Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Polymorphisms in CYP2E1 Gene and Association Analysis among Chronic HBV Patients

Abstract Cytochrome P450 2E1 (CYP2E1) is a member of the cy-tochrome P450 superfamily, and it is a key enzyme re-sponsible for the metabolic activation of many small- molecular-weight compounds such as alcohol, which is classified as a human carcinogen. In this study, we identified 19 single nucleotide polymorphisms (SNPs) in CYP2E1 in Korean population. In these SNPs, we exam-ined possible genetic association of CYP2E1 polymor-phisms with HBV clearance and the risk of hepato-cellular carcinoma (HCC). Five common polymorphic sites were selected, CYP2E1 polymorphisms at rs381-3867, rs3813870, rs2070673, rs2515641 and rs2480257, considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n=1,092). Statistical analysis demonstrated that CYP2E1 polymorphisms and haplotypes show no significant as-sociation with HBV clearance, HCC occurrence and on-set age of HCC (p＞0.05). Previous studies, however, have shown contradictory findings on associations of CYP2E1 polymorphisms with CYP2E1 activities and HCC risk. Comparing the contrasting results of previous researches suggest that CYP2E1 polymorphism is asso-ciated with CYP2E1 activity induced by ethanol, but is not directly associated with HCC risk. CYP2E1 varia-tion/haploype information identified in this study will pro-vide valuable information for future studies on CYP2E1.Keywords: cytochrome P450 2E1 (CYP2E1), hepatocell-ular carcinoma (HCC), hepatitis B virus (HBV), chronic hepatitis (CH), liver cirrhosis (LC), polymorphism
Chromosome-level genome assembly of the greenfin horse-faced filefish (Thamnaconus septentrionalis) using Oxford Nanopore PromethION sequencing and Hi-C technology

The greenfin horse-faced filefish, Thamnaconus septentrionalis, is a valuable commercial fish species that is widely distributed in the Indo-West Pacific Ocean. It has characteristic blue-green fins, rough skin and spine-like first dorsal fin. T. septentrionalis is of a conservation concern as a result of sharply population decline, and it is an important marine aquaculture fish species in China. The genomic resources of this filefish are lacking and no reference genome has been released. In this study, the first chromosome-level genome of T. septentrionalis was constructed using Nanopore sequencing and Hi-C technology. A total of 50.95 Gb polished Nanopore sequence were generated and were assembled to 474.31 Mb genome, accounting for 96.45% of the estimated genome size of this filefish. The assembled genome contained only 242 contigs, and the achieved contig N50 was 22.46 Mb, reaching a surprising high level among all the sequenced fish species. Hi-C scaffolding of the genome resulted in 20 pseudo-chromosomes containing 99.44% of the total assembled sequences. The genome contained 67.35 Mb repeat sequences, accounting for 14.2% of the assembly. A total of 22,067 protein-coding genes were predicted, of which 94.82% were successfully annotated with putative functions. Furthermore, a phylogenetic tree was constructed using 1,872 single-copy gene families and 67 unique gene families were identified in the filefish genome. This high quality assembled genome will be a valuable genomic resource for understanding the biological characteristics and for facilitating breeding of T. septentrionalis.
E3 ligase RFWD3 is a novel modulator of stalled fork stability in BRCA2-deficient cells

BRCA1/2 help maintain genomic integrity by stabilizing stalled forks for repair and thus act as tumor suppressors. Duan et al. identify the E3 ligase RFWD3 as a novel modulator of stalled fork stability in BRCA2-deficient cells and show that blocking fork degradation by depleting MRE11 is not sufficient for full fork recovery.
The Validity of Teacher Rating Scales for the Assessment of ADHD Symptoms in the Classroom: A Systematic Review and Meta-Analysis

Objective: To assess attention-deficit/hyperactivity disorder (ADHD) symptoms in the classroom, most often teacher rating scales are used. However, clinical interviews and observations are recommended as gold standard assessment. This systematic review and meta-analysis evaluates the validity of teacher rating scales. Method: Twenty-two studies (N = 3,947 children) assessing ADHD symptoms using teacher rating scale and either semi-structured clinical interview or structured classroom observation were meta-analyzed. Results: Results showed convergent validity for rating scale scores, with the strongest correlations (r = .55–.64) for validation against interviews, and for hyperactive–impulsive behavior. Divergent validity was confirmed for teacher ratings validated against interviews, whereas validated against observations this was confirmed for inattention only. Conclusion: Teacher rating scales appear a valid and time-efficient measure to assess classroom ADHD; although validated against semi-structured clinical interviews, there were only a few studies available. Low correlations between ratings and structured observations of inattention suggest that observations could add information above rating scales.
Integrating TMS, EEG, and MRI as an Approach for Studying Brain Connectivity

The human brain is a complex network in which hundreds of brain regions are interconnected via thousands of axonal pathways. The capability of such a complex system emerges from specific interactions among smaller entities, a set of events that can be described by the activation of interconnections between brain areas. Studies that focus on brain connectivity have the aim of understanding and modeling brain function, taking into account the spatiotemporal dynamics of neural communication between brain regions. Much of the current knowledge regarding brain connectivity has been obtained from stand-alone neuroimaging methods. Nevertheless, the use of a multimodal approach seems to be a powerful way to investigate effective brain connectivity, overcoming the limitations of unimodal approaches. In this review, we will present the advantages of an integrative approach in which transcranial magnetic stimulation–electroencephalography coregistration is combined with magnetic resonance imaging methods to explore effective neural interactions. Moreover, we will describe possible implementations of the integrative approach in open- and closed-loop frameworks where real-time brain activity becomes a contributor to the study of cognitive brain networks.
Interrelationships Between Intimate Partner Violence, Coping Style, Depression, and Quality of Life Among the Regular Female Sexual Partners of Men Who Have Sex With Men

The regular female sexual partners of men who have sex with men (MSM), namely, “Tongqi” in China, increasingly attract attention in the field of public health due to their high levels of depression and intimate partner violence (IPV), and their potential risk of HIV infection. Few studies have explored the relationships among IPV, coping style, depression, and quality of life (QOL) in this population. To examine these relationships, a cross-sectional online survey was conducted in China from February 2016 to March 2017. A questionnaire, including the Revised Conflict Tactics Scales, the Simplified Coping Style Questionnaire, the Center for Epidemiologic Studies Depression Scale, and the World Health Organization Quality of Life Scale, was completed by a total of 194 Chinese Tongqi. Structural equation modeling (SEM) was used to test the relationships among IPV, coping style, depression, and QOL. IPV (β = −0.12, p = .002), depression (β = −0.79, p < .001), and active coping style directly (β = 0.17, p < .001) affected the QOL of this group of women; IPV also indirectly affected QOL through the mediating effect of passive coping style and depression, and the positive coping style indirectly affected QOL through the mediating effect of depression. The proposed model showed good fit of indices, χ2/d = 43.72/34 = 1.286 < 3, p = . 123, root mean square error of approximation (RMSEA) = 0.038. Chinese Tongqi experienced high levels of IPV, which led to a poor QOL, partially through the mediating role of passive coping strategy and depression. Future studies or interventions should emphasize the IPV experienced by Chinese Tongqi and provide psychological support so as to improve the overall well-being of this vulnerable female population.
Community providers' experiences with evidence-based practices: The role of therapist race/ethnicity.

OBJECTIVES Examining therapists' experiences implementing evidence-based practices (EBPs) is fundamental to understanding how these interventions are perceived, adapted, and delivered in community settings. However, little is known about racial/ethnic variation in the experiences of therapists serving racial/ethnic minority youth and their families. Through an innovative QUAN → qual → QUAN mixed-methods approach, we examined differences in therapists' perceptions, adaptations performed, and client-engagement challenges in the largest county-operated department of mental health in the United States. METHOD Surveys were completed by 743 therapists (Latinx [44%], White [34%], other ethnic minority [22%]), most of whom were female (88%), master's level (85%), and unlicensed (58%). A subset of therapists (n = 60) completed semistructured interviews. RESULTS Latinx therapists reported more positive experiences implementing EBPs, making more adaptations to EBPs, and encountering fewer client-engagement challenges than therapists from other racial/ethnic groups. Qualitative analyses expanded on these results, revealing that Latinx therapists commonly described adapting EBPs in terms of language and culture to improve fit and promote client engagement. Informed by these qualitative themes, a refined statistical model revealed that the ability to deliver EBPs in languages other than English might have accounted for differences in therapist-reported EBP adaptations and client-engagement challenges. CONCLUSIONS The findings suggest that racial/ethnic minority therapists have positive experiences in implementing EBPs in community settings. In the case of Latinx therapists, bilingual/bicultural competence may facilitate adapting EBPs in ways that reduce perceptions of engagement challenges with racially/ethnically diverse clients. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Bioinformatics Analysis and High-Throughput Sequencing to Identify Differentially Expressed Genes in Nebulin Gene (NEB) Mutations Mice

Background High-throughput sequencing of the pathological tissue of 59 patients with thyroid cancer was compared with the normal population. It was found that the mutation frequency of the Nebulin gene (NEB) at amino acid 1133 locus of thyroid cancer patients was much higher than that of the normal population, suggesting that NEB mutation may be related to thyroid cancer. Therefore, we constructed the NEB mutant mice for further investigation. Material/Methods The RNA extracted from the thyroid of wild-type and NEB mutant mice was analyzed by high-throughput sequencing, and the differential expression was analyzed by edgeR software. Several differentially expressed genes were selected for quantitative real-time PCR (qRT-PCR) verification, and these genes were analyzed with Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results A total of 624 genes were significantly enriched. Analysis of GO function and pathway significant enrichment showed that differentially expressed genes were enriched in thyroid cancer, myocardial contraction, and autoimmune thyroid disease. The qRT-PCR results were consistent with the high-throughput sequencing results. Conclusions Our data indicate that the expression of some cancer-driving genes and cancer suppressor genes are significantly changed in NEB mutant mice compared to wild-type mice, which suggests that NEB function plays an important role in regulating the expression of cancer-related genes in the thyroid gland.
Nucleosides LIII Syntheses and Reactions of 6,7-Dipyridyllumazine and 2' -Deoxylumazine N-1 Nucleosides

Summary The chemical syntheses of 6,7-(α-pyridyl)-1-(2,3,5-tri-O-benzoy-β-D-ribofuranosyl)-lumazine (6) and the corresponding free nucleoside 7 are described. Thiation of 6 with P4S10 gave a salt type adduct derivative of 4-thiolumazine 8 which afforded the free nucleoside 9 on deblocking. Treatment of 8 with methanolic NH3 gave the isopterin-N-1 nucleoside 10. 2,2' -Anhydro compound 13 was obtained by the diphenyl carbonate technique and characterised as the diacetate 14. Acid hydrolysis of 14 gave the arabino-nucleoside 15. which was isolated also from hydrolysis of 14 with hydroxide ion. Reaction of 7 with acetyl bromide gave the 2'-bromo-2'-deoxy derivative 11 as minor product together with triacetate 12 as the main analogue. Reduction of the bromo function in 11 into the expected 2'-deoxy analogue during the treatment with tri-n-butyltin hydride has failed and the 2.2' -anhydro compound 15 was the only product isolated. Alternatively. the 6,7-bis-(α-pyridyl)-1-(2-deoxy-3.5-di-O-toloulyl-α and β-D-ribofuranosyl)-Iumazine (17) and (19) were synthesized from direct condensation of sugar 16 and the silylated base 4. Debolcking of 17 and 19 with sodium methoxide gave the free analogues 18 and 20 respectively.
A Mechanistic Approach on Oxygen Vacancy-Engineered CeO2 Nanosheets Concocts over an Oyster Shell Manifesting Robust Photocatalytic Activity toward Water Oxidation

Lethargic kinetics is the foremost bottleneck of the photocatalytic water oxidation reaction. Hence, in this respect, the CeO2 coral reef made up of nanosheets is studied focusing on the oxygen vacancy that affects the water oxidation reaction. First, CeO2 was prepared in an oyster shell/crucible with the presence/absence of urea by a simple calcination technique to tune the oxygen vacancy. More oxygen vacancy was detected in CeO2 prepared from urea and oyster shell, which is evidenced from Raman and PL analyses. Further, the oyster shell-treated sample was found to be of nanosheet type with numerous pores as observed via TEM analysis. The theoretical approach was adopted to expose the role of oxygen vacancies and the fate of scavenging agents in the water oxidation mechanism. It was observed that an oxygen vacancy plays a vital role in minimizing the activation energy hump and opposes the reverse reaction. The apparent conversion efficiency of 7.1% is calculated for the oxygen evolution reaction. Oxygen vacancy, quantum confinement effect, and charge separation efficiency are mainly responsible for the better photocatalyzed water oxidation reaction and hydroxyl radical production. This investigation will help in providing valuable information toward designing cost-effective oxygen vacancy-oriented nanosheet systems and the importance of vacancy in the water-splitting reaction.
Possible transmitter functions of acetylcholine and an RFamide-like substance in Sagitta (Chaetognatha)

The locomotor muscle fibres of the chaetognath Sagitta are probably multiply innervated and, although linked by numerous gap junctions, do not appear to be coupled electrically. Acetylcholine evokes contraction of the locomotor muscle; iontophoretic application of acetylcholine evokes membrane depolarizations and a series of spikes resembling those seen during spontaneous activity. Both effects are reversibly abolished by (+)-tubocurarine. Acetylcholinesterase is found associated with the sarcolemmata, and it is suggested that acetylcholine is a possible candidate for the neuromuscular transmitter. Immunocytochemical studies with antisera raised against the sequence Arg-Phe-amide (RFamide) show that many neurons in the brain and ventral ganglia contain an RFamide-like material. Some of these neurons are associated with the innervation of sensory organs; others may belong to coordinating systems. At present, these observations do not indicate the affinity of the Chaetognatha to any other invertebrate phylum.
Factors Impacting Differential Outcomes in the Definitive Radiation Treatment of Anal Cancer Between HIV-Positive and HIV-Negative Patients.

BACKGROUND Anal squamous cell carcinoma (ASCC) is uncommon, yet seen more frequently in the setting of HIV. Chemoradiotherapy is the definitive modality of treatment for patients with ASCC; this study examines factors impacting clinical outcomes in a large cohort of human immunodeficiency virus (HIV)-positive and -negative patients. METHODS A retrospective review was conducted of patients treated for nonmetastatic ASCC at a single institution between 2005 and 2018. Freedom from local recurrence (FFLR), freedom from distant metastasis, and overall survival (OS) were calculated using the Kaplan-Meier method, and univariate and multivariate analysis were performed using the Cox proportional hazards model. RESULTS During the study period, 111 patients initiated definitive treatment for ASCC. Median age of the entire cohort was 56.7 years (interquartile range, 51.5-63.5), with 52 patients (46.8%) being HIV-positive. At median follow-up of 28.0 months, the 2- and 5-year FFLR were 78.2% (95% confidence interval [CI], 70.4-87.0) and 74.6% (95% CI, 65.8-84.5), respectively. Multivariate analysis revealed time from diagnosis to treatment initiation (median, 8 weeks; hazard ratio, 1.06; 95% CI, 1.03-1.10) to be significantly associated with worse FFLR and OS. HIV-positive patients had a trend toward worse FFLR (log-ranked p = .06). For HIV-positive patients with post-treatment CD4 less than 150 cells per mm3 , there was significantly worse OS (log-ranked p = .015). CONCLUSION A trend toward worse FFLR was seen in HIV-positive patients, despite similar baseline disease characteristics as HIV-negative patients. Worse FFLR and OS was significantly associated with increased time from diagnosis to treatment initiation. Poorer OS was seen in HIV-positive patients with a post-treatment CD4 count less than 150 cells per mm3 . IMPLICATIONS FOR PRACTICE Human immunodeficiency virus (HIV)-positive patients with anal squamous cell carcinoma can represent a difficult clinical scenario. Definitive radiation with concurrent chemotherapy is highly effective, but can result in significant toxicity and decrease in CD4 count that could predispose to HIV-related complications. As HIV-positive patients have largely been excluded from prospective clinical trials, this study seeks to provide greater understanding of their outcomes with radiation therapy, potential predictors of worse local control and overall survival, and those most at risk of after completion of treatment.
Combined inhibition of PIM and CDK4/6 suppresses both mTOR signaling and Rb phosphorylation and potentiates PI3K inhibition in cancer cells

Aberrant activation of mitogenic signaling pathways in cancer promotes growth and proliferation of cells by activating mTOR and S6 phosphorylation, and D-cyclin kinases and Rb phosphorylation, respectively. Correspondingly, inhibition of phosphorylation of both Rb and S6 is required for robust anti-tumor efficacy of drugs that inhibit cell signaling. The best-established mechanism of mTOR activation in cancer is via PI3K/Akt signaling, but mTOR activity can also be stimulated by CDK4 and PIM kinases. In this study, we show that the CDK4/6 inhibitor abemaciclib inhibits PIM kinase and S6 phosphorylation in cancer cells and concurrent inhibition of PIM, CDK4, and CDK6 suppresses both S6 and Rb phosphorylation. TSC2 or PIK3CA mutations obviate the requirement for PIM kinase and circumvent the inhibition of S6 phosphorylation by abemaciclib. Combination with a PI3K inhibitor restored suppression of S6 phosphorylation and synergized to curtail cell growth. By combining abemaciclib with a PI3K inhibitor, three pathways (Akt, PIM, and CDK4) to mTOR activation are neutralized, suggesting a potential combination strategy for the treatment of PIK3CA-mutant ER+ breast cancer.
Age, tissue, genotype and virus infection regulate Wolbachia levels in Drosophila

The bacterial symbiont Wolbachia can protect insects against viral pathogens, and the varying levels of antiviral protection are correlated with the endosymbiont load within the insects. To understand why Wolbachia strains differ in their antiviral effects, we investigated the factors controlling Wolbachia density in five closely related strains in their natural Drosophila hosts. We found that Wolbachia density varied greatly across different tissues and between flies of different ages, and these effects depended on the host–symbiont association. Some endosymbionts maintained largely stable densities as flies aged while others increased, and these effects in turn depended on the tissue being examined. Measuring Wolbachia rRNA levels in response to viral infection, we found that viral infection itself also altered Wolbachia levels, with Flock House virus causing substantial reductions in symbiont loads late in the infection. This effect, however, was virus‐specific as Drosophila C virus had little impact on Wolbachia in all of the five host systems. Because viruses have strong tissue tropisms and antiviral protection is thought to be cell‐autonomous, these effects are likely to affect the virus‐blocking phenomenon. However, we were unable to find any evidence of a correlation between Wolbachia and viral titres within the same tissues. We conclude that Wolbachia levels within flies are regulated in a complex host–symbiont–virus‐dependent manner and this trinity is likely to influence the antiviral effects of Wolbachia.
Diversity and paleoenvironmental implications of an elasmobranch assemblage from the Oligocene–Miocene boundary of Ecuador

The occurrence and diversity of elasmobranchs from the Oligocene–Miocene boundary from Tropical America is poorly known in comparison with the paleodiversity from younger Neogene intervals of the region. Here we describe a new elasmobranch assemblage from the rich fossil site of Montañita-Olón (Dos Bocas Formation, Santa Elena, Ecuador), where other vertebrates have already been described: for example, sea turtles and cetaceans. We report a total of 27 elasmobranch taxa, 19 of which are new fossil records for Ecuador, 10 new records for the Central Eastern Pacific and four new records for South America. Additionally, in order to reconstruct the environment where these marine remains were deposited, we performed abundance, paleobathymetric and habitat preference analyses, concluding that they were likely deposited in an outer neritic (open shelf) environment. The study of Oligocene and early Miocene marine elasmobranchs faunas in Tropical America is key to addressing the issues in the evolutionary history of this group.