Miracle-dz/UniFAR-FTUs huggingface dataset:
Promoting Public Engagement during the COVID-19 Crisis: How Effective Is the Wuhan Local Government’s Information Release?

During times of public crises (such as COVID-19), governments must act swiftly to release crisis information effectively and efficiently to the public. This paper provides a general overview of the way that the Wuhan local government use Weibo as a channel to engage with their citizens during the COVID-19 pandemic. Based on the media richness, dialogic loop, and a series of theoretically relevant factors, such as content type, text length, and information source, we try to examine how citizen engage with their local government. By analyzing the data mining samples from Wuhan Release, the official Sina Weibo account of Wuhan’s local government, results show that, despite the unstable situation COVID-19 over the crisis, there exist three stages of a crisis on the whole. Combining the behavior of the government and the public, duration from 31 December 2019 to 19 January 2020 could be seen as the development period, then the outbreak period (30 January 2020 to 28 February 2020), and a grace period (29 February 2020 to19 April 2020). Public attention to different types of information changes over time, but curbing rumors has always been a priority. Media richness features partially influent citizen engagement. Text length is significantly positively associated with citizen engagement through government social media. However, posts containing information sources have a negative impact on citizen engagement.
Aberrant Splicing in GJB1 and the Relevance of 5′ UTR in CMTX1 Pathogenesis

The second most common form of Charcot-Marie-Tooth disease (CMT) follows an X-linked dominant inheritance pattern (CMTX1), referring to mutations in the gap junction protein beta 1 gene (GJB1) that affect connexin 32 protein (Cx32) and its ability to form gap junctions in the myelin sheath of peripheral nerves. Despite the advances of next-generation sequencing (NGS), attention has only recently also focused on noncoding regions. We describe two unrelated families with a c. -17+1G>T transversion in the 5′ untranslated region (UTR) of GJB1 that cosegregates with typical features of CMTX1. As suggested by in silico analysis, the mutation affects the regulatory sequence that controls the proper splicing of the intron in the corresponding mRNA. The retention of the intron is also associated with reduced levels of the transcript and the loss of immunofluorescent staining for Cx32 in the nerve biopsy, thus supporting the hypothesis of mRNA instability as a pathogenic mechanism in these families. Therefore, our report corroborates the role of 5′ UTR of GJB1 in the pathogenesis of CMTX1 and emphasizes the need to include this region in routine GJB1 screening, as well as in NGS panels.
Mental Health Disturbances and Related Problems in Italian University Medical Students from 2000 to 2020: An Integrative Review of Qualitative and Quantitative Studies

Background and objectives: The presence of mental health problems in the population of medical students in Italy has been evaluated in several cross-sectional studies, which have used different methodologies and study designs. However, a global overview of the prevalence of mental health problems in Italian medical students is not available, although this would be essential for promoting preventive strategies and supportive treatments. Materials and Methods: An integrative review aiming to describe the prevalence of mental health problems in Italian medical students has been performed. Results: The most relevant findings are the high prevalence of substance use, in particular alcohol and nicotine, and of depressive and anxiety disorders in Italian medical students. In particular, substance use ranges from 13 to 86%, which is higher compared to Italian students coming from other faculties. Italian medical students show a high rate of smoking and of depressive symptoms of about 20%. Conclusions: Our findings highlight the need to develop appropriate supportive interventions for the medical student population, which are rarely provided and implemented among the routine activities of Italian medical universities. A relevant aspect to be considered is the stigma and anticipated discrimination attached to mental disorders, which reduce the help-seeking process in medical students.
Extended Interactions between HIV-1 Viral RNA and tRNALys3 Are Important to Maintain Viral RNA Integrity

The reverse transcription of the human immunodeficiency virus 1 (HIV-1) initiates upon annealing of the 3′-18-nt of tRNALys3 onto the primer binding site (PBS) in viral RNA (vRNA). Additional intermolecular interactions between tRNALys3 and vRNA have been reported, but their functions remain unclear. Here, we show that abolishing one potential interaction, the A-rich loop: tRNALys3 anticodon interaction in the HIV-1 MAL strain, led to a decrease in viral infectivity and reduced the synthesis of reverse transcription products in newly infected cells. In vitro biophysical and functional experiments revealed that disruption of the extended interaction resulted in an increased affinity for reverse transcriptase (RT) and enhanced primer extension efficiency. In the absence of deoxyribose nucleoside triphosphates (dNTPs), vRNA was degraded by the RNaseH activity of RT, and the degradation rate was slower in the complex with the extended interaction. Consistently, the loss of vRNA integrity was detected in virions containing A-rich loop mutations. Similar results were observed in the HIV-1 NL4.3 strain, and we show that the nucleocapsid (NC) protein is necessary to promote the extended vRNA: tRNALys3 interactions in vitro. In summary, our data revealed that the additional intermolecular interaction between tRNALys3 and vRNA is likely a conserved mechanism among various HIV-1 strains and protects the vRNA from RNaseH degradation in mature virions.
Charge Storage Mechanism of MnO2 Electrode Used in Aqueous Electrochemical Capacitor

The charge storage mechanism in MnO2 electrode, used in aqueous electrolyte, was investigated by cyclic voltammetry and X-ray photoelectron spectroscopy. Thin MnO2 films deposited on a platinum substrate and thick MnO2 composite electrodes were used. First, the cyclic voltammetry data established that only a thin layer of MnO2 is involved in the redox process and electrochemically active. Second, the X-ray photoelectron spectroscopy data revealed that the manganese oxidation state was varying from III to IV for the reduced and oxidized forms of thin film electrodes, respectively, during the charge/discharge process. The X-ray photoelectron spectroscopy data also show that Na+ cations from the electrolyte were involved in the charge storage process of MnO2 thin film electrodes. However, the Na/Mn ratio for the reduced electrode was much lower than what was anticipated for charge compensation dominated by Na+, thus suggesting the involvement of protons in the pseudofaradaic mechanism. An important finding o.
Discovery of potent and specific inhibitors targeting the active site of MMP-9 from the engineered SPINK2 library

Matrix metalloproteinases (MMPs) contribute to many physiological and pathological phenomena via the proteolysis of extracellular matrix components. Specific blocking of the active site of each MMP sheds light on its particular role. However, it remains difficult to acquire an active-site inhibitor with high specificity for only the target MMP due to the highly conserved structure around the active site of MMPs. Recently, we reported that potent and specific inhibitors of serine proteases were obtained from our proprietary engineered serine protease inhibitor Kazal type 2 (SPINK2) library. In this research, using this library, we succeeded in obtaining potent and specific MMP-9 inhibitors. The obtained inhibitors bound to the active site of MMP-9 and inhibited MMP-9 with low nanomolar Ki values. The inhibitors did not cross-react with other MMPs that we tested. Further analysis using MMP-9 mutants demonstrated that the inhibitors recognize not only the residues around the conserved active site of MMP-9 but also different and unique residues in exosites that are distant from each other. This unique recognition manner, which can be achieved by the large interface provided by engineered SPINK2, may contribute to the generation of specific active-site inhibitors of MMPs.
Modeling CNS Involvement in Pompe Disease Using Neural Stem Cells Generated from Patient-Derived Induced Pluripotent Stem Cells

Pompe disease is a lysosomal storage disorder caused by autosomal recessive mutations in the acid alpha-glucosidase (GAA) gene. Acid alpha-glucosidase deficiency leads to abnormal glycogen accumulation in patient cells. Given the increasing evidence of central nervous system (CNS) involvement in classic infantile Pompe disease, we used neural stem cells, differentiated from patient induced pluripotent stem cells, to model the neuronal phenotype of Pompe disease. These Pompe neural stem cells exhibited disease-related phenotypes including glycogen accumulation, increased lysosomal staining, and secondary lipid buildup. These morphological phenotypes in patient neural stem cells provided a tool for drug efficacy evaluation. Two potential therapeutic agents, hydroxypropyl-β-cyclodextrin and δ-tocopherol, were tested along with recombinant human acid alpha-glucosidase (rhGAA) in this cell-based Pompe model. Treatment with rhGAA reduced LysoTracker staining in Pompe neural stem cells, indicating reduced lysosome size. Additionally, treatment of diseased neural stem cells with the combination of hydroxypropyl-β-cyclodextrin and δ-tocopherol significantly reduced the disease phenotypes. These results demonstrated patient-derived Pompe neural stem cells could be used as a model to study disease pathogenesis, to evaluate drug efficacy, and to screen compounds for drug discovery in the context of correcting CNS defects.
Searching for Something Positive in Future Negative: The Adolescent and Adult Time Inventory–Time Attitudes Scale

The Adolescent and Adult Time Inventory–Time Attitudes Scale (AATI-TA) measures emotional engagement with the past, present, and future, and scores have been shown to relate meaningfully to health outcomes. For past, present, and future, five items are used to assess both positive and negative attitudes. Although evidence for the hypothesized six-factor solution has been widely reported, some studies have indicated problems with the Future Negative items. Given that a large and growing literature has emerged on the six-factor AATI-TA, and that AATI-TA scores have shown much better and more consistent fit than other temporal psychology measures, we sought to investigate the future negative factor in detail. Secondary analyses were performed on two datasets. The first was a University convenience sample (N = 410) and the second was an adolescent sample (N = 1,612). Confirmatory factor analyses revealed that the fit for the five Future Negative items was poor. Modification indices suggested that a correlated error term between Items 4 and 10 would result in good fit, and this was indeed the case. Models without Item 4 or Item 10 also yielded acceptable fit. Analyses using all four operationalizations of Future Negative (original scale, without Item 4 or Item 10, or with the correlated error between Items 4 and 10) to predict symptoms of anxiety and depression, and emotional self-efficacy revealed minor differences in the predictive validity coefficients. Potential ways forward, including a correlated error term or the dropping or replacement of Item 10, are discussed.
Bisphosphonates Reduce Smoking-Induced Osteoporotic-Like Alterations by Regulating RANKL/OPG in an Osteoblast and Osteoclast Co-Culture Model

Co-culture models have become mandatory for obtaining better insights into bone homeostasis, which relies on the balance between osteoblasts and osteoclasts. Cigarette smoking (CS) has been proven to increase the risk of osteoporosis; however, there is currently no proven treatment for osteoporosis in smokers excluding cessation. Bisphosphonates (BPs) are classical anti-osteoclastic drugs that are commonly used in examining the suitability of bone co-culture systems in vitro as well as to verify the response to osteoporotic stimuli. In the present study, we tested the effects of BPs on cigarette smoke extract (CSE)-affected cells in the co-culture of osteoblasts and osteoclasts. Our results showed that BPs were able to reduce CSE-induced osteoporotic alterations in the co-culture of osteoblasts and osteoclasts such as decreased matrix remodeling, enhanced osteoclast activation, and an up-regulated receptor activator of nuclear factor (NF)-kB-ligand (RANKL)/osteoprotegerin (OPG) ratio. In summary, BPs may be an effective alternative therapy for reversing osteoporotic alterations in smokers, and the potential mechanism is through modulation of the RANKL/OPG ratio.
Antimicrobial Peptide K11 Selectively Recognizes Bacterial Biomimetic Membranes and Acts by Twisting Their Bilayers

K11 is a synthetic peptide originating from the introduction of a lysine residue in position 11 within the sequence of a rationally designed antibacterial scaffold. Despite its remarkable antibacterial properties towards many ESKAPE bacteria and its optimal therapeutic index (320), a detailed description of its mechanism of action is missing. As most antimicrobial peptides act by destabilizing the membranes of the target organisms, we investigated the interaction of K11 with biomimetic membranes of various phospholipid compositions by liquid and solid-state NMR. Our data show that K11 can selectively destabilize bacterial biomimetic membranes and torque the surface of their bilayers. The same is observed for membranes containing other negatively charged phospholipids which might suggest additional biological activities. Molecular dynamic simulations reveal that K11 can penetrate the membrane in four steps: after binding to phosphate groups by means of the lysine residue at the N-terminus (anchoring), three couples of lysine residues act subsequently to exert a torque in the membrane (twisting) which allows the insertion of aromatic side chains at both termini (insertion) eventually leading to the flip of the amphipathic helix inside the bilayer core (helix flip and internalization).
New Insights into the Ecology and Physiology of Methanomassiliicoccales from Terrestrial and Aquatic Environments

Members of the archaeal order Methanomassiliicoccales are methanogens mainly associated with animal digestive tracts. However, environmental members remain poorly characterized as no representatives not associated with a host have been cultivated so far. In this study, metabarcoding screening combined with quantitative PCR analyses on a collection of diverse non-host-associated environmental samples revealed that Methanomassiliicoccales were very scarce in most terrestrial and aquatic ecosystems. Relative abundance of Methanomassiliicoccales and substrates/products of methanogenesis were monitored during incubation of environmental slurries. A sediment slurry enriched in Methanomassiliicoccales was obtained from a freshwater sample. It allowed the reconstruction of a high-quality metagenome-assembled genome (MAG) corresponding to a new candidate species, for which we propose the name of Candidatus ‘Methanomassiliicoccus armoricus MXMAG1’. Comparison of the annotated genome of MXMAG1 with the published genomes and MAGs from Methanomassiliicoccales belonging to the 2 known clades (‘free-living’/non-host-associated environmental clade and ‘host-associated’/digestive clade) allowed us to explore the putative physiological traits of Candidatus ‘M. armoricus MXMAG1’. As expected, Ca. ‘Methanomassiliicoccus armoricus MXMAG1’ had the genetic potential to produce methane by reduction of methyl compounds and dihydrogen oxidation. This MAG encodes for several putative physiological and stress response adaptations, including biosynthesis of trehalose (osmotic and temperature regulations), agmatine production (pH regulation), and arsenic detoxication, by reduction and excretion of arsenite, a mechanism that was only present in the ‘free-living’ clade. An analysis of co-occurrence networks carried out on environmental samples and slurries also showed that Methanomassiliicoccales detected in terrestrial and aquatic ecosystems were strongly associated with acetate and dihydrogen producing bacteria commonly found in digestive habitats and which have been reported to form syntrophic relationships with methanogens.
The Effect of Direct Electric Current on the Plastic Behavior of AA7075 Aluminum Alloy in Different States of Hardening

Electrically-Assisted Forming (EAF) techniques are interesting and promising for the automotive industry. Electrically-assisted tensile tests were carried out on specimens of AA7075 aluminum alloy in different states of hardening, namely T6 (the as-received state) and the supersaturated solid solution state. All the tests were carried out in quasi-static conditions under the application of direct electric current (DC) in the range of 90 to 540 A. The experimental results showed that with a DC density of 10 A/mm2 the uniform strain and strain at fracture increased when the AA7075 was in the supersaturated solid solution state. A correlation between the mechanical results and microstructural features analysed through transmission electron microscopy was assessed. An explanation of the investigated phenomena based on the electron wind theory, heterogeneous microscale Joule heating and the Portevin–Le Chatelier (PLC) effect was finally proposed.
Hyper-Progressive Disease: The Potential Role and Consequences of T-Regulatory Cells Foiling Anti-PD-1 Cancer Immunotherapy

Simple Summary Since immune cells were found to attack cancer cells, strategies have been developed to sustain anti-cancer immune functions to prevent them from becoming exhausted in the midst of war. Immune checkpoint blockade therapy has gained significant traction with its ability to fast-track activation of immune cells as well as revive dormant immune cells. A prominent target for such treatment is programmed cell death protein 1 (PD-1). The natural role of PD-1 is in regulating the activity of immune cells, hence the term ‘checkpoint’. Blocking PD-1 can be effective especially when immune cells have easy access to cancer tissues. However, the immune cell population also contains cells that protect cancer cells from anti-cancer immune cells. One of these is the regulatory T-cell (Treg) subset, which is also regulated by PD-1. In this article, we review the downside of blocking PD-1 in Tregs when using PD-1 blockade therapy to treat cancer. Abstract Antibody-mediated disruption of the programmed cell death protein 1 (PD-1) pathway has brought much success to the fight against cancer. Nevertheless, a significant proportion of patients respond poorly to anti-PD-1 treatment. Cases of accelerated and more aggressive forms of cancer following therapy have also been reported. Termed hyper-progressive disease (HPD), this phenomenon often results in fatality, thus requires urgent attention. Among possible causes of HPD, regulatory T-cells (Tregs) are of suspect due to their high expression of PD-1, which modulates Treg activity. Tregs are a subset of CD4+ T-cells that play a non-redundant role in the prevention of autoimmunity and is functionally dependent on the X chromosome-linked transcription factor FoxP3. In cancer, CD4+FoxP3+ Tregs migrate to tumors to suppress anti-tumor immune responses, allowing cancer cells to persist. Hence, Treg accumulation in tumors is associated with poor prognosis. In mice, the anti-tumor efficacy of anti-PD-1 can be enhanced by depleting Tregs. This suggests Tregs pose resistance to anti-PD-1 therapy. In this article, we review the relevant Treg functions that suppress tumor immunity and the potential effects anti-PD-1 could have on Tregs which are counter-productive to the treatment of cancer, occasionally causing HPD.
Enhanced Neural Empathic Responses in Patients with Spino-Bulbar Muscular Atrophy: An Electrophysiological Study

Background: Spino-bulbar muscular atrophy is a rare genetic X-linked disease caused by testosterone insensitivity. An inverse correlation has been described between testosterone levels and empathic responses. The present study explored the profile of neural empathic responding in spino-bulbar muscular atrophy patients. Methods: Eighteen patients with spino-bulbar muscular atrophy and eighteen healthy male controls were enrolled in the study. Their event-related potentials were recorded during an “Empathy Task” designed to distinguish neural responses linked with experience-sharing (early response) and mentalizing (late response) components of empathy. The task involved the presentation of contextual information (painful vs. neutral sentences) and facial expressions (painful vs. neutral). An explicit dispositional empathy-related questionnaire was also administered to all participants, who were screened via neuropsychological battery tests that did not reveal potential cognitive deficits. Due to electrophysiological artefacts, data from 12 patients and 17 controls were finally included in the analyses. Results: Although patients and controls did not differ in terms of dispositional, explicit empathic self-ratings, notably conservative event-related potentials analyses (i.e., spatio-temporal permutation cluster analyses) showed a significantly greater experience-sharing neural response in patients compared to healthy controls in the Empathy-task when both contextual information and facial expressions were painful. Conclusion: The present study contributes to the characterization of the psychological profile of patients with spino-bulbar muscular atrophy, highlighting the peculiarities in enhanced neural responses underlying empathic reactions.