temporal lobe epilepsy is the most common type of epilepsy. Early surgical treatment is superior to prolonged medical therapy in refractory temporal lobe epilepsy. Successful surgical operations depend on the correct localization of the epileptogenic zone.

The Psychopharmacology of Effort-Related Decision Making: Dopamine, Adenosine, and Insights into the Neurochemistry of Motivation.

Effort-based decision making is studied using tasks that offer choices between high-effort options leading to more highly valued reinforcers versus low-effort/low-reward options. These tasks have been used to study the involvement of neural systems, including mesolimbic dopamine and related circuits, in effort-related aspects of motivation. Moreover, such tasks are useful as animal models of some of the motivational symptoms that are seen in people with depression, schizophrenia, Parkinson's disease, and other disorders.

Invasive Streptococcus pneumoniae infection among hospitalized patients in Jingzhou city, China, 2010-2012.

Background: Streptococcus pneumoniae (Sp) is a leading cause of bacterial pneumonia, meningitis, and sepsis and a major source of morbidity and mortality worldwide. Invasive pneumococcal disease (IPD) is defined as isolation of Sp from a normally sterile site, including blood or cerebrospinal fluid. The aim of this study is to describe outcomes as well as clinical and epidemiological characteristics of hospitalized IPD case patients in central China.

Regular patterns of the effects of hydrogen-containing additives on the formation of CdSe monomer.

It is unclear at the molecular level why HY (HY = RSH, or ROH, or RNH2) with HPPh2 additives kinetically affects the reaction pathway to the formation of different monomers (Ph2P-SeCd-Y or Ph2P-SeCdSe-Y) in the systhesis of semiconductor nanocrystals. In the present work, it was found that in a [Cd(OA)2 + Se[double bond, length as m-dash]P(C8H17)3 + HPPh2 + HY] mixture, HY behaves as a mediator for the formation of the initial kind of monomer, besides as a hydrogen/proton donor in the release of oleic acid and as an accelerant in the Se-P bond cleavage, which follows the mechanism of hydrogen-shift/nucleophilic-attack. The capability of the HY additive to provide a H-source decreases in the order SePPh2H > RSH > HPPh2 > ROH > RNH2, while the performance of HY to accelerate Se-P bond cleavage decreases in the order HPPh2 > RSH > RNH2 > ROH.

Activity of the Chimeric Lysin ClyR against Common Gram-Positive Oral Microbes and Its Anticaries Efficacy in Rat Models.

Dental caries is a common disease caused by oral bacteria. and are the primary cariogenic microbes that often survive as biofilms on teeth. In this study, we evaluated the activity of ClyR, a well-known chimeric lysin with extended streptococcal host range, against common Gram-positive oral microbes and its anticaries efficacy in rat models.

C1q/TNF-α-Related Protein 1 (CTRP1) Maintains Blood Pressure Under Dehydration Conditions.

Rationale: Circulating CTRP1 (C1q/TNF-α [tumor necrosis factor-α]-related protein 1) levels are increased in hypertensive patients compared with those in healthy subjects. Nonetheless, little is known about the molecular and physiological function of CTRP1 in blood pressure (BP) regulation.

Objective: To investigate the physiological/pathophysiological role of CTRP1 in BP regulation.

Serum level of brain-derived neurotrophic factor in Parkinson's disease: a meta-analysis.

Brain-derived neurotrophic factor (BDNF), a critical modulator in the neurodevelopment and maintenance of both central and peripheral nervous systems, is regarded as a potential therapeutic target of Parkinson's disease (PD). However, its association with PD remains unclear and the data are inconsistent. To explore the correlation, studies reporting BDNF levels in PD patients and healthy controls are searched and a sample of 1496 participants are pooled in the meta-analysis, demonstrating significantly decreased serum levels of BDNF in PD patients when compared with the healthy controls (SMD = -1.

Toward a More Complete, Flexible, and Safer Speed Planning for Autonomous Driving via Convex Optimization.

In this paper, we present a complete, flexible and safe convex-optimization-based method to solve speed planning problems over a fixed path for autonomous driving in both static and dynamic environments. Our contributions are five fold. First, we summarize the most common constraints raised in various autonomous driving scenarios as the requirements for speed planner developments and metrics to measure the capacity of existing speed planners roughly for autonomous driving.

Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML.

Background: Mutations in the gene encoding isocitrate dehydrogenase 1 ( IDH1) occur in 6 to 10% of patients with acute myeloid leukemia (AML). Ivosidenib (AG-120) is an oral, targeted, small-molecule inhibitor of mutant IDH1.

Methods: We conducted a phase 1 dose-escalation and dose-expansion study of ivosidenib monotherapy in IDH1-mutated AML.