Oncogenic mutant KRAS inhibition through oxidation at cysteine 118.

Specific reactive oxygen species activate the GTPase Kirsten rat sarcoma virus (KRAS) by reacting with cysteine 118 (C118), leading to an electron transfer between C118 and nucleoside guanosine diphosphate (GDP), which causes the release of GDP. Here, we have mimicked permanent oxidation of human KRAS at C118 by replacing C118 with aspartic acid (C118D) in KRAS to show that oncogenic mutant KRAS is selectively inhibited via oxidation at C118, both in vitro and in vivo. Moreover, the combined treatment of hydrogen-peroxide-producing pro-oxidant paraquat and nitric-oxide-producing inhibitor N(ω)-nitro-l-arginine methyl ester selectively inhibits human mutant KRAS activity by inducing oxidization at C118.

Respiratory viruses affecting health and performance in equine athletes.

Some respiratory viruses can affect equine athletes, with acute respiratory clinical signs leading to a reduced ability to perform. The direct association between equine respiratory viruses and athletic performance is unclear in subclinically affected horses. This narrative review summarises the current evidence on respiratory viruses most commonly detected in performing horses, including equine herpesviruses, equine influenza virus, equine rhinitis viruses, equine arteritis virus, and equine adenovirus 1.

Viral and immune dynamics of genital human papillomavirus infections in young women with high temporal resolution.

Human papillomavirus (HPV) infections drive one in 20 new cancer cases, exerting a particularly high burden on women. Most anogenital HPV infections are cleared in less than two years, but the underlying mechanisms that favour persistence in around 10% of women remain largely unknown. Notwithstanding, it is precisely this information that is crucial for improving treatment, screening, and vaccination strategies.

What does a verbal working memory task measure? The process-specific and age-dependent nature of attentional demands in verbal working memory tasks.

Most models of verbal working memory (WM) consider attention as an important determinant of WM. The detailed nature of attentional processes and the different dimensions of verbal WM they support remains, however, poorly investigated. The present study distinguished between attentional capacity (scope of attention) and attentional control (control of attention) and examined their respective role for two fundamental dimensions of verbal WM: the retention of item versus serial order information and the simple versus complex nature of WM tasks.

Determinants of adherence to obesity medication: A narrative review.

The increasing prevalence of obesity, complex nature of this chronic disease, and risks of developing obesity-related comorbidities outline the need for sustainable and effective management for people living with obesity. In addition to behavioral interventions, obesity medications (OMs) are increasingly considered an integral part of management of people living with obesity. OM adherence is essential to achieve the health benefits of these medications.

Maleic Acid-Butanol Pretreatment to Enhance Cellulose Accessibility for Enzymatic Hydrolysis and Ethanol Production from Oil Palm Empty Fruit Bunch.

Pretreatment of lignocellulosic biomass is crucial yet challenging for sustainable energy production. This study focuses on enhancing enzymatic accessibility of cellulose in oil palm empty fruit bunches by optimizing pretreatment parameters to improve glucose and ethanol yields while reducing fermentation inhibitors. It evaluates the impact of maleic acid concentrations on biorefinery processes.

Lower perturbational complexity index after transcranial magnetic stimulation in schizophrenia patients.

Background: Informational integration and differentiation of the cortex can be tested by methods such as the perturbational complexity index (PCI) combined with TMS-induced activity perturbation. The PCI is obtained by stimulating the cortex with TMS and measuring the resulting spatiotemporal cortical responses with high-density EEG.

Methods: We have compared PCI between 26 patients with schizophrenia (15 males), 15 of them First Episode (FE) (7 males), and 22 healthy controls (12 males).

A tailored substrate-based approach using focal pulsed field catheter ablation in patients with atrial fibrillation and advanced atrial substrate: Procedural data and 6-months success rates.

Background: Focal pulsed-field ablation (F-PFA) integrated in electroanatomical mapping (EAM) systems allows tailored lesion sets in patients with atrial fibrillation (AF).

Objective: To determine feasibility, safety and 6-months outcome of F-PFA for a tailored substrate-based catheter ablation (CA) approach in patients with AF and advanced atrial substrate.

Methods: Consecutive patients with AF and advanced atrial substrate treated by a F-PFA system (Cardiofocus) through contact-force sensing catheters integrated in EAM systems were prospectively enrolled.

Enhancing cognitive functions in aged dogs and cats: a systematic review of enriched diets and nutraceuticals.

With advancements in veterinary care and the growing recognition of pets as integral member of the family, the lifespans of dogs and cats have significantly increased, leading to a higher prevalence of age-related conditions, including cognitive dysfunction syndrome (CDS). CDS adversely impacts pets' quality of life and presents emotional and practical challenges for owners. Given its similarities to Alzheimer's disease in humans, CDS has gained attention as a target for nutrition-based interventions aimed at preserving cognitive function.

The One-step No-prep technique for non-invasive full-mouth rehabilitation of worn dentition using PICN CAD-CAM restorations: Up to 9-year results from a prospective and retrospective clinical study.

Objectives: To report up to 9-year results of a prospective and retrospective study on non-invasive full-mouth rehabilitation of worn dentition with PICN CAD-CAM restorations using the One-Step No-Prep technique. The secondary objective is to evaluate the influence of restoration thickness on fracture of restorations.

Methods: A total of 580 Vita Enamic restorations (218 anterior and 362 posterior; 260 monoblock (MO) and 320 multiColor (MC)) in 24 patients were clinically evaluated once a year (up 9 months to 9 years) according to FDI criteria.

Fine-tuning of gene expression through the Mettl3-Mettl14-Dnmt1 axis controls ESC differentiation.

The marking of DNA, histones, and RNA is central to gene expression regulation in development and disease. Recent evidence links N6-methyladenosine (mA), installed on RNA by the METTL3-METTL14 methyltransferase complex, to histone modifications, but the link between mA and DNA methylation remains scarcely explored. This study shows that METTL3-METTL14 recruits the DNA methyltransferase DNMT1 to chromatin for gene-body methylation.

Purification of mineral oil aromatic hydrocarbons and separation based on the number of aromatic rings using a liquid chromatography silica column. An alternative to epoxidation.

The analysis of mineral oil aromatic hydrocarbons (MOAH) in vegetable oils is currently associated with high uncertainty due to various factors ranging from sample preparation to data interpretation. One significant factor is the coelution of biogenic compounds of terpenic origin with the MOAH fraction during chromatographic analysis. The common purification method is epoxidation, a chemical reaction that changes the polarity of the interferences, allowing their separation from MOAH.

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.

Cannabidiol and Hydroxypropyl-β-Cyclodextrin for the Development of Deflated Spherical-Shaped Inhalable Powder.

In addition to the known therapeutic indications for cannabidiol, its administration by inhalation appears to be of great interest. Indeed, there is evidence of cannabidiol's efficacy in several physiological pathways, suggesting its potential for a wide range of applications for both local and systemic pulmonary administration like cancers. Significant advances in pulmonary drug delivery have led to innovative strategies to address the challenges of increasing the respirable fraction of drugs and standardizing inhalable products.

Upper limb functional testing: does age, gender, and sport influence performance?

Background: Musculoskeletal adaptations are common in overhead athletes. As they also are involved in injury prevention, there has been an increase in their evaluation through shoulder screening over the last years. However, for some evaluations, and especially for functional testing, there is a lack of normative values, which limits the interpretation of the values measured.

Compact and cGMP-compliant automated synthesis of [F]FSPG on the Trasis AllinOne™.

Background: (S)-4-(3-F-Fluoropropyl)-ʟ-glutamic acid ([F]FSPG) is a positron emission tomography radiotracer used to image system x, an antiporter that is upregulated in several cancers. Not only does imaging system x with [F]FSPG identify tumours, but it can also provide an early readout of response and resistance to therapy. Unfortunately, the clinical production of [F]FSPG has been hampered by a lack of robust, cGMP-compliant methods.

Unlocking the potential of azide-phosphine Staudinger reaction for the synthesis of poly(arylene iminophosphorane)s and materials therefrom.

Iminophosphoranes with the general formula (RP═NR') have great potential in synthetic chemistry as valuable precursors/intermediates in organic synthesis or as building blocks for various organic compounds. However, the synthetic approaches and conditions to prepare iminophosphoranes are still poorly understood, limiting the utility of this chemistry for organic materials. In this article, a simple and efficient synthesis of previously unattainable poly(arylene iminophosphoranes) is reported.

Bivalves as a Mercury Bioindicator: A National Isotopic Survey along the Coast of South Korea.

Mercury (Hg) is a contaminant that poses health risks for human populations relying on seafood consumption. To mitigate its impact, identifying and monitoring Hg sources have become priorities, notably under the Minamata Convention. Bivalves are commonly used as sentinels in contaminant biomonitoring but can accumulate Hg from diverse environmental media.

Voice Quality as Digital Biomarker in Bipolar Disorder: A Systematic Review.

Background: Voice analysis has emerged as a potential biomarker for mood state detection and monitoring in bipolar disorder (BD). The systematic review aimed to summarize the evidence for voice analysis applications in BD, examining (1) the predictive validity of voice quality outcomes for mood state detection, and (2) the correlation between voice parameters and clinical symptom scales.

Methods: A PubMed, Scopus, and Cochrane Library search was carried out by two investigators for publications investigating voice quality in BD according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements.

Contamination levels and distribution of persistent and non-persistent pollutants in paired hair, urine and serum samples from a Belgian non-occupationally exposed population.

Designing ideal human biomonitoring studies involves the selection of reliable markers of exposure in adequate biological matrix. Besides conventional matrices such as blood or urine, hair has been increasingly investigated as a promising noninvasive alternative. However, understanding the pollutant distribution between differing biological compartments is essential for reliable interpretation of data collected.

Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans.

IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. The absence of IKKα causes fetal encasement syndrome in humans, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and causes combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features.

A one health approach for integrated vector management monitoring and evaluation.

The French Agency for Food, Environmental and Occupational Health & Safety (Anses) has set up a multidisciplinary working group (WG) to develop an innovative One Health approach for the monitoring and evaluation of an integrated vector management system (IVMS) on a territorial scale. Four existing evaluation guidelines and methods have been combined into a semi-quantitative evaluation approach that takes into account all the dimensions of an integrated process. We propose a set of 34 criteria divided into three sections (objectives and management, implementation, integration) that correspond to the main functional components of an IVMS.

Severe dual fungal infection after bispecific antibody therapy: A case of invasive aspergillosis and mucormycosis in immunocompromised patient.

Bispecific antibody is a new treatment for hematological disease, especially for lymphoma, myeloma and acute lymphoblastic leukemia. This class of treatment presents the same kind of side effect as CAR-T cell which are immune-mediated. Nevertheless, infectious complication remains a major concerns with related mortality.