KRAS inhibitors: resistance drivers and combinatorial strategies.

In 1982, the RAS genes HRAS and KRAS were discovered as the first human cancer genes, with KRAS later identified as one of the most frequently mutated oncogenes. Yet, it took nearly 40 years to develop clinically effective inhibitors for RAS-mutant cancers. The discovery in 2013 by Shokat and colleagues of a druggable pocket in KRAS paved the way to FDA approval of the first covalently binding KRAS inhibitors, sotorasib and adagrasib, in 2021 and 2022, respectively.

Objective and Automated Facial Palsy Grading and Outcome Assessment After Facial Palsy Reanimation Surgery - A Prospective Observational Study.

Background: Facial palsy (FP) is a widespread condition affecting over 3 million people annually, with a complex etiology requiring tailored, multidisciplinary management. Despite advancements, there remains a lack of reliable, automated tools for objective pre- and postoperative assessment, limiting progress in treatment optimization. This study introduces the AI Research Metrics Model (CAARISMA ® ARMM) to evaluate FP severity and outcomes following microsurgical gracilis muscle transfer.

An improved matrix deposition technique for thin layer chromatography coupled to MALDI-TOF mass spectrometry (TLC-MALDI).

Analytical thin layer chromatography (TLC) is a simple yet powerful chromatographic technique that is widely used for the qualitative characterization of complex mixtures such as plant extracts. For their qualitative and visual characterisation, a large number of more or less specific colour reactions are at hand and numerous reference substances are available as well. However, the identification of extract components by colour and the comparison of retention times is not straightforward.

Nucleosomal asymmetry shapes histone mark binding and promotes poising at bivalent domains.

Promoters of developmental genes in embryonic stem cells (ESCs) are marked by histone H3 lysine 4 trimethylation (H3K4me3) and H3K27me3 in an asymmetric nucleosomal conformation, with each sister histone H3 carrying only one of the two marks. These bivalent domains are thought to poise genes for timely activation upon differentiation. Here, we show that asymmetric bivalent nucleosomes recruit repressive H3K27me3 binders but fail to enrich activating H3K4me3 binders, thereby promoting a poised state.

Expression of claudin-18.2 in cholangiocarcinoma: a comprehensive immunohistochemical analysis from a German tertiary centre.

Aims: Anti-claudin-18.2 (CLDN18.2) therapy was recently approved for the treatment of gastric or gastro-oesophageal junction adenocarcinoma.

Cancer Organoids as reliable disease models to drive clinical development of novel therapies.

On September 23-24 (2024) the 6th Workshop IRE on Translational Oncology, titled "Cancer Organoids as Reliable Disease Models to Drive Clinical Development of Novel Therapies," took place at the IRCCS Regina Elena Cancer Institute in Rome. This prominent international conference focused on tumor organoids, bringing together leading experts from around the world.A central challenge in precision oncology is modeling the dynamic tumor ecosystem, which encompasses numerous elements that evolve spatially and temporally.

Challenges and opportunities of acquiring cortical recordings for chronic adaptive deep brain stimulation.

Deep brain stimulation (DBS), a proven treatment for movement disorders, also holds promise for the treatment of psychiatric and cognitive conditions. However, for DBS to be clinically effective, it may require DBS technology that can alter or trigger stimulation in response to changes in biomarkers sensed from the patient's brain. A growing body of evidence suggests that such adaptive DBS is feasible, it might achieve clinical effects that are not possible with standard continuous DBS and that some of the best biomarkers are signals from the cerebral cortex.

Establishing an end-to-end workflow for SNSPD fabrication and characterization.

The outstanding performance of superconducting nanowire single-photon detectors (SNSPDs) has expanded their application areas from quantum technologies to astronomy, space communication, imaging, and LiDAR. As a result, there has been a surge in demand for these devices, that commercial products cannot readily meet. Consequently, more research and development efforts are being directed towards establishing in-house SNSPD manufacturing, leveraging existing nano-fabrication capabilities that can be customized and fine-tuned for specific needs.

Mesenchymal stromal cells reduce inflammation and improve lung function in a mouse model of cystic fibrosis lung disease.

Mesenchymal stromal cells (MSCs) are multipotent adult stem cells which possess immunomodulatory and repair capabilities. In this study, we investigated whether MSC therapy could modulate inflammation and lung damage in the lungs of Scnn1b-transgenic mice overexpressing the β-subunit of the epithelial sodium channel (β-ENaC), a model with features of Cystic Fibrosis lung disease. Human bone marrow derived MSC cells were intravenously delivered to mice, prior to collection of bronchoalveolar lavage (BALF) and tissue.

Real-world multicentre cohort study on choices and effectiveness of immunotherapies in NMOSD and MOGAD.

Background: Recurrent attacks in neuromyelitis optica spectrum disorders (NMOSDs) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can lead to severe disability. We aimed to analyse the real-world use of immunotherapies in patients with NMOSD and MOGAD, focusing on changes in treatment strategies, effects on attack rates (ARR) and risk factors for attacks.

Methods: This longitudinal registry-based cohort study included 493 patients (320 with aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive NMOSD (65%), 44 with AQP4-IgG seronegative NMOSD (9%) and 129 MOGAD (26%)) with 1247 treatments from 19 German and one Austrian centre from the registry of the neuromyelitis optica study group (NEMOS).

A Training for Parents Prevents Clinically Relevant Handling Errors in the Use of Long-Term Antiseizure Medication.

Background: Medication handling errors (ME) in long-term antiseizure medication (ASM) compromise patient safety. Training programs to prevent those errors by parents are scarce.

Patients: The intervention concept is designed for parents of children and adolescents aged 0-18 years with at least one long-term ASM.

Upregulation of haematopoetic cell kinase (Hck) activity by a secreted parasite effector protein (Ta9) drives proliferation of Theileria annulata-transformed leukocytes.

Reversible transformation of bovine leukocytes by the intracellular parasites Theileria annulata and Theileria parva is central to pathogenesis of the diseases they cause, tropical theileriosis and East Coast Fever, respectively. Parasite-dependent constitutive activation of major host transcription factors such as AP-1 (Activating Protein 1) and NF-κB (Nuclear Factor-Kappa B) sustains the transformed state. Although parasite interaction with host cell signaling pathways upstream of AP-1 have been studied, the precise contribution of Theileria encoded factors capable of modulating AP-1 transcriptional activity, and other infection-altered signaling pathways is not fully understood.

Automated 24-sector grid-map algorithm for prostate mpMRI improves precision and efficacy of prostate lesion location reporting.

Background: The Prostate Imaging-Reporting and Data System (PI-RADS) calls for reporting the prostate index lesion and the location within the transition (TZ) or peripheral zone (PZ) and location on a corresponding sector map. The aim of this study was to train a deep learning DL-based algorithm for automatic prostate sector mapping and to validate its' performance.

Methods: An automatic 24-sector grid-map (ASG) of the prostate was developed, based on an automatic zone-specific deep learning segmentation of the prostate.

Legacy effects of an invasive legume more strongly impact bacterial than plant communities in a Mediterranean-type ecosystem.

The impacts of invasive plants on ecosystem processes and functions may persist as "legacy effects" after their removal. Understanding these effects on native plant-soil interactions is critical for guiding ecological restoration efforts. This study examines the legacy effects of the invasive legume Acacia saligna (Labill.

Klebsiella pneumoniae Glycoconjugate Vaccine Leads Based on Semi-Synthetic O1 and O2ac Antigens.

Klebsiella pneumoniae (KP) is a common opportunistic pathogen that emerged as a new critical threat to human health, due to its hypervirulence and widespread resistance against many antibiotics, including carbapenems. Alternative intervention strategies such as vaccines are not available.  Cell-surface lipopolysaccharides (LPS) and capsular polysaccharides (CPS) are attractive targets for vaccine development.

Symptoms Prior to Diagnosis of Multiple Sclerosis in Individuals Younger Than 18 Years.

Importance: A growing body of literature suggests the presence of a prodromal period with nonspecific signs and symptoms before onset of multiple sclerosis (MS).

Objective: To systematically assess diseases and symptoms diagnosed in the 5 years before a first MS- or central nervous system (CNS) demyelinating disease-related diagnostic code in pediatric patients compared with controls without MS and controls with another immune-mediated disorder, juvenile idiopathic arthritis (JIA).

Design, Setting, And Participants: This population-based, matched case-control study included children and adolescents (aged <18 years) in Germany with statutory health insurance from January 2010 to December 2020.

Cacao agroforestry adoption by smallholder farmers and forest loss prevention in the Maya Golden Landscape, Belize.

Unsustainable land use practices have led to increased forest loss rates. Implementing cacao agroforestry can reduce forest loss by preventing the clear-cutting of forests for monoculture plantations. However, research is needed on its effectiveness in preventing forest loss and the factors influencing its adoption between full-time and part-time farmers.

Eating disorders and disordered eating symptoms in individuals at clinical high risk for psychosis: a systematic review and meta-analysis.

Background: Eating disorders (EDs) are among the least studied mental disorders in individuals at clinical high risk for psychosis (CHR-P). The primary aim (a) of this systematic review and meta-analysis was to identify factors predicting ED diagnoses in CHR-P individuals. The secondary aim (b) was providing a comprehensive clinical description of individuals with both CHR-P and EDs/ED-related symptoms.

A stratified treatment algorithm in psychiatry: a program on stratified pharmacogenomics in severe mental illness (Psych-STRATA): concept, objectives and methodologies of a multidisciplinary project funded by Horizon Europe.

Schizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, their clinical and psychosocial characteristics. Effective translation of theoretical knowledge into clinical practice is essential for achieving this goal.

Higher Versus Lower Protein Delivery in Critically Ill Patients: A Systematic Review and Bayesian Meta-Analysis.

Objectives: Recent multicenter trials suggest that higher protein delivery may result in worse outcomes in critically ill patients, but uncertainty remains. An updated Bayesian meta-analysis of recent evidence was conducted to estimate the probabilities of beneficial and harmful treatment effects.

Data Sources: An updated systematic search was performed in three databases until September 4, 2024.

Eating- and Weight-Related Disorders in the Armed Forces.

Background/objectives: Like in the general population, the prevalences of eating- and weight-related health issues in the armed forces are increasing. Relevant medical conditions include the eating disorders (EDs) anorexia nervosa, bulimia nervosa, binge eating disorder, and avoidant restrictive food intake disorder (ARFID), as well as body dysmorphic disorder, muscle dysmorphia, and the relative energy deficiency in sport (RED-S) syndrome.

Methods: We performed a narrative literature review on eating- and weight-related disorders in the armed forces.

Yes, I Can: The Interplay of Need for Cognition and Task Confidence in Cognitive Task Performance.

Need for Cognition (NFC) refers to the enjoyment of and the search for intellectual challenges. Although numerous studies suggest associations between NFC and cognitive performance, the processes and factors that may mediate the relationship are not yet well understood. Based on the literature suggesting that self-efficacy (SE) expectancies mediate the relationship between NFC and cognitive performance, we sought to investigate this relationship systematically under controlled laboratory conditions.

Does Students' Level of Intelligence Moderate the Relationship Between Socio-Economic Status and Academic Achievement?

The association between school students' social background and school achievement is well documented. Recent studies demonstrated that this association might be moderated by the level of cognitive potential. Based on these results, we recruited an elementary school sample ( = 837) and an adolescent sample at the end of their compulsory school time ( = 2100) to investigate whether the associations between students' social background and their academic achievement in math and language arts were moderated by the level of their general cognitive competencies, i.