Cultural-Psychological Differences, Social Acceptance of Same-Sex Relationships, and Dating App Use Motives of Young GBMSM: A Comparative Study Across Hong Kong, Taipei, and Osaka.

Gay-specific mobile dating apps such as Grindr are popular among young gay, bisexual, and other men who have sex with men (GBMSM) worldwide. However, how the use of these apps differs between regions is underexplored. In this study, we drew on the uses and gratifications literature and cross-cultural studies to examine how cultural-psychological differences (sensation seeking and communication apprehension) and social acceptance of same-sex relationships are associated with the motives for using gay dating apps in three East Asian cities.

Comparison of assistance preferences of older adults with different functional dependence levels on domestic tasks performed by robots.

Background: Robots have the potential to assist older adults in their home-based daily living tasks. Previous studies indicated that older adults generally accept robot assistance. However, the preferences of older adults with different functional dependence levels are lacking.

New trading strategy in investment and a new anomaly: A study of the hedge funds from emerging and developed markets.

This paper introduces a new trading strategy in investment: including the asset (Asset A) with the highest mean, the asset (Asset B) that stochastically dominates many other assets, and the asset (Asset C) with the smallest standard deviation in their portfolio to form portfolios in the efficient frontier for emerging and developed markets that could get higher expected utility and/or expected arbitrage opportunities. To test whether our proposed new trading strategy performs better, we set a few conjectures including the conjectures that investors should include any one, two, or three of Assets A, B, and C from emerging and developed markets. We test whether the conjectures hold by employing both mean-variance and stochastic dominance (SD) approaches to examine the performance of the portfolio formed by using hedge funds from emerging and developed markets with and without Assets A, B, and C, the naïve 1/N portfolio, and all other assets studied in our paper.

NAD rescues aging-induced blood-brain barrier damage via the CX43-PARP1 axis.

Blood-brain barrier (BBB) function deteriorates during aging, contributing to cognitive impairment and neurodegeneration. It is unclear what drives BBB leakage in aging and how it can be prevented. Using single-nucleus transcriptomics, we identified decreased connexin 43 (CX43) expression in cadherin-5 (Cdh5) cerebral vascular cells in naturally aging mice and confirmed it in human brain samples.

Transient neonatal hemolytic anemia due to the novel gamma globin gene mutation HBG2:C.290T>C, p.Leu97Pro (hemoglobin Wareham).

Unstable gamma globin variants can cause transient neonatal hemolytic anemia. We have identified a novel variant in a newborn who presented with jaundice and anemia requiring phototherapy and red blood cell transfusion. The patient was found to be heterozygous for the mutation HGB2:c.

Pharmacologic induction of PGC-1α stimulates fetal haemoglobin gene expression.

Sickle cell disease (SCD) is a genetic disorder that affects millions around the world. Enhancement of fetal γ-globin levels and fetal haemoglobin (HbF) production in SCD patients leads to diminished severity of many clinical features of the disease. We recently identified the transcriptional co-activator PGC-1α as a new protein involved in the regulation of the globin genes.

Strategies to improve pharmacogenomic-guided treatment options for patients with β-hemoglobinopathies.

Drug efficacy and toxicity are closely related to the unique genetic profile of individuals, or pharmacogenomics. Despite the fact that cardiology, psychiatry and oncology are among the clinical specialties in which pharmacogenomics has become a clinical reality, the utility of pharmacogenomics has yet to be demonstrated for several other medical specialties. Over the last 15 years, genomic variants in a number of loci have been shown to be significantly associated with the fetal hemoglobin (HbF) response to hydroxyurea, the only approved drug for HbF induction for sickle cell disease.

A Novel β-Thalassemia Mutation, : c.356_357delTT [Codon 118 (-TT)] in an Iraqi Kurd.

We report a novel frameshift β-thalassemia (β-thal) mutation due to a two-nucleotide deletion at codon 118 of the β-globin gene (: c.356_357delTT) in a 4-year-old Iraqi Kurd female presenting as transfusion-dependent β-thal. This frameshift mutation, unlike many others involving the third exon, behaved as a recessive β defect and not as dominant β-thal mutation.

Alpha-thalassemia. Case report alpha-thalassemia in a Costa Rican family, A case report.

This case report highlights the importance for health care providers to be aware of the αlpha-thalassemia syndromes, their relevance to clinical care and family counseling, appropriate diagnostic algorithm for definitive diagnosis.

BCL2L1 is associated with γ-globin gene expression.

Fetal hemoglobin (HbF) expression is partially governed by the trans-acting quantitative trait loci BCL11A and MYB and a cis-acting locus linked to the HBB gene cluster. Our previous analysis of the Genotype-Tissue Expression database suggested that BCL2L1 was associated with HbF gene expression. In erythroid progenitors from patients with sickle cell disease, BCL2L1 messenger RNA (mRNA) levels were positively correlated with HBG mRNA and total HbF concentration (r2 = 0.

Knockout of MCT1 results in total absence of spermatozoa, sex hormones dysregulation, and morphological alterations in the testicular tissue.

Lactate is a key metabolite for the normal occurrence of spermatogenesis. In the testis, lactate is produced by the Sertoli cells and transported to germline cells. Monocarboxylate transporters (MCTs) are key players in that process.

Alterations in folate-dependent one-carbon metabolism as colon cell transition from normal to cancerous.

Folate-dependent one-carbon cycle metabolism (FOCM) plays a critical role in maintaining genomic stability through regulating DNA biosynthesis, repair and methylation. Folate metabolites as well as other metabolites in the FOCM are hypothesized to be altered when cells transition from normal to cancerous state. Using cells at different stages in their development into colorectal cancer, the FOCM metabolites were profiled as an effort to phenotype the cells, and the metabolite levels were compared to the expressions of related genes.

Stimulation Modeling on Three-Dimensional Anisotropic Diffusion of MRI Tracer in the Brain Interstitial Space.

To build a mathematical model based magnetic resonance (MR) method to simulate drug anisotropic distribution in the interstitial space (ISS) of the brain. An injection of signal intensity-related gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), which is an exogenous drug, was administered, and its diffusion was traced in the ISS of the brain using MRI. Dynamic MRI scans were performed to monitor and record the changes in signal intensity in each pixel of the region of interest.

Editing aberrant splice sites efficiently restores β-globin expression in β-thalassemia.

The thalassemias are compelling targets for therapeutic genome editing in part because monoallelic correction of a subset of hematopoietic stem cells (HSCs) would be sufficient for enduring disease amelioration. A primary challenge is the development of efficient repair strategies that are effective in HSCs. Here, we demonstrate that allelic disruption of aberrant splice sites, one of the major classes of thalassemia mutations, is a robust approach to restore gene function.

Exploratory metabolomic study to identify blood-based biomarkers as a potential screen for colorectal cancer.

Introduction: colorectal cancer (CRC) continues to be difficult to diagnose due to the lack of reliable and predictive biomarkers.

Objective: to identify blood-based biomarkers that can be used to distinguish CRC cases from controls.

Methods: a workflow for untargeted followed by targeted metabolic profiling was conducted on the plasma samples of 26 CRC cases and ten healthy volunteers (controls) using liquid chromatography-mass spectrometry (LCMS).

AMG 176, a Selective MCL1 Inhibitor, Is Effective in Hematologic Cancer Models Alone and in Combination with Established Therapies.

The prosurvival BCL2 family member MCL1 is frequently dysregulated in cancer. To overcome the significant challenges associated with inhibition of MCL1 protein-protein interactions, we rigorously applied small-molecule conformational restriction, which culminated in the discovery of AMG 176, the first selective MCL1 inhibitor to be studied in humans. We demonstrate that MCL1 inhibition induces a rapid and committed step toward apoptosis in subsets of hematologic cancer cell lines, tumor xenograft models, and primary patient samples.

The association of HBG2, BCL11A, and HMIP polymorphisms with fetal hemoglobin and clinical phenotype in Iraqi Kurds with sickle cell disease.

Introduction: Fetal hemoglobin (HbF) is the major modifier for sickle cell disease (SCD) severity. HbF is modulated mainly by three major quantitative trait loci (QTL) on chromosomes 2, 6, and 11.

Methods: Five SNPs in the three QTLs (HBG2, rs7482144; BCL11A, rs1427407 and rs10189857; and HBS1L-MYB intergenic region, rs28384513 and rs9399137) were investigated by multiplex PCR and reverse hybridization, and their roles in HbF and clinical phenotype variability in Iraqi Kurds with SCD were assessed.

Induced pluripotent stem cell-based mapping of β-globin expression throughout human erythropoietic development.

Robust β-globin expression in erythroid cells derived from induced pluripotent stem cells (iPSCs) increases the resolution with which red blood cell disorders such as sickle cell disease and β thalassemia can be modeled in vitro. To better quantify efforts in augmenting β-globin expression, we report the creation of a β-globin reporter iPSC line that allows for the mapping of β-globin expression throughout human erythropoietic development in real time at single-cell resolution. Coupling this tool with single-cell RNA sequencing (scRNAseq) identified features that distinguish β-globin-expressing cells and allowed for the dissection of the developmental and maturational statuses of iPSC-derived erythroid lineage cells.

Dapsone protects brain microvascular integrity from high-fat diet induced LDL oxidation.

Atherosclerosis was considered to induce many vascular-related complications, such as acute myocardial infarction and stroke. Abnormal lipid metabolism and its peroxidation inducing blood-brain barrier (BBB) leakage were associated with the pre-clinical stage of stroke. Dapsone (DDS), an anti-inflammation and anti-oxidation drug, has been found to have protective effects on vascular.

Simultaneous quantitation of folates, flavins and B metabolites in human plasma by LC-MS/MS assay: Applications in colorectal cancer.

An analytical method using electrospray ionization and high- performance liquid chromatography/tandem mass spectrometry (LC/ESI-MS/MS) was developed to quantify the vitamin B metabolites found in the folate one-carbon metabolism, using 50 μL of human plasma. Analytes in plasma were extracted using protein precipitation after being stabilized in 1% ascorbic acid. The analytes were separated using a Kinetex 2.