Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Neuronal Cell Lines as An In Vitro Toxicological Tool for the Evaluation of Novel Psychoactive Substances

Novel psychoactive substances (NPS) are synthetic substances belonging to diverse groups, designed to mimic the effects of scheduled drugs, resulting in altered toxicity and potency. Up to now, information available on the pharmacology and toxicology of these new substances is very limited, posing a considerable challenge for prevention and treatment. The present in vitro study investigated the possible mechanisms of toxicity of two emerging NPS (i) 4′-methyl-alpha-pyrrolidinoexanophenone (3,4-MDPHP), a synthetic cathinone, and (ii) 2-chloro-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA), a phenethylamine. In addition, to apply our model to the class of synthetic opioids, we evaluated the toxicity of fentanyl, as a reference compound for this group of frequently abused substances. To this aim, the in vitro toxic effects of these three compounds were evaluated in dopaminergic-differentiated SH-SY5Y cells. Following 24 h of exposure, all compounds induced a loss of viability, and oxidative stress in a concentration-dependent manner. 2-Cl-4,5-MDMA activates apoptotic processes, while 3,4-MDPHP elicits cell death by necrosis. Fentanyl triggers cell death through both mechanisms. Increased expression levels of pro-apoptotic Bax and caspase 3 activity were observed following 2-Cl-4,5-MDMA and fentanyl, but not 3,4-MDPHP exposure, confirming the different modes of cell death.
Association of genetic variants of FBXO32 and FOXO6 in the FOXO pathway with breast cancer risk

Forkhead box class O (FOXO) transcription factors play a pivotal role in regulating a variety of biological processes, including organismal development, cell signaling, cell metabolism, and tumorigenesis. Therefore, we hypothesize that genetic variants in FOXO pathway genes are associated with breast cancer (BC) risk. To test this hypothesis, we conducted a large meta‐analysis using 14 published genome‐wide association study (GWAS) data sets in the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) study. We assessed associations between 5214 (365 genotyped in DRIVE and 4849 imputed) common single‐nucleotide polymorphisms (SNPs) in 55 FOXO pathway genes and BC risk. After multiple comparison corrections by the Bayesian false‐discovery probability method, we found five SNPs to be significantly associated with BC risk. In stepwise multivariate logistic regression analysis with adjustment for age, principal components, and previously published SNPs in the same data set, three independent SNPs (i.e., FBXO32 rs10093411 A>G, FOXO6 rs61229336 C>T, and FBXO32 rs62521280 C>T) remained to be significantly associated with BC risk (p = 0.0008, 0.0011, and 0.0017, respectively). Additional expression quantitative trait loci analysis revealed that the FBXO32 rs62521280 T allele was associated with decreased messenger RNA (mRNA) expression levels in breast tissue, while the FOXO6 rs61229336 T allele was found to be associated with decreased mRNA expression levels in the whole blood cells. Once replicated by other investigators, these genetic variants may serve as new biomarkers for BC risk.
Update on the Classification and Pathophysiological Mechanisms of Pediatric Cardiorenal Syndromes

Cardiorenal syndrome (CRS) is defined as a disorder resulting from the abnormal interaction between the heart and kidney, in which acute or chronic dysfunction of one organ may lead to acute and/or chronic dysfunction of the other. The functional interplay between the heart and kidney is characterized by a complex bidirectional symbiotic interaction, regulated by a wide array of both genetic and environmental mechanisms. There are at least five known subtypes of CRS, based on the severity of clinical features and the degree of heart/renal failure. The fourth subtype (cardiorenal syndrome type 4 (CRS4)) is characterized by a primary chronic kidney disease (CKD), which in turn leads to a decreased cardiac function. Impairment of renal function is among the most important pathophysiological factors contributing to heart failure (HF) in the pediatric age group, and cardiovascular complications could be one of the most important causes of mortality in pediatric patients with advanced CKD. In this context, a loss of glomerular filtration rate directly correlates with both the progression of cardiovascular complications in CRS and the risk of HF. This review describes the interaction pathways between the heart and kidney and the recently identified pathophysiological mechanisms underlying pediatric CRS, with a special focus on CRS4, which encompasses both primary CKD and cardiovascular disease (CVD).
Lewy Body Dementias: A Coin with Two Sides?

Lewy body dementias (LBDs) consist of dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), which are clinically similar syndromes that share neuropathological findings with widespread cortical Lewy body deposition, often with a variable degree of concomitant Alzheimer pathology. The objective of this article is to provide an overview of the neuropathological and clinical features, current diagnostic criteria, biomarkers, and management of LBD. Literature research was performed using the PubMed database, and the most pertinent articles were read and are discussed in this paper. The diagnostic criteria for DLB have recently been updated, with the addition of indicative and supportive biomarker information. The time interval of dementia onset relative to parkinsonism remains the major distinction between DLB and PDD, underpinning controversy about whether they are the same illness in a different spectrum of the disease or two separate neurodegenerative disorders. The treatment for LBD is only symptomatic, but the expected progression and prognosis differ between the two entities. Diagnosis in prodromal stages should be of the utmost importance, because implementing early treatment might change the course of the illness if disease-modifying therapies are developed in the future. Thus, the identification of novel biomarkers constitutes an area of active research, with a special focus on α-synuclein markers.
A Cluster Randomized Controlled Trial Feasibility Study of a WhatsApp-Delivered Intervention to Promote Healthy Eating Habits in Male Firefighters

This cluster randomized controlled trial (CRCT)-designed study aimed to explore the feasibility of a promotion pamphlet and/or WhatsApp as a suitable mode of delivery to promote healthy eating habits with fruit and vegetables (F&V) among firefighters. Convenience and snowball sampling methods were used. Forty-five firefighters from 23 fire stations were recruited and they all received the printed pamphlet, while the intervention group participants (n = 20) received additional teaching material through WhatsApp every two weeks for eight weeks. Feasibility outcomes included retention, practicality, and implementation. The participants reported high levels of satisfaction with the intervention. There were significant improvements in the mean numbers of days consuming F&V (p = 0.002; p = 0.031) in the intervention group, and for fruit consumption (p = 0.033) in the control group between the baseline (T0) and 3 months after completion of intervention (T1). High levels of participants’ satisfaction with the intervention revealed that a full-scale CRCT of the WhatsApp-delivered intervention promoting healthy eating could be feasible, especially as a means of increasing the numbers of days they consumed F&V and the numbers of servings of these consumed per day.
Interférométrie Simultanée avec Deux Espèces Atomiques ⁸⁷Rb/⁸⁵Rb et Applications aux Mesures Inertielles

Dans la problematique emergente des experiences visant a tester le Principe d'Equivalence a l'aide de capteurs inertiels a atomes froids, cette these porte sur la realisation et la caracterisation d'un interferometre atomique double espece simultane (⁸⁷Rb et ⁸⁵Rb) qui permet l'obtention d'une mesure extremement sensible de l'acceleration differentielle. L'interferometre, de type Mach-Zehnder, repose sur la manipulation simultanee des ondes de matiere atomiques a l'aide de transitions Raman stimulees. Le systeme laser est base sur le doublage en frequence d'une unique source laser a 1560 nm. L'ensemble des frequences lasers requises pour la manipulation des deux isotopes (piegeage, refroidissement, selection, interferometrie et detection) sont generees par modulation en phase de cette source. Une modelisation detaillee des reponses inertielles de l'interferometre ainsi que l'analyse d'une methode d'extraction de la phase differentielle a partir du signal elliptique ont ete menees. La mesure de l'acceleration differentielle a conduit a un test atomique du Principe d'Equivalence Faible de η(⁸⁷Rb,85Rb) = (1.3 ± 3.2) × 10⁻⁷, a l'etat de l'art. L'aspect simultane de la mesure a permis de mettre en evidence la rejection du bruit de vibration par effet de mode commun pour la premiere fois avec deux especes differentes, le facteur de rejection etant aujourd'hui de 50 000. Les performances actuelles de l'instrument sur la mesure d'acceleration differentielle montrent une sensibilite de 1.23×10⁻⁷g/√Hz et une resolution de 2×10⁻⁹g pour des temps d'integration inferieurs a quelques heures. Pour finir, des modes de fonctionnement innovants d'interferometres atomiques double espece pour la mesure d'acceleration embarquee sont explores.
Chronic and Transient Hyperglycemia Induces Changes in the Expression Patterns of IL6 and ADIPOQ Genes and Their Associated Epigenetic Modifications in Differentiating Human Visceral Adipocytes

Adipokines secreted by hypertrophic visceral adipose tissue (VAT) instigate low-grade inflammation, followed by hyperglycemia (HG)-related metabolic disorders. The latter may develop with the participation of epigenetic modifications. Our aim was to assess how HG influences selected epigenetic modifications and the expression of interleukin 6 (IL-6) and adiponectin (APN; gene symbol ADIPOQ) during the adipogenesis of human visceral preadipocytes (HPA-v). Adipocytes (Ads) were chronically or transiently HG-treated during three stages of adipogenesis (proliferation, differentiation, maturation). We measured adipokine mRNA, protein, proven or predicted microRNA expression (RT-qPCR and ELISA), and enrichment of H3K9/14ac, H3K4me3, and H3K9me3 at gene promoter regions (chromatin immunoprecipitation). In chronic HG, we detected different expression patterns of the studied adipokines at the mRNA and protein levels. Chronic and transient HG-induced changes in miRNA (miR-26a-5p, miR-26b-5p, let-7d-5p, let-7e-5p, miR-365a-3p, miR-146a-5p) were mostly convergent to altered IL-6 transcription. Alterations in histone marks at the IL6 promoter were also in agreement with IL-6 mRNA. The open chromatin marks at the ADIPOQ promoter mostly reflected the APN transcription during NG adipogenesis, while, in the differentiation stage, HG-induced changes in all studied marks were in line with APN mRNA levels. In summary, HG dysregulated adipokine expression, promoting inflammation. Epigenetic changes coexisted with altered expression of adipokines, especially for IL-6; therefore, epigenetic marks induced by transient HG may act as epi-memory in Ads. Such changes in the epigenome and expression of adipokines could be instrumental in the development of inflammation and metabolic deregulation of VAT.
Reliability and Validity of the Polhemus Liberty System for Upper Body Segment and Joint Angular Kinematics of Elite Golfers

Golf swing analysis is common in both recreational and professional levels where players are searching for improvements in shot accuracy and distance. The use of motion analysis systems such as the portable Polhemus Liberty system is gaining interest by coaches and players; however, to date, no research has examined the usefulness of the Polhemus Liberty system for golf swing analysis. Therefore, the purpose of this study was to determine the reliability of the Polhemus Liberty system and validity compared to the VICON Nexus motion analysis system when assessing segment (pelvis and thorax) and joint (shoulder, elbow and wrist) angular kinematics during a golf swing at key events (address, top of backswing and impact). Fifteen elite amateur/professional golfers performed ten golf swing trials within specified bounds using their 5-iron club. Reliability was assessed using interclass coefficient, effect size and t-test statistics by all participants completing two separate testing sessions on separate days following the same experimental protocol. Validity was assessed using effect size, Pearson correlation and t-test statistics by comparing swings captured using both Polhemus Liberty and VICON Nexus concurrently. Results demonstrated no difference in ball outcome results using the Trackman launch monitor (P > 0.05) and that the Polhemus Liberty system was reliable across the two sessions for all segment (pelvis and thorax) and joint (lead shoulder (gleno-humeral joint), elbow and wrist) angular kinematics (P > 0.05). Validity analysis showed that the Polhemus Liberty system for the segments (pelvis and thorax) and joints (lead shoulder and wrist) were different compared to the VICON Nexus data at key events during the golf swing. Although validity could not be confirmed against VICON Nexus modeling, the Polhemus Liberty system may still be useful for golf swing analysis across training sessions. However, caution should be applied when comparing data from the system to published research data using different motion analysis methods.
A Pilot Study to Validate a Wearable Inertial Sensor for Gait Assessment in Older Adults with Falls

The high prevalence of falls and the enormous impact they have on the elderly population is a cause for concern. We aimed to develop a walking-monitor gait pattern (G-STRIDE) for older adults based on a 6-axis inertial measurement (IMU) with the application of pedestrian dead reckoning algorithms and tested its structural and clinical validity. A cross-sectional case–control study was conducted with 21 participants (11 fallers and 10 non-fallers). We measured gait using an IMU attached to the foot while participants walked around different grounds (indoor flooring, outdoor floor, asphalt, etc.). The G-STRIDE consisted of a portable inertial device that monitored the gait pattern and a mobile app for telematic clinical analysis. G-STRIDE made it possible to measure gait parameters under normal living conditions when walking without assessing the patient in the outpatient clinic. Moreover, we verified concurrent validity with convectional outcome measures using intraclass correlation coefficients (ICCs) and analyzed the differences between participants. G-STRIDE showed high estimation accuracy for the walking speed of the elderly and good concurrent validity compared to conventional measures (ICC = 0.69; p < 0.000). In conclusion, the developed inertial-based G-STRIDE can accurately classify older people with risk to fall with a significance as high as using traditional but more subjective clinical methods (gait speed, Timed Up and Go Test).
Global Proteomic Profiling of Pediatric AML: A Pilot Study

Simple Summary The second most common childhood leukemia, acute myeloid leukemia (AML), is a heterogeneous disease with a poor prognosis. In order to improve outcomes, efforts to understand the genomic/transcriptomic landscape of AML have been performed. However, there is a significant gap in our understanding of leukemic cell proteomics. In comparison to the proteome, the transcriptome alone cannot adequately represent the biological functions within cells and it is often not a target for immediate drug development. In the current study, we investigated cytogenetic differences at the proteomic level and sought potential predictive biomarkers and druggable proteins. Abstract Acute Myeloid Leukemia (AML) is a heterogeneous disease with several recurrent cytogenetic abnormalities. Despite genomics and transcriptomics profiling efforts to understand AML’s heterogeneity, studies focused on the proteomic profiles associated with pediatric AML cytogenetic features remain limited. Furthermore, the majority of biological functions within cells are operated by proteins (i.e., enzymes) and most drugs target the proteome rather than the genome or transcriptome, thus, highlighting the significance of studying proteomics. Here, we present our results from a pilot study investigating global proteomic profiles of leukemic cells obtained at diagnosis from 16 pediatric AML patients using a robust TMT-LC/LC-MS/MS platform. The proteome profiles were compared among patients with or without core binding factor (CBF) translocation indicated by a t(8;21) or inv(16) cytogenetic abnormality, minimal residual disease status at the end of the first cycle of chemotherapy (MRD1), and in vitro chemosensitivity of leukemic cells to cytarabine (Ara-C LC50). Our results established proteomic differences between CBF and non-CBF AML subtypes, providing insights to AML subtypes physiology, and identified potential druggable proteome targets such as THY1 (CD90), NEBL, CTSF, COL2A1, CAT, MGLL (MAGL), MACROH2A2, CLIP2 (isoform 1 and 2), ANPEP (CD13), MMP14, and AK5.
Convolutional Neural Networks Cascade for Automatic Pupil and Iris Detection in Ocular Proton Therapy †

Eye tracking techniques based on deep learning are rapidly spreading in a wide variety of application fields. With this study, we want to exploit the potentiality of eye tracking techniques in ocular proton therapy (OPT) applications. We implemented a fully automatic approach based on two-stage convolutional neural networks (CNNs): the first stage roughly identifies the eye position and the second one performs a fine iris and pupil detection. We selected 707 video frames recorded during clinical operations during OPT treatments performed at our institute. 650 frames were used for training and 57 for a blind test. The estimations of iris and pupil were evaluated against the manual labelled contours delineated by a clinical operator. For iris and pupil predictions, Dice coefficient (median = 0.94 and 0.97), Szymkiewicz–Simpson coefficient (median = 0.97 and 0.98), Intersection over Union coefficient (median = 0.88 and 0.94) and Hausdorff distance (median = 11.6 and 5.0 (pixels)) were quantified. Iris and pupil regions were found to be comparable to the manually labelled ground truths. Our proposed framework could provide an automatic approach to quantitatively evaluating pupil and iris misalignments, and it could be used as an additional support tool for clinical activity, without impacting in any way with the consolidated routine.
CD163 as a Potential Biomarker of Monocyte Activation in Ischemic Stroke Patients

In ischemic stroke patients, a higher monocyte count is associated with disease severity and worse prognosis. The complex correlation between subset phenotypes and functions underscores the importance of clarifying the role of monocyte subpopulations. We examined the subtype-specific distribution of the CD163+ and CD80+ circulating monocytes and evaluated their association with the inflammatory status in 26 ischemic stroke patients and 16 healthy controls. An increased percentage of CD163+/CD16+ and CD163+/CD14++ events occurred 24 and 48 h after a stroke compared to the controls. CD163+ expression was more pronounced in CD16+ non-classical and intermediate monocytes, as compared to CD14+ classical subtype, 24 h after stroke. Conversely, the percentage of CD80+/CD16+ events was unaffected in patients; meanwhile, the percentage of CD80+/CD14+ events significantly increased only 24 h after stroke. Interleukin (IL)-1beta, TNF-alpha, and IL-4 mRNA levels were higher, while IL-10 mRNA levels were reduced in total monocytes from patients versus controls, at either 24 h or 48 h after stroke. The percentage of CD163+/CD16+ events 24 h after stroke was positively associated with NIHSS score and mRS at admission, suggesting that stroke severity and disability are relevant triggers for CD163+ expression in circulating CD16+ monocytes.
Combined Effect of Laboratory-Simulated Fire and Chromium Pollution on Microbial Communities in an Agricultural Soil

Simple Summary Soil quality and fertility rely on soil microorganisms which contribute to nutrient cycling and plant nutrition. Accidental or intentional fires can almost completely kill soil microbiota and cause soil sterilization. Fires can also destroy soil organic matter (OM), thus causing the release of potentially toxic elements such as Cr that can further disturb soil recolonization by surviving bacteria. The identification of species able to cope with such altered environments is highly relevant to restore soil life in degraded soils and to remediate polluted sites. In this study, we identified soil microorganisms potentially suitable to colonize fire-affected areas and tolerate high concentrations of bioavailable and toxic Cr, and which therefore could be useful for the above-mentioned purposes. Abstract Fire events in agricultural soils can modify not only soil properties but also the structure of soil microbial communities, especially in soils containing high concentrations of potentially toxic elements (PTEs). The recolonization of burned soils can in fact favor the proliferation of certain microorganisms, more adaptable to post-fire soil conditions and higher PTE availability, over others. In this study, we simulated with laboratory experiments the microbial recolonization of an agricultural soil containing high Cr concentrations after heating at 500 °C for 30 min, to mimic the burning of crop residues. Changes in soil properties and Cr speciation were assessed, as well as soil microbial structure by means of 16S rRNA gene sequencing. Both altered soil conditions and increased Cr availability, especially Cr(VI), appeared to be responsible for the reduction in species diversity in heated soils and the proliferation of Firmicutes. Indeed, already after 3 days from the heat treatment, Firmicutes increased from 14% to 60% relative abundance. In particular, Paenibacillus was the most abundant genus identified after the simulation, with an average relative abundance of 40%. These bacteria are known to be good fire-responders and Cr-tolerant. These results could be useful to identify bacterial strains to be used as bioindicators of altered environments and for the recovery of fire-impacted polluted sites.
Gemcitabine-Based Chemoradiotherapy Enhanced by a PARP Inhibitor in Pancreatic Cancer Cell Lines

Pancreatic ductal adenocarcinoma is a devastating disease with a 5-year overall survival of 9% for all stages. Gemcitabine-based chemoradiotherapy for locally advanced pancreatic cancer is highly toxic. We conducted an in vitro study to determine whether poly(ADP-ribose) polymerase-1 inhibition radiosensitized gemcitabine-based chemotherapy. Human pancreatic cancer cell lines, MIA PaCa-2, AsPC-1, BxPC-3 and PANC-1 were treated with gemcitabine (10 nM) and/or olaparib (1 µM). Low-LET gamma single dose of 2, 5 and 10 Gy radiations were carried out. Clonogenic assay, PAR immunoblotting, cell cycle distribution, γH2Ax, necrotic and autophagic cell death quantifications were performed. Treatment with olaparib alone was not cytotoxic, but highly radiosensitized cell lines, particularly at high dose per fraction A non-cytotoxic concentration of gemcitabine radiosensitized cells, but less than olaparib. Interestingly, olaparib significantly enhanced gemcitabine-based radiosensitization in PDAC cell lines with synergistic effect in BxPC-3 cell line. All cell lines were radiosensitized by the combination of gemcitabine and olaparib, through an increase of unrepaired double-strand, a G2 phase block and cell death. Radiosensitization was increased with high dose of radiation. The combination of olaparib with gemcitabine-based chemoradiotherapy could lead to an enhancement of local control in vivo and an improvement in disease-free survival.