Miracle-dz/UniFAR-FTUs huggingface dataset:
Lipoprotein-Induced Increases in Cholesterol and 7-Ketocholesterol Result in Opposite Molecular-Scale Biophysical Effects on Membrane Structure

Under hypercholesterolemic conditions, exposure of cells to lipoproteins results in a subtle membrane increase in the levels of cholesterol and 7-ketocholesterol, as compared to normal conditions. The effect of these physiologically relevant concentration increases on multicomponent bilayer membranes was investigated using coarse-grained molecular dynamics simulations. Significant changes in the structural and dynamic properties of the bilayer membranes resulted from these subtle increases in sterol levels, with both sterol species inducing decreases in the lateral area and inhibiting lateral diffusion to varying extents. Cholesterol and 7-ketocholesterol, however, exhibited opposite effects on lipid packing and orientation. The results from this study indicate that the subtle increases in membrane sterol levels induced by exposure to lipoproteins result in molecular-scale biophysical perturbation of membrane structure.
Evaluation of Passive Safety Injection System Performance Under Large Break LOCA for Qinshan PWR

In this work, a brand new passive safety injection system has been designed for the ocean-based Qinshan Phase I nuclear power plant to update and replace the traditional active ones. The passive safety injection system is made up of high pressure, medium pressure, lower pressure safety injection system, and a two-stage automatic depressurization system. To evaluate the safety injection system performance, double-ended cold leg large break LOCA has been analyzed by best-estimated safety analysis RELAP5 code. The main operation and safety parameters such as primary system pressure, safe injection mass flow rates, core water level, and peak cladding temperature have been presented. The results conclude that the safety injection system can act as similar to that of the AP1000, which can assure sufficient core cooling and keep the reactor covered by the cold water under the most severe LBLOCA condition.
Transcriptome Response to Cadmium Exposure in Barley (Hordeum vulgare L.)

Cadmium is an environmental pollutant with high toxicity that negatively affects plant growth and development. To understand the molecular mechanisms of plant response to cadmium stress, we have performed a genome-wide transcriptome analysis on barley plants treated with an increased concentration of cadmium. Differential gene expression analysis revealed 10,282 deregulated transcripts present in the roots and 7,104 in the shoots. Among them, we identified genes related to reactive oxygen species metabolism, cell wall formation and maintenance, ion membrane transport and stress response. One of the most upregulated genes was PLANT CADMIUM RESISTACE 2 (HvPCR2) known to be responsible for heavy metal detoxification in plants. Surprisingly, in the transcriptomic data we identified four different copies of the HvPCR2 gene with a specific pattern of upregulation in individual tissues. Heterologous expression of all five barley copies in a Cd-sensitive yeast mutant restored cadmium resistance. In addition, four HvPCR2 were located in tandem arrangement in a single genomic region of the barley 5H chromosome. To our knowledge, this is the first example showing multiplication of the PCR2 gene in plants.
Computerized Dual-Task Testing of Gait Visuomotor and Cognitive Functions in Parkinson’s Disease: Test-Retest Reliability and Validity

Background Mobility and cognitive impairments in Parkinson’s disease (PD) often coexist and are prognostic of adverse health events. Consequently, assessment and training that simultaneously address both gait function and cognition are important to consider in rehabilitation and promotion of healthy aging. For this purpose, a computer game-based rehabilitation treadmill platform (GRP) was developed for dual-task (DT) assessment and training. Objective The first objective was to establish the test-retest reliability of the GRP assessment protocol for DT gait, visuomotor and executive cognitive function in PD patients. The second objective was to examine the effect of task condition [single task (ST) vs. DT] and disease severity (stage 2 vs. stage 3) on gait, visuomotor and cognitive function. Methods Thirty individuals aged 55 to 70 years, diagnosed with PD; 15 each at Hoehn and Yahr scale stage 2 (PD-2) and 3 (PD-3) performed a series of computerized visuomotor and cognitive game tasks while sitting (ST) and during treadmill walking (DT). A treadmill instrumented with a pressure mat was used to record center of foot pressure and compute the average and coefficient of variation (COV) of step time, step length, and drift during 1-min, speed-controlled intervals. Visuomotor and cognitive game performance measures were quantified using custom software. Testing was conducted on two occasions, 1 week apart. Results With few exceptions, the assessment protocol showed moderate to high intraclass correlation coefficient (ICC) values under both ST and DT conditions for the spatio-temporal gait measures (average and COV), as well as the visuomotor tracking and cognitive game performance measures. A significant decline in gait, visuomotor, and cognitive game performance measures was observed during DT compared to ST conditions, and in the PD-3 compared to PD-2 groups. Conclusion The high to moderate ICC values along with the lack of systematic errors in the measures indicate that this tool has the ability to repeatedly record reliable DT interference (DTI) effects over time. The use of interactive digital media provides a flexible method to produce and evaluate DTI for a wide range of executive cognitive activities. This also proves to be a sensitive tool for tracking disease progression. Clinical Trial Registration www.ClinicalTrials. gov, identifier NCT03232996.
From Therapeutic Factors to Mechanisms of Change in the Creative Arts Therapies: A Scoping Review

Empirical studies in the creative arts therapies (CATs; i.e., art therapy, dance/movement therapy, drama therapy, music therapy, psychodrama, and poetry/bibliotherapy) have grown rapidly in the last 10 years, documenting their positive impact on a wide range of psychological and physiological outcomes (e.g., stress, trauma, depression, anxiety, and pain). However, it remains unclear how and why the CATs have positive effects, and which therapeutic factors account for these changes. Research that specifically focuses on the therapeutic factors and/or mechanisms of change in CATs is only beginning to emerge. To gain more insight into how and why the CATs influence outcomes, we conducted a scoping review (Nstudies = 67) to pinpoint therapeutic factors specific to each CATs discipline, joint factors of CATs, and more generic common factors across all psychotherapy approaches. This review therefore provides an overview of empirical CATs studies dealing with therapeutic factors and/or mechanisms of change, and a detailed analysis of these therapeutic factors which are grouped into domains. A framework of 19 domains of CATs therapeutic factors is proposed, of which the three domains are composed solely of factors unique to the CATs: “embodiment,” “concretization,” and “symbolism and metaphors. ” The terminology used in change process research is clarified, and the implications for future research, clinical practice, and CATs education are discussed.
Real-World Analysis of Survival and Clinical Events in a Cohort of Italian Perinatally HIV-1 Infected Children From 2001 to 2018

Background: Combined antiretroviral therapy (cART) has been associated with a steep decrease in mortality and morbidity in HIV-1 infected children. New antiretroviral molecules and drug classes have been developed and the management of HIV-infected children has improved, but recent data on survival are limited. Methods: An observational retrospective study investigating changes in mortality and morbidity was conducted on 1,091 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. Results: Three hundred and fifty-four (32%) AIDS events and 26 (2%) deaths occurred overtime. Mortality rates decreased from 0.4/100 person-years in 2001–2006 to 0.27/100 person-years in 2007–2012 and 0.07/100 person-years in 2013–2018. Notably, 92% of the dead children were born in Italy, but only 50% were followed-up since birth or within three months of age. Seventy three percent of children had started cART at age ≥6 months; 23% were treated for <30 days before death. B and C clinical events progressively decreased (P < 0.0001). Opportunistic infections significantly decreased over time, but still were the most common events in all the periods (6.76/100 person-years in 2013–2018). In the last period, severe bacterial infections were the most common ones. Cancer rates were 0.07/100; 0.17/100; 0.07/100 person-years in the three periods, respectively. Conclusions: Progressive reductions both in mortality and in rates of class B and C clinical events and OIs have been observed during the cART era. However, deaths were still registered; more than half of dead children were enrolled after birth and had belatedly started cART.
Extended Visual Sequence Learning Leaves a Local Trace in the Spontaneous EEG

We have previously demonstrated that, in rested subjects, extensive practice in a motor learning task increased both electroencephalographic (EEG) theta power in the areas involved in learning and improved the error rate in a motor test that shared similarities with the task. A nap normalized both EEG and performance changes. We now ascertain whether extensive visual declarative learning produces results similar to motor learning. Thus, during the morning, we recorded high-density EEG in well rested young healthy subjects that learned the order of different visual sequence task (VSEQ) for three one-hour blocks. Afterward, a group of subjects took a nap and another rested quietly. Between each VSEQ block, we recorded spontaneous EEG (sEEG) at rest and assessed performance in a motor test and a visual working memory test that shares similarities with VSEQ. We found that after the third block, VSEQ induced local theta power increases in the sEEG over a right temporo-parietal area that was engaged during the task. This local theta increase was preceded by increases in alpha and beta power over the same area and was paralleled by performance decline in the visual working memory test. Only after the nap, VSEQ learning rate improved and performance in the visual working memory test was restored, together with partial normalization of the local sEEG changes. These results suggest that intensive learning, like motor learning, produces local theta power increases, possibly reflecting local neuronal fatigue. Sleep may be necessary to resolve neuronal fatigue and its effects on learning and performance.
Honeymoon Period in Newborn Rats With CDH Is Associated With Changes in the VEGF Signaling Pathway

Background: Patients with congenital diaphragmatic hernia (CDH) have a short postnatal period of ventilatory stability called the honeymoon period, after which changes in pulmonary vascular reactivity result in pulmonary hypertension. However, the mechanisms involved are still unknown. The aim of this study was to evaluate mechanical ventilation's effect in the honeymoon period on VEGF, VEGFR-1/2 and eNOS expression on experimental CDH in rats. Materials and Methods: Neonates whose mothers were not exposed to nitrofen formed the control groups (C) and neonates with left-sided defects formed the CDH groups (CDH). Both were subdivided into non-ventilated and ventilated for 30, 60, and 90 min (n = 7 each). The left lungs (n = 4) were evaluated by immunohistochemistry of the pulmonary vasculature (media wall thickness), VEGF, VEGFR-1/2 and eNOS. Western blotting (n = 3) was performed to quantify the expression of VEGF, VEGFR-1/2 and eNOS. Results: CDH had lower biometric parameters than C. Regarding the pulmonary vasculature, C showed a reduction in media wall thickness with ventilation, while CDH presented reduction with 30 min and an increase with the progression of the ventilatory time (honeymoon period). CDH and C groups showed different patterns of VEGF, VEGFR-1/2 and eNOS expressions. The receptors and eNOS findings were significant by immunohistochemistry but not by western blotting, while VEGF was significant by western blotting but not by immunohistochemistry. Conclusion: VEGF, its receptors and eNOS were altered in CDH after mechanical ventilation. These results suggest that the VEGF-NO pathway plays an important role in the honeymoon period of experimental CDH.
Prognostic Signature of Osteosarcoma Based on 14 Autophagy-Related Genes

Background: Osteosarcoma is a common malignancy of bone with inferior survival outcome. Autophagy can exert multifactorial influence on tumorigenesis and tumor progression. However, the specific function of genes related to autophagy in the prognosis of osteosarcoma patients remains unclear. Herein, we aimed to explore the association of genes related to autophagy with the survival outcome of osteosarcoma patients. Methods: The autophagy-associated genes that were related to the prognosis of osteosarcoma were optimized by LASSO Cox regression analysis. The survival of osteosarcoma patients was forecasted by multivariate Cox regression analysis. The immune infiltration status of 22 immune cell types in osteosarcoma patients with high and low risk scores was compared by using the CIBERSORT tool. Results: The risk score model constructed according to 14 autophagy-related genes (ATG4A, BAK1, BNIP3, CALCOCO2, CCL2, DAPK1, EGFR, FAS, GRID2, ITGA3, MYC, RAB33B, USP10, and WIPI1) could effectively predict the prognosis of patients with osteosarcoma. A nomogram model was established based on risk score and metastasis. Conclusion: Autophagy-related genes were identified as pivotal prognostic signatures, which could guide the clinical decision making in the treatment of osteosarcoma.
The Role of Cysteine Peptidases in Hematopoietic Stem Cell Differentiation and Modulation of Immune System Function

Cysteine cathepsins are primarily involved in the degradation and recycling of proteins in endo-lysosomal compartments but are also gaining recognition as pivotal proteolytic contributors to various immune functions. Through their extracellular proteolytic activities within the hematopoietic stem cell niche, they are involved in progenitor cell mobilization and differentiation. Cysteine cathepsins, such as cathepsins L and S contribute to antigen-induced adaptive immunity through major histocompatibility complex class II antigen presentation whereas cathepsin X regulates T-cell migration. By regulating toll-like receptor signaling and cytokine secretion cysteine cathepsins activate innate immune cells and affect their functional differentiation. Cathepsins C and H are expressed in cytotoxic T lymphocytes and natural killer cells and are involved in processing of pro-granzymes into proteolytically active forms. Cytoplasmic activities of cathepsins B and L contribute to the maintenance of homeostasis of the adaptive immune response by regulating cell death of T and B lymphocytes. The expression pattern, localization, and activity of cysteine cathepsins is tightly connected to their function in immune cells. Furthermore, cysteine cathepsins together with their endogenous inhibitors, serve as mediators in the interplay between cancer and immune cells that results in immune cell anergy. The aim of the present article is to review the mechanisms of dysregulation of cysteine cathepsins and their inhibitors in relation to immune dysfunction to address new possibilities for regulation of their function.
Estimating the Impact of the COVID-19 Pandemic on Maternal and Perinatal Health Care Services in Italy: Results of a Self-Administered Survey

The coronavirus disease 2019 (COVID-19) pandemic is strongly changing the way most people live their lives, and disrupting specialist healthcare systems. Such public health disruptions have resulted in significant collateral damage with particular implications for vulnerable populations, including the perinatal population. This Study aims to estimate the impact of the COVID-19 pandemic on Italian maternal and perinatal health care services. A questionnaire was designed to evaluate the COVID-19 impact on Italian maternal and perinatal healthcare facilities and their activities and provision of services from March to May 2020. The survey was completed by hospital-based and community-based Italian maternal and perinatal healthcare facilities. Most of these were located in Lombardy or Veneto (the most affected Italian regions). 70% of all facilities reported that the first wave of the COVID-19 pandemic negatively influenced the functioning of one or more aspects of the perinatal service; only 28.4% of facilities all over the country continued to provide outpatient routine visits and examinations as usual; 23.4% of facilities became understaffed during the index period due to various reasons such as ward transfer and sick leave. This is the first Italian study, and among very few international studies that describe the effects of the COVID-19 pandemic on antenatal and postnatal healthcare facilities and their provision of activities and services. Our findings confirm that healthcare systems even in high-income countries were not entirely prepared to handle such a global health emergency; indeed, specialized maternal and perinatal healthcare services have been disrupted by this global health emergency.
Excess Mortality in Italy During the COVID-19 Pandemic: Assessing the Differences Between the First and the Second Wave, Year 2020

COVID-19 dramatically influenced mortality worldwide, in Italy as well, the first European country to experience the Sars-Cov2 epidemic. Many countries reported a two-wave pattern of COVID-19 deaths; however, studies comparing the two waves are limited. The objective of the study was to compare all-cause excess mortality between the two waves that occurred during the year 2020 using nationwide data. All-cause excess mortalities were estimated using negative binomial models with time modeled by quadratic splines. The models were also applied to estimate all-cause excess deaths “not directly attributable to COVD-19”, i.e., without a previous COVID-19 diagnosis. During the first wave (25th February−31st May), we estimated 52,437 excess deaths (95% CI: 49,213–55,863) and 50,979 (95% CI: 50,333–51,425) during the second phase (10th October−31st December), corresponding to percentage 34.8% (95% CI: 33.8%–35.8%) in the second wave and 31.0% (95%CI: 27.2%–35.4%) in the first. During both waves, all-cause excess deaths percentages were higher in northern regions (59.1% during the first and 42.2% in the second wave), with a significant increase in the rest of Italy (from 6.7% to 27.1%) during the second wave. Males and those aged 80 or over were the most hit groups with an increase in both during the second wave. Excess deaths not directly attributable to COVID-19 decreased during the second phase with respect to the first phase, from 10.8% (95% CI: 9.5%–12.4%) to 7.7% (95% CI: 7.5%–7.9%), respectively. The percentage increase in excess deaths from all causes suggests in Italy a different impact of the SARS-CoV-2 virus during the second wave in 2020. The decrease in excess deaths not directly attributable to COVID-19 may indicate an improvement in the preparedness of the Italian health care services during this second wave, in the detection of COVID-19 diagnoses and/or clinical practice toward the other severe diseases.
Genetic and Flower Volatile Diversity in Natural Populations of Origanum vulgare subsp. hirtum (Link) Ietsw. in Bulgaria: Toward the Development of a Core Collection

We studied the genetic and flower volatile diversity in natural populations of Origanum vulgare subsp. hirtum (Link) Ietsw. in Bulgaria using simple sequence repeat (SSR) and sequence-related amplified polymorphism (SRAP) markers and gas chromatography/mass spectrometry (GC/MS) analysis of flower volatiles from individual plants. Two regions, including the Kresna Gorge and Eastern Rhodopes, typical for the species comprising eight populations and 239 individual plants were included in this study. An analysis with 11 SSR markers and eight SRAP primer combinations showed that SRAP markers were substantially more informative than the SSR markers and were further used for genetic diversity analysis. The results showed low-range to mid-range genetic differentiation between the populations with pairwise fixation index (Fst) values ranging between 0.0047 and 0.11. A total of 10 genetic clusters were identified. An analysis of the flower volatile diversity identified a total of 63 compounds with the vast majority of plants belonging to the carvacrol chemotype and just a single plant to the thymol chemotype. Large deviations were observed for individual compounds within each region as well as within the populations. Hierarchical clustering showed a clear sample grouping based on the two different regions. In addition, an in-depth analysis identified six major and 23 minor metabolite clusters. The overall data set and cluster analysis were further used for the development and testing of a simple and straightforward strategy for the selection of individual plants for the development of a core collection representing the sampled natural populations for this species in Bulgaria. The proposed strategy involves precise genetic clustering of the tested plants followed by the selection of a minimal set from each genetic cluster representing the different metabolite clusters. The selected core set was further compared with a core set extracted by the PowerCore software. A comparison of the genetic and metabolic affiliation of the members of both sets showed that the reported approach selected representatives from each genetic cluster and minor metabolic cluster, whereas some metabolic clusters were unrepresented in the PowerCore set. The feasibility and efficiency of applying the pointed strategy for the development of a core collection representing both the genetic and metabolite diversity of natural populations in aromatic and medicinal plants toward subsequent steps of selection and breeding are discussed.
Cardiomyocyte Protection by Hibernating Brown Bear Serum: Toward the Identification of New Protective Molecules Against Myocardial Infarction

Ischemic heart disease remains one of the leading causes of death worldwide. Despite intensive research on the treatment of acute myocardial infarction, no effective therapy has shown clinical success. Therefore, novel therapeutic strategies are required to protect the heart from reperfusion injury. Interestingly, despite physical inactivity during hibernation, brown bears (Ursus arctos) cope with cardiovascular physiological conditions that would be detrimental to humans. We hypothesized that bear serum might contain circulating factors that could provide protection against cell injury. In this study, we sought to determine whether addition of bear serum might improve cardiomyocyte survival following hypoxia–reoxygenation. Isolated mouse cardiomyocytes underwent 45 min of hypoxia followed by reoxygenation. At the onset of reoxygenation, cells received fetal bovine serum (FBS; positive control), summer (SBS) or winter bear serum (WBS), or adult serums of other species, as indicated. After 2 h of reoxygenation, propidium iodide staining was used to evaluate cell viability by flow cytometry. Whereas, 0.5% SBS tended to decrease reperfusion injury, 0.5% WBS significantly reduced cell death, averaging 74.04 ± 7.06% vs. 79.20 ± 6.53% in the FBS group. This cardioprotective effect was lost at 0.1%, became toxic above 5%, and was specific to the bear. Our results showed that bear serum exerts a therapeutic effect with an efficacy threshold, an optimal dose, and a toxic effect on cardiomyocyte viability after hypoxia–reoxygenation. Therefore, the bear serum may be a potential source for identifying new therapeutic molecules to fight against myocardial reperfusion injury and cell death in general.