Incongruence between confirmed and suspected clinical cases of Japanese encephalitis virus infection.

Background: Japanese encephalitis (JE) is a notifiable infectious disease in China. Information on every case of JE is reported to the superior health administration department. However, reported cases include both laboratory-confirmed and clinically diagnosed cases.

Carbon-reinforced NiS/TiCT MXene composite as an anode for superior-performance lithium-ion capacitors.

Lithium ion capacitors (LICs) are a new generation of energy storage devices that combine the super energy storage capability of lithium ion batteries with the satisfactory power density of supercapacitors. The development of high-performance LICs still faces great challenges due to the unbalanced reaction kinetics at the anode and cathode. Therefore, it is an inevitable need to enhance the electron/ion transfer capability of the anode materials.

The dynamic dysregulated network identifies stage-specific markers during lung adenocarcinoma malignant progression and metastasis.

Brain metastasis occurs in approximately 30% of patients with lung adenocarcinoma (LUAD) and is closely associated with poor prognosis, recurrence, and death. However, dynamic gene regulation and molecular mechanism driving LUAD progression remain poorly understood. In this study, we performed a comprehensive single-cell transcriptome analysis using data from normal, early stage, advanced stage, and brain metastasis LUAD.

LncTarD 2.0: an updated comprehensive database for experimentally-supported functional lncRNA-target regulations in human diseases.

An updated LncTarD 2.0 database provides a comprehensive resource on key lncRNA-target regulations, their influenced functions and lncRNA-mediated regulatory mechanisms in human diseases. LncTarD 2.

Identifying enhancer-driven subtype-specific prognostic markers in breast cancer based on multi-omics data.

Breast cancer is a cancer of high complexity and heterogeneity, with differences in prognosis and survival among patients of different subtypes. Copy number variations (CNVs) within enhancers are crucial drivers of tumorigenesis by influencing expression of their targets. In this study, we performed an integrative approach to identify CNA-driven enhancers and their effect on expression of target genes in four breast cancer subtypes by integrating expression data, copy number data and H3K27ac data.

Association of admission hyperglycemia and all-cause mortality in acute myocardial infarction with percutaneous coronary intervention: A dose-response meta-analysis.

Objective: The aim of this study is to evaluate the associations between admission hyperglycemia and the risk of all-cause mortality in patients with acute myocardial infarction (AMI) with or without diabetes, to find optimal admission glucose intervention cut-offs, and to clarify the shape of the dose-response relations.

Methods: Medline/PubMed and EMBASE were searched from inception to 1 April 2022. Cohort studies reporting estimates of all-cause mortality risk in patients with admission hyperglycemia with AMI were included.

Comprehensive characterization of clonality of driver genes revealing their clinical relevance in colorectal cancer.

Background: Genomic studies of colorectal cancer have revealed the complex genomic heterogeneity of the tumor. The acquisition and selection of genomic alterations may be critical to understanding the initiation and progression of this disease.

Methods: In this study, we have systematically characterized the clonal architecture of 97 driver genes in 536 colorectal cancer patients from TCGA.

Improved process intermediate stability through the identification and elimination of reactive glycation residues - a monoclonal antibody case study.

The manufacturing of therapeutic biologics can result in a heterogeneous population of charge variants, encompassing many quality attributes which could impact activity and pharmacokinetics. Monitoring the relative abundance of these charge variants to demonstrate process consistency is an expectation of regulatory agencies. Control of the relative abundance of charge variants is also necessary to ensure product comparability across the product lifecycle.

Functional regulations between genetic alteration-driven genes and drug target genes acting as prognostic biomarkers in breast cancer.

Differences in genetic molecular features including mutation, copy number alterations and DNA methylation, can explain interindividual variability in response to anti-cancer drugs in cancer patients. However, identifying genetic alteration-driven genes and characterizing their functional mechanisms in different cancer types are still major challenges for cancer studies. Here, we systematically identified functional regulations between genetic alteration-driven genes and drug target genes and their potential prognostic roles in breast cancer.

Laparoscopic-assisted endoscopic full-thickness resection of a large gastric schwannoma: A case report.

Background: Schwannomas, also known as neurinomas, are benign tumors derived from Schwann cells. Gastrointestinal schwannomas are rare and are most frequently reported in the stomach. They are usually asymptomatic and are difficult to diagnose preoperatively; however, endoscopy and imaging modalities can provide beneficial preliminary diagnostic data.

Simultaneous Inhibition of PD-1 and Stimulation of CD40 Signaling Pathways by Anti-PD-L1/CD40L Bispecific Fusion Protein Synergistically Activate Target and Effector Cells.

Bispecific antibodies (BsAbs) or fusion proteins (BsAbFPs) present a promising strategy for cancer immunotherapy. Numerous BsAbs targeting coinhibitory and costimulatory pathways have been developed for retargeting T cells and antigen presenting cells (APCs). It is challenging to assess the potency of BsAb that engages two different signaling pathways simultaneously in a single assay format, especially when the two antigen targets are expressed on different cells.

Characterization of N-Terminal Glutamate Cyclization in Monoclonal Antibody and Bispecific Antibody Using Charge Heterogeneity Assays and Hydrophobic Interaction Chromatography.

N-terminal glutamate (E) cyclization to form pyroglutamate (pE) generates charge heterogeneities for mAbs and proteins. Thus far, pE formation rate in lyophilized formulation as compared to in liquid formulation has not been reported. Impact of pE on antibody biological activity has only been predicted or assessed using stressed samples that may contain other confounding degradations besides pE.

A single homogeneous assay for simultaneous measurement of bispecific antibody target binding.

Bispecific antibodies (BsAbs) are engineered to simultaneously bind two different antigens, and offer promising clinical outcomes for various diseases. The dual binding properties of BsAbs may enable superior efficacies and/or potencies compared to standard monoclonal antibodies (mAbs) or combination mAb therapies. Characterizing BsAb binding properties is critical during biotherapeutic development, where data is leveraged to predict efficacy and potency, assess critical quality attributes and improve antibody design.

Development of a mechanism of action-reflective, dual target cell-based reporter bioassay for a bispecific monoclonal antibody targeting human CTLA-4 and PD-1.

T-cell-mediated immunotherapy has generated much excitement after the success of therapeutic biologics targeting immune checkpoint molecules. Bispecific antibodies (BsAbs) that recognize two antigen targets are a fast-growing class of biologics offering promising clinical benefits for cancer immunotherapy. Due to the complexity of the molecule structure and the potential mechanism of action (MOA) that involves more than one signaling pathway, it is critical to develop appropriate bioassays for measuring potency and characterizing the biological properties of BsAbs.

Comprehensive landscape of epigenetic-dysregulated lncRNAs reveals a profound role of enhancers in carcinogenesis in BC subtypes.

Aberrant expression of long non-coding RNAs (lncRNA) is associated with altered DNA methylation and histone modifications during carcinogenesis. However, identifying epigenetically dysregulated lncRNAs and characterizing their functional mechanisms in different cancer subtypes are still major challenges for cancer studies. In this study, we systematically analyzed the epigenetic alterations of lncRNAs at important regulatory elements in three breast cancer subtypes.

Comparative physiological and transcriptomic analysis of pear leaves under distinct training systems.

Canopy architecture is critical in determining the light interception and distribution, and subsequently the photosynthetic efficiency and productivity. However, the physiological responses and molecular mechanisms by which pear canopy architectural traits impact on photosynthesis remain poorly understood. Here, physiological investigations coupled with comparative transcriptomic analyses were performed in pear leaves under distinct training systems.

Prevention of Fab-arm exchange and antibody reduction via stabilization of the IgG4 hinge region.

IgG4s are dynamic molecules that undergo a process called Fab-arm exchange. Disulfide bonds between heavy chains are transiently reduced, resulting in half antibodies that reform intact antibodies with other IgG4 half antibodies. In vivo, therapeutic IgG4s can recombine with endogenous IgG4s, resulting in a heterogeneous mixture of bispecific antibodies.

Deamidation in Moxetumomab Pasudotox Leading to Conformational Change and Immunotoxin Activity Loss.

Asparagine (Asn) deamidation is a common posttranslational modification in which Asn is converted to aspartic acid or isoaspartic acid. By introducing a negative charge, deamidation could potentially impact the binding interface and biological activities of protein therapeutics. We identified a deamidation variant in moxetumomab pasudotox, an immunotoxin Fv fusion protein drug derived from a 38-kDa truncated Pseudomonas exotoxin A (PE38) for the treatment of hairy-cell leukemia.

LncTarD: a manually-curated database of experimentally-supported functional lncRNA-target regulations in human diseases.

Long non-coding RNAs (lncRNAs) are associated with human diseases. Although lncRNA-disease associations have received significant attention, no online repository is available to collect lncRNA-mediated regulatory mechanisms, key downstream targets, and important biological functions driven by disease-related lncRNAs in human diseases. We thus developed LncTarD (http://biocc.

Identifying functions and prognostic biomarkers of network motifs marked by diverse chromatin states in human cell lines.

Epigenetic modifications play critical roles in modulating gene expression, yet their roles in regulatory networks in human cell lines remain poorly characterized. We integrated multiomics data to construct directed regulatory networks with nodes and edges labeled with chromatin states in human cell lines. We observed extensive association of diverse chromatin states and network motifs.

Charge variants characterization and release assay development for co-formulated antibodies as a combination therapy.

Combination therapy is a fast-growing strategy to maximize therapeutic benefits to patients. Co-formulation of two or more therapeutic proteins has advantages over the administration of multiple medications, including reduced medication errors and convenience for patients. Characterization of co-formulated biologics can be challenging due to the high degree of similarity in the physicochemical properties of co-formulated proteins, especially at different concentrations of individual components.

Heated humidification did not improve compliance of positive airway pressure and subjective daytime sleepiness in obstructive sleep apnea syndrome: A meta-analysis.

Introduction: We performed a meta-analysis on whether heated humidification during positive airway pressure (PAP) could improve compliance and subjective daytime sleepiness in obstructive sleep apnea syndrome (OSAS) patients.

Materials And Methods: We searched PubMed, EMBASE, Medline, Cochrane Library, Clinical Trials, Web of Science and Scopus from inception to Oct 29, 2017. We made meta-analysis on the all available randomized controlled trials (RCTs) which assessed effects of heated humidification intervention on PAP compliance and subjective daytime sleepiness, by subgroups of automatic adjusting positive airway pressure/ continuous positive airway pressure (APAP/CPAP) usage and patients with/without upper airway symptoms prior to PAP therapy.

Characterization and analysis of scFv-IgG bispecific antibody size variants.

Bispecific antibodies are an emergent class of biologics that is of increasing interest for therapeutic applications. In one bispecific antibody format, single-chain variable fragments (scFv) are linked to or inserted in different locations of an intact immunoglobulin G (IgG) molecule to confer dual epitope binding. To improve biochemical stability, cysteine residues are often engineered on the heavy- and light-chain regions of the scFv to form an intrachain disulfide bond.