A "Goldilocks Zone" for Recruiting BET Proteins with Bromodomain-1-Selective Ligands.

Synthetic genome readers/regulators (SynGRs) are bifunctional molecules that are rationally designed to bind specific genomic sequences and engage cellular machinery that regulates the expression of targeted genes. The prototypical SynGR1 targets GAA trinucleotide repeats and recruits the BET family of transcriptional regulatory proteins via a flexibly tethered ligand, JQ1. This pan-BET ligand binds both tandem bromodomains of BET proteins (BD1 and BD2).

Real-World Effectiveness, Economic, and Humanistic Outcomes of Selected Oral Antipsychotics in Patients with Schizophrenia: A Systematic Review Evaluating Global Evidence.

Background: Schizophrenia is a complex, chronic mental health disorder that confers a substantial disease burden globally. Oral antipsychotic treatments (OATs) are the mainstay for treating early and advanced stages of schizophrenia. Our systematic review aimed to synthesize literature describing real-world effectiveness, economic, and humanistic outcomes of OATs (asenapine, brexpiprazole, cariprazine, iloperidone, lumateperone, lurasidone, olanzapine/samidorphan, paliperidone, and quetiapine) for successful management of the disease.

Modular binder technology by NGS-aided, high-resolution selection in yeast of designed armadillo modules.

Establishing modular binders as diagnostic detection agents represents a cost- and time-efficient alternative to the commonly used binders that are generated one molecule at a time. In contrast to these conventional approaches, a modular binder can be designed in silico from individual modules to, in principle, recognize any desired linear epitope without going through a selection and hit-validation process, given a set of preexisting, amino acid-specific modules. Designed armadillo repeat proteins (dArmRP) have been developed as modular binder scaffolds, and we report here the generation of highly specific dArmRP modules by yeast surface display selection, performed on a rationally designed dArmRP library.

Exploring the factors influencing academic learning performance using online learning systems.

-Online learning has become vital and fundamental for learning success in higher education institutions to cope with various learning methodologies or crises such as COVID-19. Therefore, this study investigates factors influencing the academic learning performance among diploma and bachelor's degree students who utilize online e-learning systems in Jordan. Using a conceptual model developed from an extensive previous literature review, the study used a quantitative research methodology to collect data via survey questionnaires.

Dundee Annual Neurosurgery Skills Event (DANSE)-Improving the Availability and Affordability of Neurosurgical Skills Workshops for Medical Students.

 Neurosurgery can be a daunting career choice for medical students, with preparation for trainee application often being inaccessible and expensive. This article describes a student-led neurosurgical skills event supported by local neurosurgery faculty members. Such event was designed to offer a means to bridge this gap by providing an opportunity to practice neurosurgical techniques in simulation, and learn about what a career in neurosurgery involves.

Dual Antitubercular and Antileishmanial Profiles of Quinoxaline Di--Oxides Containing an Amino Acidic Side Chain.

We present a new category of quinoxaline di-N-oxides (QdNOs) containing amino acid side chains with dual antituberculosis and antileishmanial activity. These compounds were synthesized by combining a regioselective 2,5-piperazinedione opening and a Beirut reaction and were screened for their activity against and the promastigote and amastigote forms of representative species of the genus. Most QdNOs exhibited promising antitubercular activity with IC values ranging from 4.

Emotional, Psychological, and Social Well-being Experience of Long-Term Living with Type 1 Diabetes Mellitus: A Patient-Psychiatrist-Endocrinologist Perspective.

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease that impacts blood glucose levels and can also lead to an increased prevalence of psychiatric conditions. Living with T1DM has been associated with a significant impact on a person's social, mental, and psychological quality of life (QoL). Stressors related to T1DM include the demands of managing the condition, acceptance of the diagnosis, and recognition of the sizeable personal responsibility involved in managing the condition.

Impact of Living with Stigma in Persons with Type 1 Diabetes: A Patient-Physician Perspective.

Type 1 diabetes mellitus (T1D) is an autoimmune disorder characterized by a complete deficiency in insulin due to the destruction of pancreatic beta cells. Globally, T1D accounts for nearly 5-10% of the total diabetes cases. Living with this life-long condition has a significant emotional, psychological, physical, mental, and social impact.

Domain-Selective BET Ligands Yield Next-Generation Synthetic Genome Readers/Regulators with Nonidentical Cellular Functions.

SynTEF1, a prototype synthetic genome reader/regulator (SynGR), was designed to target GAA triplet repeats and restore the expression of frataxin () in Friedreich's ataxia patients. It achieves this complex task by recruiting BRD4, via a pan-BET ligand (JQ1), to the GAA repeats by using a sequence-selective DNA-binding polyamide. When bound to specific genomic loci in this way, JQ1 functions as a chemical prosthetic for acetyl-lysine residues that are natural targets of the two tandem bromodomains (BD1 and BD2) in bromo- and extra-terminal domain (BET) proteins.

Geographical Diversity in the Age Specific Anti Müllerian Hormone Levels in Infertile Women: A Hospital based Cohort Study.

Background: Serum anti-Mullerian hormone (AMH) is a significant determinant of ovarian reserve. It is still not clear about the rate at which AMH declines with age and varies across populations.

Aim: The present study examined the AMH levels specific to the North and South Indian populations and attempted to establish an age-dependent reference parametrically.

S1-END-seq reveals DNA secondary structures in human cells.

DNA becomes single stranded (ssDNA) during replication, transcription, and repair. Transiently formed ssDNA segments can adopt alternative conformations, including cruciforms, triplexes, and quadruplexes. To determine whether there are stable regions of ssDNA in the human genome, we utilized S1-END-seq to convert ssDNA regions to DNA double-strand breaks, which were then processed for high-throughput sequencing.

Nondegenerate Saturation Mutagenesis: Library Construction and Analysis via MAX and ProxiMAX Randomization.

Protein engineering can enhance desirable features and improve performance outside of the natural context. Several strategies have been adopted over the years for gene diversification, and engineering of modular proteins in particular is most effective when a high-throughput, library-based approach is employed. Nondegenerate saturation mutagenesis plays a dynamic role in engineering proteins by targeting multiple codons to generate massively diverse gene libraries.

Genetic architecture of seed glycerolipids in Asian cultivated rice.

Glycerolipids are essential for rice development and grain quality but its genetic regulation remains unknown. Here we report its genetic base using metabolite-based genome-wide association study and metabolite-based quantitative traits locus (QTL) analyses based on lipidomic profiles of seeds from 587 Asian cultivated rice accessions and 103 chromosomal segment substitution lines, respectively. We found that two genes encoding phosphatidylcholine (PC):diacylglycerol cholinephosphotransferase (OsLP1) and granule-bound starch synthase I (Waxy) contribute to variations in saturated triacylglycerol (TAG) and lyso-PC contents, respectively.

Mitochondrial DNA Levels in Trophectodermal Cells Show No Association with Blastocyst Development and Pregnancy Outcomes.

Background: In patients undergoing assisted reproduction, levels of mitochondrial DNA (mtDNA) in the trophectodermal cells of the developing blastocyst are suggested to be associated with its ability to implant. However, discrepancies exist regarding the use of mtDNA levels as a reliable biomarker to predict outcomes of assisted reproduction.

Aims: The aim of the study is to explore the association of trophectodermal mtDNA levels to determine blastocyst quality, implantation potential of blastocyst and clinical outcomes in couples who have undergone pre-implantation genetic testing for aneuploidy (PGT-A).

Severe Hypertriglyceridaemia Leading to Factitious Hypobicarbonataemia.

Unlabelled: Anion gap metabolic acidosis is a laboratory finding commonly encountered in patients with sepsis, diabetic ketoacidosis, acute kidney injury and toxic alcohol ingestion. Serum blood chemistry assessment detects this abnormality. However, this can be falsely low in situations of high triglyceride levels due to lipid interference with measurement of the bicarbonate levels and through volume displacement by these large molecules.

Effects of exogenous C18 unsaturated fatty acids on milk lipid synthesis in bovine mammary epithelial cells.

We determined the effects of a combination of C18 unsaturated fatty acids (C18-UFAs) consisting of oleic, linoleic, and linolenic acids on milk lipogenesis in bovine mammary epithelial cells (BMECs). By orthogonal experiments to determine cellular triacylglycerol (TAG) accumulation, a combination of 200 μmol/l C18 : 1, 50 μmol/l C18 : 2, and 2 μmol/l C18 : 3 was selected as C18-UFAs combination treatment, and culture in medium containing fatty acid-free bovine serum albumin was used as the control. The expression of genes related to milk lipid synthesis and intracellular FA composition was measured.

Intravitreal ziv-aflibercept in diabetic vitreous hemorrhage.

Background: To evaluate the safety and efficacy of intravitreal ziv-aflibercept (IVZ) in the management of vitreous hemorrhage (VH) in eyes with previously lasered proliferative diabetic retinopathy (PDR).

Methods: In a prospective multicenter study, previously lasered eyes who had dense VH from PDR underwent intravitreal injection of ziv-aflibercept (IVZ) (1.25 mg aflibercept).

Out-of-Hospital 30-day Deaths After Cardiac Surgery Are Often Underreported.

Background: Operative mortality (in-hospital during the index admission or within 30 days of the procedure after discharge) is commonly used as a quality of care measure for public reporting of cardiac surgery outcomes, but the ability to capture out-of-hospital deaths accurately remains undetermined. The objective of the study was to estimate the impact of incomplete reporting of out-of-hospital deaths on hospital risk-adjusted mortality and outlier status.

Methods: New York State's 2014 to 2016 cardiac registry data were used to compare the capture of 30-day postprocedure deaths after discharge with and without the use of national and state-level vital statistics data for all 54,442 patients undergoing isolated coronary artery bypass graft, cardiac valve surgery, or both.

Comparison between two different protocols of negative pressure therapy for healing of chronic ulcers.

Background: Negative pressure therapy plays an important role in the healing process of different types of wounds.

Aim Of The Study: this study aimed to compare between modified and traditional method of vacuum wound closure for chronic wounds.

Subjects: Thirty participants with chronic ulcers completed the study, their ages ranged from 47 to 65 years, from Benha city, divided randomly into two groups, it was carried out from December 2017 to March 2019.

Multiple Versus Single Arterial Coronary Bypass Graft Surgery for Multivessel Disease.

Background: Despite recent guideline statements, there is still wide practice variation in the use of multiple arterial grafts (MAGs) versus single arterial grafts (SAGs) for patients with multivessel disease undergoing coronary artery bypass graft surgery. This may be related to differences in findings between observational and randomized controlled studies.

Objectives: This study sought to compare intermediate-term MAG and SAG outcomes with enhanced matching to reduce selection bias.

"For Mass Eye and Ear Special Issue" Adaptive Optics in the Evaluation of Diabetic Retinopathy.

Retinal imaging is a fundamental tool for clinical and research efforts in the evaluation and management of diabetic retinopathy. Adaptive optics (AO) is an imaging technique that enables correction of over 90% of the optical aberrations of an individual eye induced primarily by the tear film, cornea and lens. The two major tasks of any AO system are to measure the optical imperfections of the eye and to then compensate for these aberrations to generate a corrected wavefront of reflected light from the eye.

Mitral valve repair versus replacement for patients with preserved left ventricular function without heart failure symptoms.

Objective: The purposes of this study are to compare outcomes of mitral valve repair (MV-repair) and mitral valve replacement for patients with severe mitral regurgitation with preserved ventricular function and no congestive heart failure (CHF) symptoms and to examine variations in surgeon choice of procedure and outcomes by surgeon volume.

Methods: In total, 2259 consecutive patients in 42 New York State hospitals with the characteristics mentioned previously who underwent mitral valve repair (1801, 79.7%) or replacement between January 1, 2008, and December 31, 2014, were identified from a mandatory statewide clinical registry.

Statistical Model of Optical Coherence Tomography Angiography Parameters That Correlate With Severity of Diabetic Retinopathy.

Purpose: To determine whether combining quantitative optical coherence tomography angiography (OCTA) parameters can achieve high sensitivity and specificity to distinguish eyes with nonproliferative diabetic retinopathy (NPDR) from those with proliferative diabetic retinopathy (PDR) as well as eyes with diabetes and no DR (NoDR) from those with clinical DR (any DR).

Methods: This cross-sectional study included 28 eyes (17 patients) with NoDR, 54 eyes (34 patients) with NPDR, and 56 eyes (36 patients) with PDR. OCTA images were processed to quantify the foveal avascular zone (FAZ) area, acircularity, vessel density, skeletonized vessel density, fractal dimension, and intersections and average vessel diameter for the superficial (SCP) and the deep capillary plexus (DCP).

Safety of 5914 intravitreal ziv-aflibercept injections.

Purpose: To analyse the pooled safety data of intravitreal ziv-aflibercept (IVZ) therapy for various retinal conditions.

Methods: This was a retrospective, observational study which included patients from 14 participating centres who received IVZ. The medical records of patients who received IVZ from March 2015 through October 2017 were evaluated.