Discovery of the First Efficacious Adenosine 2A Receptor Negative Allosteric Modulators for High Adenosine Cancer Immunotherapies.

Inhibition of the adenosine 2A receptor (AR) is recognized as a promising immunotherapeutic strategy but is challenged by the ubiquity of AR function in the immune system. To develop a safe yet efficacious immunotherapy, the discovery of a novel negative allosteric modulator (NAM) was preferred. Leveraging an in-house, sensitive, high-throughput screening cellular assay, novel AR NAM scaffolds were identified, followed by an extensive structure-activity relationship (SAR) study, leading to the discovery of potent 2-amino-3,5-dicyanopyridine derivatives.

Safety and Efficacy of Incorporating Actellic 300 CS into Soil Wall Plaster for Control of Malaria Vectors in Rural Northeastern Uganda.

Indoor residual spraying (IRS) and the use of insecticide-treated bednets for malaria vector control have contributed substantially to a reduction in malaria disease burden. However, these control tools have important shortcomings including being donor-dependent, expensive, and often failing because of insufficient uptake. We assessed the safety and efficacy of a user-friendly, locally tailored malaria vector control approach dubbed "Hut Decoration for Malaria Control" (HD4MC) based on the incorporation of a WHO-approved insecticide, Actellic 300 CS, into a customary hut decoration practice in rural Uganda where millions of the most vulnerable and malaria-prone populations live in mud-walled huts.

Prevalence of Vitamin K2 Deficiency and Its Association with Coronary Artery Disease: A Case-Control Study.

Background/objectives: Vitamin K2 analogs are associated with decreased vascular calcification, which may provide protective benefits for individuals with coronary artery disease (CAD) by stimulating anti-calcific proteins like matrix Gla protein and adjusting innate immune responses. This study addresses a significant gap in understanding the association between serum levels of vitamin K2 analogs in different CAD types and examines their correlations with clinical risk parameters in CAD patients.

Methods: This case-control study enrolled CAD patients and healthy controls to assess and compare serum concentrations of two vitamin K2 analogs including menaquinone-4 (MK-4) and menaquinone-7 (MK-7) via ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS).

Changes in immunofluorescence staining during islet regeneration in a cystic fibrosis-related diabetes (CFRD) ferret model.

Background: Knockout (KO) ferrets with the cystic fibrosis transmembrane conductance regulator (CFTR) exhibit distinct phases of dysglycemia and pancreatic remodeling prior to cystic fibrosis-related diabetes (CFRD) development. Following normoglycemia during the first month of life (Phase l), hyperglycemia occurs during the subsequent 2 months (Phase Il) with decreased islet mass, followed by a period of near normoglycemia (Phase Ill) in which the islets regenerate. We aimed to characterize islet hormone expression patterns across these Phases.

Trajectory of beta cell function and insulin clearance in stage 2 type 1 diabetes: natural history and response to teplizumab.

Aims/hypothesis: We aimed to analyse TrialNet Anti-CD3 Prevention (TN10) data using oral minimal model (OMM)-derived indices to characterise the natural history of stage 2 type 1 diabetes in placebo-treated individuals, to describe early metabolic responses to teplizumab and to explore the predictive capacity of OMM measures for disease-free survival rate.

Methods: OMM-estimated insulin secretion, sensitivity and clearance and the disposition index were evaluated at baseline and at 3, 6 and 12 months post randomisation in placebo- and teplizumab-treated groups, and, within each group, in slow- and rapid-progressors (time to stage 3 disease >2 or 2 years). OMM metrics were also compared with the standard AUC C-peptide.

Gut Microbial Changes Associated With Obesity in Youth With Type 1 Diabetes.

Context: Obesity is prevalent in type 1 diabetes (T1D) and is problematic with higher risk for diabetes complications. It is unknown to what extent gut microbiome changes are associated with obesity and T1D.

Objective: This work aimed to describe the gut microbiome and microbial metabolite changes associated with obesity in T1D.

Video-tracked entry and exit behaviour at washed and damaged pyrethroid-treated bednets.

Insecticide-treated nets (ITNs) are the most effective method for malaria prevention in Africa. Using near-infrared video tracking in a laboratory environment, we recorded and assessed bednet entry and exit by a northern Tanzanian population of at a human-occupied untreated net and a PermaNet® 2.0 ITN.

Evaluation of dental students and alumni's confidence level in orthodontic diagnosis and treatment-planning: A qualitative study.

Background: Orthodontic education, besides some other factors, influences the confidence level of recently graduated dentists to diagnose subjects seeking orthodontic treatment and provide treatment plans. This study aims to explore the factors that influence the confidence level of undergraduate dental students to diagnose subjects seeking orthodontic treatment and provide treatment plans after graduation.

Methods: A qualitative study was undertaken using focus groups and interviews.

Consensus Guidance for Monitoring Individuals With Islet Autoantibody-Positive Pre-Stage 3 Type 1 Diabetes.

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programs are being increasingly emphasized. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk for (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in nonspecialized settings.

Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes.

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb) children and adults who are at risk of (confirmed single IAb) or living with (multiple IAb) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings.

Diapocynin treatment induces functional and structural improvements in an advanced disease state in the mdx mice.

Duchenne muscular dystrophy (DMD) is the most common muscular disorder affecting children. It affects nearly 1 male birth over 5000. Oxidative stress is a pervasive feature in the pathogenesis of DMD.

Safety and effects of acetylated and butyrylated high amylose maize starch in recently diagnosed youths with type 1 diabetes; a Pilot Study.

Acetylated and butyrylated high amylose starch (HAMS-AB) is a prebiotic shown to be effective in type 1 diabetes (T1D) prevention in mouse models and is safe in adults with established T1D. HAMS-AB alters the gut microbiome profile with increased bacterial fermenters that produce short chain fatty acids (SCFAs) with anti-inflammatory and immune-modulatory effects. We performed a pilot study using a cross-over design to assess the safety and efficacy of 4 weeks of oral HAMS-AB consumption by recently diagnosed (< 2 years of diagnosis) youths with T1D.

Cross-Country Discrepancies in Monkeypox Vaccine Hesitancy Among Postgraduate and Undergraduate Medical Students.

Background: Medical students hold significant importance, as they represent the future of healthcare provision. This study aimed to explore psychological antecedents towards the monkeypox (mpox) vaccines among postgraduate and undergraduate medical students across countries.

Methods: A cross-sectional survey was conducted among medical students aged 18 years old and above in 7 countries; Egypt, Romania, Malaysia, and Yemen, Iraq, India, and Nigeria.

Early Metabolic Endpoints Identify Persistent Treatment Efficacy in Recent-Onset Type 1 Diabetes Immunotherapy Trials.

Objective: Mixed-meal tolerance test-stimulated area under the curve (AUC) C-peptide at 12-24 months represents the primary end point for nearly all intervention trials seeking to preserve β-cell function in recent-onset type 1 diabetes. We hypothesized that participant benefit might be detected earlier and predict outcomes at 12 months posttherapy. Such findings would support shorter trials to establish initial efficacy.

Comparisons of Metabolic Measures to Predict T1D vs Detect a Preventive Treatment Effect in High-Risk Individuals.

Context: Metabolic measures are frequently used to predict type 1 diabetes (T1D) and to understand effects of disease-modifying therapies.

Objective: Compare metabolic endpoints for their ability to detect preventive treatment effects and predict T1D.

Methods: Six-month changes in metabolic endpoints were assessed for (1) detecting treatment effects by comparing placebo and treatment arms from the randomized controlled teplizumab prevention trial, a multicenter clinical trial investigating 14-day intravenous teplizumab infusion and (2) predicting T1D in the TrialNet Pathway to Prevention natural history study.

Overview of Tissue Engineering and Drug Delivery Applications of Reactive Electrospinning and Crosslinking Techniques of Polymeric Nanofibers with Highlights on Their Biocompatibility Testing and Regulatory Aspects.

Traditional electrospinning is a promising technique for fabricating nanofibers for tissue engineering and drug delivery applications. The method is highly efficient in producing nanofibers with morphology and porosity similar to the extracellular matrix. Nonetheless, and in many instances, the process has faced several limitations, including weak mechanical strength, large diameter distributions, and scaling-up difficulties of its fabricated electrospun nanofibers.

Gut microbial changes associated with obesity in youth with type 1 diabetes.

Unlabelled: Obesity is increasingly prevalent in type 1 diabetes (T1D) and is associated with management problems and higher risk for diabetes complications. Gut microbiome changes have been described separately in each of T1D and obesity, however, it is unknown to what extent gut microbiome changes are seen when obesity and T1D concomitantly occur.

Objective: To describe the gut microbiome and microbial metabolite changes associated with obesity in T1D.