A European Survey to Identify Challenges in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease.

Background And Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe subtype, metabolic dysfunction-associated steatohepatitis (MASH), are highly prevalent and strongly associated with obesity and type 2 diabetes (T2D). This study sought to identify challenges to the diagnosis, treatment and management of people living with MASLD and MASH and understand the key barriers to adopting relevant clinical guidelines.

Methods: A real-world, cross-sectional study (BARRIERS-MASLD) consisting of a quantitative survey and qualitative interviews of physicians in France, Germany, Italy, Spain and the United Kingdom was conducted from March to September 2023.

Anticipatory smooth pursuit eye movements scale with the probability of visual motion: The role of target speed and acceleration.

Sensory-motor systems can extract statistical regularities in dynamic uncertain environments, enabling quicker responses and anticipatory behavior for expected events. Anticipatory smooth pursuit eye movements (aSP) have been observed in primates when the temporal and kinematic properties of a forthcoming visual moving target are fully or partially predictable. To investigate the nature of the internal model of target kinematics underlying aSP, we tested the effect of varying the target kinematics and its predictability.

The intriguing role of L-cysteine in the modulation of chiroplasmonic properties of chiral gold nano-arrows.

Developing chiral plasmonic nanostructures represents a significant scientific challenge due to their multidisciplinary potential. Observations have revealed that the dichroic behavior of metal plasmons changes when chiral molecules are present in the system, offering promising applications in various fields such as nano-optics, asymmetric catalysis, polarization-sensitive photochemistry and molecular detection. In this study, we explored the synthesis of plasmonic gold nanoparticles and the role of cysteine in their chiroplasmonic properties.

How Residual Fertility Impacts the Efficiency of Crop Pest Control by the Sterile Insect Technique.

The sterile insect technique (SIT) is a biological control technique based on mass-rearing, radiation-based sterilization that can induce fitness costs, and releases of the pest species targeted for population control. Sterile matings, between females and sterilized males, can reduce the overall population growth rate and cause a fall in population density. However, a proportion of irradiated males may escape sterilization, resulting in what is called residual fertility.

Sex Differences in the Incidence of Sudden Cardiac Arrest/Death in Competitive Athletes: A Systematic Review and Meta-analysis.

Background: Although many studies have demonstrated a lower incidence of sudden cardiac arrest or death (SCA/D) in female athletes than in male, there is limited understanding of the specific underlying causes.

Objective: This systematic review aimed to assess the disparities in SCA/D incidence between male and female competitive athletes and explore the associated etiologies.

Methods: A comprehensive search was conducted for retrospective and prospective studies examining SCA/D incidence in male and female athletes.

Right-censored models by the expectile method.

Based on the expectile loss function and the adaptive LASSO penalty, the paper proposes and studies the estimation methods for the accelerated failure time (AFT) model. In this approach, we need to estimate the survival function of the censoring variable by the Kaplan-Meier estimator. The AFT model parameters are first estimated by the expectile method and afterwards, when the number of explanatory variables can be large, by the adaptive LASSO expectile method which directly carries out the automatic selection of variables.

Modelling the Impact of HIF on Metabolism and the Extracellular Matrix: Consequences for Tumour Growth and Invasion.

The extracellular matrix (ECM) is a complex structure involved in many biological processes with collagen being the most abundant protein. Density of collagen fibers in the matrix is a factor influencing cell motility and migration speed. In cancer, this affects the ability of cells to migrate and invade distant tissues which is relevant for designing new therapies.

A Qualitative Approach to Quality of Life in Fibrous Bone Dysplasia /McCune Albright Syndrome: Looking Beyond Quantitative Analysis.

This study explores FD/MAS patient's perceptions about their disease and its impact on their quality of life. We have evaluated quality of life (QoL) in French Fibrous Dysplasia/MacCune-Albright Syndrome (FD/MAS) patients using a qualitative approach with focus groups to explore perceptions, symptoms and limitations associated with FD/MAS and a quantitative method with the Short Form-36 (SF36) to quantify QoL. Focus groups revealed the heterogeneity of FD forms and allowed for understanding the reasons of reduced QoL.

Anti-PD1-/PDL1-induced chronic intestinal pseudo-obstruction: three cases treated with vedolizumab after corticosteroid failure with mixed results.

Immune checkpoint inhibitors (ICI), i.e., anti-PD1/PDL1 and anti-CTLA-4, have reshaped the prognosis of many cancers.

Basic Science and Pathogenesis.

This is a maximal intensity projection of CA1 pyramidal cell transfected with plasmid with the reporter GFP using single cell electroporation technique. In this particular case the organotypic slices were prepared from p5-7 pups in a tissue chopper (McIlwain). And maintained in MEM bases media with added glutamax with a change in 2 alternative dyas at 37°C and 5% CO for 4 days in-vitro (DIV) before electroporating with a glass pipette of 7-10mΩ resistance by applying 4 square pulses of -ve voltage of -2.

Mapping emissions in Cyprus using TROPOMI observations: evaluation of the flux-divergence scheme using multiple parameter sets.

The production of nitrogen oxides (NO = NO + NO ) is substantial in urban areas and from fossil fuel-fired power plants, causing both local and regional pollution, with severe consequences for human health. To estimate their emissions and implement air quality policies, authorities often rely on reported emission inventories. The island of Cyprus is de facto divided into two different political entities, and as a result, such emissions inventories are not systematically available for the whole island.

Role of the HGF/c-MET pathway in resistance to immune checkpoint inhibitors in advanced non-small cell lung cancer.

Most of advanced non-small cell lung cancer (NSCLC) patients will experience tumor progression with immunotherapy (IO). Preliminary data suggested an association between high plasma HGF levels and poor response to IO in advanced NSCLC. Our study aimed to evaluate further the role of the HGF/MET pathway in resistance to IO in advanced NSCLC.

Basic Science and Pathogenesis.

Background: Memory consolidation is an essential process for our everyday lives that is severely disrupted in Alzheimer's Disease (AD). Memories are initially encoded in the hippocampus before being consolidated in the neocortex by synaptic plasticity processes that depend on protein synthesis. However, how molecular pathways affect synaptic signalling during memory consolidation in health and disease is unclear.

Basic Science and Pathogenesis.

Background: BIN1 is a major susceptibility gene for AD and BIN1 protein interacts with Tau. However, the contribution of BIN1 and its isoforms to AD pathogenesis remains unclear. We recently described that human BIN1 isoform1 (BIN1iso1) induces an accumulation of early endosome vesicles leading to neurodegeneration in Drosophila retina and that the early endosome size regulation was conserved in human induced neurons.

Basic Science and Pathogenesis.

Background: Recent studies highlight distinct patterns of cortical atrophy between amnestic (typical) and non-amnestic (atypical, with subtypes: behavioural, dysexecutive, logopenic and visuospatial) clinical phenotypes of Alzheimer's disease (AD). The current study aimed to assess regional MRI patterns of cortical atrophy across AD phenotypes, and their association with amyloid-beta (Aβ), phosphorylated tau (pTau), axonal degeneration (NfL) and microvascular deterioration (COLIV).

Method: Postmortem In-situ 3DT1 3T-MRI data was collected for 33 AD (17 typical, 16 atypical) and 16 control brain donors.

Basic Science and Pathogenesis.

Alzheimer's disease (AD) is the most common dementia in humans that today concerns 50 million individuals worldwide and will affect more than 100 million people in 2050. Except for familial AD cases (<5% of AD patients) for which AD pathology connects to mutations in critical genes involved in the processing of the amyloid precursor protein into neurotoxic Aß peptides, it remains unknown what provokes the overproduction and deposition of Aß peptides in the brain of sporadic AD cases (>95% of AD patients). Some nanosized materials, e.

Basic Science and Pathogenesis.

Background: Aging is the main risk factor of cognitive neurodegenerative diseases such as Alzheimer's disease, with epigenome alterations as a contributing factor, however, it is not clear which biological mechanisms are common or disease-specific. Here we investigated epigenomic/genomic signatures in the hippocampus of mouse models of aging and of tauopathy, an AD-related feature.

Methods: Aging was modelled by comparing 18-month- versus 3-month-old WT mice.

Basic Science and Pathogenesis.

Background: PhospholipaseC γ2 (PLCG2) is known to have direct link with genetic risk factors for Alzheimer's like dementia (AD). PLCG2 has been previously demonstrated to have association with Aß uptake through microglia. And mostly expressed in dentate gyrus (DG) network of hippocampus.

Basic Science and Pathogenesis.

Background: P-tau217 has emerged as a compelling alternative to long-established p-tau181 to accurately measure tau modifications in biofluids in response to brain Abeta and tau deposition in Alzheimer's disease (AD). Understanding the specificity and significance of p-tau217 changes over AD stages is critical to interpret its potential response to treatments against Abeta and tau aggregation.

Methods: We measured p-tau217 phosphorylation by mass spectrometry.

Basic Science and Pathogenesis.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare, hereditary cerebrovascular disease which causes stroke, complex migraine, and cognitive impairment. Given its monogenic nature, CADASIL is considered a 'pure' model of small vessel disease and vascular dementia. CADASIL is caused by NOTCH3 pathogenic variants with a broad resulting phenotypic spectrum.

Basic Science and Pathogenesis.

Background: Protein metabolism and turnover can be monitored using tracer methods, notably stable isotope labeling kinetics (SILK) based on 13C-leucine incorporation. This approach has been used in Alzheimer's disease, specifically analyzing the turnover in cerebrospinal fluid of biomarkers of interest, including amyloid peptides, leading to major pathophysiological insights (Nature medicine 12:856-861). This was achieved using immunoprecipitation mass spectrometry, which enables to track a small number of targets present in low concentration.

Basic Science and Pathogenesis.

Background: Amyloid-targeting antibodies have been shown to be remarkably effective at clearing amyloid plaques from the Alzheimer's disease (AD) brain. To date, preclinical assessments have used animal models that develop only amyloid pathology, whereas AD patients present with tau pathology, neuroinflammation, and other concurrent neuropathologies. Deciphering how successful anti-amyloid therapies impact the synergistic interplay of amyloid and tau will be critical in determining which secondary disease processes can be slowed, interrupted, or reversed by amyloid-targeting immunotherapies.

Basic Science and Pathogenesis.

Background: Over-representation of several health conditions (such as diabetes, hearing loss, etc) have been identified up to 15 years before Alzheimer's Disease (AD) diagnosis through the study of electronic health records [1]. Mechanisms underlying these associations remain elusive. We propose to study the associations between these co-pathologies (proxied by genetic risk scores), and the physiological and clinical evolution of AD patients.

Clinical Manifestations.

Future clinical trials targeting Alzheimer's disease (AD) on new disease modifying drugs necessitate a paradigm shift towards early identification of individuals at risk. Emerging evidence indicates that subtle alterations in language and speech characteristics may manifest concurrently with the progression of neurodegenerative disorders like AD. These changes manifest as discernible variations, assessable through semantic nuances, word choices, sentiment, grammar usage (linguistic features), and phonetic/acoustic traits (paralinguistic features).

Clinical Manifestations.

Background: While Alzheimer Disease (AD) patients' difficulty to recognize face identity (Werheid & Clare, 2007) has been mainly attributed to episodic and semantic memory impairments, these patients can also show abnormal difficulties at matching of unfamiliar faces for their identity, suggesting impaired perceptual function (Lavallée et al., 2016). However, since this latter evidence is based on explicit behavioural measures, the difficulties of AD patients can be due to many factors (e.