Miracle-dz/UniFAR-FTUs huggingface dataset:
SARS-CoV-2 Spike Targets USP33-IRF9 Axis via Exosomal miR-148a to Activate Human Microglia

SARS-CoV-2, the novel coronavirus infection has consistently shown an association with neurological anomalies in patients, in addition to its usual respiratory distress syndrome. Multi-organ dysfunctions including neurological sequelae during COVID-19 persist even after declining viral load. We propose that SARS-CoV-2 gene product, Spike, is able to modify the host exosomal cargo, which gets transported to distant uninfected tissues and organs and can initiate a catastrophic immune cascade within Central Nervous System (CNS). SARS-CoV-2 Spike transfected cells release a significant amount of exosomes loaded with microRNAs such as miR-148a and miR-590. microRNAs gets internalized by human microglia and suppress target gene expression of USP33 (Ubiquitin Specific peptidase 33) and downstream IRF9 levels. Cellular levels of USP33 regulate the turnover time of IRF9 via deubiquitylation. Our results also demonstrate that absorption of modified exosomes effectively regulate the major pro-inflammatory gene expression profile of TNFα, NF-κB and IFN-β. These results uncover a bystander pathway of SARS-CoV-2 mediated CNS damage through hyperactivation of human microglia. Our results also attempt to explain the extra-pulmonary dysfunctions observed in COVID-19 cases when active replication of virus is not supported. Since Spike gene and mRNAs have been extensively picked up for vaccine development; the knowledge of host immune response against spike gene and protein holds a great significance. Our study therefore provides novel and relevant insights regarding the impact of Spike gene on shuttling of host microRNAs via exosomes to trigger the neuroinflammation.
Agro-Morphological, Yield, and Genotyping-by-Sequencing Data of Selected Wheat (Triticum aestivum) Germplasm From Pakistan

Citation: Islam M, Abdullah, Zubaida B, Amin N, Khan RI, Shafqat N, Masood R, Waseem S, Tahir J, Ahmed I, Naeem M and Ahmad H (2021) Agro-Morphological, Yield, and Genotyping-by-Sequencing Data of Selected Wheat (Triticum aestivum) Germplasm From Pakistan. Front. Genet. 12:617772. doi: 10.3389/fgene.2021. 617772 Agro-Morphological, Yield, and Genotyping-by-Sequencing Data of Selected Wheat (Triticum aestivum) Germplasm From Pakistan
A Comparison of Perceptions of Estonian and Latvian Hunters With Regard to the Control of African Swine Fever

Since the first detected African swine fever (ASF) cases in Lithuanian wild boar in 2014, the virus has occurred in many other member states of the European Union (EU), most recently in Belgium in 2018 and in Germany in 2020. Passive surveillance and various control measures are implemented as part of the strategy to stop disease spread in the wild boar population. Within this framework, hunters perform important activities, such as the removal of carcasses, fencing or hunting. Therefore, the successful implementation of these measures largely depends on their acceptability by hunters. Methods of participatory epidemiology can be used to determine the acceptance of control measures. The use of participatory methods allows the involvement of key stakeholders in the design, the implementation and the analysis of control and surveillance activities. In the present study, two studies that had been conducted using participatory epidemiology with hunters in Estonia and Latvia were compared on the topics recruitment, participants, facilitators, focus group discussion (FGDs) and their contents. The aim was to evaluate similarities and differences in the two studies and to identify a broader spectrum of possibilities to increase the willingness of hunters supporting the fight against ASF. Evaluating all conducted FGDs in both countries showed primarily similarities in the perceptions and opinions of the hunters in Estonia and Latvia. One notable difference was that passive surveillance in Latvia was perceived mostly as topic of duty and ethics rather than an issue driven by incentives. Participatory methods have proven to be an effective tool in the evaluation of the acceptance of established ASF control systems. The results of this study point out further chances for improving the cooperation with hunters in the future. Nevertheless, the importance of gathering and analyzing the opinions of hunters in all ASF affected countries individually is highlighted.
Three-Dimensional Imaging in Stem Cell-Based Researches

Stem cells have an important role in regenerative therapies, developmental biology studies and drug screening. Basic and translational research in stem cell technology needs more detailed imaging techniques. The possibility of cell-based therapeutic strategies has been validated in the stem cell field over recent years, a more detailed characterization of the properties of stem cells is needed for connectomics of large assemblies and structural analyses of these cells. The aim of stem cell imaging is the characterization of differentiation state, cellular function, purity and cell location. Recent progress in stem cell imaging field has included ultrasound-based technique to study living stem cells and florescence microscopy-based technique to investigate stem cell three-dimensional (3D) structures. Here, we summarized the fundamental characteristics of stem cells via 3D imaging methods and also discussed the emerging literatures on 3D imaging in stem cell research and the applications of both classical 2D imaging techniques and 3D methods on stem cells biology.
Spatial-Temporal Functional Mapping Combined With Cortico-Cortical Evoked Potentials in Predicting Cortical Stimulation Results

Functional human brain mapping is commonly performed during invasive monitoring with intracranial electroencephalographic (iEEG) electrodes prior to resective surgery for drug resistant epilepsy. The current gold standard, electrocortical stimulation mapping (ESM), is time consuming, sometimes elicits pain, and often induces after discharges or seizures. Moreover, there is a risk of overestimating eloquent areas due to propagation of the effects of stimulation to a broader network of language cortex. Passive iEEG spatial-temporal functional mapping (STFM) has recently emerged as a potential alternative to ESM. However, investigators have observed less correspondence between STFM and ESM maps of language than between their maps of motor function. We hypothesized that incongruities between ESM and STFM of language function may arise due to propagation of the effects of ESM to cortical areas having strong effective connectivity with the site of stimulation. We evaluated five patients who underwent invasive monitoring for seizure localization, whose language areas were identified using ESM. All patients performed a battery of language tasks during passive iEEG recordings. To estimate the effective connectivity of stimulation sites with a broader network of task-activated cortical sites, we measured cortico-cortical evoked potentials (CCEPs) elicited across all recording sites by single-pulse electrical stimulation at sites where ESM was performed at other times. With the combination of high gamma power as well as CCEPs results, we trained a logistic regression model to predict ESM results at individual electrode pairs. The average accuracy of the classifier using both STFM and CCEPs results combined was 87.7%, significantly higher than the one using STFM alone (71.8%), indicating that the correspondence between STFM and ESM results is greater when effective connectivity between ESM stimulation sites and task-activated sites is taken into consideration. These findings, though based on a small number of subjects to date, provide preliminary support for the hypothesis that incongruities between ESM and STFM may arise in part from propagation of stimulation effects to a broader network of cortical language sites activated by language tasks, and suggest that more studies, with larger numbers of patients, are needed to understand the utility of both mapping techniques in clinical practice.
Further Support for the Psychometric Properties of the Farsi Version of Perth Alexithymia Questionnaire

Alexithymia is defined as the lack of words to describe emotions and is associated with different psychopathologies. Various tools have been developed for measuring alexithymia; each has its limitations. A new questionnaire, Perth Alexithymia Questionnaire (PAQ), was developed to simultaneously assess positive and negative dimensions. Validation of such a tool in different cultures allows cross-cultural health psychology studies and facilitates knowledge transfer in the field. We aimed to examine the psychometric features of the PAQ in the Farsi-speaking population in Iran. Four-hundred-twenty-nine university students were asked to complete the PAQ, the Toronto Alexithymia Scale (TAS-20), Beck Depression Inventory (BDI-II), Beck Anxiety Inventory (BAI), and emotion regulation questionnaire (ERQ). Concurrent validity, discriminant validity, internal consistency, and test-retest reliability and factor structure were investigated. Confirmatory factor analysis showed a five-factor model identical to the original questionnaire. The questionnaire indicated good internal consistency (0.82 < α < 0.94). Test-retest reliability was acceptable for all subscales. The correlations between PAQ and its subscales with BDI-II, BAI, and TAS, and expression suppression subscale of ERQ were strong for concurrent validity. Concerning the discriminant validity, PAQ and its subscales were not correlated with reappraisal subscales of ERQ. The present findings suggest that the Farsi version of PAQ has strong psychometric properties and is appropriate for use in the Farsi-speaking population.
Transcriptome Signatures Predict Phenotypic Variations of Candida auris

Health care facilities are facing serious threats by the recently emerging human fungal pathogen Candida auris owing to its pronounced antifungal multidrug resistance and poor diagnostic tools. Distinct C. auris clades evolved seemingly simultaneously at independent geographical locations and display both genetic and phenotypic diversity. Although comparative genomics and phenotypic profiling studies are increasing, we still lack mechanistic knowledge about the C. auris species diversification and clinical heterogeneity. Since gene expression variability impacts phenotypic plasticity, we aimed to characterize transcriptomic signatures of C. auris patient isolates with distinct antifungal susceptibility profiles in this study. First, we employed an antifungal susceptibility screening of clinical C. auris isolates to identify divergent intra-clade responses to antifungal treatments. Interestingly, comparative transcriptional profiling reveals large gene expression differences between clade I isolates and one clade II strain, irrespective of their antifungal susceptibilities. However, comparisons at the clade levels demonstrate that minor changes in gene expression suffice to drive divergent drug responses. Finally, we functionally validate transcriptional signatures reflecting phenotypic divergence of clinical isolates. Thus, our results suggest that large-scale transcriptional profiling allows for predicting phenotypic diversities of patient isolates, which may help choosing suitable antifungal therapies of multidrug-resistant C. auris.
Health-Related Quality of Life Based on EQ-5D Utility Score in Patients With Tuberculosis: A Systematic Review

Background: Tuberculosis (TB) has significant effects on patients’ health-related quality of life (HRQOL) and this study was conducted to evaluate the HRQOL based on EQ-5D utility score according to various health statuses of TB patients. Methods: A systematic literature review was conducted to select articles on HRQOLs outcomes of TB patients since 2000. A total of 1,710 articles were searched for primary screening and seven studies that directly assessed all types of TB patients using the EQ-5D were finally selected. Results: The EQ-5D scores of TB patients were in the ranges of 0.43–0.70. After the completion of TB treatment, the utility weights increased to the ranges of 0.88–0.98 and the EQ VAS values showed similar trend as the results of the EQ-5D. The EQ-5D score for multi-drug-resistant TB was very low at 0.51 during treatment but increased to 0.88 after the treatment was completed. The utility weights of latent TB were not significantly different from those of the general population. Conclusion: This study showed that the HRQOL based on the EQ-5D utility score of TB patients has significantly decreased, and the TB treatment has a significantly positive effect on the quality of life of patients.
Nomogram to Predict Cognitive Dysfunction After a Minor Ischemic Stroke in Hospitalized-Population

An easily scoring system to predict the risk of cognitive impairment after minor ischemic stroke has not been available. We aimed to develop and externally validate a nomogram for predicting the probability of post-stroke cognitive impairment (PSCI) among hospitalized population with minor stroke. Moreover, the association of Trimethylamine N-oxide (TMAO) with PSCI is also investigated. We prospectively conducted a developed cohort on collected data in stroke center from June 2017 to February 2018, as well as an external validation cohort between June 2018 and February 2019. The main outcome is cognitive impairment defined as <22 Montreal Cognition Assessment (MoCA) score points 6 – 12 months following a minor stroke onset. Based on multivariate logistic models, the nomogram model was generated. Plasma TMAO levels were assessed at admission using liquid chromatography tandem mass spectrometry. A total of 228 participants completed the follow-up data for generating the nomogram. After multivariate logistic regression, seven variables remained independent predictors of PSCI to compose the nomogram included age, female, Fazekas score, educational level, number of intracranial atherosclerotic stenosis (ICAS), HbA1c, and cortical infarction. The area under the receiver-operating characteristic (AUC-ROC) curve of model was 0.829, C index was good (0.810), and the AUC-ROC of the model applied in validation cohort was 0.812. Plasma TMAO levels were higher in patients with cognitive impairment than in them without cognitive dysfunction (median 4.56 vs. 3.22 μmol/L; p ≤ 0.001). In conclusion, this scoring system is the first nomogram developed and validated in a stroke center cohort for individualized prediction of cognitive impairment after minor stroke. Higher plasma TMAO level at admission suggests a potential marker of PSCI.
Root Exudates Alter the Expression of Diverse Metabolic, Transport, Regulatory, and Stress Response Genes in Rhizosphere Pseudomonas

Plants live in association with microorganisms that positively influence plant development, vigor, and fitness in response to pathogens and abiotic stressors. The bulk of the plant microbiome is concentrated belowground at the plant root-soil interface. Plant roots secrete carbon-rich rhizodeposits containing primary and secondary low molecular weight metabolites, lysates, and mucilages. These exudates provide nutrients for soil microorganisms and modulate their affinity to host plants, but molecular details of this process are largely unresolved. We addressed this gap by focusing on the molecular dialog between eight well-characterized beneficial strains of the Pseudomonas fluorescens group and Brachypodium distachyon, a model for economically important food, feed, forage, and biomass crops of the grass family. We collected and analyzed root exudates of B. distachyon and demonstrated the presence of multiple carbohydrates, amino acids, organic acids, and phenolic compounds. The subsequent screening of bacteria by Biolog Phenotype MicroArrays revealed that many of these metabolites provide carbon and energy for the Pseudomonas strains. RNA-seq profiling of bacterial cultures amended with root exudates revealed changes in the expression of genes encoding numerous catabolic and anabolic enzymes, transporters, transcriptional regulators, stress response, and conserved hypothetical proteins. Almost half of the differentially expressed genes mapped to the variable part of the strains’ pangenome, reflecting the importance of the variable gene content in the adaptation of P. fluorescens to the rhizosphere lifestyle. Our results collectively reveal the diversity of cellular pathways and physiological responses underlying the establishment of mutualistic interactions between these beneficial rhizobacteria and their plant hosts.
Bispecific T-Cell Engaging Antibodies Against MUC16 Demonstrate Efficacy Against Ovarian Cancer in Monotherapy and in Combination With PD-1 and VEGF Inhibition

Immunotherapy for ovarian cancer is an area of intense investigation since the majority of women with relapsed disease develop resistance to conventional cytotoxic therapy. The paucity of safe and validated target antigens has limited the development of clinically relevant antibody-based immunotherapeutics for this disease. Although MUC16 expression is almost universal in High Grade Serous Ovarian Cancers, engagement of the shed circulating MUC16 antigen (CA-125) presents a theoretical risk of systemic activation and toxicity. We designed and evaluated a series of bispecific tandem single-chain variable fragments specific to the retained portion of human MUC16 ectodomain (MUC16ecto) and human CD3. These MUC16ecto- BiTEDs retain binding in the presence of soluble MUC16 (CA-125) and show cytotoxicity against a panel of ovarian cancer cells in vitro. MUC16ecto- BiTEDs delay tumor progression in vivo and significantly prolong survival in a xenograft model of ovarian peritoneal carcinomatosis. This effect was significantly enhanced by antiangiogenic (anti-VEGF) therapy and immune checkpoint inhibition (anti-PD1). However, the combination of BiTEDs with anti-VEGF was superior to combination with anti-PD1, based on findings of decreased peritoneal tumor burden and ascites with the former. This study shows the feasibility and efficacy of MUC16ecto- specific BiTEDs and provides a basis for the combination with anti-VEGF therapy for ovarian cancer.
Induced Local and Systemic Defense Responses in Tomato Underlying Interactions Between the Root-Knot Nematode Meloidogyne incognita and the Potato Aphid Macrosiphum euphorbiae

Plants mediate interactions between different herbivores that attack simultaneously or sequentially aboveground (AG) and belowground (BG) organs. The local and systemic activation of hormonal signaling pathways and the concomitant accumulation of defense metabolites underlie such AG-BG interactions. The main plant-mediated mechanisms regulating these reciprocal interactions via local and systemic induced responses remain poorly understood. We investigated the impact of root infection by the root-knot nematode (RKN) Meloidogyne incognita at different stages of its infection cycle, on tomato leaf defense responses triggered by the potato aphid Macrosiphum euphorbiae. In addition, we analyzed the reverse impact of aphid leaf feeding on the root responses triggered by the RKN. We focused specifically on the signaling pathways regulated by the phytohormones jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), and indole-3-acetic acid (IAA) as well as steroidal glycoalkaloids as induced defense compounds. We found that aphid feeding did not induce AG hormonal signaling, but it repressed steroidal glycoalkaloids related responses in leaves, specifically when feeding on plants in the vegetative stage. Root infection by the RKN impeded the aphid-triggered repression of the steroidal glycoalkaloids-related response AG. In roots, the RKN triggered the SA pathway during the entire infection cycle and the ABA pathway specifically during its reproduction stage. RKN infection also elicited the steroidal glycoalkaloids related gene expression, specifically when it was in the galling stage. Aphid feeding did not systemically alter the RKN-induced defense responses in roots. Our results point to an asymmetrical interaction between M. incognita and Ma. euphorbiae when co-occurring in tomato plants. Moreover, the RKN seems to determine the root defense response regardless of a later occurring attack by the potato aphid AG.
Nonlinear Optical Properties of Thiolate-Protected Gold Clusters: A Theoretical Survey of the First Hyperpolarizabilities

A series of thiolate-protected gold clusters has been successfully crystallized in recent years, and on the basis of these crystal structures, we investigate the static first hyperpolarizabilities β0 of eight model clusters [Aum(SH)n]z (m = 18–38) by means of density-functional theory. We used simplified ligands −SH, which may lead to higher symmetries than in actual systems (e.g., with −SCH2CH2Ph or −SPh ligands). A dependence of the obtained values on the exchange-correlation functional during geometry optimization was found. No correlation between cluster size and β0 was identified. Instead, the symmetry of the clusters seems to dominate the NLO properties. Our survey predicts strong NLO responses in the chiral Au38(SR)24 cluster, whereas centrosymmetric structures such as the [Au25(SR)18)]− yield hyperpolarizabilities close to zero. This is in line with recent experimental results obtained by second-harmonic generation. The centrosymmetry of the Au25 cluster is efficiently destroyed by ligand exchange.
Research Paper: Problem-Solving Ability and Quality of Life of Mothers of Children With Autism Spectrum Disorder

Methods: This was a descriptive and correlational study. The study population consisted of the mothers of children with AS in Isfahan City, Iran. The required sample was selected from one autism center (out of three) using a convenience sampling method. Then, a sample of 150 mothers was randomly selected. Accordingly, they completed the 12-item Quality of Life and the 35item Problem-Solving Inventory (PSI). The obtained data were analyzed using the Pearson correlation coefficient and stepwise regression analysis.
Warning-Introducing Commits vs Bug-Introducing Commits: A tool, statistical models, and a preliminary user study

This paper partially replicates prior works on building historical commits [1], commit risk modeling [2], and a comparison of statistical bug models and static bug finders [3]. We examine 8 Maven-based projects with an average lifespan of 5.8 years. To historically build these projects across a total of 45k commits, we develop a series of techniques, such as flexibly selecting the version of a library that is closest to the commit date. We are able to build a per project average of 78.4% of all commits, a doubling in buildability compared to prior work. We also develop a git blame strategy to assign warnings even when a commit does not build.We run JLint and FindBugs and create a logistic regression model to predict if a commit that introduces a warning has higher odds of introducing a bug. The static bug finders model accounted for only 13% of the deviance, while the statistical bug model accounted for 19.5%. We had expected static bug finder warnings to improve the predictive power of models of bug introducing changes, but we clearly attained a negative result.To understand this negative result, we perform a preliminary user study of developers who introduced new warnings in 37 projects. We found that while warnings might not predict bugs, 53% and 21% of warnings in Findbugs and Jlint respectively are useful. We also study whether just-in-time warnings presentation on each commit impacted usefulness. We find that the later a warning is shown to a developer, the less useful it is perceived to be (a median of 11.5 days versus 23 days for non useful warnings). Based on our findings, we modify the existing COMMITGURU interface to add new warnings to the specific line in a changed file. The empirical study data [4] and WARNINGSGURU tool [5] are publicly available.