Harmonization of Vaccine Ligand Binding Assays Validation.

The urgency and importance of organizing a global effort to harmonize clinical assay validation specific to the vaccine industry was identified during the drafting of the 2020 White Paper in Bioanalysis due to the lack of clarity and regulatory guidance/guidelines in vaccine immunoassay validation. Indeed, the Workshop on Recent Issues in Bioanalysis (WRIB) issues the White Paper in Bioanalysis yearly, which is one of the high-profile articles of the Journal focused on detailed discussions and recommendations on vaccine assay validation. Since 2017, participation in the WRIB working groups by vaccine assay validation experts and regulators has rapidly increased due to its unique format where industry leaders and regulators can meet and exchange ideas on topics of interest to both groups.

Development and Validation of a Cell-Based Binding Neutralizing Antibody Assay for an Antibody-Drug Conjugate.

The utilization of antibody-drug conjugates (ADCs) has gained considerable attention in the field of targeted cancer therapy due to their ability to synergistically combine the specificity of monoclonal antibodies (mAbs) and the potency of small molecular drugs. However, the immunogenic nature of the antibody component within ADCs warrants the need for robust immunogenicity testing, including a neutralizing antibody (NAb) assay. Since the mechanism of action (MOA) of the ADC is to first bind to the target cells and then release the payload intracellularly to kill the cells, the most relevant NAb assay format would be a cell-based killing assay.

Safety and feasibility of same-day discharge following uncomplicated transvenous lead extraction.

Introduction: Transvenous lead extraction (TLE), while mostly a safe procedure, has risk of serious periprocedural complications. As such, overnight hospitalization remains a routine practice. In our center, we routinely discharge patients on the same day following an uncomplicated TLE.

Management of Early Postoperative Bleeding After OAGB: A Single-center Experience.

Introduction: One anastomosis gastric bypass (OAGB) has gained popularity among bariatric surgeons due to the shorter operative time, fewer sites for anastomotic leaks and internal herniation, shorter learning curve, ease of reversibility and revision with equivalent results to Roux en Y gastric bypass in terms of weight loss and co-morbidity resolution. We present our experience in managing early postoperative bleeding after OAGB.

Patients And Methods: Patients who underwent OAGB in Bariatric Surgery Unit, Ain Shams University Hospitals between January 2016 and January 2023 were followed up for 30 days for early postoperative complications.

Novel streamlined technique for left atrial appendage closure using a radiofrequency wire-based large access system.

Introduction: Transseptal puncture (TSP) to allow for large delivery sheath left atrial (LA) access remains a challenging aspect of LA appendage closure (LAAC) in patients with prior history of TSP, thick or lipomatous septum, atrial septal aneurysms, or other complex cardiac anatomies. This study investigates the use of the VersaCross large access (VLA) system (Baylis Medical/Boston Scientific) to improve procedural efficiency of LAAC compared to the standard needle workflow.

Methods And Results: Fifty LAAC procedures using WATCHMAN FLX between November 2021 and September 2022 were retrospectively analyzed comparing the VLA workflow (n = 25) to the standard needle workflow (n = 25).

Molecular insights into hereditary elliptocytosis and pyropoikilocytosis: NGS uncovers multiple potential candidate genes.

Hereditary elliptocytosis (HE) and pyropoikilocytosis (HPP) are considered a group of hemolytic anemias (HE/HPP) due to inherited abnormalities of erythrocyte membrane proteins with a worldwide distribution. Most cases are associated with molecular abnormalities linked to spectrin, band 4.1, and ankyrin.

The potential effect of Moringa oleifera ethanolic leaf extract against oxidative stress, immune response disruption induced by abamectin exposure in Oreochromis niloticus.

Abamectin (ABM), a naturally fermented product of Streptomyces avermitilis, is applied to pest control in livestock and agriculture fields. The aim of the current study is to evaluate the protective effects of Moringa oleifera leaf ethanolic extract (MOE) on biochemical changes including oxidative stress indices, immune response marker, lipid profiles as well as mRNA expression of immune related genes, and abamectin (ABM, 5% EC) residue levels in Nile tilapia (Oreochromis niloticus) exposed to a sub-lethal concentration (0.5 µg/l) for 28 days.

A Novel Neutralization Antibody Assay Method to Overcome Drug Interference with Better Compatibility with Acid-Sensitive Neutralizing Antibodies.

Immunogenicity testing to detect and characterize anti-drug antibody (ADA) is required for almost all biotherapeutics. Monoclonal antibody biotherapeutics usually have long half-lives and for high-dose indications such as oncology, high level of drug will be present in the testing samples and interfere with ADA and/or neutralization antibody (NAb) measurement. To overcome this drug interference, acid-dissociation-based sample pre-treatment such as Bead-Extraction and Acid Dissociation (BEAD) has been successfully applied.

One-Step Regio- and Stereoselective Electrochemical Synthesis of Orexin Receptor Antagonist Oxidative Metabolites.

Synthesis of drug metabolites, which often have complex structures, is an integral step in the evaluation of drug candidate metabolism, pharmacokinetic (PK) properties, and safety profiles. Frequently, such synthetic endeavors entail arduous, multiple-step de novo synthetic routes. Herein, we present the one-step Shono-type electrochemical synthesis of milligrams of chiral α-hydroxyl amide metabolites of two orexin receptor antagonists, MK-8133 and MK-6096, as revealed by a small-scale (pico- to nano-mole level) reaction screening using a lab-built online electrochemistry (EC)/mass spectrometry (MS) (EC/MS) platform.

Prediction of frozen virus stability based on degradation mechanisms, real-time data and modeling.

Critical virus reagents in regulated bioanalytical assays require stability monitoring. Although stability at ultra-low frozen temperatures is generally assumed, published data are limited and real-time studies are time consuming. The authors reviewed literature data, typical mechanisms of molecular degradation, glass transition temperatures of commonly used buffers and available real-time storage data to model frozen virus reagent stability.

Neutralization Activity of Anti-drug Antibodies Against a Biotherapeutic Can Be Predicted from a Comprehensive Pharmacokinetics, Pharmacodynamics, and Anti-drug Antibody Data Analysis.

Historically, a neutralization antibody (NAb) assay is considered critical in immunogenicity assessment of biologic therapeutics, even with low anti-drug antibody (ADA) positive rates. In 2019, FDA new guidelines issued on immunogenicity testing acknowledged the possibility of using "a highly sensitive PD marker or an appropriately designed PK assay or both that generate data that inform clinical activity" to replace a NAb assay. In the current manuscript, we present data for PK, PD, and ADA assays which collectively succeed to replace the standalone NAb assay.

Residue, dissipation, and dietary intake evaluation of fenpyroximate acaricide in/on guava, orange, and eggplant under open field condition.

Fenpyroximate is a widely used acaricide applicable in many crops. In this study, the residue behavior of fenpyroximate on eggplant, orange, and guava was investigated. The chronic and acute dietary intake was calculated at several sampling points, and preharvest intervals (PHI) were proposed to ensure compliance with the existing maximum residue levels.

Covid-19 in Egyptian hemodialysis and kidney transplant children: retrospective analysis of single center experience.

Background: Chronic kidney disease stage 5 (CKD 5) populations have peculiar risk for severe Covid-19 infection. Moreover; pediatric data are sparse and lacking. The aim of this study is to report our experience in CKD 5 children treated by hemodialysis (CKD 5D) and CKD 5 children after kidney transplantation (KTR) during one year of Covid-19 pandemic.

A New Laparoscopic Entry Point in Patients With Previous Laparotomy: A Prospective Comparative Study.

Introduction: Intraperitoneal access and establishing pneumoperitoneum for laparoscopy is a critical step especially in patients who underwent previous laparotomy due to the higher risk of visceral or vascular injuries. In this study, we propose a new entry point for safe laparoscopic access in cases having previous laparotomy.

Materials And Methods: This is a prospective controlled randomized trial conducted between January 2016 and January 2022 in Ain Shams University Hospitals.

Computer-controlled Intraligamentary local anaesthesia in extraction of mandibular primary molars: randomised controlled clinical trial.

Background: Local anesthesia (LA) poses a threat in children more than the treatment process itself, so pediatric dentists are always demanding less painful techniques. Computer-controlled Intraligamentary anaesthesia (CC-ILA) is designed to reduce injection pain and side effects of conventional techniques. The present study aims to assess the pain experience using Computer-controlled Intraligamentary anaesthesia (CC-ILA) during injection and its effectiveness in controlling pain during extraction of mandibular primary molars in pediatric patients.

Meary angle for the prediction of mitral valve prolapse risk in non-syndromic patients with pes planus, a cross-sectional study.

Objectives: Mitral Valve Prolapse (MVP) is a common valvular abnormality accounting for 2% of the population. There is a reported association between pes planus (PP) and MVP in some syndromes such as Marfan. However, this association has not been tested in non-syndromic cases.

Diminishing GSH-Adduct Formation of Tricyclic Diazepine-based Mutant IDH1 Inhibitors.

Mutant isocitrate dehydrogenase 1 (IDH1) has been identified as an attractive oncology target for which >70% of grade II and III gliomas and ∼10% of acute myeloid leukemia (AML) harbor somatic IDH1 mutations. These mutations confer a neomorphic gain of function, leading to the production of the oncometabolite ()-2-hydroxyglutarate (2-HG). We identified and developed a potent, selective, and orally bioavailable brain-penetrant tricyclic diazepine scaffold that inhibits mutant IDH1.

Highly sensitive LC-MS method for stereochemical quality control of a pharmaceutical drug substance intermediate.

Stereochemical quality control for pharmaceutical drug substance intermediates is a daunting task, especially considering the need to separate multiple stereoisomers simultaneously with low ppm level sensitivity. To address these challenges, we have successfully implemented chiral column screening, and developed an ultrasensitive liquid chromatography-mass spectrometry (LC-MS) method to separate four stereoisomers including the API intermediate, its enantiomer, and two other diastereomers. Parameters such as mobile phase additives, MS fragmentor, and column temperature were optimized to achieve the desired selectivity and sensitivity.

Clinical and neurophysiological characterization of early neuromuscular involvement in children and adolescents with nephropathic cystinosis.

Background: Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder characterized by kidney and extra-renal complications due to the accumulation of cystine crystals in various tissues and organs. Herein, we describe the early neuromuscular complications in a cohort of pediatric nephropathic cystinosis patients.

Methods: We prospectively evaluated the clinical, biochemical, and neurophysiological data of 15 cystinosis patients.

Post-COVID-19 functional status: Relation to age, smoking, hospitalization, and previous comorbidities.

Rational: Recently, a new "Post-COVID-19 Functional Status (PCFS) scale" is recommended in the current COVID-19 pandemic. It is proposed that it could be used to display direct retrieval and the functional sequelae of COVID-19.

Aim Of The Study: The aim of the study was to assess the PCFS and to evaluate if age, gender, smoking, hospitalization, and comorbidities have any effect on functional limitations in recovered COVID-19 patients.

Native vs. active vitamin D in children with chronic kidney disease: a cross-over study.

Background: The rationale for the prescription of vitamin D analogues in patients with chronic kidney disease (CKD) is still a matter of debate. We aimed to compare native vs. active forms of vitamin D on pre-dialysis children with CKD and evaluate effects on calcium (Ca), phosphorus (P), and parathyroid hormone (PTH).

Subtle cardiac dysfunction in nephropathic cystinosis: insight from tissue Doppler imaging and 2D speckle tracking echocardiography.

Background: Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder that initially affects the kidney progressing to multi-organ failure due to accumulation of cystine in all tissue compartments.

Objective: The main objective of this study is the evaluation of cardiac function in cystinosis patients using non-conventional echocardiographic modalities like pulsed wave tissue Doppler imaging (PW-TDI) and 2D speckle tracking echocardiography (2D-STE).

Methods: This is a case control study conducted on fifteen patients with cystinosis and 15 normal controls.

Direct Drug Analysis in Polymeric Implants Using Desorption Electrospray Ionization - Mass Spectrometry Imaging (DESI-MSI).

Purpose: Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) coupled with gas-phase ion mobility spectrometry was used to characterize the drug distribution in polymeric implants before and after exposure to accelerated in vitro release (IVR) media. DESI-MSI provides definitive chemical identification and localization of formulation components, including 2D chemical mapping of individual components with essentially no sample preparation.

Methods: Polymeric implants containing 40% (w/w) entecavir and poly(D,L-lactide) (PLA) were prepared and then exposed to either acidified PBS (pH 2.

Pediatric kidney transplantation in Egypt: Results of 10-year single-center experience.

Pediatric kidney transplantation is a multidisciplinary therapy that needs special consideration and experience. In this study, we aimed to present CUCH experience; over a 10-year period, as a specialized center of kidney transplantation in children. We studied 148 transplantations performed at a single center from 2009 to 2018.

Validation of the patient assessment of chronic illness care (PACIC) short form scale in heart transplant recipients: the international cross-sectional bright study.

Background: Transplant recipients are chronically ill patients, who require lifelong follow-up to manage co-morbidities and prevent graft loss. This necessitates a system of care that is congruent with the Chronic Care Model. The eleven-item self-report Patient Assessment of Chronic Illness Care (PACIC) scale assesses whether chronic care is congruent with the Chronic Care Model, yet its validity for heart transplant patients has not been tested.