Childhood interstitial lung disease survivors in adulthood: a European collaborative study.

Background: Interstitial lung disease (ILD) is rarer in children (chILD) than adults, but with increasing diagnostic awareness, more cases are being discovered. chILD prognosis is often poor, but increasing numbers are now surviving into adulthood.

Aim: To characterize chILD-survivors and identify their impact on adult-ILD centers.

Perspective matters in recovery: the views of persons with severe mental illness, family and mental health professionals on collaboration during recovery, a qualitative study.

Background: Recovery from severe mental illness, including psychosis has been described as a personal and unique process, but it rarely is a journey undertaken without profound influences of significant others (family, mental health professionals). Diverging perspectives between persons with severe mental illness, family and professionals are frequent during the recovery process, notably in psychotic disorders. We aimed to explore processes of collaboration during recovery, to inform recovery supporting practices.

Highly sensitive reporter cell line for detection of interferon types I-III and their neutralization by antibodies.

Interferons (IFNs) are a critical component of innate immune defenses and limit viral disease severity. To advance studies on IFNs and their neutralization by pathogenic autoantibodies, we generated a Renilla luciferase-based reporter cell line capable of detecting the activities of IFN-Is, IFN-II, and IFN-IIIs. The reporter cell line exhibits a 125- to 2000-fold higher sensitivity to IFNs than a commonly used alternative biological reporter system and allows for a rapid and simple live-cell workflow for detecting low titer amounts of neutralizing anti-IFN antibodies.

Loss of tolerance precedes triggering and lifelong persistence of pathogenic type I interferon autoantibodies.

Autoantibodies neutralizing type I interferons (IFN-Is) can underlie infection severity. Here, we trace the development of these autoantibodies at high-resolution using longitudinal samples from 1,876 well-treated individuals living with HIV over a 35-year period. Similar to general populations, ∼1.

A new variant in the gene: diverse clinical phenotypes and expression in the lung.

Introduction: Pulmonary fibrosis is a severe disease which can be familial. A genetic cause can only be found in ∼40% of families. Searching for shared novel genetic variants may aid the discovery of new genetic causes of disease.

Correctly structured problem lists lead to better and faster clinical decision-making in electronic health records compared to non-curated problem lists: A single-blinded crossover randomized controlled trial.

Background: Correctly structured problem lists in electronic health records (EHRs) offer major benefits to patient care. Without structured lists, diagnosis information is often scatteredly documented in free text, which may contribute to errors and inefficient information retrieval. This study aims to assess whether EHRs with correctly structured problem lists result in better and faster clinical decision-making compared to non-curated problem lists.

Treatment sequences and drug costs from diagnosis to death in multiple myeloma.

Novel therapies for multiple myeloma (MM) have improved patient survival, but their high costs strain healthcare budgets. End-of-life phases of treatment are generally the most expensive, however, these high costs may be less justifiable in the context of a less pronounced clinical benefit. To manage drug expenses effectively, detailed information on end-of-life drug administration and costs are crucial.

It is not all about the alpha: elevated expression of p53β variants is associated with lower probability of survival in a retrospective melanoma cohort.

Background: Melanoma is the deadliest type of skin cancer and despite improvements in treatment outcomes, melanoma claimed 57,043 lives in 2020. In most malignancies, p53 mutation rates are above 50% and provide prognostic indications. However, in melanoma where less than a quarter of cases harbour a p53 mutation, the significance of the tumour suppressor may be questioned.

Ixazomib, daratumumab and low-dose dexamethasone in intermediate-fit patients with newly diagnosed multiple myeloma: an open-label phase 2 trial.

Background: The outcome of non-transplant eligible newly diagnosed multiple myeloma (NDMM) patients is heterogeneous, partly depending on frailty level. The aim of this study was to prospectively investigate the efficacy and safety of Ixazomib-Daratumumab-low-dose dexamethasone (Ixa-Dara-dex) in NDMM intermediate-fit patients.

Methods: In this phase II multicenter HOVON-143 study, IMWG Frailty index based intermediate-fit patients, were treated with 9 induction cycles of Ixa-Dara-dex, followed by maintenance with ID for a maximum of 2 years.

p53 isoform expression promotes a stemness phenotype and inhibits doxorubicin sensitivity in breast cancer.

In breast cancer, dysregulated TP53 expression signatures are a better predictor of chemotherapy response and survival outcomes than TP53 mutations. Our previous studies have shown that high levels of Δ40p53 are associated with worse disease-free survival and disruption of p53-induced DNA damage response in breast cancers. Here, we further investigated the in vitro and in vivo implications of Δ40p53 expression in breast cancer.

p53 Dysregulation in Breast Cancer: Insights on Mutations in the Network and p53 Isoform Expression.

In breast cancer, p53 expression levels are better predictors of outcome and chemotherapy response than mutation. Several molecular mechanisms that modulate p53 levels and functions, including p53 isoform expression, have been described, and may contribute to deregulated p53 activities and worse cancer outcomes. In this study, and regulators of the p53 pathway were sequenced by targeted next-generation sequencing in a cohort of 137 invasive ductal carcinomas and associations between the identified sequence variants, and p53 and p53 isoform expression were explored.

Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study.

Background: Patients with haematological malignancies have impaired antibody responses to SARS-CoV-2 vaccination. We aimed to investigate whether a fourth mRNA COVID-19 vaccination improved antibody quantity and quality.

Methods: In this cohort study, conducted at 5 sites in the Netherlands, we compared antibody concentrations 28 days after 4 mRNA vaccinations (3-dose primary series plus 1 booster vaccination) in SARS-CoV-2 naive, immunocompromised patients with haematological malignancies to those obtained by age-matched, healthy individuals who had received the standard primary 2-dose mRNA vaccination schedule followed by a first booster mRNA vaccination.

DNA-based seed intake quantification for enhanced ecological risk assessment of small mammals.

To prevent the non-acceptable effects of agrochemicals on arable fields, Environmental Risk Assessment (ERA) aims to assess and protect against a wide range of risks due to stressors to non-target species. While exposure to stress is a key factor in ERA models, exposure values are difficult to obtain and rely on laboratory studies with often debatable relevance to field situations. To improve intake estimates, data from realistic field-based scenarios are needed.

The role of truncated p53 isoforms in the DNA damage response.

The tumour suppressor p53 is activated following genotoxic stress and regulates the expression of target genes involved in the DNA damage response (DDR). The discovery that p53 isoforms alter the transcription of p53 target genes or p53 protein interactions unveiled an alternative DDR. This review will focus on the role p53 isoforms play in response to DNA damage.

Genetic Variant Overlap Analysis Identifies Established and Putative Genes Involved in Pulmonary Fibrosis.

In only around 40% of families with pulmonary fibrosis (PF) a suspected genetic cause can be found. Genetic overlap analysis of Whole Exome Sequencing (WES) data may be a powerful tool to discover new shared variants in novel genes for PF. As a proof of principle, we first selected unrelated PF patients for whom a genetic variant was detected (n = 125) in established PF genes and searched for overlapping variants.

Optimizing Screening for Early Disease Detection in Familial Pulmonary Fibrosis (FLORIS): A Prospective Cohort Study Design.

: Familial pulmonary fibrosis (FPF) can be defined as pulmonary fibrosis in two or more first-degree family members. The first-degree family members of FPF patients are at high risk of developing FPF and are eligible for screening. Reproducible studies investigating risk factors for disease are much needed.

Emergence and Potential Extinction of Genetic Lineages of Human Metapneumovirus between 2005 and 2021.

Human metapneumovirus (HMPV) is one of the leading causes of respiratory illness (RI), primarily in infants. Worldwide, two genetic lineages (A and B) of HMPV are circulating that are antigenically distinct and can each be further divided into genetic sublineages. Surveillance combined with large-scale whole-genome sequencing studies of HMPV are scarce but would help to identify viral evolutionary dynamics.

Alterations in the p53 isoform ratio govern breast cancer cell fate in response to DNA damage.

Our previous studies have shown that p53 isoform expression is altered in breast cancer and related to prognosis. In particular, a high ∆40p53:p53α ratio is associated with worse disease-free survival. In this manuscript, the influence of altered Δ40p53 and p53α levels on the response to standard of care DNA-damaging agents used in breast cancer treatment was investigated in vitro.