Miracle-dz/UniFAR-FTUs huggingface dataset:
Saudi English for specific purpose students’ attitudes toward the learning of English language: An investigative study

Students’ attitudes are usually consulted before launching any learning/teaching program since they are the center of the learning process. This study is also motivated by such an aim as it gauges the attitudes of Saudi health track students on learning English for specific purpose (ESP). Furthermore, the students’ perceptions toward the culture of English are sought. It also explores the factors that impact the students in their endeavors. The study applies mixed methods by conducting a survey and follow-up interviews to gather information from 57 Saudi students enrolled at the preparatory year program (PYP), and interviews with 25 students. Findings show that the students have a moderately positive attitude toward learning English. Further, students’ responses aggregate toward moderate attitudes toward learning the target culture. In addition to that, the study reports some factors which shape the students’ positive attitudes toward learning English: (1) teaching quality, (2) classroom scenario, and (3) classroom environment. The study indicates the necessity of engaging students in a relaxed learning environment. As far as the English as a foreign language (EFL) teachers are concerned, they need to take into consideration their students’ interests while preparing and delivering the lectures.
Medicine-related problems: A recurrent issue among residents living in nursing homes

Aim: To examine the incidence and nature of medicine-related problems over time experienced by nursing home residents. Method: We analyzed records collected in the Reducing Medicine-Induced Deterioration and Adverse Events (ReMInDAR) trial. The trial pharmacists provided services to reduce medicine-induced deterioration and adverse reactions for residents every 8-weeks over a year. The problems identified by the pharmacists were documented in reports and subsequently classified independently by research pharmacists using the D.O. C.U. M.E. N.T system. The number and type of problems at each service and time to develop a new problem post first session were assessed. All analyses were performed using R software (Version 4.1.1). Results: The cohort was 115 nursing home residents who received 575 services. In the 12-months, a total of 673 medicine-related problems or symptom reports were identified in 112 residents. Most residents (75%) experienced a new medicine-related problem by the fourth month post the first assessment. After the first session, the proportion of residents with a new medicine-related problem or symptom report declined at each repeated pharmacy session (59% at visit 2 vs. 28% at visit 6, p < 0.01). Conclusion: Residents living in nursing homes frequently experience medicine-related problems. Our results suggest clinical pharmacist services performed every 4-months may have the potential to reduce the medicine-related problems in nursing homes.
Genomic signatures of artificial selection in fecundity of Pacific white shrimp, Penaeus vannamei

Penaeus vannamei is the most important economic shrimp in the world. Many selective breeding programs are carried out to improve its production and performance traits. Although significant differences in the reproductive ability of female P. vannamei under artificial breeding conditions have been reported, the genome-wide adaption of the reproductive ability of domesticated female P. vannamei is less investigated. In this study, whole-genome analysis was performed along with pooled DNA sequencing on two fecundity separated bulks, high fecundity bulk (HB), and low fecundity bulk (LB). Each bulk contained 30 individuals from 3 commercial populations. A sequencing depth of >30× was achieved for each bulk, leading to the identification of 625,181 and 629,748 single nucleotide polymorphisms (SNPs) in HB and LB, respectively. Fixation index (Fst) combined with p ratio allowed for the identification of 145 selective sweep regions, with a sequence length of 14.5 Mb, accounting for 0.59% of the genome. Among the 145 selective sweep regions, a total of 64,046 SNPs were identified, and further verification was performed by genotyping 50 candidate SNPs on 60 samples from the offspring of the three populations. Furthermore, 121 genes were screened from the sweep regions. GO annotation and KEGG enrichment analyses showed that partial genes were essential for fecundity regulation. This study provides important information for in-depth investigation of genomic characteristics for long-term selective breeding on the fecundity of female P. vannamei and will also be important for genome-assisted breeding of P. vannamei in the future.
S-3′-hydroxy-7′, 2′, 4′-trimethoxyisoxane, a novel ferroptosis inducer, promotes NSCLC cell death through inhibiting Nrf2/HO-1 signaling pathway

Background: Ferroptosis is a newly discovered and promising non-apoptotic programmed cell death (PCD), and inducing ferroptosis in cancer cells could open up a novel avenue for drug screening and cancer therapy. S-3′-hydroxy-7′, 2′, 4′-trimethoxyisoxane (ShtIX), a new isoflavane compound, has been reported to possess cytotoxicity in non-small cell lung cancer (NSCLC). The aim of this research is to explore the ShtIX-induced cell death form and its underlying molecular mechanism in NSCLC cells. Methods: Cell proliferation, cell cycle arrest, and cell death tests were used to assess the ability of ShtIX to kill NSCLC cells. Iron metabolism, Fe2+ content, reactive oxygen species (ROS) production, lipid peroxide (MDA) level, glutathione (GSH) level, and glutathione peroxidase 4 (GPX4) level were used to determine ferroptosis caused by ShtIX. We employed western blot, quantitative real-time PCR, and Nrf2 interference in NSCLC cells to investigate the roles of Nrf2/HO-1 in ShtIX-induced ferroptosis. In a xenograft nude mouse model, the anticancer efficacy of ShtIX and the function of ferroptosis were studied. Results: Our research shows that ShtIX can selectively kill NSCLC cells while sparing normal cells and that ShtIX-induced cell death can be efficiently reversed by the ferroptosis inhibitors and the iron chelator, but not by other cell death inhibitors. After cells were treated with ShtIX, there was an increase in Fe2+ content and lipid peroxidation accumulation, as well as a drop in GSH and GPX4 levels, all of which are indicators of ferroptosis. ShtIX also reduced the expression of Nrf2 and HO-1, and genetic Nrf2 silencing in NSCLC enhanced the effect of ShtIX-induced ferroptosis. Additionally, ShtIX retards tumor growth and induced ferroptosis through Nrf2/HO-1 signal pathway in the A549 xenograft model, whereas Fer-1 lessens the anticancer effect. Conclusion: This work provided the evidence that ShtIX caused ferroptosis in NSCLC cells, and inhibiting the Nrf2/HO-1 pathway can considerably exacerbate the effect of ShtIX-induced ferroptosis. The study establishes ShtIX as a promising natural ferroptosis inducer for the treatment of NSCLC.
CENP-A is a potential prognostic biomarker and correlated with immune infiltration levels in glioma patients

Background: Centromeric protein A (CENP-A), an essential protein involved in chromosomal segregation during cell division, is associated with several cancer types. However, its role in gliomas remains unclear. This study examined the clinical and prognostic significance of CENP-A in gliomas. Methods: Data of patients with glioma were collected from the Cancer Genome Atlas. Logistic regression, the Kruskal–Wallis test, and the Wilcoxon signed-rank test were performed to assess the relationship between CENP-A expression and clinicopathological parameters. The Cox regression model and Kaplan–Meier curve were used to analyze the association between CENP-A and survival outcomes. A prognostic nomogram was constructed based on Cox multivariate analysis. Gene set enrichment analysis (GSEA) was conducted to identify key CENP-A-related pathways and biological processes. Results: CENP-A was upregulated in glioma samples. Increased CENP-A levels were significantly associated with the world health organization (WHO) grade [Odds ratio (OR) = 49.88 (23.52–129.06) for grade 4 vs. grades 2 and 3], primary therapy outcome [OR = 2.44 (1.64–3.68) for progressive disease (PD) and stable disease (SD) vs. partial response (PR) and complete response (CR)], isocitrate dehydrogenase (IDH) status [OR = 13.76 (9.25–20.96) for wild-type vs. mutant], 1p/19q co-deletion [OR = 5.91 (3.95–9.06) for no codeletion vs. co-deletion], and age [OR = 4.02 (2.68–6.18) for > 60 vs. ≤ 60]. Elevated CENP-A expression was correlated with shorter overall survival in both univariate [hazard ratio (HR): 5.422; 95% confidence interval (CI): 4.044–7.271; p < 0.001] and multivariate analyses (HR: 1.967; 95% CI: 1.280–3.025; p < 0.002). GSEA showed enrichment of numerous cell cycle-and tumor-related pathways in the CENP-A high expression phenotype. The calibration plot and C-index indicated the favorable performance of our nomogram for prognostic prediction in patients with glioma. Conclusion: We propose a role for CENP-A in glioma progression and its potential as a biomarker for glioma diagnosis and prognosis.
FGF/FGFR-related lncRNAs based classification predicts prognosis and guides therapy in gastric cancer

Fibroblast growth factor (FGF) and its receptor (FGFR) play crucial roles in gastric cancer (GC). Long non-coding RNAs (lncRNAs) are defined as RNA molecules of around 200 nucleotides or more, which are not translated into proteins. As well-known regulatory factors, lncRNAs are considered as biomarkers for prognosis and treatment response in GC. It is of importance to identify FGF/FGFR-related lncRNAs in GC. Here, some FGF/FGFR-related lncRNAs were identified in GC based on the data from public databases, the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Then a four-lncRNAs (FGF10-AS1, MIR2052HG, POU6F2-AS2, and DIRC1) risk score (RS) model was established for predicting GC’s prognosis by using Cox analysis. According to the median value of RS, GC patients were divided into low and high RS group. Low RS group displayed high tumor mutation burden and infiltration of immune cells, as well as more sensitivity to immunotherapy or chemotherapy. High RS group showed high infiltration of stromal cells and more oncogenic signatures. In addition, a comprehensive analysis was carried out and found that high RS group may exhibit specific sensitivity to Panobinostat (histone deacetylases inhibitor) and Tivantinib (MET inhibitor). In summary, our study not only offers a novel personalized prognostication classification model according to FGF/FGFR-related lncRNAs, but also provides a new strategy for subclass-specific precision treatment in GC.
Identifying novel genetic loci associated with polycystic ovary syndrome based on its shared genetic architecture with type 2 diabetes

Genome-wide association studies (GWAS) have identified several common variants associated with polycystic ovary syndrome (PCOS). However, the etiology behind PCOS remains incomplete. Available evidence suggests a potential genetic correlation between PCOS and type 2 diabetes (T2D). The publicly available data may provide an opportunity to enhance the understanding of the PCOS etiology. Here, we quantified the polygenic overlap between PCOS and T2D using summary statistics of PCOS and T2D and then identified the novel genetic variants associated with PCOS behind this phenotypic association. A bivariate causal mixture model (MiXeR model) found a moderate genetic overlap between PCOS and T2D (Dice coefficient = 44.1% and after adjusting for body mass index, 32.1%). The conditional/conjunctional false discovery rate method identified 11 potential risk variants of PCOS conditional on associations with T2D, 9 of which were novel and 6 of which were jointly associated with two phenotypes. The functional annotation of these genetic variants supports a significant role for genes involved in lipid metabolism, immune response, and the insulin signaling pathway. An expression quantitative trait locus functionality analysis successfully repeated that 5 loci were significantly associated with the expression of candidate genes in many tissues, including the whole blood, subcutaneous adipose, adrenal gland, and cerebellum. We found that SCN2A gene is co-localized with PCOS in subcutaneous adipose using GWAS-eQTL co-localization analyses. A total of 11 candidate genes were differentially expressed in multiple tissues of the PCOS samples. These findings provide a new understanding of the shared genetic architecture between PCOS and T2D and the underlying molecular genetic mechanism of PCOS.
Locating a novel autosomal recessive genetic variant in the cattle glucokinase gene using only WGS data from three cases and six carriers

New Mendelian genetic conditions, which adversely affect livestock, arise all the time. To manage them effectively, some methods need to be devised that are quick and accurate. Until recently, finding the causal genomic site of a new autosomal recessive genetic disease has required a two-stage approach using single-nucleotide polymorphism (SNP) chip genotyping to locate the region containing the new variant. This region is then explored using fine-mapping methods to locate the actual site of the new variant. This study explores bioinformatic methods that can be used to identify the causative variants of recessive genetic disorders with full penetrance with just nine whole genome-sequenced animals to simplify and expedite the process to a one-step procedure. Using whole genome sequencing of only three cases and six carriers, the site of a novel variant causing perinatal mortality in Irish moiled calves was located. Four methods were used to interrogate the variant call format (VCF) data file of these nine animals, they are genotype criteria (GCR), autozygosity-by-difference (ABD), variant prediction scoring, and registered SNP information. From more than nine million variants in the VCF file, only one site was identified by all four methods (Chr4: g.77173487A>T (ARS-UCD1.2 (GCF_002263795.1)). This site was a splice acceptor variant located in the glucokinase gene (GCK). It was verified on an independent sample of animals from the breed using genotyping by polymerase chain reaction at the candidate site and autozygosity-by-difference using SNP-chips. Both methods confirmed the candidate site. Investigation of the GCR method found that sites meeting the GCR were not evenly spread across the genome but concentrated in regions of long runs of homozygosity. Locating GCR sites was best performed using two carriers to every case, and the carriers should be distantly related to the cases, within the breed concerned. Fewer than 20 animals need to be sequenced when using the GCR and ABD methods together. The genomic site of novel autosomal recessive Mendelian genetic diseases can be located using fewer than 20 animals combined with two bioinformatic methods, autozygosity-by-difference, and genotype criteria. In many instances it may also be confirmed with variant prediction scoring. This should speed-up and simplify the management of new genetic diseases to a single-step process.
Sensing local energetics to acutely regulate mitophagy in skeletal muscle

The energetic requirements of skeletal muscle to sustain movement, as during exercise, is met largely by mitochondria, which form an intricate, interconnected reticulum. Maintenance of a healthy mitochondrial reticulum is essential for skeletal muscle function, suggesting quality control pathways are spatially governed. Mitophagy, the process by which damaged and/or dysfunctional regions of the mitochondrial reticulum are removed and degraded, has emerged as an integral part of the molecular response to exercise. Upregulation of mitophagy in response to acute exercise is directly connected to energetic sensing mechanisms through AMPK. In this review, we discuss the connection of mitophagy to muscle energetics and how AMPK may spatially control mitophagy through multiple potential means.
Transiently Nav1.8-expressing neurons are capable of sensing noxious stimuli in the brain

While current research highlights the role of Nav1. 8 sensory neurons from the peripheral nervous system, the anatomical and physiological characterization of encephalic Nav1.8 neurons remains unknown. Here, we use a Cre/fluorescent reporter mouse driven by the Nav1.8 gene promoter to reveal unexpected subpopulations of transiently-expressing Nav1.8 neurons within the limbic circuitry, a key mediator of the emotional component of pain. We observed that Nav1.8 neurons from the bed nuclei of the stria terminalis (BST), amygdala, and the periaqueductal gray (vPAG) are sensitive to noxious stimuli from an experimental model of chronic inflammatory pain. These findings identify a novel role for central Nav1.8 neurons in sensing nociception, which could be researched as a new approach to treating pain disorders.
Cost-effectiveness analysis of personalised versus standard dosimetry for selective internal radiation therapy with TheraSphere in patients with hepatocellular carcinoma

Aims To perform a cost-effectiveness analysis (CEA) comparing personalised dosimetry with standard dosimetry in the context of selective internal radiation therapy (SIRT) with TheraSphere for the management of adult patients with locally advanced hepatocellular carcinoma (HCC) from the Italian Healthcare Service perspective. Materials and methods A partition survival model was developed to project costs and the quality-adjusted life years (QALYs) over a lifetime horizon. Clinical inputs were retrieved from a published randomised controlled trial. Health resource utilisation inputs were extracted from the questionnaires administered to clinicians in three oncology centres in Italy, respectively. Cost parameters were based on Italian official tariffs. Results Over a lifetime horizon, the model estimated the average QALYs of 1.292 and 0.578, respectively, for patients undergoing personalised and standard dosimetry approaches. The estimated mean costs per patient were €23,487 and €19,877, respectively. The incremental cost-utility ratio (ICUR) of personalised versus standard dosimetry approaches was €5,056/QALY. Conclusions Personalised dosimetry may be considered a cost-effective option compared to standard dosimetry for patients undergoing SIRT for HCC in Italy. These findings provide evidence for clinicians and payers on the value of personalised dosimetry as a treatment option for patients with HCC.
The effects of different types of Tai Chi exercises on motor function in patients with Parkinson's disease: A network meta-analysis

Background Tai Chi can show improvement in balance and motor ability of elderly patients with PD. However, there were few reports on differences in outcomes associated with different types of Tai Chi on improving exercise capacity in elderly patients with PD. We compared the improvement of motor function in Parkinson's patients with different types of Tai Chi, for finding an optimal intervention. Methods The following databases were searched from the beginning of the establishment of each database to 10 January 2022: PubMed, EMBASE, The Cochrane Library, CNKI, Wanfang Database, and VIP Database. Randomized controlled trials incorporating different types of Tai Chi for PD were included. The outcome measures were UPDRSIII and BBS. NMA was conducted using Stata 15.0 based on a frequentist framework. Results A total of twenty trials were eligible, including 996 participants. In conventional meta-analysis, as for the UPDRSIII scale, 24-form simplified Tai Chi (SMD = −1.272, 95% CI [−2.036, −0.508], P < 0.05, I2 > 50%), Tai Chi exercise program (SMD = −0.839, 95% CI [−1.828, 0.151], P > 0.05, I2 > 50%), 8-form simplified Yang style Tai Chi (SMD = −0.325, 95% CI [−1.362, 0.713], P > 0.05, I2 > 50%), and 8-form simplified Chen style Tai Chi (SMD = −0.28, 95% CI [−0.97, 0.42], P > 0.05, I2 > 50%) were statistically more efficient than the control group. For BBS outcome, 24-form simplified Tai Chi (MD = 3.979, 95% CI [3.364, 4.595], P < 0.05, I2 <50%), Tai Chi exercise program (MD = 5.00, 95% CI [2.07, 7.93], P > 0.05, I2 > 50%), and 8-form simplified Chen style Tai Chi (MD = 1.25, 95% CI [0.52, 1.98], P < 0.05, I2 > 50%) were better than the control group. In the network meta-analysis, the results of UPDRSIII were as follows: 24-form > TCEP > 8-form YS > 8-form CS > control. The ranking probability of BBS was as follows: TCEP > 24-form > 8-form CS > control. Conclusion Among the four treatments studied, 24-form Tai Chi and Tai Chi exercise programs have shown better efficacy than other types. Our study provides new insights into exercise therapy for PD and may contribute to the formulation of a clinical exercise prescription. Systematic review registration Identifier: CRD42021285005.
Exploring the multidimensional heterogeneities of glioblastoma multiforme based on sample-specific edge perturbation in gene interaction network

Glioblastoma multiforme (GBM) is the most malignant brain cancer with great heterogeneities in many aspects, such as prognosis, clinicopathological features, immune landscapes, and immunotherapeutic responses. Considering that gene interaction network is relatively stable in a healthy state but widely perturbed in cancers, we sought to explore the multidimensional heterogeneities of GBM through evaluating the degree of network perturbations. The gene interaction network perturbations of GBM samples (TCGA cohort) and normal samples (GTEx database) were characterized by edge perturbations, which were quantized through evaluating the change in relative gene expression value. An unsupervised consensus clustering analysis was performed to identify edge perturbation-based clusters of GBM samples. Results revealed that the edge perturbation of GBM samples was stronger than that of normal samples. Four edge perturbation-based clusters of GBM samples were identified and showed prominent heterogeneities in prognosis, clinicopathological features, somatic genomic alterations, immune landscapes, and immunotherapeutic responses. In addition, a sample-specific perturbation of gene interaction score (SPGIScore) was constructed based on the differently expressed genes (DEGs) among four clusters, and exhibited a robust ability to predict prognosis. In conclusion, the bioinformatics approach based on sample-specific edge perturbation in gene interaction network provided a new perspective to understanding the multidimensional heterogeneities of GBM.