bluuebunny/crossref_metadata_2025 huggingface dataset:
PEMBELAJARAN MODEL INTERAKTIF RAMAH ORANG TUA DAN GURU (PKM BA AISYIAH BULAKREJO II DAN TK DESA SIDOREJO 03)
Authors: Endrawati Susi , Sutrisno Trismianto Asmo
Published: October 2020

Children are the gift of God the Almighty, the jewel of the hearts of parents and the future of the Nation. Parents are obliged to guide, educate and seek their welfare as much as possible. As a form of guidance and education sought, it is non-formal education in the family environment and formal in the school environment. Parents hope that their sons and daughters get good education from competent kindergarten teachers. Community service is carried out in two partner institutions, namely BA. Aisyiah Bulakrejo II and TK Desa Sidorejo 03 which are located in the Sukoharjo sub-district area. The purpose of this community service is to help school institutions improve the pedagogical skills of kindergarten teachers, so they can be more qualified in delivering teaching and learning materials in the classroom. The limited operational funds that are often experienced by the two TK schools, resulting in insufficient availability of game equipment, to be equal to the number of students The target that has been achieved is the creation of interactive learning models, with 1) Conducting teaching media technology workshops for kindergarten teachers, 2) Train teacher skills in making used APE materials, 3) Create APE marketing media and learning media through the website http://peragaedukatif.web.id/web/wp-login.php. This program is able to make the creativity of kindergarten teachers in learning more interesting and easy to understand. The proliferation of informatics technology provides opportunities for kindergarten teachers to be able to design and create multimedia interactive learning models.
Hifdz Al-Maal dalam Regulasi Rahasia Perbankan
Authors: Nurhisam Luqman , Aprilianto Dimas
Published: October 2020

Bank secrecy refer to secrets in the relationship between a bank and a customer. In accordance with Article 40 paragraph (1) of Law Number 10 Year 1998 concerning Banking, it is stated that banks are required to keep confidential information regarding their depositing customers and their deposits. The research was conducted using the library research method, which looks for normative sources of law by reviewing the laws and regulations that apply or are applied to a particular legal problem. The approach used is the statutory approach, namely the approach taken by examining laws relating to bank secrecy. The purpose of this study is to further examine how Islamic law views the regulation of bank secrecy in Indonesia. The results of this study are related to the maintenance of one of the basic needs elements, namely assets that must be protected (hifdz al-maal), so if other parties ask for an explanation of the financial condition of a customer from a bank, this is not allowed.
Learning from the Perspectives of Albert Bandura and Abdullah Nashih Ulwan: Implications Towards the 21st Century Education
Authors: Abdullah Norillah , Syed Hassan Sharifah Sariah , Abdelmagid Mohamed , Mat Ali Siti Nazilah
Published: October 2020

A vast existing literature in educational research has been explored on Social Cognitive Theory (SCT) with the focus on addressing self-efficacy, self-regulation and social interactions in learning. This theory is used as a framework to predict behaviours and interventions. However, researchers have managed to comprehend and adopt the theory comprehensively with regards to all the factors involved specifically in the domain of pedagogical potentials in education and metaphysics. Thus, this paper has two-fold purposes. Firstly, this paper seeks to revisit the SCT from Islamic perspectives. Secondly, it attempts to propose a new pedagogical framework adapted from both theories for enhancing classroom teaching and learning. For this, the theoretical approach of Abdullah Nashih Ulwan has been compared and contrasted with an analytical approach by framing the references of the theory and the domain in education and well-being. Based on the analytic summary, this research has adopted comparative holistic visual representation by analyzing the SCT and Islamic perspectives. In consequence, a proposed learning model is given for a comprehensive view from both perspectives. The findings will advocate teachers and researchers when dealing with holistic human behaviour and personality development.
Trends of Values Education Research in Turkey: A Content Analysis of Published Articles
Authors: Yazar Taha , Tutal Özgür
Published: October 2020

In recent years there has been a large increase in the number of research that deal with values education in Turkey. There are several reviews to determine the trends of these studies. However, these reviews were mostly limited to theses, dissertations and proceedings, and it is necessary to review articles on values education. The data of the research conducted with the qualitative research method was gathered by document analysis. 479 articles were included in the research after duplicates and the articles published in non-refereed journals were removed. Content analysis was used to analyze the obtained data. According to the findings of the research; (a) the highest number of articles were published in 2017, (b) qualitative research methods were the most common research methods, (c) most frequently document analysis was preferred as the data collection tool, and content analysis was preferred as the analysis method, (d) data were collected from pre-service teachers the most and purposeful sampling was the most favored sampling method, (e) the sample size is mostly less than 50, (f) mostly the answer to a single research question was sought, (g) the majority of articles were written by two authors, (h) most articles were written by assistant professors as titles and by teachers of the Ministry of National Education on an institutional basis, (i) the articles mostly used domestic sources (j) the majority of the articles were written in Turkish and had not an English extended summary, (k) the most favored journal was The Journal of Values Education.
HEDGES EXPRESSIONS IN CONFESSIONAL DISCOURSE OF IDA CRADDOCK’S SUICIDE NOTES
Authors: Bahar Rizkya Fajarani , Ariyanti Lisetyo
Published: October 2020

Some people commited suicide tried to express what they felt and left message explaining the causes of why they committed suicide. The suicide note was written by the person who commited suicide as a purpose to give a sign to other people. One of those people was Ida Craddck who was a 19th century American. She advocated freedom of speech and women rights who committed suicide because of inappropriate decision from the judge. Her books were prosecuted by Anthony Comstock as obscene literature. This study was aimed to examine the hedges expressions that maintained the functions of confessional texts which were used by Craddock. The results found that hedges were used on her confessions to support her criticism and wish to the public. Those criticism and wish were confessed by Craddock to aware the public about people’s freedom condition. Her confessions had function to tell her personal story that led her to suicide which could be learnt by other people so that they could have a better life. Finally, hedges were used to express her uncertainty of the truth of what she confessed about her cause of death.
Front-matter
Authors: Armansyah TR Teuku
Published: October 2020

Front-matter
Back-matter
Authors: Armansyah TR Teuku
Published: October 2020

back-matter
Feature-Oriented Joint Time-Lapse Seismic and Electromagnetic History Matching Using Ensemble Methods
Authors: Zhang Yanhui , Hoteit Ibrahim
Published: October 2020

We propose a feature-oriented ensemble history-matching workflow with a focus on the integration of time-lapse seismic and electromagnetic (EM) data. The developed workflow consists of two main steps. First, the rock cross-properties, such as water saturation and porosity relating to both seismic and EM attributes, are estimated by joint inversion of seismic and EM data using an iterative ensemble smoother (ES). Second, the remaining model parameters of interest, such as permeability, are calibrated using the updated cross-properties. To assimilate the inverted-saturation information efficiently, we take a feature-oriented integration approach in which front positions are identified from the inverted-saturation field. Related model parameters are then conditioned to the interpreted fronts using the iterative ES with a distance parameterization. The novelty of the proposed approach consists of combining the feature-oriented history matching with ensemble-based geophysical inversion to achieve an efficient joint integration of multiple sources of geophysical data. The performance of the proposed history-matching workflow is examined using a 2D channelized reservoir model and a more-realistic 3D reservoir model with a crosswell configuration for seismic and EM surveys. It is demonstrated that the developed workflow provides a novel and effective way to calibrate reservoir models with multiple sources of geophysical data. The experimental results show a positive synergy effect on the characterization of model variables by jointly assimilating seismic and EM data.
Wearable Hip-assist Robot Modulates Cortical Activation during Gait in Stroke Patients: A Functional Near-Infrared Spectroscopy Study
Authors: Lee Su-Hyun , Lee Hwang-Jae , Shim Youngbo , Chang Won Hyuk , Choi Byung-Ok , Ryu Gyu-Ha , Kim Yun-Hee
Published: October 2020

Background Gait dysfunction is common in post-stroke patients as a result of impairment in cerebral gait mechanism. Powered robotic exoskeletons are promising tools to maximize neural recovery by delivering repetitive walking practice. Objectives The purpose of this study was to investigate the modulating effect of the Gait Enhancing and Motivating System-Hip (GEMS-H) on cortical activation during gait in patients with chronic stroke. Methods. Twenty chronic stroke patients performed treadmill walking at a self-selected speed either with assistance of GEMS-H (GEMS-H) or without assistance of GEMS-H (NoGEMS-H). Changes in oxygenated hemoglobin (oxyHb) concentration in the bilateral primary sensorimotor cortex (SMC), premotor cortices (PMC), supplemental motor areas (SMA), and prefrontal cortices (PFC) were recorded using functional near infrared spectroscopy. Results Walking with the GEMS-H promoted symmetrical SMC activation, with more activation in the affected hemisphere than in NoGEMS-H conditions. GEMS-H also decreased oxyHb concentration in the late phase over the ipsilesional SMC and bilateral SMA (P < 0.05). Conclusions The results of the present study reveal that the GEMS-H promoted more SMC activation and a balanced activation pattern that helped to restore gait function. Less activation in the late phase over SMC and SMA during gait with GEMS-H indicates that GEMS-H reduces the cortical participation of stroke gait by producing rhythmic hip flexion and extension movement and allows a more coordinate and efficient gait patterns. Clinical trial registration NCT03048968. Registered 06 Feb 2017.
Expanding Medical Student Interaction In Neurology With A Redesigned Student Interest Group In Neurology (Sign) Chapter
Authors: Gummi Rohit , Smith Ross , Govindarajan Raghav
Published: October 2020

Background: Student Interest Group in Neurology (SIGN) chapters across the medical schools in the United States provide opportunities for medical students to participate in clinical, research, and service activities in neurology. Despite these, applicants for the field of neurology have traditionally been low.Methods: Following changes were introduced: an open board style SIGN chapter executive committee with greater active engagement of first and second year students. New activities included journal clubs, hands on workshops, celebration/cause events (example ALS walk). In addition, a free neurology clinic was introduced. Activities were planned in consultation with office of medical education, and were organized during ‘down times’. Data on student enrollment, activities successfully carried out, students interested in neurology residency, number of neurology-related research projects with student involvement were collected prior to changes and compared to values after changes were introduced.Results: Post intervention, student engagement in neurology activities and projects increased significantly. However, a similar increase in applications to neurology residency was not yet observed.Conclusions: An open chapter with early engagement and involvement of first and second year medical students, creating a variety of chapter activities with greater hands on involvement, planned in conjunction with office of medical education has reinvigorated our SIGN chapter.
Prognostic value of the ALBI grade among patients with single hepatocellular carcinoma without macrovascular invasion
Authors: Chen Wenhao , Zhang Zijian , Wang Huan , Xiong Li , Wen Yu , Zhou Jiangjiao , Kong Fanhua , Zou Heng
Published: October 2020

Background: Although evidence for the application of albumin–bilirubin (ALBI) grading system to assess liver function in hepatocellular carcinoma (HCC) is available, less is known whether it can be applied to determine the prognosis of single HCC with different tumor sizes. This study aimed to address this gap.Methods: Here, we enrolled patients who underwent hepatectomy due to single HCC from the year 2010 to 2014. Analyses were performed to test the potential of ALBI grading system to monitor the long-term survival of single HCC subjects with varying tumor sizes.Results: Overall, 265 participants were recruited. The overall survival (OS) among patients whose tumors were ≤ 7 cm was remarkably higher compared to those whose tumors were > 7 cm. The Cox proportional hazards regression model identified the tumor differentiation grade, ALBI grade, and maximum tumor size as key determinants of the OS. The ALBI grade could stratify the patients who had a single tumor ≤ 7 cm into two distinct groups with different prognoses. The OS between ALBI grades 1 and 2 was comparable for patients who had a single tumor > 7 cm.Conclusions: We show that ALBI grading system can predict disease outcomes of single HCC patients with tumor size ≤ 7 cm. However, the ALBI grade may not predict capability the prognosis of patients with single tumor > 7 cm.
Quantitative dynamic contrast-enhanced MR imaging can be used to predict the pathologic stages of oral tongue squamous cell carcinoma
Authors: Guo Na , Zeng Weike , Deng Hong , Hu Huijun , Cheng Ziliang , Yang Zehong , Jiang Shuqi , Duan Xiaohui , Shen Jun
Published: October 2020

Background: To investigate whether quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) pharmacokinetic parameters can be used to predict the pathologic stages of oral tongue squamous cell carcinoma (OTSCC). Methods: For this prospective study, DCE-MRI was performed in participants with OTSCC from May 2016 to June 2017. The pharmacokinetic parameters, including K trans , K ep , V e , and V p , were derived from DCE-MRI by utilizing a two-compartment extended Tofts model and a three-dimensional volume of interest. The postoperative pathologic stage was determined in each patient based on the 8th AJCC cancer staging manual. The quantitative DCE-MRI parameters were compared between stage I-II and stage III-IV lesions. Logistic regression analysis was used to determine independent predictors of tumor stages, followed by receiver operating characteristic (ROC) analysis to evaluate the predictive performance. Results: The mean K trans , K ep and V p values were significantly lower in stage III-IV lesions compared with stage I-II lesions ( p = 0.013, 0.005 and 0.011, respectively). K ep was an independent predictor for the advanced stages as determined by univariate and multivariate logistic analysis. ROC analysis showed that K ep had the highest predictive capability, with a sensitivity of 64.3%, a specificity of 82.6%, a positive predictive value of 81.8%, a negative predictive value of 65.5%, and an accuracy of 72.5%. Conclusion: The quantitative DCE-MRI parameter K ep can be used as a biomarker for predicting pathologic stages of OTSCC.
Factors associated with the Uptake of Immediate Postpartum Intrauterine Contraceptive Devices(PPIUCD) in Rwanda: A Mixed Methods Study
Authors: Kanakuze Chris Adrien , Dan Kaye K , Musabirema Priscilla , Pascal Nkubito , Mbalinda Scovia Nalugo
Published: October 2020

Background: Rwanda has a high unmet need for family planning which could be reduced by improving access to postpartum intrauterine contraceptives device (PPIUCD) insertion. The objective of the study was to assess the prevalence and factors associated with the uptake of PPIUCD among postpartum women in Muhima Hospital.Methods: A concurrent mixed-method study was used. Three hundred eight three (383) immediate postpartum mothers, and 10 health services providers were interviewed using a structured questionnaire and in-depth interviews respectively. Logistics regression was done to assess for factors associated with PPIUCD uptake and thematic analysis was used for qualitative data.Results: The prevalence for PPIUCD use was 28.1% , women who had spontaneous vaginal delivery were more likely to take up PPIUCD (Adjusted Odds Ratio (AOR) 2.623, 95%CI=2.017-6.507 compared to those who had cesarean section; women who received PPIUCD counselling during the antenatal period were more likely to use PPIUCD ((AOR 2.072, 95%CI=1.018-4.218) as compared to those who didn’t receive any form of counselling; mothers who received spouse approval were more likely to use PPIUCD (AOR 2.591,95%CI= 1.485-4.492); as compared to those who didn’t receive any spousal approval; women who had more than one child were more likely to use PPIUCD (AOR =2.265, 95%CI=1.472-3.163) as compared to prime gravida; Mothers with birth to pregnancy interval less than two years were more likely to use PPIUCD (AOR =2.123, CI =1.477-2.706) as compared to those who had birth to pregnancy interval more than 2 years. From the qualitative findings, health education of mothers and partners on PPIUCD, training of health care providers, and availability of supplies to provide PPIUCD influenced the use of PPIUCD. Conclusion: The acceptability to use for PPIUCD was high in this population. PPIUCD uptake was associated with normal birth, PPIUCD counselling, spousal approval, parity, birth interval, level of education. Health education of mothers and partners on PPIUCD, training of health providers, and availability of supplies to provide PPIUCD influenced uptake of PPIUCD.
Assessment of the susceptibility status of Aedes aegypti (Diptera: Culicidae) populations to pyriproxyfen and malathion in a nation-wide monitoring of insecticide resistance performed in Brazil from 2017 to 2018.
Authors: Campos Kauara Brito , Martins Ademir Jesus , Rodovalho Cynara de Melo , Bellinato Diogo Fernandes , Dias Luciana dos Santos , Macoris Maria de Lourdes da Graça , Andrighetti Maria Teresa Macoris , Lima José Bento Pereira , Obara Marcos Takashi
Published: October 2020

Background: Chemical mosquito control using malathion has been applied in Brazil since 1985. To obtain chemical control effectiveness, vector susceptibility insecticide monitoring is required. This study aimed to describe bioassay standardizations and determine the susceptibility profile of Ae. aegypti populations to malathion and pyriproxyfen, used on a national scale in Brazil between 2017 and 2018, and discuss the observed impacts in arbovirus control. Methods: The diagnostic-doses (DD) of pyriproxyfen and malathion were determined as the double of adult emergence inhibition (EI) and lethal doses for 99% of the Rockefeller reference strain, respectively. To monitor natural populations, samplings were performed in 132 Brazilian cities, through egg traps. Colonies were raised in the laboratory for one or two generations (F1 or F2) and submitted to susceptibility tests, where larvae were exposed to the pyriproxyfen DD (0.03 µg/L) and adults, to the malathion DD determined in the present study (20 µg), in addition to the one established by the World Health Organization (WHO) DD (50 µg) in a bottle assay. Dose-response (DR) bioassays with pyriproxyfen were performed on populations that did not achieve 98% EI in the DD assays. Results: Susceptibility alterations to pyriproxyfen were recorded in six (4.5%) Ae. aegypti populations from the states of Bahia and Ceará, with Resistance Ratios (RR95) ranging from 1.51 to 3.58. Concerning malathion, 73 (55.3%) populations distributed throughout the country were resistant when exposed to the local DD 20µg/bottle. On the other hand, no population was resistant, and only 10 (7.6%) populations in eight states were considered as exhibiting decreased susceptibility (mortality ratios between 90 and 98%) when exposed to the WHO DD (50 µg/bottle). Conclusions: The feasibility of conducting an insecticide resistance monitoring action on a nation-wide scale was confirmed herein, employing standardized and strongly coordinated sampling methods and laboratory bioassays. Brazilian Ae. aegypti populations exhibiting decreased susceptibility to pyriproxyfen were identified. The local DD for malathion was more sensitive than the WHO DD for early decreased susceptibility detection.
Association of VEGF Haplotypes with Breast Cancer Risk in North-West Indians
Authors: Sambyal Vasudha , Guleria Kamlesh , Kapahi Ruhi , Manjari Mridu , Sudan Meena , Uppal Manjit Singh , Singh Neeti Rajan
Published: October 2020

Background: Angiogenesis is a complex and coordinated process regulated by different growth factors and is one of the hallmark features of cancer. VEGF is one of the most important endothelial cell mitogen and has a critical role in normal physiological and tumor angiogenesis. The objective of this study was to investigate the potential association of haplotypes of six VEGF polymorphisms with breast cancer risk in North-West Indians. Methods: Samples of 250 breast cancer patients and 250 age and gender matched controls were genotyped for VEGF -2578C/A, -2549I/D, -460T/C, +405C/G, -7C/T and +936C/T polymorphisms. Haplotypes were generated to determine the better contribution of VEGF polymorphisms to breast cancer risk. Results: Haplotypes CDTCCC (OR = 0.56, 95%CI, 0.38-0.81; p = 0.003) and CDTGCC (OR = 0.63, 95%CI, 0.44-0.92; p = 0.018) of VEGF -2578C/A, -2549I/D, -460T/C, +405C/G, -7C/T and +936C/T polymorphisms were significantly associated with decreased risk of breast cancer. CDTCCC haplotype was also significantly associated with reduced risk of breast cancer in pre and post menopausal as well as both obese and non obese patients. Haplotype CDTGCC was marginally associated (p = 0.07) with reduced risk of breast cancer in non-obese patients as compared with non-obese controls where as haplotype AICGTC was marginally associated (p = 0.09) with reduced risk of breast cancer in obese patients when compared with non-obese patients. The CDTGCC haplotype was significantly associated with increased risk of breast cancer in premenopausal obese patients (OR = 1.98, 95%CI, 1.10-3.56; p = 0.02). Conclusions: Our data indicated that CDTCCC and CDTGCC haplotypes of VEGF -2578C/A, -2549I/D, -460T/C, +405C/G, -7C/T and +936C/T polymorphisms were significantly associated with breast cancer risk in North-West Indians. Further studies on multiethnic groups with larger sample size are required to confirm our results.
Effect of Controlled Hypertension on Hemostasis Before Closure of the Operative Incision in Patients Undergoing Vertical Partial Laryngectomy: A Randomized Controlled Study
Authors: Fu Danyun , Pan Yiting , Fan Qing , Guo Ying , Zhang Ming
Published: October 2020

Background: To evaluate the efficacy of controlled hypertension on hemostasis before closure of the operative incision in vertical partial laryngectomy (VPL).Methods: Seventy males scheduled for VPL were randomly assigned to Group H who received either ephedrine or phenylephrine to maintain a mean arterial pressure (MAP) of 90–110 mmHg 10 min before the operative incision closure or to Group N who received normal saline. The primary endpoint was the volume of drainage after surgery. Heart rate, MAP, surgical field bleeding score before and after drug administration, the amount of liquid administered, operation and recovery durations were recorded. Heart rate, MAP, incisional bleeding score, coughing score, nausea and vomiting score, and frequency of bloody sputum aspiration were also recorded when the patient left the postanesthesia care unit and at 6 and 24 hours postoperatively.Results: The intraoperative bleeding score of the surgical field was significantly higher in patients receiving vasopressor. The volume of drainage in control group was more than that in Group H at different time points after surgery. Compared with Group N, Group H had a significantly lower incisional bleeding score and frequency of bloody sputum aspiration at all time-points after surgery, and a significantly lower nausea and vomiting score at 6 and 24 hours postoperatively. Conclusion: Controlled hypertension (MAP 90–110 mmHg) before wound closure may be used as an alternative way to detect intraoperative bleeding points in patients undergoing VPL, which also decreased the postoperative volume of drainage and the incidences of nausea and vomiting.Trial registration: The China Clinical Research Information Service (registration number, ChiCTR1900026097). Registered 21 September 2019, http://www.chictr.org.cn/showproj.aspx?proj=37850
Identification of key target genes and pathway analysis in nonalcoholic fatty liver disease via integrated bioinformatics analysis
Authors: Chen Xi , Zhang Lian , Wang Yanyan , Li Ruien , Yang Ming , Gao Lei
Published: October 2020

Background
This study aimed to explore the mechanisms underlying nonalcoholic fatty liver disease (NAFLD) and develop new diagnostic biomarkers for nonalcoholic steatohepatitis (NASH).
Methods
The microarray dataset GES83452 was downloaded from the NCBI-GEO database, and the differentially expressed RNAs (DERs) were screened between the NAFLD and non-NAFLD samples of the baseline and 1-year follow-up time point group based on the Limma package. Subsequently, the lncRNA–miRNA–mRNA regulation network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on the regulated target genes in the ceRNA regulatory network were performed based on DAVID. Finally, PharmGKB database was used to search for the gene-related drug molecules, and the gene–drug connection network was constructed.
Results
A total of 561 DERs (268 downregulated and 293 upregulated) were screened in the baseline time point group, and 1163 DERs (522 downregulated and 641 upregulated) were screened in the 1-year follow-up time point group. A total of 74 lncRNA–miRNA pairs and 523 miRNA–mRNA pairs were obtained to construct lncRNA–miRNA–mRNA regulatory network. Subsequently, functional enrichment analysis revealed 28 GO and 9 KEGG pathways in the ceRNA regulatory network. LEPR and CXCL10 are involved in the Cytokine–cytokine receptor interaction (P = 1.86E-02), and the FOXO1 is involved in both the Insulin signaling pathway (P = 1.79E-02) and the pathways in cancer (P = 2.87E-02).
Conclusion
LEPR, CXCL10, and FOXO1 were the characteristic target genes for NAFLD.
The Pathogenesis of Proventricular Dilatation Disease Caused by Parrot Bornaviruses: A Possible Role For Neuropeptide Y (Npy)
Authors: Chen Jingshu , Guo Jianhua , Tian Yanan , Tizard Ian
Published: October 2020

Background

Psittacine Bornaviruses cause a unique disease syndrome in parrots and related birds. Known as proventricular dilatation disease (PDD), it is characterized by massive dilatation of their proventriculus as a result of excessive food accumulation within that organ. This leads to gastric obstruction and eventually, to death by starvation.
Results

In a preliminary study on the transcriptome of psittacine bornavirus-infected human astroglia it was noted that the gene encoding neuropeptide Y was significantly upregulated. In a subsequent study of cockatiels experimentally infected with the same strain of psittacine bornavirus, their brains were examined by RNA-seq to determine which genes were being actively transcribed. It was confirmed that among the genes whose expression was significantly increased relative to control, uninfected birds was that for neuropeptide Y.
Conclusions

Neuropeptide Y is known to cause overeating in birds. We hypothesize therefore that the clinical manifestations of proventricular dilatation disease are a result of the excessive production of neuropeptide Y by bornavirus-infected brain cells acting in association with damage to the neurons of the proventricular myenteric plexus.
Outcome Following Local Injection of A Liquid Amnion Allograft for Treatment of Equine Tendonitis or Desmitis – 100 Cases.
Authors: Duddy Hugh R , Schoonover Mike J , Hague Brent A
Published: October 2020

Background: Tendon and ligament injuries are significant causes of loss of use and early retirement in performance horses. Amniotic fluid and tissue are excellent sources of growth factors and cytokines important in tendon and ligament healing. Thus, a liquid amnion allograft (LAA) may be beneficial in the treatment of equine tendonitis and desmitis. Objectives: Report the outcome achieved (i.e. ability to return to work) for horses diagnosed with tendonitis or desmitis lesions treated with local injection of LAA and to compare these outcomes to those reported for other regenerative medicine modalities.Study design: Prospective, multi-center, non-blinded clinical trial.Methods: Equine veterinarians at 14 sites were selected to participate in the data collection for the trial. Criterion for inclusion was a horse presenting with lameness which was attributed to tendonitis or desmitis by diagnostic anesthesia and/or imaging. These horses were subsequently treated by local injection of the lesion with LAA by the attending veterinarian. Standardized questionnaires describing each horse’s signalmant, discipline, ability to return to work, and any adverse events were completed and submitted by the attending veterinarian following a minimum of six months follow-up.Results: Questionnaires for 100 horses with 128 tendonitis and desmitis lesions met the inclusion criteria. Of these, 72 horses with 94 lesions returned to or exceeded their original level of work, 10 horses with 13 lesions returned to work but could not perform to previous standards, and 18 horses with 20 lesions did not return to work as a result of the injury. The attending veterinarian for 92 horses reported satisfaction with the LAA and the response to therapy. Adverse events following administration of LAA were reported in 13 horses. Conclusions: Treatment of tendonitis and desmitis lesions by local injection of LAA achieves a similar rate of horses returning to previous level of performance as other regenerative modalities such as mesenchymal stem cells, platelet-rich plasma, and autologous conditioned serum; however, blinded placebo-controlled studies are indicated.
Associated Risk Factors and Prevalence of Sleep Disorders in Patients With Rheumatoid Arthritis.
Authors: Santos-Moreno Pedro , Castro Carlos Alberto , Villarreal Laura , Sánchez-Vanegas Guillermo
Published: October 2020

Background: Rheumatoid arthritis (RA) is an autoimmune chronic pathology, present in between 0.5% and 1% of adults. This disease is accompanied by comorbidities such as sleep disorders (SD) that occur in between 54% and 70% of the population with RA. The objective of this study was to identify the associated risk factors and the prevalence of sleep disorders in a group of patients with rheumatoid arthritis in a referral center for the management of autoimmune diseases in Bogotá, Colombia.Methods: An analytical cross-sectional study was carried out on a population of patients with Rheumatoid Arthritis (RA) evaluated with the DSM-V. The factors related to sleep disorders and disease activity of were explored. The prevalence of sleep disorders was determined, and a multivariate logistic regression analysis was conducted.Results: the study analyzed a total of 1436 patients, with a median age of 56 years. The prevalence of sleep disorders was 31.1%. There was an association between the presence of sleep disorders and Disease Activity Score 28 (DAS28) (OR: 3.8 CI 95%: 3-5), Health Assessment Questionnaire (HAQ) (OR: 3.2 CI 95%: 2.5-4.1), self-care activities (OR: 0.6 CI 95%: 0.4-0.9), and somatic symptom disorder (OR: 1.8, CI 95%: 1.3-2.6). Conclusions: An association (p-value <0.05) was found between SDs and disease activity (DAS28), functional capacity (HAQ), scholarship level, smoking, sedentary lifestyle, metabolic diseases, and leisure and self-care activities. In one third of patients SD were prevalent. It is suggested that patients be approached comprehensively carrying out behavioral and cognitive activities.
An Association Study of Candidate Gene Variants in Chinese Nonsyndromic Cleft Lip with or without Palate Subjects
Authors: Niu Zhenmin , Peng Li , Chen Jiapei , Wan Teng , Wu Dandan , Yang Yusheng , Wang Guomin , Yang Lin , Huang Wei , Chen Zhenqi
Published: October 2020

Background: Nonsyndromic cleft lip with or without palate is a common birth defect of complex etiology involving the interaction of genetic factors and environmental exposures. Previous reports identified several candidate genes and risk variants of the disease, and their functions were verified by model animal studies. Methods: In order to depict the composition of the orofacial cleft susceptibility loci in Chinese population, we genotyped ten common SNPs of six genes (VAX1, MAFB, PAX7, ABCA4, NTN1 and NOG) in 249 nonsyndromic cleft lip with or without palate individuals, 62 nonsyndromic cleft palate only individuals and 480 controls. Results: Three loci: VAX1 rs7078160, MAFB rs11696257 and NTN1 rs4791774 showed significant relevance with NSCL/P. Carrying both VAX1 rs7078160 and NTN1 rs4791774 further increased the risk, compared with carrying only one of them. Conclusions: This result supported that SNPs of genes VAX1, MAFB and NTN1 are associated with NSCL/P in Chinese subjects.
Cell-Free DNA and Circulating Tumor Cell Kinetics in a Pre-Clinical Head and Neck Cancer Model Undergoing Radiation Therapy
Authors: Muhanna Nidal , Eu Donovan , Chan Harley HL , Douglas Catriona , Townson Jason , Grappa Marco A Di , Mohamadi Reza M , Kelley Shana O. , Bratman Scott V , Irish Jonathan C
Published: October 2020

Background: Monitoring circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), known as liquid biopsies, continue to be developed as diagnostic and prognostic markers for a wide variety of cancer indications, mainly due to their minimally invasive nature and ability to offer a wide range of phenotypic and genetic information. While liquid biopsies maintain significant promising benefits, there is still limited information regarding the kinetics of ctDNA and CTCs following radiation therapy which remains a vital treatment modality in head and neck cancers. This study aims to describe the kinetics of ctDNA and CTCs following radiation exposure in a preclinical rabbit model with VX2 induced buccal carcinoma. Methods: Seven rabbits were inoculated with VX2 cells in the buccal mucosa and subjected to radiation. At selected time points, blood sampling was performed to monitor differing levels of ctDNA and CTC. Plasma ctDNA was measured with quantitative PCR for papillomavirus E6 while CTCs were quantified using an immunomagnetic nanoparticles within a microfluidic device. Comparisons of CTC detection with EpCAM compared to multiple surface markers (EGFR, HER2 and PSMA) was evaluated and correlated with the tumor size.Results: Plasma ctDNA reflects the overall tumor burden within the animal model. Analysis of correlations between ctDNA with tumor and lymph node volumes showed a positive correlation (R= 0.452 and R = 0.433 [p <0.05]), respectively. Over the course of treatment, ctDNA levels declined and quickly becomes undetectable following tumor eradication. While during the course of treatment, ctDNA levels were noted to rise particularly upon initiation of radiation following scheduled treatment breaks. Levels of CTCs were observed to increase 1 week following inoculation of tumor to the primary site. For CTC detection, the use of multiple surface markers showed a greater sensitivity when compared to detection using only EpCAM. Plasma CTC levels remained elevated following radiation therapy which may account for an increased shedding of CTCs following radiation.Conclusion: This study demonstrates the utility of ctDNA and CTCs detection in response to radiation treatment in a preclinical head and neck model, allowing for better understanding of liquid biopsy applications in both clinical practice and research development.
Rare and Potentially Pathogenic Variants in Hydroxycarboxylic Acid Receptor Genes Identified in Breast Cancer Cases.
Authors: Sams Cierla McGuire , Shepp Kasey , Pugh Jada , Bishop Madison R. , Merner Nancy D.
Published: October 2020

BackgroundThree genes, clustered together on chromosome 12, comprise a group of Hydroxycarboxylic Acid Receptors (HCARs), HCAR1, HCAR2, and HCAR3. These paralogous genes encode different G-protein coupled receptors that are responsible for detecting glycolytic metabolites and controlling fatty acid oxidation. Though better known for regulating lipid metabolism in adipocytes, more recently HCARs have been functionally associated with breast cancer proliferation/survival; HCAR2 has been described as a tumor suppressor, and HCAR1 and HCAR3 as oncogenes. Thus, we sought to identify genetic variants in HCAR1, HCAR2, and HCAR3 that could potentially be associated with breast cancer. MethodsDue to the extreme homology between HCAR1, HCAR2, and HCAR3, primers were carefully designed to amplify each gene separately through nested PCRs followed by Sanger sequencing. Forty-six unrelated breast cancer cases were screened for rare, non-synonymous coding variants. ResultsUpon screening, a total of four variants were identified in four different cases, each with estrogen receptor-positive (ER+) breast cancer. The variants were identified exclusively in HCAR1 and HCAR3. In HCAR1, two highly conserved and potentially damaging missense variants were identified, c.58C>G;p.Pro20Ala and c.721C>T;p.Leu241Phe. Statistical analyses revealed that c.58C>G;p.Pro20Ala was in significantly more cases than controls. In HCAR3, in addition to the breast cancer-associated missense variant c.560G>A;p.Arg187Gln, a frameshift mutation, c.1117delC;p.Gln373Lysfs*82, was detected that greatly extends the C-terminus and changes the secondary and tertiary protein structure. ConclusionsDue to the important role of HCARs in breast cancer, it is vital to understand how these genetic variants play a role in breast cancer risk and proliferation, as well as their consequences on treatment strategies. Due to the small sample size, additional and larger studies will be needed to validate these findings. Nevertheless, the identification of these potentially pathogenic variants supports the need to investigate their functional consequences.
Identification of repurposable cytoprotective drugs in Vanishing White Matter Disease patient-derived cells
Authors: Ng Neville , Cabral-da-Silva Mauricio Castro , Maksour Simon , Berg Tracey , Engel Martin , Silva Dina M. , Do-Ha Dzung , Lum Jeremy S. , Muñoz Sonia Sanz , Suarez-Bosche Nadia , Stevens Claire H. , Ooi Lezanne
Published: October 2020

Background Vanishing white matter disease (VWMD) is a rare leukodystrophy caused by mutations of the guanine exchange factor eIF2B. VWMD typically presents with juvenile onset, and there are few treatments for the disease. Recent progress in the field has established mitochondrial dysfunction and endoplasmic reticulum (ER) stress to be strongly implicated in observed glial cell pathology. Drug repurposing offers a rapid approach toward translation of therapeutics using already-licensed drugs. Objective The aim of this study was to use fibroblasts and induced pluripotent stem cell (iPSC)-derived astrocytes from patients bearing the EIF2B5R113H/A403V or EIF2B2G200V/E213G VWMD mutations to identify potentially repurposable FDA-approved drugs based on in vitro assays. Methods Cell viability in the presence or absence of stress was assessed by resazurin reduction activity and assays for mitochondrial membrane potential, and oxidative stress. Integrated stress response markers, including eIF2α phosphorylation, GADD34 and CHOP were quantified by fluorescent western blot. Results Dysregulated GADD34 and CHOP were identified in patient fibroblasts and iPSC-derived astrocytes under induced stress conditions. A drug screen from a 2,400 FDA-approved drug library with EIF2B5R113H/A403V VWMD patient fibroblasts identified 113 anti-inflammatory drugs as a major class of hits with cytoprotective effects. A panel of potential candidate drugs, including berberine, deflazacort, ursodiol, zileuton, guanabenz and Anavex 2-73, and preclinical ISRIB, increased cell survival of EIF2B5R113H/A403V or EIF2B2G200V/E213G VWMD astrocytes, and were further investigated for their effect on the integrated stress response and mitochondrial stress. Ursodiol demonstrated capacity to ameliorate oxidative stress and loss of mitochondrial membrane potential in VWMD patient iPSC-derived astrocytes in the presence or absence of stress conditions. Conclusion Patient-derived cells can be used to identify cellular phenotypes and for large-scale drug screening. Anti-inflammatory compounds, such as berberine, deflazacort, ursodiol and zileuton are potentially repurposable drug candidates for VWMD that should be further investigated for translation in vivo.
De novo profiling of long non-coding RNAs involved in MC-LR–induced liver injury in whitefish: discovery and perspectives
Authors: Florczyk Maciej , Brzuzan Paweł , Woźny Maciej
Published: October 2020

BackgroundMicrocystin-LR (MC-LR) is a potent hepatotoxin for which a substantial gap in knowledge persists regarding the underlying molecular mechanisms of liver toxicity and injury. Although long non-coding RNAs (lncRNAs) have been extensively studied in model organisms, and their roles have been identified in various cellular processes including participation in regulation of gene expression together with microRNAs, our knowledge concerning the role of lncRNAs in liver injury is limited even in mammals. Given that lncRNAs show low levels of sequence conservation, their role becomes even more unclear in non-model organisms without an annotated genome, like whitefish (Coregonus lavaretus). The objective of this study was to discover and profile aberrantly expressed polyadenylated lncRNAs that are involved in MC-LR–induced liver injury in whitefish.ResultsUsing polyA-enriched RNA-Seq data, we de novo assembled a high quality whitefish liver transcriptome. This enabled us to find 94 differentially expressed (DE) putative evolutionary-conserved lncRNAs (orthologous to known lncRNAs in other species), such as MALAT1, HOTTIP, HOTAIR or HULC and 4,429 DE putative novel whitefish lncRNAs, which differed from annotated protein-coding transcripts (PCTs) in terms of minimum free energy, GC base-pair content and length. Additionally, we identified DE non-coding transcripts that might be 3’ autonomous untranslated regions of mRNAs (3’UTRs). We found that, in response to MC-LR treatment, these potential 3’UTRs could either be coexpressed with PCTs from the same mRNA, or the 3’UTRs were upregulated while the corresponding PCTs were downregulated, suggesting 3’UTR-dependent gene regulation.ConclusionsTo our knowledge this is the first report on aberrantly expressed lncRNAs in MC-LR–induced liver injury in whitefish. We found both evolutionary conserved lncRNAs as well as novel whitefish lncRNAs that could serve as biomarkers of severe and chronic liver injury. The lncRNA sequence data files and raw sequence files are available in the Dryad Digital Repository and the NCBI Sequence Read Archive, respectively.
Sustainable Development in the Wake of Covid-19
Authors: Nerini Francesco Fuso , Henrysson Maryna , Swain Ashok , Swain Ranjula Bali
Published: October 2020

The ´decade of action´ to achieve the ambitious 17 Sustainable Development Goals by 2030 is off to a very challenging start. With progress on the achievement of most SDGs already lagging behind even before the Covid-19 crisis – our analysis finds that the pandemic negatively affects the achievement of 144 targets (almost 90%) of the SDGs. However, 66 targets (ca. 40%) could potentially benefit from the changes spurred by the crisis, given that the appropriate decisions are made. Holistic response and leadership are needed to ensure an inclusive economic recovery while protecting the environment. Furthermore, our analysis of the literature documents the unprecedented speed of the international community to assess the impacts of the pandemic. Future research should gather data to better understand the impacts of the pandemic locally and globally, and produce long-term analyses to inform the sustainable recovery across all SDGs.
Genome-Wide DNA Methylation Variations Between Grass Carp with Different Ages
Authors: He Libo , Zhu Denghui , Chu Pengfei , Li Yongming , Liao Lanjie , Huang Rong , Zhu Zuoyan , Wang Yaping
Published: October 2020

Background: Grass carp is an important farmed fish in China that infected by many pathogens, especially grass carp reovirus (GCRV). Notably, grass carp showed age-dependent susceptibility to GCRV, while the mechanism remains unclear. Herein, we performed a genome-wide survey of differences in DNA methylation and gene expression between five months old grass carp (FMO, sensitive to GCRV) and three years old grass carp (TYO, resistant to GCRV) aim to uncover the mechanism.Results: Colorimetric quantification revealed global methylation level of TYO fish was higher than that of FMO fish. Whole-genome bisulfite sequencing (WGBS) of two groups revealed 6,214 differentially methylated regions (DMRs) and 4,052 differentially methylated genes (DMGs), with most of DMRs and DMGs showed hypermethylation patterns in TYO fish. Correlation analysis indicated that DNA hypomethylation in promoter negative correlated with gene expression, whereas positive correlation was found between gene-body DNA hypermethylation and gene expression. Enrichment analysis revealed that promoter hypo-DMGs in TYO fish were significant enriched in pathways involved in immune response while gene-body hyper-DMGs in TYO fish were significant enriched in terms related to RNA transcription, biosynthetic, and energy production. RNA-seq indicated these terms or pathways involved in immune response, biosynthetic, and energy production also significant enriched for the up-regulated genes in TYO fish. Conclusions: Collectively, these results revealed the genome-wide DNA methylation variations between grass carp with different ages. DNA methylation and gene expression variations in genes involved in immune response, biosynthetic, and energy production may contributed to the age-dependent susceptibility to GCRV in grass carp. Our results will provide important information for the disease-resistant breeding programs of grass carp and may also benefit to the research of age-dependent diseases in human.