bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of network pharmacology and molecular docking to elucidate the potential mechanism of Eucommia ulmoides-Radix Achyranthis Bidentatae against osteoarthritis
Authors: Jian Gong-hui , Su Bing-zhu , Zhou Wen-jia , Xiong Hui 
Published: August 2020

AbstractBackgroundOsteoarthritis is a disabling disease, which seriously affects the quality of life of patients. Increasing evidence has indicated that Chinese herbal medicine includingEucommia ulmoides(EU) andRadix Achyranthis Bidentatae(RAB) have potential in the treatment of osteoarthritis, and this is associated with their multi-target and multi-link action characteristics. Although their potential anti-arthritic activity has been reported, the exact mechanism of EU-RAB action in osteoarthritis remains unexplored. Therefore, this study explores the mechanism of EU-RAB against osteoarthritis using network pharmacology and molecular docking technology.MethodsPublic databases including TCMSP、BATMAN-TCM、OMIM and Genecards were used to predict the bioactive ingredients and putative targets of EU-RAB against osteoarthritis. Enrichment analysis was performed to expound the biological functions and associated pathways of the hub targets. Cytoscape software was used to construct a “compounds-targets-pathways” network for elucidating the comprehensive molecular mechanism of EU-RAB against osteoarthritis. Molecular docking was used to verify the correlation between the main active ingredients and hub targets.ResultsNetwork pharmacological analysis of EU-RAB in the treatment of osteoarthritis, identified 50 active ingredients including quercetin, kaempferol, wogonin, and baicalein with important biological effect. A total of 68 key targets were screened, including IL-6, EGFR, MAPK8, etc., and they were found to be enriched in a series of signaling pathways, such as apoptosis, TNF, MAPK, PI3K/AKT, and IL-17 signaling pathways. Moreover, molecular docking analysis showed that the main ingredients were tightly bound to the core targets, further confirming the anti-arthritic effects.ConclusionBased on network pharmacology and molecular docking analysis, the present study provides insights into the potential mechanism of EU-RAB in osteoarthritis after successfully screening for associated key target genes and signaling pathways. These findings further provide a theoretical basis for further pharmacological research into the potential mechanism of EU-RAB in osteoarthritis.
mGluR5 regulates REST/NRSF signaling through N-cadherin/β-catenin complex in Huntington’s disease
Authors: de Souza Jéssica M. , Abd-Elrahman Khaled S. , Ribeiro Fabiola M. , Ferguson Stephen S. G. 
Published: August 2020

AbstractRepressor element 1-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a transcription repressor and its expression is regulated by the Wnt pathway through β-catenin. Metabotropic glutamate receptor 5 (mGluR5) signaling plays a key role in controlling neuronal gene expression. Interestingly, REST/NRSF nuclear translocation and signaling, as well as mGluR5 signaling are altered in the presence of mutant huntingtin. It remains unclear whether mGluR5 can modulate Wnt and REST/NRSF signaling under physiological conditions and whether this modulation is altered in Huntington’s disease (HD). Using primary corticostriatal neurons derived from wild type mouse embryos, we find that targeting mGluR5 using the agonist, DHPG, or the negative allosteric modulator, CTEP, modulates REST/NRSF expression by regulating the assembly of N-cadherin/ β-catenin complex in a Src kinase-dependent manner. We have validated our in vitro findings in vivo using two HD mouse models. Specifically, we show that pharmacological inhibition of mGluR5 inzQ175 mice and genetic ablation of mGluR5 in BACHD mice corrected the pathological activation of Src and rescued REST/NRSF-dependent signaling. Together, our data provide evidence that mGluR5 regulates REST/NRSF expression via the Wnt pathway and highlight the contribution of impaired REST/ NRSF signaling to HD pathology.
3DeFDR: statistical methods for identifying cell type-specific looping interactions in 5C and Hi-C data
Authors: Fernandez Lindsey R. , Gilgenast Thomas G. , Phillips-Cremins Jennifer E. 
Published: August 2020

AbstractAn important unanswered question in chromatin biology is the extent to which long-range looping interactions change across developmental models, genetic perturbations, drug treatments, and disease states. Computational tools for rigorous assessment of cell type-specific loops across multiple biological conditions are needed. We present 3DeFDR, a simple and effective statistical tool for classifying dynamic loops across biological conditions from Chromosome-Conformation-Capture-Carbon-Copy (5C) and Hi-C data. Our work provides a statistical framework and open-source coding libraries for sensitive detection of cell type-specific loops in high-resolution 5C and Hi-C data from multiple cellular conditions.
De novo assembly of transcriptome dataset from leaves of Dryobalanops aromatica (Syn. Dryobalanops sumatrensis) seedlings grown in two contrasting potting media
Authors: Siregar Iskandar Zulkarnaen , Dwiyanti Fifi Gus , Siregar Ulfah Juniarti , Matra Deden Derajat 
Published: August 2020

Abstract
Objectives
Efforts to restore tropical peat swamp forests in Indonesia face huge challenges of potential failures due to socio-economic factors and ecological dynamics attributed to lack of knowledge on the adaptive mechanisms of potential tree species such as Kapur (Dryobalanops aromatica C.F.Gaertn Syn. Dryobalanops sumatrensis J.F. Gmelin A.J.G.H Kostermans). This species is a multi-purpose tree that, commonly grows in mineral soils, but also in peat swamp as previously reported, which raised a fundamental question regarding the molecular mechanism of this adaptation. Therefore, a dataset was created aiming to detect candidates of adaptive genes in D. aromatica seedlings, cultivated in two contrasting potting media, namely mineral soil and peat media, based on RNA Sequencing Transcriptome Analysis.

Data description
The RNA transcriptome data of D. aromatica’s seedlings derived from young leaves of three one-year-old seedlings, raised in each dry mineral soil media and peat media, were generated by using Illumina HiSeq 4000 platform in NovogenAIT, Singapore. The acquired data, as the first transcriptome dataset for D. aromatica, is of a great importance in understanding molecular mechanism and responses of the involved genes of D. aromatica to the contrasting, growing potting media conditions that could also be useful to generate molecular markers.
Assessment of tumor suppressor promoter methylation in healthy individuals
Authors: Poduval Deepak B. , Ognedal Elisabet , Sichmanova Zuzana , Valen Eivind , Iversen Gjertrud T. , Minsaas Laura , Lønning Per E. , Knappskog Stian 
Published: August 2020

Abstract
Background
The number of tumor suppressor genes for which germline mutations have been linked to cancer risk is steadily increasing. However, while recent reports have linked constitutional normal tissue promoter methylation of BRCA1 and MLH1 to ovarian and colon cancer risk, the role of epigenetic alterations as cancer risk factors remains largely unknown, presenting an important area for future research. Currently, we lack fast and sensitive methods for assessment of promoter methylation status across known tumor suppressor genes.

Results
In this paper, we present a novel NGS-based approach assessing promoter methylation status across a large panel of defined tumor suppressor genes to base-pair resolution. The method omits the limitations related to commonly used array-approaches. Our panel includes 565 target regions covering the promoters of 283 defined tumor suppressors, selected by pre-specified criteria, and was applied for rapid targeted methylation-specific NGS. The feasibility of the method was assessed by analyzing normal tissue DNA (white blood cells, WBC) samples from 34 healthy postmenopausal women and by performing preliminary assessment of the methylation landscape of tumor suppressors in these individuals. The mean target coverage was 189.6x providing a sensitivity of 0.53%, sufficient for promoter methylation assessment of low-level methylated genes like BRCA1. Within this limited test-set, we detected 206 regions located in the promoters of 149 genes to be differentially methylated (hyper- or hypo-) at > 99% confidence level. Seven target regions in gene promoters (CIITA, RASSF1, CHN1, PDCD1LG2, GSTP1, XPA, and ZNF668) were found to be hyper-methylated in a minority of individuals, with a > 20 percent point difference in mean methylation across the region between individuals. In an exploratory hierarchical clustering analysis, we found that the individuals analyzed may be grouped into two main groups based on their WBC methylation profile across the 283 tumor suppressor gene promoters.

Conclusions
Methylation-specific NGS of our tumor suppressor panel, with detailed assessment of differential methylation in healthy individuals, presents a feasible method for identification of novel epigenetic risk factors for cancer.
Nutrient-supplemented propagation of Saccharomyces cerevisiae improves its lignocellulose fermentation ability
Authors: van Dijk Marlous , Mierke Friederike , Nygård Yvonne , Olsson Lisbeth 
Published: August 2020

AbstractPropagation conditions have been shown to be of considerable importance for the fermentation ability of Saccharomyces cerevisiae. The limited tolerance of yeast to inhibitors present in lignocellulosic hydrolysates is a major challenge in second-generation bioethanol production. We have investigated the hypothesis that the addition of nutrients during propagation leads to yeast cultures with improved ability to subsequently ferment lignocellulosic materials. This hypothesis was tested with and without short-term adaptation to wheat straw or corn stover hydrolysates during propagation of the yeast. The study was performed using the industrial xylose-fermenting S. cerevisiae strain CR01. Adding a mixture of pyridoxine, thiamine, and biotin to unadapted propagation cultures improved cell growth and ethanol yields during fermentation in wheat straw hydrolysate from 0.04 g g−1 to 0.19 g g−1 and in corn stover hydrolysate from 0.02 g g−1 to 0.08 g g−1. The combination of short–term adaptation and supplementation with the vitamin mixture during propagation led to ethanol yields of 0.43 g g−1 in wheat straw hydrolysate fermentation and 0.41 g g−1 in corn stover hydrolysate fermentation. These ethanol yields were improved compared to ethanol yields from cultures that were solely short-term adapted (0.37 and 0.33 g g−1). Supplementing the propagation medium with nutrients in combination with short-term adaptation was thus demonstrated to be a promising strategy to improve the efficiency of industrial lignocellulosic fermentation.
Correlation between immunity from BCG and the morbidity and mortality of COVID-19
Authors: Wickramasinghe Dakshitha , Wickramasinghe Nilanka , Kamburugamuwa Sohan Anjana , Arambepola Carukshi , Samarasekera Dharmabandhu N. 
Published: August 2020

Abstract
Background
To investigate the association between parameters indicating immunity from BCG at country level (presence of BCG vaccination policy, BCG coverage, age-specific incidence of tuberculosis (TB)) and the morbidity and mortality of COVID-19.

Methods
Country-specific data for COVID-19 cases and deaths, demographic details, BCG coverage and policy, age-specific TB incidence and income level were obtained. The crude COVID-19 cases and deaths per 100,000 population were calculated and assessed against the parameters indicating immunity from BCG using linear regression analysis.

Results
Univariate analysis identified higher income level of a country to be significantly associated with COVID-19 cases (p < 0.0001) and deaths (p < 0.0001) but not with its case fatality rate. The association between COVID-19 and TB was strongest for TB incidence in patients > 65-years (Cases (rs = − 0.785,p = 0.0001)) and deaths (rs = − 0.647,p = 0.0001).
Multivariate analysis identified the higher income level of a country and not having a universal BCG vaccination policy to affect the COVID-19 cases. The deaths were inversely affected by the presence of BCG vaccination policy and coverage; and positively by the TB incidence in patients > 65-years.

Conclusion
Significant inverse correlations observed between cases and deaths of COVID-19 and BCG related parameters highlights immunity from BCG as a likely explanation for the variation in COVID-19 across countries.
Measuring the impact of chronic low back pain on everyday functioning: content validity of the Roland Morris disability questionnaire
Authors: Burbridge Claire , Randall Jason A. , Abraham Lucy , Bush Elizabeth Nicole 
Published: August 2020

Abstract
Background
Robust outcome measures are needed to assess and monitor the impact of chronic low back pain (CLBP) on physical functioning. The Roland Morris Disability Questionnaire (RMDQ) is a well-established measure designed to capture the impacts of back pain on everyday functioning, with a particular emphasis on physical functioning. It has documented evaluation of psychometric properties. However, there is no documented qualitative evidence to confirm the content validity of the tool, nor have changes made for electronic administration been debriefed in participants with CLBP.

Methods
In-depth, semi-structured, concept elicitation and cognitive debriefing interviews were conducted with 23 US participants with confirmed CLBP. Interviews allowed participants to describe the impact of CLBP on their day-to-day functioning and discuss comprehension and suitability of the RMDQ. Interviews were transcribed verbatim and analyzed using thematic analysis.

Results
Concept elicitation and cognitive debriefing revealed the substantial burden associated with CLBP, highlighting 15 key areas of functional impact. These were grouped into overarching themes of mobility (walking, stairs, sitting/standing, bending/kneeling, lifting, lying down), activities (chores/housework, dressing, washing, driving, work) and other (relationships/socializing, mood, sleep, appetite), which are consistent with those evaluated within the RMDQ.
All participants found the RMDQ to be relevant with most reporting that the instructions, recall period, and response options were suitable. A few suggested minor changes, however, none were consistent or necessary to support content validity. Updates to the measure for electronic administration and to clarify the response options were well received.

Conclusion
The qualitative data from individuals with CLBP confirmed that the RMDQ has content validity and, alongside documented psychometric evidence, supports the use of the RMDQ as a reliable and valid tool to assess the impact of CLBP on physical functioning.
Exploring the influence of socio-cultural factors and environmental resources on the health related quality of life of children and adolescents after congenital heart disease surgery: parental perspectives from a low middle income country
Authors: Ladak Laila A. , Gallagher Robyn , Hasan Babar S. , Awais Khadija , Abdullah Ahmed , Gullick Janice 
Published: August 2020

Abstract
Background
Health related quality of life (HRQOL) is an important indicator of long-term well-being, influenced by environmental factors such as family, culture, societal norms and available resources. This study aimed to explore parental perspectives on the influence of socio-cultural factors and environmental resources on the HRQOL of children and adolescents after congenital heart disease (CHD) surgery.

Methods
Using a descriptive, qualitative design, semi-structured interviews of children/adolescents who had CHD surgery in this low-middle income country (LMIC) were collected between July to December 2017. There were 20 families enrolled, which included 18 parent dyads (mother and father) and two single mothers, making a total of 38 participants. Initial inductive analysis was further refined using the Social Ecological Model as an analytic lens.

Results
At the intrapersonal level, unrealistic expectations of surgery, residual CHD symptoms and difficulty maintaining educational progress were of great concern. There were low levels of health literacy and understanding about CHD among family and friends, however, strong kinship ties were an important resource at the interpersonal level. These families lived in poverty and mothers often carried the sole burden of care for their sick children. At the institutional level, there were unclear expectations of the child’s needs at school, and parents had poor access to psychological, family-planning and genetic counselling, and poor access to CHD education resources. At a sociocultural level, religion and trust in God were important coping factors, however, CHD was a gendered experience with particular concerns around scarring and the marriageability of girls. Parents noted the deficit of antenatal and specialist CHD services and felt the consequence of a lack of a universal health care system at the public policy level.

Conclusion
Socio-ecological factors have the potential to explain the issues and challenges that children living in LMIC experience with CHD after surgery. The study findings will help to inform future interventions to be implemented in countries like Pakistan.
A cervical tuberculous abscess mimicking a fourth branchial cleft cyst in a child: PCR, the key to fast diagnosis
Authors: Riahi Inès , Fradi Rim , Jaafoura Habib , Kanzari Lamia 
Published: August 2020

Abstract
Background
Anterior cervical tuberculous abscess is a rare presentation of extrapulmonary tuberculosis even in endemic countries.

Case presentation
We report a case of a 14-year-old girl with a 5 day history of an anterior mass. The diagnosis of an infected fourth branchial cleft cyst was first evoked. Fine-needle aspiration cytology was suggestive of tuberculosis. Polymerase chain reaction analysis was the key to the diagnosis of a tuberculous abscess.

Conclusions
In endemic countries, abscesses occurring in uncommon sites should be dealt with a high degree of suspicion for tuberculosis. Early diagnosis is essential to initiate specific and effective treatment. Pre-operative diagnosis avoids invasive surgery and related complications.
Machine learning discriminates a movement disorder in a zebrafish model of Parkinson's disease
Authors: Hughes Gideon L. , Lones Michael A. , Bedder Matthew , Currie Peter D. , Smith Stephen L. , Pownall Mary Elizabeth 
Published: August 2020

ABSTRACT
Animal models of human disease provide an in vivo system that can reveal molecular mechanisms by which mutations cause pathology, and, moreover, have the potential to provide a valuable tool for drug development. Here, we have developed a zebrafish model of Parkinson's disease (PD) together with a novel method to screen for movement disorders in adult fish, pioneering a more efficient drug-testing route. Mutation of the PARK7 gene (which encodes DJ-1) is known to cause monogenic autosomal recessive PD in humans, and, using CRISPR/Cas9 gene editing, we generated a Dj-1 loss-of-function zebrafish with molecular hallmarks of PD. To establish whether there is a human-relevant parkinsonian phenotype in our model, we adapted proven tools used to diagnose PD in clinics and developed a novel and unbiased computational method to classify movement disorders in adult zebrafish. Using high-resolution video capture and machine learning, we extracted novel features of movement from continuous data streams and used an evolutionary algorithm to classify parkinsonian fish. This method will be widely applicable for assessing zebrafish models of human motor diseases and provide a valuable asset for the therapeutics pipeline. In addition, interrogation of RNA-seq data indicate metabolic reprogramming of brains in the absence of Dj-1, adding to growing evidence that disruption of bioenergetics is a key feature of neurodegeneration.
This article has an associated First Person interview with the first author of the paper.
A longitudinal study on parotid and submandibular gland changes assessed by magnetic resonance imaging and ultrasonography in post-radiotherapy nasopharyngeal cancer patients
Authors: Wu Vincent W.C. , Ying Michael TC , Kwong Dora LW , Khong Pek-Lan , Wong Gary KW , Tam Shing-yau 
Published: August 2020

Objectives: With regard to the intensity modulated radiotherapy (IMRT) of nasopharyngeal carcinoma (NPC) patients, this longitudinal study evaluated the radiation-induced changes in the parotid and submandibular glands in terms of gland size, echogenicity and haemodynamic parameters. Methods: 21 NPC patients treated by IMRT underwent MRI and ultrasound scans before radiotherapy, and at 6, 12, 18 and 24 months after treatment. Parotid and submandibular gland volumes were measured from the MRI images, whereas the parotid echogenicity and haemodynamic parameters including the resistive index, pulsatility index, peak systolic velocity and end diastolic velocity were evaluated by ultrasonography. Trend lines were plotted to show the pattern of changes. The correlations of gland doses and the post-RT changes were also studied. Results: The volume of the parotid and submandibular glands demonstrated a significant drop from pre-RT to 6 months post-RT. The parotid gland changed from hyperechoic before RT to either isoechoic or hypoechoic after treatment. The resistive index and pulsatility index decreased from pre-RT to 6 month post-RT, then started to increase at 12 month time interval. Both peak systolic velocity and end diastolic velocity increased after 6 months post-RT then followed a decreasing trend up to 24 months post-RT. There was mild correlation between post-RT gland dose and gland volume, but not with haemodynamic changes. Conclusions: Radiation from IMRT caused shrinkage of parotid and submandibular glands in NPC patients. It also changed the echogenicity and vascular condition of the parotid gland. The most significant changes were observed at 6 months after radiotherapy. Advances in knowledge: It is the first paper that reports on the longitudinal changes of salivary gland volume, echogenicity and haemodynamic parameters altogether in NPC patients after radiotherapy. The results are useful for the prediction of glandular changes that is associated with xerostomia, which help to provide timely management of the complication when the patients attend follow-up visits.