Bi-allelic variants in DAP3 result in reduced assembly of the mitoribosomal small subunit with altered apoptosis and a Perrault-syndrome-spectrum phenotype.

The mitochondrial ribosome (mitoribosome) synthesizes 13 protein subunits of the oxidative phosphorylation system encoded by the mitochondrial genome. The mitoribosome is composed of 12S rRNA, 16S rRNA, and 82 mitoribosomal proteins encoded by nuclear genes. To date, variants in 12 genes encoding mitoribosomal proteins are associated with rare monogenic disorders and frequently show combined oxidative phosphorylation deficiency.

Methodological Challenges in Randomized Controlled Trials of mHealth Interventions: Cross-Sectional Survey Study and Consensus-Based Recommendations.

Background: Mobile health (mHealth) refers to using mobile communication devices such as smartphones to support health, health care, and public health. mHealth interventions have their own nature and characteristics that distinguish them from traditional health care interventions, including drug interventions. Thus, randomized controlled trials (RCTs) of mHealth interventions present specific methodological challenges.

Radiographic and visual response to the type II RAF inhibitor tovorafenib in children with relapsed/refractory optic pathway glioma in the FIREFLY-1 trial.

Background: Due to their anatomical locations, optic pathway gliomas (OPGs) can rarely be cured by resection. Given the importance of preserving visual function, we analyzed radiological and visual acuity (VA) outcomes for the type II RAF inhibitor tovorafenib in the OPG subgroup of the phase 2 FIREFLY-1 trial.

Methods: FIREFLY-1 investigated the efficacy (arm 1, n=77), safety, and tolerability (arms 1/2) of tovorafenib (420 mg/m2 once weekly; 600 mg maximum) in patients with BRAF-altered relapsed/refractory pediatric low-grade glioma (pLGG).

40 Hz Visual Stimulation During Sleep Evokes Neuronal Gamma Activity in NREM and REM Stages.

Study Objectives: Visual stimulation at 40 Hz is being tested as a non-invasive approach against dementias such as Alzheimer's disease. Applying it during sleep could increase convenience, duration, and efficacy of stimulation. Here, we tested the feasibility of 40 Hz visual stimulation during sleep in a proof-of-concept study.

The Clinical Relevance of Prior Metabolic and Bariatric Surgery in Alcohol-Related Liver Disease in a Nationwide Belgian Liver Transplant Population.

Background And Aims: Patients with a history of metabolic and bariatric surgery (MBS) are susceptible to developing alcohol use disorder. Outcome after transplantation for alcohol-related liver disease (ALD) has not been studied in-depth.

Methods: We included adult patients who underwent a liver transplantation (LT) in Belgium between 1 January 2013 and 31 December 2022 for ALD.

3D analysis of soft tissue dimensional changes after dental implant placement with butt-joint vs. conical connection: a 12-month randomized control trial.

Purpose: to quantify the soft tissue dimensional changes after single-gap implant placement, during healing abutment and crown delivery phase for butt-joint and conical implant-abutment connection type.

Methods: forty patients were enrolled in the study and received randomly allocated implants with butt-joint and conical implant-abutment connection type. A standard healing abutment was placed after 6 months for two weeks.

Exploring the implementation of a novel, transdiagnostic, hybrid ecological momentary intervention for improving resilience in youth (EMIcompass): A process evaluation in the realist framework.

Objectives: Previous research indicates that the hybrid compassion-focused intervention EMIcompass may reduce stress reactivity and improve quality of life. Our aim was to investigate what components of the intervention work for whom, how, and under which circumstances to contribute to the enhancement of resilience.

Methods: We conducted a process evaluation using a realist framework.

Food Allergy Genetics and Epigenetics: A Review of Genome-Wide Association Studies.

In this review, we provide an overview of food allergy genetics and epigenetics aimed at clinicians and researchers. This includes a brief review of the current understanding of genetic and epigenetic mechanisms, inheritance of food allergy, as well as a discussion of advantages and limitations of the different types of studies in genetic research. We specifically focus on the results of genome-wide association studies in food allergy, which have identified 16 genetic variants that reach genome-wide significance, many of which overlap with other allergic diseases, including asthma, atopic dermatitis, and allergic rhinitis.

Trends of mapping knowledge structure and themes of cancer sonodynamic therapy: a text-mining study.

Background: Sonodynamic therapy (SDT) is a non-invasive cancer treatment technique stemming from photodynamic therapy (PDT) and has garnered escalated interest among researchers in recent years. Numerous aspects of cancer SDT remain contentious, and the global research trajectory within this domain remains insufficiently explored. This study seeks to delineate the comprehensive knowledge framework, developmental trends, and pivotal research focal points concerning cancer SDT.

Evaluating the Impact of Laundry Detergents on the Skin Microbiome of Atopic Dermatitis Patients-A Clinical Study.

Background And Aims: Remnants of laundry detergent ingredients are suspected to be in constant contact with the skin. Allergy sufferers need assurance that the chemicals in everyday products do not cause such disruption. The purpose of this study was to evaluate the effects and tolerability of common laundry detergents on the skin microbiome in individuals with atopic dermatitis.

The role of cognitive motivation and self-regulation in coping with occupational demands.

Cognitive motivation (COM) in conjunction with self-regulation (SR) was demonstrated to be positively linked to mental health in educational and clinical contexts. We introduce COM and SR in the occupational context and hypothesize these traits-based on their conceptual link to hardiness - to counteract health-risking stressors. Data from two large cross-sectional studies in Germany comprise a sample of 1,022 psychosomatic rehabilitation in-patients and a healthy sample of 298 employees of various occupations.

SGLT2-Inhibition in Patients With Alport Syndrome.

Introduction: Large-scale trials showed positive outcomes of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in adults with chronic kidney disease (CKD). Whether the use of SGLT2i is safe and effective in patients with the common hereditary CKD Alport syndrome (AS) has not yet been investigated specifically in larger cohorts.

Methods: This observational, multicenter, international study (NCT02378805) assessed 112 patients with AS after start of SGLT2i.

Definition of sinonasal and otological exacerbation in patients with primary ciliary dyskinesia: an expert consensus.

Background: Recurrent infections of the nose, sinuses and ears are common problems for people with primary ciliary dyskinesia. While pulmonary exacerbations in primary ciliary dyskinesia are defined, there is no definition for ear-nose-throat exacerbations, a potential outcome for research and clinical trials.

Methods: We set up an expert panel of 24 ear-nose-throat specialists, respiratory physicians, other healthcare professionals and patients to develop consensus definitions of sinonasal and otological exacerbations in children and adults with primary ciliary dyskinesia for research settings.

Diet, physical activity, and sleep in relation to postprandial glucose responses under free-living conditions: an intensive longitudinal observational study.

Background: It remains unclear what lifestyle behaviors are optimal for controlling postprandial glucose responses under real-world circumstances in persons without diabetes. We aimed to assess associations of diet, physical activity, and sleep with postprandial glucose responses in Asian adults without diabetes under free-living conditions.

Methods: We conducted an observational study collecting intensive longitudinal data using smartphone-based ecological momentary assessments, accelerometers, and continuous glucose monitors over nine free-living days in Singaporean men and women aged 21-69 years without diabetes.

Quantification and time course of subjective psychotropic and somatic effects of tetrahydrocannabinol - a prospective, single-blind, placebo-controlled exploratory trial in healthy volunteers.

Background: Cannabis is increasingly used and debates about the legalisation of the recreational use of cannabis are ongoing. In this prospective, placebo-controlled study in healthy volunteers not regularly consuming cannabis, subjective psychotropic and somatic effects after a single dose of intravenous THC were assessed and quantified over 48 h.

Methods: Twenty-five healthy volunteers received a single IV bolus of THC and 6 received normal saline.

Core outcome set of daily monitoring of gastrointestinal function in adult critically ill patients: a modified Delphi consensus process (COSMOGI).

Purpose: Gastrointestinal (GI) dysfunction is common in critically ill patients and associated with poor outcomes. There is a lack of standardised methods for daily monitoring of GI function. COSMOGI aimed to develop a Core Outcome Set (COS) for daily monitoring of GI function to improve consistency and comparability in future studies in critically ill patients.

Craving induction through virtual reality cue-exposure for patients with alcohol dependence in rehabilitation treatment.

New therapeutic approaches for alcohol dependence (AD) include virtual reality (VR)-based treatments offering scalable options for cue exposure (CE), a well-established strategy in cognitive behavioral therapy. This study aimed to evaluate the feasibility and tolerability of a new VR-CE paradigm. On an explorative basis, factors influencing the induction of craving were examined.

Efficient reinterpretation of rare disease cases using Exomiser.

Whole genome sequencing has transformed rare disease research; however, 50-80% of rare disease patients remain undiagnosed after such testing. Regular reanalysis can identify new diagnoses, especially in newly discovered disease-gene associations, but efficient tools are required to support clinical interpretation. Exomiser, a phenotype-driven variant prioritisation tool, fulfils this role; within the 100,000 Genomes Project (100kGP), diagnoses were identified after reanalysis in 463 (2%) of 24,015 unsolved patients after previous analysis for variants in known disease genes.

A biomathematical model of SARS-CoV-2 in Syrian hamsters.

When infected with SARS-CoV-2, Syrian hamsters (Mesocricetus auratus) develop moderate disease severity presenting key features of human COVID-19. We here develop a biomathematical model of the disease course by translating known biological mechanisms of virus-host interactions and immune responses into ordinary differential equations. We explicitly describe the dynamics of virus population, affected alveolar epithelial cells, and involved relevant immune cells comprising for example CD4+ T cells, CD8+ T cells, macrophages, natural killer cells and B cells.

The Reha-Toolbox project: Linking item subsets of three established rehabilitation PROMs to nine domains of the Patient Reported Outcomes Measurement Information System (PROMIS).

Objective: The overarching goal of the patient-reported outcomes measurement information system (PROMIS) is to standardize patient-reported outcomes (PROs) across settings and health conditions globally. Following this purpose, the Reha-Toolbox study aimed to link item subsets of the World Health Organization Disability Assessment Schedule (WHODAS 2.0), the Indicators of Rehabilitation Status (IRES-3), and the Hamburg Modules for the Assessment of Psychosocial Health (HEALTH-49) to the standardized metrics provided by PROMIS.

Rivastigmine interferes with the pharmacological activity of hydromethylthionine on presynaptic proteins in the line 66 model of frontotemporal dementia.

The negative interference of treatments between the acetylcholinesterase inhibitor rivastigmine and the tau aggregation inhibitor hydromethylthionine mesylate (HMTM) has been reported in Line 1 tau-transgenic mice, which overexpress a truncated species of tau protein that is found in the core of paired helical filaments in Alzheimer´s disease (AD). However, little is known about whether such interactions could affect synapses in mice overexpressing tau carrying pathogenic mutations. Here, we have used Line 66 (L66) mice which overexpress full-length human tau carrying the P301S mutation as a model in which tau accumulates in synapses.

Hemophagocytic lymphohistiocytosis in HIV-associated HHV8-positive multicentric castleman disease.

Objective: The clinical and laboratory characteristics of HHV8-associated Multicentric Castleman Disease (MCD) in people living with HIV (PLWH) overlap with those of Hemophagocytic Lymphohistiocytosis (HLH) disease and indeed the two diagnoses may co-exist. A risk-stratified treatment approach to MCD based on Rituximab immunotherapy for mild cases and chemo-immunotherapy for severe cases has been shown to yield excellent outcomes in PLWH. In contrast, HLH disease, previously known as secondary HLH, has a dismal prognosis even when promptly treated according to guidelines.

Dextromethorphan inhibits collagen and collagen-like cargo secretion to ameliorate lung fibrosis.

Excessive deposition of fibrillar collagen in the interstitial extracellular matrix (ECM) of human lung tissue causes fibrosis, which can ultimately lead to organ failure. Despite our understanding of the molecular mechanisms underlying the disease, no cure for pulmonary fibrosis has yet been found. We screened a drug library and found that dextromethorphan (DXM), a cough expectorant, reduced the amount of excess fibrillar collagen deposited in the ECM in cultured primary human lung fibroblasts, a bleomycin mouse model, and a cultured human precision-cut lung slice model of lung fibrosis.