Exploitation of phylum-spanning omics resources reveals complexity in the nematode FLP signalling system and provides insights into flp-gene evolution.

Background: Parasitic nematodes significantly undermine global human and animal health and productivity. Parasite control is reliant on anthelmintic administration however over-use of a limited number of drugs has resulted in escalating parasitic nematode resistance, threatening the sustainability of parasite control and underscoring an urgent need for the development of novel therapeutics. FMRFamide-like peptides (FLPs), the largest family of nematode neuropeptides, modulate nematode behaviours including those important for parasite survival, highlighting FLP receptors (FLP-GPCRs) as appealing putative novel anthelmintic targets.

Electrolyzed Saline Prevents Virus Transmission in Dental Procedures: An In Vitro Study.

In dentistry, disinfection with antimicrobials is employed under different conditions and at different time points. During the COVID-19 pandemic, the use of disinfectant dental sprays was proposed, among other measures, to help prevent the transmission of infections during dental procedures that require highly effective antiseptics at particularly short contact times. The study aimed to evaluate the efficacy of electrolyzed saline (EOS) compared with other antiseptics in terms of the spread of enveloped and nonenveloped viruses by ultrasonic scaler (USS)-generated dental spray.

Nivolumab plus Ipilimumab in Microsatellite-Instability-High Metastatic Colorectal Cancer.

Background: Patients with microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) metastatic colorectal cancer have poor outcomes with standard chemotherapy with or without targeted therapies. Nivolumab plus ipilimumab has shown clinical benefit in nonrandomized studies of MSI-H or dMMR metastatic colorectal cancer.

Methods: In this phase 3 open-label trial, we randomly assigned patients with unresectable or metastatic colorectal cancer and MSI-H or dMMR status according to local testing to receive, in a 2:2:1 ratio, nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies.

An Assessment of Surface Contamination and Dermal Exposure to 5-Fluorouracil in Healthcare Settings by UPLC-MS/MS Using a New Atmospheric Pressure Ionization Source.

5-Fluorouracil (5-FU) is a well-known cytostatic drug, which is often used in cancer treatments. Yet, it is also a very dangerous compound for people who are occupationally exposed to it for a long time, such as pharmacy employees, nurses and cleaning staff. We aimed to improve and implement a LC-MS/MS method for 5-FU quantification on surface contamination samples collected with swabs in a pharmacy department and outpatient nursing station of a university hospital.

TKI resistance in brain metastasis: A CTLA4 state of mind.

Resistance to tyrosine kinase inhibitors (TKIs) in lung cancer brain metastasis (LCBM) remains a clinical challenge. Recently in Cancer Cell, Fu et al. reveal how TKIs reshape the immune microenvironment of LCBM and propose CTLA4 blockade as a promising strategy to overcome resistance.

A hands-on tutorial on quantitative structure-activity relationships using fully expressive graph neural networks.

This hands-on tutorial offers a practical guide to implementing Graph Neural Networks (GNNs) within the scope of Quantitative Structure-Activity Relationship (QSAR) modeling. Readers will be guided through a detailed, step-by-step process of applying a state-of-the-art GNN algorithm for activity predictions. It is anticipated that this practical tutorial will provide readers with sufficient knowledge to apply GNNs to their problems as well as to gain a good intuition of the underlying concepts.

The relation between visual orienting functions, visual perception, and functional vision in children with (suspected) cerebral visual impairment.

Background: Brain-based impairments in visual perception (VP), termed cerebral visual impairment (CVI), are heterogeneous.

Aims: To investigate relations between functional vision and (1) visual orienting functions (VOF) and (2) VP.

Methods And Procedures: Forty-four children (Males = 20; Mean age = 9y11m) with (suspected) CVI were tested with an adapted virtual toy box (vTB) paradigm (eye tracking visual search task (VST) and a recognition/memory task), VP tests, a preferential looking eye tracking (PL-ET) paradigm, and the Flemish cerebral visual impairment questionnaire.

Exploring the utility of complementary separations in liquid chromatography.

An alternative strategy is explored for the separation of samples by liquid chromatography (LC). Unlike traditional approaches that aim to resolve all components in a given sample within a single LC separation, the proposed strategy uses two or more distinct separations carried out with a different gradient program and/or using different separation chemistries i.e.

An evaluation of health-related quality of life and its relation with functional vision in children with cerebral visual impairment.

Background: Health-related Quality of Life (HRQOL) and its relation with functional vision is understudied in cerebral visual impairment (CVI).

Aims: Characterising HRQOL, comparing child self- and parent proxy-reports, and exploring relations with functional vision.

Methods And Procedures: Seventy-three children with CVI (n females = 33; n males = 40; Mean performance age = 7y2m) were included.

Global analysis of neuropeptide receptor conservation across phylum Nematoda.

Background: The phylum Nematoda is incredibly diverse and includes many parasites of humans, livestock, and plants. Peptide-activated G protein-coupled receptors (GPCRs) are central to the regulation of physiology and numerous behaviors, and they represent appealing pharmacological targets for parasite control. Efforts are ongoing to characterize the functions and define the ligands of nematode GPCRs, with already most peptide GPCRs known or predicted in Caenorhabditis elegans.

Exploiting the role of CSF NfL, CHIT1, and miR-181b as potential diagnostic and prognostic biomarkers for ALS.

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder characterized by relentless and progressive loss of motor neurons. A molecular diagnosis, supported by the identification of specific biomarkers, might promote the definition of multiple biological subtypes of ALS, improving patient stratification and providing prognostic information. Here, we investigated the levels of neurofilament light chain (NfL), chitotriosidase (CHIT1) and microRNA-181b (miR-181b) in the cerebrospinal fluid (CSF) of ALS subjects (N = 210) as well as neurologically healthy and neurological disease controls (N = 218, including N = 74 with other neurodegenerative diseases) from a large European multicentric cohort, evaluating their specific or combined utility as diagnostic and prognostic biomarkers.

Studying the Effect of Expectations on High-Frequency Electrical Stimulation-Induced Pain and Pinprick Hypersensitivity.

Negative expectations can increase pain, but can they promote the development of central sensitization? This study used an inert treatment and verbal suggestions to induce expectations of increased high-frequency electrical stimulation (HFS)-induced pain and assessed their effects on pain ratings during HFS and HFS-induced pinprick hypersensitivity. Fifty healthy volunteers were randomly allocated to either a control group (N = 25) or a nocebo group (N = 25). Participants in both groups received a patch containing water on the right forearm.

PPP2R5E: New gene potentially involved in specific learning disorders and myopathy.

Protein phosphatase 2A (PP2A) is a family of multifunctional enzymatic complexes crucial for cellular signalling, playing a pivotal role in brain function and development. Mutations in specific genes encoding PP2A complexes have been associated with neurodevelopmental disorders with hypotonia and high risk of seizures. In the current work, we present an individual with specific learning problems, motor coordination disorders, hypotonia and behavioural issues.

Indium-Iron Oxide Nanosized Solid Solutions as Photocatalysts for the Degradation of Pollutants under Visible Radiation.

A series of solid solutions of indium and iron oxides with different In/Fe ratios (InFeO, with x + y = 2) were synthesized in the form of nanoparticles (diameter of ca. 30-40 nm) with the purpose of generating enhanced photocatalysts with an intermediate band gap compared to those of the monometallic oxides, InO and FeO. The materials were prepared by co-precipitation from an aqueous solution of iron and indium nitrates and extensively characterized with a combination of techniques.

PP2A phosphatase regulatory subunit PPP2R3C is a new positive regulator of the hedgehog signaling pathway.

Cellular signaling pathways rely on posttranslational modifications (PTMs) to finely regulate protein functions, particularly transcription factors. The Hedgehog (Hh) signaling cascade, crucial for embryonic development and tissue homeostasis, is susceptible to aberrations that lead to developmental anomalies and various cancers. At the core of Hh signaling are Gli proteins, whose dynamic balance between activator (GliA) and repressor (GliR) states shapes cellular outcomes.

Diversely evolved xibalbin variants from remipede venom inhibit potassium channels and activate PKA-II and Erk1/2 signaling.

Background: The identification of novel toxins from overlooked and taxonomically exceptional species bears potential for various pharmacological applications. The remipede Xibalbanus tulumensis, an underwater cave-dwelling crustacean, is the only crustacean for which a venom system has been described. Its venom contains several xibalbin peptides that have an inhibitor cysteine knot (ICK) scaffold.

Burnout and predictive factors among medical students: a cross-sectional survey.

Background: Burnout is a growing problem in medical education, and is usually characterised by three dimensions: emotional exhaustion, cynicism, and reduced professional efficacy. Currently, the majority of burnout studies have been conducted in western high-income countries, overshadowing findings from low- and middle-income countries. Our objective is to investigate burnout and its associated predictive factors in Morocco, aiming to guide intervention strategies, while also assessing differences between the preclinical and clinical years.

Speech-Identification During Standing as a Multitasking Challenge for Young, Middle-Aged and Older Adults.

While listening, we commonly participate in simultaneous activities. For instance, at receptions people often stand while engaging in conversation. It is known that listening and postural control are associated with each other.

A personal view on the history of toxins: From ancient times to artificial intelligence.

Bioactive substances found in plants, microorganisms and animals have fascinated mankind since time immemorial. This review will focus on the progress that has been made over the centuries and our growing insights. The developments relate to both the discovery and characterization of novel bioactive substances, as well as the ceaseless implementation of refined techniques, the use of high-end instruments and breakthroughs in artificial intelligence with deep learning-based computational methods.

Assisted Active Learning for Model-Based Method Development in Liquid Chromatography.

In recent decades, there has been a growing interest in fully automated methods for tackling complex optimization problems across various fields. Active learning (AL) and its variant, assisted active learning (AAL), incorporating guidance or assistance from external sources into the learning process, play key roles in this automation by enabling the autonomous selection of optimal experimental conditions to efficiently explore the problem space. These approaches are particularly valuable in situations wherein experimentation is costly or time-consuming.

The genetics of amyotrophic lateral sclerosis.

Purpose Of Review: Amyotrophic lateral sclerosis (ALS) has a strong genetic basis, but the genetic landscape of ALS appears to be complex. The purpose of this article is to review recent developments in the genetics of ALS.

Recent Findings: Large-scale genetic studies have uncovered more than 40 genes contributing to ALS susceptibility.