AAVone: A Cost-Effective, Single-Plasmid Solution for Efficient AAV Production with Reduced DNA Impurities.

Currently, the most common approach for manufacturing GMP-grade adeno-associated virus (AAV) vectors involves transiently transfecting mammalian cells with three plasmids that carry the essential components for production. The requirement for all three plasmids to be transfected into a single cell and the necessity for high quantities of input plasmid DNA, limits AAV production efficiency, introduces variability between production batches, and increases time and labor costs. Here, we developed an all-in-one, single-plasmid AAV production system, called AAVone.

Active Property-Structure Integrated Reconfiguration of Individual Resonant Nanoparticles.

Property-structure reconfigurable nanoparticles (NPs) provide additional flexibility for effectively and flexibly manipulating light at the nanoscale. This has facilitated the development of various multifunctional and high-performance nanophotonic devices. Resonant NPs based on dielectric active materials, especially phase change materials, are particularly promising for achieving reconfigurability.

Fractionated FLASH radiation in xenografted lung tumors induced FLASH effect at a split dose of 2 Gy.

Purpose: To explore the minimum split dose of FLASH radiotherapy (FLASH).

Material And Methods: Lungs of nude mice were used to verify the capacity of normal tissue sparing of FLASH, while tumor-bearing nude mice were used to evaluate the curative power. Xenografted tumor models were established in Balb/c-nu mice using A549 cells at a concentration of With the same total dose (20 Gy), the dose rate of FLASH was 200 Gy/s when conventional radiotherapy(CONV) was 0.

A Hybrid Spectral Library and Protein Sequence Database Search Strategy for Bottom-Up and Top-Down Proteomic Data Analysis.

Tandem mass spectrometry (MS/MS) is widely employed for the analysis of complex proteomic samples. While protein sequence database searching and spectral library searching are both well-established peptide identification methods, each has shortcomings. Protein sequence databases lack fragment peak intensity information, which can result in poor discrimination between correct and incorrect spectrum assignments.

Diagnostic Value of Carcinoembryonic Antigen Combined with Multi-Inflammatory Cell Ratios in Colorectal Cancer.

Purpose: To evaluate the diagnostic value of carcinoembryonic antigen (CEA) combined with inflammatory cell ratios in colorectal cancer (CRC).

Methods: This retrospective study compared the data of CRC patients with healthy controls. The CEA levels were measured, and the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were calculated.

Carbon nanotube filter functionalized with MIL-101(Fe) for enhanced flow-through electro-Fenton.

Herein, an electrochemical carbon nanotubes (CNT) filter modified with MIL-101(Fe) has been designed for the electro-Fenton applications by serving as a functional flow-through electrode. Under an electric field, the hybrid filter enabled the in situ generation of HOvia the two-electron oxygen reduction reaction, which promoted the production of HO by the accelerated Fe/Fe cycling of MIL-101(Fe). It was observed that 93.

Adaptive support ventilation attenuates postpneumonectomy acute lung injury in a porcine model.

Objectives: An optimal ventilation strategy that causes as little mechanical stress and inflammation as possible is critical for patients undergoing pneumonectomy. The aim of this study was to determine whether adaptive support ventilation (ASV) can provide protective ventilation to the remaining lung after pneumonectomy with minimal mechanical stress and less inflammation than volume-control ventilation (VCV).

Methods: In this study, 15 pigs were randomly allocated to 3 groups (n = 5 for each group): the control group, the VCV group and the ASV group.

Trends in Recurrent Coronary Heart Disease After Myocardial Infarction Among US Women and Men Between 2008 and 2017.

Background: Rates for recurrent coronary heart disease (CHD) events have declined in the United States. However, few studies have assessed whether this decline has been similar among women and men.

Methods: Data were used from 770 408 US women and 700 477 US men <65 years of age with commercial health insurance through MarketScan and ≥66 years of age with government health insurance through Medicare who had a myocardial infarction (MI) hospitalization between 2008 and 2017.

Atherosclerotic Risk and Statin Use Among Patients With Peripheral Artery Disease.

Background: Peripheral artery disease (PAD) is associated with increased risk for atherosclerotic cardiovascular disease (ASCVD) events.

Objectives: The goal of this study was to compare the risk for ASCVD events and the use of statins among patients with PAD versus those with coronary heart disease (CHD) or cerebrovascular disease.

Methods: The authors conducted a retrospective cohort study of adults age ≥19 years with commercial or Medicare health insurance who had a history of PAD, CHD, or cerebrovascular disease on December 31, 2014.

Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia.

A subset of B cell acute lymphoblastic leukemia (B-ALL) patients will relapse and succumb to therapy-resistant disease. The bone marrow microenvironment may support B-ALL progression and treatment evasion. Utilizing single-cell approaches, we demonstrate B-ALL bone marrow immune microenvironment remodeling upon disease initiation and subsequent re-emergence during conventional chemotherapy.

Agreement of claims-based methods for identifying sepsis with clinical criteria in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.

Background: Claims-based algorithms are commonly used to identify sepsis in health services research because the laboratory features required to define clinical criteria may not be available in administrative data.

Methods: We evaluated claims-based sepsis algorithms among adults in the US aged ≥65 years with Medicare health insurance enrolled in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Suspected infections from baseline (2003-2007) through December 31, 2012 were analyzed.

Adaptive Support Ventilation Attenuates Ventilator Induced Lung Injury: Human and Animal Study.

Adaptive support ventilation (ASV) is a closed-loop ventilation, which can make automatic adjustments in tidal volume (V) and respiratory rate based on the minimal work of breathing. The purpose of this research was to study whether ASV can provide a protective ventilation pattern to decrease the risk of ventilator-induced lung injury in patients of acute respiratory distress syndrome (ARDS). In the clinical study, 15 ARDS patients were randomly allocated to an ASV group or a pressure-control ventilation (PCV) group.

The E3 ubiquitin ligase SPOP controls resolution of systemic inflammation by triggering MYD88 degradation.

The response to systemic infection and injury requires the rapid adaptation of hematopoietic stem cells (HSCs), which proliferate and divert their differentiation toward the myeloid lineage. Significant interest has emerged in understanding the signals that trigger the emergency hematopoietic program. However, the mechanisms that halt this response of HSCs, which is critical to restore homeostasis, remain unknown.

Association of Region and Hospital and Patient Characteristics With Use of High-Intensity Statins After Myocardial Infarction Among Medicare Beneficiaries.

Importance: High-intensity statin use after myocardial infarction (MI) varies by patient characteristics, but little is known about differences in use by hospital or region.

Objective: To explore the relative strength of associations of region and hospital and patient characteristics with high-intensity statin use after MI.

Design, Setting, And Participants: This retrospective cohort analysis used Medicare administrative claims and enrollment data to evaluate fee-for-service Medicare beneficiaries 66 years or older who were hospitalized for MI from January 1, 2011, through June 30, 2015, with a statin prescription claim within 30 days of discharge.

Adherence to Statin Therapy Among US Adults Between 2007 and 2014.

Background Prior studies suggest that persistence with and adherence to statin therapy is low. Interventions to improve statin persistence and adherence have been developed over the past decade. Methods and Results This was a retrospective cohort study of adults aged ≥21 y with commercial or government health insurance in the MarketScan (Truven Health Analytics) and Medicare databases who initiated statins in 2007-2014 and (1) started treatment after a myocardial infarction (n=201 573), (2) had diabetes mellitus but without coronary heart disease (CHD; n=610 049), or (3) did not have CHD or diabetes mellitus (n=2 244 868).

Validation of the REGARDS Severe Sepsis Risk Score.

There are no validated systems for characterizing long-term risk of severe sepsis in community-dwelling adults. We tested the ability of the REasons for Geographic and Racial Differences in Stroke-Severe Sepsis Risk Score (REGARDS-SSRS) to predict 10-year severe sepsis risk in separate cohorts of community-dwelling adults. We internally tested the REGARDS-SSRS on the REGARDS-Medicare subcohort.

Regulation of the terminal maturation of iNKT cells by mediator complex subunit 23.

Invariant natural killer T cells (iNKT cells) are a specific subset of T cells that recognize glycolipid antigens and upon activation rapidly exert effector functions. This unique function is established during iNKT cell development; the detailed mechanisms of this process, however, remain to be elucidated. Here the authors show that deletion of the mediator subunit Med23 in CD4CD8 double positive (DP) thymocytes completely blocks iNKT cell development at stage 2.

Med23 serves as a gatekeeper of the myeloid potential of hematopoietic stem cells.

In response to myeloablative stresses, HSCs are rapidly activated to replenish myeloid progenitors, while maintaining full potential of self-renewal to ensure life-long hematopoiesis. However, the key factors that orchestrate HSC activities during physiological stresses remain largely unknown. Here we report that Med23 controls the myeloid potential of activated HSCs.

Titration to High-Intensity Statin Therapy Following Acute Myocardial Infarction in Patients With and Without Diabetes Mellitus.

Background: Patients with diabetes mellitus (DM) have a high risk for cardiovascular disease (CVD) events after an acute myocardial infarction (AMI). High-intensity statins reduce CVD risk following AMI among patients with and without DM.

Methods: We determined the proportion of Medicare beneficiaries 66 to 75 years of age taking a low/moderate-intensity statin with (n = 6718) and without (n = 6414) DM who titrated to a high-intensity statin dosage (i.

Sex Differences in High-Intensity Statin Use Following Myocardial Infarction in the United States.

Background: Historically, women have been less likely than men to receive guideline-recommended statin therapy for the secondary prevention of myocardial infarction (MI).

Objectives: The authors examined contemporary sex differences in prescription fills for high-intensity statin therapy following an MI, overall and across population subgroups, and assessed whether sex differences were attenuated following recent efforts to reduce sex disparities in the use of cardiovascular disease preventive therapies.

Methods: The authors studied 16,898 (26% women) U.

Trends in Use of High-Intensity Statin Therapy After Myocardial Infarction, 2011 to 2014.

Background: Data prior to 2011 suggest that a low percentage of patients hospitalized for acute coronary syndromes filled high-intensity statin prescriptions upon discharge. Black-box warnings, generic availability of atorvastatin, and updated guidelines may have resulted in a change in high-intensity statin use.

Objectives: The aim of this study was to examine trends and predictors of high-intensity statin use following hospital discharge for myocardial infarction (MI) between 2011 and 2014.

Risk factors for the development of pulmonary oil embolism after transcatheter arterial chemoembolization of hepatic tumors.

Pulmonary oil embolism (POE) is a rare fatal complication after transcatheter arterial embolization (TAE) and transcatheter arterial chemoembolization (TACE). As risk factors have not been clearly delineated, the aim of the present study was to identify the risk factors for development of POE after TACE. A retrospective analysis was carried out on patients with unresectable hepatocellular carcinoma who received TAE or TACE at the Tri-Service General Hospital (Taiwan) between January 2005 and December 2008.

Suppression of antimicrobial peptide expression by ureaplasma species.

Ureaplasma species commonly colonize the adult urogenital tract and are implicated in invasive diseases of adults and neonates. Factors that permit the organisms to cause chronic colonization or infection are poorly understood. We sought to investigate whether host innate immune responses, specifically, antimicrobial peptides (AMPs), are involved in determining the outcome of Ureaplasma infections.