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.

Good and bad indications for adjuvant radiotherapy after transoral laser microsurgery for laryngeal cancer.

Purpose Of Review: To summarize current evidence regarding the indication of adjuvant treatment after transoral laser microsurgery (TOLMS).

Recent Findings: Apart from well known risk factors, margins represent the key point in the decision-making. If margins are affected, additional treatment is mandatory.

The evolution of cooperation in spatial public goods game with tolerant punishment based on reputation threshold.

Reputation and punishment are significant guidelines for regulating individual behavior in human society, and those with a good reputation are more likely to be imitated by others. In addition, society imposes varying degrees of punishment for behaviors that harm the interests of groups with different reputations. However, conventional pairwise interaction rules and the punishment mechanism overlook this aspect.

Balancing landscape values and tourism choices: Integrating participatory mapping and the IPBES Values Typology.

The United Nations Educational, Scientific and Cultural Organization (UNESCO) Biosphere Reserves aim to balance nature and human coexistence, but increasing tourism challenges landscape management. The Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) stresses the importance of understanding stakeholder values for effective management of natural spaces through a typology of intrinsic, instrumental, and relational values. This study applies this IPBES typology to tourism preferences in the Archipelago Sea Biosphere Reserve (ABR) using Public Participation Geographic Information Systems (PPGIS).

Predictors of Gambling Severity Among Female Gamblers: Cross-Country Study with Spanish and Italian Clinical Population.

A large body of research has evidenced different risk factors associated with the severity of gambling. However, most of the research has been conducted with a male population, and consequently it has been inferred that the female population presents the same experiences and characteristics. Research on female gamblers is limited, with the result that their gambling-related problems are not effectively addressed.

First-line immune-based combinations or sunitinib in favorable-risk metastatic renal cell carcinoma: a real-world retrospective comparison from the ARON-1 study.

Introduction: Renal cell carcinoma (RCC) is one of the most common types of urogenital cancer. The introduction of immune-based combinations, including dual immune-checkpoint inhibitors (ICI) or ICI plus tyrosine kinase inhibitors (TKIs), has radically changed the treatment landscape for metastatic RCC, showing varying efficacy across different prognostic groups based on the International Metastatic RCC Database Consortium (IMDC) criteria.

Materials And Methods: This retrospective multicenter study, part of the ARON-1 project, aimed to evaluate the outcomes of favorable-risk metastatic RCC patients treated with immune-based combinations or sunitinib.

Associations between frailty and cognitive impairment in Parkinson´s disease: a cross-sectional study.

Background: The presence of frailty is common in people with Parkinson's disease, as is cognitive dysfunction. Previous research on frailty has focused on the physical aspects of the pathology.

Aims: To analyze the relationship between frailty and cognitive impairment in patients with Parkinson's disease and to know which disease characteristics are associated with frailty.

The economic burden of diabetes in spinal fusion surgery: a systematic review and meta-analysis.

Purpose: This study aimed at comparing the costs of spinal fusion surgery between patients with and without diabetes.

Methods: Following PRISMA guidelines, a systematic search of four databases was conducted. A meta-analysis was performed on comparative studies examining diabetic versus non-diabetic adults undergoing cervical/lumbar fusion in terms of cost.

Basic Science and Pathogenesis.

Background: Senescence is a cellular response to stress or damage leading to a state of irreversible growth arrest. As we age, the number of senescent cells increases and directly contributes to age-related conditions including cancer and neurodegenerative diseases. As a result, there is a growing interest to therapeutically target senescence either with drugs eliminating senescent cells (senolytics) or with strategies to modulate their secretory phenotype among others.

Clinical characteristics and risk factors for the acquisition of an enteric infection by Aeromonas spp. in patients with digestive or nephrological diseases.

The role of aeromonads as contributors to gastrointestinal pathology remains controversial. The aim of this study was to analyse the clinical characteristics and risk factors for the acquisition of an enteric infection by Aeromonas spp. in patients with digestive or nephrological diseases.

Spatial expression of fibroblast activation protein-α in clear cell renal cell carcinomas revealed by multiplex immunoprofiling analysis of the tumor microenvironment.

Clear cell renal cell carcinoma (ccRCC) is one of the most challenging neoplasms because of its phenotypic variability and intratumoral heterogeneity. Because of its variability, ccRCC is a good test bench for the application of new technological approaches to unveiling its intricacies. Multiplex immunofluorescence (mIF) is an emerging method that enables the simultaneous and detailed assessment of tumor and stromal cell subpopulations in a single tissue section.

Basic Science and Pathogenesis.

Background: Autosomal dominant Alzheimer's Disease (ADAD) represents around 0.5% of all AD cases, and is caused by mutations in PSEN1, PSEN2 and APP genes. Gene expression studies can be useful for unravelling the physiopathology of AD and identifying potential biomarkers.

Basic Science and Pathogenesis.

Background: Published data have highlighted associations between Alzheimer's disease (AD) susceptibility loci and AD-related brain changes. The amyloid imaging to prevent AD (AMYPAD) consortium is a European collaboration consisting of several parent cohorts, four of which had raw genotype array data available. We sought to integrate and harmonise the genetic data, calculate AD polygenic risk scores (PRS), and investigate their association with global amyloid deposition.

Basic Science and Pathogenesis.

Background: Down syndrome (DS) is strongly associated with Alzheimer's disease (AD), attributable to APP overexpression, displaying common features with early-onset AD (EOAD) and late-onset AD (LOAD) like Amyloid-β (Aβ) and tau pathology. Here, we evaluated the Aβ plaques proteome of DS, EOAD and LOAD.

Method: We used unbiased localized proteomics to analyze amyloid plaques and the adjacent plaque-devoid tissue ('AD non-plaque') from post-mortem paraffin-embedded tissues in three subtypes of AD (n = 20/group): DS (59.

Basic Science and Pathogenesis.

Background: Epigenetic mechanisms as a potential underlying pathogenic mechanism of neurodegenerative diseases have been the scope of several studies performed so far. However, there is a gap in analyzing different forms of early-onset dementia to minimize the effect of aging and the use of Lymphoblastoid cell lines (LCLs) as a possible disease model for earlier clinical phases.

Method: We performed a genome-wide DNA methylation analysis in 64 samples (from prefrontal cortex and lymphoblastoid cell lines) from Alzheimer's Disease (AD) and Frontotemporal dementia (FTD) using the Illumina Infinium MethylationEPIC V2.

Basic Science and Pathogenesis.

Background: In-vivo magnetic resonance imaging (MRI) has recently shown that patients with clinically diagnosed Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) exhibit degeneration of the cholinergic nucleus basalis of Meynert and its white matter (WM) projections through the cingulum and external capsule pathways. Here, we propose an imaging-pathologic validation study aimed at investigating cholinergic WM pathways using post-mortem MRI of autopsy-confirmed AD, Lewy body dementia (LBD), and other neurodegenerative diseases (OTH).

Method: We included 53 brain donors (34 AD, 10 LBD, and 9 OTH, mainly including frontotemporal lobe degeneration and vascular disease, Table 1).

Basic Science and Pathogenesis.

Background: Current evidence suggests that hippocampal subfields have partially different genetic architecture and may improve the sensitivity of the detection of Alzheimer's disease (AD). In this study, we investigated whether genetic predisposition to AD contributes to the accelerated rate of hippocampal volume atrophy across sex and AD stages and how this contribution is specifically driven by functional variants located in the APOE gene.

Methods: The study comprised 1,051 participants from ADNI cohort (75.

Basic Science and Pathogenesis.

Background: Alzheimer's Disease (AD) is a neurodegenerative proteinopathy in which Aβ can misfold and aggregate into seeds that structurally corrupt native proteins, mimicking a prion-like process. These amyloid aggregation and propagation processes are influenced by three factors: the origin of the Aβ seed, time of incubation and host. However, the mechanism underlying the differential effect of each factor is poorly known.

Basic Science and Pathogenesis.

Background: The increased vulnerability of Alzheimer's disease patients to severe SARS-CoV-2 infection raises crucial concerns, especially with the potential transition of the COVID-19 pandemic to an endemic state. Given the rising prevalence of Alzheimer's in an aging world-wide population, elucidating whether SARS-CoV-2 infection may induce or accelerate neurodegeneration becomes imperative.

Method: To investigate the neurodegenerative effects of SARS-CoV-2 infection, we generated brain organoids using human induced pluripotent stem lines from one non-demented control, one with sporadic Alzheimer's, and one with familial Alzheimer's.

Basic Science and Pathogenesis.

Background: An elevated neutrophil-lymphocyte ratio (NLR) has been associated with Alzheimer's disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into whether the NLR is directly linked with AD pathology or a result of underlying comorbidities.

Method: We explored the relationship between the NLR and AD biomarkers in the cerebrospinal fluid (CSF) of cognitively unimpaired (CU) subjects.

Basic Science and Pathogenesis.

Background: Murine studies have identified blood proteins that influence brain aging, but translating these findings to humans remains challenging. We used an innovative approach to investigate whether genetically predicted blood levels of proteins linked to brain aging in animal models are associated with cognitive performance in individuals at risk of Alzheimer's disease (AD) [Figure 1].

Method: Through systematic review, we identified 13 circulating proteins with an aging/rejuvenating effect on the mouse brain.

Integrated Analysis of Methylome and Transcriptome Responses to Exercise Training in Children with Overweight/Obesity.

We examined the effects of a 20-week exercise intervention on whole-blood genome-wide DNA methylation signature and its association with the exercise-induced changes in gene expression profiles in boys and girls with overweight/obesity (OW/OB). Twenty-three children (10.05 ± 1.

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: Preclinical Alzheimer's disease may be linked to impaired cerebral amyloid clearance. We aim to obtain dynamic parameters of cortical and ventricular clearance of C-PIB and compare them with CSF amyloid values in a population of healthy volunteers.

Method: We evaluated 8 healthy volunteers (4 men and mean age: 64.

Basic Science and Pathogenesis.

Background: The accumulation of misfolded tau proteins, an Alzheimer's disease (AD) hallmark, starts decades before the emergence of cognitive decline and clinical diagnosis. Autopsy studies support a predictable progression of tau pathology through large-scale systems. However, less is known about the specific progression patterns.