Miracle-dz/UniFAR-FTUs huggingface dataset:
Ontology-Based Classification and Analysis of Adverse Events Associated With the Usage of Chloroquine and Hydroxychloroquine

Multiple methodologies have been developed to identify and predict adverse events (AEs); however, many of these methods do not consider how patient population characteristics, such as diseases, age, and gender, affect AEs seen. In this study, we evaluated the utility of collecting and analyzing AE data related to hydroxychloroquine (HCQ) and chloroquine (CQ) from US Prescribing Information (USPIs, also called drug product labels or package inserts), the FDA Adverse Event Reporting System (FAERS), and peer-reviewed literature from PubMed/EMBASE, followed by AE classification and modeling using the Ontology of Adverse Events (OAE). Our USPI analysis showed that CQ and HCQ AE profiles were similar, although HCQ was reported to be associated with fewer types of cardiovascular, nervous system, and musculoskeletal AEs. According to EMBASE literature mining, CQ and HCQ were associated with QT prolongation (primarily when treating COVID-19), heart arrhythmias, development of Torsade des Pointes, and retinopathy (primarily when treating lupus). The FAERS data was analyzed by proportional ratio reporting, Chi-square test, and minimal case number filtering, followed by OAE classification. HCQ was associated with 63 significant AEs (including 21 cardiovascular AEs) for COVID-19 patients and 120 significant AEs (including 12 cardiovascular AEs) for lupus patients, supporting the hypothesis that the disease being treated affects the type and number of certain CQ/HCQ AEs that are manifested. Using an HCQ AE patient example reported in the literature, we also ontologically modeled how an AE occurs and what factors (e.g., age, biological sex, and medical history) are involved in the AE formation. The methodology developed in this study can be used for other drugs and indications to better identify patient populations that are particularly vulnerable to AEs.
Study Abroad: An Empirical Study Based on Expectancy-Value Theory and Self-Determination Theory

Push-pull theory, consumer decision-making models and rational choice theory are commonly used to explain international student mobility (ISM). Despite their merits, the individual’s motivation to study abroad is ignored. Based on two motivation theories— expectancy-value theory (EVT) and self-determination theory (SDT), this study examines whether students’ intention to study abroad originates from the students themselves or compromises social pressure and how the external factors defined in push-pull theory work with these motivations to affect their decision-making. A quantitative study was conducted with a sample size of 736 international students in China. The findings show that the decision to study abroad is a highly subjective and intrinsically driven behavior in which realizing one’s self-worth or fulfilling one’s purpose of life plays the most significant role. Making a decision needs a “cost-benefits calculus,” but the utility value of study abroad was positioned behind attainment value and identified motivation. The heterogeneity of international students’ motivation was also differentiated by both their gender and their parents’ educational backgrounds.
A Modified Implementation Mapping Methodology for Evaluating and Learning From Existing Implementation

When empirically supported interventions are implemented in real-world practice settings, the process of how these interventions are implemented is highly relevant for their potential success. Implementation Mapping is a method that provides step-by-step guidance for systematically designing implementation processes that fit the respective intervention and context. It includes needs assessments among relevant stakeholders, the identification of implementation outcomes and determinants, the selection and design of appropriate implementation strategies, the production of implementation protocols and an implementation outcome evaluation. Implementation Mapping is generally conceptualized as a tool to prospectively guide implementation. However, many implementation efforts build on previous or ongoing implementation efforts, i.e., “existing implementation. ” Learnings from existing implementation may offer insights critical to the success of further implementation activities. In this article, we present a modified Implementation Mapping methodology to be applied when evaluating existing implementation. We illustrate the methodology using the example of evaluating ongoing organized colorectal cancer screening programs in Switzerland. Through this example, we describe how we identify relevant stakeholders, implementation determinants and outcomes as well as currently employed implementation strategies. Moreover, we describe how we compare the types of strategies that are part of existing implementation efforts with those that implementation science would suggest as being suited to address identified implementation determinants. The results can be used for assessing the current state of implementation outcomes, refining ongoing implementation strategies, and informing future implementation efforts.
Identification of Hub Genes With Differential Correlations in Sepsis

As a multifaceted syndrome, sepsis leads to high risk of death worldwide. It is difficult to be intervened due to insufficient biomarkers and potential targets. The reason is that regulatory mechanisms during sepsis are poorly understood. In this study, expression profiles of sepsis from GSE134347 were integrated to construct gene interaction network through weighted gene co-expression network analysis (WGCNA). R package DiffCorr was utilized to evaluate differential correlations and identify significant differences between sepsis and healthy tissues. As a result, twenty-six modules were detected in the network, among which blue and darkred modules exhibited the most significant associations with sepsis. Finally, we identified some novel genes with opposite correlations including ZNF366, ZMYND11, SVIP and UBE2H. Further biological analysis revealed their promising roles in sepsis management. Hence, differential correlations-based algorithm was firstly established for the discovery of appealing regulators in sepsis.
Processing of Spoken Emotions in Schizophrenia: Forensic and Non-forensic Patients Differ in Emotional Identification and Integration but Not in Selective Attention

Patients with schizophrenia (PwS) typically demonstrate deficits in visual processing of emotions. Less is known about auditory processing of spoken-emotions, as conveyed by the prosodic (tone) and semantics (words) channels. In a previous study, forensic PwS (who committed violent offenses) identified spoken-emotions and integrated the emotional information from both channels similarly to controls. However, their performance indicated larger failures of selective-attention, and lower discrimination between spoken-emotions, than controls. Given that forensic schizophrenia represents a special subgroup, the current study compared forensic and non-forensic PwS. Forty-five PwS listened to sentences conveying four basic emotions presented in semantic or prosodic channels, in different combinations. They were asked to rate how much they agreed that the sentences conveyed a predefined emotion, focusing on one channel or on the sentence as a whole. Their performance was compared to that of 21 forensic PwS (previous study). The two groups did not differ in selective-attention. However, better emotional identification and discrimination, as well as better channel integration were found for the forensic PwS. Results have several clinical implications: difficulties in spoken-emotions processing might not necessarily relate to schizophrenia; attentional deficits might not be a risk factor for aggression in schizophrenia; and forensic schizophrenia might have unique characteristics as related to spoken-emotions processing (motivation, stimulation).
Erg25 Controls Host-Cholesterol Uptake Mediated by Aus1p-Associated Sterol-Rich Membrane Domains in Candida glabrata

The uptake of cholesterol from the host is closely linked to the proliferation of pathogenic fungi and protozoa during infection. For some pathogenic fungi, cholesterol uptake is an important strategy for decreasing susceptibility to antifungals that inhibit ergosterol biosynthesis. In this study, we show that Candida glabrata ERG25, which encodes an enzyme that demethylates 4,4-dimethylzymosterol, is required for cholesterol uptake from host serum. Based on the screening of C. glabrata conditional knockdown mutants for each gene involved in ergosterol biosynthesis, ERG25 knockdown was found to decrease lethality of infected mice. ERG25 knockdown impairs the plasma membrane localization of the sterol importer Aus1p, suggesting that the accumulated 4,4-dimethylzymosterol destabilizes the lipid domain with which Aus1p functionally associates. ERG25 knockdown further influences the structure of the membrane compartment of Can1p (MCC)/eisosomes (ergosterol-rich lipid domains), but not the localization of the membrane proteins Pma1p and Hxt1p, which localize to sterol-poor domains. In the sterol-rich lipid domain, Aus1p-contining domain was mostly independent of MCC/eisosomes, and the nature of these domains was also different: Ausp1-contining domain was a dynamic network-like domain, whereas the MCC/eisosomes was a static dot-like domain. However, deletion of MCC/eisosomes was observed to influence the localization of Aus1p after Aus1p was transported from the endoplasmic reticulum (ER) through the Golgi apparatus to the plasma membrane. These findings suggest that ERG25 plays a key role in stabilizing sterol-rich lipid domains, constituting a promising candidate target for antifungal therapy.
Phytotherapy for the Treatment of Glioblastoma: A Review

Background Phytotherapy; the study of extracts of natural origin in the treatment of disease, has scarcely been applied in the management of GBM. A body of literature exists studying in-vitro, the use of natural extracts against GBM cells. Given persisting poor prognoses, we evaluated, through systematic literature-review the therapeutic potential of naturally sourced extracts in-vivo. Methods Using OVID, MEDLINE and EMBASE databases were searched with compound search term. Abstracts and full-texts were double-screened by independent reviewers. Results Nine hundred and eighty-seven articles, excluding duplicated were screened, leading to the inclusion of 14. Amongst murine studies, Ashwagandha, Coptis Chinensis and Fructus Ligustri Lucidi in unprocessed forms, produced significant reductions in tumour volume. Amongst human studies, Perrilyl alcohol, derived from Lavender, reduced angiogenic cytokines in 31% of subjects, halted 6 month disease progression in 48.2% of subjects, and improved mean survival by 4.9 months in separate studies, respectively. Conclusion Although cursory, current trends in literature demonstrate the value of inhaled Lavender extract in the treatment of GBM, offering tangible clinical benefit to patients receiving conventional treatments. Furthermore, the administration of 8, discrete extracts in mice to produce significant responses in survival and tumour volume, suggest there is further scope for study. Although additional safety tests are required, currently, phytotherapeutics are the crossover to clinical translation, and additional trials are warranted to expound upon thus far promising results.
Injectable Photo-Crosslinked Bioactive BMSCs-BMP2-GelMA Scaffolds for Bone Defect Repair

Injectable hydrogels offer a new therapy option for irregular bone deformities. Based on gelatin methacryloyl (GelMA), bone marrow mesenchymal stem cells (BMSCs), and bone morphogenetic protein 2 (BMP2), we created a photo-crosslinked composite bioactive scaffold. The composite scaffolds had appropriate mechanical properties for stem cells adhesion and proliferation, as well as good biocompatibility and the ability to stimulate BMSCs osteogenic differentiation in vitro. The synergistic effect of BMSCs and BMP2 enabled the composite bioactive scaffold to exhibit higher osteogenic potential in vivo than scaffolds loaded alone with BMSCs or BMP2, according to imaging and histology studies. In conclusion, by promoting the osteogenic differentiation of BMSCs, the composite bioactive scaffold based on BMSCs-BMP2-GelMA has demonstrated remarkable application potential in bone regeneration and bone defects repair.
The Good, the Bad, and the Ugly of Urbanization: Response of a Bird Community in the Neotropical Andes

Urbanization constitutes one of the most aggressive drivers of habitat and biodiversity loss worldwide. However, studies focused on determining the response of local biodiversity to urbanization are still scarce, especially in tropical ecosystems. Urban ecosystems are characterized by low biological productivity which in turn leads to a reduction in biodiversity. However, the responses to urbanization should be species dependent. For instance, changes in the availability of resources can favor certain species with specific characteristics. We assessed the effects of the urbanization process on a bird community in a city located in the Tropical Andes of southern Ecuador, a region widely recognized for its diversity and endemism of birds. We selected three independent localities in each of the four levels of the urbanization gradient in the study area (forest, forest-pasture, pasture, and urban). In each locality, we sampled the bird community by visual and auditory surveys along 1 km transects between 2016 and 2017. We recorded a total of 1,257 individuals belonging to 74 bird species. We evaluated if the responses of richness and abundance of birds are dependent on trophic guild and foraging strata. We found a significant decrease in bird species richness and abundance from forest to urban sites. However, the response of birds was dependent on the trophic guild and foraging strata. Granivorous birds showed a positive response associated with the urbanization gradient while insectivorous birds showed a negative response. Insectivorous birds were more abundant in forest sites and decreased in abundance across the urbanization gradient. We found that the proportion of birds using different foraging strata drastically changed along urban gradient. Forest sites exhibited a bird community using a variety of habitats, but the bird community became simpler toward the most urbanized sites. Our findings showed different effects of urbanization on bird communities. The ugly: urbanization leads to a dramatic reduction in the diversity of birds, which is consistent in cities with different characteristics and ecological contexts. On the other hand, the responses of bird guilds to urbanization are species dependent. Some guilds are positively impacted by urbanization and show increases in species richness and abundance while other guilds are negatively impacted.
MiR-124 Regulates IQGAP1 and Participates in the Relationship Between Morphine Dependence Susceptibility and Cognition

Background Long-term excessive use of morphine leads to addictive diseases and affects cognitive function. Cognitive performance is associated with genetic characteristics.MiR-124 plays a critical regulatory role in neurogenesis, synaptic development, brain plasticity, and the use of addictive substances. As a scaffold protein, IQGAP1 affects learning and memory dose-dependent. However, the role of miR-124 and its target protein as potential addiction biomarkers and the impact on cognitive function have not been fully explored. Method A total of 40 patients with morphine dependence and 40 cases of healthy people were recruited. We collected basic and clinical information about the two groups. The Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9(PHQ-9), Montreal Cognition Assessment Scale (MoCA), Pittsburgh Sleep Quality Index (PSQI) were used to assess the severity of depression, anxiety, depressive symptoms, cognitive dysfunction, and sleep quality. Results Compared to the control group, the morphine-dependent group had higher GAD-7, PHQ-9, PSQI scores, and more elevated miR-124 levels but lower MOCA scores and IQGAP1 levels. MiR-124, IQGAP1, the average intake last year were related to OASI scores.MiR-124, IQGAP1, PHQ-9 were associated with MOCA scores. In the multiple regression model, the levels of miR-124 and IQGAP1 were independent factors influencing the severity of morphine dependence. The level of miR-124 was an independent factor influencing the severity of cognitive impairment in patients with morphine dependence. In addition, the luciferase report confirmed that IQGAP1 mRNA is the direct target of miR-124. Conclusion MiR-124 and its target protein IQGAP1 are involved in the regulation of addiction and cognitive function in patients with morphine dependence.
Bt GS57 Interaction With Gut Microbiota Accelerates Spodoptera exigua Mortality

The Beet armyworm Spodoptera exigua (Lepidoptera: Noctuidae, Spodoptera) is an important global polyphagous pest. Pathogen infection could destroy the intestinal microbial homeostasis of insects, leading to the death of the host. However, the effect of the host intestinal microbial community on the insecticidal effect of Bacillus thuringiensis is rarely studied. In this study, the genome characteristics of Bt GS57 and the diversity and functions of the gut bacteria in S. exigua are investigated using crystal morphology, biological activity, and Illumina HiSeq high-throughput sequencing. The total size of the Bt GS57 genome is 6.17 Mbp with an average G + C content of 35.66%. Furthermore, the Bt GS57 genome contains six cry genes: cry1Ca, cry1Da, cry2Ab, cry9Ea, cry1Ia, and cry1Aa, and a vegetative insecticidal protein gene vip3Aa. The Bt GS57 strain can produce biconical crystals, mainly expressing 70 kDa and 130 kDa crystal proteins. The LC50 value of the Bt GS57 strain against the S. exigua larvae was 0.339 mg mL–1. Physiological and biochemical reactions showed that Bt GS57 belongs to B.t. var. thuringiensis. In addition, we found that B. thuringiensis can cause a dynamic change in the gut microbiota of S. exigua, with a significant reduction in bacterial diversity and a substantial increase in bacterial load. In turn, loss of gut microbiota significantly decreased the B. thuringiensis susceptibility of S. exigua larvae. Our findings reveal the vital contribution of the gut microbiota in B. thuringiensis-killing activity, providing new insights into the mechanisms of B. thuringiensis pathogenesis in insects.
Dissection of the Genetic Architecture for Quantities of Gliadins Fractions in Wheat (Triticum aestivum L.)

Gliadin is a group of grain storage proteins that confers extensibility/viscosity to the dough and are vital to end-use quality in wheat. Moreover, gliadins are one of the important components for nutritional quality because they contain the nutritional unprofitable epitopes that cause chronic immune-mediated intestinal disorder in genetically susceptible individuals designated celiac disease (CD). The main genetic loci encoding the gliadins were revealed by previous studies; however, the genes related to the content of gliadins and their fractions were less elucidated. To illustrate the genetic basis of the content of gliadins and their fractions comprehensively, a recombinant inbred line (RIL) population that consisted of 196 lines was constructed from the two parents, Luozhen No.1 and Zhengyumai 9987. Quantitative trait loci (QTL) controlling the content of total gliadins and their fractions (ω-, α-, and γ-gliadin) were screened genome-widely under four environments across 2 years. Totally, thirty QTL which explained 1.97–12.83% of the phenotypic variation were detected to be distributed on 17 chromosomes and they were gathered into 12 clusters. One hundred and one pairs of epistatic QTL (E-QTL) were revealed, among which five were involved with the total gliadins and its fractions content QTL located on chromosome 1AS, 1DS, 4DS, 1DL, and 6AS. Three Kompetitive Allele-Specific PCR (KASP) markers were developed from three major QTL clusters located on chromosomes 6A, 6D, and 7D, respectively. The present research not only dissects the genetic loci for improving the content of gliadins and their three fractions, but may also contribute to marker-assisted selection of varieties with appropriate gliadin fractions content for end-use quality and health benefit at the early developmental stages and early breeding generations.
Mango Pectic Oligosaccharides: A Novel Prebiotic for Functional Food

Prebiotics are functional food ingredients that assist probiotic growth and render many other health benefits. Mango peel is the biomass of the processing industry and has recently been value-added as a dietary fiber pectin. Besides its general use as a food additive, mango peel pectin (MPP) is partially hydrolyzed by pectinase to obtain pectic oligosaccharides (POSs) that have recently gained attention as novel prebiotic products and in medical research. This review describes probiotic candidates responsible for the digestion of pectin derivatives and the advantages of POSs as functional additives and their current best retrieval options. Mango pectic oligosaccharide (MPOS) recovery from low methoxyl MPP from mango with prebiotic performance both in vivo and in vitro environments is discussed. Current research gaps and potential developments in the field are also explored. The overall worthiness of this article is the potential use of the cheap-green food processing bioresource for high-value components.
Theory-Informed Design of a Tailored Strategy for Implementing Household TB Contact Investigation in Uganda

Since 2012, the World Health Organization has recommended household contact investigation as an evidence-based intervention to find and treat individuals with active tuberculosis (TB), the most common infectious cause of death worldwide after COVID-19. Unfortunately, uptake of this recommendation has been suboptimal in low- and middle-income countries, where the majority of affected individuals reside, and little is known about how to effectively deliver this service. Therefore, we undertook a systematic process to design a novel, theory-informed implementation strategy to promote uptake of contact investigation in Uganda, using the COM-B (Capability-Opportunity-Motivation-Behavior) model and the Behavior Change Wheel (BCW) framework. We systematically engaged national, clinic-, and community-based stakeholders and collectively re-examined the results of our own formative, parallel mixed-methods studies. We identified three core behaviors within contact investigation that we wished to change, and multiple antecedents (i.e., barriers and facilitators) of those behaviors. The BCW framework helped identify multiple intervention functions targeted to these antecedents, as well as several policies that could potentially enhance the effectiveness of those interventions. Finally, we identified multiple behavior change techniques and policies that we incorporated into a multi-component implementation strategy, which we compared to usual care in a household cluster-randomized trial. We introduced some components in both arms, including those designed to facilitate initial uptake of contact investigation, with improvement relative to historical controls. Other components that we introduced to facilitate completion of TB evaluation—home-based TB-HIV evaluation and follow-up text messaging—returned negative results due to implementation failures. In summary, the Behavior Change Wheel framework provided a feasible and transparent approach to designing a theory-informed implementation strategy. Future studies should explore the use of experimental methods such as micro-randomized trials to identify the most active components of implementation strategies, as well as more creative and entrepreneurial methods such as human-centered design to better adapt the forms and fit of implementation strategies to end users.