bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of ONT and CCS sequencing technologies on the polyploid genome of a medicinal plant showed that high error rate of ONT reads are not suitable for self-correction
Authors: Zeng Peng , Tian Zunzhe , Han Yuwei , Zhang Weixiong , Zhou Tinggan , Peng Yingmei , Hu Hao , Cai Jing 
Published: August 2022

Abstract
Background
Many medicinal plants are known for their complex genomes with high ploidy, heterozygosity, and repetitive content which pose severe challenges for genome sequencing of those species. Long reads from Oxford nanopore sequencing technology (ONT) or Pacific Biosciences Single Molecule, Real-Time (SMRT) sequencing offer great advantages in de novo genome assembly, especially for complex genomes with high heterozygosity and repetitive content. Currently, multiple allotetraploid species have sequenced their genomes by long-read sequencing. However, we found that a considerable proportion of these genomes (7.9% on average, maximum 23.7%) could not be covered by NGS (Next Generation Sequencing) reads (uncovered region by NGS reads, UCR) suggesting the questionable and low-quality of those area or genomic areas that can’t be sequenced by NGS due to sequencing bias. The underlying causes of those UCR in the genome assembly and solutions to this problem have never been studied.

Methods
In the study, we sequenced the tetraploid genome of Veratrum dahuricum (Turcz.) O. Loes (VDL), a Chinese medicinal plant, with ONT platform and assembled the genome with three strategies in parallel. We compared the qualities, coverage, and heterozygosity of the three ONT assemblies with another released assembly of the same individual using reads from PacBio circular consensus sequencing (CCS) technology, to explore the cause of the UCR.

Results
By mapping the NGS reads against the three ONT assemblies and the CCS assembly, we found that the coverage of those ONT assemblies by NGS reads ranged from 49.15 to 76.31%, much smaller than that of the CCS assembly (99.53%). And alignment between ONT assemblies and CCS assembly showed that most UCR can be aligned with CCS assembly. So, we conclude that the UCRs in ONT assembly are low-quality sequences with a high error rate that can’t be aligned with short reads, rather than genomic regions that can’t be sequenced by NGS. Further comparison among the intermediate versions of ONT assemblies showed that the most probable origin of those errors is a combination of artificial errors introduced by “self-correction” and initial sequencing error in long reads. We also found that polishing the ONT assembly with CCS reads can correct those errors efficiently.

Conclusions
Through analyzing genome features and reads alignment, we have found the causes for the high proportion of UCR in ONT assembly of VDL are sequencing errors and additional errors introduced by self-correction. The high error rates of ONT-raw reads make them not suitable for self-correction prior to allotetraploid genome assembly, as the self-correction will introduce artificial errors to > 5% of the UCR sequences. We suggest high-precision CCS reads be used to polish the assembly to correct those errors effectively for polyploid genomes.
The inhibitory effect and mechanism of Yi-qi-hua-yu-jie-du decoction on the drug resistance of gastric cancer stem cells based on ABC transporters
Authors: Huang Wenjie , Wen Fang , Gu Peixing , Liu Jiatong , Xia Yun , Li Ye , Zhou Jiayu , Song Siyuan , Ruan Shuai , Gu Suping , Chen Xiaoxue , Shu Peng 
Published: August 2022

Abstract
Background
The drug resistance of tumor stem cells is an obstacle in gastric cancer (GC) treatment and the high expression of ABC transporters is a classic reason for drug resistance. This study aimed to construct a reliable GC drug-resistant stem cell model and explore the inhibitory effect and mechanism of Yi-qi-hua-yu-jie-du medicated serum (YQHY) on the drug resistance of GC stem cells based on ABC transporters.

Methods
The tumor stemness biomarker CD44 was primary identification from WGCNA. The magnetic-activated cell sorting (MACS) method was used to separate CD44( +)BGC823/5-Fu (BGC823/5–Fu-CSCs) cells and the stemness characteristics were verified from multiple dimensions. Then, the drug resistance index and expression of ABC transporter genes MDR1 and MRP1 were detected in CD44(−)/CD44(+) cells. The inhibition and apoptosis rates of the cells administrated with YQHY or/and 5-Fu were calculated to confirm that YQHY can suppress the drug resistance of BGC823/5-Fu-CSCs. Afterwards, the effects of YQHY on the expression of MDR1 and MRP1 and the activation of the PI3K/Akt/Nrf2 pathway were observed. Finally, under the administration of IGF-1 (the activator of PI3K/Akt pathway) and Nrf2 siRNA, the mechanism of YQHY on reversing the drug resistance of BGC823/5–Fu-CSCs through inhibiting the expression of MDR1 and MRP1 via PI3K/Akt/Nrf2 was verified.

Results
CD44 was a reliable GC stemness biomarker and can be applied to construct the drug-resistant GC stem cell model CD44(+)BGC823/5-Fu. The growth rate, cell proliferation index, soft agar colony formation, expression of stemness specific genes and tumorigenesis ability of CD44(+)BGC823/5-Fu cells were significantly higher than those of CD44(−)BGC823/5-Fu cells. BGC823/5–Fu-CSCs exhibited strong drug resistance to 5-Fu and high expression of ABC transporter genes MDR1 and MRP1 compared to CD44(-) cells. YQHY increased the inhibition and apoptosis rates to efficiently inhibit the drug resistance of BGC823/5–Fu-CSCs. Meanwhile, it suppressed the expression of MDR1 and MRP1 and restrained the activation of PI3K/Akt/Nrf2 signaling pathway. Finally, it was found that IGF-1 partially restored the activation of PI3K/Akt/Nrf2 pathway, alleviated the inhibition of MDR1 and MRP1, blocked the proliferation-inhibitory and apoptosis-promotion effects. YQHY and si-Nrf2 synergistically suppressed the MDR1/MRP1 expression and the drug resistance of BGC823/5–Fu-CSCs.

Conclusions
CD44 was a reliable GC stemness biomarker, and the high expression of ABC transporter genes MDR1 and MRP1 was an important feature of drug-resistant stem cells. YQHY inhibited the MDR1 and MRP1 expression via PI3K/Akt/Nrf2 pathway, thus reversing the drug resistance of BGC823/5–Fu-CSCs.
Therapeutic approach with commercial supplements for pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels
Authors: Álvarez-Córdoba Mónica , Reche-López Diana , Cilleros-Holgado Paula , Talaverón-Rey Marta , Villalón-García Irene , Povea-Cabello Suleva , Suárez-Rivero Juan M. , Suárez-Carrillo Alejandra , Munuera-Cabeza Manuel , Piñero-Pérez Rocío , Sánchez-Alcázar José A. 
Published: August 2022

Abstract
Background
Neurodegeneration with brain iron accumulation (NBIA) is a group of rare neurogenetic disorders frequently associated with iron accumulation in the basal nuclei of the brain characterized by progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. Pantothenate kinase-associated neurodegeneration (PKAN) is one of the most widespread NBIA subtypes. It is caused by mutations in the gene of pantothenate kinase 2 (PANK2) that result in dysfunction in PANK2 enzyme activity, with consequent deficiency of coenzyme A (CoA) biosynthesis, as well as low levels of essential metabolic intermediates such as 4′-phosphopantetheine, a necessary cofactor for essential cytosolic and mitochondrial proteins.

Methods
In this manuscript, we examined the therapeutic effectiveness of pantothenate, panthetine, antioxidants (vitamin E and omega 3) and mitochondrial function boosting supplements (L-carnitine and thiamine) in mutant PANK2 cells with residual expression levels.

Results
Commercial supplements, pantothenate, pantethine, vitamin E, omega 3, carnitine and thiamine were able to eliminate iron accumulation, increase PANK2, mtACP, and NFS1 expression levels and improve pathological alterations in mutant cells with residual PANK2 expression levels.

Conclusion
Our results suggest that several commercial compounds are indeed able to significantly correct the mutant phenotype in cellular models of PKAN. These compounds alone or in combinations are of common use in clinical practice and may be useful for the treatment of PKAN patients with residual enzyme expression levels.
HPV genotyping by L1 amplicon sequencing of archived invasive cervical cancer samples: a pilot study
Authors: Warden Charles D. , Cholli Preetam , Qin Hanjun , Guo Chao , Wang Yafan , Kancharla Chetan , Russell Angelique M. , Salvatierra Sylvana , Mutsvunguma Lorraine Z. , Higa Kerin K. , Wu Xiwei , Wilczynski Sharon , Pillai Raju , Ogembo Javier Gordon 
Published: August 2022

Abstract
Background
Human papillomavirus (HPV) is the primary cause of invasive cervical cancer (ICC). The prevalence of various HPV genotypes, ranging from oncogenically low- to high-risk, may be influenced by geographic and demographic factors, which could have critical implications for the screening and prevention of HPV infection and ICC incidence. However, many technical factors may influence the identification of high-risk genotypes associated with ICC in different populations.

Methods
We used high-throughput sequencing of a single amplicon within the HPV L1 gene to assess the influence of patient age, race/ethnicity, histological subtype, sample type, collection date, experimental factors, and computational parameters on the prevalence of HPV genotypes detected in archived DNA (n = 34), frozen tissue (n = 44), and formalin-fixed paraffin-embedded (FFPE) tissue (n = 57) samples collected in the Los Angeles metropolitan area.

Results
We found that the percentage of off-target human reads and the concentration of DNA amplified from each sample varied by HPV genotype and by archive type. After accounting for the percentage of human reads and excluding samples with especially low levels of amplified DNA, the HPV prevalence was 95% across all ICC samples: HPV16 was the most common genotype (in 56% of all ICC samples), followed by HPV18 (in 21%). Depending upon the genotyping parameters, the prevalence of HPV58 varied up to twofold in our cohort. In archived DNA and frozen tissue samples, we detected previously established differences in HPV16 and HPV18 frequencies based on histological subtype, but we could not reproduce those findings using our FFPE samples.

Conclusions
In this pilot study, we demonstrate that sample collection, preparation, and analysis methods can influence the detection of certain HPV genotypes and must be carefully considered when drawing any biological conclusions based on HPV genotyping data from ICC samples.
An ensemble-based drug–target interaction prediction approach using multiple feature information with data balancing
Authors: El-Behery Heba , Attia Abdel-Fattah , El-Fishawy Nawal , Torkey Hanaa 
Published: August 2022

AbstractBackgroundRecently, drug repositioning has received considerable attention for its advantage to pharmaceutical industries in drug development. Artificial intelligence techniques have greatly enhanced drug reproduction by discovering therapeutic drug profiles, side effects, and new target proteins. However, as the number of drugs increases, their targets and enormous interactions produce imbalanced data that might not be preferable as an input to a prediction model immediately.MethodsThis paper proposes a novel scheme for predicting drug–target interactions (DTIs) based on drug chemical structures and protein sequences. The drug Morgan fingerprint, drug constitutional descriptors, protein amino acid composition, and protein dipeptide composition were employed to extract the drugs and protein’s characteristics. Then, the proposed approach for extracting negative samples using a support vector machine one-class classifier was developed to tackle the imbalanced data problem feature sets from the drug–target dataset. Negative and positive samplings were constructed and fed into different prediction algorithms to identify DTIs. A 10-fold CV validation test procedure was applied to assess the predictability of the proposed method, in addition to the study of the effectiveness of the chemical and physical features in the evaluation and discovery of the drug–target interactions.ResultsOur experimental model outperformed existing techniques concerning the curve for receiver operating characteristic (AUC), accuracy, precision, recall F-score, mean square error, and MCC. The results obtained by the AdaBoost classifier enhanced prediction accuracy by 2.74%, precision by 1.98%, AUC by 1.14%, F-score by 3.53%, and MCC by 4.54% over existing methods.
The effects of Rosa foetida extract along with self-care education on primary dysmenorrhea: study protocol for a randomized clinical trial
Authors: Shabani Fatemeh , Omidvar Shabnam , Sajadi Kaboudi Parvin , Pasha Hajar , Khafri Soraya , Najafzadehvarzi Hossein , Nasiri Amiri Fatemeh , Faramarzi Mahbobeh , Bouzari Zinatossadat 
Published: August 2022

Abstract
Background
Dysmenorrhea is one of the most common disorders among young women. Medicinal herbs are one of the alternative methods for the treatment of dysmenorrhea. This study will investigate the effect of Rosa foetida extract, along with self-care behavior education on primary dysmenorrhea among female students of Babol University of medical sciences.

Methods/design
A randomized clinical trial will be performed on single students, aged 18 to 24 years. The research samples will be divided into three groups. The students will receive self-care behavior education on dysmenorrhea. Following the education, two of the groups will receive Rosa foetida extract capsules and placebo capsules in two consecutive cycles every 8 h for two successive days, respectively. The capsules will have similar physical appearance. The third group will not receive any medication. Data will be collected through demographic characteristic questionnaire, visual analog scale, dysmenorrhea self-care behaviors scale questionnaire, pictorial chart, and menstrual distress scale questionnaire. In order to determine and compare the effect of pharmacological and educational interventions on the severity of dysmenorrhea in groups, an ANOVA analysis of variance test with repeated measures will be used by SPSS software version 22.

Discussion
The results will show the effects of Rosa foetida extract along with self-care behavior education on primary dysmenorrhea, and beneficial effects that may be found in the trial of this plant may be of use for women with the same problem.

Ethics and dissemination
The study is approved by the Ethics Committee of Babol University of Medical Sciences (IR.MUBABOL.REC.1397.059).

Trial registration
IRCT 20190318043086N1. Registered on 14 June 2019.
Influence of digital media in the oral health education of mother-child pairs: study protocol of a parallel double-blind randomized clinical trial
Authors: Ribeiro Yuri Jivago Silva , Ferreira Luanna Gonçalves , Nelson-Filho Paulo , Arnez Maya Fernanda Manfrin , Paula-Silva Francisco Wanderley Garcia 
Published: August 2022

Abstract
Background
Dental caries is the most common non transmissible chronic disease in childhood and the control of dental biofilm in children is one of the greatest challenges in oral disease prevention. Digital media applications can help patients in improving their oral hygiene performance and reducing the number of appointments due to pain and discomfort reasons. This study aims to investigate the use of an smartphone application (WhatsApp) to deliver oral health education to mother-child pairs, with the ultimate goal of controlling dental biofilm and caries through digital activities focused on oral hygiene.

Methods
This study was designed as a randomized, double-blind, parallel clinical trial involving 100 pairs of mothers and children (6–12 years old). The mothers and children will be randomly allocated to the control group (n = 50 pairs), who will receive a single visit conventional oral health education, or to the experimental group (n = 50 pairs), who will receive both a single visit conventional oral health education and educational videos through WhatsApp Messenger, twice a week. Before randomization of the groups and after the intervention, pairs will be evaluated regarding to plaque index (VPI), gingival bleeding index (GBI), and number of decayed, missing and filled permanent or primary teeth (DMF-T) modified by the inclusion of active non-cavitated carious lesions (Nyvad criteria). Socioeconomic data, dental history, and oral health literacy will obtained using questionnaires (Oral Health Literacy Assessment Task for Paediatric Dentistry; BOHLAT-P). Chi-square, Student’s t-test, paired Student’s t-test, Mann-Whitney, and Friedman tests will be used with a 5% significance level.

Discussion
This intervention proposal is designed to motivate behavioral change in mother-child pairs. We hypothesize that adding digital media to traditional oral health programs will provoke improvements in oral hygiene behavior and health outcomes. To our knowledge, this is the first study evaluating the effect of educational videos communicated by digital media (WhatsApp) on the oral health of mother-child pairs evaluated by long-term dental examinations. In addition, we will assess the maternal level of comprehension of the provided information via a literacy assessment tool. The clinical trial is registered at the Brazilian Registry of Clinical Trials (No. RBR-7s8bw6m).
A randomized, double-blind, placebo-controlled 12-week trial of infliximab in patients with juvenile-onset spondyloarthritis
Authors: Burgos-Vargas Rubén , Loyola-Sanchez Adalberto , Ramiro Sofia , Reding-Bernal Arturo , Alvarez-Hernandez Everardo , van der Heijde Desirée , Vázquez-Mellado Janitzia 
Published: August 2022

AbstractObjectiveTo assess the efficacy and safety of infliximab versus placebo in the treatment of patients with juvenile-onset spondyloarthritis (JoSpA).MethodsPhase III, randomized, double-blind, placebo-controlled trial of 12 weeks that included patients ≤ 18 years old with JoSpA not responding to nonsteroidal anti-inflammatory drugs, sulfasalazine, or methotrexate. Patients were randomly assigned 1:1 to the infusion of infliximab 5mg/kg or placebo; completers entered then an open-label extension (OLE) period of 42 weeks. The primary endpoint was the number of active joints. Secondary outcomes included the assessment of disease activity, tender entheses, spinal mobility, serum C-reactive protein (CRP), the Bath Ankylosing Spondylitis Disease Activity and Functional Index, and the Childhood Health Assessment Questionnaire (CHAQ).ResultsWe randomized 12 patients to infliximab and 14 to placebo. No significant differences were found between groups at baseline. At week 12, the mean number of active joints was 1.4 (SD 2.4) in the infliximab group and 4.1 (SD 3.0) in the placebo group (p= 0.0002). A repeated-measures mixed model analysis that included all endpoints in the study demonstrated sustained favourable outcomes of infliximab for active joints, tender joints, swollen joints, and tender enthesis counts, as well as for CHAQ and CRP (p< 0.01). Adverse events were more frequent in the infliximab group, including infections and infusion reactions, but none of them was serious.ConclusionInfliximab is efficacious for patients with JoSpA with an inadequate response to conventional treatment. No serious adverse events with the use of infliximab were observed.
Identification of TMEM129, encoding a ubiquitin-protein ligase, as an effector gene of osteoarthritis genetic risk
Authors: Brumwell Abby , Aubourg Guillaume , Hussain Juhel , Parker Eleanor , Deehan David J. , Rice Sarah J. , Loughlin John 
Published: August 2022

Abstract
Background
Osteoarthritis is highly heritable and genome-wide studies have identified single nucleotide polymorphisms (SNPs) associated with the disease. One such locus is marked by SNP rs11732213 (T > C). Genotype at rs11732213 correlates with the methylation levels of nearby CpG dinucleotides (CpGs), forming a methylation quantitative trait locus (mQTL). This study investigated the regulatory activity of the CpGs to identify a target gene of the locus.

Methods
Nucleic acids were extracted from the articular cartilage of osteoarthritis patients. Samples were genotyped, and DNA methylation was quantified by pyrosequencing at 14 CpGs within a 259-bp interval. CpGs were tested for enhancer effects in immortalised chondrocytes using a reporter gene assay. DNA methylation at the locus was altered using targeted epigenome editing, with the impact on gene expression determined using quantitative polymerase chain reaction.

Results
rs11732213 genotype correlated with DNA methylation at nine CpGs, which formed a differentially methylated region (DMR), with the osteoarthritis risk allele T corresponding to reduced levels of methylation. The DMR acted as an enhancer and demethylation of the CpGs altered expression of TMEM129. Allelic imbalance in TMEM129 expression was identified in cartilage, with under-expression of the risk allele.

Conclusions
TMEM129 is a target of osteoarthritis genetic risk at this locus. Genotype at rs11732213 impacts DNA methylation at the enhancer, which, in turn, modulates TMEM129 expression. TMEM129 encodes an enzyme involved in protein degradation within the endoplasmic reticulum, a process previously implicated in osteoarthritis. TMEM129 is a compelling osteoarthritis susceptibility target.
Effect of income level on stroke incidence and the mediated effect of simultaneous diagnosis of metabolic syndrome diseases; a nationwide cohort study in South Korea
Authors: Jeong Seungmin , Cho Sung-il , Kong So Yeon 
Published: August 2022

AbstractBackgroundThis study aimed to determine whether a simultaneous diagnosis of main components of metabolic syndrome (MetS) (hypertension, diabetes mellitus, and dyslipidemia) plays a mediator between income level and stroke.MethodsWe used the National Health Insurance Service National Sample Cohort database from 2006 to 2015. The mediator variables were the number of main MetS components diagnosed simultaneously (two or more/three or more). We used a weighting approach method of causal mediation analysis to apply counterfactual frameworks to the Cox proportional hazards regression model.ResultsA total of 213,526 people were included with 1,690,665.3 person-years of followed up. Compared with the high-income group, the risk of being diagnosed with two or more components of MetS significantly increased in all other income groups [middle-income OR 1.05 (95% CI 1.02–1.08); low-income OR 1.09 (95% CI 1.05–1.12); Medical Aid beneficiaries OR 1.39 (95% CI 1.32–1.47)]. A lower level of income was significantly associated with a higher risk of stroke compared with the high-income group [middle-income HR 1.15 (95% CI 1.07–1.25); low-income HR 1.19 (95% CI 1.10–1.29); Medical Aid beneficiaries HR 1.63 (95% CI 1.48–1.80)]. In the Medical Aid beneficiaries, simultaneous diagnosis of the main metabolic components acted as a significant mediator between income levels and stroke incidence, with 26.6% mediated when diagnosed with two or more diseases and 21.1% when diagnosed with all three.ConclusionsCo-diagnosis of MetS components played a significant mediator role between income level and stroke incidence.