Toxicogenomic assessment of in vitro macrophages exposed to profibrotic challenge reveals a sustained transcriptomic immune signature.

Immune signalling is a crucial component in the progression of fibrosis. However, approaches for the safety assessment of potentially profibrotic substances, that provide information on mechanistic immune responses, are underdeveloped. This study aimed to develop a novel framework for assessing the immunotoxicity of fibrotic compounds.

Machine learning models of cerebral oxygenation (rcSO) for brain injury detection in neonates with hypoxic-ischaemic encephalopathy.

The present study was designed to test the potential utility of regional cerebral oxygen saturation (rcSO) in detecting term infants with brain injury. The study also examined whether quantitative rcSO features are associated with grade of hypoxic ischaemic encephalopathy (HIE). We analysed 58 term infants with HIE (>36 weeks of gestational age) enrolled in a prospective observational study.

Importance of H-FABP in Early Diagnosis of Acute Myocardial Infarction.

Background: Over the years, troponins have aced the para-clinical tests for confirming the diagnosis of acute myocardial infarction. However, the rise in their levels is entirely time-dependent, which can cause a delay in the initiation of treatment protocols. Heart fatty acid binding protein (H-FABP) can serve comparatively as a better biological marker for overcoming this flaw of troponins, as it is quickly released into the bloodstream once the myocardial injury occurs due to decreased blood supply.

Genetics and Pharmacogenetics of Atrial Fibrillation: A Mechanistic Perspective.

The heritability of atrial fibrillation (AF) is well established. Over the last decade genetic architecture of AF has been unraveled by genome-wide association studies and family-based studies. However, the translation of these genetic discoveries has lagged owing to an incomplete understanding of the pathogenic mechanisms underlying the genetic variants, challenges in classifying variants of uncertain significance (VUS), and limitations of existing disease models.

Evolution of pathologic B-cell subsets and serum environment-specific sIgEs in patients with atopic dermatitis and controls, from infancy to adulthood.

Background: While B-cells have historically been implicated in allergy development, a growing body of evidence supports their role in atopic dermatitis (AD). B-cell differentiation across ages in AD, and its relation to disease severity scores, has not been well defined.

Objective: To compare the frequency of B-cell subsets in blood of 0-5, 6-11, 12-17, and ≥18 years old patients with AD versus age-matched controls.

The Role of SPECT/CT and PET/CT Hybrid Imaging in the Management of Ectopic Thyroid Carcinoma-A Systematic Review.

Background And Objectives: Thyroid ectopy represents a rare disease with an incidence of 0.3-1/100,000. It occurs due to the defective embryological process of the thyroid gland development.

A Network Toxicology Approach for Mechanistic Modelling of Nanomaterial Hazard and Adverse Outcomes.

Hazard assessment is the first step in evaluating the potential adverse effects of chemicals. Traditionally, toxicological assessment has focused on the exposure, overlooking the impact of the exposed system on the observed toxicity. However, systems toxicology emphasizes how system properties significantly contribute to the observed response.

A Multi-Dimensional Approach to Map Disease Relationships Challenges Classical Disease Views.

The categorization of human diseases is mainly based on the affected organ system and phenotypic characteristics. This is limiting the view to the pathological manifestations, while it neglects mechanistic relationships that are crucial to develop therapeutic strategies. This work aims to advance the understanding of diseases and their relatedness beyond traditional phenotypic views.

Clinical and Paraclinical Considerations Regarding ki67's Role in the Management of Differentiated Thyroid Carcinoma-A Literature Review.

: The ki67 nuclear protein is a tool for diagnosis and prognosis in oncology that is used to evaluate cell proliferation. Differentiated thyroid carcinoma is usually a slow-growing neoplasm, the most common type being the papillary form. Some clinical and pathological aspects may predict aggressive behaviour.

Temporal evolution of electrographic seizures in newborn infants with hypoxic-ischaemic encephalopathy requiring therapeutic hypothermia: a secondary analysis of the ANSeR studies.

Background: Despite extensive research on neonatal hypoxic-ischaemic encephalopathy, detailed information about electrographic seizures during active cooling and rewarming of therapeutic hypothermia is sparse. We aimed to describe temporal evolution of seizures and determine whether there is a correlation of seizure evolution with 2-year outcome.

Methods: This secondary analysis included newborn infants recruited from eight European tertiary neonatal intensive care units for two multicentre studies (a randomised controlled trial [NCT02431780] and an observational study [NCT02160171]).

Integrative network analysis suggests prioritised drugs for atopic dermatitis.

Background: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease whose pathophysiology involves the interplay between genetic and environmental factors, ultimately leading to dysfunction of the epidermis. While several treatments are effective in symptom management, many existing therapies offer only temporary relief and often come with side effects. For this reason, the formulation of an effective therapeutic plan is challenging and there is a need for more effective and targeted treatments that address the root causes of the condition.

Advancing chemical safety assessment through an omics-based characterization of the test system-chemical interaction.

Assessing chemical safety is essential to evaluate the potential risks of chemical exposure to human health and the environment. Traditional methods relying on animal testing are being replaced by 3R (reduction, refinement, and replacement) principle-based alternatives, mainly depending on test methods and the Adverse Outcome Pathway framework. However, these approaches often focus on the properties of the compound, missing the broader chemical-biological interaction perspective.

Novel voxelwise residual analysis of [C]raclopride PET data improves detection of low-amplitude dopamine release.

Existing methods for voxelwise transient dopamine (DA) release detection rely on explicit kinetic modeling of the [C]raclopride PET time activity curve, which at the voxel level is typically confounded by noise, leading to poor performance for detection of low-amplitude DA release-induced signals. Here we present a novel data-driven, task-informed method-referred to as Residual Space Detection (RSD)-that transforms PET time activity curves to a residual space where DA release-induced perturbations can be isolated and processed. Using simulations, we demonstrate that this method significantly increases detection performance compared to existing kinetic model-based methods for low-magnitude DA release (simulated +100% peak increase in basal DA concentration).

Risk factors for involuntary admission in a Romanian patient sample.

Background: Involuntary admission is widely used in psychiatry, usually requiring that the patient present an imminent danger to himself or others. Previous studies have established several predictors for involuntary admission, but they have been almost exclusively conducted in Western European or North American countries. By contrast, data on this topic from Eastern European countries is virtually absent.

Leukemic conversion involving mutations of type 1 -mutated primary myelofibrosis in a patient treated for HCV cirrhosis: a case report.

Somatic frameshift mutations in exon 9 of calreticulin () gene are recognized as disease drivers in primary myelofibrosis (PMF), one of the three classical Philadelphia-negative myeloproliferative neoplasms (MPNs). Type 1/type 1-like mutations particularly confer a favorable prognostic and survival advantage in PMF patients. We report an unusual case of PMF incidentally diagnosed in a 68-year-old woman known with hepatitis C virus (HCV) cirrhosis who developed a progressive painful splenomegaly, without anomalies in blood cell counts.

Integrative genetic and genomic networks identify microRNA associated with COPD and ILD.

Chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) are clinically and molecularly heterogeneous diseases. We utilized clustering and integrative network analyses to elucidate roles for microRNAs (miRNAs) and miRNA isoforms (isomiRs) in COPD and ILD pathogenesis. Short RNA sequencing was performed on 351 lung tissue samples of COPD (n = 145), ILD (n = 144) and controls (n = 64).

DREAM: an R package for druggability evaluation of human complex diseases.

Motivation: De novo drug development is a long and expensive process that poses significant challenges from the design to the preclinical testing, making the introduction into the market slow and difficult. This limitation paved the way to the development of drug repurposing, which consists in the re-usage of already approved drugs, developed for other therapeutic indications. Although several efforts have been carried out in the last decade in order to achieve clinically relevant drug repurposing predictions, the amount of repurposed drugs that have been employed in actual pharmacological therapies is still limited.

Three new species of Gromia (Protista, Rhizaria) identified from the Romanian Black Sea shelf.

The protist genus Gromia was first described in 1835 by Dujardin and while gromiids are prominent in the marine environment, Gromia oviformis was, for a long time, the only valid species regularly recorded. To date, 16 species that are morphologically and/or genetically distinct have been described. While recent studies are documenting their diversity and their ecological importance, G.

A curated gene and biological system annotation of adverse outcome pathways related to human health.

Adverse outcome pathways (AOPs) are emerging as a central framework in modern toxicology and other fields in biomedicine. They serve as an extension of pathway-based concepts by depicting biological mechanisms as causally linked sequences of key events (KEs) from a molecular initiating event (MIE) to an adverse outcome. AOPs guide the use and development of new approach methodologies (NAMs) aimed at reducing animal experimentation.

KNeMAP: a network mapping approach for knowledge-driven comparison of transcriptomic profiles.

Motivation: Transcriptomic data can be used to describe the mechanism of action (MOA) of a chemical compound. However, omics data tend to be complex and prone to noise, making the comparison of different datasets challenging. Often, transcriptomic profiles are compared at the level of individual gene expression values, or sets of differentially expressed genes.

Quality of Life in People With Subjective Cognitive Decline.

Objective: Quality of life is extensively studied in older persons, but there are few studies that investigate it in people with subjective cognitive decline. Our aim was to evaluate the quality of life in a Romanian sample of individuals with subjective cognitive decline compared to controls while accounting for different possible moderators. To our knowledge, this is the first study to evaluate the quality of life in a Romanian subjective cognitive decline sample.

Crisaborole reverses dysregulation of the mild to moderate atopic dermatitis proteome toward nonlesional and normal skin.

Background: Safe and effective long-term topical treatments for atopic dermatitis (AD) remain limited.

Objective: In this phase 2a, single-center, intrapatient, and vehicle-controlled study, we examine the mechanism of action of crisaborole 2% ointment, a topical nonsteroidal PDE4 (phosphodiesterase-4) inhibitor, in a proteomic analysis of 40 adults with mild to moderate AD and 20 healthy subjects.

Methods: Within the AD cohort, 2 target lesions were randomized in an intrapatient (1:1) manner to double-blind crisaborole/vehicle applied twice daily for 14 days.