Hepatocellular carcinoma hosts cholinergic neural cells and tumoral hepatocytes harboring targetable muscarinic receptors.

Background & Aims: Owing to unexplained interpatient variation and treatment failure in hepatocellular carcinoma (HCC), novel therapeutic approaches remain an urgent clinical need. Hepatic neurons, belonging to the autonomic nervous system (ANS), mediate liver/whole body crosstalk. Pathological innervation of the ANS has been identified in cancer, nurturing tumor stroma and conferring stronger carcinogenic properties.

When to stop immunotherapy for advanced melanoma: the emulated target trials.

Background: Immune checkpoint inhibitors (ICIs) have demonstrated their efficacy with a 7.5-year overall survival (OS) close to 50% for advanced stages. The design of clinical trials provides for treatment until progression or toxicity, or for a maximum duration of two years.

Psychiatric and cognitive symptoms of Parkinson's disease: A life's tale.

Introduction: Neuropsychiatric symptoms are highly prevalent in Parkinson's disease (PD) and significantly affect the quality of life of patients and their significant others. The aim of this work is to describe typical neuropsychiatric symptoms and their treatment.

Methods: This is a narrative opinion paper, illustrated by a fictional case report.

The clinically relevant MEK inhibitor mirdametinib combined with D-cycloserine and prediction error disrupts fear memory in PTSD models.

This study establishes mirdametinib as the first MEK inhibitor that can undergo clinical development for psychiatric indications such as post-traumatic stress disorder (PTSD). PTSD is characterized by persistent traumatic memories with limited effective treatment options. A body of evidence suggests that memory storage is dynamic and constantly updated through post-retrieval modification a process termed reconsolidation.

Clinical, Dosimetric and Radiomic Features Predictive of Lung Toxicity After (Chemo)Radiotherapy.

Background: Treatment of locally advanced non small cell lung cancer (LA-NSCLC) is based on (chemo)radiotherapy, which may cause acute lung toxicity: radiation pneumonitis (RP). Its frequency seems to increase by the use of adjuvant durvalumab therapy.

Aims: To identify clinical, dosimetric, and radiomic factors associated with grade (G)≥2 RP and build a prediction model based on selected parameters.

Predictors of poor outcome in acute stroke patients with posterior cerebral artery occlusion and medical management.

Background And Aims: The clinical evolution of acute ischemic stroke patients with isolated proximal posterior cerebral artery (PCA) occlusion treated with medical management alone has been poorly described. We aimed to determine the clinical and radiological factors associated with poor functional outcome in this population.

Methods: We conducted a multicenter international retrospective study of consecutive stroke patients with isolated occlusion of the first (P1) or second (P2) segment of PCA admitted within 6hrs from symptoms onset in 26 stroke centers in France, Switzerland and the USA, treated with best medical management alone.

Potential impact of tide-regulation barriers on the formation of methylmercury in the Venice Lagoon (Italy).

Methylmercury (MeHg), a neurotoxic pollutant, is formed mainly under anaerobiosis. The "Modulo Sperimentale Elettromeccanico" (MOSE), built to temporarily close the Venice Lagoon and protect the city from flooding, induces changes in the hydrological regime, reducing water circulation and decreasing in the dissolved oxygen concentrations of the lagoon. Our study shows the potential changes in sediment and overlying water physico-chemistry in a simulated MOSE closing-event by incubating sediment cores for 48 h in the laboratory and deploying benthic chambers.

Exploring aortic stiffness in aging mice: a comprehensive methodological overview.

Stiffening of the vascular network is associated with the early stages of vascular aging, leading to cardiovascular disorders (hypertension), renal failures, or neurodegenerative diseases (Alzheimer's). Unfortunately, many people remain undiagnosed because diagnostic methods are either unsuitable for a large population or unfamiliar to clinicians which favor the hypertension evaluation. In preclinical research, stiffness studies are often partially conducted.

Processing Fluency and Predictive Processing: How the Predictive Mind Becomes Aware of its Cognitive Limitations.

Predictive processing is an influential theoretical framework for understanding human and animal cognition. In the context of predictive processing, learning is often reduced to optimizing the parameters of a generative model with a predefined structure. This is known as Bayesian parameter learning.

Prevent hypoglycaemia when using automated insulin delivery systems in type 1 diabetes requires near normal glycaemic variability.

Aim: Although newer technologies of insulin delivery in type 1 diabetes have facilitated an improvement in glycaemic control the risk of hypoglycaemia remains a threat. Therefore, it is important to define the thresholds of glycaemic variability below which the risk of hypoglycaemia can be eliminated or at least minimized.

Methods: Randomized controlled trials conducted from 2017 to 2023 comparing Sensor-Augmented-Pumps and Augmented Insulin Delivery Systems (n = 16 and 22 studies, respectively) were selected.

An Extended Phenotype of PPP1R13L Cardiocutaneous Syndrome.

Dilated cardiomyopathy (DCM) is a rare disease in children and a leading cause of heart failure. There are numerous causes of DCM including genetic causes leading to isolated or syndromic presentations, with a wide variety of implicated genes. Among them, PPP1R13L is associated with a recessive syndrome leading to cardiac anomalies with skin, teeth, and hair abnormalities.

Plastid translocon recycling in dinoflagellates demonstrates the portability of complex plastids between hosts.

The plastids of photosynthetic organisms on land are predominantly "primary plastids," derived from an ancient endosymbiosis of a cyanobacterium. Conversely, the plastids of marine photosynthetic organisms were mostly gained through subsequent endosymbioses of photosynthetic eukaryotes generating so-called "complex plastids." The plastids of the major eukaryotic lineages-cryptophytes, haptophytes, ochrophytes, dinoflagellates, and apicomplexans-were posited to derive from a single secondary endosymbiosis of a red alga in the "chromalveloate" hypothesis.

A novel light-harvesting ZIF-9-TCPP as a promising FRET-based ratiometric fluorescence probe for sperm mobility.

The concentration of zinc ions in semen is significantly correlated with sperm viability and male fertility. In this work, a reliable ratiometric fluorescence probe (ZIF-9-TCPP) based on the efficient Förster resonance energy transfer (FRET) process between two luminophores, benzimidazole (BIM) and -tetra (4-carboxyphenyl) porphyrin (TCPP) for Zn detection has been constructed, where the emissions of BIM and TCPP are used as reference and detection signals. The proximity of BIM and TCPP in one framework (ZIF-9-TCPP) and the overlapped spectra between BIM and TCPP afford the attainment of a highly efficient FRET (around 90% efficiency).

Cardiolipin deficiency disrupts CoQ redox state and induces steatohepatitis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive disorder marked by lipid accumulation, leading to steatohepatitis (MASH). A key feature of the transition to MASH involves oxidative stress resulting from defects in mitochondrial oxidative phosphorylation (OXPHOS). Here, we show that pathological alterations in the lipid composition of the inner mitochondrial membrane (IMM) directly instigate electron transfer inefficiency to promote oxidative stress.

Lift-Out Specimen Preparation and Multiscale Correlative Investigation of Li-Ion Battery Electrodes Using Focused Ion Beam-Secondary Ion Mass Spectrometry Platforms.

Advanced characterization is paramount to understanding battery cycling and degradation in greater detail. Herein, we present a novel methodology of battery electrode analysis, employing focused ion beam (FIB) secondary-ion mass spectrometry platforms coupled with a specific lift-out specimen preparation, allowing us to optimize analysis and prevent air contamination. Correlative microscopy, combining electron microscopy and chemical imaging of a liquid electrolyte Li-ion battery electrode, is performed over the entire electrode thickness down to subparticle domains.

Diatom pyrenoids are encased in a protein shell that enables efficient CO fixation.

Pyrenoids are subcompartments of algal chloroplasts that increase the efficiency of Rubisco-driven CO fixation. Diatoms fix up to 20% of global CO, but their pyrenoids remain poorly characterized. Here, we used in vivo photo-crosslinking to identify pyrenoid shell (PyShell) proteins, which we localized to the pyrenoid periphery of model pennate and centric diatoms, Phaeodactylum tricornutum and Thalassiosira pseudonana.