STEAP4 with copper reductase activity suppresses tumorigenesis by regulating the cell cycle in hepatocellular carcinoma cells.

Background: Abnormal expression of six-transmembrane epithelial antigen of prostate 4 (STEAP4) has been implicated in the carcinogenesis of hepatocellular carcinoma (HCC). However, the biological role and regulatory mechanisms of STEAP4 in HCC remain unclear.

Methods And Results: Here, we analyzed STEAP4 expression levels and differentially expressed genes (DEGs) between STEAP4 high- and low-expression groups using multiple databases.

Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis.

Background: Pancreatic ductal adenocarcinoma (PDAC) requires innovative therapeutic strategies to counteract its progression and metastatic potential. Since the majority of patients are diagnosed with advanced metastatic disease, treatment strategies targeting not only the primary tumor but also metastatic lesions are needed. Tumor-Associated Macrophages (TAMs) have emerged as central players, significantly influencing PDAC progression and metastasis.

Bronchoscopic biopsies - a novel source for primary airway epithelial cells in respiratory research.

Background: Using primary airway epithelial cells (AEC) is essential to mimic more closely different types and stages of lung disease in humans while reducing or even replacing animal experiments. Access to lung tissue remains limited because these samples are generally obtained from patients who undergo lung transplantation for end-stage lung disease or thoracic surgery for (mostly) lung cancer. We investigated whether forceps or cryo biopsies are a viable alternative source of AEC compared to the conventional technique.

Self-reported frequency of handwashing among pet and non-pet owners in different situations: results of four surveys of the general adult population in Germany.

Background: Zoonotic diseases are partly associated with pets. However, data is sparse on pet owners' compliance with preventive recommendations. Also, research focuses on self-reports, which are subject to overestimation biases, i.

Trimethylamine-N-oxide accelerates osteoporosis by PERK activation of ATF5 unfolding.

Imbalances in gut microbiota and their metabolites have been implicated in osteoporotic disorders. Trimethylamine-n-oxide (TMAO), a metabolite of L-carnitine produced by gut microorganisms and flavin-containing monooxygenase-3, is known to accelerate tissue metabolism and remodeling; however, its role in bone loss remained unexplored. This study investigates the relationship between gut microbiota dysbiosis, TMAO production, and osteoporosis development.

Twenty-first century surface UV radiation changes deduced from CMIP6 models. Part II: effects on UV index and plant growth weighted irradiance.

This paper investigates the evolution of changes in surface ultraviolet (UV) radiation globally, emphasizing the significant impacts of key factors influencing its variability, i.e., total column ozone, aerosols, clouds, and surface reflectivity.

Ecologically sustainable benchmarking of AI models for histopathology.

Deep learning (DL) holds great promise to improve medical diagnostics, including pathology. Current DL research mainly focuses on performance. DL implementation potentially leads to environmental consequences but approaches for assessment of both performance and carbon footprint are missing.

Molecular Signaling Pathways of Quercetin in Alzheimer's Disease: A Promising Arena.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and memory deficit. Even with extensive research and studies, presently, there is no effective treatment for the management of AD. Besides, most of drugs used in the treatment of AD did not avert the AD neuropathology, and the disease still in a progressive status.

2-year results from an observational study of proactive treatment regimens with intravitreal aflibercept 2 mg in patients with nAMD in clinical practice: XTEND study UK cohort.

Objectives: The 36-month XTEND (NCT03939767) multicentre, observational, prospective study examined the effectiveness of proactive treatment regimens of intravitreal aflibercept (IVT-AFL) 2 mg in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice. The 12- and 24-month outcomes from the XTEND UK cohort are reported.

Methods: Patients aged ≥50 years with nAMD planned to receive IVT-AFL 2 mg were eligible.

Mass Balance Recovery, Absorption, Metabolism, and Excretion of Elinzanetant in Healthy Human Volunteers and in vitro Biotransformation.

Background: Elinzanetant is a dual neurokinin-1,3 receptor antagonist in development for the treatment of menopausal vasomotor symptoms. The objectives of these studies were to characterize the mass balance and biotransformation of elinzanetant.

Methods: In the clinical evaluation, whole blood, plasma, urine, and feces were collected from healthy fasted male volunteers (n = 6) following a single dose of 120 mg [C]-elinzanetant oral suspension for analysis of total radioactivity and metabolite profiling.

Safety and cognitive pharmacodynamics following dose escalations with 3-methylmethcathinone (3-MMC): a first in human, designer drug study.

3-Methylmethcathinone (3-MMC) is a designer drug that belongs to the group of synthetic cathinones. The compound has been scheduled in many jurisdictions because of public health concerns associated with excessive use. To date, there are no clinical studies that have evaluated the risk profile of 3-MMC in the recreational range of low to moderate doses.

Cognate reflex prediction as hypothesis test for a genealogical relation between the Panoan and Takanan language families.

We present a novel approach for testing genealogical relations between language families. Our method, which has previously only been applied to closely related languages, makes predictions for cognate reflexes based on the regularity of proposed sound correspondences between language families that are hypothesized to be related. We test the hypothesis about a genealogical relation between Panoan and Takanan, two linguistic families of the Amazon.

Structure and composition of early biofilms formed on dental implants are complex, diverse, subject-specific and dynamic.

Biofilm-associated peri-implant infections pose a major problem in modern medicine. The understanding of biofilm development is hampered by biofilm complexity and the lack of robust clinical models. This study comprehensively characterized the dynamics of early biofilm formation in the transmucosal passage of implant abutments in 12 patients.

Thromboembolic Events in the Hemodialysis Setting: Understanding Risk Profiles and Cumulative Incidences to Inform Clinical Trial Design.

Background: People with kidney failure have a high risk of cardiovascular morbidity/death, including thromboembolic events. Factor XIa inhibitors are a new class of anticoagulants in development that may offer antithrombotic benefits with a lower risk of incremental bleeding events than traditional therapies. We investigated major adverse vascular events (MAVEs), a relevant composite outcome for testing novel antithrombotic agents, in a large cohort of patients on hemodialysis, to better understand the key requirements to adequately design a phase 3 trial.

Pericytes and Extracellular Vesicle Interactions in Neurovascular Adaptation to Chronic Arterial Hypertension.

Background: Chronic arterial hypertension restructures the vascular architecture of the brain, leading to a series of pathological responses that culminate in cerebral small-vessel disease. Pericytes respond dynamically to vascular challenges; however, how they manifest under the continuous strain of hypertension has not been elucidated.

Methods And Results: In this study, we characterized pericyte behavior alongside hypertensive states in the spontaneously hypertensive stroke-prone rat model, focusing on their phenotypic and metabolic transformation.

Ten-Year Outcomes and Predictors of Mortality Following Catheter Ablation of Ventricular Tachycardia.

Background: Catheter ablation is the primary treatment option for idiopathic ventricular tachycardia (VT). It plays a key role in acute therapy of electrical storm, treatment of VTs in patients with structural heart disease (SHD), and can reduce VT burden. Here we report on 10-year clinical outcomes following VT ablation from patients enrolled in the prospective German Ablation Registry.

Management of dyslipidaemia in patients with comorbidities - facing the challenge Value and limitations of lipid lowering drugs in liver disease Effects/Interactions of lipid-lowering agents on/with the liver.

Objectives: This review aims to examine the evidence on the benefits and risks of lipid lowering drugs in patients with liver disease. Elevated liver enzyme levels often lead to cautious discontinuation of these drugs, potentially withholding from patients their benefit in reducing cardiovascular disease morbidity and mortality.

Methods And Results: Using a literature search of PubMed, we examine the efficacy and safety profiles of various lipid lowering agents, including statins, ezetimibe, bempedoic acid, PCSK9 inhibitors, fibrates, and icosapent ethyl, focusing particularly on their potential side effects related to liver health.

Global prevalence, resistance rates, and underlying resistance mechanisms of clinical Mycoplasma and Ureaplasma species.

Mycoplasmas are significant pathogens in human health, implicated in a range of clinical conditions from respiratory infections to urogenital disorders. Their resistance to commonly used antibiotics poses a substantial challenge to treatment and control. This study aims to provide a comprehensive overview of the global distribution of clinical mycoplasmas, elucidate their resistance to various antibiotics, and identify the genetic and molecular mechanisms underlying their resistance.

Rationale for phosphodiesterase-4 inhibition as a treatment strategy for interstitial lung diseases associated with rheumatic diseases.

Interstitial lung disease (ILD) associated with rheumatoid arthritis or with connective tissue diseases such as systemic sclerosis can be collectively named systemic autoimmune rheumatic disease-associated ILDs (SARD-ILDs) or rheumatic musculoskeletal disorder-associated ILDs. SARD-ILDs result in substantial morbidity and mortality, and there is a high medical need for effective therapies that target both fibrotic and inflammatory pathways in SARD-ILD. Phosphodiesterase 4 (PDE4) hydrolyses cyclic AMP, which regulates multiple pathways involved in inflammatory processes.

Anatomy-centred deep learning improves generalisability and progression prediction in radiographic sacroiliitis detection.

Purpose: To examine whether incorporating anatomy-centred deep learning can improve generalisability and enable prediction of disease progression.

Methods: This retrospective multicentre study included conventional pelvic radiographs of four different patient cohorts focusing on axial spondyloarthritis collected at university and community hospitals. The first cohort, which consisted of 1483 radiographs, was split into training (n=1261) and validation (n=222) sets.

Unravelling the role of health literacy among individuals with multimorbidity: a systematic review and meta-analysis.

Objective: To examine existing literature regarding health literacy levels and their association with multimorbidity and the potential underlying mechanisms behind the said association.

Design: Systematic review and meta-analysis.

Data Sources: The databases MEDLINE, EMBASE, CINAHL and Science Direct were searched for articles published between 1 January 2000 and 31 October 2023 using a systematic search strategy.

Transforming Households with Refraction and Innovative Financial Technology (THRIFT): study protocol for a randomised controlled trial of vision interventions and online banking among the elderly in Kurigram.

Introduction: Presbyopia, difficulty in seeing close-ups, affects a billion people globally. Mobile financial services (MFS) have been mandated since January 2021 for Bangladesh government social safety net payments, including old age allowance (OAA) and widow allowance (WA). We report the protocol for the Transforming Households with Refraction and Innovative Financial Technology randomised trial assessing the impact on the use of online banking of providing presbyopic safety net beneficiaries with reading glasses, and brief smartphone and mobile banking app training.