Park7 deletion leads to sex-specific transcriptome changes involving NRF2-CYP1B1 axis in mouse midbrain astrocytes.

Loss-of-function mutations in PARK7, encoding for DJ-1, can lead to early onset Parkinson's disease (PD). In mice, Park7 deletion leads to dopaminergic deficits during aging, and increased sensitivity to oxidative stress. However, the severity of the reported phenotypes varies.

Sport-specific differences in ACL injury, treatment and return to sports: Basketball.

Basketball is an intense, fast-paced game that is physically, highly demanding. Certain aspects of the game, such as the quick pivoting and cutting movements, predispose the players to serious knee injuries, including anterior cruciate ligament (ACL) tears. While an ACL tear can be a devastating condition for players, multidisciplinary management of the injury can provide the players with a reasonable chance to return to play at the pre-injury level.

Impact of molecular diagnostics and targeted cancer therapy on patient outcomes (MODIFY): a retrospective study of the implementation of precision oncology.

High-throughput genomic analyses are being implemented in clinical practice. MODIFY is a retrospective study of the first introduction of genomic profiling and molecular tumor boards in the country of Luxembourg. The primary objective was to assess whether patients derived a clinical benefit by measuring the percentage of patients who presented a progression-free survival (PFS) on matched therapy (PFS2) 1.

Genetically stratified Parkinson's disease with freezing of gait is related to specific pattern of cognitive impairment and non-motor dominant endophenotype.

Background: Freezing of gait (FOG) is an important milestone in the individual disease trajectory of people with Parkinson's disease (PD). Based on the of FOG etiology, the mechanism behind FOG implies higher executive dysfunction in PD. To test this model, we investigated the FOG-related phenotype and cognitive subdomains in idiopathic PD (iPD) patients without genetic variants linked to PD from the Luxembourg Parkinson's study.

Policy for transitioning childhood-onset growth hormone deficiency from pediatric to adult endocrine care in Belgium.

Growth hormone (GH) deficiency (GHD) in children and adolescents can vary in severity and origin, with GH replacement therapy proving effective in achieving genetic target height. Optimal outcomes are seen in those treated early and with higher doses. As patients approach adult height, priorities shift towards optimizing metabolic effects, maintaining body composition, and enhancing bone mass and muscle strength.

Socio-ethical challenges and opportunities for advancing diversity, equity, and inclusion in digital medicine.

Digitalization in medicine offers a significant opportunity to transform healthcare systems by providing novel digital tools and services to guide personalized prevention, prediction, diagnosis, treatment and disease management. This transformation raises a number of novel socio-ethical considerations for individuals and society as a whole, which need to be appropriately addressed to ensure that digital medical devices (DMDs) are widely adopted and benefit all patients as well as healthcare service providers. In this narrative review, based on a broad literature search in PubMed, Web of Science, Google Scholar, we outline five core socio-ethical considerations in digital medicine that intersect with the notions of equity and digital inclusion: (i) access, use and engagement with DMDs, (ii) inclusiveness in DMD clinical trials, (iii) algorithm fairness, (iv) surveillance and datafication, and (v) data privacy and trust.

Assessing the clinical utility of inertial sensors for home monitoring in Parkinson's disease: a comprehensive review.

This review screened 296 articles on wearable sensors for home monitoring of people with Parkinson's Disease within the PubMed Database, from January 2017 to May 2023. A three-level maturity framework was applied for classifying the aims of 59 studies included: demonstrating technical efficacy, diagnostic sensitivity, or clinical utility. As secondary analysis, user experience (usability and patient adherence) was evaluated.

Iron-sulfur cluster loss in mitochondrial CISD1 mediates PINK1 loss-of-function phenotypes.

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra of the midbrain. Familial cases of PD are often caused by mutations of PTEN-induced kinase 1 (PINK1) and the ubiquitin ligase Parkin, both pivotal in maintaining mitochondrial quality control. CISD1, a homodimeric mitochondrial iron-sulfur-binding protein, is a major target of Parkin-mediated ubiquitination.

Dopamine Pathway and Parkinson's Risk Variants Are Associated with Levodopa-Induced Dyskinesia.

Background: Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including GBA1 and LRRK2.

Objectives: Our goal was to investigate the effects of genetic variants on risk and time to LID.

[Chat messenger use in the care of patients with Parkinson's disease].

Background: The demand for chat messaging apps for communication between physicians, therapists and patients is increasing. The expectations for this form of communication and uncertainties regarding introduction and use are heterogeneous.

Objective: The implementation of chat messengers in the care of patients with Parkinson's disease should be facilitated by recommendations regarding introduction and usage.

Levodopa-induced dyskinesia in Parkinson's disease: Insights from cross-cohort prognostic analysis using machine learning.

Background: Prolonged levodopa treatment in Parkinson's disease (PD) often leads to motor complications, including levodopa-induced dyskinesia (LID). Despite continuous levodopa treatment, some patients do not develop LID symptoms, even in later stages of the disease.

Objective: This study explores machine learning (ML) methods using baseline clinical characteristics to predict the development of LID in PD patients over four years, across multiple cohorts.

Converging peripheral blood microRNA profiles in Parkinson's disease and progressive supranuclear palsy.

MicroRNAs act via targeted suppression of messenger RNA translation in the DNA-RNA-protein axis. The dysregulation of microRNA(s) reflects the epigenetic changes affecting the cellular processes in multiple disorders. To understand the complex effect of dysregulated microRNAs linked to neurodegeneration, we performed a cross-sectional microRNA expression analysis in idiopathic Parkinson's disease ( = 367), progressive supranuclear palsy ( = 35) and healthy controls ( = 416) from the Luxembourg Parkinson's Study, followed by prediction modelling, enriched pathway analysis and target simulation of dysregulated microRNAs using probabilistic Boolean modelling.

Progression subtypes in Parkinson's disease identified by a data-driven multi cohort analysis.

The progression of Parkinson's disease (PD) is heterogeneous across patients, affecting counseling and inflating the number of patients needed to test potential neuroprotective treatments. Moreover, disease subtypes might require different therapies. This work uses a data-driven approach to investigate how observed heterogeneity in PD can be explained by the existence of distinct PD progression subtypes.

Cognition and Other Non-Motor Symptoms in an At-Risk Cohort for Parkinson's Disease Defined by REM-Sleep Behavior Disorder and Hyposmia.

Background: REM-sleep behavior disorder (RBD) and other non-motor symptoms such as hyposmia were proposed by the Movement Disorder Society as research criteria for prodromal Parkinson's disease (P-PD). Global cognitive deficit was later added.

Objective: To compare non-motor symptoms, focusing on cognition, between a P-PD group and a matched control group.

Variant-specific effects of GBA1 mutations on dopaminergic neuron proteostasis.

Glucocerebrosidase 1 (GBA1) mutations are the most important genetic risk factors for Parkinson's disease (PD). Clinically, mild (e.g.

Which Comprehensive Geriatric Assessment (CGA) instruments are currently used in Germany: a survey.

Background: The Comprehensive Geriatric Assessment (CGA) records geriatric syndromes in a standardized manner, allowing individualized treatment tailored to the patient's needs and resources. Its use has shown a beneficial effect on the functional outcome and survival of geriatric patients. A recently published German S1 guideline for level 2 CGA provides recommendations for the use of a broad variety of different assessment instruments for each geriatric syndrome.

Comprehensive blood metabolomics profiling of Parkinson's disease reveals coordinated alterations in xanthine metabolism.

Parkinson's disease (PD) is a highly heterogeneous disorder influenced by several environmental and genetic factors. Effective disease-modifying therapies and robust early-stage biomarkers are still lacking, and an improved understanding of the molecular changes in PD could help to reveal new diagnostic markers and pharmaceutical targets. Here, we report results from a cohort-wide blood plasma metabolic profiling of PD patients and controls in the Luxembourg Parkinson's Study to detect disease-associated alterations at the level of systemic cellular process and network alterations.

Impact of Formalin- and Cryofixation on Raman Spectra of Human Tissues and Strategies for Tumor Bank Inclusion.

Reliable training of Raman spectra-based tumor classifiers relies on a substantial sample pool. This study explores the impact of cryofixation (CF) and formalin fixation (FF) on Raman spectra using samples from surgery sites and a tumor bank. A robotic Raman spectrometer scans samples prior to the neuropathological analysis.

Computational Assessment of Spectral Heterogeneity within Fresh Glioblastoma Tissue Using Raman Spectroscopy and Machine Learning Algorithms.

Understanding and classifying inherent tumor heterogeneity is a multimodal approach, which can be undertaken at the genetic, biochemical, or morphological level, among others. Optical spectral methods such as Raman spectroscopy aim at rapid and non-destructive tissue analysis, where each spectrum generated reflects the individual molecular composition of an examined spot within a (heterogenous) tissue sample. Using a combination of supervised and unsupervised machine learning methods as well as a solid database of Raman spectra of native glioblastoma samples, we succeed not only in distinguishing explicit tumor areas-vital tumor tissue and necrotic tumor tissue can correctly be predicted with an accuracy of 76%-but also in determining and classifying different spectral entities within the histomorphologically distinct class of vital tumor tissue.

Programme Dementia Prevention (pdp): A Nationwide Program for Personalized Prevention in Luxembourg.

Background: With continuously aging societies, an increase in the number of people with cognitive decline is to be expected. Aside from the development of causative treatments, the successful implementation of prevention strategies is of utmost importance to reduce the high societal burden caused by neurodegenerative diseases leading to dementia among which the most common cause is Alzheimer's disease.

Objective: The aim of the Luxembourgish "programme dementia prevention (pdp)" is to prevent or at least delay dementia in an at-risk population through personalized multi-domain lifestyle interventions.

Luxembourg Parkinson's study -comprehensive baseline analysis of Parkinson's disease and atypical parkinsonism.

Background: Deep phenotyping of Parkinson's disease (PD) is essential to investigate this fastest-growing neurodegenerative disorder. Since 2015, over 800 individuals with PD and atypical parkinsonism along with more than 800 control subjects have been recruited in the frame of the observational, monocentric, nation-wide, longitudinal-prospective Luxembourg Parkinson's study.

Objective: To profile the baseline dataset and to explore risk factors, comorbidities and clinical profiles associated with PD, atypical parkinsonism and controls.