Adaptation and validation of a tool for the quality assessment of genetic counseling in Brazil: perspectives from clinical geneticists.

In 2018, Portuguese researchers proposed the "Tool for Quality Assessment of Genetic Counseling," a 5-point Likert scale comprising 50 items across five dimensions, designed to assess genetic counseling from the professional's perspective. This descriptive, cross-sectional study aimed to adapt this tool to Brazilian Portuguese, validate it among Brazilian clinical geneticists, and conduct a preliminary assessment of the quality of genetic counseling in Brazil. The adaptation process involved expert-driven content validation and calculation of the Content Validity Index (CVI) to ensure equivalence between the original and adapted versions.

Coronavirus Cryptic Landscape and Draft Genome of a Novel CoV Clade Related to MERS From Bats Circulating in Northeastern Brazil.

We identified seven distinct coronaviruses (CoVs) in bats from Brazil, classified into 229E-related (Alpha-CoV), Nobecovirus, Sarbecovirus, and Merbecovirus (Beta-CoV), including one closely related to MERS-like CoV with 82.8% genome coverage. To accomplish this, we screened 423 oral and rectal swabs from 16 different bat species using molecular assays, RNA sequencing, and evolutionary analysis.

Light-Triggered Protease-Mediated Release of Actin-Bound Cargo from Synthetic Cells.

Synthetic cells offer a versatile platform for addressing biomedical and environmental challenges, due to their modular design and capability to mimic cellular processes such as biosensing, intercellular communication, and metabolism. Constructing synthetic cells capable of stimuli-responsive secretion is vital for applications in targeted drug delivery and biosensor development. Previous attempts at engineering secretion for synthetic cells have been confined to non-specific cargo release via membrane pores, limiting the spatiotemporal precision and specificity necessary for selective secretion.

Non-canonical imprinting, manifesting as post-fertilization placenta-specific parent-of-origin dependent methylation, is not conserved in humans.

Genomic imprinting is the parent-of-origin dependent monoallelic expression of genes often associated with regions of germline-derived DNA methylation that are maintained as differentially methylated regions (gDMRs) in somatic tissues. This form of epigenetic regulation is highly conserved in mammals and is thought to have co-evolved with placentation. Tissue-specific gDMRs have been identified in human placenta, suggesting that species-specific imprinting dependent on unorthodox epigenetic establishment or maintenance may be more widespread than previously anticipated.

The interplay of sex and genotype in disease associations: a comprehensive network analysis in the UK Biobank.

Background: Disease comorbidities and longer-term complications, arising from biologically related associations across phenotypes, can lead to increased risk of severe health outcomes. Given that many diseases exhibit sex-specific differences in their genetics, our objective was to determine whether genotype-by-sex (GxS) interactions similarly influence cross-phenotype associations. Through comparison of sex-stratified disease-disease networks (DDNs)-where nodes represent diseases and edges represent their relationships-we investigate sex differences in patterns of polygenicity and pleiotropy between diseases.

Changes in sensor recorded activity patterns and neuropsychiatric symptoms after deep brain stimulation for Parkinson's disease: 5 case reports.

Background: Effects of subthalamic nucleus deep brain stimulation (STN-DBS) on neuropsychiatric symptoms of Parkinson's disease (PD) remain debated. Sensor technology might help to objectively assess behavioural changes after STN-DBS.

Case Presentation: 5 PD patients were assessed 1 before and 5 months after STN-DBS with the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III in the medication ON (plus postoperatively stimulation ON) condition, the Montreal Cognitive Assessment, the Questionnaire for Impulsive-Compulsive Behaviors in Parkinson's Disease Rating Scale present version, the Hospital Anxiety and Depression Scale and the Starkstein Apathy Scale.

Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

Exploration of linear and interpretable models for quantification of cell parameters via contactless short-wave infrared hyperspectral sensing.

The development of optical sensors for label-free quantification of cell parameters has numerous uses in the biomedical arena. However, using current optical probes requires the laborious collection of sufficiently large datasets that can be used to calibrate optical probe signals to true metabolite concentrations. Further, most practitioners find it difficult to confidently adapt black box chemometric models that are difficult to troubleshoot in high-stakes applications such as biopharmaceutical manufacturing.

Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice.

The Nr4a nuclear hormone receptors are transcriptionally upregulated in response to antigen recognition by the T cell receptor (TCR) in the thymus and are implicated in clonal deletion, but the mechanisms by which they operate are not clear. Moreover, their role in central tolerance is obscured by redundancy among the Nr4a family members and by their reported functions in Treg generation and maintenance. Here we take advantage of competitive bone marrow chimeras and the OT-II/RIPmOVA model to show that Nr4a1 and Nr4a3 are essential for the upregulation of Bcl2l11/BIM and thymic clonal deletion by self-antigen.

Fixation for Osteochondral Lesions of the Talus Leads to Successful Clinical Outcomes in 9 out of 10 Patients: a Systematic Review.

Importance: Osteochondral lesions of the talus (OLT) with an osteochondral fragment are amendable for fixation. Fixation aims to stabilize the osteochondral fragment while retaining the native cartilage. Though fixation for OLT is a promising treatment, no systematic overview of the literature on its efficacy and safety exists.

Hydrogel coils in intracranial aneurysm treatment: a multicenter, prospective, randomized open-label trial.

Objective: Studies have demonstrated the effectiveness of hydrogel-coated coils (HGCs) to achieve the composite endpoint of decreased recanalization rates and greater safety. Herein, the authors aimed to assess the true ability of second-generation HGCs to prevent recanalization.

Methods: This randomized controlled study, the HYBRID (Hydrocoil Versus Bare Platinum Coil in Recanalization Imaging Data) trial, comparing HGCs with bare platinum coils (BPCs), was conducted in 43 Japanese institutions.

Developing Research-Oriented Health Professionals: Understanding Students' Perceptions and Needs for Extracurricular Research Opportunities.

Background: Undergraduate training in research principles is often mandated by healthcare profession regulators in Ireland to prepare graduates for higher specialist training. Students can be offered the opportunity to participate in extracurricular research activities, in addition to those embedded in the curricula. This cross-sectional study aims to explore student attitudes towards research and to understand their motivations for engaging in research-related activities and any barriers that might prevent them from doing so.

Brain-wide neuronal circuit connectome of human glioblastoma.

Glioblastoma (GBM) infiltrates the brain and can be synaptically innervated by neurons, which drives tumor progression. Synaptic inputs onto GBM cells identified so far are largely short-range and glutamatergic. The extent of GBM integration into the brain-wide neuronal circuitry remains unclear.

Once-weekly IcoSema versus once-weekly semaglutide in adults with type 2 diabetes: the COMBINE 2 randomised clinical trial.

Aims/hypothesis: COMBINE 2 assessed the efficacy and safety of once-weekly IcoSema (a combination therapy of basal insulin icodec and semaglutide) vs once-weekly semaglutide (a glucagon-like peptide-1 analogue) 1.0 mg in individuals with type 2 diabetes inadequately managed with GLP-1 receptor agonist (GLP-1 RA) therapy, with or without additional oral glucose-lowering medications.

Methods: This 52 week, randomised, multicentre, open-label, parallel group, Phase IIIa trial was conducted across 121 sites in 13 countries/regions.

A phase I/II study of adoptive immunotherapy using donor liver graft-derived NK cell-enriched immune cells to prevent severe infection after liver transplantation.

Bloodstream infections (BSIs) are significant postoperative complications associated with high mortality rates after liver transplantation (LT). Natural killer (NK) cells, which are key components of the innate immune system, have demonstrated potential to combat both infections and cancer. The use of activated NK cells to mitigate post-LT infections, particularly BSIs, has attracted considerable interest.

Prostate cancer cells elevate glycolysis and G6PD in response to caffeic acid phenethyl ester-induced growth inhibition.

Background: Caffeic acid phenethyl ester (CAPE) is the main bioactive component of poplar type propolis. We previously reported that treatment with caffeic acid phenethyl ester (CAPE) suppressed the cell proliferation, tumor growth, as well as migration and invasion of prostate cancer (PCa) cells via inhibition of signaling pathways of AKT, c-Myc, Wnt and EGFR. We also demonstrated that combined treatment of CAPE and docetaxel altered the genes involved in glycolysis and tricarboxylic acid (TCA) cycle.

Unfolded protein response modulates Tyrosinase levels and melanin production during melanogenesis.

Background: Melanocytes protect the body from ultraviolet radiation by synthesizing melanin. Tyrosinase, a key enzyme in melanin production, accumulates in the endoplasmic reticulum (ER) during melanin synthesis, potentially causing ER stress. However, regulating ER function for melanin synthesis has been less studied than controlling Tyrosinase activity.

Why are we not exploring the potential of lower limb muscle power to identify people with sarcopenia?

Sarcopenia refers to a neuromuscular disease characterized by age-related declines in muscle mass and function. Since Professor Rosenberg first introduced the concept of sarcopenia in 1989, numerous operational paradigms have been proposed, tested, and validated against negative outcomes. The most recent recommendations advocate that dynapenia, or reduced of muscle strength, should be used alongside low muscle mass for the identification of sarcopenia.

Vitamin A deficiency and male-specific effects on heart function in mice.

Hepatic stores of Vitamin A (retinol) are mobilized and metabolized in the heart following myocardial infarction. The physiological consequences of this mobilization are poorly understood. Here we used dietary depletion in a lecithin retinol acyltransferase mutant mouse line to induce Vitamin A deficiency and investigate the effects on cardiac function and recovery from myocardial infarction.

Characterization of Cutaneous Radiation Syndrome in a Mouse Model Using [18F]F- Fluorodeoxyglucose Positron Emission Tomography.

Ionizing radiation on the skin has the potential to cause various sequelae affecting quality of life and even leading to death due to multi-system failure. The development of radiation dermatitis is attributed to oxidative damage to the skin's basal layer and alterations in immune response, leading to inflammation. Past studies have shown that [18F]F-2-fluoro-2-deoxyglucose positron emission tomography-computed tomography ([18F]F-FDG PET/CT) can be used effectively for the detection of inflammatory activity, especially in conditions like hidradenitis suppurativa, psoriasis, and early atherosclerosis.

Normal tissue complication probability model for severe radiation-induced lymphopenia in patients with pancreatic cancer treated with concurrent chemoradiotherapy.

Background And Purpose: Radiation-induced lymphopenia (RIL) may be associated with a worse prognosis in pancreatic cancer. This study aimed to develop a normal tissue complication probability (NTCP) model to predict severe RIL in patients with pancreatic cancer undergoing concurrent chemoradiotherapy (CCRT).

Materials And Methods: We reviewed pancreatic cancer patients treated at our facility for model training and internal validation.

Utility of using far-field R-wave signals in the detection of fatal ventricular arrhythmia.

Current guidelines recommend cardioverter-defibrillator (ICD) programming, including faster detection rates, longer detection durations, and strict discrimination for supraventricular tachycardia (SVT) to prevent unnecessary ICD treatment. This delayed-style ICD programming could lead to a rise in the possibility of VF undersensing. To avoid this risk, an innovative algorithm known as VF Therapy Assurance (VFTA; Abbott, Sylmar, CA) has been developed.

Association between vitamin D levels with IL-6 and IL-10 in umbilical cord blood of infants.

A worldwide issue, vitamin D deficiency affects pregnant mothers and babies everywhere, including Indonesia. It involves the adaptive immune system by controlling the production of pro-and anti-inflammatory cytokines and the balance between humoral (Th2) and cell-mediated (Th1) immunity. The aim of this study was to investigate the relationship between vitamin D and the cytokines IL-6 and IL-10 in infants.

Effects of Malted Rice Amazake Consumption on Nutritional Status and Gut Microbiome in Older Patients and Residents of an Integrated Facility for Medical and Long-Term Care.

Malnutrition is observed in approximately 20-50% of hospitals and long-term care facilities. We examined the effects of malted rice amazake beverage on the nutritional status and gut microbiome of older patients and residents in an integrated long-term care facility; 13 older patients and residents (84.6 ± 9.