Off-label use of biologics in urticarial vasculitis: a European retrospective cohort study.

Objectives: Urticarial vasculitis (UV) is characterized by atypical urticarial lesions and leukocytoclastic vasculitis, sometimes with extracutaneous manifestations. First-line treatment is based on colchicine, hydroxychloroquine, dapsone or low-dose glucocorticoids. In refractory forms, the use of biologics has been anecdotally described as potentially effective.

Prolonged persistence of mutagenic DNA lesions in somatic cells.

DNA is subject to continual damage, leaving each cell with thousands of individual DNA lesions at any given moment. The efficiency of DNA repair means that most known classes of lesion have a half-life of minutes to hours, but the extent to which DNA damage can persist for longer durations remains unknown. Here, using high-resolution phylogenetic trees from 89 donors, we identified mutations arising from 818 DNA lesions that persisted across multiple cell cycles in normal human stem cells from blood, liver and bronchial epithelium.

Angiogenic factors versus fetomaternal Doppler for fetal growth restriction at term: an open-label, randomized controlled trial.

Small fetuses, with estimated fetal weight (EFW) below the tenth percentile, are classified as fetal growth restriction (FGR) or small for gestational age (SGA) based on prenatal ultrasound. FGR fetuses have a greater risk of stillbirth and perinatal complications and may benefit from serial ultrasound scans to guide early delivery. Abnormal serum angiogenic factors, such as the soluble fms-like tyrosine kinase-1 (sFlt-1):placental growth factor (PlGF) ratio, have shown potential to more accurately distinguish FGR from SGA, with fewer false positives.

Enhanced Photoluminescence of Europium-Doped TiO Nanoparticles Using a Single-Source Precursor Strategy.

TiO:Eu nanoparticles with varying europium concentrations were successfully synthesized via a one-pot sol-gel approach using a molecular heterometallic single-source precursor (SSP) Eu-Ti. For comparison, nanomaterials with similar europium levels were also produced by impregnating europium salts onto the same TiO substrate. All the nanomaterials were thoroughly characterized using Eu elemental analysis, powder X-ray diffraction (XRD), scanning (SEM), transmission (TEM), scanning transmission electron microscopy (STEM), Brunauer-Emmett-Teller (BET) analysis, thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and photoluminescence (PL).

A single exposure to prolonged flexor carpi radialis muscle vibration increases sensorimotor cortical areas activity.

Prolonged local vibration (LV) is thought to promote brain plasticity through repeated Ia afferents discharge. However, the underlying mechanisms remain unclear. This study therefore aimed at determining the acute after-effects of 30-min LV of the flexor carpi radialis muscle (FCR) on sensorimotor (S1, M1) and posterior parietal cortex (PPC) areas activity.

Impact of suspected preterm labour in foetal cardiovascular and metabolic programming: a prospective cohort study protocol.

Introduction: Suspected preterm labour (SPL) is an obstetric complication that occurs in 9% of all pregnancies and is the leading cause of antenatal hospital admissions. More than half of women with SPL deliver a premature baby which is a known risk factor for developing cardiovascular and metabolic disorders in childhood and later in adult life. On the other hand, the other half of these women will deliver at term, labelled as 'false preterm labour'.

Disease prediction with multi-omics and biomarkers empowers case-control genetic discoveries in the UK Biobank.

The emergence of biobank-level datasets offers new opportunities to discover novel biomarkers and develop predictive algorithms for human disease. Here, we present an ensemble machine-learning framework (machine learning with phenotype associations, MILTON) utilizing a range of biomarkers to predict 3,213 diseases in the UK Biobank. Leveraging the UK Biobank's longitudinal health record data, MILTON predicts incident disease cases undiagnosed at time of recruitment, largely outperforming available polygenic risk scores.

Direct and indirect reference intervals of 25-hydroxyvitamin D: it is not a real vitamin D deficiency pandemic.

Introduction: Many studies report vitamin D (25-OH-D) deficiency, although there is no consensus among scientific societies on cut-offs and reference intervals (RI). The aim of this study is to establish and compare RI for serum 25-OH-D by direct and indirect methods.

Materials And Methods: Two studies were performed in Zaragoza (Spain).

Characterising the contribution of rare protein-coding germline variants to prostate cancer risk and severity in 37,184 cases.

The etiology of prostate cancer, the second most common cancer in men globally, has a strong heritable component. While rare coding germline variants in several genes have been identified as risk factors from candidate gene and linkage studies, the exome-wide spectrum of causal rare variants remains to be fully explored. To more comprehensively address their contribution, we analysed data from 37,184 prostate cancer cases and 331,329 male controls from five cohorts with germline exome/genome sequencing and one cohort with imputed array data from a population enriched in low-frequency deleterious variants.

Efficiency and tolerance of second-line triple BRAF inhibitor/MEK inhibitor/anti-PD1 combined therapy in BRAF mutated melanoma patients with central nervous system metastases occurring during first-line combined targeted therapy: a real-life survey.

Although current systemic therapies significantly improved the outcome of advanced melanoma, the prognosis of patient with central nervous system (CNS) metastases remains poor especially when clinically symptomatic. We aimed to investigate the efficiency of CNS targets and tolerance of second-line combined anti-PD1/dual-targeted anti-BRAF/anti-MEK therapy implemented in patients with CNS progression after initially efficient first-line combined targeted therapy in patients with BRAF-mutated melanoma in a real-life setting. A monocentric retrospective analysis including all such patients treated from January 2017 to January 2022 was conducted in our tertiary referral center.

Mutational signature, cancer driver genes mutations and transcriptomic subgroups predict hepatoblastoma survival.

Background: Hepatoblastoma is the most frequent pediatric liver cancer. The current treatments lead to 80% of survival rate at 5 years. In this study, we evaluated the clinical relevance of molecular features to identify patients at risk of chemoresistance, relapse and death of disease.

Modelling the impact of liver regeneration on hepatoblastoma patient-derived-xenograft tumor growth.

Background: Twenty percent of children with hepatoblastoma (HB) have lung metastasis at diagnosis. Treatment protocols recommend surgical removal of chemotherapy-refractory lung nodules, however no chronological order is established. As hepatectomy is followed by release of growth factors, it has been proposed that partial hepatectomy (PH) could boost local or distant residual tumor growth.

[Topical treatment for age-related macular degeneration: Where are we now?].

The therapeutic management of age-related macular degeneration (AMD) is a major public health issue. One of its two late forms, neovascular AMD, is currently treated by intravitreal injections of pharmaceutical active ingredients. Although it is very effective in treating pathologies of the posterior segment of the eye, the intravitreal route is not an ideal option for the long-term management of a chronic disease such as AMD.

The lifelong natural history of clonal hematopoiesis and its links to myeloid neoplasia.

The study of somatic mutations and the associated clonal mosaicism across the human body has transformed our understanding of aging and its links to cancer. In proliferative human tissues, stem cells compete for dominance, and those with an advantage expand clonally to outgrow their peers. In the hematopoietic system, such expansion is termed clonal hematopoiesis (CH).

Clonal selection of hematopoietic stem cells after gene therapy for sickle cell disease.

Gene therapy (GT) provides a potentially curative treatment option for patients with sickle cell disease (SCD); however, the occurrence of myeloid malignancies in GT clinical trials has prompted concern, with several postulated mechanisms. Here, we used whole-genome sequencing to track hematopoietic stem cells (HSCs) from six patients with SCD at pre- and post-GT time points to map the somatic mutation and clonal landscape of gene-modified and unmodified HSCs. Pre-GT, phylogenetic trees were highly polyclonal and mutation burdens per cell were elevated in some, but not all, patients.

When mechanical engineering inspired from physiology improves postural-related somatosensory processes.

Despite numerous studies uncovering the neural signature of tactile processing, tactile afferent inputs relating to the contact surface has not been studied so far. Foot tactile receptors being the first stimulated by the relative movement of the foot skin and the underneath moving support play an important role in the sensorimotor transformation giving rise to a postural reaction. A biomimetic surface, i.

Preneoplastic liver colonization by 11p15.5 altered mosaic cells in young children with hepatoblastoma.

Pediatric liver tumors are very rare tumors with the most common diagnosis being hepatoblastoma. While hepatoblastomas are predominantly sporadic, around 15% of cases develop as part of predisposition syndromes such as Beckwith-Wiedemann (11p15.5 locus altered).

Rare variant associations with plasma protein levels in the UK Biobank.

Integrating human genomics and proteomics can help elucidate disease mechanisms, identify clinical biomarkers and discover drug targets. Because previous proteogenomic studies have focused on common variation via genome-wide association studies, the contribution of rare variants to the plasma proteome remains largely unknown. Here we identify associations between rare protein-coding variants and 2,923 plasma protein abundances measured in 49,736 UK Biobank individuals.