Miracle-dz/UniFAR-FTUs huggingface dataset:
Bridging Scales in Alzheimer's Disease: Biological Framework for Brain Simulation With The Virtual Brain

Despite the acceleration of knowledge and data accumulation in neuroscience over the last years, the highly prevalent neurodegenerative disease of AD remains a growing problem. Alzheimer's Disease (AD) is the most common cause of dementia and represents the most prevalent neurodegenerative disease. For AD, disease-modifying treatments are presently lacking, and the understanding of disease mechanisms continues to be incomplete. In the present review, we discuss candidate contributing factors leading to AD, and evaluate novel computational brain simulation methods to further disentangle their potential roles. We first present an overview of existing computational models for AD that aim to provide a mechanistic understanding of the disease. Next, we outline the potential to link molecular aspects of neurodegeneration in AD with large-scale brain network modeling using The Virtual Brain (www.thevirtualbrain.org), an open-source, multiscale, whole-brain simulation neuroinformatics platform. Finally, we discuss how this methodological approach may contribute to the understanding, improved diagnostics, and treatment optimization of AD.
Autophagy in Human T-Cell Leukemia Virus Type 1 (HTLV-1) Induced Leukemia

Viruses play an important role in the development of certain human cancers. They are estimated to contribute 16% to all human cancers. Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus to be discovered and is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), an aggressive T-cell malignancy with poor prognosis. HTLV-1 viral proteins interact with mechanisms and proteins present in host cells for their own benefit, evading the immune system and promoting the establishment of disease. Several viruses manipulate the autophagy pathway to achieve their infective goals, and HTLV-1 is not the exception. HTLV-1 Tax viral protein engages NF-κB and autophagy pathways prone favoring viral replication and T cell transformation. In this review we focus on describing the relationship of HTLV-1 with the autophagy machinery and its implication in the development of ATLL.
New Perspectives in Different Gene Expression Profiles for Early and Locally Advanced Non-Small Cell Lung Cancer Stem Cells

Introduction Lung cancer is one of the most common cancers in the world, causing over 1.7 million deaths in 2018. Thus far, no effective treatments against lung cancer for advanced stages have been found. For early stages, although surgery is considered the gold standard treatment, 30–55% of patients develop recurrence within the first 5 years of surgery. Our aim is to assess whether cancer stem cells (CSC) display overexpression of a pool of genes that were previously identified for adenocarcinoma recurrence in patients with early and locally advanced stages of non-small cell lung cancer (NSCLC). Methods This cross-sectional study was carried out by harvesting surgical tumor specimens obtained from patients harboring early (I-II) and locally advanced (IIIA) stages of NSCLC. For each patient, cell sorting was performed to identify and isolate the ALDHhigh (CSC) and ALDHlow (cancer cells) populations. The mRNA expressions of 31 recurrence-related genes (target genes) in both ALDHhigh and ALDHlow populations were then assessed and compared. Results Surgical specimens were obtained from 22 patients harboring NSCLC. Sixteen (51.6%) out of 31 recurrence-related genes were significantly overexpressed in ALDHhigh cells in the early stages and 9 (29.0%) were overexpressed in the locally advanced stages of NSCLC. Overall, the relative mRNA expressions for these recurrence-related genes were higher in early-stage patients. The average fold change, considering all 31 recurrence-related genes together, was 4.5 (95% CI = 3.1-6.3) in early-stage patients and 1.6 (95% CI = 1.2-2.2) in locally advanced-stage patients. Conclusions Our study represents the first attempt toward identifying genes associated with recurrence that are overexpressed in cancer stem cells in patients with early and locally advanced stages of NSCLC. This finding may contribute to the identification of new target therapies tailored for NSCLC stages.
Heterogeneity in Risk-Taking During the COVID-19 Pandemic: Evidence From the UK Lockdown

In two pre-registered online studies during the COVID-19 pandemic and the early 2020 lockdown (one of which with a UK representative sample) we elicit risk-tolerance for 1,254 UK residents using four of the most widely applied risk-taking tasks in behavioral economics and psychology. Specifically, participants completed the incentive-compatible Balloon Analog Risk Task (BART) and the Binswanger-Eckel-Grossman (BEG) multiple lotteries task, as well as the Domain-Specific Risk-Taking Task (DOSPERT) and the self-reported questions for risk-taking used in the German Socio-economic Panel (SOEP) study. In addition, participants in the UK representative sample answered a range of questions about COVID-19-related risky behaviors selected from the UCL COVID-19 Social Survey and the ICL-YouGov survey on COVID-19 behaviors. Consistently with pre-COVID-19 times, we find that risk tolerance during the UK lockdown (i) was higher in men than in women and (ii) decreased with age. Undocumented in pre-COVID-19 times, we find some evidence for healthier participants displaying significantly higher risk-tolerance for self-reported risk measures. We find no systematic nor robust patterns of association between the COVID-19 risky behaviors and the four risk-taking tasks in our study. Moreover, we find no evidence in support of the so-called “risk compensation” hypothesis. If anything, it appears that participants who took greater risk in real-life COVID-19-relevant risky behaviors (e.g., isolating or taking precautions) also exhibited higher risk-tolerance in our experimental and self-reported risk-taking measures.
Dynamic Histone H3 Modifications Regulate Meiosis Initiation via Respiration

Meiosis is essential for genetic stability and diversity during sexual reproduction in most eukaryotes. Chromatin structure and gene expression are drastically changed during meiosis, and various histone modifications have been reported to participate in this unique process. However, the dynamic of histone modifications during meiosis is still not well investigated. Here, by using multiple reaction monitoring (MRM) based LC-MS/MS, we detected dynamic changes of histone H3 lysine post-translational modifications (PTMs). We firstly quantified the precise percentage of H3 modifications on different lysine sites during mouse and yeast meiosis, and found H3 acetylation and methylation were dramatically changed. To further study the potential functions of H3 acetylation and methylation in meiosis, we performed histone H3 lysine mutant screening in yeast, and found that yeast strains lacking H3K18 acetylation (H3K18ac) failed to initiate meiosis due to insufficient IME1 expression. Further studies showed that the absence of H3K18ac impaired respiration, leading to the reduction of Rim101p, which further upregulated a negative regulator of IME1 transcription, Smp1p. Together, our studies reveal a novel meiosis initiation pathway mediated by histone H3 modifications.
Spontaneous Activity in Primary Visual Cortex Relates to Visual Creativity

Cognitive and neural processes underlying visual creativity have attracted substantial attention. The current research uses a critical time point analysis (CTPA) to examine how spontaneous activity in the primary visual area (PVA) is related to visual creativity. We acquired the functional magnetic resonance imaging (fMRI) data of 16 participants at the resting state and during performing a visual creative synthesis task. According to the CTPA, we then classified spontaneous activity in the PVA into critical time points (CTPs), which reflect the most useful and important functional meaning of the entire resting-state condition, and the remaining time points (RTPs). We constructed functional brain networks based on the brain activity at two different time points and then subsequently based on the brain activity at the task state in a separate manner. We explore the relationship between resting-state and task-fMRI (T-fMRI) functional brain networks. Our results found that: (1) the pattern of spontaneous activity in the PVA may associate with mental imagery, which plays an important role in visual creativity; (2) in comparison with the RTPs-based brain network, the CTP-network showed an increase in global efficiency and a decrease in local efficiency; (3) the regional integrated properties of the CTP-network could predict the integrated properties of the creative-network while the RTP-network could not. Thus, our findings indicated that spontaneous activity in the PVA at CTPs was associated with a visual creative task-evoked brain response. Our findings may provide an insight into how the visual cortex is related to visual creativity.
Characterization of the Tumor Immune Microenvironment in Lung Squamous Cell Carcinoma Using Imaging Mass Cytometry

Background Lung squamous cell carcinoma (LUSC) is a major subtype of non-small cell lung cancer. The tumor immune microenvironment (TIME) affects the anti-tumor immune response and the patient’s prognosis, although the TIME in LUSC patients is incompletely understood. Methods We retrospectively collected surgical specimens from patients with previously untreated primary LUSC. Histopathological examination was used to identify tumor regions and adjacent regions, and imaging mass cytometry was used to characterize the immune cells in those regions. The results were compared between regions and between patients. Results We identified heterogeneity in the TIME on comparing different patients with LUSC, although the tumor region and adjacent region both exhibited an immune response to the tumor. The TIME typically included a large number of infiltrating and activated T-cells, especially CD8+ T-cells, which closely interacted with the tumor cells in the tumor region. There was limited infiltration of B-cells, NK cells, and NKT cells, while the major immune suppressor cells were CD33+ myeloid-derived cells. We also identified a novel population of CD3−CD4+ cells with high expression of Foxp3 and TNFα, which might modulate the tumor microenvironment and play a proinflammatory role in the TIME. Conclusions The TIME of LUSC appears to be immunogenic and heterogenous, with predominant infiltration of activated CD8+ T-cells. The interactions between the tumor cells and T-cells facilitate the anti-tumor activity. A novel subpopulation of CD3−CD4+ cells with high TNFα and Foxp3 expression may modulate the tumor microenvironment and play a proinflammatory role.
The Unequal Distribution of Linguistic Capital in a Transnational Economic Order

Foreign language proficiency is an unequally distributed form of linguistic capital that is becoming increasingly important in contemporary societies: first, it enables persons to participate transnationally in educational activities and in labor markets beyond the national institutions of their home country. It is also crucial for integrating an increasing share of the population with a migration background into the labor market. Thus, this article focuses on the explanation of language proficiency. Its main aim is to enrich the discussion in this field by deriving hypotheses from the sociological theory of reproduction and the discourse on migrant integration. Variables are included which have not been tested in a broad fashion in previous empirical research. We use data on different groups of migrants and non-migrants in multilingual Switzerland, where we could study the determinants of the unequal distribution of language proficiency in three official languages and foreign language repertoire in general. Our main results show that the hypotheses derived from the two theoretical discussions are empirically supported overall and contribute substantially to the explanation of language proficiency. However, most of these variables indicate the importance of unequally distributed opportunities for learning languages, thus highlighting that language learning may be part of the general process of reproducing social inequality structures.
Grand Challenges in Remote Sensing Image Analysis and Classification

Over the past ∼20 years, the proliferation of sensors and platforms in both the public and private sectors, combined with the open data policies of NASA, ESA, and other national space agencies, have resulted in a dramatic increase in the availability of remotely sensed data and the widespread adoption of remote sensing as an essential tool for a wide range of applications. Unlike many of the specialty research topics covered by the Frontiers journals, remote sensing image analysis and classification spans a wide range of disparate research disciplines, making the identification of grand challenges fundamentally different from that in more narrowly focused disciplines. For this reason, the challenges discussed in this article will be related to topically-relevant standards intended to maximize the utility of the work published by the journal. Discipline-specific bibliometrics compiled since the early 2000s suggest that remote sensing articles achieve disproportionate impact, even relative to their rapid and sustained growth in number. Figure 1 quantifies both of these trends since 2003, showing the aggregate impact factor of remote sensing publications on average more than tripling as the number of articles per year grew almost 8fold. This may be due, in part, to the wide range of disciplines in which remote sensing is now used. Figure 2 shows comparative bibliometrics for remote sensing and several of these disciplines, as well as two that contribute methodologies (Imaging Science, and Artificial Intelligence—including machine learning) that have long been used in remote sensing image analysis and classification. Despite the comparatively small number of remote sensing journals (30 in 2019), the average number of citations per article is among the highest of these disciplines. Taken together, the continued growth in both volume and impact of remote sensing articles, and their relevance to such a wide range of related disciplines, emphasize the importance of standards going forward. This brief essay will discuss three fundamental criteria essential to the standard of articles published in the Image Analysis and Classification specialty section.
The Effect of Persuasive Messages in Promoting Home-Based Physical Activity During COVID-19 Pandemic

We tested the plausibility of a persuasion model to understand the effects of messages framed in terms of gain, non-loss, loss, and non-gain, and related to the physical, mental and social consequences of doing physical activity at home during the lockdown restrictions. 272 Italian participants responded to a questionnaire on their attitude and intention at Time 1, frequency of past behavior, and self-efficacy related to exercising at home. Then, participants were randomly assigned to four different message conditions: (a) gain messages focused on the positive outcomes associated with doing physical activity at home; (b) non-loss messages focused on the avoided negative outcomes associated with doing physical activity at home; (d) loss messages focused on the negative outcomes associated with not doing physical activity at home; (c) non-gain messages focused on the missed positive outcomes associated with not doing physical activity at home. After reading the messages, participants answered a series of questions regarding their perception of threat and fear, their evaluation of the messages, and their attitude and intention toward exercising at home at Time 2. Using multigroup structural equation modeling, we compared message conditions, and tested whether the effects of the messages on attitude and intention at Time 2 were mediated by message-induced threat, message-induced fear, and message evaluation. Results showed that the perception of the messages as not threatening was the key point to activate a positive evaluation of the recommendation. The highest persuasive effect was observed in the case of the non-loss frame, which did not threaten the receivers, triggered a moderated fear and, in turn, activated a positive evaluation of the recommendation, as well as higher attitude and intention to do home-based physical activity at Time 2. Overall, these results advance our comprehension of the effects of message framing on receivers' attitudes and intentions toward home-based physical activity.
Posttraumatic Stress Symptoms, Quality of Life, and Stress Burden in Caregivers of Patients With Severe Mental Illness: An Underestimated Health Concern

Caregivers of patients with severe mental disorders experience a heavy stress burden that can manifest as psychiatric symptoms mimicking posttraumatic stress disorder (PTSD) and can negatively impact interpersonal relationships and work performance. The present study investigated the prevalence of PTSD symptoms, quality of life (QoL), and stress burden in caregivers of patients with severe mental illness. A total of 70 caregivers of severely mentally ill patients and 70 control subjects who were caregivers of patients with a chronic debilitating medical illness (cardiovascular disease) were recruited from university hospital outpatient facilities. Severe mental illness was defined based on a Global Assessment of Functioning score <50 and duration of illness >2 years. Both groups were evaluated with the Zarit Burden interview, a QoL questionnaire, and Posttraumatic Diagnostic Scale (PDS). The results showed that 37.14% (n = 26) of caregivers of patients with severe mental illness showed PTS symptoms compared to 0% of caregivers of patients with physical illness, and 15.17% (n = 11) met the diagnostic criteria for PTSD. Caregivers of patients with severe mental illness had higher stress burden and lower QoL scores than the control group (p < 0.05). These results indicate that caregivers of patients with severe mental illness have a high stress burden that may lead to PTSD, highlighting the importance of providing psychological support to this group.
Pathological Findings in COVID-19 as a Tool to Define SARS-CoV-2 Pathogenesis. A Systematic Review

Introduction: The World Health Organization declared the COVID-19 pandemic in March 2020. COVID-19 still represents a worldwide health emergency, which causesa severe disease that has led to the death of many patients. The pathophysiological mechanism of SARS-CoV-2 determining the tissue damage is not clear and autopsycan be auseful tool to improve the knowledge of this infection and, thus, it can help achieve a timely diagnosis and develop an appropriate therapy. This is an overview of the main post-mortem findings reporting data on the infection effects on several organs. Methods: A systematic literature search was conducted in the PubMed database searching for articles from 1 January to August 31, 2020. Thearticles were selected identifying words/concepts in the titles and/or abstracts that indicated the analysis of the morphological/pathological tissue injuries related to SARS-CoV-2 disease by several investigations. Results: A total of 63 articles were selected. The main investigated tissue was the lung showing a diffuse alveolar damage (DAD) frequently associated with pulmonary thrombotic microangiopathy. Inflammatory findings and vascular damage were observed in other organs such as heart, liver, kidney, brain, spleen, skin and adrenal gland. The immunohistochemical analysis showed tissue inflammatory cells infiltrates. The virus presence was detected by several investigations such as RT-PCR, immunohistochemistry and electron microscope, showing the effect ofSARS-CoV-2not exclusively in the lung. Discussion: The evidence emerging from this review highlighted the importance of autopsy to provide a fundamental base in the process of understanding the consequences ofSARS-CoV-2 infection. COVID-19 is strictly related to a hyper inflammatory state that seems to start with DAD and immuno-thrombotic microangiopathy. Massive activation of the immune system and microvascular damage might also be responsible for indirect damage to other organs, even if the direct effect of the virus on these tissues cannot be excluded.
Tremella fuciformis Polysaccharides Inhibited Colonic Inflammation in Dextran Sulfate Sodium-Treated Mice via Foxp3+ T Cells, Gut Microbiota, and Bacterial Metabolites

Tremella fuciformis is an edible medicinal mushroom, and its polysaccharide components are found to confer various health benefits. This study identified the protective effects of polysaccharides of Tremella fuciformis (TPs) against dextran sulfate sodium (DSS)-induced colitis in mice. High dose of TPs (HTPs) could prevent the colon from shortening, reduce activity of colonic myeloperoxidase and serum diamine oxidase (DAO), decrease the concentration of D-lactate, and alleviate the colonic tissue damage in colitic mice. HTPs treatment stimulated Foxp3+T cells, and promoted the production of anti-inflammatory cytokines whereas it reduced the production of pro-inflammatory and the portion of immunoglobulin A (IgA)-coated bacteria, which was related to modulation of immune responses. 16S rRNA sequencing analysis showed that TPs could significantly increase gut community diversity, and restore the relative abundances of Lactobacillus, Odoribacter, Helicobacter, Ruminococcaceae, and Marinifilaceae. According to metabolomic analysis, HTPs induced specific microbial metabolites akin to that in normal mice. Tyrosine biosynthesis, tryptophan metabolism, and bile acid metabolism were influenced in the HTPs group compared with those in the DSS group. HTPs could alleviate DSS-induced colitis by immunoregulation and restored the gut microbiota and microbial metabolites. The results indicated that HTPs have potential to be developed as a food supplement to ameliorate intestinal diseases.
HIV-1 Capsid Core: A Bullet to the Heart of the Target Cell

The first step of the intracellular phase of retroviral infection is the release of the viral capsid core in the cytoplasm. This structure contains the viral genetic material that will be reverse transcribed and integrated into the genome of infected cells. Up to recent times, the role of the capsid core was considered essentially to protect this genetic material during the earlier phases of this process. However, increasing evidence demonstrates that the permanence inside the cell of the capsid as an intact, or almost intact, structure is longer than thought. This suggests its involvement in more aspects of the infectious cycle than previously foreseen, particularly in the steps of viral genomic material translocation into the nucleus and in the phases preceding integration. During the trip across the infected cell, many host factors are brought to interact with the capsid, some possessing antiviral properties, others, serving as viral cofactors. All these interactions rely on the properties of the unique component of the capsid core, the capsid protein CA. Likely, the drawback of ensuring these multiple functions is the extreme genetic fragility that has been shown to characterize this protein. Here, we recapitulate the busy agenda of an HIV-1 capsid in the infectious process, in particular in the light of the most recent findings.