Use of alternatives to animal testing for Environmental Safety Assessment (ESA): Report from the 2023 EPAA partners' forum.

Environmental Safety Assessments (ESA) are mandatory for several regulatory purposes and are an important component of stewardship/sustainability initiatives. Fish testing is used for assessing chemical toxicity and bioaccumulation potential; amphibians are included in some jurisdictions and their use is increasing to assess endocrine disruption. Alternative methods are becoming more available, covering the principles of the 3Rs (i.

The role of non-respiratory arousals in residual daytime sleepiness in patients with obstructive sleep apnea treated with positive airway pressure: An analysis of the European Sleep Apnea Database registry.

Study Objectives: To assess the impact of the non-respiratory arousal burden at baseline polysomnography (PSG) on residual daytime sleepiness in positive airway pressure (PAP)-treated obstructive sleep apnea (OSA).

Methods: We included OSA patients from the European Sleep Apnea Database registry with available arousal data who had at least 2 treatment follow-up visits. The primary outcome was the Epworth Sleepiness Scale (ESS) score under PAP.

The role of the somatosensory cortex in self-paced movement impairment in Parkinson's disease.

Objective: The aim of this work was to study the differences at the whole-brain level between self-paced and cued movement processing in Parkinson's disease (PD).

Methods: High density electroencephalogram (HD-EEG) was recorded during the performance of self-paced movements (Bereitschaftspotential - BP) and visually cued movements (VMT) in PD patients (n = 38) and in a group of healthy controls (HC, n = 23). Oscillatory changes in the alpha, beta, and gamma frequencies were evaluated and correlated to the clinical scales- MDS-UPDRS and Freezing of Gait Questionnaire (FOGQ).

Protease activity of NIa-Pro determines systemic pathogenicity of clover yellow vein virus.

Clover yellow vein virus (ClYVV), a potyvirus that infects various dicotyledonous plants, poses a significant threat to the cultivation of legumes. Although potyviral NIa-Pro was extensively studied in viral infection cycle and host antiviral responses, the contribution of NIa-Pro protease activity to virus systemic symptoms has not yet been reported. In this study, we developed infectious clones of a ClYVV isolated from Pisum sativum.

Prevalence of FGFR2b Protein Overexpression in Advanced Gastric Cancers During Prescreening for the Phase III FORTITUDE-101 Trial.

Purpose: Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) protein overexpression is an emerging biomarker in gastric cancer and gastroesophageal junction cancer (GC). We assessed FGFR2b protein overexpression prevalence in nearly 3,800 tumor samples as part of the prescreening process for a global phase III study in patients with newly diagnosed advanced or metastatic GC.

Methods: As of June 28, 2024, 3,782 tumor samples from prescreened patients from 37 countries for the phase III FORTITUDE-101 trial (ClinicalTrials.

The translation initiation factor eIF3M2 upregulates HEAT SHOCK PROTEIN 70 to maintain pollen tube membrane integrity during heat shock.

Pollen germination and pollen tube (PT) growth are extremely sensitive to high temperatures. During heat stress (HS), global translation shuts down and favors the maintenance of the essential cellular proteome for cell viability and protection against protein misfolding. Here, we demonstrate that under normal conditions, the Arabidopsis (Arabidopsis thaliana) eukaryotic translation initiation factor subunit eif3m1/eif3m2 double mutant exhibits poor pollen germination, loss of PT integrity and an increased rate of aborted seeds.

Functional traits mediate the effect of land use on drivers of community stability within and across trophic levels.

Understanding how land use affects temporal stability is crucial to preserve biodiversity and ecosystem functions. Yet, the mechanistic links between land-use intensity and stability-driving mechanisms remain unclear, with functional traits likely playing a key role. Using 13 years of data from 300 sites in Germany, we tested whether and how trait-based community features mediate the effect of land-use intensity on acknowledged stability drivers (compensatory dynamics, portfolio effect, and dominant species variability), within and across plant and arthropod communities.

ApoNecV: A macro for cell death type differentiation.

The evaluation of large experimental datasets is a fundamental aspect of research in every scientific field. Streamlining this process can improve the reliability of results while making data analysis more efficient and faster to execute. In biomedical research it is often very important to determine the type of cell death after various treatments.

Half a Century of Temperate Non-Forest Vegetation Changes: No Net Loss in Species Richness, but Considerable Shifts in Taxonomic and Functional Composition.

In recent decades, global change and local anthropogenic pressures have severely affected natural ecosystems and their biodiversity. Although disentangling the effects of these factors is difficult, they are reflected in changes in the functional composition of plant communities. We present a comprehensive, large-scale analysis of long-term changes in plant communities of various non-forest habitat types in the Czech Republic based on 1154 vegetation-plot time series from 53 resurvey studies comprising 3909 vegetation-plot records.

Curcumin: A Potential Detoxifier Against Chemical and Natural Toxicants.

The human body gets exposed to a variety of toxins intentionally or unintentionally on a regular basis from sources such as air, water, food, and soil. Certain toxins can be synthetic, while some are biological. The toxins affect the various parts of the body by activating numerous pro-inflammatory markers, like oxidative stresses, that tend to disturb the normal function of the organs ultimately.

Interactions among Zinc, Iron, and Paraquat in the Physiological and Toxicological Responses of the Egyptian Cotton Leafworm .

Agricultural pollutants co-interact and affect the vital functions, stress tolerance, resistance, immunity, and survival of insect pests. These metal-herbicide interactions have inevitable but remarkable effects on insects, which remain poorly understood. Here, we examined the effects of the interactions among zinc (Zn), iron (Fe), and paraquat (PQ) at a sublethal dose on the physiological response of the Egyptian cotton leafworm .

Pulsed Electric Field Induces Significant Changes in the Metabolome of Species and Decreases Their Viability and Toxigenicity.

fungi are widespread pathogens of food crops, primarily associated with the formation of mycotoxins. Therefore, effective mitigation strategies for these toxicogenic microorganisms are required. In this study, the potential of pulsed electric field (PEF) as an advanced technology of increasing use in the food processing industry was investigated to minimize the viability of pathogens and to characterize the PEF-induced changes at the metabolomic level.

Exploring Multi-Pathology Brain Segmentation: From Volume-Based to Component-Based Deep Learning Analysis.

Detection and segmentation of brain abnormalities using Magnetic Resonance Imaging (MRI) is an important task that, nowadays, the role of AI algorithms as supporting tools is well established both at the research and clinical-production level. While the performance of the state-of-the-art models is increasing, reaching radiologists and other experts' accuracy levels in many cases, there is still a lot of research needed on the direction of in-depth and transparent evaluation of the correct results and failures, especially in relation to important aspects of the radiological practice: abnormality position, intensity level, and volume. In this work, we focus on the analysis of the segmentation results of a pre-trained U-net model trained and validated on brain MRI examinations containing four different pathologies: Tumors, Strokes, Multiple Sclerosis (MS), and White Matter Hyperintensities (WMH).

The e-STROKE Study: The Design of a Prospective Observational Multicentral Study.

The e-STROKE study is a prospective, multicenter observational study designed to assess the impact of various CT parameters (including e-ASPECT, CT perfusion (CTP), collateral flow status, and the size and location of the ischemic lesion) on the clinical outcomes of patients with ischemic stroke, as evaluated by the modified Rankins Scale (mRS) three months post-stroke. This study also aims to investigate whether the use of multimodal CT imaging increases the number of patients eligible for recanalization therapy. The analysis will integrate data from the RES-Q registry and radiological data from the e-STROKE system provided by Brainomix Ltd.

The Representational Challenge of Integration and Interoperability in Transformed Health Ecosystems.

: Health and social care systems around the globe are currently undergoing a transformation towards personalized, preventive, predictive, participative precision medicine (5PM), considering the individual health status, conditions, genetic and genomic dispositions, etc., in personal, social, occupational, environmental, and behavioral contexts. This transformation is strongly supported by technologies such as micro- and nanotechnologies, advanced computing, artificial intelligence, edge computing, etc.

Current Status of Bioprinting Using Polymer Hydrogels for the Production of Vascular Grafts.

Cardiovascular disease is one of the leading causes of death and serious illness in Europe and worldwide. Conventional treatment-replacing the damaged blood vessel with an autologous graft-is not always affordable for the patient, so alternative approaches are being sought. One such approach is patient-specific tissue bioprinting, which allows for precise distribution of cells, material, and biochemical signals.

Secondary Syphilis Presenting With an Interstitial Granuloma Annulare-Like Histopathologic Pattern: A Report of 2 Cases.

Syphilis, known as "the great mimicker," is caused by the spirochete Treponema pallidum and is characterized by a diverse array of clinical and histopathologic presentations. In secondary cutaneous syphilis, the most consistent morphological features include a superficial and deep perivascular infiltrate containing plasma cells, varying degrees of endothelial swelling, irregular acanthosis, elongation of rete ridges, a vacuolated pattern, and the presence of plasma cells. Although serologic tests are essential for definitive diagnosis, spirochetes can sometimes be directly identified in silver-stained tissue slides or through immunohistochemistry.

Fitting Copulas with Maximal Entropy.

We deal with two-dimensional copulas from the perspective of their differential entropy. We formulate a problem of finding a copula with maximum differential entropy when some copula values are given. As expected, the solution is a copula with a piecewise constant density (a checkerboard copula).

Spectral Analysis of Light-Adapted Electroretinograms in Neurodevelopmental Disorders: Classification with Machine Learning.

Electroretinograms (ERGs) show differences between typically developing populations and those with a diagnosis of autism spectrum disorder (ASD) or attention deficit/hyperactivity disorder (ADHD). In a series of ERGs collected in ASD ( = 77), ADHD ( = 43), ASD + ADHD ( = 21), and control ( = 137) groups, this analysis explores the use of machine learning and feature selection techniques to improve the classification between these clinically defined groups. Standard time domain and signal analysis features were evaluated in different machine learning models.

Bosworth fracture: Pathoanatomy, Complications, and Medium-term Results of Treatment.

Background: Bosworth fractures (BFs) with entrapment of a fibular fragment behind the posterior malleolus (PM) are rare but potentially serious injuries to the ankle. Despite an increased awareness through a more regular use of computed tomography (CT) scanning, there is still a scarcity of clinical outcome studies.

Methods: Over a course of 25 years, data on 23 patients treated for BF at our institutions (mean age 44 years) were collected prospectively.

Somatic mutations and DNA methylation identify a subgroup of poor prognosis within lower-risk myelodysplastic syndromes.

Lower risk (LR) myelodysplastic syndromes (MDS) are heterogeneous hematopoietic stem and progenitor disorders caused by the accumulation of somatic mutations in various genes including epigenetic regulators that may produce convergent DNA methylation patterns driving specific gene expression profiles. The integration of genomic, epigenomic, and transcriptomic profiling has the potential to spotlight distinct LR-MDS categories on the basis of pathophysiological mechanisms. We performed a comprehensive study of somatic mutations and DNA methylation in a large and clinically well-annotated cohort of treatment-naive patients with LR-MDS at diagnosis from the EUMDS registry (ClinicalTrials.

Dysregulation of transposable elements and PIWI-interacting RNAs in myelodysplastic neoplasms.

Background: Myelodysplastic neoplasms (MDS) are heterogeneous hematopoietic disorders characterized by ineffective hematopoiesis and genome instability. Mobilization of transposable elements (TEs) is an important source of genome instability leading to oncogenesis, whereas small PIWI-interacting RNAs (piRNAs) act as cellular suppressors of TEs. However, the roles of TEs and piRNAs in MDS remain unclear.

Remodeling the light-adapted electroretinogram using a bayesian statistical approach.

Objective: To present a remodeling of the electroretinogram waveform using a covariance matrix to identify regions of interest and distinction between a control and attention deficit/hyperactivity disorder (ADHD) group. Electroretinograms were recorded in n = 25 ADHD (16 male; age 11.9 ± 2.

Effect of selected Indonesian plants on Giardia intestinalis in an experimental in vitro model.

Background: This study evaluated in vitro antigiardial activity in four Indonesian plants (Archidendron fagifolium, Diospyros sumatrana, Piper betle and Shorea sumatrana) extracted in methanol, methanol-tetrahydrofuran, and water. These plants exhibiting promising anti-parasitic activity were selected on the basis of collected behavioral data and their ability to decrease parasite load in Sumatran orangutans. Extracts of Arabidopsis thaliana, a plant routinely used as a laboratory model in research, were used as a negative control.