Miracle-dz/UniFAR-FTUs huggingface dataset:
NAT2 gene polymorphisms and endometriosis risk: A PRISMA-compliant meta-analysis

Objective Endometriosis is a common chronic, gynecological disease. Despite many studies on the role of N-acetyltransferase 2 (NAT2) in endometriosis, its clinical significance is unclear. In this study, associations between NAT2 phenotypes as well as single nucleotide polymorphisms (SNPs) within NAT2 (i.e. rs1799929, rs1799930, rs1208, and rs1799931) and endometriosis risk were evaluated using a meta-analysis approach. Methods Embase, PubMed, ClinicalTrials.gov, CNKI (China National Knowledge Infrastructure), Wanfang databases, Cochrane Library for clinical trials, and Web of Science were searched to identify relevant articles. ORs (odds ratios) and 95% CIs (95% confidence intervals) were used to estimate the associations between NAT2 polymorphisms and endometriosis risk. Heterogeneity among included studies was also assessed. In addition, a subgroup analysis of NAT2 phenotypes and endometriosis risk based on ethnicity was performed. Results Nine case-control studies met the inclusion criteria. The odds ratio was 2.30 (95% CI: 1.61–3.28) for the NAT2 slow acetylation phenotype versus the intermediate + fast acetylation phenotype in the Asian population. These results suggest that Asian individuals with the NAT2 slow acetylation phenotype have a 130% increased risk of endometriosis. A significant association was also found for rs1799930 (OR = 0.74; 95% CI, 0.59–0.92), suggesting that individuals with this mutant genotype have a 26% decreased risk of endometriosis. Conclusions The rs1799930 mutant genotypes are associated with a decreased risk of endometriosis. No statistically significant associations were found between rs1799931, rs1208, or rs1799929 and endometriosis. Based on a subgroup analysis based on ethnicity, the NAT2 slow acetylation phenotype was found to increase the risk of endometriosis in Asians. No statistically significant associations were found between the NAT2 slow acetylation phenotype and endometriosis risk in Caucasians. Accordingly, NAT2 phenotypes and SNPs are potential biomarkers for the diagnosis and treatment of endometriosis.
Improving accuracy for finite element modeling of endovascular coiling of intracranial aneurysm

Background Computer modeling of endovascular coiling intervention for intracranial aneurysm could enable a priori patient-specific treatment evaluation. To that end, we previously developed a finite element method (FEM) coiling technique, which incorporated simplified assumptions. To improve accuracy in capturing real-life coiling, we aimed to enhance the modeling strategies and experimentally test whether improvements lead to more accurate coiling simulations. Methods We previously modeled coils using a pre-shape based on mathematical curves and mechanical properties based on those of platinum wires. In the improved version, to better represent the physical properties of coils, we model coil pre-shapes based on how they are manufactured, and their mechanical properties based on their spring-like geometric structures. To enhance the deployment mechanics, we include coil advancement to the aneurysm in FEM simulations. To test if these new strategies produce more accurate coil deployments, we fabricated silicone phantoms of 2 patient-specific aneurysms in duplicate, deployed coils in each, and quantified coil distributions from intra-aneurysmal cross-sections using coil density (CD) and lacunarity (L). These deployments were simulated 9 times each using the original and improved techniques, and CD and L were calculated for cross-sections matching those in the experiments. To compare the 2 simulation techniques, Euclidean distances (dMin, dMax, and dAvg) between experimental and simulation points in standardized CD-L space were evaluated. Univariate tests were performed to determine if these distances were significantly different between the 2 simulations. Results Coil deployments using the improved technique agreed better with experiments than the original technique. All dMin, dMax, and dAvg values were smaller for the improved technique, and the average values across all simulations for the improved technique were significantly smaller than those from the original technique (dMin: p = 0.014, dMax: p = 0.013, dAvg: p = 0.045). Conclusion Incorporating coil-specific physical properties and mechanics improves accuracy of FEM simulations of endovascular intracranial aneurysm coiling.
Drug‐Eluting Stent Targeting Sp‐1‐Attenuated Restenosis by Engaging YAP‐Mediated Vascular Smooth Muscle Cell Phenotypic Modulation

Background Activation of the YAP (Yes‐associated protein) pathway has been demonstrated to be related to smooth muscle cells (SMCs) phenotypic modulation and vessel restenosis. The aim of this study was to illustrate the molecular mechanisms that regulate the expression of YAP during the process of SMCs phenotypic switch. Whether the molecular basis identified in the study could be a potential therapeutic target for drug‐eluting stents is further tested. Methods and Results In cell culture and in rat carotid arterial injury models, Sp‐1 (specificity protein 1) expression was significantly induced, and correlated with SMCs proliferative phenotype. Overexpression of Sp‐1 promoted SMCs proliferation and migration. Conversely, siSp‐1 transfection or Sp‐1 inhibitor Mithramycin A treatment attenuates SMC proliferation and migration. Through gain‐ and loss‐function assays, we demonstrated that YAP was involved in Sp‐1‐mediated SMC phenotypic switch. Mechanistically, activated Sp‐1 regulated YAP transcriptional expression through binding to its promoter. Moreover, we fabricated a Sp‐1 inhibitor Mithramycin A‐eluting stent and further tested it. In the rabbit carotid model, Mithramycin A‐eluting stent inhibited YAP transcription and attenuated in‐stent restenosis through regulating YAP‐mediated SMC phenotypic switch. Conclusions Sp‐1 controls phenotypic modulation of SMC by regulating transcription factor YAP. Drug‐eluting stent targeting Sp‐1 might represent a novel therapeutic strategy to prevent in‐stent restenosis.
Towards a stronger halogen bond involving astatine: unexpected adduct with Bu3PO stabilized by hydrogen bonding.

The halogen bond is a powerful tool for the molecular design, and pushing the limits of its strength is of major interest. Bearing the most potent halogen-bond donor atom, astatine monoiodide (AtI) was recently successfully probed [Nature Chemistry 2018, 10, 428-434]. In this work, we continue the exploration of adducts between AtI and Lewis bases with the tributylphosphine oxide (Bu3PO) ligand, revealing the unexpected experimental occurrence of two distinct chemical species with 1:1 and 1:2 stoichiometries. The 1:1 Bu3PO…AtI complex is found to exhibit the strongest astatine-mediated halogen bond so far (with a formation constant of 104.24±0.35). Quantum chemical calculations unveil the intriguing nature of the 1:2 2Bu3PO…AtI adduct, involving a halogen bond between AtI and one Bu3PO molecular unit plus CHΛO hydrogen bonds chelating the second Bu3PO unit.
The Role of Soluble Polysaccharides in Tannin-Cell Wall Interactions in Model Solutions and in Wines

The interactions between tannins and soluble and insoluble cell wall components are, in part, responsible for the low quantities of tannins found in wines compared with the quantities in grapes. The use of polysaccharides to compete with cell wall components could be an interesting approach for improving the chromatic and sensory characteristics of wines. The effect of two commercial polysaccharides, pectin and mannan, on limiting tannin-cell wall interactions was studied in a model solution, measuring the concentration of tannins and polysaccharides remaining in solution after the different interactions by chromatography. The treatment was also tested in a small-scale vinification. Soluble polysaccharides were added to the must and the wines were evaluated at the end of alcoholic fermentation and after six months in the bottle. In the model solution, the commercial polysaccharides formed soluble complexes with the tannins and limited the interactions with cell wall components, with some differences between skin and seed tannins. In the case of the wines, the treatments resulted in wines with a higher color intensity and phenolic content. Sensory analysis resulted in higher scores for the wines with added polysaccharides, since the complexation of tannins with the polysaccharides increased the roundness and body of the resulting wines.
β‐Caryophyllene, a dietary terpenoid, inhibits nicotine taking and nicotine seeking in rodents

β‐Caryophyllene (BCP) is a plant‐derived terpenoid used as a food additive for many decades. Recent studies indicate that BCP is a cannabinoid CB2 receptor agonist with medical benefits for a number of human diseases. However, little is known about its therapeutic potential for drug abuse and addiction.
Helicobacter pylori Eradication According to Sequencing-Based 23S Ribosomal RNA Point Mutation Associated with Clarithromycin Resistance

Background/Aims: Clarithromycin resistance in Helicobacter pylori is associated with point mutations in the 23S ribosomal RNA (rRNA) gene. We investigated the point mutations in the 23S rRNA genes of patients with clarithromycin-resistant H. pylori and compared the H. pylori eradication rates based on the point mutations. Methods: A total of 431 adult patients with H. pylori infection were recruited in Kangdong Sacred Heart Hospital in 2017 and 2018. Patients who did not have point mutations related to clarithromycin resistance and/or had clinically insignificant point mutations were treated with PAC (proton pump inhibitor, amoxicillin, clarithromycin) for seven days, while patients with clinically significant point mutations were treated with PAM (proton pump inhibitor, amoxicillin, metronidazole) for seven days. H. pylori eradication rates were compared. Results: Sequencing-based detection of point mutations identified four mutations that were considered clinically significant (A2142G, A2142C, A2143G, A2143C). The clarithromycin resistance rate was 21.3% in the overall group of patients. A2143G was the most clinically significant point mutation (84/431, 19.5%), while T2182C was the most clinically insignificant point mutation (283/431, 65.7%). The overall H. pylori eradication rate was 83.7%, and the seven-day PAM-treated clarithromycin-resistance group showed a significantly lower eradication rate than the seven-day PAC-treated nonresistance group (ITT; 55.4% (51/92) vs. 74.3% (252/339), p = 0.001, PP; 66.2% (51/77) vs. 88.4% (252/285), p = 0.0001). Conclusions: There were significantly lower eradication rates in the patients with clarithromycin-resistant H. pylori when treated with PAM for seven days. A future study comparing treatment regimens in clarithromycin-resistant H. pylori-infected patients may be necessary.
MicroRNAs as tumour suppressors in canine and human melanoma cells and as a prognostic factor in canine melanomas: MicroRNA expression in canine and human melanomas

Malignant melanoma (MM) is one of the most aggressive cancers in dogs and in humans. However, the molecular mechanisms of its development and progression remain unclear. Presently, we examined the expression profile of microRNAs (miRs) in canine oral MM tissues and paired normal oral mucosa tissues by using the microRNA-microarray assay and quantitative RT-PCR. Importantly, a decreased expression of miR-203 was significantly associated with a shorter survival time. Also, miR-203 and -205 were markedly down-regulated in canine and human MM cell lines tested. Furthermore, the ectopic expression of miR-205 had a significant inhibitory effect on the cell growth of canine and human melanoma cells tested by targeting erbb3. Our data suggest that miR-203 is a new prognostic factor in canine oral MMs and that miR-205 functions as a tumour suppressor by targeting erbb3 in both canine and human MM cells.
Assessing the Effects of Information System Quality and Relationship Quality on Continuance Intention in E-Tourism

The advance of electronic commerce has resulted in successful e-travel services. Through the development of e-travel information, consumers can plan their trip without time and space limitations. This study proposes a model regarding the formation of the relationship quality (customer satisfaction and trust), information system quality, perceived value, and customers’ intention to continue in the e-tourism environment. The study is based on 351 e-travel users in Taiwan. The result shows that customer satisfaction has a positive effect on continuance intention. Information system quality has a positive relationship with customer satisfaction, trust, and customer continuance intention. Furthermore, the perceived value has an effect on customer satisfaction and trust. However, the perceived value is partially related to customer continuance intention through customer satisfaction. The managerial implications of this study are discussed.
SUMOylation prevents huntingtin fibrillization and localization onto lipid membranes.

Huntington's disease (HD), a genetic neurodegenerative disease, is caused by an expanded polyglutamine (polyQ) domain in the first exon of the huntingtin protein (htt). PolyQ expansion destabilizes protein structure, resulting in aggregation into a variety of oligomers, protofibrils, and fibrils. Beyond the polyQ domain, adjacent protein sequences influence the aggregation process. Specifically, the first seventeen N-terminal amino acids (Nt17) directly preceding the polyQ domain promote the formation of α-helix-rich oligomers that represent intermediate species associated with fibrillization. Due to its propensity to form an amphipathic α-helix, Nt17 also facilitates lipid binding. Three lysine residues (K6, K9, and K15) within Nt17 can be SUMOylated, which modifies htt's accumulation and toxicity within cells in a variety of HD models. The impact of SUMOylation on htt aggregation and direct interaction with lipid membranes was investigated. SUMOylation of htt-exon1 inhibited fibril formation while promoting larger, amorphous aggregate species. These amorphous aggregates were SDS soluble, but nonetheless exhibited levels of β-sheet structure similar to that of htt-exon1 fibrils. In addition, SUMOylation prevented htt binding, aggregation, and accumulation on model lipid bilayers comprised of total brain lipid extract. Collectively, these observations demonstrate that SUMOylation promotes a distinct htt aggregation pathway that may affect htt toxicity.
Association of Elite Sports Status with Gene Variants of Peroxisome Proliferator Activated Receptors and Their Transcriptional Coactivator

Background: Although the scientific literature regarding sports genomics has grown during the last decade, some genes, such as peroxisome proliferator activated receptors (PPARs), have not been fully described in terms of their role in achieving extraordinary sports performance. Therefore, the purpose of this systematic review was to determine which elite sports performance constraints are positively influenced by PPARs and their coactivators. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used, with a combination of PPAR and sports keywords. Results: In total, 27 studies that referred to PPARs in elite athletes were included, where the Ala allele in PPARG rs1801282 was associated with strength and power elite athlete status in comparison to subelite athlete status. The C allele in PPARA rs4253778 was associated with soccer, and the G allele PPARA rs4253778 was associated with endurance elite athlete status. Other elite status endurance alleles were the Gly allele in PPARGC1A rs8192678 and the C allele PPARD rs2016520. Conclusions: PPARs can be used for estimating the potential to achieve elite status in human physical performance in strength and power, team, and aerobic sports disciplines. Carrying specific PPAR alleles can provide a partial benefit to achieving elite sports status, but does not preclude achieving elite status if they are absent.
Division of Parent Care among Adult Children.

OBJECTIVE Many older adults rely on their children's support to sustain community residence. Although filial norms encourage adult children to help their parents, not every child provides parent care in times of need. The majority of prior studies have adopted an individualistic perspective to examine factors associated with individual children's caregiving behavior. This study complements previous work by using the family systems perspective to understand how caregiving responsibilities are allocated among children in the family and how the pattern of care division evolves over time. METHOD Data came from seven rounds of the National Health and Aging Trends Study (2011-2017), in which community-dwelling respondents were asked about all of their children and which children provided them with care. Multilevel models were estimated to examine how caregiving responsibilities were distributed among children and how the children's caregiving efforts responded to changes in their parents' frailty. RESULTS About three quarters of older adults reported receiving help from only one child, and the average of monthly care hours was about 50 at baseline. As parents' frailty increased, the proportion of children providing parents rose and the allocation of parent-care hours became more equal.
Histological Grade and Magnetic Resonance Imaging Quantitative T1rho/T2 Mapping in Osteoarthritis of the Knee: A Study in 20 Patients

Background Magnetic resonance imaging (MRI) of osteoarthritis (OA) of the knee is a preoperative method of joint assessment. Histology of the joint is invasive and performed after surgery. T1rho/T2 MRI mapping is a new preoperative method of quantifying joint changes. This study aimed to analyze and compare the histological changes in the joint cartilage with the use of quantitative T1rho/T2 MRI mapping in patients with OA of the knee. Material/Methods Twenty patients with OA of the knee (20 knees) underwent preoperative MRI with T1rho mapping, T2 mapping, T1-weighted, and T2-weighted fat-suppressed MRI sequences. The degree of OA of the knee on MRI was graded according to the Osteoarthritis Research Society International (OARSI) criteria and the Kellgren-Lawrence grading system. Histological grading of OA used the OARSI criteria. Four tibiofemoral condyles were assessed histologically, and the degree of cartilage destruction was determined using the OARSI criteria. Two investigators performed cartilage segmentation for T1rho/T2 values. Results Histology of the four knee joint condyles confirmed mild to severe OA. The histology of the cartilage thickness (P<0.001) and the MRI findings of the distal medial condyle (P<0.00) were significantly different from the other three knee joint condyles. The T2 and T1rho values of each condyle were significantly correlated with the histological grade (II–IV) of the joint condyles, including the cartilage volume, cartilage defects, thickness, and bone lesions (P<0.05). Conclusions In 20 patients with OA of the knee, preoperative T2/T1rho MRI identified Grade II–IV OA changes in the joint.
Promising 2,6,9-Trisubstituted Purine Derivatives for Anticancer Compounds: Synthesis, 3D-QSAR, and Preliminary Biological Assays

We designed, synthesized, and evaluated novel 2,6,9-trisubstituted purine derivatives for their prospective role as antitumor compounds. Using simple and efficient methodologies, 31 compounds were obtained. We tested these compounds in vitro to draw conclusions about their cell toxicity on seven cancer cells lines and one non-neoplastic cell line. Structural requirements for antitumor activity on two different cancer cell lines were analyzed with SAR and 3D-QSAR. The 3D-QSAR models showed that steric properties could better explain the cytotoxicity of compounds than electronic properties (70% and 30% of contribution, respectively). From this analysis, we concluded that an arylpiperazinyl system connected at position 6 of the purine ring is beneficial for cytotoxic activity, while the use of bulky systems at position C-2 of the purine is not favorable. Compound 7h was found to be an effective potential agent when compared with a currently marketed drug, cisplatin, in four out of the seven cancer cell lines tested. Compound 7h showed the highest potency, unprecedented selectivity, and complied with all the Lipinski rules. Finally, it was demonstrated that 7h induced apoptosis and caused cell cycle arrest at the S-phase on HL-60 cells. Our study suggests that substitution in the purine core by arylpiperidine moiety is essential to obtain derivatives with potential anticancer activity.
Deciphering the role of miR-71 in Echinococcus multilocularis early development in vitro

Echinococcosis represents a major public health problem worldwide and is considered a neglected disease by the World Health Organization. The etiological agents are Echinococcus tapeworms, which display elaborate developmental traits that imply a complex control of gene expression. MicroRNAs (miRNAs), a class of small regulatory RNAs, are involved in the regulation of many biological processes such as development and metabolism. They act through the repression of messenger RNAs (mRNAs) usually by binding to the 3’ untranslated region (3’UTR). Previously, we described the miRNome of several Echinococcus species and found that miRNAs are highly expressed in all life cycle stages, suggesting an important role in gene expression regulation. However, studying the role of miRNAs in helminth biology remains a challenge. To develop methodology for functional analysis of miRNAs in tapeworms, we performed miRNA knockdown experiments in primary cell cultures of Echinococcus multilocularis, which mimic the development of metacestode vesicles from parasite stem cells in vitro. First, we analysed the miRNA repertoire of E. multilocularis primary cells by small RNA-seq and found that miR-71, a bilaterian miRNA absent in vertebrate hosts, is one of the top five most expressed miRNAs. Using genomic information and bioinformatic algorithms for miRNA binding prediction, we found a high number of potential miR-71 targets in E. multilocularis. Inhibition of miRNAs can be achieved by transfection of antisense oligonucleotides (anti-miRs) that block miRNA function. To this end, we evaluated a variety of chemically modified anti-miRs for miR-71 knockdown. Electroporation of primary cells with 2’-O-methyl modified anti-miR-71 led to significantly reduced miR-71 levels. Transcriptomic analyses showed that several predicted miR-71 targets were up-regulated in anti-miR-treated primary cells, including genes potentially involved in parasite development, host parasite interaction, and several genes of as yet unknown function. Notably, miR-71-silenced primary cell cultures showed a strikingly different phenotype from control cells and did not develop into fully mature metacestodes. These findings indicate an important function of miR-71 in Echinococcus development and provide, for the first time, methodology to functionally study miRNAs in a tapeworm.