Engineered myeloid precursors differentiate into osteoclasts and resorb heterotopic ossification in mice.

Introduction: Heterotopic ossification (HO) occurs following orthopedic trauma, spinal cord injuries, brain trauma and limb amputations. Once symptomatic, HO causes pain, limited mobility and decreased quality of life. Current treatments are limited and have significant complications with high recurrence rates, underscoring the need for improved therapeutic interventions.

Caregiver Global Impression Observations from EMBARK: A Phase 3 Study Evaluating Delandistrogene Moxeparvovec in Ambulatory Patients with Duchenne Muscular Dystrophy.

Introduction: Duchenne muscular dystrophy (DMD) is a rare, progressive, debilitating neuromuscular disease. The early childhood onset and debilitating nature of the disease necessitate decades of caretaking for most patients. Caregivers have a critical role in evaluating patients' physical functioning and/or response to treatment.

Sources of bias in studies reporting birth prevalence of congenital anomalies: a scoping review and reporting checklist.

Background: Data on the birth prevalence of congenital anomalies in low- and middle-income countries report wide variations in prevalence estimates. We conducted a scoping review to identify the sources of bias in studies reporting birth prevalence of congenital anomalies in World Health Organization South-East Asia region (SEAR) countries.

Methods: PubMed and Google Scholar databases were screened for relevant literature.

Divergent downstream biosynthetic pathways are supported by L-cysteine synthases of .

's () autarkic lifestyle within the host involves rewiring its transcriptional networks to combat host-induced stresses. With the help of RNA sequencing performed under various stress conditions, we identified that genes belonging to sulfur metabolism pathways are significantly upregulated during oxidative stress. Using an integrated approach of microbial genetics, transcriptomics, metabolomics, animal experiments, chemical inhibition, and rescue studies, we investigated the biological role of non-canonical L-cysteine synthases, CysM and CysK2.

Dispensing pharmacy chains and direct anticoagulants: Potential associations with patient outcomes.

Purpose: Pharmacy chains can differ with respect to the characteristics of their patient populations as well as their nonprescription products, services, and practices, and thus may serve as a surrogate for potential unmeasured confounding in observational studies of prescription drugs. This study evaluates whether a single-source drug can have different patient outcomes based on the dispensing pharmacy chain.

Methods: Separate analyses for two anticoagulant drugs, rivaroxaban and apixaban, were conducted using Medicare Fee-for-Service claims evaluating the association between dispensing pharmacy chain and outcomes of acute myocardial infarction, ischemic stroke, intracranial hemorrhage, gastrointestinal (GI) bleeding, all-cause mortality, and major GI bleeding.

Incorporating Prior Data in Quantitative Benefit-Risk Assessments: Case Study of a Bayesian Method.

Background: Multiple criteria decision analysis (MCDA) and stochastic multi-criteria acceptability analysis (SMAA) in their current implementation cannot incorporate prior or external information on benefits and risks. We demonstrate how to incorporate prior data using a Bayesian mixture model approach while conducting quantitative benefit-risk assessments (qBRA) for medical products.

Methods: We implemented MCDA and SMAA in a Bayesian framework.

Scalable Incident Detection via Natural Language Processing and Probabilistic Language Models.

Post marketing safety surveillance depends in part on the ability to detect concerning clinical events at scale. Spontaneous reporting might be an effective component of safety surveillance, but it requires awareness and understanding among healthcare professionals to achieve its potential. Reliance on readily available structured data such as diagnostic codes risk under-coding and imprecision.

Retinal inflammation in murine models of type 1 and type 2 diabetes with diabetic retinopathy.

Aims/hypothesis: The loss of pericytes surrounding the retinal vasculature in early diabetic retinopathy underlies changes to the neurovascular unit that lead to more destructive forms of the disease. However, it is unclear which changes lead to loss of retinal pericytes. This study investigated the hypothesis that chronic increases in one or more inflammatory factors mitigate the signalling pathways needed for pericyte survival.

Evaluation of association of anti-PEG antibodies with anaphylaxis after mRNA COVID-19 vaccination.

Background: The mechanism for anaphylaxis following mRNA COVID-19 vaccination has been widely debated; understanding this serious adverse event is important for future vaccines of similar design. A mechanism proposed is type I hypersensitivity (i.e.

Lead derivatization of ethyl 6-bromo-2-((dimethylamino)methyl)-5-hydroxy-1-phenyl-1H-indole-3-carboxylate and 5-bromo-2-(thiophene-2-carboxamido) benzoic acid as FabG inhibitors targeting ESKAPE pathogens.

Our previous studies on FabG have identified two compounds 5-bromo-2-(thiophene-2-carboxamido) benzoic acid (A) and ethyl 6-bromo-2-((dimethylamino)methyl)-5-hydroxy-1-phenyl-1H-indole-3-carboxylate(B) as best hits with allosteric mode of inhibition. FabG is an integral part of bacterial fatty acid biosynthetic system FAS II shown to be an essential gene in most ESKAPE Pathogens. The current work is focussed on lead expansion of these two hit molecules which ended up with forty-three analogues (twenty-nine analogues from lead compound A and fourteen compounds from lead compound B).

Role of Runx2 in Calcific Aortic Valve Disease in Mouse Models.

Calcific aortic valve disease is common in the aging population and is characterized by the histological changes of the aortic valves including extracellular matrix remodeling, osteochondrogenic differentiation, and calcification. Combined, these changes lead to aortic sclerosis, aortic stenosis (AS), and eventually to heart failure. Runt-related transcription factor 2 (Runx2) is a transcription factor highly expressed in the calcified aortic valves.

Socio-demographic profile and its influences on rehabilitation in children undergoing revision cochlear implantation - MERF experience.

Introduction: Revision cochlear implant surgery (RIS) is an unusual and unfortunate event, but not an uncommon occurrence in today's time, with more and more children being implanted. It is accepted that a pediatric cochlear implant recipient may require one or two revision procedures during their lifetime. The indication of RIS can be due to a multitude of causes like trauma, device failure (hard failure or soft failure), infection at the implant site, electrode extrusion, device migration, magnet migration, and upgradation in the technology.

Early antibody responses associated with survival in COVID19 patients.

Neutralizing antibodies to the SARS CoV-2 spike proteins have been issued Emergency Use Authorizations and are a likely mechanism of vaccines to prevent COVID-19. However, benefit of treatment with monoclonal antibodies has only been observed in clinical trials in outpatients with mild to moderate COVID-19 but not in patients who are hospitalized and/or have advanced disease. To address this observation, we evaluated the timing of anti SARS-CoV-2 antibody production in hospitalized patients with the use of a highly sensitive multiplexed bead-based immunoassay allowing for early detection of antibodies to SARS-CoV-2.

3-Aryl-substituted imidazo[1,2-a]pyridines as antituberculosis agents.

Novel inhibitors are needed to tackle tuberculosis. Herein, we report the 3-aryl-substituted imidazo[1,2-a]pyridines as potent antituberculosis agents. A small library of 3-aryl-substituted imidazo[1,2-a]pyridines was synthesized using direct arylation, followed by nitro reduction and finally Pd-catalyzed C-N coupling reactions.

Hearing Loss-a Camouflaged Manifestation of COVID 19 Infection.

The symptomatology of novel Severe Acute Respiratory Syndrome Corona virus type 2 infection runs the entire gamut of mild to moderate and serious illness among the affected individuals. As listed in recent literature, respiratory, cardiovascular, gastrointestinal, olfactory and gustatory systems are commonly involved. With the growing knowledge about the disease, varied manifestations have been identified and lately, otorhinolaryngology dysfunctions in COVID 19 have been described.

Electronic phenotyping of health outcomes of interest using a linked claims-electronic health record database: Findings from a machine learning pilot project.

Objective: Claims-based algorithms are used in the Food and Drug Administration Sentinel Active Risk Identification and Analysis System to identify occurrences of health outcomes of interest (HOIs) for medical product safety assessment. This project aimed to apply machine learning classification techniques to demonstrate the feasibility of developing a claims-based algorithm to predict an HOI in structured electronic health record (EHR) data.

Materials And Methods: We used the 2015-2019 IBM MarketScan Explorys Claims-EMR Data Set, linking administrative claims and EHR data at the patient level.

Undiagnosed haemoglobinopathies among pregnant women attending antenatal care clinics in Pune, India.

Pregnant women with iron deficiency and those who are carriers of haemoglobinopathies present with anaemia of varying severity. There is no antenatal screening for haemoglobinopathies in India. The objective of this study was to determine the prevalence of undiagnosed haemoglobinopathy carriers in a random sample of pregnant women attending antenatal care clinics in Pune city, India.

Weighted estimators of the complier average causal effect on restricted mean survival time with observed instrument-outcome confounders.

A major concern in any observational study is unmeasured confounding of the relationship between a treatment and outcome of interest. Instrumental variable (IV) analysis methods are able to control for unmeasured confounding. However, IV analysis methods developed for censored time-to-event data tend to rely on assumptions that may not be reasonable in many practical applications, making them unsuitable for use in observational studies.