CDK5 interacts with MST2 and modulates the Hippo signalling pathway.

MST2 (STK3) is a major upstream kinase in the Hippo signalling pathway, an evolutionary conserved pathway in regulation of organ size, self-renewal and tissue homeostasis. Its downstream effectors are the transcriptional regulators YAP and TAZ. This pathway is regulated by a variety of factors, such as substrate stiffness or cell-cell contacts.

Detection of focal cortical dysplasia: Development and multicentric evaluation of artificial intelligence models.

Objective: Focal cortical dysplasia (FCD) is a common cause of drug-resistant focal epilepsy but can be challenging to detect visually on magnetic resonance imaging. Three artificial intelligence models for automated FCD detection are publicly available (MAP18, deepFCD, MELD) but have only been compared on single-center data. Our first objective is to compare them on independent multicenter test data.

Ultra-High Dose Rate Helium Ion Beams: Minimizing Brain Tissue Damage while Preserving Tumor Control.

Ultra-high dose rate radiotherapy with electrons and protons has shown potential for cancer treatment by effectively targeting tumors while sparing healthy tissues (FLASH effect). This study aimed to investigate the potential FLASH sparing effect of ultra-high-dose rate helium ion irradiation, focusing on acute brain injury and subcutaneous tumor response in a preclinical in vivo setting. Raster-scanned helium ion beams were used to compare the effects of standard dose rate (SDR at 0.

Proton Pump Inhibitor Use and Incident Cardiovascular Disease in Older Postmenopausal Women.

Background: Epidemiological studies have been inconsistent regarding an association between proton pump inhibitor (PPI) use and risk of primary cardiovascular disease (CVD) events.

Methods: We studied 85,189 postmenopausal women (mean age 63 years at baseline) without known CVD at enrollment into the Women's Health Initiative Observational Study (1993-1998). PPI use was determined from medication inventories at baseline and Year-3.

Solvation Dynamics of Thermoresponsive Polymer Films: The Influence of Salt Series in Water and Mixed Water/Methanol Atmosphere.

Understanding the salt effects on solvation behaviors of thermoresponsive polymers is crucial for designing and optimizing responsive systems suitable for diverse environments. In this work, the effect of potassium salts (CHCOOK, KCl, KBr, KI, and KNO) on solvation dynamics of poly(4-(N-(3'-methacrylamidopropyl)-N,N-dimethylammonio) butane-1-sulfonate) (PSBP), poly(N-isopropylmethacrylamide) (PNIPMAM), and PSBP-b-PNIPMAM films is investigated under saturated water and mixed water/methanol vapor via advanced in situ neutron/optical characterization techniques. These findings reveal that potassium salts enhance the films' hygroscopicity or methanol-induced swellability.

Cognitive-behavioural therapy for insomnia mechanism of action: Exploring the homeostatic K-complex involvement.

Investigating the mechanisms of action of cognitive-behavioural therapy for insomnia (CBT-I), the first-line treatment for chronic insomnia disorder (ID), can contribute to the overall understanding of insomnia and its treatment. To date, no study has examined the relationship between K-complexes (KC) and CBT-I, despite the known homeostatic and protective function of this relevant sleep brainwave. This retrospective multicentre study aims to explore the relationship between electroencephalographic (EEG) indices and CBT-I, with a particular focus on evaluating an index of sleep homeostasis identified by KC.

Systematic literature review and meta-analysis informing the EULAR points to consider on the initiation of targeted therapies in patients with inflammatory arthritis and a history of cancer.

Background: Targeted therapies have been associated with potential risk of malignancy, which is a common concern in daily rheumatology practice in patients with inflammatory arthritis (IA) and a history of cancer.

Objectives: To perform a systematic literature review to inform a Task Force formulating EULAR points to consider on the initiation of targeted therapies in patients with IA and a history of cancer.

Methods: Specific research questions were defined within the Task Force before formulating the exact research queries with a librarian.

2024 EULAR points to consider on the initiation of targeted therapies in patients with inflammatory arthritis and a history of cancer.

Background: Potential associations between targeted therapies and a new cancer in patients with inflammatory arthritis (IA) and a previous malignancy are a frequent concern in daily rheumatology practice.

Objectives: To develop points to consider (PTC) to assist rheumatologists when initiating a targeted therapy in the context of a previous malignancy.

Methods: Following EULAR standardised operating procedures, a task force met to define the research questions for a systematic literature review and to formulate the overarching principles (OPs) and the PTC.

Does Asthma Affect the Risk of Developing Breast Cancer?

Background: The role of the immune system in cancer defense is likely underappreciated. While there has been longstanding interest in the role of atopic diseases in cancer, only a few studies have tested this hypothesis.

Methods: We analyzed data from 202,055 women participating in the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHS II) to explore whether asthma is associated with breast cancer.

Past and future effects of climate on the metapopulation dynamics of a Northeast Atlantic seabird across two centuries.

Forecasting population responses to rapidly changing marine ecosystems requires mechanistic models integrating complex demographic processes, fitted to long time series, across large spatial scales. We used a Bayesian metapopulation model fit to colony census data and climatic covariates spanning 1900-2100 for all Northeast Atlantic colonies of an exemplar seabird, the Northern gannet (Morus bassanus) to investigate metapopulation dynamics under two climate scenarios. Fecundity varied non-linearly with near-surface air temperature and recruitment was depressed by sea surface temperature.

Coefficients in Taylor's law increase with the time scale of water clarity measurements in a global suite of lakes.

Identifying the scaling rules describing ecological patterns across time and space is a central challenge in ecology. Taylor's law of fluctuation scaling, which states that the variance of a population's size or density is proportional to a positive power of the mean size or density, has been widely observed in population dynamics and characterizes variability in multiple scientific domains. However, it is unclear if this phenomenon accurately describes ecological patterns across many orders of magnitude in time, and therefore links otherwise disparate observations.

Spatial proteomics reveals sirtuin 1 to be a determinant of T-cell infiltration in human melanoma.

Background: The tumour microenvironment significantly influences the clinical response of patients to therapeutic immune checkpoint inhibition (ICI), but a comprehensive understanding of the underlying immune-regulatory proteome is still lacking.

Objectives: To decipher targetable biologic processes that determine tumour-infiltrating lymphocytes (TiLs) as a cellular equivalent of clinical response to ICI.

Methods: We mapped the spatial distribution of proteins in TiL-enriched vs.

Balance between photoreduction efficiency, cofactor affinity, and allosteric coupling of halogenase flavoenzymes.

Flavin-dependent halogenases (FDHs) are promising candidates for the sustainable production of halogenated organic molecules by biocatalysis. FDHs require only oxygen, halide and a fully reduced flavin adenine dinucleotide (FADH) cofactor to generate the reactive HOX that diffuses 10 Å to the substrate binding pocket and enables regioselective oxidative halogenation. A key challenge for the application of FDHs is the regeneration of the FADH.

Value-Based Indication-Specific Pricing and Weighted-Average Pricing: Estimated Price and Cost Savings for Cancer Drugs.

Objectives: For US Medicare and Medicaid, single drug prices do not reflect the value of supplemental indications. Value-based indication-specific and weighted-average pricing has been suggested for drugs with multiple indications. Under indication-specific pricing, a distinct price is assigned to the differential value a drug offers in each indication.

Gender/Sex Preferences May Moderate the Relationship between Cohabitation and Sibling Incest.

The current study examined the extent to which gender/sex preference moderated the role of cohabitation on incest avoidance in an online sample of 1,623 adults with at least one opposite-sex sibling. Consistent with previous research, we found that longer cohabitation with a sibling was associated with decreased sexual interest in sexual contact between hypothetical siblings. We extended the literature by finding that gender/sex preferences contribute significantly to our understanding of incest avoidance.

Phenomenology of Psychedelic Experiences and Psychedelic-Associated Distressing Effects: Quantifying Subjective Experiences.

The range of phenomena that can be induced by psychedelic substances is broad and variable, including effects on perception, cognition, and emotion. The umbrella term "psychedelic phenomenology" is used to refer to a combination of altered experiential features, such as hallucinations or ego dissolution, which together constitute a psychedelic experience. However, there is no consensus on the set of alterations of consciousness that qualifies an altered state to be a "psychedelic state.

The Use of Cannabis-Based Medicine in Selected Neurological Disorders.

Cannabis-based medicine (CBM) is used in a wide variety of different neurological disorders. While the use of CBM in the treatment of pain, AIDS wasting, loss of appetite, and spasticity is well established, CBM application in movement disorders and neurodegenerative disorders is still an emerging topic. The purpose of this chapter is to summarize current evidence behind the use of CBM in selected neurological diseases, mainly movement and neurodegenerative disorders.

Sustained Vascular Inflammatory Effects of SARS-CoV-2 Spike Protein on Human Endothelial Cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with systemic inflammation and vascular injury, which contribute to the development of acute respiratory syndrome (ARDS) and the mortality of COVID-19 infection. Moreover, multiorgan complications due to persistent endothelial dysfunction have been suspected as the cause of post-acute sequelae of SARS-CoV-2 infection. Therefore, elucidation of the vascular inflammatory effect of SARS-CoV-2 will increase our understanding of how endothelial cells (ECs) contribute to the short- and long-term consequences of SARS-CoV-2 infection.

Metacontrast masking does not change with different display technologies: A comparison of CRT and LCD monitors.

Most vision labs have had to replace the formerly dominant CRT screens with LCDs and several studies have investigated whether changing the display type leads to changes in perceptual phenomena, since fundamental properties of the stimulation, e.g., the transition time between frames, differ between these different display technologies.

Preoperative CT-Scan Angiography Reconstruction Before Right Colectomy with Complete Mesocolon Excision: A Systematic Review and Meta-analysis.

Background: Complete mesocolon excision (CME) and central vascular ligation for right colonic cancers have been developed to improve oncological outcomes. However, it has been linked with a higher risk of morbidity and technical difficulties in operating near major vessels. This study investigated the impact of preoperative surgical planning utilizing CT reconstruction on surgical outcomes in right colectomy with CME.

Characterizing tick diversity among caprine hosts of Kerala, India: a phylogenetic study.

Background: Ticks are prominent vectors of numerous pathogens that adversely affect human and animal health. Monitoring tick population dynamics is key in developing ideal tick-borne disease surveillance systems and critical vector control programmes. This study aimed to conduct the morphological and molecular characterization of ticks infesting domesticated goats in Kerala, India.

Economic evaluation of critically ill adult CAR-T cell recipients-analysis from a healthcare payer perspective.

Background: CAR-T cell (chimeric antigen receptor T) therapy is now part of standard of care treatment of B‑cell lineage malignancies. Although it is an effective treatment, it comes along with adverse side effects and toxicities that may require intensive care therapy. The costs related to critical care therapy in critically ill patients after CAR‑T administration have not been evaluated.

Scoliosis development in 5q-spinal muscular atrophy under disease modifying therapies.

Purpose: 5q-spinal muscular atrophy (SMA) is a treatable neuromuscular disorder associated with scoliosis in up to 90% of patients. New SMA therapies could mark a paradigm shift in scoliosis management, but their effects on scoliosis development remain unclear. This study aims to observe scoliosis progression in the current treatment landscape to inform management strategies.

Membrane-embedded CdaA is required for efficient synthesis of second messenger cyclic di-AMP.

Cyclic di-adenylate monophosphate (cyclic di-AMP) is an important second messenger in microorganisms. Cyclic di-AMP regulates bacterial cell volume and turgor via control of potassium and compatible solute transport but is also involved in many other processes, including the activation of the metazoan innate immune response to bacterial infections. We compare the activity of full-length membrane-embedded CdaA, the enzyme that synthesizes cyclic di-AMP, with the water-soluble catalytic domain CdaA-DAC.