Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Real-world multicentre cohort study on choices and effectiveness of immunotherapies in NMOSD and MOGAD.

Background: Recurrent attacks in neuromyelitis optica spectrum disorders (NMOSDs) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can lead to severe disability. We aimed to analyse the real-world use of immunotherapies in patients with NMOSD and MOGAD, focusing on changes in treatment strategies, effects on attack rates (ARR) and risk factors for attacks.

Methods: This longitudinal registry-based cohort study included 493 patients (320 with aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive NMOSD (65%), 44 with AQP4-IgG seronegative NMOSD (9%) and 129 MOGAD (26%)) with 1247 treatments from 19 German and one Austrian centre from the registry of the neuromyelitis optica study group (NEMOS).

Symptoms Prior to Diagnosis of Multiple Sclerosis in Individuals Younger Than 18 Years.

Importance: A growing body of literature suggests the presence of a prodromal period with nonspecific signs and symptoms before onset of multiple sclerosis (MS).

Objective: To systematically assess diseases and symptoms diagnosed in the 5 years before a first MS- or central nervous system (CNS) demyelinating disease-related diagnostic code in pediatric patients compared with controls without MS and controls with another immune-mediated disorder, juvenile idiopathic arthritis (JIA).

Design, Setting, And Participants: This population-based, matched case-control study included children and adolescents (aged <18 years) in Germany with statutory health insurance from January 2010 to December 2020.

Relevance of Preoperative Cognitive Impairment for Predicting Postoperative Delirium in Surgical Medicine: A Prospective Cohort Study.

Background: Post-operative delirium is a dreaded complication after surgery in older patients. The identification of risk factors for delirium and comprehensive geriatric assessment is an extensive part of recent research. However, the preoperative assessment of risk factors, such as impaired cognition, is frequently not standardized.

Long-Term Safety and Effectiveness of Canakinumab in Patients with MKD/HIDS: Interim Analysis of the RELIANCE Registry.

Introduction: Interim analysis of the long-term safety and effectiveness of canakinumab, at a patient level, in the mevalonate kinase deficiency/hyperimmunoglobulin-D syndrome (MKD/HIDS) cohort of the RELIANCE registry.

Methods: From June 2018, the RELIANCE registry enrolled paediatric (aged ≥ 2 years) and adult patients (aged ≥ 18 years) with MKD/HIDS who were receiving canakinumab as part of their routine medical care. Safety, physician- and patient-reported measures of disease activity and dosing patterns were evaluated at baseline and every 6 months until end-of-study visit.

Psychosocial work stressors and mental health in Ph.D. students in Germany-Evidence from two cross-sectional samples.

Background: Ph.D. students have been shown to report a lower mental health status compared to the general population.

TKK130 is a 3-Hydroxy-Propanamidine (HPA) with Potent Antimalarial Activity and a High Barrier to Resistance.

Malaria continues to pose a significant burden on populations in endemic areas and requires innovative treatment options. Here, we report the synthesis and preclinical evaluation of the novel 3-hydroxypropanamidine (HPA) , which shows excellent antiplasmodial activity against drug-sensitive and -resistant strains. Moreover, in various human cell lines, the compound shows no cytotoxicity and excellent parasite selectivity.

Bayesian Reanalyses of the Trials TOMAHAWK and COACT.

Background: The timing of coronary angiography in patients with successfully resuscitated out-of-hospital cardiac arrest and missing ST-segment elevations on the electrocardiogram has been investigated in 2 large randomized controlled trials, TOMAHAWK (Angiography After Out-of-Hospital Cardiac Arrest Without ST-Segment Elevation) and COACT (Coronary Angiography After Cardiac Arrest Trial). Both trials found neutral results for immediate vs delayed/selective coronary angiography on short-term all-cause mortality. The TOMAHAWK trial showed a tendency towards harm with immediate coronary angiography, though not statistically significant with traditional frequentist methods.

Disturbed spatial WNT activation - a potential driver of the reticularized skin phenotype in Systemic Sclerosis (SSc).

Objectives: Little is known on the mechanisms necessary to maintain the physiological adult human skin integrity. This study aims to quantitatively describe anatomical changes in systemic sclerosis (SSc)-skin compared to controls and investigate the underlying mechanisms.

Methods: Skin morphology was histologically assessed in twenty-three SSc-patients, eighteen controls and fifteen patients with hypertrophic scars.

An international expert survey on the worldwide digitalization in psychiatry: Global findings from the WPA survey.

Background: The World Psychiatric Association (WPA) Working Group on Digital Psychiatry aims to digitally supplement, support and improve mental health and care literacy, acceptance and accessibility across WPA member countries and National Psychiatric Associations (NPAs). To help with this goal, the present study was set to explore first the global status of digital mental health and care across NPAs METHODS: An international expert survey on the digitalization level across all 145 WPA NPAs was electronically distributed through Qualtrics. Descriptive statistics were carried out on the global dataset.

Effect of feeding in elevated side-lying and paced bottle feeding on swallow-breathe coordination in healthy preterm infants - First results.

Background: Preterm infants face challenges in their suck-swallow-breathe coordination leading to an increased risk of aspiration. Key components of the swallowing process are present around 34 to 35 weeks postmenstrual age (PMA), but preterm infants fatigue early affecting timing, quality and efficiency in swallowing and prolonging breathing pauses. Feeding strategies need to address these specific challenges in suck-swallow-breathe coordination.

Novel type 2 diabetes prediction score based on traditional risk factors and circulating metabolites: model derivation and validation in two large cohort studies.

Background: We aimed to evaluate the incremental predictive value of metabolomic biomarkers for assessing the 10-year risk of type 2 diabetes when added to the clinical Cambridge Diabetes Risk Score (CDRS).

Methods: We utilized 86,232 UK Biobank (UKB) participants (recruited between 13 March 2006 and 1 October 2010) for model derivation and internal validation. Additionally, we included 4383 participants from the German ESTHER cohort (recruited between 1 July 2000 and 30 June 2002 for external validation).

SLP2 and MIC13 synergistically coordinate MICOS assembly and crista junction formation.

The MICOS complex, essential for cristae organization, comprises MIC10 and MIC60 subcomplexes, with MIC13 as a crucial subunit. mutations cause severe mitochondrial hepato-encephalopathy, cristae defects, and MIC10-subcomplex loss. We demonstrate that depletion of the mitochondrial protease YME1L in KO stabilizes MIC10-subcomplex, restoring MIC60-MIC10 interaction and crista junction (CJ) defects, indicating MIC13 is crucial for MIC10-subcomplex stabilization rather than MIC60-MIC10 bridging.

Physical activity and tobacco smoking in the German adult population.

Background: Physical inactivity and tobacco smoking remain the leading causes of morbidity and mortality worldwide. In Germany, smoking prevalence is high at around 30%, and only 45% achieve the WHO recommendation for physical activity (PA). Understanding how smoking and physical inactivity co-occur can inform interventions targeting these behaviours.

Pericytes and Extracellular Vesicle Interactions in Neurovascular Adaptation to Chronic Arterial Hypertension.

Background: Chronic arterial hypertension restructures the vascular architecture of the brain, leading to a series of pathological responses that culminate in cerebral small-vessel disease. Pericytes respond dynamically to vascular challenges; however, how they manifest under the continuous strain of hypertension has not been elucidated.

Methods And Results: In this study, we characterized pericyte behavior alongside hypertensive states in the spontaneously hypertensive stroke-prone rat model, focusing on their phenotypic and metabolic transformation.

A multisite validation of brain white matter pathways of resilience to chronic back pain.

Chronic back pain (CBP) is a global health concern with significant societal and economic burden. While various predictors of back pain chronicity have been proposed, including demographic and psychosocial factors, neuroimaging studies have pointed to brain characteristics as predictors of CBP. However, large-scale, multisite validation of these predictors is currently lacking.

Built-in selection or confounder bias? Dynamic Landmarking in matched propensity score analyses.

Background: Propensity score matching has become a popular method for estimating causal treatment effects in non-randomized studies. However, for time-to-event outcomes, the estimation of hazard ratios based on propensity scores can be challenging if omitted or unobserved covariates are present. Not accounting for such covariates could lead to treatment estimates, differing from the estimate of interest.

Visual quality of life in NMOSD and MOGAD: profiles, dynamics and associations with ageing and vision.

Objective: In this multicentric study, we were interested in the vision-related quality of life and its association with visual impairment in neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in comparison to multiple sclerosis (MS) and healthy controls.

Methods: We analysed extracted data from the German NEMOS registry including National Eye Institute Visual Function Questionnaire (NEI-VFQ) scores, high and low contrast visual acuity (HCVA, LCVA), visually evoked potentials (VEP) and the scores for the expanded disability status scale (EDSS) and other neurological tests which assessed their disease-related impairment. The mean follow-up time of our patients was 1.

De-escalating and discontinuing disease-modifying therapies in multiple sclerosis.

The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains open and critical.

The New Tumour Biomarker miRNA-371-3p Influences Cisplatin Sensitivity of Testicular Germ Cell Tumour Cell Lines.

Cisplatin is used to treat a variety of malignancies, including testicular germ cell tumours (TGCTs). Although cisplatin-based chemotherapy yields high response rates, a subset of patients develop cisplatin resistance, limiting treatment options and worsening prognosis. Therefore, there is a high clinical need for new therapeutic strategies targeting cisplatin-resistant TGCTs.