Miracle-dz/UniFAR-FTUs huggingface dataset:
Deep Brain Stimulation and Hypoxemic Perinatal Encephalopathy: State of Art and Perspectives

Cerebral palsy (CP) is a heterogeneous group of non-progressive syndromes with lots of clinical variations due to the extent of brain damages and etiologies. CP is majorly defined by dystonia and spasticity. The treatment of acquired dystonia in CP is very difficult. Many pharmacological treatments have been tried and surgical treatment consists of deep brain stimulation (continuous electrical neuromodulation) of internal globus pallidus (GPi). A peculiar cause of CP is neonatal encephalopathy due to an anoxic event in the perinatal period. Many studies showed an improvement of dystonia in CP patients with bilateral GPi DBS. However, it remains a variability in the range of 1% to 50%. Published case-series concerned mainly small population with a majority of adult patients. Selection of patients according to the clinical pattern, to the brain lesions observed on classical imaging and to DTI is the key of a high success rate of DBS in children with perinatal hypoxemic encephalopathy. Only a large retrospective study with a high number of patients in a homogeneous pediatric population with a long-term follow-up or a prospective multicenter trial investigation could answer with a high degree of certitude of the real interest of this therapeutic in children with hypoxemic perinatal encephalopathy.
Cytokine Adsorption onto the Modified Carbon Sorbent Surface in vitro in Peritonitis

рых хирургических заболеваний, нередко приводит к ге нерализации процесса, развитию септического шока, по лиорганной недостаточности и высокой летальности [1—4]. В последнее десятилетие были проведены углубленные клинико экспериментальные исследования по разработ ке патогенетических методов регуляции и коррекции им мунологических нарушений в органах и системах орга низма при перитоните [5, 6]. К способам регулирования можно отнести постепенное изменение в спектре регуля торных пептидов биологической активности цитокинов, Цель исследования — оценить эффективность сорбции цитокинов из плазмы крови больных разлитым гнойным перитонитом углеродным сорбентом с локально модифицированной аминокапроновой кислотой поверхностью. Материал и методы. Материалом для исследования служила плазма крови, полученная при проведении плазма9 фереза у 10 больных острым панкреатитом, осложнившимся панкреонекрозом и разлитым гнойным перитони9 том, в которой до сорбции и после сорбции определяли содержание цитокинов: интерлейкина91β (IL91β), интер9 лейкина94 (IL94) и интерлейкина98 (IL98) методом иммуноферментного анализа. Проведена сравнительная оценка сорбционных свойств углеродного гемосорбента и сорбента, модифицированного аминокапроновой кис9 лотой. Результаты. Модифицирование поверхности углеродного адсорбента аминокапроновой кислотой с по9 следующей ее поликонденсацией приводит к увеличению содержания поверхностных функциональных групп (кислород9 и азотсодержащих), усиливающих гидрофильность поверхности и специфический характер сорбции, что позволяет значительно повысить эффективность сорбции ряда цитокинов различной гидрофобности, тем са9 мым выступать в качестве средства контроля и управления концентрацией в плазме крови регуляторных белков, прежде всего провоспалительного цитокина IL91β, хемокина IL98 и цитокина Т9хелперного клона — IL94. Ключе вые слова: перитонит, цитокины, углеродный сорбент.
Ascophyllum nodosum Based Extracts Counteract Salinity Stress in Tomato by Remodeling Leaf Nitrogen Metabolism

Biostimulants have rapidly and widely been adopted as growth enhancers and stress protectants in agriculture, however, due to the complex nature of these products, their mechanism of action is not clearly understood. By using two algal based commercial biostimulants in combination with the Solanum lycopersicum cv. MicroTom model system, we assessed how the modulation of nitrogen metabolites and potassium levels could contribute to mediate physiological mechanisms that are known to occur in response to salt/and or osmotic stress. Here we provide evidence that the reshaping of amino acid metabolism can work as a functional effector, coordinating ion homeostasis, osmotic adjustment and scavenging of reactive oxygen species under increased osmotic stress in MicroTom plant cells. The Superfifty biostimulant is responsible for a minor amino acid rich-phenotype and could represent an interesting instrument to untangle nitrogen metabolism dynamics in response to salinity and/or osmotic stress.
Analysis of Wine and Its Use in Tracing the Origin of Grape Cultivation

Abstract The concentrations of elemental and volatile components in wine and the effect of biological, meteorological, and anthropogenic factors on their levels are important for authentication and quality assurance. Sample preparation for atomic absorption and inductively coupled plasma spectrometries for elemental analysis as well as chromatographic and electronic nose (EN) analytical methods for volatile compounds are reviewed. The International Organization of Vine and Wine (OIV) and countries that produce and import wine developed methods and set limits on metal abundance to ensure that all metal concentrations are well below toxic threshold limits. With the use of data analysis tools, elemental analysis can enable wines to be traced back to their geographic region of origin. When paired with volatile and isotopic analysis the accuracy of this authentication greatly improves. Tracing studies are reviewed to demonstrate the capabilities of these analyses.
Cognitive Control of Working Memory: A Model-Based Approach

Working memory (WM)-based decision making depends on a number of cognitive control processes that control the flow of information into and out of WM and ensure that only relevant information is held active in WM’s limited-capacity store. Although necessary for successful decision making, recent work has shown that these control processes impose performance costs on both the speed and accuracy of WM-based decisions. Using the reference-back task as a benchmark measure of WM control, we conducted evidence accumulation modeling to test several competing explanations for six benchmark empirical performance costs. Costs were driven by a combination of processes running outside of the decision stage (longer non-decision time) and inhibition of the prepotent response (lower drift rates) in trials requiring WM control. Individuals also set more cautious response thresholds when expecting to update WM with new information versus maintain existing information. We discuss the promise of this approach for understanding cognitive control in WM-based decision making.
Extracellular Vesicles as a Therapeutic Tool for Kidney Disease: Current Advances and Perspectives

Extracellular vesicles (EVs) have been described as important mediators of cell communication, regulating several physiological processes, including tissue recovery and regeneration. In the kidneys, EVs derived from stem cells have been shown to support tissue recovery in diverse disease models and have been considered an interesting alternative to cell therapy. For this purpose, however, several challenges remain to be overcome, such as the requirement of a high number of EVs for human therapy and the need for optimization of techniques for their isolation and characterization. Moreover, the kidney’s complexity and the pathological process to be treated require that EVs present a heterogeneous group of molecules to be delivered. In this review, we discuss the recent advances in the use of EVs as a therapeutic tool for kidney diseases. Moreover, we give an overview of the new technologies applied to improve EVs’ efficacy, such as novel methods of EV production and isolation by means of bioreactors and microfluidics, bioengineering the EV content and the use of alternative cell sources, including kidney organoids, to support their transfer to clinical applications.
Epigenomic Analysis of RAD51 ChIP-seq Data Reveals cis-regulatory Elements Associated with Autophagy in Cancer Cell Lines

Simple Summary RAD51 is a key enzyme involved in homologous recombination during DNA double-strand break repair. However, recent studies suggest that non-canonical roles of RAD51 may exist. The aim of our study was to assess regulatory roles of RAD51 by reanalyzing RAD51 ChIP-seq data in GM12878, HepG2, K562, and MCF-7 cell lines. We identified 5137, 2611, 7192, and 3498 RAD51-associated cis-regulatory elements in GM12878, HepG2, K562, and MCF-7 cell lines, respectively. Intriguingly, gene ontology analysis revealed that promoters of the autophagy pathway-related genes were most significantly occupied by RAD51 in all four cell lines, predicting a non-canonical role of RAD51 in regulating autophagy-related genes. Abstract RAD51 is a recombinase that plays a pivotal role in homologous recombination. Although the role of RAD51 in homologous recombination has been extensively studied, it is unclear whether RAD51 can be involved in gene regulation as a co-factor. In this study, we found evidence that RAD51 may contribute to the regulation of genes involved in the autophagy pathway with E-box proteins such as USF1, USF2, and/or MITF in GM12878, HepG2, K562, and MCF-7 cell lines. The canonical USF binding motif (CACGTG) was significantly identified at RAD51-bound cis-regulatory elements in all four cell lines. In addition, genome-wide USF1, USF2, and/or MITF-binding regions significantly coincided with the RAD51-associated cis-regulatory elements in the same cell line. Interestingly, the promoters of genes associated with the autophagy pathway, such as ATG3 and ATG5, were significantly occupied by RAD51 and regulated by RAD51 in HepG2 and MCF-7 cell lines. Taken together, these results unveiled a novel role of RAD51 and provided evidence that RAD51-associated cis-regulatory elements could possibly be involved in regulating autophagy-related genes with E-box binding proteins.
Monolayer MoS2 photodetectors with a buried-gate field-effect transistor structure

Unlike zero-bandgap graphene, molybdenum disulfide (MoS2) has an adjustable bandgap and high light absorption rate, hence photodetectors based on MoS2 have attracted tremendous research attention. Most of the reported MoS2 photodetectors adopted back-gate field-effect transistor (FET) structure due to its easy fabrication and modulation features. However, the back-gate FET structure requires very high gate voltage up to 100 V, and it is impossible to modulate each device in an array with this structure independently. This work demonstrated a monolayer MoS2 photodetector based on a buried-gate FET structure whose experimental results showed that both the electrical and photoelectrical properties could be well modulated by a gate voltage as low as 3 V. A photoresponsivity above 1 A W−1 was obtained under a 395 nm light-emitting diode light illumination, which is over 2 orders of magnitude higher than that of a reported back-gate photodetector based on monolayer MoS2 (7.5 mA W−1). The photoresponsivity can be further improved by increasing the buried gate voltage and source-drain voltage. These results are of significance for the practical applications of MoS2 photodetectors, especially in the low voltage and energy-saving areas.
AutoPPI: An Ensemble of Deep Autoencoders for Protein–Protein Interaction Prediction

Proteins are essential molecules, that must correctly perform their roles for the good health of living organisms. The majority of proteins operate in complexes and the way they interact has pivotal influence on the proper functioning of such organisms. In this study we address the problem of protein–protein interaction and we propose and investigate a method based on the use of an ensemble of autoencoders. Our approach, entitled AutoPPI, adopts a strategy based on two autoencoders, one for each type of interactions (positive and negative) and we advance three types of neural network architectures for the autoencoders. Experiments were performed on several data sets comprising proteins from four different species. The results indicate good performances of our proposed model, with accuracy and AUC values of over 0.97 in all cases. The best performing model relies on a Siamese architecture in both the encoder and the decoder, which advantageously captures common features in protein pairs. Comparisons with other machine learning techniques applied for the same problem prove that AutoPPI outperforms most of its contenders, for the considered data sets.
Anatomo-Functional Origins of the Cortical Silent Period: Spotlight on the Basal Ganglia

The so-called cortical silent period (CSP) refers to the temporary interruption of electromyographic signal from a muscle following a motor-evoked potential (MEP) triggered by transcranial magnetic stimulation (TMS) over the primary motor cortex (M1). The neurophysiological origins of the CSP are debated. Previous evidence suggests that both spinal and cortical mechanisms may account for the duration of the CSP. However, contextual factors such as cortical fatigue, experimental procedures, attentional load, as well as neuropathology can also influence the CSP duration. The present paper summarizes the most relevant evidence on the mechanisms underlying the duration of the CSP, with a particular focus on the central role of the basal ganglia in the “direct” (excitatory), “indirect” (inhibitory), and “hyperdirect” cortico-subcortical pathways to manage cortical motor inhibition. We propose new methods of interpretation of the CSP related, at least partially, to the inhibitory hyperdirect and indirect pathways in the basal ganglia. This view may help to explain the respective shortening and lengthening of the CSP in various neurological disorders. Shedding light on the complexity of the CSP’s origins, the present review aims at constituting a reference for future work in fundamental research, technological development, and clinical settings.
Characterization of PARP6 Function in Knockout Mice and Patients with Developmental Delay

PARP6, a member of a family of enzymes (17 in humans) known as poly-ADP-ribose polymerases (PARPs), is a neuronally enriched PARP. While previous studies from our group show that Parp6 is a regulator of dendrite morphogenesis in rat hippocampal neurons, its function in the nervous system in vivo is poorly understood. Here, we describe the generation of a Parp6 loss-of-function mouse model for examining the function of Parp6 during neurodevelopment in vivo. Using CRISPR-Cas9 mutagenesis, we generated a mouse line that expressed a Parp6 truncated variant (Parp6TR) in place of Parp6WT. Unlike Parp6WT, Parp6TR is devoid of catalytic activity. Homozygous Parp6TR do not exhibit obvious neuromorphological defects during development, but nevertheless die perinatally. This suggests that Parp6 catalytic activity is important for postnatal survival. We also report PARP6 mutations in six patients with several neurodevelopmental disorders, including microencephaly, intellectual disabilities, and epilepsy. The most severe mutation in PARP6 (C563R) results in the loss of catalytic activity. Expression of Parp6C563R in hippocampal neurons decreases dendrite morphogenesis. To gain further insight into PARP6 function in neurons we also performed a BioID proximity labeling experiment in hippocampal neurons and identified several microtubule-binding proteins (e.g., MAP-2) using proteomics. Taken together, our results suggest that PARP6 is an essential microtubule-regulatory gene in mice, and that the loss of PARP6 catalytic activity has detrimental effects on neuronal function in humans.
New DNA Methylation Signals for Malignant Pleural Mesothelioma Risk Assessment

Simple Summary Our study investigated DNA methylation differences in easily accessible white blood cells (WBCs) between malignant pleural mesothelioma (MPM) cases and asbestos-exposed cancer-free controls. A multiple regression model highlighted that the methylation level of two single CpGs (cg03546163 in FKBP5 and cg06633438 in MLLT1) are independent MPM markers. The epigenetic changes at the FKBP5 and MLLT1 genes were robustly associated with MPM in asbestos-exposed subjects. Interaction analyses showed that MPM cases and cancer-free controls showed DNAm differences which may be linked to asbestos exposure. Abstract Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm. Patients are usually diagnosed when current treatments have limited benefits, highlighting the need for noninvasive tests aimed at an MPM risk assessment tool that might improve life expectancy. Three hundred asbestos-exposed subjects (163 MPM cases and 137 cancer-free controls), from the same geographical region in Italy, were recruited. The evaluation of asbestos exposure was conducted considering the frequency, the duration and the intensity of occupational, environmental and domestic exposure. A genome-wide methylation array was performed to identify novel blood DNA methylation (DNAm) markers of MPM. Multiple regression analyses adjusting for potential confounding factors and interaction between asbestos exposure and DNAm on the MPM odds ratio were applied. Epigenome-wide analysis (EWAS) revealed 12 single-CpGs associated with the disease. Two of these showed high statistical power (99%) and effect size (>0.05) after false discovery rate (FDR) multiple comparison corrections: (i) cg03546163 in FKBP5, significantly hypomethylated in cases (Mean Difference in beta values (MD) = −0.09, 95% CI = −0.12|−0.06, p = 1.2 × 10−7), and (ii) cg06633438 in MLLT1, statistically hypermethylated in cases (MD = 0.07, 95% CI = 0.04|0.10, p = 1.0 × 10−6). Based on the interaction analysis, asbestos exposure and epigenetic profile together may improve MPM risk assessment. Above-median asbestos exposure and hypomethylation of cg03546163 in FKBP5 (OR = 20.84, 95% CI = 8.71|53.96, p = 5.5 × 10−11) and hypermethylation of cg06633438 in MLLT1 (OR = 11.71, 95% CI = 4.97|29.64, p = 5.9 × 10−8) genes compared to below-median asbestos exposure and hyper/hypomethylation of single-CpG DNAm, respectively. Receiver Operation Characteristics (ROC) for Case-Control Discrimination showed a significant increase in MPM discrimination when DNAm information was added in the model (baseline model, BM: asbestos exposure, age, gender and white blood cells); area under the curve, AUC = 0.75; BM + cg03546163 at FKBP5. AUC = 0.89, 2.1 × 10−7; BM + cg06633438 at MLLT1. AUC = 0.89, 6.3 × 10−8. Validation and replication procedures, considering independent sample size and a different DNAm analysis technique, confirmed the observed associations. Our results suggest the potential application of DNAm profiles in blood to develop noninvasive tests for MPM risk assessment in asbestos-exposed subjects.
Turbulent Flame Propagation Characteristics of High Hydrogen Content Fuels

This final report describes the results of an effort to better understand turbulent flame propagation, especially at conditions relevant to gas turbines employing fuels with syngas or hydrogen mixtures. Turbulent flame speeds were measured for a variety of hydrogen/carbon monoxide (H2/CO) and hydrogen/methane (H2/CH4) fuel mixtures with air as the oxidizer. The measurements include global consumption speeds (ST,GC) acquired in a turbulent jet flame at pressures of 1-10 atm and local displacement speeds (ST,LD) acquired in a low-swirl burner at atmospheric pressure. The results verify the importance of fuel composition in determining turbulent flame speeds. For example, different fuel-air mixtures having the same unstretched laminar flame speed (SL,0) but different fuel compositions resulted in significantly different ST,GC for the same turbulence levels (u'). This demonstrates the weakness of turbulent flame speed correlations based simply on u'/SL,0. The results were analyzed using a steady-steady leading points concept to explain the sensitivity of turbulent burning rates to fuel (and oxidizer) composition. Leading point theories suggest that the premixed turbulent flame speed is controlled by the flame front characteristics at the flame brush leading edge, or, in other words, by the flamelets that advance farthest into the unburned mixture (the so-called leading points). more » For negative Markstein length mixtures, this is assumed to be close to the maximum stretched laminar flame speed (SL,max) for the given fuel-oxidizer mixture. For the ST,GC measurements, the data at a given pressure were well-correlated with an SL,max scaling. However the variation with pressure was not captured, which may be due to non-quasi-steady effects that are not included in the current model. For the ST,LD data, the leading points model again faithfully captured the variation of turbulent flame speed over a wide range of fuel-compositions and turbulence intensities. These results provide evidence that the leading points model can provide useful predictions of turbulent flame speed over a wide range of operating conditions and flow geometries. « less
Mortality Risk from Respiratory Diseases Due to Non-Optimal Temperature among Brazilian Elderlies

Over the past decade, Brazil has experienced and continues to be impacted by extreme climate events. This study aims to evaluate the association between daily average temperature and mortality from respiratory disease among Brazilian elderlies. A daily time-series study between 2000 and 2017 in 27 Brazilian cities was conducted. Data outcomes were daily counts of deaths due to respiratory diseases in the elderly aged 60 or more. The exposure variable was the daily mean temperature from Copernicus ERA5-Land reanalysis. The association was estimated from a two-stage time series analysis method. We also calculated deaths attributable to heat and cold. The pooled exposure–response curve presented a J-shaped format. The exposure to extreme heat increased the risk of mortality by 27% (95% CI: 15–39%), while the exposure to extreme cold increased the risk of mortality by 16% (95% CI: 8–24%). The heterogeneity between cities was explained by city-specific mean temperature and temperature range. The fractions of deaths attributable to cold and heat were 4.7% (95% CI: 2.94–6.17%) and 2.8% (95% CI: 1.45–3.95%), respectively. Our results show a significant impact of non-optimal temperature on the respiratory health of elderlies living in Brazil. It may support proactive action implementation in cities that have critical temperature variations.
Survey of Viral Reactivations in Elite Athletes: A Case-Control Study

Exercise-induced immune perturbations have been proposed to increase susceptibility to viral infections. We investigated the replication of persisting viruses as indicators of immune function in elite cross-country skiers after ten months of sustained high-performance exercise. The viruses evaluated, nine human herpesviruses (HHVs) and torque teno virus (TTV), are typically restrained in health but replicate actively in immunosuppressed individuals. We collected sera from 27 Finnish elite cross-country skiers at the end of the competition’s season and 27 matched controls who perform moderate exercise. We quantified all the HHVs and—TTV via highly sensitive qPCRs. To verify equal past exposures between the groups, we assessed the IgG antibody prevalences toward HHV-4 (Epstein–Barr virus, EBV) and HHV-5 (human cytomegalovirus, HCMV). We found equal TTV DNA prevalences in athletes (63%) and controls (63%) and loads with respective geometric means of 1.7 × 103 and 1.2 × 103 copies/mL of serum. Overall, the copy numbers were low and consistent with those of healthy individuals. Neither of the groups presented with herpesvirus viremia despite similar past exposures to HHVs (seroprevalences of EBV 70% vs. 78% and HCMV 52% vs. 44% in athletes and controls, respectively). We found no evidence of increased replication of persistent viruses in elite athletes, arguing against impaired viral immunity due to high-performance exercise.