Shifting Paradigms: A Deep Dive Into Public Perceptions of Gender-affirming Surgery.

Background: Given the growing demand for gender-affirming surgery (GAS) in recent years, it is essential to explore the public perceptions of GAS. Understanding the public's opinions and attitudes toward GAS will provide valuable insights for shaping educational initiatives to enhance public knowledge and awareness.

Methods: This cross-sectional study used the Prolific Academic platform to distribute an online survey among adult participants residing in the United States in August 2023.

A novel micelleplex for tumour-targeted delivery of CRISPR-Cas9 against KRAS-mutated lung cancer.

CRISPR-Cas9 has emerged as a highly effective and customizable genome editing tool, holding significant promise for the treatment of KRAS mutations in lung cancer. In this study, we introduce a novel micelleplex, named C14-PEI, designed to co-deliver Cas9 mRNA and sgRNA efficiently to excise the mutated KRAS allele in lung cancer cells. C14-PEI is synthesised from 1,2-epoxytetradecane and branched PEI 600 Da a ring-opening reaction.

Cold waves in the Amazon rainforest and their ecological impact.

Cold waves crossing the Amazon rainforest are an extraordinary phenomenon likely to be affected by climate change. We here describe an extensive cold wave that occurred in June 2023 in Amazonian-Andean forests and compare environmental temperatures to experimentally measured thermal tolerances and their impact on lowland animal communities (insects and wild mammals). While we found strong reductions in activity abundance of all animal groups under the cold wave, tropical lowland animals showed thermal tolerance limits below the lowest environmental temperatures measured during the cold wave.

Impact of Acute Energy Drink Consumption on Heart Rate Variability in Children and Adolescents. A Randomized Trial.

The EDUCATE study investigated the acute impact of energy drink (ED) consumption on heart rate variability (HRV) in children and adolescents, with a focus on how these stimulant-rich beverages influence cardiac autonomic function. Given the popularity of EDs among young people, this study assessed the immediate cardiovascular response to ED intake. This randomized, double-blind, placebo-controlled crossover trial involved 26 healthy participants aged 10-18 years.

Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial.

Patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer (BC) have low pathological complete response (pCR) rates with neoadjuvant chemotherapy. A subset of ER+/HER2- BC contains dense lymphocytic infiltration. We hypothesized that addition of an anti-programmed death 1 agent may increase pCR rates in this BC subtype.

Deep Learning-Enabled Assessment of Right Ventricular Function Improves Prognostication After Transcatheter Edge-to-Edge Repair for Mitral Regurgitation.

Background: Right ventricular (RV) function has a well-established prognostic role in patients with severe mitral regurgitation (MR) undergoing transcatheter edge-to-edge repair (TEER) and is typically assessed using echocardiography-measured tricuspid annular plane systolic excursion. Recently, a deep learning model has been proposed that accurately predicts RV ejection fraction (RVEF) from 2-dimensional echocardiographic videos, with similar diagnostic accuracy as 3-dimensional imaging. This study aimed to evaluate the prognostic value of the deep learning-predicted RVEF values in patients with severe MR undergoing TEER.

The Outcomes of Pediatric, Adolescent, and Young Adult Oncology Patients With Non-neutropenic Fever: A Scoping Review of the Literature.

Background: There are established and well-followed guidelines for pediatric oncology patients who have neutropenic fever. However, there are no explicit criteria for this patient group, and over 50% of pediatric oncology patients with fever do not present with neutropenia.

Objective: In this scoping review, we have explored the outcomes of non-neutropenic fever in pediatric, adolescent, and young adult patients with cancer-directed treatment.

Feasibility and potential diagnostic value of [F]PI-2620 PET in patients with down syndrome and Alzheimer's disease: a case series.

Purpose Of The Report: Adults with Down Syndrome (DS) have a substantially increased risk for Alzheimer's disease (AD) due to the triplicated amyloid-precursor-protein gene on chromosome 21, resulting in amyloid and tau accumulation. However, tau PET assessments are not sufficiently implemented in DS-AD research or clinical work-up, and second-generation tau tracers such as [F]PI-2620 have not been thoroughly characterized in adults with DS. We aim at illustrating feasibility and potential diagnostic value of tau PET imaging with [F]PI-2620 for the diagnosis of DS-AD.

Only IF/TA in the Histological Evaluation of Post-Reperfusion Baseline Biopsies Correlates With Kidney Transplant Outcome.

Here, we retrospectively evaluated the informational yield of 338 post-reperfusion kidney transplant biopsies (including 95 living donations) assessed according to BANFF for the histological characteristics interstitial fibrosis and tubular atrophy (IF/TA), glomerulosclerosis, arteriosclerosis, and acute tubular injury (ATI). Associations with delayed graft function (DGF) and death-censored graft survival were explored through Cox-regression analyses. The maximum follow-up time was 11.

Bayesian-optimized deep learning for identifying essential genes of mitophagy and fostering therapies to combat drug resistance in human cancers.

Dysregulated mitophagy is essential for mitochondrial quality control within human cancers. However, identifying hub genes regulating mitophagy and developing mitophagy-based treatments to combat drug resistance remains challenging. Herein, BayeDEM (Bayesian-optimized Deep learning for identifying Essential genes of Mitophagy) was proposed for such a task.

Direct-acting oral anticoagulant removal by intraoperative hemoadsorption in CABG and/or single valve surgery: interim analysis of the International Safe and Timely Antithrombotic Removal (STAR) registry.

Objective: Patients on direct-acting oral anticoagulants (DOACs) are at high risk of perioperative bleeding complications. Intraoperative hemoadsorption is a novel strategy to reduce perioperative bleeding in patients on DOACs undergoing non-deferable cardiac surgery. The international STAR-registry reports real-world clinical outcomes associated with this application.

Deep Learning for Biomarker Discovery in Cancer Genomes.

Background: Genomic data is essential for clinical decision-making in precision oncology. Bioinformatic algorithms are widely used to analyze next-generation sequencing (NGS) data, but they face two major challenges. First, these pipelines are highly complex, involving multiple steps and the integration of various tools.

Nutrient Digestibility in Zoo-Kept Tapirs (Tapirus spp) as Compared to Other Herbivores.

Tapirs are hindgut fermenters with a natural diet dominated by browse, with a certain proportion of wild fruit. By contrast, diets fed to tapirs in zoos are often dominated by domestic fruit and other sources of easily digestible carbohydrates, which have been linked to obesity and various health problems. We aimed at better understanding the digestive physiology of tapirs, measuring the digestive efficiency of 13 lowland (Tapirus terrestris) and five Malayan (Tapirus indicus) tapirs from five zoos on various zoo diets by recording intake and total faecal excretion.

Longitudinal association between DNA methylation and type 2 diabetes: findings from the KORA F4/FF4 study.

Background: Type 2 diabetes (T2D) has been linked to changes in DNA methylation levels, which can, in turn, alter transcriptional activity. However, most studies for epigenome-wide associations between T2D and DNA methylation comes from cross-sectional design. Few large-scale investigations have explored these associations longitudinally over multiple time-points.

A reproducible representation of healthy tibiofemoral kinematics during stair descent using REFRAME - part I: REFRAME foundations and validation.

In clinical movement biomechanics, kinematic measurements are collected to characterise the motion of articulating joints and investigate how different factors influence movement patterns. Representative time-series signals are calculated to encapsulate (complex and multidimensional) kinematic datasets succinctly. Exacerbated by numerous difficulties to consistently define joint coordinate frames, the influence of local frame orientation and position on the characteristics of the resultant kinematic signals has been previously proven to be a major limitation.

Bi-allelic KICS2 mutations impair KICSTOR complex-mediated mTORC1 regulation, causing intellectual disability and epilepsy.

Nutrient-dependent mTORC1 regulation upon amino acid deprivation is mediated by the KICSTOR complex, comprising SZT2, KPTN, ITFG2, and KICS2, recruiting GATOR1 to lysosomes. Previously, pathogenic SZT2 and KPTN variants have been associated with autosomal recessive intellectual disability and epileptic encephalopathy. We identified bi-allelic KICS2 variants in eleven affected individuals presenting with intellectual disability and epilepsy.

German evidence- and consensus-based guideline on the management of penile urethritis.

Urethritis is a common condition predominantly caused by sexually transmitted pathogens such as Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium. It is not possible to differentiate with certainty between pathogens on the basis of clinical characteristics alone. However, empirical antibiotic therapy is often initiated in clinical practice.

Treatment of Venous Thromboembolism with Edoxaban over 18 Months: Results from ETNA-VTE Europe.

Background:  The benefits and risks of extending anticoagulant treatment beyond the first 3 to 6 months in patients with venous thromboembolism (VTE) in clinical practice are not well understood.

Methods:  ETNA-VTE Europe is a prospective, noninterventional, post-authorization study in unselected patients with VTE treated with edoxaban in eight European countries for up to 18 months. Recurrent VTE, major bleeding, and all-cause death were the primary study outcomes.

Targeting the Type I Interferon Pathway in Glomerular Kidney Disease: Rationale and Therapeutic Opportunities.

Type I interferons (IFNs) are immunostimulatory molecules that can activate the innate and adaptive immune systems. In cases of immune dysfunction, prolonged activation of the type I IFN pathway has been correlated with kidney tissue damage in a wide range of kidney disorders, such as lupus nephritis (LN) and focal segmental glomerulosclerosis (FSGS). Genetic mutations, such as risk variants in conjunction with elevated type I IFN expression, are also associated with higher rates of chronic kidney disease in patients with LN and collapsing FSGS.

Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning.

Efficient and accurate nanocarrier development for targeted drug delivery is hindered by a lack of methods to analyze its cell-level biodistribution across whole organisms. Here we present Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental and deep learning pipeline to comprehensively quantify the targeting of nanocarriers throughout the whole mouse body at single-cell resolution. SCP-Nano reveals the tissue distribution patterns of lipid nanoparticles (LNPs) after different injection routes at doses as low as 0.

A truncated variant of the ribosome-associated trigger factor specifically contributes to plant chloroplast ribosome biogenesis.

Molecular chaperones are essential throughout a protein's life and act already during protein synthesis. Bacteria and chloroplasts of plant cells share the ribosome-associated chaperone trigger factor (Tig1 in plastids), facilitating maturation of emerging nascent polypeptides. While typical trigger factor chaperones employ three domains for their task, the here described truncated form, Tig2, contains just the ribosome binding domain.

Genetic predisposition to high circulating levels of interleukin 6 and risk for Alzheimer's disease. Discovery and replication.

Importance: Aging is accompanied by immune dysregulation, which has been implicated in Alzheimer's disease (AD) pathogenesis. Individuals who are genetically predisposed to elevated levels of proinflammatory mediators might be at increased risk for AD.

Objective: To investigate whether genetic propensity for higher circulating levels of interleukin 6 (IL-6) is associated with AD risk.