Methylarginine targeting chimeras for lysosomal degradation of intracellular proteins.

A paradigm shift in drug development is the discovery of small molecules that harness the ubiquitin-proteasomal pathway to eliminate pathogenic proteins. Here we provide a modality for targeted protein degradation in lysosomes. We exploit an endogenous lysosomal pathway whereby protein arginine methyltransferases (PRMTs) initiate substrate degradation via arginine methylation.

The prevalence of bilateral hearing loss in the United States in 2019: a small area estimation modelling approach for obtaining national, state, and county level estimates by demographic subgroup.

Background: The goal of this study was to re-estimate rates of bilateral hearing loss Nationally, and create new estimates of hearing loss prevalence at the U.S. State and County levels.

Relationship of hemoglobin levels with outcomes in deceased donor kidney transplant: a retrospective cohort study.

Introduction: Anemia is frequent in patients undergoing replacement therapy for kidney failure. Anemia in the pre- and post-transplantation period might be related to kidney transplant outcomes. The current study therefore sought to assess the relationship between anemia, delayed allograft function (DGF), chronic kidney allograft dysfunction (CAD), and death from any cause following kidney transplantation from a deceased donor.

Vitamin B is governed by the local compartmentalization of metabolic enzymes during growth.

Vitamin B is a vital micronutrient across cell types and tissues, and dysregulated B levels contribute to human disease. Despite its importance, how B vitamer levels are regulated is not well understood. Here, we provide evidence that B dynamics are rapidly tuned by precise compartmentation of pyridoxal kinase (PDXK), the rate-limiting B enzyme.

Plasma activated water: a study of gas type, electrode material, and power supply selection and the impact on the final frontier.

An in-depth study of plasma activated water (PAW) generation was conducted to link changes in power supply, electrode material, input gas, and treatment time to the resulting reaction chemistry, all while maintaining a consistent electrode geometry. These changes in chemistry can help tailor PAW for different space applications. An AC, DC, and nanosecond pulsed power supply were each used to generate PAW with stainless steel, copper, tungsten, or platinum electrodes while utilizing air, nitrogen, carbon dioxide, helium, or argon as the feed gas.

Simplifying the B Complex: How Vitamins B6 and B9 Modulate One Carbon Metabolism in Cancer and Beyond.

Vitamin B micronutrients are essential regulators of one carbon metabolism that ensures human health. Vitamin B9, or folate, lies at the heart of the folate cycle and converges with the methionine cycle to complete the one carbon pathway. Additionally, vitamin B6 contributes by orchestrating the flux of one carbon cycling.

-ITD Expression as a Potential Biomarker for the Assessment of Treatment Response in Patients with Acute Myeloid Leukemia.

-internal tandem duplication (ITD) analysis is not typically performed in cDNA samples and is not considered an appropriate marker for monitoring measurable residual disease (MRD). The aims of this study were to compare -ITD mutation analysis in DNA and cDNA samples at diagnosis and to demonstrate the usefulness of its expression measurement as an MRD marker after allogeneic stem cell transplantation (allo-HSCT) or FLT3 inhibitor (FLT3i) administration. A total of 46 DNA and cDNA diagnosis samples, 102 DNA and cDNA post-allo-HSCT samples from 34 patients and 37 cDNA samples from 7 patients with refractory/relapse AML treated with FLT3i were assessed for the -ITD mutation through fragment analysis.

Metabolism and Endocrine Disorders: What Wnt Wrong?

A fundamental question in cell biology underlies how nutrients are regenerated to maintain and renew tissues. Physiologically, the canonical Wnt signaling is a vital pathway for cell growth, tissue remodeling, and organ formation; pathologically, Wnt signaling contributes to the development of myriad human diseases such as cancer. Despite being the focus of intense research, how Wnt intersects with the metabolic networks to promote tissue growth and remodeling has remained mysterious.

Which Role Plays 2-Hydroxybutyric Acid on Insulin Resistance?

Type 2 Diabetes Mellitus (T2D) is defined as a chronic condition caused by beta cell loss and/or dysfunction and insulin resistance (IR). The discovering of novel biomarkers capable of identifying T2D and other metabolic disorders associated with IR in a timely and accurate way is critical. In this review, 2-hydroxybutyric acid (2HB) is presented as that upheaval biomarker with an unexplored potential ahead.

Charge Carrier Relaxation in Colloidal FAPbI Nanostructures Using Global Analysis.

We study the hot charge carrier relaxation process in weakly confined hybrid lead iodide perovskite colloidal nanostructures, FAPbI (FA = formaminidium), using femtosecond transient absorption (TA). We compare the conventional analysis method based on the extraction of the carrier temperature () by fitting the high-energy tail of the band-edge bleach with a global analysis method modeling the continuous evolution of the spectral lineshape in time using a simple sequential kinetic model. This practical approach results in a more accurate way to determine the charge carrier relaxation dynamics.

Predicting overall and major postoperative morbidity in gastric cancer patients.

Background: Postoperative complications after gastric cancer resection vary in different series and they might have a significant impact in long-term outcomes. Our aim was to build a prediction rule on gastric cancer patients' overall and major morbidity risks.

Methods: This retrospective study included 1223 patients from a single center who were resected between 1992 and 2016.

Validation of Candidate Gene-Based Markers and Identification of Novel Loci for Thousand-Grain Weight in Spring Bread Wheat.

Increased thousand-grain weight (TGW) is an important breeding target for indirectly improving grain yield (GY). Fourteen reported candidate genes known to enhance TGW were evaluated in two independent and existing datasets of wheat at CIMMYT, the Elite Yield Trial (EYT) from 2015 to 2016 (EYT2015-16) and the Wheat Association Mapping Initiative (WAMI) panel, to study their allele effects on TGW and to verify their suitability for marker-assisted selection. Of these, significant associations were detected for only one gene () in the EYT2015-16 and two genes ( and ) in WAMI.

Comparative Study of Confidence Intervals for Proportions in Complex Sample Surveys.

The most widespread method of computing confidence intervals (CIs) in complex surveys is to add and subtract the margin of error (MOE) from the point estimate, where the MOE is the estimated standard error multiplied by the suitable Gaussian quantile. This Wald-type interval is used by the American Community Survey (ACS), the largest US household sample survey. For inferences on small proportions with moderate sample sizes, this method often results in marked under-coverage and lower CI endpoint less than 0.

Cortical morphometry in frontoparietal and default mode networks in math-gifted adolescents.

Math-gifted subjects are characterized by above-age performance in intelligence tests, exceptional creativity, and high task commitment. Neuroimaging studies reveal enhanced functional brain organization and white matter microstructure in the frontoparietal executive network of math-gifted individuals. However, the cortical morphometry of these subjects remains largely unknown.

Comparative analysis of basaloid and conventional squamous cell carcinomas of the esophagus: prognostic relevance of clinicopathological features and protein expression.

Basaloid squamous cell carcinoma (BSCC), a variant of squamous cell carcinoma (SCC), is a rare and aggressive epithelial malignancy which has been reported in only 0.1-11 % of primary esophageal carcinomas. In this study, a comparison of clinicopathological features and protein expression between esophageal BSCC (EBSCC) and conventional esophageal SCC (ESCC) cases from Brazil was performed in order to find factors that can be relevant to better characterize EBSCC.

Feedback interaction of research, advocacy, and clinical care applied to ALS research in South America.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing motor neuron loss and weakness. Worldwide prevalence is 4-6/100,000. Incidence is 1.

High malnutrition rate in Venezuelan Yanomami compared to Warao Amerindians and Creoles: significant associations with intestinal parasites and anemia.

Background: Children in rural areas experience the interrelated problems of poor growth, anemia and parasitic infections. We investigated the prevalence of and associations between intestinal helminth and protozoan infections, malnutrition and anemia in school-age Venezuelan children.

Methods: This cross-sectional study was conducted in 390 children aged 4-16 years from three rural areas of Venezuela: the Amazon Region, Orinoco Delta and Carabobo State.

White matter microstructure correlates of mathematical giftedness and intelligence quotient.

Recent functional neuroimaging studies have shown differences in brain activation between mathematically gifted adolescents and controls. The aim of this study was to investigate the relationship between mathematical giftedness, intelligent quotient (IQ), and the microstructure of white matter tracts in a sample composed of math-gifted adolescents and aged-matched controls. Math-gifted subjects were selected through a national program based on detecting enhanced visuospatial abilities and creative thinking.

Frataxin deficiency unveils cell-context dependent actions of insulin-like growth factor I on neurons.

Background: Friedreich's ataxia (FRDA) is a neurodegenerative disease caused by deficiency of the mitochondrial iron chaperone frataxin (Fxn). FRDA has no cure, but disease-modifying strategies to increase frataxin are under study. Because insulin-like growth factor I (IGF-I) has therapeutic effects in various types of cerebellar ataxia and exerts protective actions on mitochondrial function, we explored the potential Fxn-stimulating activity of this growth factor on brain cells.

A systematic review on the role of anticonvulsants in the treatment of acute bipolar depression.

Despite the high morbidity and mortality associated with bipolar depression, the optimal treatment for this phase is still a matter of debate. The aim of the current review was to provide updated evidence about the efficacy and tolerability of anticonvulsants in the treatment of acute bipolar depression. A comprehensive review of randomized controlled trials (RCTs) evaluating the use of anticonvulsants for the treatment of acute bipolar depression up to June 2011 was conducted by means of the PubMed-Medline database.

Halitosis in obese patients and those undergoing bariatric surgery.

Background: Patients undergoing bariatric surgery often complain of bad breath. However, the relationship between bariatric surgery and halitosis is relatively unknown. The purpose of the present study was to evaluate and compare the occurrence of halitosis among patients before and after a specific type of bariatric surgery, Roux-en-Y gastric bypass, and its relationship with the tongue coating index, plaque index, and salivary flow rate.

Six-month functional outcome of a bipolar disorder cohort in the context of a specialized-care program.

Objectives: A marked disparity between functional recovery and symptomatic improvement has been demonstrated in bipolar disorder. However, most of the previous studies have been conducted in the United States, and there is little prospective research from Europe on this topic. The main objective of the present six-month follow-up study was to assess functioning in a sample of Spanish bipolar disorder patients following an acute episode or subsyndromal state.

Mathematically gifted adolescents use more extensive and more bilateral areas of the fronto-parietal network than controls during executive functioning and fluid reasoning tasks.

The main goal of this study was to investigate the neural substrates of fluid reasoning and visuospatial working memory in adolescents with precocious mathematical ability. The study population comprised two groups of adolescents: 13 math-gifted adolescents and 14 controls with average mathematical skills. Patterns of activation specific to reasoning tasks in math-gifted subjects were examined using functional magnetic resonance images acquired while the subjects were performing Raven's Advanced Progressive Matrices (RAPM) and the Tower of London (TOL) tasks.

Effects of atypical antipsychotics on neurocognition in euthymic bipolar patients.

Background: Different factors may influence cognitive functioning in bipolar disorder such as the effect of subsyndromal symptoms, the history of psychotic symptomatology or substance abuse, negative symptomatology, chronicity, sleep disturbances, and hormonal factors. The effect of pharmacologic treatment on cognition is still uncertain because of an insufficient number of studies examining this issue.

Objective: The aims of this study were to compare neuropsychologic performance of treated bipolar patients with that of controls, including unmedicated patients and healthy subjects, as well as to evaluate possible neurocognitive differences among 3 different atypical antipsychotics.