Performance of the accelerated assessment of the European Medicines Agency.

Aims: In Europe, the European Medicines Agency (EMA) has an accelerated pathway to prioritize approval of medicines. Approved drugs are then assessed by Health Technology Assessment (HTA) bodies before being made available to patients. The aim of the study was to evaluate the characteristics of the drugs admitted to the EMA accelerated assessment (AA) and scrutinize the downstream HTA procedures regarding these medicines and the final assessment regarding added therapeutic value (ATV).

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

Residues of dry cow antimicrobials in colostrum and extended-spectrum and AmpC β-lactamaseproducing Escherichia coli in feces from young dairy calves.

The duration of excretion of dry cow antimicrobials is hard to predict and therefore the level of antimicrobial residues in colostrum can differ considerably between cows. The feeding of colostrum with antimicrobial residues to newborn calves may lead to antimicrobial resistance in calves. The aim of this study was to quantify the prevalence and residue level of dry cow antimicrobials in colostrum from dairy cows.

Validation of prognostic models predicting mortality or ICU admission in patients with COVID-19 in low- and middle-income countries: a global individual participant data meta-analysis.

Background: We evaluated the performance of prognostic models for predicting mortality or ICU admission in hospitalized patients with COVID-19 in the World Health Organization (WHO) Global Clinical Platform, a repository of individual-level clinical data of patients hospitalized with COVID-19, including in low- and middle-income countries (LMICs).

Methods: We identified eligible multivariable prognostic models for predicting overall mortality and ICU admission during hospital stay in patients with confirmed or suspected COVID-19 from a living review of COVID-19 prediction models. These models were evaluated using data contributed to the WHO Global Clinical Platform for COVID-19 from nine LMICs (Burkina Faso, Cameroon, Democratic Republic of Congo, Guinea, India, Niger, Nigeria, Zambia, and Zimbabwe).

Recreational and Occupational Physical Activity and Risk of Adverse Events in Truncating Founder Variant Carriers.

Background: founder variants cause hypertrophic cardiomyopathy leading to heart failure and malignant ventricular arrhythmias. Exercise is typically regarded as a risk factor for disease expression although evidence is conflicting. Stratifying by type of exercise may discriminate low- from high-risk activities in these patients.

Prognostic value of radiologic and pathological response in colorectal cancer liver metastases upon systemic induction treatment: subgroup analysis of the CAIRO5 trial.

Background: RECIST may not be optimal for assessing treatment response with current systemic regimens. We evaluated RECIST, morphologic, and pathologically documented response (pathological response) in patients with initially unresectable colorectal cancer liver-only metastases (CRLM).

Patients And Methods: Four hundred and eighty-nine patients from the phase III CAIRO5 trial were included who were treated with FOLFOX/FOLFIRI/FOLFOXIRI and bevacizumab or panitumumab.

Comparative iron management in hemodialysis and peritoneal dialysis patients: a systematic review.

Background: Patients with kidney failure undergoing dialysis often suffer from anemia. Iron deficiency, along with a shortage in erythropoietin, is a common cause. Peritoneal dialysis (PD) patients may have a different iron metabolism compared to hemodialysis (HD) patients.

Independent and joint effects of genomic and exposomic loads for schizophrenia on distressing and persisting psychotic experiences in adolescence.

To assess the longitudinal associations of genomic and exposomic liabilities for schizophrenia, both independently and jointly, with distressing psychotic experiences (PEs) and their persistence in early adolescence. The Adolescent Brain and Cognitive Development Study data from children with European ancestry were used (n=5,122). The primary outcome was past-month distressing PEs at 3-year follow-up.

Impact of personalized response-directed surgery and adjuvant therapy on survival after neoadjuvant immunotherapy in stage III melanoma: Comparison of 3-year data from PRADO and OpACIN-neo.

Background: Pathologic response following neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma serves as a surrogate marker for long-term outcomes. This may support more personalized, response-directed treatment strategies.

Methods: The OpACIN-neo and PRADO trials were phase 2 studies evaluating neoadjuvant treatment with ipilimumab and nivolumab in stage III melanoma.

Identification and characterization of alopecia areata subgroups regarding quality of life impairment based on demographic, clinical, psychological, and social factors.

The benign dermatological hair condition Alopecia Areata (AA) is known to impair Quality of Life (QoL), especially mental and social health, due to the accompanying visible appearance changes. Previous studies have identified demographic, clinical, social, and psychological variables related to QoL. Yet, the novelty of this study lies in examining how QoL differences in AA relate to (combinations of) these variables.

Challenges in the Implementation of EU Risk Minimisation Measures for Medicinal Products in Clinical Practice Guidelines: Mixed Methods Multi-Case Study.

Introduction: Risk minimisation measures (RMMs) aim to ensure safe use of medicines, but their implementation in clinical practice is complicated by the diversity of stakeholders whose clinical decision making they seek to inform. Clinical practice guidelines (CPGs) are considered integral in clinical decision making.

Objectives: To determine the extent to which RMMs are included in the relevant CPGs and to describe factors that determine RMM inclusion.

QCD challenges from pp to AA collisions: 4th edition.

This paper is a write-up of the ideas that were presented, developed and discussed at the fourth International Workshop on QCD Challenges from pp to AA, which took place in February 2023 in Padua, Italy. The goal of the workshop was to focus on some of the open questions in the field of high-energy heavy-ion physics and to stimulate the formulation of concrete suggestions for making progresses on both the experimental and theoretical sides. The paper gives a brief introduction to each topic and then summarizes the primary results.

The state-of-the-art of N-of-1 therapies and the IRDiRC N-of-1 development roadmap.

In recent years, a small number of people with rare diseases caused by unique genetic variants have been treated with therapies developed specifically for them. This pioneering field of genetic N-of-1 therapies is evolving rapidly, giving hope for the individualized treatment of people living with very rare diseases. In this Review, we outline the concept of N-of-1 individualized therapies, focusing on genetic therapies, and illustrate advances and challenges in the field using cases for which therapies have been successfully developed.

Vitamin D status, physical activity and long-term mortality risk after myocardial infarction: a prospective analysis in the Alpha Omega Cohort.

Aim: In post-myocardial infarction (MI) patients, we examined independent and combined associations of vitamin D status and physical activity (PA) with long-term mortality, including effect modification by health determinants.

Methods: We conducted a prospective analysis of 4,837 MI patients from the Alpha Omega Cohort. Baseline blood samples (2002-2006) were assessed for plasma 25-hydroxyvitamin D (25[OH]D) levels using LC-MS/MS.

Protorhabditis nematodes and pathogen-antagonistic bacteria interactively promote plant health.

Background: Fertilization practices control bacterial wilt-causing Ralstonia solanacearum by shaping the soil microbiome. This microbiome is the start of food webs, in which nematodes act as major microbiome predators. However, the multitrophic links between nematodes and the performance of R.

Autoimmune Encephalitis and Paraneoplastic Neurologic Syndromes: A Nationwide Study on Epidemiology and Antibody Testing Performance.

Background And Objectives: Autoimmune encephalitis (AIE) and paraneoplastic neurologic syndromes (PNSs) encompass a heterogeneous group of antibody-associated disorders. Both the number of syndromes and commercially available antibody tests have increased considerably over the past decade. High-quality population-based data on epidemiology of these disorders and real-world performance of antibody tests are needed.

Diversity of heart failure phenotypes in transthyretin amyloid cardiomyopathy. More than just heart failure with preserved ejection fraction.

Introduction: Current guidelines recommend suspecting transthyretin amyloid cardiomyopathy (ATTR-CM) in patients over 65 years of age with unexplained left ventricular (LV) hypertrophy in a non-dilated LV, heart failure (HF) and preserved ejection fraction (HFpEF), hypertrophic cardiomyopathy or severe aortic stenosis. However, there is evidence indicating a high prevalence of ATTR-CM in other HF phenotypes. As such, this study aimed to characterize the diversity of HF phenotypes of ATTR-CM by examining the LV ejection fraction and LV dilatation using echocardiography.

A co-created citizen science project on the short term effects of outdoor residential woodsmoke on the respiratory health of adults in the Netherlands.

Background And Aim: Woodsmoke from household fireplaces contributes significantly to outdoor air pollution in the Netherlands. The current understanding of the respiratory health effects of exposure to smoke from residential wood burning is limited. This study investigated the association between short-term changes in outdoor woodsmoke exposure and lung function, respiratory symptoms, and medication use in adults in the Netherlands.

Potential New Methods to Analyze Basal and Total Endogenous Protein Losses of Host and Bacterial Origin in Pigs.

Background: Current systems for assessing protein quality such as the Digestible Indispensable Amino Acid Score correct apparent amino acid (AA) digestibility for basal endogenous protein losses (bEPL), ignoring the potential influence of the diet on these losses. However, the quantification of total endogenous protein losses (tEPL) poses a challenge.

Objectives: To evaluate different methods for quantifying tEPL and bEPL, and to assess their potential in discriminating between tEPL originating from bacteria and host.