Conserved patterns of transcriptional dysregulation, heterogeneity, and cell states in clear cell kidney cancer.

Clear cell kidney cancers are characterized both by conserved oncogenic driver events and by marked intratumor genetic and phenotypic heterogeneity, which help drive tumor progression, metastasis, and resistance to therapy. How these are reflected in transcriptional programs within the cancer and stromal cell components remains an important question with the potential to drive novel therapeutic approaches to treating cancer. To better understand these programs, we perform single-cell transcriptomics on 75 multi-regional biopsies from kidney tumors and normal kidney.

Social Determinants of Uncorrected Distance and Near Visual Impairment in an Older Adult Population.

Purpose: Uncorrected visual impairment (VI) significantly impacts life quality and exacerbates age-related health issues. Social determinants of health (SDOH) are associated with uncorrected VI, but quantitative evidence is limited. This study investigated the link between SDOH and uncorrected VI among aging adults to identify disparities and improve vision care.

Anatomic Approach to Fetal Hydrocephalus.

Hydrocephalus is an imprecise term and refers to the imbalance of brain parenchyma and cerebral spinal fluid in the cranial vault. Ventriculomegaly, or enlargement of the ventricular system, is often the more precise term and is therefore preferred. Appropriate imaging and measurement techniques are critical to detect ventriculomegaly and grade its severity.

Do reproductive endocrinology and infertility fellowship websites reflect a commitment to diversity, equity, and inclusion?

Objective: To characterize the frequency of diversity elements (DEs) in reproductive endocrinology and infertility (REI) fellowship websites and analyze these elements according to program characteristics.

Design: Forty-nine REI fellowship websites were assessed for 20 DEs that represent programmatic commitments to diversity, equity, and inclusion (DEI). Program websites were categorized by the number of discrete DEs featured: low (0-6); moderate (7-13); or high (14-20).

Sports experience, affects and life satisfaction in Portuguese athletes with disabilities.

This study aims to validate the Portuguese version of the Satisfaction with Life Scale (Cronbach's alpha = 0.82) and the Positive and Negative Affect Scale (Cronbach's alpha = 0.86 for positive affect and 0.

evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease.

Background: Disease-modifying therapies targeting the diverse pathophysiology of Alzheimer's disease (AD), including neuroinflammation, represent potentially important and novel approaches. The glucagon-like peptide-1 receptor agonist semaglutide is approved for the treatment of type 2 diabetes and obesity and has an established safety profile. Semaglutide may have a disease-modifying, neuroprotective effect in AD through multimodal mechanisms including neuroinflammatory, vascular, and other AD-related processes.

Innovative method integrates play fairway analysis supported with GIS and seismic modeling for geothermal potential evaluation in a basement reservoir.

The growing demand for clean and sustainable energy sources has prompted the investigation of numerous renewable and ecologically friendly options. Among these, geothermal energy is particularly noteworthy because of its widespread availability, compact size, and consistent, weather-independent power production. A geothermal play fairway analysis (GPFA) model was created for the study area, which is located in Békés county, southeastern Hungary.

KLF5 loss sensitizes cells to ATR inhibition and is synthetic lethal with ARID1A deficiency.

ATR plays key roles in cellular responses to DNA damage and replication stress, a pervasive feature of cancer cells. ATR inhibitors (ATRi) are in clinical development for treating various cancers, including those with high replication stress, such as is elicited by ARID1A deficiency, but the cellular mechanisms that determine ATRi efficacy in such backgrounds are unclear. Here, we have conducted unbiased genome-scale CRISPR screens in ARID1A-deficient and proficient cells treated with ATRi.

PARP-1 Inhibition Increases Oxidative Stress in Ets-1-Expressing MDA-MB-231 Breast Cancer Cells.

Background: The Ets-1 transcription factor plays a primordial role in regulating the expression of numerous genes implicated in cancer progression. In a previous study, we revealed that poly(ADP-ribose) polymerase-1 (PARP-1) inhibition by PJ-34 results in Ets-1 level increase in cells, which is related with cell death of Ets-1-expressing cancer cells.

Aims: The mechanism of the antitumor effect of PARP-1 inhibition was investigated in the Ets-1-expressing MDA-MB-231 breast cancer cells.

Desmoplastic melanoma in Sweden in 2009-2022: A population-based registry study demonstrating distinctive tumour characteristics, incidence and survival trends.

Background: Desmoplastic melanoma (DM) is a rare subtype, accounting for less than 5% of primary cutaneous invasive melanomas. DM often arises in chronically sun-exposed skin, in older individuals. While the incidence of cutaneous melanoma has increased globally, trends specific to DM are less documented and studies on survival outcomes for DM are inconsistent.

The transcription factor FOXQ1 in cancer.

FOXQ1 is a member of the large forkhead box (FOX) family of transcription factors that is involved in all aspects of mammalian development, physiology, and pathobiology. FOXQ1 has emerged as a major regulator of epithelial-to-mesenchymal transition and tumour metastasis in cancers, especially carcinomas of the digestive tract. Accordingly, FOXQ1 induction is recognised as an independent prognostic factor for worse overall survival in several types of cancer, including gastric and colorectal cancer.

Oral Health Care: A Systematic Review of Clinical Practice Guidelines.

Maintaining good oral hygiene is essential for preventing and managing oral health problems. This systematic review aimed to identify and assess clinical practice guidelines on oral hygiene, focusing on quality and key areas. A comprehensive search was conducted in PubMed, CINAHL, Scopus, Cochrane, and organizational websites.

Safety and immunogenicity of an optimized self-replicating RNA platform for low dose or single dose vaccine applications: a randomized, open label Phase I study in healthy volunteers.

Self-replicating RNA (srRNA) technology, in comparison to mRNA vaccines, has shown dose-sparing by approximately 10-fold and more durable immune responses. However, no improvements are observed in the adverse events profile. Here, we develop an srRNA vaccine platform with optimized non-coding regions and demonstrate immunogenicity and safety in preclinical and clinical development.

Safety of Adjunctive Intraarterial Tenecteplase Following Mechanical Thrombectomy: The ALLY Pilot Trial.

Background: Recent studies suggest that the use of adjunctive intraarterial alteplase after mechanical thrombectomy (MT) may improve outcomes; however, there are limited data on the use of intraarterial tenecteplase, a newer-generation lytic, in this acute ischemic stroke patient population. Here, we evaluate the use of intraarterial tenecteplase in the ALLY pilot study (Adjunctive Intraarterial Tenecteplase Following Mechanical Thrombectomy).

Methods: ALLY was a prospective, single-center, nonrandomized pilot study assessing the feasibility and safety of intraarterial tenecteplase up to 4.

Comparative Clinical Study on Magnesium Absorption and Side Effects After Oral Intake of Microencapsulated Magnesium (MAGSHAPE Microcapsules) Versus Other Magnesium Sources.

Background/objectives: Magnesium (Mg)-based food supplements contribute to the maintenance of adequate levels of Mg that are essential for overall health and well-being. The aim of this double-blind, randomized, cross-over clinical study was to assess the plasma Mg levels in volunteers following the oral administration of a magnesium-based nutraceutical ingredient, MAGSHAPE microcapsules (Mg-MS), in comparison to other commonly used magnesium sources, including the following: Mg Oxide (MgO), Mg Citrate (Mg-C), and Mg bisglycinate (Mg-BG).

Methods: A total of 40 healthy women and men were put on a low-Mg diet for 7 days, and after 8 h of fasting, a blood sample was taken from a digital puncture before (0 h) and 1 h, 4 h, and 6 h after the oral intake of each product.

The Acacia ( (L.) P.J.H. Hurter & Mabb.): Traditional Uses and Recent Advances on Its Pharmacological Attributes and Potential Activities.

For thousands of years, has been widely used as an herbal medicine to treat some diseases and symptoms, including respiratory, gastrointestinal and urogenital ailments. The present study was adapted to document and assemble existing information about and its evidence-based ethnopharmacological activities, with brief reviews on the description, geographical distribution, ecology, medical uses and phytochemistry. A literature review and information up to 2024 was performed in various scientific databases, including PubMed, Science Direct and Google Scholar.

Epigenetic and Cellular Reprogramming of Doxorubicin-Resistant MCF-7 Cells Treated with Curcumin.

The MCF-7R breast cancer cell line, developed by treating the parental MCF-7 cells with increasing doses of doxorubicin, serves as a model for studying acquired multidrug resistance (MDR). MDR is a major challenge in cancer therapy, often driven by overexpression of the efflux pump P-glycoprotein (P-gp) and epigenetic modifications. While many P-gp inhibitors show promise in vitro, their nonspecific effects on the efflux pump limit in vivo application.

Correction: Danek, P.J.; Daniel, W.A. Long-Term Treatment with Atypical Antipsychotic Iloperidone Modulates Cytochrome P450 2D (CYP2D) Expression and Activity in the Liver and Brain via Different Mechanisms. 2021, , 3472.

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A Randomized Controlled Trial to Test the Effects of Repetitive Peripheral Magnetic Stimulation Versus Neuromuscular Electrical Stimulation in Patients with Spastic Hemiparesis After Stroke (REPMAST): Study Protocol.

Background/objectives: Innovative therapies are needed to reduce disability, facilitate activities of daily living, and improve the quality of life in patients with stroke. Non-invasive methods of stimulating the peripheral and central nervous system are increasingly being used to enhance the effects of existing therapies in stroke rehabilitation. One potentially relevant method for achieving greater improvement is repetitive peripheral magnetic stimulation (rPMS).

Vps4a Mediates a Unified Membrane Repair Machinery to Attenuate Ischemia/Reperfusion Injury.

Background: Cardiac ischemia/reperfusion disrupts plasma membrane integrity and induces various types of programmed cell death. The ESCRT (endosomal sorting complex required for transport) proteins, particularly AAA-ATPase Vps4a (vacuolar protein sorting 4a), play an essential role in the surveillance of membrane integrity. However, the role of ESCRT proteins in the context of cardiac injury remains unclear.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Outcomes and predictive factors for fluid resolution following three loading injections of faricimab for treatment-naïve neovascular age-related macular degeneration.

To evaluate the outcomes and predictive factors for fluid resolution following three loading injections of faricimab for neovascular age-related macular degeneration(AMD). This retrospective study included patients diagnosed with treatment-naïve neovascular AMD who received three monthly injections of faricimab. Changes in best-corrected visual acuity(BCVA) and central retinal thickness(CRT) following treatment were evaluated.

Fast barrier-free switching in synthetic antiferromagnets.

We analytically solve the Landau-Lifshitz equations for the collective magnetization dynamics in a synthetic antiferromagnet (SAF) nanoparticle and uncover a regime of barrier-free switching under a short small-amplitude magnetic field pulse applied perpendicular to the SAF plane. We give examples of specific implementations for forming such low-power and ultra-fast switching pulses. For fully optical, resonant, barrier-free SAF switching we estimate the power per write operation to be  pJ, 10-100 times smaller than for conventional quasi-static rotation, which should be attractive for memory applications.

FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial.

Introduction: Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). The strong association between gut and liver inflammation has driven several pathogenic hypotheses to which the intestinal microbiome is proposed to contribute. Pilot studies of faecal microbiota transplantation (FMT) in PSC and IBD are demonstrated to be safe and associated with increased gut bacterial diversity.

Epidemiology of invasive disease in adults in England, 2013-2017.

Extraintestinal pathogenic (ExPEC) causes invasive disease (IED), including bacteraemia and (uro)sepsis, resulting in a high disease burden, especially among older adults. This study describes the epidemiology of IED in England (2013-2017) by combining laboratory surveillance and clinical data. A total of 191 612 IED cases were identified.