Neurologic immune-related adverse events (nirAEs) represent rare, yet severe side effects associated with immune checkpoint inhibitor (ICI) therapy. Given the absence of established diagnostic biomarkers for nirAEs, we aimed to evaluate the diagnostic utility of serum Neurofilament Light Chain (NfL) and Glial Fibrillary Acidic Protein (GFAP). Fifty-three patients were included at three comprehensive cancer centers, of these 20 patients with manifest nirAEs and 11 patients with irHypophysitis.
View Article and Find Full Text PDFBackground: Limited reports are available regarding bonding of universal adhesives to primary teeth' enamel.
Aim: To evaluate the effect of application mode and aging on microtensile bond strength (μTBS) of universal adhesives to primary enamel.
Design: Ninety-six human primary molars were randomly assigned to three groups: SU: Scotchbond Universal (3M); CU: Clearfil Universal Bond Quick (Kuraray Noritake); iBU: iBond Universal (Heraeus Kulzer), then subdivided according to phosphoric acid etching time into three subgroups (SG): SG1: 0s; SG2: 15s; SG3: 30s.
Osteoarthritis (OA) poses a significant healthcare burden with limited treatment options. While genome-wide association studies (GWASs) have identified over 100 OA-associated loci, translating these findings into therapeutic targets remains challenging. To address this gap, we mapped gene expression, chromatin accessibility, and 3D chromatin structure in primary human articular chondrocytes in both resting and OA-mimicking conditions.
View Article and Find Full Text PDFObjective: The objective of this review is to evaluate the effect of cochlear implants on cognitive function in pediatric patients with hearing loss.
Introduction: Cognitive impairments have been reported in children with hearing loss. This is supported by the auditory scaffolding hypothesis, which describes sound as the basis for processing sequential information.
Objective: This cross-sectional study aimed to investigate the use, quality, and caries-preventive effects of fissure sealants (FSs) in 8- to 10-year-olds with and without molar-incisor hypomineralization (MIH).
Materials And Methods: A total of 5,418 children (2,692 males, 2,726 females) were examined via standard instruments (dental mirrors, CPI probes, adequate lighting, mobile examination tables, and air syringes) and methods for the recording of caries (DMFT index, WHO method) and FSs. The classification of MIH followed the recommendations of the European Academy of Pediatric Dentistry (EAPD).
Osteoarthritis affects millions worldwide, yet effective treatments remain elusive due to poorly understood molecular mechanisms. While genome-wide association studies (GWAS) have identified over 100 OA-associated loci, identifying the genes impacted at each locus remains challenging. Several studies have mapped expression quantitative trait loci (eQTL) in chondrocytes and colocalized them with OA GWAS variants to identify putative OA risk genes; however, the degree to which genetic variants influence OA risk via alternative splicing has not been explored.
View Article and Find Full Text PDFPlatelet-rich plasma (PRP) is an autologous blood product containing concentrated platelets, growth factors, and anti-inflammatory cytokines that promote healing and regeneration. Platelets release active components through a degranulation process, which is inhibited by certain nonsteroidal anti-inflammatory drugs (NSAIDs). Current deferral guidelines are not established, but NSAIDs are expected to have a time-dose relationship with platelet inhibition.
View Article and Find Full Text PDFGenome-wide association studies have identified loci associated with Alzheimer's Disease (AD), but identifying the exact causal variants and genes at each locus is challenging due to linkage disequilibrium and their largely non-coding nature. To address this, we performed a massively parallel reporter assay of 3,576 AD-associated variants in THP-1 macrophages in both resting and proinflammatory states and identified 47 expression-modulating variants (emVars). To understand the endogenous chromatin context of emVars, we built an activity-by-contact model using epigenomic maps of macrophage inflammation and inferred condition-specific enhancer-promoter pairs.
View Article and Find Full Text PDF(1) Background: Intrinsic defense mechanisms are pivotal host strategies to restrict viruses already at early stages of their infection. Here, we addressed the question of how the autophagy receptor sequestome 1 (/p62, hereafter referred to as p62) interferes with human cytomegalovirus (HCMV) infection. (2) Methods: CRISPR/Cas9-mediated genome editing, mass spectrometry and the expression of p62 phosphovariants from recombinant HCMVs were used to address the role of p62 during infection.
View Article and Find Full Text PDFObjectives: Patients with progressive neurologic illness still lack access to quality palliative care services. Barriers to the comprehensive provision of neuropalliative care include gaps in palliative care education. To address this barrier, a novel international model of neuropalliative care education e-learning program was launched in 2022.
View Article and Find Full Text PDFAdverse outcome pathways (AOPs) describe toxicological processes from a dynamic perspective by linking a molecular initiating event to a specific adverse outcome via a series of key events and key event relationships. In the field of computational toxicology, AOPs can potentially facilitate the design and development of in silico prediction models for hazard identification. Various AOPs have been introduced for several types of hepatotoxicity, such as steatosis, cholestasis, fibrosis, and liver cancer.
View Article and Find Full Text PDFPurpose: Part 2 of this German S3 clinical practice guideline provides recommendations for the process of manufacturing composite restorations. It covers key aspects like caries removal, field isolation, matrix and adhesive techniques, as well as light curing and polishing. The outcomes of interest include survival rates and restoration quality.
View Article and Find Full Text PDFIntroduction: The aim of this cross-sectional epidemiological study was to record caries and enamel hypomineralisation (EH), including molar-incisor hypomineralisation (MIH), and assess associations between both entities in 8- to 10-year-olds from Bavaria, Germany.
Methods: A total of 5,418 children (mean age 9.8 years; 2,726 females, 2,692 males) were examined using the dmft/DMFT index with additional inclusion of initial or non-cavitated carious lesions (it/IT).
The global burden of Inflammatory bowel disease (IBD) has been rising over the last decades. IBD is an intestinal disorder with a complex and largely unknown etiology. The disease is characterized by a chronically inflamed gastrointestinal tract, with intermittent phases of exacerbation and remission.
View Article and Find Full Text PDFIntroduction: We have recently demonstrated that -expressing ( ) cells give rise to mainly type-III neuronal taste bud cells that are responsible for sour and salt taste. The two tissue compartments containing cells in the surrounding of taste buds include the connective tissue core of taste papillae and von Ebner's glands (vEGs) that are connected to the trench of circumvallate and foliate papillae.
Methods: In this study, we performed single cell RNA-sequencing of the epithelium of mouse circumvallate/vEG complex and used inducible Cre mouse models to map the cell lineages of vEGs and/or connective tissue (including stromal and Schwann cells).
To underpin scientific evaluations of chemical risks, agencies such as the European Food Safety Authority (EFSA) heavily rely on the outcome of systematic reviews, which currently require extensive manual effort. One specific challenge constitutes the meaningful use of vast amounts of valuable data from new approach methodologies (NAMs) which are mostly reported in an unstructured way in the scientific literature. In the EFSA-initiated project 'AI4NAMS', the potential of large language models (LLMs) was explored.
View Article and Find Full Text PDFThe spontaneous rupture of an ovarian artery aneurysm (OAA) is an extremely uncommon and life-threatening event. Here, we describe the case of a 34-year-old G6P5015 female who underwent spontaneous vaginal delivery. Following delivery, she experienced hypotension and reported right-sided abdominal pain.
View Article and Find Full Text PDFBrominated flame retardants are used in many household products to reduce flammability, but often leach into the surrounding environment over time. Hexabromocyclododecane (HBCD) is a brominated flame retardant detected in human blood across the world. HBCD exposure can result in neurological problems and altered lipid metabolism, but to date, the two remain unlinked.
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