C21ORF2 mutations point towards primary cilia dysfunction in amyotrophic lateral sclerosis.

Progressive loss of motor neurons is the hallmark of the neurodegenerative disease amyotrophic lateral sclerosis (ALS), but the underlying disease mechanisms remain incompletely understood. In this study, we investigate the effects of C21ORF2 mutations, a gene recently linked to ALS, and find that primary cilia are dysfunctional. Human patient-derived mutant C21ORF2 motor neurons have a reduced ciliary frequency and length.

High-Statistics Measurement of Collins and Sivers Asymmetries for Transversely Polarized Deuterons.

New results are presented on a high-statistics measurement of Collins and Sivers asymmetries of charged hadrons produced in deep inelastic scattering of muons on a transversely polarized ^{6}LiD target. The data were taken in 2022 with the COMPASS spectrometer using the 160 GeV muon beam at CERN, statistically balancing the existing data on transversely polarized proton targets. The first results from about two-thirds of the new data have total uncertainties smaller by up to a factor of three compared to the previous deuteron measurements.

Final COMPASS Results on the Transverse-Spin-Dependent Azimuthal Asymmetries in the Pion-Induced Drell-Yan Process.

The COMPASS Collaboration performed measurements of the Drell-Yan process in 2015 and 2018 using a 190  GeV/c π^{-} beam impinging on a transversely polarized ammonia target. Combining the data of both years, we present final results on the amplitudes of five azimuthal modulations, which correspond to transverse-spin-dependent azimuthal asymmetries (TSAs) in the dimuon production cross section. Three of them probe the nucleon leading-twist Sivers, transversity, and pretzelosity transverse-momentum dependent (TMD) parton distribution functions (PDFs).

Heartbeat evoked potentials and autonomic arousal during dissociative seizures: insights from electrophysiology and neuroimaging.

Introduction: Dissociative seizures often occur in the context of dysregulated affective arousal and entail dissociative symptoms such as a disintegration of bodily awareness. However, the interplay between affective arousal and changes in interoceptive processing at the onset of dissociative seizures is not well understood.

Methods: Using retrospective routine data obtained from video-electroencephalography telemetry in a university hospital epilepsy monitoring unit, we investigate ictal changes in cardiac indices of autonomic arousal and heartbeat evoked potentials (HEPs) in 24 patients with dissociative seizures.

Reverse shoulder arthroplasty with a 155° neck-shaft angle inlay implant design without reattachment of the subscapularis tendon results in satisfactory functional internal rotation and no instability: a cohort study.

Background: The aim of this study was to use the Activities of Daily Living which require Internal Rotation (ADLIR) questionnaire to assess the functional internal rotation in patients who had undergone reverse shoulder arthroplasty (RSA) without reattachment of the subscapularis (SSc) tendon at a minimum follow-up of 2 years. The secondary aim was to report the objective range of motion (ROM) and the rate of postoperative instability.

Materials And Methods: All consecutive primary RSA procedures without reattachment of the SSc tendon that were performed using a Delta Xtend prosthesis (an inlay system with a 155° neck-shaft angle) between January 2015 and December 2020 were identified to ensure a minimum follow-up of 2 years.

COPD basal cells are primed towards secretory to multiciliated cell imbalance driving increased resilience to environmental stressors.

Introduction: Environmental pollutants injure the mucociliary elevator, thereby provoking disease progression in chronic obstructive pulmonary disease (COPD). Epithelial resilience mechanisms to environmental nanoparticles in health and disease are poorly characterised.

Methods: We delineated the impact of prevalent pollutants such as carbon and zinc oxide nanoparticles, on cellular function and progeny in primary human bronchial epithelial cells (pHBECs) from end-stage COPD (COPD-IV, n=4), early disease (COPD-II, n=3) and pulmonary healthy individuals (n=4).

Sfrp1 inhibits lung fibroblast invasion during transition to injury-induced myofibroblasts.

Background: Fibroblast-to-myofibroblast conversion is a major driver of tissue remodelling in organ fibrosis. Distinct lineages of fibroblasts support homeostatic tissue niche functions, yet their specific activation states and phenotypic trajectories during injury and repair have remained unclear.

Methods: We combined spatial transcriptomics, multiplexed immunostainings, longitudinal single-cell RNA-sequencing and genetic lineage tracing to study fibroblast fates during mouse lung regeneration.

LncRNA U90926 is dispensable for the development of obesity-associated phenotypes in vivo.

Obesity is a global health problem characterized by excessive fat accumulation, driven by adipogenesis and lipid accumulation. Long non-coding RNAs (lncRNAs) have recently been implicated in regulating adipogenesis and adipose tissue function. Mouse lncRNA U90926 was previously identified as a repressor of in vitro adipogenesis in 3T3-L1 preadipocytes.

Skeletal Muscle Gene Expression Signatures of Obese High and Low Responders to Endurance Exercise Training.

Context: Exercise training is known to improve glucose tolerance and reverse insulin resistance in people with obesity. However, some individuals fail to improve or even decline in their clinical traits following exercise intervention.

Objective: This study focused on gene expression and DNA methylation signatures in skeletal muscle of low (LRE) and high responders (RES) to 8 weeks of supervised endurance training.

Nanoparticle-Exposure-Triggered Virus Reactivation Induces Lung Emphysema in Mice.

Nanoparticles (NPs) released from engineered materials or combustion processes as well as persistent herpesvirus infection are omnipresent and are associated with chronic lung diseases. Previously, we showed that pulmonary exposure of a single dose of soot-like carbonaceous NPs (CNPs) or fiber-shaped double-walled carbon nanotubes (DWCNTs) induced an increase of lytic virus protein expression in mouse lungs latently infected with murine γ-herpesvirus 68 (MHV-68), with a similar pattern to acute infection suggesting virus reactivation. Here we investigate the effects of a more relevant repeated NP exposure on lung disease development as well as herpesvirus reactivation mechanistically and suggest an avenue for therapeutic prevention.

A toxic gain-of-function mechanism in C9orf72 ALS impairs the autophagy-lysosome pathway in neurons.

Background: Motor neurons (MNs), which are primarily affected in amyotrophic lateral sclerosis (ALS), are a specialized type of neurons that are long and non-dividing. Given their unique structure, these cells heavily rely on transport of organelles along their axons and the process of autophagy to maintain their cellular homeostasis. It has been shown that disruption of the autophagy pathway is sufficient to cause progressive neurodegeneration and defects in autophagy have been associated with various subtypes of ALS, including those caused by hexanucleotide repeat expansions in the C9orf72 gene.

Redox state and altered pyruvate metabolism contribute to a dose-dependent metformin-induced lactate production of human myotubes.

Metformin-induced glycolysis and lactate production can lead to acidosis as a life-threatening side effect, but slight increases in blood lactate levels in a physiological range were also reported in metformin-treated patients. However, how metformin increases systemic lactate concentrations is only partly understood. Because human skeletal muscle has a high capacity to produce lactate, the aim was to elucidate the dose-dependent regulation of metformin-induced lactate production and the potential contribution of skeletal muscle to blood lactate levels under metformin treatment.

Arthroscopic posterior capsulolabral repair grants adequate outcomes in shoulders with posterior instability without glenoid cartilage lesions.

Introduction: Posterior capsulolabral repair (posterior Bankart) is effective to restore shoulder stability and relieve pain, though a recent meta-analysis reported recurrent instability in 9.5% of patients, and that only 62.7% were able to resume sports.

Differences in DNA methylation of HAMP in blood cells predicts the development of type 2 diabetes.

Objectives: Better disease management can be achieved with earlier detection through robust, sensitive, and easily accessible biomarkers. The aim of the current study was to identify novel epigenetic biomarkers determining the risk of type 2 diabetes (T2D).

Methods: Livers of 10-week-old female New Zealand Obese (NZO) mice, slightly differing in their degree of hyperglycemia and liver fat content and thereby in their diabetes susceptibility were used for expression and methylation profiling.

Insights into energy balance dysregulation from a mouse model of methylmalonic aciduria.

Inherited disorders of mitochondrial metabolism, including isolated methylmalonic aciduria, present unique challenges to energetic homeostasis by disrupting energy-producing pathways. To better understand global responses to energy shortage, we investigated a hemizygous mouse model of methylmalonyl-CoA mutase (Mmut)-type methylmalonic aciduria. We found Mmut mutant mice to have reduced appetite, energy expenditure and body mass compared with littermate controls, along with a relative reduction in lean mass but increase in fat mass.

Outcomes of Secondary Arthroscopic Distal Clavicle Resection for Shoulders With Symptomatic Acromioclavicular Joint Arthropathy After Isolated Rotator Cuff Repair With Complete Tendon Healing.

Background: Recent meta-analyses have advised against distal clavicle resection (DCR) as an adjuvant procedure during rotator cuff repair (RCR), whether performed routinely or in shoulders diagnosed with symptomatic acromioclavicular joint (ACJ) arthropathy. However, the efficacy of DCR as a secondary procedure in patients with persistent pain attributed to symptomatic ACJ arthropathy remains unknown.

Purpose: To evaluate outcomes of secondary DCR in patients with failed nonoperative treatment of symptomatic ACJ arthropathy after isolated RCR with complete tendon healing.

Acute and long-term exercise adaptation of adipose tissue and skeletal muscle in humans: a matched transcriptomics approach after 8-week training-intervention.

Background: Exercise exerts many health benefits by directly inducing molecular alterations in physically utilized skeletal muscle. Molecular adaptations of subcutaneous adipose tissue (SCAT) might also contribute to the prevention of metabolic diseases.

Aim: To characterize the response of human SCAT based on changes in transcripts and mitochondrial respiration to acute and repeated bouts of exercise in comparison to skeletal muscle.

Food Accessibility in the Suburbs of the Metropolitan City of Antwerp (Belgium): A Factor of Concern in Local Public Health and Active and Healthy Aging.

Population aging and declining birth rates are key demographic trends of the 21st century. While the overall life expectancy and healthy life years increase, the quality of life and functional capacity worsens due to non-communicable diseases strongly related to aging. Therefore, aging citizens are often vulnerable to food insecurity.

A pilot-study focusing on internal rotation after reverse total shoulder arthroplasty using the Activities of Daily Living which require Internal Rotation (ADLIR) score.

Background: Loss of internal rotation remains an issue after reverse total shoulder arthroplasty (RTSA). Our goal is to define the expected functional internal rotation after RTSA using the Activities of Daily Living which require Internal Rotation (ADLIR) score in a homogenous population of patients treated with RTSA.

Methods: 35 patients with a minimum follow-up of two years after RTSA were evaluated using the ADLIR and Constant-Murley questionnaires.

Dendritic Cells or Macrophages? The Microenvironment of Human Clear Cell Renal Cell Carcinoma Imprints a Mosaic Myeloid Subtype Associated with Patient Survival.

Since their initial description by Elie Metchnikoff, phagocytes have sparked interest in a variety of biologic disciplines. These important cells perform central functions in tissue repair and immune activation as well as tolerance. Myeloid cells can be immunoinhibitory, particularly in the tumor microenvironment, where their presence is generally associated with poor patient prognosis.