Miracle-dz/UniFAR-FTUs huggingface dataset:
Protective Role of Kynurenine 3-Monooxygenase in Allograft Rejection and Tubular Injury in Kidney Transplantation

Renal tubular epithelial cells (TECs) are the primary targets of ischemia–reperfusion injury (IRI) and rejection by the recipient’s immune response in kidney transplantation (KTx). However, the molecular mechanism of rejection and IRI remains to be identified. Our previous study demonstrated that kynurenine 3-monooxygenase (KMO) and kynureninase were reduced in ischemia–reperfusion procedure and further decreased in rejection allografts among mismatched pig KTx. Herein, we reveal that TEC injury in acutely rejection allografts is associated with alterations of Bcl2 family proteins, reduction of tight junction protein 1 (TJP1), and TEC-specific KMO. Three cytokines, IFN γ , TNFα, and IL1β, reported in our previous investigation were identified as triggers of TEC injury by altering the expression of Bcl2, BID, and TJP1. Allograft rejection and TEC injury were always associated with a dramatic reduction of KMO. 3HK and 3HAA, as direct and downstream products of KMO, effectively protected TEC from injury via increasing expression of Bcl-xL and TJP1. Both 3HK and 3HAA further prevented allograft rejection by inhibiting T cell proliferation and up-regulating aryl hydrocarbon receptor expression. Pig KTx with the administration of DNA nanoparticles (DNP) that induce expression of indoleamine 2,3-dioxygenase (IDO) and KMO to increase 3HK/3HAA showed an improvement of allograft rejection as well as murine skin transplant in IDO knockout mice with the injection of 3HK indicated a dramatic reduction of allograft rejection. Taken together, our data provide strong evidence that reduction of KMO in the graft is a key mediator of allograft rejection and loss. KMO can effectively improve allograft outcome by attenuating allograft rejection and maintaining graft barrier function.
Axon-Specific Mitochondrial Pathology in SPG11 Alpha Motor Neurons

Pathogenic variants in SPG11 are the most frequent cause of autosomal recessive complicated hereditary spastic paraplegia (HSP). In addition to spastic paraplegia caused by corticospinal degeneration, most patients are significantly affected by progressive weakness and muscle wasting due to alpha motor neuron (MN) degeneration. Mitochondria play a crucial role in neuronal health, and mitochondrial deficits were reported in other types of HSPs. To investigate whether mitochondrial pathology is present in SPG11, we differentiated MNs from induced pluripotent stem cells derived from SPG11 patients and controls. MN derived from human embryonic stem cells and an isogenic SPG11 knockout line were also included in the study. Morphological analysis of mitochondria in the MN soma versus neurites revealed specific alterations of mitochondrial morphology within SPG11 neurites, but not within the soma. In addition, impaired mitochondrial membrane potential was indicative of mitochondrial dysfunction. Moreover, we reveal neuritic aggregates further supporting neurite pathology in SPG11. Correspondingly, using a microfluidic-based MN culture system, we demonstrate that axonal mitochondrial transport was significantly impaired in SPG11. Overall, our data demonstrate that alterations in morphology, function, and transport of mitochondria are an important feature of axonal dysfunction in SPG11 MNs.
Polarity Reversal Effect of a Memristor From the Circuit Point of View and Insights Into the Memristor Fuse

As the memristor device is asymmetrical in nature, it is not a bilateral element like the resistor in terms of circuit functionality. Thus, it causes hindrance in some memristor-based applications such as in cellular nonlinear network neighborhood connections and in some application areas where its orientation is essentially expected to act as a bilateral circuit element reliable for bidirectional communication, for example, in signal and image processing or in electrical synapse devices. We introduce a memristor-based network for each purpose where we replace the conventional series resistances by memristors. The memristor asymmetry is described from the circuit point of view allowing us to observe its interaction within the network. Moreover, a memristor fuse is proposed in order to achieve the memristive effect with symmetry, which is formed basically by connecting two memristors antiserially. We, therefore, analyze the memristor fuse from its basic principle along with the theoretical analysis and then observe the response from the circuit point of view.
Contextual Fear Memory Maintenance Changes Expression of pMAPK, BDNF and IBA-1 in the Pre-limbic Cortex in a Layer-Specific Manner

Post-traumatic stress disorder (PTSD) is a debilitating and chronic fear-based disorder. Pavlovian fear conditioning protocols have long been utilised to manipulate and study these fear-based disorders. Contextual fear conditioning (CFC) is a particular Pavlovian conditioning procedure that pairs fear with a particular context. Studies on the neural mechanisms underlying the development of contextual fear memories have identified the medial prefrontal cortex (mPFC), or more specifically, the pre-limbic cortex (PL) of the mPFC as essential for the expression of contextual fear. Despite this, little research has explored the role of the PL in contextual fear memory maintenance or examined the role of neuronal mitogen-activated protein kinase (pMAPK; ERK 1/2), brain-derived neurotrophic factor (BDNF), and IBA-1 in microglia in the PL as a function of Pavlovian fear conditioning. The current study was designed to evaluate how the maintenance of two different long-term contextual fear memories leads to changes in the number of immune-positive cells for two well-known markers of neural activity (phosphorylation of MAPK and BDNF) and microglia (IBA-1). Therefore, the current experiment is designed to assess the number of immune-positive pMAPK and BDNF cells, microglial number, and morphology in the PL following CFC. Specifically, 2 weeks following conditioning, pMAPK, BDNF, and microglia number and morphology were evaluated using well-validated antibodies and immunohistochemistry (n = 12 rats per group). A standard CFC protocol applied to rats led to increases in pMAPK, BDNF expression and microglia number as compared to control conditions. Rats in the unpaired fear conditioning (UFC) procedure, despite having equivalent levels of fear to context, did not have any change in pMAPK, BDNF expression and microglia number in the PL compared to the control conditions. These data suggest that alterations in the expression of pMAPK, BDNF, and microglia in the PL can occur for up to 2 weeks following CFC. Together the data suggest that MAPK, BDNF, and microglia within the PL of the mPFC may play a role in contextual fear memory maintenance.
Imbalance of Peripheral Lymphocyte Subsets in Patients With Ankylosing Spondylitis: A Meta-Analysis

Ankylosing spondylitis is a complicated consequence of genetic predisposition and environmental factors. Enthesitis is believed to be the hallmark of ankylosing spondylitis, and the chronic inflammatory state of this disease is perpetuated by the disturbances of both the innate immune system and the acquired immune system. To clarify the alteration of immune system in patients with AS, we conducted a meta-analysis concerning the proportions of major lymphocyte subsets in the peripheral blood of AS patients. We systematically searched PubMed and China National Knowledge Infrastructure (CNKI) for articles related to this subject. A total of 95 articles involving 4,020 AS patients and 3,065 healthy controls were included in the analysis. This meta-analysis is performed on R platform using R package “meta”, and Egger’s tests were used to determine the presence of publication bias. Results showed that the percentages of T cells, NK cells and NKT cells were not significantly different between AS patients and healthy controls, but B cells were significantly increased. Among the subsets of T cells, the proportions of CD4+ T cells, Th17 cells, Tfh cells as well as Th1/Th2 ratio were significantly increased, while Tregs were significantly decreased. Subgroup analysis showed that the proportions of Th17 among both PBMCs, T cells and CD4+ T cells were significantly elevated, while Tregs were only significantly lower in PBMCs. Subgroup analysis also demonstrated that Tregs defined by “CD4+CD25+FoxP3+”, “CD4+CD25+CD127low”or “CD4+CD25+CD127-”were significantly downregulated, indicating that the selection of markers could be critical. Further study is warranted in order to elucidate the complicated interactions between different lymphocyte subsets in AS patients. This study implied that the disequilibrium between Th17 and Tregs, as well as between Th1 and Th2 could contribute to the pathogenesis of ankylosing spondylitis, further cementing the understanding that ankylosing spondylitis is a consequence of disrupted balance of innate immune system and acquired immune system.
Effect of Nocturnal Oxygen Therapy on Daytime Pulmonary Hemodynamics in Patients With Chronic Obstructive Pulmonary Disease Traveling to Altitude: A Randomized Controlled Trial

Introduction We investigated whether nocturnal oxygen therapy (NOT) mitigates the increase of pulmonary artery pressure in patients during daytime with chronic obstructive pulmonary disease (COPD) traveling to altitude. Methods Patients with COPD living below 800 m underwent examinations at 490 m and during two sojourns at 2,048 m (with a washout period of 2 weeks < 800 m between altitude sojourns). During nights at altitude, patients received either NOT (3 L/min) or placebo (ambient air 3 L/min) via nasal cannula according to a randomized crossover design. The main outcomes were the tricuspid regurgitation pressure gradient (TRPG) measured by echocardiography on the second day at altitude (under ambient air) and various other echocardiographic measures of the right and left heart function. Patients fulfilling predefined safety criteria were withdrawn from the study. Results Twenty-three COPD patients [70% Global Initiative for Chronic Obstructive Lung Disease (GOLD) II/30% GOLD III, mean ± SD age 66 ± 5 years, FEV1 54% ± 13% predicted] were included in the per-protocol analysis. TRPG significantly increased when patients traveled to altitude (from low altitude 21.7 ± 5.2 mmHg to 2,048 m placebo 27.4 ± 7.3 mmHg and 2,048 m NOT 27.8 ± 8.3 mmHg) difference between interventions (mean difference 0.4 mmHg, 95% CI −2.1 to 3.0, p = 0.736). The tricuspid annular plane systolic excursion was significantly higher after NOT vs. placebo [2.6 ± 0.6 vs. 2.3 ± 0.4 cm, mean difference (95% confidence interval) 0.3 (0.1 − 0.5) cm, p = 0.005]. During visits to 2,048 m until 24 h after descent, eight patients (26%) using placebo and one (4%) using NOT had to be withdrawn because of altitude-related adverse health effects (p < 0.001). Conclusion In lowlanders with COPD remaining free of clinically relevant altitude-related adverse health effects, changes in daytime pulmonary hemodynamics during a stay at high altitude were trivial and not modified by NOT. Clinical Trial Registration www.ClinicalTrials. gov, identifier NCT02150590.
Mistrust and Beliefs in Conspiracy Theories Differently Mediate the Effects of Psychological Factors on Propensity for COVID-19 Vaccine

Vaccination is considered a key factor in the sanitary resolution of the COVID-19 pandemic. However, vaccine hesitancy can undermine its diffusion with severe consequences on global health. While beliefs in conspiracy theories, mistrust in science and in policymakers, and mistrust in official information channels may also increment vaccine hesitancy, understanding their psychological causes could improve our capacity to respond to the pandemic. Thus, we designed a cross-sectional study with the aim of probing vaccine propensity in the Italian population and explored its relationship with sociodemographic and psychological variables, and with misbeliefs in COVID-19. A battery of questionnaires was administered to a sample of 374 Italian adults during the first national lockdown (April 2020). The materials included an original instrument—Beliefs in COVID-19 Inventory—and questionnaires measuring perceived stress, anxiety, death anxiety, psychological distress, psychoticism, paranoia, anger, and somatization. The exploratory factor analysis (EFA) on Beliefs in COVID-19 suggested the existence of three factors: belief in conspiracy theories, mistrust in medical information, and mistrust in medicine and science. These factors were positively correlated with female sex, age, religious beliefs, psychiatric conditions, and psychological variables, while negatively correlated with education levels. We conducted a mediation analysis by means of a structural equation model, including psychological factors as predictors, beliefs in COVID-19 scales as mediators, and vaccine propensity as an outcome. The model showed that death anxiety had a direct positive effect on the propensity to get vaccinated. It also showed that death anxiety reduced the propensity to get vaccinated through a mediated path in believing in conspiracy theories, whereas paranoia was linked to a reduction in vaccination adherence with the mediation effect of mistrust in medical science. Psychological distress reduced vaccination propensity by increasing both conspiracy beliefs and mistrust. On the other hand, anxiety increased the propensity to get vaccinated through a decrease in both belief in conspiracy theories and mistrust in science. Our results suggest that psychological dimensions are differentially related to belief in conspiracy theories, to mistrust in science, and to the propensity to get vaccinated. Based on this result, we propose an original interpretation of how conspiracy beliefs build on a paranoid and suspicious attitude. We also discuss the possible clinical implications of treatment for such pathological beliefs.
Appraisal of China's Response to the Outbreak of COVID-19 in Comparison With SARS

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, was first reported in Wuhan, China, in December 2019 and has since become a pandemic. The COVID-19 containment measures were comparable to those used with severe acute respiratory syndrome (SARS), although these were stricter and more organized, and were initiated earlier and on a larger scale. Based on the lessons learned from SARS, the Chinese government acted aggressively in response to COVID-19, through a unified and effective commanding system, using law-based and science-driven strategies, and coordinated deployment of medical resources. Additionally, the application of high-tech measures, traditional Chinese medicine, and hierarchical medical systems also played an important role in control measures. Despite the remarkable performance, the initial delay in response suggests that the coordination between public health and medical services, reserve and coordination of emergency materials, and capacity for disease control and prevention need to be strengthened.
The Effect of COVID-19 on Herding Behavior in Eastern European Stock Markets

Unlike past health crises that were more localized, the highly contagious coronavirus disease 2019 (COVID-19) crisis is impacting the world to an unprecedented extent. This is the first study examining how and whether the COVID-19 pandemic affects herding behavior in the Eastern European stock markets. Using samples from the stock markets of Russia, Poland, the Czech Republic, Hungary, Croatia, and Slovenia from January 1, 2010 to March 10, 2021, we demonstrate that the COVID-19 pandemic has increased herding behavior in all the sample stock markets. Our results show that the COVID-19 crisis reinforces the impact of global market returns on herding behavior in these specific stock markets. We find that COVID-19 strengthens the spillover effect of regional herding on herding behavior. Thus, financial authorities should monitor investors in the stock market to avoid the increase in herding behavior as well as the reinforcement of the global market returns and regional return dispersion on herding during the period of pandemic.
Entrepreneurial Intention and Perceived Social Support From Academics-Scientists at Chilean Universities

Within Ajzen's Planned Behavior Theory framework, this article tests a model to estimate the predictors of entrepreneurial intention in academic scientists working in Chile. We adapted into Spanish the entrepreneurship intention questionnaire. We tested the entrepreneurship intention model on a sample of 1,027 scientists leading research projects funded by the Chilean Scientific and Technological Development Fund (FONDECYT), the country's primary scientific research grant. The results show strong empirical support for the entrepreneurship intention model proposed while highlighting some critical issues specific to entrepreneurial intention in scientists. In particular, we found an indirect effect of perceived subjective social support on entrepreneurial intention, which is mediated by entrepreneurial attitude and perceived behavioral control toward entrepreneurship. These results suggest that policies orientated toward promoting academic entrepreneurship should include developing a healthy social environment toward it, meaning that entrepreneurial intention is not only an individual but an organizational challenge. These policies should analyze the social norms guiding the scientists' reference groups to increase their effectiveness.
α-Synuclein: An All-Inclusive Trip Around its Structure, Influencing Factors and Applied Techniques

Alpha-synuclein (αSyn) is a highly expressed and conserved protein, typically found in the presynaptic terminals of neurons. The misfolding and aggregation of αSyn into amyloid fibrils is a pathogenic hallmark of several neurodegenerative diseases called synucleinopathies, such as Parkinson’s disease. Since αSyn is an Intrinsically Disordered Protein, the characterization of its structure remains very challenging. Moreover, the mechanisms by which the structural conversion of monomeric αSyn into oligomers and finally into fibrils takes place is still far to be completely understood. Over the years, various studies have provided insights into the possible pathways that αSyn could follow to misfold and acquire oligomeric and fibrillar forms. In addition, it has been observed that αSyn structure can be influenced by different parameters, such as mutations in its sequence, the biological environment (e.g., lipids, endogenous small molecules and proteins), the interaction with exogenous compounds (e.g., drugs, diet components, heavy metals). Herein, we review the structural features of αSyn (wild-type and disease-mutated) that have been elucidated up to present by both experimental and computational techniques in different environmental and biological conditions. We believe that this gathering of current knowledge will further facilitate studies on αSyn, helping the planning of future experiments on the interactions of this protein with targeting molecules especially taking into consideration the environmental conditions.
The Zero Violence Brave Club: A Successful Intervention to Prevent and Address Bullying in Schools

Bullying among peers in schools is a growing problem affecting children and adolescents from an early age worldwide. The consequences of bullying victimization in the emotional development of children and youth and their academic achievement are adverse for them and the rest of the school community, with its negative impact extending into the mid and long run. The Zero Violence Brave Club is implemented in schools in the framework of the Dialogic Model of Violence Prevention, a successful educational action according to the INCLUD-ED project [Strategies for inclusion and social cohesion in Europe from Education] (6th Framework Program of Research of the European Commission). The Zero Violence Brave Club has decreased peer bullying in schools by establishing and cultivating a culture of zero tolerance to violence in educational centers located in diverse socioeconomic and cultural contexts. This evidence-based intervention is grounded in the principle that only the person who denounces violence suffered by a peer and takes a stand always on the victim's side—and those who support her or him—against the aggressor can be considered brave. This article reports a qualitative study of the Zero Violence Brave Club as a successful intervention in seven schools in Spain. The schools are diverse in terms of public or private ownership, religious or lay background, and population served (different proportions of cultural minorities and students with special needs), challenging the misconception that the impact of educational interventions depends on the context. Interviews were conducted with teachers in the schools implementing the Zero Violence Brave Club in their class, using the communicative methodology of research. The results shed light on specific mechanisms through which the Zero Violence Brave Club prevents and responds to bullying in schools, such as emptying of social attractiveness any aggressive behaviors or attitudes. Benefits on mental health and psychological wellbeing are also reported.
Peak Running Velocity or Critical Speed Under Field Conditions: Which Best Predicts 5-km Running Performance in Recreational Runners?

This study aimed to examine which variable, between the peak running velocity determined on the track field (Vpeak_TF) and critical speed (CS), is the best predictor of the 5-km running performance in recreational runners. Twenty-five males performed three tests to determine the Vpeak_TF, CS, and 5-km running performance on the track field, with a minimal interval of 48 h between each test. The Vpeak_TF protocol started with a velocity of 8 km⋅h–1, followed by an increase of 1 km⋅h–1 every 3 min until volitional exhaustion, which was controlled by sound signals, with cones at every 25 m indicating when the participants were required to pass the cone’s position to maintain the required velocity. The participants performed three time trials (TTs) (1: 2,600 m; 2: 1,800 m; and 3: 1,000 m) on the same day, with a 30-min rest period to determine the CS through the combinations of three (CS1,2,3) and two TTs (CS1,2, CS1,3, and CS2,3). The 5-km running performance time was recorded to determine the test duration, and the mean velocity (MV) was calculated. There was a significant difference observed between the Vpeak_TF and the MV 5-km running performance. However, no differences were found between the CS values and the MV 5-km running performance. A correlation was observed between the Vpeak_TF (R = −0.90), CS1,2,3 (R = −0.95), CS1,3 (R = −0.95), and the 5-km running performance time. Linear regression indicated that the Vpeak_TF (R2 = 0.82), CS1,2,3 (R2 = 0.90), and CS1,3 (R2 = 0.90) significantly predicted the 5-km running performance time. The CS results showed a higher predictive power for the 5-km running performance, slightly better than the Vpeak_TF. Also, CS1,2,3 and the CS1,3 presented the highest predictive power for the 5-km running performance of recreational runners.