17β-estradiol promotes extracellular vesicle release and selective miRNA loading in ERα-positive breast cancer.

The causes and consequences of abnormal biogenesis of extracellular vesicles (EVs) are not yet well understood in malignancies, including in breast cancers (BCs). Given the hormonal signaling dependence of estrogen receptor-positive (ER+) BC, we hypothesized that 17β-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. We report that physiological doses of 17β-estradiol promote EV secretion specifically from ER+ BC cells via inhibition of miR-149-5p, hindering its regulatory activity on SP1, a transcription factor that regulates the EV biogenesis factor nSMase2.

The crosstalk between FGF21 and GH leads to weakened GH receptor signaling and IGF1 expression and is associated with growth failure in very preterm infants.

Background: Fibroblast growth factor 21 (FGF21) is an essential metabolic regulator that adapts to changes in nutritional status. Severe childhood undernutrition induces elevated FGF21 levels, contributing to growth hormone (GH) resistance and subsequent linear growth attenuation potentially through a direct action on chondrocytes.

Methods: In this study, we assessed expression of the components of both GH and FGF21 pathways in rare and unique human growth plates obtained from children.

Computational investigation of the phase behavior of colloidal squares with offset magnetic dipoles.

Colloidal particles with anisotropic shapes and interactions display rich phase behavior and have potential as structural bases for materials with controllable properties. In this paper, we explore the self-assembling characteristics of a new class of particles that have been shown experimentally to form reconfigurable structures: microscopic cube-shaped colloids with a magnetic dipole that is transversely offset from the particle's center of mass. We have performed simulations of the dynamics of large numbers of dipolar squares in two-dimensions using discontinuous molecular dynamics (DMD).

Biomarkers to predict disease progression and therapeutic response in isolated methylmalonic acidemia.

Methylmalonic Acidemia (MMA) is a heterogenous group of inborn errors of metabolism caused by a defect in the methylmalonyl-CoA mutase (MMUT) enzyme or the synthesis and transport of its cofactor, 5'-deoxy-adenosylcobalamin. It is characterized by life-threatening episodes of ketoacidosis, chronic kidney disease, and other multiorgan complications. Liver transplantation can improve patient stability and survival and thus provides clinical and biochemical benchmarks for the development of hepatocyte-targeted genomic therapies.

Methodological and Reporting Quality of Noninferiority Randomized Controlled Trials Comparing Antiretroviral Therapies: A Systematic Review.

Background: It is unclear whether the reporting quality of antiretroviral (ARV) noninferiority (NI) randomized controlled trials (RCTs) has improved since the CONSORT guideline release in 2006. The primary objective of this systematic review was assessing the methodological and reporting quality of ARV NI-RCTs. We also assessed reporting quality by funding source and publication year.

Utilizing Simulation to Evaluate Robotic Skill Acquisition and Learning Decay.

Background: We aim to evaluate how new robotic skills are acquired and retained by having participants train and retest using exercises on the robotic platform. We hypothesized that participants with a 3-month break from the robotic platform will have less learning decay and increased retention compared with those with a 6-month break.

Methods: This was a prospective randomized trial in which participants voluntarily enrolled and completed an initial training phase to reach proficiency in 9 robot simulator exercises.

Mechanical Surface Treatments for Controlling Surface Integrity and Corrosion Resistance of Mg Alloy Implants: A Review.

The present paper aims to provide an overview of the current state-of-the-art mechanical surface modification technologies and their response in terms of surface roughness, surface texture, and microstructural change due to cold work-hardening, affecting the surface integrity and corrosion resistance of different Mg alloys. The process mechanics of five main treatment strategies, namely, shot peening, surface mechanical attrition treatment, laser shock peening, ball burnishing, and ultrasonic nanocrystal surface modification, were discussed. The influence of the process parameters on plastic deformation and degradation characteristics was thoroughly reviewed and compared from the perspectives of surface roughness, grain modification, hardness, residual stress, and corrosion resistance over short- and long-term periods.

On the post-pandemic travel boom: How capacity building and smart tourism technologies in rural areas can help - evidence from Iran.

While there have been numerous studies investigating the impact of the COVID-19 pandemic on tourism, few research projects have examined the impact of the outbreak on using smart tourism technologies (STT), especially in developing countries. This study adopted thematic analysis, with data collected using in-person interviews. The participants for the study were selected using the snow-balling technique.

Selective Enhancer Dependencies in -Intact and -Rearranged Germinal Center B-cell Diffuse Large B-cell Lymphoma.

Unlabelled: High expression of and its target genes define a subset of germinal center B-cell diffuse large B-cell lymphoma (GCB-DLBCL) associated with poor outcomes. Half of these high-grade cases show chromosomal rearrangements between the locus and heterologous enhancer-bearing loci, while focal deletions of the adjacent non-coding gene are enriched in -intact cases. To identify genomic drivers of activation, we used high-throughput CRISPR-interference (CRISPRi) profiling of candidate enhancers in the locus and rearrangement partner loci in GCB-DLBCL cell lines and mantle cell lymphoma (MCL) comparators that lacked common rearrangements between and immunoglobulin (Ig) loci.

Multi-trait genomic selection improves the prediction accuracy of end-use quality traits in hard winter wheat.

Improvement of end-use quality remains one of the most important goals in hard winter wheat (HWW) breeding. Nevertheless, the evaluation of end-use quality traits is confined to later development generations owing to resource-intensive phenotyping. Genomic selection (GS) has shown promise in facilitating selection for end-use quality; however, lower prediction accuracy (PA) for complex traits remains a challenge in GS implementation.

Erosion-inhibiting potential of the stannous fluoride-enriched CPP-ACP complex in vitro.

Currently available anti-erosive agents only provide partial protection, emphasizing the need to enhance their performance. By characterizing erosive enamel wear at the nanoscale, the aim of this in vitro study was to assess the anti-erosive effects of SnF and CPP-ACP both individually and synergistically. Erosion depths were assessed longitudinally on 40 polished human enamel specimens after 1, 5, and 10 erosion cycles.

Incidence and risk factors for care-related pain in children with physical disabilities.

Background: The daily life of children with a physical disability is organized around interventions and care, which is coordinated by a multidisciplinary team. Little is known about the incidence of care-related pain in pediatric rehabilitation centers and health facilities for children.

Aim: To determine the incidence and intensity of care-related pain in children with physical disabilities, identify risk factors for pain and practices used to prevent care-related pain in pediatric rehabilitation centers and health facilities for children in France.

The Spinal Cord as Organ of Risk: Assessment for Acute and Subacute Neurological Adverse Effects after Microbeam Radiotherapy in a Rodent Model.

Microbeam radiotherapy (MRT), a high dose rate radiotherapy technique using spatial dose fractionation at the micrometre range, has shown a high therapeutic efficacy in vivo in different tumour entities, including lung cancer. We have conducted a toxicity study for the spinal cord as organ of risk during irradiation of a target in the thoracic cavity. In young adult rats, the lower thoracic spinal cord was irradiated over a length of 2 cm with an array of quasi-parallel microbeams of 50 µm width, spaced at a centre-to-centre distance of 400 µm, with MRT peak doses up to 800 Gy.

The TNF Mouse as a Model of Intestinal Fibrosis.

Crohn disease (CD) is a highly morbid chronic inflammatory disease. Although many patients with CD also develop fibrostenosing complications, there are no medical therapies for intestinal fibrosis. This is due, in part, to a lack of high-fidelity biomimetic models to enhance understanding and drug development, which highlights the need for developing in vivo models of inflammatory bowel disease-related intestinal fibrosis.

Deep resequencing of the 1q22 locus in non-lobar intracerebral hemorrhage.

Objective: Genome-wide association studies have identified as a susceptibility locus for cerebral small vessel diseases (CSVDs), including non-lobar intracerebral hemorrhage (ICH) and lacunar stroke. In the present study we performed targeted high-depth sequencing of in ICH cases and controls to further characterize this locus and prioritize potential causal mechanisms, which remain unknown.

Methods: 95,000 base pairs spanning , including and / were sequenced in 1,055 spontaneous ICH cases (534 lobar and 521 non-lobar) and 1,078 controls.

Proteome changes in a human retinal pigment epithelial cell line during oxidative stress and following antioxidant treatment.

Age related macular degeneration (AMD) is the most common cause of blindness in the elderly. Oxidative stress contributes to retinal pigment epithelium (RPE) dysfunction and cell death thereby leading to AMD. Using improved RPE cell model systems, such as human telomerase transcriptase-overexpressing (hTERT) RPE cells (hTERT-RPE), pathophysiological changes in RPE during oxidative stress can be better understood.

Hypocalcemia in Trauma is Determined by the Number of Units Transfused, Not Whole Blood Versus Component Therapy.

Introduction: Blood component resuscitation is associated with hypocalcemia (HC) (iCal <0.9 mmol/L) that contributes to coagulopathy and death in trauma patients. It is unknown whether or not whole blood (WB) resuscitation helps mitigate the risk of HC in trauma patients.

Crystal structures, Hirshfeld analysis, and energy framework analysis of two differently 3'-substituted 4-methylchalcones: 3'-(N=CHCH-p-CH)-4-methylchalcone and 3'-(NHCOCH)-4-methylchalcone.

Two crystal structures of chalcones, or 1,3-diarylprop-2-en-1-ones, are presented; both contain a p-methyl substitution on the 3-Ring, but differ with respect to the m-substitution on the 1-Ring. Their systematic names are (2E)-3-(4-methylphenyl)-1-(3-{[(4-methylphenyl)methylidene]amino}phenyl)prop-2-en-1-one (CHNO) and N-{3-[(2E)-3-(4-methylphenyl)prop-2-enoyl]phenyl}acetamide (CHNO), which are abbreviated as 3'-(N=CHCH-p-CH)-4-methylchalcone and 3'-(NHCOCH)-4-methylchalcone, respectively. Both chalcones represent the first reported acetamide-substituted and imino-substituted chalcone crystal structures, adding to the robust library of chalcone structures within the Cambridge Structural Database.

Priority acute and preventive migraine treatment benefits: Results of the Migraine Clinical Outcome Assessment System (MiCOAS) qualitative study of people living with migraine.

Background: There is renewed emphasis on including patients in determining, defining, and prioritizing outcomes for migraine treatment.

Objectives: To obtain insights directly from people living with migraine on their priorities for treatment.

Methods: A total of 40 qualitative interviews were conducted as part of the Migraine Clinical Outcome Assessment System project, a United States Food and Drug Administration grant-funded program to develop a core set of patient-centered outcome measures for migraine clinical trials.

Genetic control of grain amino acid composition in a UK soft wheat mapping population.

Wheat (Triticum aestivum L.) is a major source of nutrients for populations across the globe, but the amino acid composition of wheat grain does not provide optimal nutrition. The nutritional value of wheat grain is limited by low concentrations of lysine (the most limiting essential amino acid) and high concentrations of free asparagine (precursor to the processing contaminant acrylamide).

Exploring Cefiderocol Resistance Mechanisms in Burkholderia pseudomallei.

Cefiderocol is a siderophore cephalosporin designed mainly for treatment of infections caused by β-lactam and multidrug-resistant Gram-negative bacteria. Burkholderia pseudomallei clinical isolates are usually highly cefiderocol susceptible, with resistance found in a few isolates. Resistance in clinical B.

Advances in Early Detection of Melanoma and the Future of At-Home Testing.

The past decade has seen numerous advancements in approaches to melanoma detection, each with the common goal to stem the growing incidence of melanoma and its mortality rate. These advancements, while well documented to increase early melanoma detection, have also garnered considerable criticism of their efficacy for improving survival rates. In this review, we discuss the current state of such early detection approaches that do not require direct dermatologist intervention.

Structural basis of the alkaline pH-dependent activation of insulin receptor-related receptor.

The insulin receptor (IR) family is a subfamily of receptor tyrosine kinases that controls metabolic homeostasis and cell growth. Distinct from IR and insulin-like growth factor 1 receptor, whose activation requires ligand binding, insulin receptor-related receptor (IRR)-the third member of the IR family-is activated by alkaline pH. However, the molecular mechanism underlying alkaline pH-induced IRR activation remains unclear.

Factors That Impact the Long-Term Outcome of Postconcussive Dizziness Among Post-9/11 Veterans.

Purpose: The primary aim of this study was to examine the factors associated with long-term outcomes of postconcussive disruptive dizziness in Veterans of the post-9/11 wars.

Method: For this observational cohort study, the Neurobehavioral Symptom Inventory-Vestibular subscale (NSI-V) score was used as an outcome measure for dizziness in 987 post-9/11 Veterans who indicated disruptive dizziness at an initial Veterans Health Administration Comprehensive Traumatic Brain Injury Evaluation (CTBIE). An NSI-V change score was calculated as the difference in the scores obtained at the initial CTBIE and on a subsequent survey.