Defective Mammary Epithelial Outgrowth in Transgenic EKAREV-NLS Mice: Correction via Estrogen Supplementation and Genetic Background Modification.

Fluorescent biosensors offer a powerful tool for tracking and quantifying protein activity in living systems with high temporospatial resolution. However, the expression of genetically encoded fluorescent proteins can interfere with endogenous signaling pathways, potentially leading to developmental and physiological abnormalities. The EKAREV-NLS mouse model, which carries a FRET-based biosensor for monitoring extracellular signal-regulated kinase (ERK) activity, has been widely utilized both in vivo and in vitro across various cell types and organs.

Population variation in fatty acid composition and response to climatic factors in Malania oleifera Chun et S.K. Lee.

Malania oleifera Chun et S.K. Lee is a woody oil tree species and is rich in nervonic acid, which is associated with brain development.

Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost.

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.

End-to-End CT Radiomics-Based Pipeline for Predicting Renal Interstitial Fibrosis Grade in CKD Patients.

Rationale And Objectives: Non-invasive assessment of renal fibrosis in patients with chronic kidney disease (CKD) remains a clinical challenge. This study aims to integrate radiomics and clinical factors to develop an end-to-end pipeline for predicting interstitial fibrosis (IF) in CKD patients.

Materials And Methods: This retrospective study included 80 patients with CKD, with 53 patients in training set and 27 patients in test set.

Psychometric validation of the Copenhagen Hip and Groin Outcome Score (HAGOS) and Oxford Hip Score (OHS) in patients with hip-abductor tendon pathology.

Objective: Validated patient-reported outcome measures for patients with hip-abductor tendon pathology are lacking. Recent studies indicate that the Copenhagen Hip and Groin Outcome Score (HAGOS), in the original or the revised scoring format, and the Oxford Hip Score (OHS) may be relevant for use in patients with hip-abductor tendon pathology. The objective of this study was to assess the validity of the Danish version of the HAGOS, the revised HAGOS, and the OHS psychometrically in patients with hip-abductor tendon pathology.

Retrovirus-based manufacturing of chimeric antigen receptor-modified T cells for cancer therapy research.

Treatment with autologous chimeric antigen receptor (CAR)-modified T cells can achieve outstanding clinical response rates in heavily pretreated patients with B and plasma cell malignancies. However, relapses occur, and they limit the efficacy of this promising treatment approach. The complex GMP-compliant production and high treatment costs cause that CAR T cells cannot yet be used in a broad population.

Rationale and Design of the HERZCHECK trial: Detection of Early Heart Failure Using Telemedicine and CMR in Structurally Weak Regions (NCT05122793).

Background And Aims: Heart failure (HF) is an imminent global health problem. Yet established screening algorithms for asymptomatic pre-HF, allowing for early and effective preventive interventions, are largely lacking. The HERZCHECK trial, conducted in structurally underserved rural regions of North-Eastern Germany, aims to close this gap by evaluating the feasibility, diagnostic efficacy, and cost-effectiveness of a fully mobile, telemedically-supervised screening approach, combining cardiac magnetic resonance imaging (CMR) and laboratory testing as central elements.

Pan-PPAR agonist lanifibranor improves insulin resistance and hepatic steatosis in patients with T2D and MASLD.

Background & Aims: Lanifibranor is a pan-PPAR agonist that improves glucose/lipid metabolism and reverses steatohepatitis and fibrosis in adults with MASH. We tested its effect on insulin resistance at the level of different target tissues in relationship to change in intrahepatic triglyceride (IHTG) content.

Methods: This phase 2, single center, study randomized (1:1) 38 patients with T2D and MASLD to receive lanifibranor 800 mg or placebo for 24 weeks.

Biological testing unification for hemodialysis membranes evaluation: A step towards standardization.

Current hemodialysis treatments can cause adverse effects, many of which are linked to the membranes used in the process. These issues are being addressed through new materials and technologies, making it urgent to establish minimum guidelines for evaluating such membranes. This review proposes standardizing the biological tests and variables to evaluate the performance of new membranes, aiming to replicate hemodialysis conditions closely.

Inhibition of IKK complex by (2 methyl butyryl) Shikonin, a naturally occurring naphthoquinone, abrogates melanoma growth and progression via modulation of the IKK/NFκB /EMT signaling axis.

Melanoma is an aggressive form of malignancy that originates from melanin-producing cells known as melanocytes underlying the basal layer of the epidermis with a poor prognosis, low survival rates, and limited treatment options. Although several specific and effective systematic strategies for treating melanoma have been established, the underlying molecular mechanism of melanoma progression, mortality and the promising therapeutic options remain elusive. Shikonin (SK), a natural naphthoquinone derived from a medicinal herbaceous plant, has been shown to inhibit the proliferation of several cancer cells.

Modification of peroxidase activity and proteome in maize exposed to cadmium in the presence of galactoglucomannan oligosaccharides.

We tested the effects of galactoglucomannan oligosaccharides (GGMOs) and/or cadmium (Cd) on peroxidase activity and the proteome in maize (Zea mays L.) roots and leaves. Our previous work confirmed that GGMOs ameliorate the symptoms of Cd stress in seedlings.

Biomarkers of RV Dysfunction in HFrEF Identified by Direct Tissue Proteomics: Extracellular Proteins Fibromodulin and Fibulin-5.

Background: Right ventricular dysfunction (RVD) is common in patients with heart failure with reduced ejection fraction, and it is associated with poor prognosis. However, no biomarker reflecting RVD is available for routine clinical use.

Methods: Proteomic analysis of myocardium from the left ventricle and right ventricle (RV) of patients with heart failure with reduced ejection fraction with (n=10) and without RVD (n=10) who underwent heart transplantation was performed.

Novel Missense DNA Variants in the IL2RG Gene Identified in Slovak X-linked Severe Combined Immunodeficiency Disease Patients: A Case Report.

X-linked severe combined immunodeficiency disease (X-SCID) is a form of inborn errors of immunity (IEI) associated with causal DNA variants of the gene. Patients with X-SCID are characterized by a combination of cellular and humoral immunodeficiencies associated with increased susceptibility to infections. The presented cases constituted two unrelated male patients from the Slovak population.

Chronic Radium-226 toxicity to and oxidative stress in the aquatic invertebrate .

The mining industry, including uranium mining and milling, is of high importance in Canada. It is, however, important to consider that ore processing can result in the creation of by-products that contain radionuclides such as radium-226 (Ra). Even with the strict discharge regulations in place, there is limited evidence to suggest that the current Canadian regulatory thresholds for Ra are protective for aquatic life.

Association between choroidal microvasculature in the eye and Alzheimer's disease risk in cognitively healthy mid-life adults: A pilot study.

Introduction: We explored associations between measurements of the ocular choroid microvasculature and Alzheimer's disease (AD) risk.

Methods: We measured the choroidal vasculature appearing in optical coherence tomography (OCT) scans of 69 healthy, mid-life individuals in the PREVENT Dementia cohort. The cohort was prospectively split into low-, medium-, and high-risk groups based on the presence of known risk factors (apolipoprotein E [] ε4 genotype and family history of dementia [FH]).

Indication of air pollution based on the comparison of mercury and other elements in the faeces of marmots from the Western Carpathians and the Dzungarian Alatau.

The Dzungarian Alatau in Central Asia and the Western Carpathians in Central Europe are exposed to anthropogenic sources of pollution that are impacting high-altitude mountain systems through long-range transport of emissions. Based on analyses of the autumn faeces of two species of marmots (Marmota baibacina from the alpine habitats of Zhongar Alatau National Park, Marmota marmota latirostris from the alpine habitats of the Western Tatras), we determined the environmental load of mercury and other chemical elements. Our results show significantly higher levels of total mercury amounts (p < 0.

The evolving landscape of live biotherapeutics in the treatment of Clostridioides difficile infection.

Clostridioides difficile (C. difficile) infection (CDI) is common after antibiotic exposure and presents significant morbidity, mortality and healthcare costs worldwide. The rising incidence of recurrent CDI, driven by hypervirulent strains, widespread antibiotic use and increased community transmission, has led to an urgent need for novel therapeutic strategies.

Association of Alzheimer's Disease Polygenic Risk Score with Concussion Severity and Recovery Metrics.

Background: Identification of genetic alleles associated with both Alzheimer's disease (AD) and concussion severity/recovery could help explain the association between concussion and elevated dementia risk. However, there has been little investigation into whether AD risk genes associate with concussion severity/recovery, and the limited findings are mixed.

Objective: We used AD polygenic risk scores (PRS) and APOE genotypes to investigate any such associations in the NCAA-DoD Grand Alliance CARE Consortium (CARE) dataset.

The vascular supply to the lateral compartment of the leg with emphasis on fibular flap harvesting.

Purpose: The aim of this study is to determine the exact locations of vascular pedicles that supply the fibularis longus and brevis, to identify the morphometric features of those vessels in the lateral compartment of the leg, and to indicate the branching points of the pedicles from the main arteries.

Methods: The popliteal arteries of 40 lower limbs from 20 adult cadavers (12 males, 8 females) were bilaterally injected with colored latex. After dissection, the branches of the arteries were identified and counted.

Effectiveness and Safety of Vildagliptin Sustained Release in the Management of Type 2 Diabetes Mellitus: Real-World Evidence in Indian Patients [NOVELTY Study].

Background And Objective: Vildagliptin sustained release (XR), a formulation that provides vildagliptin 100 mg with a once-daily dose administration, is a recent introduction to manage type 2 diabetes mellitus in India. This study aimed to evaluate the effectiveness and tolerability of vildagliptin XR in patients with type 2 diabetes in real-world clinical settings.

Methods: This was an observational, prospective, multicenter, cohort study conducted in India, which included patients with type 2 diabetes uncontrolled on metformin XR monotherapy with glycated hemoglobin (HbA1c) > 7.

An update on selective estrogen receptor modulator: repurposing and formulations.

The selective estrogen receptor modulator (SERM) raloxifene hydrochloride (RLH) is used extensively in the management and prevention of breast cancer and osteoporosis. Recent clinical studies show the repurposing of RLH in various diseases based on its structure and some clinical trials studies. Optimizing the clinical effectiveness of this important drug requires a thorough review of the formulation techniques, patent environment, and analytical procedures.

Evaluating and Enhancing Japanese Large Language Models for Genetic Counseling Support: Comparative Study of Domain Adaptation and the Development of an Expert-Evaluated Dataset.

Background: Advances in genetics have underscored a strong association between genetic factors and health outcomes, leading to an increased demand for genetic counseling services. However, a shortage of qualified genetic counselors poses a significant challenge. Large language models (LLMs) have emerged as a potential solution for augmenting support in genetic counseling tasks.

Advanced Targeted Therapy for Colorectal Cancer with Lipid Nanoparticles.

Targeted therapy for colorectal cancer (CRC) appears to have great potential with lipid nanoparticles (LNPs). The advances in LNP-based techniques, such as liposomes, exosomes, micelles, solid lipid nanoparticles (SLNs), nano-cubosomes, and plant- derived LNPs (PDLNPs), are explored in detail in this thorough review. Every platform provides distinct advantages: liposomes enable precise drug release and improved delivery; exosomes function as organic nanocarriers for focused treatment; SLNs offer greater stability; micelles enhance drug solubility and resistance; nano-cubosomes tackle low bioavailability; and PDLNPs offer biocompatible substitutes.

Encoding of cerebellar dentate neuron activity during visual attention in rhesus macaques.

The role of cerebellum in controlling eye movements is well established, but its contribution to more complex forms of visual behavior has remained elusive. To study cerebellar activity during visual attention we recorded extracellular activity of dentate nucleus (DN) neurons in two non-human primates (NHPs). NHPs were trained to read the direction indicated by a peripheral visual stimulus while maintaining fixation at the center, and report the direction of the cue by performing a saccadic eye movement into the same direction following a delay.

A collaborative interdisciplinary approach for trigger finger management.

Background: Stenosing tenosynovitis, or trigger finger, is a common cause of hand disability. This study outlines a trigger finger management protocol that redirects referrals for surgical consultations to conservative management first.

Purpose: The primary outcome variable was the protocol endpoint based on the resolution of trigger finger symptoms (i.