Miracle-dz/UniFAR-FTUs huggingface dataset:
Whole Genome Sequence Analysis of Porcine Astroviruses Reveals Novel Genetically Diverse Strains Circulating in East African Smallholder Pig Farms

Astroviruses (AstVs) are widely distributed and are associated with gastroenteritis in human and animals. The knowledge of the genetic diversity and epidemiology of AstVs in Africa is limited. This study aimed to characterize astroviruses in asymptomatic smallholder piglets in Kenya and Uganda. Twenty-four samples were randomly selected from a total of 446 piglets aged below 6 months that were initially collected for rotavirus study and sequenced for whole genome analysis. Thirteen (13/24) samples had contigs with high identity to genus Mamastrovirus. Analysis of seven strains with complete (or near complete) AstV genome revealed variable nucleotide and amino acid sequence identities with known porcine astrovirus (PoAstV) strains. The U083 and K321 strains had nucleotide sequence identities ranging from 66.4 to 75.4% with the known PoAstV2 strains; U460 strain had nucleotide sequence identities of 57.0 to 65.1% regarding the known PoAstV3; and K062, K366, K451, and K456 strains had nucleotide sequence identities of 63.5 to 80% with the known PoAstV4 strains. The low sequence identities (<90%) indicate that novel genotypes of PoAstVs are circulating in the study area. Recombination analysis using whole genomes revealed evidence of multiple recombination events in PoAstV4, suggesting that recombination might have contributed to the observed genetic diversity. Linear antigen epitope prediction and a comparative analysis of capsid protein of our field strains identified potential candidate epitopes that could help in the design of immuno-diagnostic tools and a subunit vaccine. These findings provide new insights into the molecular epidemiology of porcine astroviruses in East Africa.
Belief updating in bipolar disorder predicts time of recurrence

Bipolar disorder is a chronic relapsing condition in which mood episodes are interspersed with periods of wellbeing (euthymia). Shorter periods of euthymia are associated with poorer functioning, so it is crucial to identify predictors of relapse to facilitate treatment. Here, we test the hypothesis that specific valence-dependent learning patterns emerge prior to the clinical manifestation of a relapse, predicting its timing. The ability to update beliefs in response to positive and negative information was quantified in bipolar patients during euthymia, who were then monitored for 5 years. We found that reduced tendency to update beliefs in response to positive relative to negative information predicted earlier relapse. Less updating in response to positive information may generate pessimistic beliefs, which in turn can lead to more severe prodromal symptoms (e.g. sleep disturbance, irritability etc.). The results suggest that measuring valence-dependent belief updating could facilitate risk prediction in bipolar disorder.
A BBS1 SVA F retrotransposon insertion is a frequent cause of Bardet‐Biedl syndrome

Bardet‐Biedl syndrome (BBS) is a ciliopathy characterized by retinitis pigmentosa, obesity, polydactyly, cognitive impairment and renal failure. Pathogenic variants in 24 genes account for the molecular basis of >80% of cases. Toward saturated discovery of the mutational basis of the disorder, we carefully explored our cohorts and identified a hominid‐specific SINE‐R/VNTR/Alu type F (SVA‐F) insertion in exon 13 of BBS1 in eight families. In six families, the repeat insertion was found in trans with c.1169 T > G, p.Met390Arg and in two families the insertion was found in addition to other recessive BBS loci. Whole genome sequencing, de novo assembly and SNP array analysis were performed to characterize the genomic event. This insertion is extremely rare in the general population (found in 8 alleles of 8 BBS cases but not in >10 800 control individuals from gnomAD‐SV) and due to a founder effect. Its 2435 bp sequence contains hallmarks of LINE1 mediated retrotransposition. Functional studies with patient‐derived cell lines confirmed that the BBS1 SVA‐F is deleterious as evidenced by a significant depletion of both mRNA and protein levels. Such findings highlight the importance of dedicated bioinformatics pipelines to identify all types of variation.
Alterations in reproductive parameters and gene expression in Balb/c mice testes after exposure to silver nanoparticles

Silver nanoparticles (AgNPs) have become one of the most common nanomaterials in various commercial products; however, its potential toxicity to the male reproductive system and the possible mechanisms remains unknown. Our study aimed to investigate the toxicity of silver nanoparticle (AgNPs) in the testis and to elucidate its possible mechanisms. We exposed 6‐week‐old Balb/c male mice to AgNP daily [0 (control), 30 or 125 mg/kg BW] for 90 days. The histological structure, sperm production and levels of reproductive hormones were assessed; we also observed apoptotic cell nuclei and the ultrastructural characteristics of the testis. Microarray analyses were used to identify differentially expressed genes, and dysregulated apoptosis‐related genes and protein were also analysed. Our results indicated that 125 mg/kg AgNP changed testis morphology and decreased sperm production. AgNP treatment also increased apoptosis of germ cells and induced the presence of swollen or dissolved mitochondria in the testis. Microarray analysis showed the expression of 383 genes was altered by AgNP treatment, with apoptosis‐related genes showing the greatest changes. Furthermore, we verified dysregulated apoptosis‐related genes and proteins (caspase3 and Myc). These results demonstrated that AgNP induced changes of testis morphology, sperm production and apoptosis‐related genes, suggested this process maybe associated with apoptosis.
Hyaluronic Acid Injection Laryngoplasty for Unilateral Vocal Fold Paralysis—A Systematic Review and Meta-Analysis

Unilateral vocal fold paralysis (UVFP) is a common disorder that may cause glottal closure insufficiency and then hoarseness of voice and aspiration during swallowing. We conducted a systematic review and meta-analysis to evaluate whether hyaluronic acid (HA) injection laryngoplasty (IL) is an effective treatment for patients with UVFP. Comprehensive systematic searches were undertaken using PubMed, EBSCO Medline, and Cochrane Library databases. We appraised the quality of studies according to preset inclusion and exclusion criteria. The lengths of follow-up were divided into “short-term” (3 months or shorter), “medium-term” (6 months), and “long-term” (12 months or longer). We performed random-effect meta-analysis to estimate the changes in voice-related quality of life, perceptual evaluation by grading systems, voice lab analysis of maximal phonation time, and normalized glottal gap area, before and after HA IL. Fourteen studies were eligible for the final analysis. The results showed that patients’ glottal closure insufficiency could be improved; maximal phonation time could be prolonged; perceptual evaluations of the voice and quality of life were better after HA IL, but the duration of treatment effect varied among different studies. In conclusion, HA IL is an effective treatment for UVFP, which may achieve a long-term effect and therefore reduce the likelihood of requiring permanent medialization thyroplasty.
Prediction of PIK3CA mutations from cancer gene expression data

Breast cancers with PIK3CA mutations can be treated with PIK3CA inhibitors in hormone receptor-positive HER2 negative subtypes. We applied a supervised elastic net penalized logistic regression model to predict PIK3CA mutations from gene expression data. This regression approach was applied to predict modeling using the TCGA pan-cancer dataset. Approximately 10,000 cases were available for PIK3CA mutation and mRNA expression data. In 10-fold cross-validation, the model with λ = 0.01 and α = 1.0 (ridge regression) showed the best performance, in terms of area under the receiver operating characteristic (AUROC). The final model was developed with selected hyper-parameters using the entire training set. The training set AUROC was 0.93, and the test set AUROC was 0.84. The area under the precision-recall (AUPR) of the training set was 0.66, and the test set AUPR was 0.39. Cancer types were the most important predictors. Both insulin like growth factor 1 receptor (IGF1R) and the phosphatase and tensin homolog (PTEN) were the most significant genes in gene expression predictors. Our study suggests that predicting genomic alterations using gene expression data is possible, with good outcomes.
LitCovid: an open database of COVID-19 literature

Abstract Since the outbreak of the current pandemic in 2020, there has been a rapid growth of published articles on COVID-19 and SARS-CoV-2, with about 10 000 new articles added each month. This is causing an increasingly serious information overload, making it difficult for scientists, healthcare professionals and the general public to remain up to date on the latest SARS-CoV-2 and COVID-19 research. Hence, we developed LitCovid (https://www.ncbi.nlm.nih.gov/research/coronavirus/), a curated literature hub, to track up-to-date scientific information in PubMed. LitCovid is updated daily with newly identified relevant articles organized into curated categories. To support manual curation, advanced machine-learning and deep-learning algorithms have been developed, evaluated and integrated into the curation workflow. To the best of our knowledge, LitCovid is the first-of-its-kind COVID-19-specific literature resource, with all of its collected articles and curated data freely available. Since its release, LitCovid has been widely used, with millions of accesses by users worldwide for various information needs, such as evidence synthesis, drug discovery and text and data mining, among others.
Emerging Trends and Hot Topics in Cardiopulmonary Resuscitation Research: A Bibliometric Analysis from 2010 to 2019

Background Cardiopulmonary resuscitation (CPR) is a topic of great scientific and clinical interest that has received much attention in the past decade. Our study aimed to predict the trends in CPR research activities and evaluate hot topics via bibliometric means, quantitatively and qualitatively. Material/Methods All data were collected from a search of the Web of Science Core Collection on May 12, 2020. Retrieved information was investigated with bibliometric analysis by CiteSpace and VOSviewer software and the Online Analysis Platform of Literature Metrology to analyze and predict the trends and hotspots in this field. Results Our search returned a total of 9563 articles and reviews on CPR published from 2010 through 2019. The number of original research studies on CPR has been increasing annually. The journal Resuscitation published the greatest number of manuscripts involved CPR, and the leading country and institution with regard to contributions on CPR were the United States and the University of Pennsylvania. Keyword co-occurrence/co-citation-cluster analysis showed that the most popular terms associated with CPR occurred in the manner of cluster labels, such as therapeutic hypothermia and treatment recommendation, among others. In addition, palliative care, sepsis, extracorporeal membrane oxygenation, and brain injury were identified as new foci through burst detection analysis. Conclusions Our study showed that the scientific research focus on CPR is switching from traditional therapeutic treatments to a public health practice, with in-depth understanding and development of CPR-related techniques expanding over the past decade. These results demonstrate trends in the CPR research and detected the possible neo-foci for ensuing research.
The TFIIH subunits p44/p62 act as a damage sensor during nucleotide excision repair

Abstract Nucleotide excision repair (NER) in eukaryotes is orchestrated by the core form of the general transcription factor TFIIH, containing the helicases XPB, XPD and five ‘structural’ subunits, p62, p44, p34, p52 and p8. Recent cryo-EM structures show that p62 makes extensive contacts with p44 and in part occupies XPD’s DNA binding site. While p44 is known to regulate the helicase activity of XPD during NER, p62 is thought to be purely structural. Here, using helicase and adenosine triphosphatase assays we show that a complex containing p44 and p62 enhances XPD’s affinity for dsDNA 3-fold over p44 alone. Remarkably, the relative affinity is further increased to 60-fold by dsDNA damage. Direct binding studies show this preference derives from p44/p62’s high affinity (20 nM) for damaged ssDNA. Single molecule imaging of p44/p62 complexes without XPD reveals they bind to and randomly diffuse on DNA, however, in the presence of UV-induced DNA lesions these complexes stall. Combined with the analysis of a recent cryo-EM structure, we suggest that p44/p62 acts as a novel DNA-binding entity that enhances damage recognition in TFIIH. This revises our understanding of TFIIH and prompts investigation into the core subunits for an active role during DNA repair and/or transcription.
Effects of Hippeastrum reticulatum on memory, spatial learning and object recognition in a scopolamine-induced animal model of Alzheimer’s disease

Abstract Context The methanol extracts from Hippeastrum reticulatum (L'Hér.) Herb. (Amaryllidaceae) (HR) display acetylcholinesterase inhibitory (AChEI) activity. Objective AChEI of alkaloids isolated from HR bulbs and the ameliorating effects of the alkaloid fraction (AHR) on memory and cognitive dysfunction in scopolamine-treated mice were investigated. Materials and methods Alkaloids were isolated by column chromatography and identified by spectroscopy. AChEI was evaluated using the modified Ellman’s method. Sixty Swiss male mice were randomly divided into six groups, received samples for 15 days. Normal group received saline, scopolamine-treated group scopolamine (1.5 mg/kg, intraperitoneal injection). Test groups received AHR (5, 10 and 15 mg/kg, per os) and positive control group donepezil (5 mg/kg, per os), administered 1 h before the test, scopolamine was injected 30 min prior to testing. The cognitive-enhancing activity of AHR against scopolamine-induced memory impairments was investigated using Y-maze, the novel object recognition test (NORT) and the Morris water maze (MWM) test. Results Seven alkaloids were isolated for the first time from the genus Hippeastrum: trans-dihydronarciclasine (1), N-chloromethylnarcissidinium (2), narciprimin (3), narciclasine-4-O-β-d-xylopyranoside (4), N-methyltyramine (5), 3β,11α-dihydroxy-1,2-dehydrocrinane (6) and brunsvigine (7); three are new compounds (2, 5, 6). Among them, 2–3 and 5–6 showed AChEI in vitro with IC50 values of 29.1, 46.4, 70.1 and 104.5 µg/mL, respectively. The anti-AChEI of 2, 5 and 6 are reported for the first time. In in vivo test, AHR (15 mg/kg) significantly increased in spontaneous alternation performance in the Y-maze test (p < 0.01), it significantly increased the time spent exploring the novel object (p < 0.05) comparison with scopolamine-treated group. The administration of AHR at doses 10 and 15 mg/kg significantly decreased escapes latency and swimming distance to the platform on day 6 compared to these in day 1 (p < 0.01 and p < 0.05, respectively). Conclusions AHR could be a potential candidate of future trials for treatment of memory and cognitive dysfunction in Alzheimer’s disease.
Students’ Digital Equality and Scholarly Outcomes

Review Article Previous work by Lam [1] and Lam [2] show that social objects, cultural identities, and personality form another perspective of Roger Penrose‘s three world philosophy. Using statistical data from the Centre for Economic and Policy Research (CEPR) in the United States, the relationship between these fields can be determined. This can be achieved through the Principal Component Analysis method by using statistical software: ̳R‘. It is hoped that this data can be used to validate the sociological aspect of the three worlds philosophy. Certainly, there have been some opposing comments against the proposed theory. As such, this study will investigate some of the main oppositions and suggest possible solutions. Furthermore, by analysing the data, one can study ICT usage amongst students, in addition to predicting their future tendencies. One may explore how the ICT usage may have effects in one‘s personality and cultural identity together with social objects. Social, cultural, and psychological factors all have effects on the academic achievements of students. These three areas influence the ICT usage of students and their scholarly results. Indeed, the culture and attitude of parents towards their child‘s ICT usage can affect their educational performance [1]. As a result, the following separate elements arise: 1) Sociological three world philosophy. 2) Parental influence. 3) ICT leadership at school. 4) Studious outcomes. This will finally coalesce into a new and more rationalized connection, which can be presented in a framework. This helps to depict the creative relationship and understand how to minimize digital equality (or inappropriate digital usage) to maximize students‘ academic performance. Realization can be achieved by manipulating both the three worlds philosophy and parental influence factors. Moreover, a school‘s successful ICT pedagogy is related to leadership, which is also connected to scholarly results. This means that digital usage can be optimized (or balanced) to produce studious outcomes. As a result, professionals such as teachers, social workers and researchers can develop corresponding strategies, such as providing philosophical education for parents, to better handle the ICT usage of children. Consequently, the digital divide in education, which has been created by modern technology, will be solved.
Development of a Malignancy Potential Binary Prediction Model Based on Deep Learning for the Mitotic Count of Local Primary Gastrointestinal Stromal Tumors

Objective The mitotic count of gastrointestinal stromal tumors (GIST) is closely associated with the risk of planting and metastasis. The purpose of this study was to develop a predictive model for the mitotic index of local primary GIST, based on deep learning algorithm. Materials and Methods Abdominal contrast-enhanced CT images of 148 pathologically confirmed GIST cases were retrospectively collected for the development of a deep learning classification algorithm. The areas of GIST masses on the CT images were retrospectively labelled by an experienced radiologist. The postoperative pathological mitotic count was considered as the gold standard (high mitotic count, > 5/50 high-power fields [HPFs]; low mitotic count, ≤ 5/50 HPFs). A binary classification model was trained on the basis of the VGG16 convolutional neural network, using the CT images with the training set (n = 108), validation set (n = 20), and the test set (n = 20). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated at both, the image level and the patient level. The receiver operating characteristic curves were generated on the basis of the model prediction results and the area under curves (AUCs) were calculated. The risk categories of the tumors were predicted according to the Armed Forces Institute of Pathology criteria. Results At the image level, the classification prediction results of the mitotic counts in the test cohort were as follows: sensitivity 85.7% (95% confidence interval [CI]: 0.834–0.877), specificity 67.5% (95% CI: 0.636–0.712), PPV 82.1% (95% CI: 0.797–0.843), NPV 73.0% (95% CI: 0.691–0.766), and AUC 0.771 (95% CI: 0.750–0.791). At the patient level, the classification prediction results in the test cohort were as follows: sensitivity 90.0% (95% CI: 0.541–0.995), specificity 70.0% (95% CI: 0.354–0.919), PPV 75.0% (95% CI: 0.428–0.933), NPV 87.5% (95% CI: 0.467–0.993), and AUC 0.800 (95% CI: 0.563–0.943). Conclusion We developed and preliminarily verified the GIST mitotic count binary prediction model, based on the VGG convolutional neural network. The model displayed a good predictive performance.
Assembly of the peripheral stalk of ATP synthase in human mitochondria

Significance The production of ATP in mitochondria requires the oxidation of energy rich compounds to generate a proton motive force (pmf), a chemical potential difference for protons across the inner membrane. This pmf powers the ATP synthase, a molecular machine with a rotary action, to synthesize ATP. The assembly of human ATP synthase from 27 nuclear encoded proteins and two mitochondrially encoded subunits in the inner organellar membrane involves the formation of intermediate modules representing the F1-catalytic domain, the peripheral stalk, associated membrane subunits, and the c8 ring in the membrane part of the rotor. Here, we describe how components of the peripheral stalk and three associated membrane subunits are assembled and introduced into the enzyme complex. The adenosine triphosphate (ATP) synthase in human mitochondria is a membrane bound assembly of 29 proteins of 18 kinds organized into F1-catalytic, peripheral stalk (PS), and c8-rotor ring modules. All but two membrane components are encoded in nuclear genes, synthesized on cytoplasmic ribosomes, imported into the mitochondrial matrix, and assembled into the complex with the mitochondrial gene products ATP6 and ATP8. Intermediate vestigial ATPase complexes formed by disruption of nuclear genes for individual subunits provide a description of how the various domains are introduced into the enzyme. From this approach, it is evident that three alternative pathways operate to introduce the PS module (including associated membrane subunits e, f, and g). In one pathway, the PS is built up by addition to the core subunit b of membrane subunits e and g together, followed by membrane subunit f. Then this b-e-g-f complex is bound to the preformed F1-c8 module by subunits OSCP and F6. The final component of the PS, subunit d, is added subsequently to form a key intermediate that accepts the two mitochondrially encoded subunits. In another route to this key intermediate, first e and g together and then f are added to a preformed F1-c8-OSCP-F6-b-d complex. A third route involves the addition of the c8-ring module to the complete F1-PS complex. The key intermediate then accepts the two mitochondrially encoded subunits, stabilized by the addition of subunit j, leading to an ATP synthase complex that is coupled to the proton motive force and capable of making ATP.