Effect of zoledronic acid and pamidronate on renal function.

Background: There is limited data on the effect bisphosphonates have on renal function and the use of bisphosphonates in patients with baseline renal dysfunction.

Objective: The purpose of this study was to determine the incidence of acute kidney injury (AKI) in patients after receiving zoledronic acid or pamidronate.

Methods: A retrospective cohort analysis was conducted of patients who received one dose of a bisphosphonate, either zoledronic acid or pamidronate.

SARS-CoV-2 spreads through cell-to-cell transmission.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible coronavirus responsible for the global COVID-19 pandemic. Herein, we provide evidence that SARS-CoV-2 spreads through cell-cell contact in cultures, mediated by the spike glycoprotein. SARS-CoV-2 spike is more efficient in facilitating cell-to-cell transmission than is SARS-CoV spike, which reflects, in part, their differential cell-cell fusion activity.

Severe Acute Respiratory Syndrome Coronavirus 2 RNAemia and Clinical Outcomes in Children With Coronavirus Disease 2019.

The burden of coronavirus disease 2019 (COVID-19) in children represents a fraction of cases worldwide, yet a subset of those infected are at risk for severe disease. We measured plasma severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in a cohort of 103 children hospitalized with COVID-19 with diverse clinical manifestations. SARS-CoV-2 RNAemia was detected in 27 (26%) of these children, lasted for a median of 6 (interquartile range, 2-9) days, and was associated with higher rates of oxygen administration, admission to the intensive care unit, and longer hospitalization.

SARS-CoV-2 Spreads through Cell-to-Cell Transmission.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible coronavirus responsible for the global COVID-19 pandemic. Herein we provide evidence that SARS-CoV-2 spreads through cell-cell contact in cultures, mediated by the spike glycoprotein. SARS-CoV-2 spike is more efficient in facilitating cell-to-cell transmission than SARS-CoV spike, which reflects, in part, their differential cell-cell fusion activity.

The larger attachment glycoprotein of respiratory syncytial virus produced in primary human bronchial epithelial cultures reduces infectivity for cell lines.

Respiratory syncytial virus (RSV) infects the upper and lower respiratory tracts and can cause lower respiratory tract infections in children and elders. RSV has traditionally been isolated, grown, studied and quantified in immortalized cell lines, most frequently HEp-2 cells. However, in vivo RSV infection is modeled more accurately in primary well differentiated human bronchial epithelial (HBE) cultures where RSV targets the ciliated cells and where the putative RSV receptor differs from the receptor on HEp-2 cells.

Enabled/VASP is required to mediate proper sealing of opposing cardioblasts during Drosophila dorsal vessel formation.

Introduction: The Drosophila dorsal vessel (DV) is comprised of two opposing rows of cardioblasts (CBs) that migrate toward the dorsal midline during development. While approaching the midline, CBs change shape, enabling dorsal and ventral attachments with their contralateral partners to create a linear tube with a central lumen. We previously demonstrated DV closure occurs via a "buttoning" mechanism where specific CBs advance ahead of their lateral neighbors, and attach creating transient holes, which eventually seal.

Combination Therapy for Solid Tumors: Taking a Classic CAR on New Adventures.

CD19-specific CAR-T cell therapies are the gold standard of adoptive cellular immunotherapy for hematopoietic malignancies. In Science Translational Medicine, Park et al. develop an oncolytic vaccinia virus that introduces truncated CD19 expression in solid tumors, which are then eradicated by CD19-specific CAR-T cells in immunodeficient and immunocompetent mouse models.

Severe SARS-CoV-2 disease in the context of a NF-κB2 loss-of-function pathogenic variant.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that emerged recently and has created a global pandemic. Symptomatic SARS-CoV-2 infection, termed coronavirus disease 2019 (COVID-19), has been associated with a host of symptoms affecting numerous organ systems, including the lungs, cardiovascular system, kidney, central nervous system, gastrointestinal tract, and skin, among others.

Objective: Although several risk factors have been identified as related to complications from and severity of COVID-19, much about the virus remains unknown.

Mathematical modelling identifies the role of adaptive immunity as a key controller of respiratory syncytial virus in cotton rats.

Respiratory syncytial virus (RSV) is a common virus that can have varying effects ranging from mild cold-like symptoms to mortality depending on the age and immune status of the individual. We combined mathematical modelling using ordinary differential equations (ODEs) with measurement of RSV infection kinetics in primary well-differentiated human bronchial epithelial cultures and in immunocompetent and immunosuppressed cotton rats to glean mechanistic details that underlie RSV infection kinetics in the lung. Quantitative analysis of viral titre kinetics in our mathematical model showed that the elimination of infected cells by the adaptive immune response generates unique RSV titre kinetic features including a faster timescale of viral titre clearance than viral production, and a monotonic decrease in the peak RSV titre with decreasing inoculum dose.

Approaches of T Cell Activation and Differentiation for CAR-T Cell Therapies.

Chimeric antigen receptor (CAR) T cell therapies are ex vivo manufactured cellular products that have been useful in the treatment of blood cancers and solid tumors. The quality of the final cellular product is influenced by several amenable factors during the manufacturing process. This review discusses several of the influences on cell product phenotype, including the raw starting material, methods of activation and transduction, and culture supplementation.

Glycan-directed CAR-T cells.

Cancer immunotherapy is rapidly advancing in the treatment of a variety of hematopoietic cancers, including pediatric acute lymphoblastic leukemia and diffuse large B cell lymphoma, with chimeric antigen receptor (CAR)-T cells. CARs are genetically encoded artificial T cell receptors that combine the antigen specificity of an antibody with the machinery of T cell activation. However, implementation of CAR technology in the treatment of solid tumors has been progressing much slower.

Introduction of a polar core into the de novo designed protein Top7.

Design of polar interactions is a current challenge for protein design. The de novo designed protein Top7, like almost all designed proteins, has an entirely nonpolar core. Here we describe the replacing of a sizable fraction (5 residues) of this core with a designed polar hydrogen bond network.

Cdc42 is required in a genetically distinct subset of cardiac cells during Drosophila dorsal vessel closure.

The embryonic heart tube is formed by the migration and subsequent midline convergence of two bilateral heart fields. In Drosophila the heart fields are organized into two rows of cardioblasts (CBs). While morphogenesis of the dorsal ectoderm, which lies directly above the Drosophila dorsal vessel (DV), has been extensively characterized, the migration and concomitant fundamental factors facilitating DV formation remain poorly understood.

Head and neck cancer: changing epidemiology and public health implications.

Characterizing the epidemiology of head and neck cancers is challenging and has received limited attention in the medical literature. Traditionally, 80%-90% of head and neck squamous cell carcinomas (HNSCCs) have been attributed to tobacco and alcohol use, but with growing public awareness and tobacco control efforts over the past few decades, there has been a downward trend in smoking prevalence in the US. There is also emerging evidence that human papillomavirus (HPV) is responsible for inconsistencies in HNSCC trends, with oncogenic HPV DNA found in approximately half of oropharyngeal cancers and in a high proportion of oropharyngeal cancers in nonsmokers and nondrinkers.

Effect of physicochemical anomalies of soda-lime silicate slides on biomolecule immobilization.

Glass microscope slides are considered by many as the substrate of choice for microarray manufacturing due to their amenability to various surface chemistry modifications. The use of silanes to attach various functional groups onto glass slides has provided a versatile tool for the covalent immobilization of many diverse biomolecules of interest. We recently noted a dramatic reduction in biomolecule immobilization efficiency on standard microscope slides prepared using a well-characterized silanization method.

Upregulation of GLUT-4 in right ventricle of rats with monocrotaline-induced pulmonary hypertension.

Background: Pulmonary hypertension is characterized by abnormal vascular remodeling leading to occlusion of pulmonary arteries and increased stress placed on the right ventricle (RV). This causes the RV to hypertrophy and eventually to failure. This study was designed to examine the effects of pulmonary hypertension in rats on right ventricular remodeling and glucose transporter protein (GLUT4) content in right (RV) and left ventricle (LV).