Liquid biopsy tracking during sequential chemo-radiotherapy identifies distinct prognostic phenotypes in nasopharyngeal carcinoma.

Liquid biopsies have the utility for detecting minimal residual disease in several cancer types. Here, we investigate if liquid biopsy tracking on-treatment informs on tumour phenotypes by longitudinally quantifying circulating Epstein-barr virus (EBV) DNA copy number in 673 nasopharyngeal carcinoma patients undergoing radical induction chemotherapy (IC) and chemo-radiotherapy (CRT). We observe significant inter-patient heterogeneity in viral copy number clearance that is classifiable into eight distinct patterns based on clearance kinetics and bounce occurrence, including a substantial proportion of complete responders (≈30%) to only one IC cycle.

Regulation of YAP by Mammalian Target of Rapamycin Complex 1 in Endothelial Cells Controls Blood Pressure Through COX-2/mPGES-1/PGE Cascade.

Endothelial cells regulate vascular tone by producing both relaxing and contracting factors to control the local blood flow. Hypertension is a common side effect of mTORC1 (mammalian target of rapamycin complex 1) inhibitors. However, the role of endothelial mTORC1 in hypertension remains elusive.

Inhibition of Interleukin-23-Mediated Inflammation with a Novel Small Molecule Inverse Agonist of RORt.

Blockade of interleukin (IL)-23 or IL-17 with biologics is clinically validated as a treatment of psoriasis. However, the clinical impact of targeting other nodes within the IL-23/IL-17 pathway, especially with small molecules, is less defined. We report on a novel small molecule inverse agonist of retinoid acid-related orphan receptor (ROR) t and its efficacy in preclinical models of psoriasis and arthritis.

Association of Risk Alleles With Cardiovascular Disease in Blacks in the Million Veteran Program.

Background: Approximately 13% of black individuals carry 2 copies of the apolipoprotein L1 () risk alleles G1 or G2, which are associated with 1.5- to 2.5-fold increased risk of chronic kidney disease.

[Effects of root growth on dynamics of microbes and enzyme activities during litter decomposition.].

To understand the influence of roots of understory plant entering litter layer on litter decomposition in forest ecosystems, we examined the effects of different treatments of Lolium multiflorum root biomass on microorganisms and enzyme activities during leaf litter decomposition of Symplocos setchuensis, a dominant species in a mid-subtropical evergreen broad-leaved forest, through a litter bag simulation experiment. Results showed that diversity index of bacterial and fungal communities of leaf litter surface under three treatments, i.e.

Accelerated diversifications in three diverse families of morphologically complex lichen-forming fungi link to major historical events.

Historical mass extinction events had major impacts on biodiversity patterns. The most recent and intensively studied event is the Cretaceous - Paleogene (K-Pg) boundary (ca. 66 million years ago [MYA]).

Severe Hepatotoxicity of Mithramycin Therapy Caused by Altered Expression of Hepatocellular Bile Transporters.

Mithramycin demonstrates preclinical anticancer activity, but its therapeutic dose is limited by the development of hepatotoxicity that remains poorly characterized. A pharmacogenomics characterization of mithramycin-induced transaminitis revealed that hepatotoxicity is associated with germline variants in genes involved in bile disposition: (multidrug resistance 3) rs2302387 and [bile salt export pump (BSEP)] rs4668115 reduce transporter expression ( < 0.05) and were associated with ≥grade 3 transaminitis developing 24 hours after the third infusion of mithramycin (25 mcg/kg, 6 hours/infusion, every day ×7, every 28 days; < 0.

A catalog of genetic loci associated with kidney function from analyses of a million individuals.

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178).

Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma.

Background: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials.

Methods: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone.

Plasma and Liver Protein Binding of -Acetylgalactosamine-Conjugated Small Interfering RNA.

Understanding small interfering RNA (siRNA) fraction unbound ( ) in relevant physiologic compartments is critical for establishing pharmacokinetic-pharmacodynamic relationships for this emerging modality. In our attempts to isolate the equilibrium free fraction of -acetylgalactosamine-conjugated siRNA using classic small-molecule in vitro techniques, we found that the hydrodynamic radius was critical in determining the size exclusion limit requirements for isolation, largely validating the siRNA "rigid rod" hypothesis. With this knowledge, we developed an orthogonally validated 50 kDa molecular-mass cutoff ultrafiltration assay to quantify in biologic matrices including human, nonhuman primate, rat, and mouse plasma, and human liver homogenate.

Structural elucidation, antioxidant and immunomodulatory activities of a novel heteropolysaccharide from cultured Paecilomyces cicadae (Miquel.) Samson.

The fine structure and chain conformation of a heteropolysaccharide (PCIPS3) from mycelium of Paecilomyces cicadae were investigated via the analysis of HPLC, IR, methylation, NMR spectroscopy and multiangle light scattering. It was determined to be a 2.23 × 10 g/mol heteropolysaccharide primarily composed of glucose, galactose and mannose in a molar ratio of 23.

Deep Learning for Automated Contouring of Primary Tumor Volumes by MRI for Nasopharyngeal Carcinoma.

Background Nasopharyngeal carcinoma (NPC) may be cured with radiation therapy. Tumor proximity to critical structures demands accuracy in tumor delineation to avoid toxicities from radiation therapy; however, tumor target contouring for head and neck radiation therapy is labor intensive and highly variable among radiation oncologists. Purpose To construct and validate an artificial intelligence (AI) contouring tool to automate primary gross tumor volume (GTV) contouring in patients with NPC.

Tisagenlecleucel Model-Based Cellular Kinetic Analysis of Chimeric Antigen Receptor-T Cells.

Tisagenlecleucel is a chimeric antigen receptor-T cell therapy that facilitates the killing of CD19 B cells. A model was developed for the kinetics of tisagenlecleucel and the impact of therapies for treating cytokine release syndrome (tocilizumab and corticosteroids) on expansion. Data from two phase II studies in pediatric and young adult relapsed/refractory B cell acute lymphoblastic leukemia were pooled to evaluate this model and evaluate extrinsic and intrinsic factors that may impact the extent of tisagenlecleucel expansion.

Robust CTCF-Based Chromatin Architecture Underpins Epigenetic Changes in the Heart Failure Stress-Gene Response.

Background: The human genome folds in 3 dimensions to form thousands of chromatin loops inside the nucleus, encasing genes and cis-regulatory elements for accurate gene expression control. Physical tethers of loops are anchored by the DNA-binding protein CTCF and the cohesin ring complex. Because heart failure is characterized by hallmark gene expression changes, it was recently reported that substantial CTCF-related chromatin reorganization underpins the myocardial stress-gene response, paralleled by chromatin domain boundary changes observed in CTCF knockout.

Duration of Electrocardiographic Monitoring of Emergency Department Patients With Syncope.

Background: The optimal duration of cardiac rhythm monitoring after emergency department (ED) presentation for syncope is poorly described. We sought to describe the incidence and time to arrhythmia occurrence to inform decisions regarding duration of monitoring based on ED risk stratification.

Methods: We conducted a prospective cohort study with enrolled adult patients (≥16 years old) presenting within 24 hours of syncope at 6 EDs.

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.

[Effect of Influent C/N Ratio on the Nutrient Removal Characteristics of SNEDPR Systems].

To determine the performance of nitrogen and phosphorus removal within a simultaneous nitrification endogenous denitrification system (SNEDPR), an extended anaerobic/low aerobic (dissolved oxygen:0.5-2.0 mg·L)-operated sequencing batch reactor (SBR) was fed with simulation wastewater.

[Association between the polymorphisms of TMPRSS6 and the levels of serum ferrtin and soluble transferrin receptor in pregnant women in Lüliang Area of Shanxi Province].

Objective: To analysis the associations between the polymorphisms of TMPRSS6 and the levels of serum ferritin( SF) and soluble transferrin receptor( s TfR) in pregnant women.

Methods: A total of 807 pregnant women were recruited by using cluster random sampling method from Lüliang in Shanxi Province in 2014. Roche Tinaquant immunoturbidimetric assay was used to measure the level of SF and s TfR, then iron deficiency( ID) was identified by the criteria of SF < 25 ng/m L and s TfR > 4.

Features of the metabolic syndrome in late adolescence are associated with impaired testicular function at 20 years of age.

Study Question: Are early signs of metabolic disorder in late adolescence associated with features of impaired testicular function many years before the majority seek parenthood?

Summary Answer: Adolescents with features of metabolic disorder at 17 years, or insulin resistance (IR) at 20 years of age, show impaired testicular function and altered hormone levels compared to those without metabolic disorder.

What Is Known Already: Controversial evidence suggests a recent decline in sperm production potentially linked to environmental influences, but its cause remains unclear. Concomitant increases in obesity and diabetes suggest that lifestyle factors may contribute to this decline in testicular function.

Effect of ultrafiltration during hemodialysis on hepatic and total-body water: an observational study.

Background: The hepatic circulation is involved in adaptive systemic responses to circulatory stress. However, it is vulnerable to both chronic hypervolemia and cardiac dysfunction. The influence of hemodialysis (HD) and ultrafiltration (UF) upon liver water content has been understudied.

Modernized Classification of Cardiac Antiarrhythmic Drugs.

Background: Among his major cardiac electrophysiological contributions, Miles Vaughan Williams (1918-2016) provided a classification of antiarrhythmic drugs that remains central to their clinical use.

Methods: We survey implications of subsequent discoveries concerning sarcolemmal, sarcoplasmic reticular, and cytosolic biomolecules, developing an expanded but pragmatic classification that encompasses approved and potential antiarrhythmic drugs on this centenary of his birth.

Results: We first consider the range of pharmacological targets, tracking these through to cellular electrophysiological effects.

Phylogenetic study and taxonomic revision of the group, including the description of a new species (Parmeliaceae, Ascomycota).

(Parmeliaceae, Ascomycota) is the most species-rich genus of lichen-forming fungi. Species boundaries are based on morphological and chemical features, varying reproductive strategies and, more recently, molecular sequence data. The isidiate group is common in arid regions of North and Central America and includes a range of morphological variation and variable secondary metabolites - salazinic or stictic acids mainly.

Separation of acrylonitrile-butadiene-styrene and polystyrene waste plastics after surface modification using potassium ferrate by froth flotation.

This work develops a simple and practical process for separation of acrylonitrile-butadienestyrene (ABS) and polystyrene (PS) waste plastics by froth flotation after surface modification using potassium ferrate. ABS plastics containing brominated flame retardants (BFRs) can release hazardous emissions during the process of disposal. Moreover, ABS and PS are typical styrene plastics with similar properties, posing severe restrictions on their separation for recycling.

Subcutaneous Injection of Nitroglycerin at the Radial Artery Puncture Site Reduces the Risk of Early Radial Artery Occlusion After Transradial Coronary Catheterization: A Randomized, Placebo-Controlled Clinical Trial.

Background: Transradial coronary catheterization is widely used as a diagnostic or interventional procedure for coronary disease. However, it can lead to adverse complications, such as radial artery occlusion. We sought to determine whether preprocedural injection of nitroglycerin at the radial artery puncture site reduces radial artery occlusion.