bluuebunny/crossref_metadata_2025 huggingface dataset:
The PHA4GE SARS-CoV-2 Contextual Data Specification for Open Genomic Epidemiology
Authors: Griffiths Emma J. , Timme Ruth E. , Page Andrew J. , Alikhan Nabil-Fareed , Fornika Dan , Maguire Finlay , Mendes Catarina Inês , Tausch Simon H. , Black Allison , Connor Thomas R. , Tyson Gregory H. , Aanensen David M. , Alcock Brian , Campos Josefina , Christoffels Alan , Gonçalves da Silva Anders , Hodcroft Emma , Hsiao William W.L. , Katz Lee S. , Nicholls Samuel M. , Oluniyi Paul E. , Olawoye Idowu B. , Raphenya Amogelang R. , Vasconcelos Ana Tereza R. , Witney Adam A. , MacCannell Duncan R.
Published: August 2020

The Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) is a global coalition that is actively working to establish consensus standards, document and share best practices, improve the availability of critical bioinformatic tools and resources, and advocate for greater openness, interoperability, accessibility and reproducibility in public health microbial bioinformatics. In the face of the current pandemic, PHA4GE has identified a clear and present need for a fit-for-purpose, open source SARS-CoV-2 contextual data standard. As such, we have developed an extension to the INSDC pathogen package, providing a SARS-CoV-2 contextual data specification based on harmonisable, publicly available, community standards. The specification is implementable via a collection template, as well as an array of protocols and tools to support the harmonisation and submission of sequence data and contextual information to public repositories. Well-structured, rich contextual data adds value, promotes reuse, and enables aggregation and integration of disparate data sets. Adoption of the proposed standard and practices will better enable interoperability between datasets and systems, improve the consistency and utility of generated data, and ultimately facilitate novel insights and discoveries in SARS-CoV-2 and COVID-19.
Evaluation of the Severity of Major Depression Using a Voice Index for Emotional Arousal
Authors: Shinohara Shuji , Toda Hiroyuki , Nakamura Mitsuteru , Omiya Yasuhiro , Higuchi Masakazu , Takano Takeshi , Saito Taku , Tanichi Masaaki , Boku Shuken , Mitsuyoshi Shunji , So Mirai , Yoshino Aihide , Tokuno Shinich
Published: August 2020

Recently, the relationship between emotional arousal and depression has been studied. Focusing on this relationship, we first developed an arousal level voice index (ALVI) to measure arousal levels using the Interactive Emotional Dyadic Motion Capture database. Then, we calculated ALVI from the voices of depressed patients from two hospitals (Ginza Taimei Clinic [GTC] and National Defense Medical College hospital [NDMC]) and compared them with the severity of depression as measured by the Hamilton Rating Scale for Depression (HAM-D). Depending on the HAM-D score, the datasets were classified into a no depression (HAM-D<8) and a depression group (HAM-D≥8) for each hospital. A comparison of the mean ALVI between the groups was performed using the Wilcoxon rank-sum test and a significant difference at the level of 10% (p = 0.094) at GTC and 1% (p = 0.0038) at NDMC was determined. The area under the curve (AUC) of the receiver operating characteristic was 0.66 when categorizing between the two groups for GTC, and the AUC for NDMC was 0.70. The relationship between arousal level and depression severity was indirectly suggested via ALVI.
 Twitter Functions in COVID-19 Pandemic and Other Natural Disasters: A Literature Review
Authors: Seddighi Hamed , Salmani Ibrahim
Published: August 2020

Background: Twitter is a major tool for communication in emergencies such as natural disasters. This online social network allows the user to produce content, and it is not designed exclusively for news releases, as opposed to other service providers. Aim: The aim of this study is to investigate Twitter uses in natural disasters and pandemics. Methods: The included studies reported the role of Twitter in natural disasters. The studies that report in settings other than the natural disasters (such as man-made disasters) and other social media were excluded. Electronic databases for a comprehensive literature search including MEDLINE, Web of Science, CINAHL, PsycINFO, Cochrane Register of Controlled Trials (CENTRAL) and EMBASE were used to identify the records that match the mentioned inclusion criteria published till May 2020. The study characteristics were extracted from the qualified studies including year of publication, findings, and geographical location of the study conduct. A narrative synthesis for this literature review was used. Results: The search identified 822 articles of which 780 articles were removed, 256 were not available, 311 papers were not relevant, 16 were duplicated articles, and 197 were non-related to the emergencies. 45 articles met the selection criteria and were included in the review. eleven themes were found in the narrative synthesis including early warning, disseminating information and misinformation, advocacy, personal gains, assessment, various roles of organizations, public mood, geographical analysis, charity, using influencers, and trust. Conclusions: It is recommended that influential individuals be identified in each country and community before disasters occur so that the necessary information can be disseminated in response to disasters. Preventing the spread of misinformation is one of the most important issues in times of disaster, especially pandemics. Disseminating accurate, transparent, and prompt information from relief organizations and governments can help. Also, analyzing Twitter data can be a good source for understanding the mental state of the community, estimating the number of injured people, estimating the points affected by natural disasters, and modeling the prevalence of epidemics. Therefore, various groups such as politicians, the government, non-governmental organizations, aid workers, and the health system can use this information to plan and implement interventions.
Ethnomedicinal Exploration of Plants Utilized by The People of Suryabinayak Municipality in Bhaktapur District, Nepal
Authors: Bhalia Alisha , Shakya Sudarshana , Kunwar Bikram , Baral Bikash , Chaudhary Sujan , Munankarmi Nabin Narayan
Published: August 2020

Ethnomedicine refers to the use of medicinal plants by a society, ethnic group or tribe for health benefits and for the prevention, treatment, and cure of different ailments. The healthy relationship between plants and humans has been continuing since the start of human civilization. The present study aims to document the medicinal information about plants used by ethnic people in different wards of Suryabinyak Municipality, Bhaktapur district, to conserve and utilize the traditional knowledge. Ethnomedicinal data were collected by a Rapid Rural Appraisal (RRA) method such as door to door surveys, direct observation. Individual interviews, field visits, and a questionnaire survey with the guidance of key informants. The present study has documented 107 medicinal plant species under 60 families which are used for prevention and treatment of 39 different diseases like Jaundice, diarrhea, dysentery, and cancer and 46 distinct health benefits like cough, cold, anti-bleeding, stomachache, diarrhea, fever, blood pressure, fracture, toothache, etc. Suryabinayak Municipality has a rich diversity in culture, ethnic groups, and medicinal plants, along with a wide geographic and climatic condition. However, with modernization, urbanization, deforestation, and increasing residential areas, the occurrence and use of medicinal plants have been diminished. Thus, documentation of this research is vital for further pharmaceutical research and enhancement and preservation of traditional knowledge of local people living in Suryabinayak Municipality and Nepal.
KEEFEKTIFAN MODEL PEMBELAJARAN TALKING STICK BERBANTUAN CD PEMBELAJARAN TERHADAP KEMAMPUAN DAYA NALARSISWA
Authors: Lestari Mulyaningrum
Published: August 2020

Tujuan penelitian ini adalah untuk mengetahui keefektifan model pembelajaran talking stick berbantuan CD pembelajaran terhadap kemampuan daya nalar siswa kelas X. Populasi penelitian ini adalah siswa kelas X MA Abadiyah Kuryokalangan Gabus, Pati. Sampel penelitian ini diambil secara cluster random sampling dan terpilihkelas X.C sebagai kelas eksperimen yang menggunakan pembelajaran talking stick berbantuan CD pembelajaran, dan kelas X.D sebagai kelas kontrol yang menggunakan pembelajaran ekspositori. Analisis data meliputi uji normalitas, homogenitas, proporsi, dan perbedaan rerata. Hasil penelitian menunjukkan: 1) hasil kemampuan daya nalar kelas eksperimen dapat mencapai ketuntasan minimal siswa sebesar 88,46 %;2) rata-rata kemampuan daya nalar kelas eksperimen yaitu 78 lebih besar dari kelas kontrol, yaitu 75,30; Saran penelitian ini: model pembelajaran talking stick berbantuan CD pembelajaran dapat digunakan sebagai alternatif dalam pembelajaran materi dimensi tiga.
NILAI ISLAM DALAM TEOREMA PHYTAGORAS
Authors: Romadhon Riski Surya
Published: August 2020

Penelitian bertujuan membuktikan berbagai konsep teori-teori yang ditemukan Phytagoras dengan prinsip-prinsp dalam islam. Jenis penelitian merupakan penelitian kualitatif dengan teknik pengkajian litelatur. Hasil penelitian menunjukkan bahwa prinsip phytagoras yaitu “untuk setiap segitiga siku siku berlaku kuadrat panjang sisi miring sama dengan jumlah kuadrat panjang sisi siku sikunya.”  Dan dapat dituliskan c2 = a2 + b2       .Semakin besar kedua kuadrat sisi siku-sikunya (a dan b) maka semakin besar sisi miringnya. Dalam islam dianjurkan untuk menjaga hablumminallah dan hablumminannas untuk mendapatkan kesuksesan didunia dan di akhirat. Diibaratkan dua sisi siku-siku segitiga tersebut. Jika semakin besar hubungan Allah dan manusia, maka semakin besar pula kesuksesan yang di dapat.
PENGELOLAAN PERILAKU HEMAT ENERGI BERDASARKAN WARNA PINTAR PADA MOBIL
Authors: Widiyastuti Wahyuning
Published: August 2020

MANAGEMENT OF ENERGY SAVING BEHAVIOR BASED ON SMART COLORS ON THE CAR. Energy constraints in the world lie behind countries to save energy. Unwittingly, the cause of the high fuel usage in cars lies of uses AC (Air Conditioner). The temperature in the car is influenced by the color of the car. Based on the problems above, inspiring researchers to analyze the color car effect  on temperature to save fuel usage.
In this study, the author uses the study method and the observation method that is observing car as the object. After conducting experiment, cars color from the lowest temperature to the color that has the highest temperature is obtained. So the car color affects the temperature of the car. If the temperature in the car is high, it will affect the use of AC which has an impact on the use of fuel. In this research, the car color sequences that are good in saving fuel are white, silver, beige, red, blue, gray, black.
MODEL PEMBELAJARAN STAD UNTUK MENINGKATKAN KEMAMPUAN MEMECAHKAN MASALAH STATISTIKA PADA PESERTA DIDIK KELAS XII MIPA 7 SMA 2 KUDUS TAHUN PELAJARAN 2018/2019
Authors: Marsiniarif Marsini
Published: August 2020

STAD LEARNING MODEL TO IMPROVE ABILITY TO SOLVE STATISTICAL PROBLEMS IN STUDENTS IN CLASS XII MIPA 7 SMA 2 KUDUS 2 YEARS LESSON 2018/. This class action research aims: 1) Determine the magnitude of the increase in mathematics activity and learning outcomes in statistical material, using the STAD learning model in class XII.MIPA 7 students of SMA 2 Kudus for semester 1 of 2018/2019 academic year. 2) Describe the changes in mathematics learning activities and statistics material, after applying the STAD learning model to students of XII.MIPA 7 SMA 2 Kudus semester 1 of 2018/2019 academic year. The research method uses Classroom Action Research with 3 cycles. Data collection techniques through: 1) observation, 2) questionnaire; and 3) test. Data Analysis Techniques with comparative descriptive techniques and interactive analysis techniques. The results showed an increase in cycle I to cycle II for the level of activity reaching 42.86% and completeness of learning outcomes reached 55.53%. Furthermore it can be concluded that Statistics learning with STAD learning models can improve student activity and quality of learning outcomes and can improve students' abilities in completing statistics.
Medication omission rates in New Zealand Residential Aged Care Homes: a national description
Authors: Garratt Stephanie M , Kerse Ngaire M , Peri Kathryn , Jonas Monique F
Published: August 2020

Background A medication omission is an event where a prescribed medication is not taken before the next scheduled dose. Medication omissions are typically classed as errors within Residential Aged Care (RAC) homes, as they have the potential to lead to harm if poorly managed, but may also stem from good clinical decision-making. This study aimed to quantify the incidence, prevalence, and types of medication omissions in RAC homes on a national scale, using a New Zealand-based sample. Methods We conducted retrospective pharmacoepidemiology of de-identified medication administration e-records from December 1st 2016 to December 31st 2017. Four tiers of de-identified data were collected: RAC home level data (ownership, levels of care), care staff level data (competency level/role), resident data (gender, age, level of care), and medication related data (omissions, categories of omissions, recorded reasons for omission). Data were analysed using SPSS version 24 and Microsoft Excel.Results A total of 11, 015 residents from 374 RAC homes had active medication charts; 8,020 resided in care over the entire sample timeframe. A mean rate of 3.59 medication doses were omitted per 100 (±7.43) dispensed doses/resident. Seventy-three percent of residents had at least one dose omission. The most common omission category used was ‘not-administered’ (49.9%), followed by ‘refused’ (34.6%). The relationship between ownership type and mean rate of omission was significant (p=0.002), corporate operated RAC homes had a slightly higher mean (3.73 versus 3.33), with greater variation. The most commonly omitted medications were Analgesics and Laxatives. Forty-eight percent of all dose omissions were recorded without a comment justifying the omission. Conclusions This unique study is the first to report rate of medication omissions per RAC resident over a one-year timeframe. Although the proportion of medications omitted reported in this study is less than previously reported by hospital-based studies, there is a significant relationship between a resident’s level of care, RAC home ownership types, and the rate of omission.
Repetitive transcranial magnetic stimulation improves neurological function after cerebral ischemia in rats by increasing CREB-regulated TrkB via activation of cAMP/PKA and Ca2+/CaMKIV signaling pathways
Authors: Chang Lisha , An Zhaowang , Zhang Jiang , Zhou Fuling , Wang Dali , Liu Jian , Zhang Yunhe
Published: August 2020

The authors have withdrawn this preprint due to author disagreement.
Extracellular vesicles derived from mesenchymal stromal cells mitigate intestinal toxicity in a mouse model of acute radiation syndrome.
Authors: Accarie Alison , L'homme Bruno , Benadjaoud Mohamedamine , Lim Sai Kiang , Guha Chadan , Benderitter Marc , Tamarat Radia , SEMONT Alexandra
Published: August 2020

Background: Human exposure to high doses of radiation resulting in acute radiation syndrome and death can rapidly escalate to a mass casualty catastrophe in the event of nuclear accidents or terrorism. The primary reason is that there is presently no effective treatment option, especially for radiation-induced gastrointestinal syndrome. This syndrome results from disruption of mucosal barrier integrity leading to severe dehydration, blood loss and sepsis. In this study, we tested whether extracellular vesicles derived from mesenchymal stromal cells (MSC) could reduce radiation-related mucosal barrier damage and reduce radiation-induced animal mortality. Methods: HumanMSC-derived extracellular vesicles were intravenously administered to NUDE mice, 3, 24 and 48 hours after lethal whole-body irradiation (10 Grays). Integrity of the small intestine epithelial barrier was assessed by morphologic analysis, immunostaining for tight junction protein (claudin-3) and in vivo permeability to 4 kDa FITC-labeled dextran. Renewal of the small intestinal epithelium was determined by quantifying epithelial cell apoptosis (TUNEL staining) and proliferation (Ki67 immunostaining). Statistical analyses were performed using one-way ANOVA followed by a Tukey test. Statistical analyses of mouse survival were performed using Kaplan-Meier and Cox methods. Results: We demonstrated that MSC-derived extracellular vesicles treatment reduced by 85% the instantaneous mortality risk in mice subjected to 10 Grays whole-body irradiation and so increased their survival time. This effect could be attributed to the efficacy of MSC-derived extracellular vesicles in reducing mucosal barrier disruption. We showed that the MSC-derived extracellular vesicles improved the renewal of the small intestinal epithelium by stimulating proliferation and inhibiting apoptosis of the epithelial crypt cells. The MSC-derived extracellular vesicles also reduced radiation-induced mucosal permeability as evidenced by the preservation of claudin-3 immunostaining at the tight junctions of the epithelium. Conclusions: MSC-derived extracellular vesicles promote epithelial repair and regeneration and preserve structural integrity of the intestinal epithelium in mice exposed to radiation-induced gastrointestinal toxicity. Our results suggest that the administration of MSC-derived extracellular vesicles could be an effective therapy for limiting acute radiation syndrome.
Slope Mass Rating-based Analysis to Assess Rockfall Hazard on Yogyakarta Southern Mountain, Indonesia
Authors: Triana Karlina , Hermawan Koko
Published: August 2020

In the Parangtritis Beach tourism area located in the Southern Mountain of Yogyakarta, karst hills were excavated to build the main accessing road and produce some of long and very steep slopes along the sides of the road. But still, there was none of the slope reinforcement installed along the road. Meanwhile, at several nearby locations within Southern Mountain, rockfall incidents have occurred many times even caused casualties. The potential of rockfall hazard also could be found in the main road of Parangtritis Beach as the study area. The purpose of this study is to determine the rockfall hazard assessment along the main road using Slope Mass Rating (SMR) analysis with the additional parameter of the slope height and the rock block size. The necessary data obtained by direct measurement and laboratory test. Geomechanics analysis, stereographic projection analysis, and hazard parameters weighting were carried out to produce the Rockfall Hazard Zonation Map of the study area. Based on 17 measurement stations, there are 4 (four) rockfall hazard classes in the study area, i.e., very low, low, moderate, and high. The class of very low, which also included road segments without slope, has the largest percentages of 83.83%, followed by the classes of moderate, low, and high with the percentage of 7.16%, 4.28%, and 4,19%, respectively. SMR was assumed as the most significant parameter that influences the rockfall hazard zonation. Historical rockfall points were overlaid over the Rockfall Hazard Zonation Map to validate the predicted hazard zones. Since 91.23% of the rockfall occurred in the moderate and high hazard classes, the zonation map considered reliable to predict future rockfall. This study also identified several landslide potential zones and provides the recommendation of slope reinforcement to be installed in the study area.
Keywords: Rockfall, Slope Mass Rating, Hazard zonation, Slope reinforcement, Hills.
LncRNA PRNCR1 promotes breast cancer proliferation and inhibits apoptosis by modulating microRNA-377/CCND2/MEK/MAPK axis
Authors: Ouyang Jian , Liu Zilong , Yuan Xiaobing , Chen Xia , Wang Yongpeng , Liu Lu , Long Chunping , Liang Hui
Published: August 2020

The authors have withdrawn this preprint due to author disagreement.
The effective interplay of (non-) selective NSAIDs with Neostigmine in animal models of analgesia and inflammation
Authors: Gowayed Mennatallah , Abdel-Bary Amany , El-Tahan Rasha A
Published: August 2020

Background

Surgical procedures cause perioperative immunosuppression and neuroendocrine stress, exerted by activation of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis. The acetylcholinesterase inhibitor (ACHEI); neostigmine, is known clinically for its analgesic effect in the perioperative phases proving high efficacy; besides possessing anti-inflammatory properties controlling immune cells and cytokine level. Hence, this study evaluated and compared the analgesic and anti-inflammatory activities of the combination of selective Cox-2 inhibitor; celecoxib, with neostigmine versus a combination of the non-selective Cox inhibitor; diclofenac, with neostigmine; in different experimental models of analgesia and inflammation in rats.

Methods

Analgesic activity of neostigmine with/without diclofenac or celecoxib was assessed in female Sprague-Dawely rats using the tail clip model and acetic acid induced writhing. Serum level of β-endorphin was assessed after the tail clip test. The anti-inflammatory activity was evaluated using acute and sub-chronic formalin induced paw edema. At the end of the sub-chronic formalin test, blood samples were collected for analysis of anti-inflammatory, liver and kidney function markers. Livers, kidneys and hind paws were also examined histopathologically.

Results

Addition of neostigmine to selective or non-selective NSAIDs (celecoxib or diclofenac) causes an increased level of analgesia of NSAIDs with rapid onset of action and short duration, while causing potentiation of the anti-inflammatory effect of neostigmine as seen in the tail clip, writhing, formalin test, Cox-1 and Cox-2 activities, serum β-endorphin, TNF-α, NF-кB and HS-CRP. All combinations of this study disturb some kidney and liver functions, however with normal histopathological appearances, while hind paws reveal improved inflammatory infiltration in all treated groups.

Conclusion : Selective and non-selective NSAIDs examined in this study could be good adjunct options to general anesthetic agents and neostigmine in perioperative stages, an outcome that needs further clinical investigation.
Methylome and transcriptome profiles in three yak tissues revealed that DNA methylation and transcription factor ZGPAT co-regulate milk production
Authors: Xin Jinwei , Chai Zhixin , Zhang Chengfu , Zhang Qiang , Zhu Yong , Cao Hanwen , Cidan Yangji , Chen Xiaoying , Jiang Hui , Zhong Jincheng , Ji Qiumei
Published: August 2020

Background Domestic yaks play an indispensable role in sustaining the livelihood of Tibetans and other ethnic groups on the Qinghai-Tibetan Plateau (QTP), by providing milk and meat, and have evolved numerous physiological adaptabilities to high-altitude landscape, such as strong capacity of blood oxygen transportation and high metabolism. The role of DNA methylation and network of gene expression underlying milk production and adaptation to high altitudes of yak need further exploration. Results We performed genome-wide DNA methylome and transcriptome analyses of breast, lungs, and gluteal muscle from yaks of different ages. We identified differentially methylated regions (DMRs) across age groups within the each tissue, and breast tissue had considerably more differentially methylated regions than that from the three younger age groups. Hypomethylated genes with high expression level might regulate milk production by influencing protein processing in the endoplasmic reticulum. Weighted gene correlation network analysis revealed that the “hub” gene ZGPAT was highly expressed in post-mature breast tissue and that it potentially regulated the transcription of 280 genes, which play roles in regulating protein synthesis, processing, and secretion. Besides, Tissue network analysis indicates that high expression of HIF1A regulates energy metabolism in the lung. Conclusions The results of this comprehensive study provide a solid basis for understanding the epigenetic mechanisms underlying milk production in yaks, which could be helpful to breeding programs aimed at improving milk production.
Prevalence, mortality and healthcare economic burden of Tuberous Sclerosis in Hong Kong: a population-based retrospective cohort study (1995-2018)
Authors: Chu William Ching-Yuen , Chiang Lorraine Lok-Wing , Chan Dorothy Chi-Ching , Wong Wilfred Hing-Sang , Chan Godfrey Chi-Fung
Published: August 2020

Background

We aim to elucidate the disease impact by accounting the prevalence, survival rate, genetics, mTOR inhibitor use and direct costs of tuberous sclerosis complex (TSC) in our local setting. TSC patients with documented visits to our local public hospitals in 1995-2018 were identified. The public hospitals captured most if not all local TSC patients. Demographics such as age, sex, death, genetic profiles were retrieved from the central electronic database. Data including prevalence, age distribution and survival rate were analysed. Direct cost was calculated with reference to the drug use and number of visits to various public hospital facilities.

Results

We identified 284 surviving TSC patients (55.3% male) in Hong Kong. The age range was from 4.5 months to 89.9 years, with a median age of 27.2 years. Paediatrics (<18 years) to adult (≥18 years) ratio was 1:2.84. The overall prevalence of TSC patients was 3.87 in 100,000 (i.e. 1 in 25,833). Genetically, TSC1:TSC2 ratio is 1:2.7.

Thirty seven patients died within the study period. The age of death ranged from 7.6 years to 77.8 years, with a median age of death at 36.6 years (IQR: 24.7-51.1 years). Most patients survived till adulthood. Survival rate at 20 and 50 years follow-up was 98.6% and 79.5% respectively.

Two hundred and twenty nine TSC patients (71.3%) had neurological manifestations, sixteen patients (5.0%) had chronic kidney diseases and five patients (1.6%) had pulmonary lymphangioleiomyomatosis. Forty seven (16.5%) TSC patients were prescribed with mTOR inhibitors within the study period. Healthcare facility utilization was further analysed in the 2008-2018 cohort. In particular, the mean number of specialist out-patient clinic visits per patient-year was 9.23 per patient-year, which was 4.91 times more than that of local general population.

Conclusions

Prevalence of local TSC patients is within the range of that reported in the literature. Local TSC patients have fair long term survival, but they require disproportionally high healthcare cost when compared with the general population, particularly in terms of outpatient (OP) visits. Although effective disease-modifying agent (i.e. mTOR inhibitor) is available, it was not widely used yet in Hong Kong despite the fact that Government approved and supported its use recently. Further research on quality of life and setting up a comprehensive patient registry are necessary for more accurate assessment of cost and benefit.
Disparities in Cervical Cancer Screening Participation in Iran: A Cross-Sectional Analysis of the 2016 Nationwide Steps Survey
Authors: Amin Rozhin , Kolahi Ali-Asghar , Jahanmehr Nader , Abadi Ali-Reza , Sohrabi Mohammad-Reza
Published: August 2020

Background: One of the most important concerns in every healthcare system is the elimination of disparities in health service utilization and achievement of health equity. This study aims to investigate the disparities in cervical cancer screening participation in Iran.Methods: A cross-sectional study was conducted using data from the National Non-Communicable Risk Factors Survey in 2016 (STEPs 2016). Data on cervical cancer screening in addition to demographic and socio-economic factors from 15975 women aged 18 and above were analyzed. The distribution of surveyed women with regard to cervical cancer screening practice was described. Chi Square and logistic regression were used to assess the association of demographic and socio-economic factors with cervical cancer screening. Socio-economic equity in screening was assessed by concentration index, and GIS analysis was used to show the provincial indices on the map of Iran.Results: Overall, 52.1% of women aged 30-59 years, had undergone cervical cancer screening at least once in their lifetime. Participation rate in cervical cancer screening programs varied between provinces; ranging from 7.6% in Sistan and Baluchestan to 61.2% in Isfahan. Young age, having no education, and being uninsured were associated with lower participation. Concentration index showed pro-poor inequity for the country and across all provinces, indicating that cervical cancer screening services are less utilised by high income groups. GIS analysis demonstrated spatial disparity across provinces of Iran.Conclusions: Equity and participation in cervical cancer screening in Iran requires improvement. For this to be achieved, new policies shall have a stronger emphasis on the lowest and the highest socio-economic population groups, while current strategies have mostly affected the people with middle socio-economic status.
High-Quality Genome Sequence Assembly of R.A73 Enterococcus faecium Isolated from Freshwater fish mucus
Authors: Jeni Rim El , Ghedira Kais , Bour Monia El , Abdelhak Sonia , Kahla Alia Ben , Bouhaouala-Zahar Balkiss
Published: August 2020

Background: Whole-genome sequencing using high throughput technologies has revolutionized and speeded up the scientific investigation of bacterial genetics, biochemistry, and molecular biology. Lactic acid bacteria (LABs) have been extensively used in fermentation and more recently as probiotics in food products that promote health. Genome sequencing and functional genomics investigations of LABs varieties provide rapid and important information about their diversity and their evolution, revealing a significant molecular basis.This study investigated the whole genome sequences of the Enterococcus faecium strain (HG937697), isolated from the mucus of freshwater fish in Tunisian dams. Genomic DNA was extracted using the Quick-GDNA kit and sequenced using the Illumina HiSeq2500 system. Sequences quality assessment was performed using FastQC software. The complete genome annotation was carried out with the RAST web server then NCBI PGAAP. Results: The Enterococcus faecium R.A73 assembled in 28 contigs consisting of 2,935,283 bps. The genome annotation revealed 2,884 genes in total including 2,834 coding sequences and 50 RNAs containing 3 rRNAs (one rRNA 16s, one rRNA 23s and one rRNA 5s) and 47 tRNAs. Twenty-two genes implicated in bacteriocin production are identified within the Enterococcus faecium R.A73 strain. Conclusion: Data obtained provide insights to further investigate the effective strategy for testing this Enterococcus faecium R.A73 strain in the industrial manufacturing process. Studying their metabolism with bioinformatics tools represents the future challenge and contribution to improving the utilization of the multi-purpose bacteria in food.
Safety studies and viral shedding of intramuscular administration of oncolytic vaccinia virus TG6002 in healthy Beagle dogs
Authors: Béguin Jérémy , Nourtier Virgine , Gantzer Murielle , Cochin Sandrine , Foloppe Johann , Balloul Jean Marc , Laloy Eve , Tierny Dominique , Klonjkowski Bernard , Quemeneur Eric , Maurey Christelle , Erbs Philippe
Published: August 2020

Background: Cancer is a leading cause of mortality for both humans and dogs. As spontaneous canine cancers appear to be relevant models of human cancers, developing new therapeutic approaches could benefit both species. Oncolytic virotherapy is a promising therapeutic approach in cancer treatment. TG6002 is a recombinant oncolytic vaccinia virus deleted in the thymidine kinase and ribonucleotide reductase genes and armed with the suicide gene FCU1 that encodes a protein which catalyses the conversion of the non-toxic 5-fluorocytosine into the toxic metabolite 5-fluorouracil. Previous studies have shown the ability of TG6002 to infect and replicate in canine tumor cell lines, and demonstrated its oncolytic potency in cell lines, xenograft models and canine mammary adenocarcinoma explants. Moreover, 5-fluorouracil synthesis has been confirmed in fresh canine mammary adenocarcinoma explants infected with TG6002 with 5-fluorocytosine. This study aims at assessing the safety profile and viral shedding after unique or repeated intramuscular injections of TG6002 in seven healthy Beagle dogs.Results: Repeated intramuscular administrations of TG6002 at the dose of 5 x 107 PFU/kg resulted in no clinical or biological adverse effects. Residual TG6002 in blood, saliva, urine and feces of treated dogs was not detected by infectious titer assay nor by qPCR, ensuring the safety of the virus in the dogs and their environment.Conclusions: These results establish the good tolerability of TG6002 in healthy dogs with undetectable viral shedding after multiple injections. This study supports the initiation of further studies in canine cancer patients to evaluate the oncolytic potential of TG6002 and provides critical data for clinical development of TG6002 as a human cancer therapy.
Reversibility of hAT-MSCs phenotypic and metabolic changes after exposure to and withdrawal form HCC-conditioned medium through regulation of the ROS/MAPK/HIF-1α signalling pathway
Authors: Wang Chenyang , Hu Jie , Chen Zheng , Wang Yifan , Lu Sinan , Zhang Yuan , Li Yufeng , Xiang Yucheng , Ji Yutian , Zeng Cheng , Ding Yuan , Wang Weilin
Published: August 2020

Background: Mesenchymal stem cells (MSCs) play an important role in tumour progression; concomitantly, MSCs also undergo profound changes in the tumour microenvironment (TME). These changes can directly impact the application and efficacy of MSC-based anti-tumour therapy. However, few studies have focused on the regulation of MSC fate in TME, which will limit the progress of MSC-based anti-tumour therapy. Herein, we investigated the effects of conditioned medium from human hepatocellular carcinoma cells (HCC-CM) on the phenotype and glucose metabolism of human adipose tissue-derived MSCs (hAT-MSCs).

Methods: The passage 2 (P2) to passage 8 (P8) naïve hAT-MSCs were exposed to conditioned medium from Hep3B, Huh7 and HCCLM3 cells for 4-8 weeks in vitro. Then, immunofluorescent, CCK-8 assay, EdU assay, Transwell assay, and flow cytometry were used to assess the alterations in cell phenotype in terms of cell morphology, secretory profiles, proliferation, migration, invasion, cell cycle, and apoptosis. In addition, glucose metabolism was evaluated by related kits. Next, the educated hAT-MSCs were subjected to withdrawal from HCC-CM for 2-4 weeks, and alterations in phenotype and glucose metabolism were reevaluated. Finally, the molecular mechanism was clarified by Western blotting.

Results: The results revealed that after exposure to HCC-CM, hAT-MSCs developed a stellate-shaped morphology. In association with cytoskeleton remodelling, hAT-MSCs showed enhanced capacities for migration and invasion, while cell proliferation was inhibited by regulating the cell cycle by downregulating cyclins and cyclin-dependent kinases and activating the mitochondrial apoptosis pathway. In terms of glucose metabolism, our results showed mitochondrial dysfunction and elevated glycolysis of hAT-MSCs. However, interestingly, when the educated hAT-MSCs were subjected to withdrawal from HCC-CM, the alterations in phenotype and glucose metabolism could be reversed, but secretory phenotype and tumour-promoting properties appear to be permanent. Further studies showed that these changes in hAT-MSCs may be regulated by the ROS/MAPK/HIF-1α signalling pathway.

Conclusion: Taken together, the effects of long-term HCC-CM treatment on phenotype and glucose metabolism in hAT-MSCs are modest and largely reversible after withdrawal, but HCC-CM endow hAT-MSCs with permanent secretory phenotype and tumour-promoting properties. This is the first report on the reversal of phenotype and glucose metabolism in tumour-associated MSCs (TA-MSCs), it is anticipated that new insights into TA-MSCs will lead to the development of novel strategies for MSC-based anti-tumour therapy.
Changing trends of birth weight with maternal age: a cross-sectional study in Xi'an city of Northwestern China
Authors: Wang Shanshan , Yang Liren , Shang Li , Yang Wenfang , Qi Cuifang , Huang Liyan , Xie Guilan , Wang Ruiqi , Chung Mei Chun
Published: August 2020

Background: Most studies have shown that maternal age is associated with birth weight. However, the specific relationship between each additional year of maternal age and birth weight remains unclear. The study aimed to analyze the specific association between maternal age and birth weight. Methods: Raw data for all live births from 2015 to 2018 were obtained from the Medical Birth Registry of Xi’an, China. A total of 490143 mother-child pairs with full-term singleton live births and the maternal age ranging from 20 to 40 years old were included in our study. Birth weight, gestational age, birth date of the newborns, maternal birth date, residence and ethnicity were collected. Generalized additive model and two-piece wise linear regression model were used to analyze the specific relationships between maternal age and birth weight, risk of low birth weight, and risk of macrosomia. Results: The relationships between maternal age and birth weight, risk of low birth weight, and risk of macrosomia were nonlinear. Birth weight increased 16.204 g per year when maternal age is less than 24 years old (95%CI: 14.323, 18.086), and increased 12.051g per year when maternal age ranged from 24 to 34 years old (95%CI: 11.609, 12.493), then decreased 0.824g per year (95% CI: -3.112, 1.464). The risk of low birth weight decreased with the increase of maternal age until 36 years old (OR= 0.917, 95%CI: 0.903, 0.932 when maternal age younger than 27 years old; OR= 0.965, 95%CI: 0.955, 0.976 when maternal age ranging from 27 to 36 years old), then increased when maternal age older than 36 years old (OR=1.133, 95%CI: 1.026, 1.250). The risk of macrosomia increased with the increase of maternal age (OR=1.102, 95%CI: 1.075, 1.129 when maternal age younger than 24 years old; OR=1.065, 95%CI: 1.060, 1.071 when maternal age ranged from 24 to 33 years old; OR=1.029, 95%CI: 1.012, 1.046 when maternal age older than 33 years old). Conclusions: For women of childbearing age (20-40 years old), the threshold of maternal age on low birth weight was 36 years old, and the risk of macrosomia increased with the increase of maternal age.
Characterizing sensitivity and coverage of clinical WGS as a diagnostic test for genetic disorders
Authors: Sun Yan , Liu Fengxia , Fan Chunna , Wang Yaoshen , Song Lijie , Fang Zhonghai , Han Rui , Wang Zhonghua , Wang Xiaodan , Yang Ziying , Xu Zhenpeng , Peng Jiguang , Shi Chaonan , Zhang Hongyun , Dong Wei , Huang Hui , Li Yun , Le Yanqun , Sun Jun , Peng Zhiyu
Published: August 2020

Background: Due to its reduced cost and incomparable advantages, WGS is likely to lead to changes in clinical diagnosis of rare and undiagnosed diseases. However, the sensitivity and breadth of coverage of clinical WGS as a diagnostic test for genetic disorders has not been fully evaluated. Here, the performance of WGS in NA12878, the YH cell line, and the Chinese trios were measured by assessing their sensitivity, PPV, depth and breadth of coverage using MGISEQ-2000. We also compared the performance of WES and WGS using NA12878. The sensitivity and PPV were tested using the family-based trio design for the Chinese trios. We further developed a systematic WGS pipeline for the analysis of 8 clinical cases. Results: In general, the sensitivity and PPV for SNV/indel detection increased with mean depth and reached a plateau at an ~40X mean depth using down-sampling samples of NA12878. With a mean depth of 40X, the sensitivity of homozygous and heterozygous SNPs of NA12878 was >99.25% and >99.50%, respectively, and the PPV was 99.97% and 98.96%. Homozygous and heterozygous indels showed lower sensitivity and PPV. The sensitivity and PPV were still not 100% even with a mean depth of ~150X. We also observed a substantial variation in the sensitivity of CNV detection across different tools, especially in CNVs with a size less than 1 kb. In general, the breadth of coverage for disease-associated genes and CNVs increased with mean depth. The sensitivity and coverage of WGS (~40X) was better than WES (~120X). Among the Chinese trios with an ~40X mean depth, the sensitivity among offspring was >99.48% and >96.36% for SNP and indel detection, and the PPVs were 99.86% and 97.93%. All 12 previously validated variants in the 8 clinical cases were successfully detected using our WGS pipeline.Conclusions: The current standard of a mean depth of 40X may be sufficient for SNV/indel detection and identification of most CNVs. It would be advisable for clinical scientists to determine the range of sensitivity and PPV for different classes of variants for a particular WGS pipeline, which would be useful when interpreting and delivering clinical reports.
Incidence and predictors of surgical site infection after distal femur fractures treated by open reduction and internal fixation: a prospective single-center study
Authors: Zhang Junzhe , Li Junyong , Zhao Kuo , Meng Hongyu , Zhu Yanbin , Zhang Yingze
Published: August 2020

Background: There remain limited data on the epidemiological characteristics and related predictors of surgical site infection (SSI) after open reduction and internal fixation (ORIF) for distal femur fractures. We designed this single-centre prospective study to explore and resolve these clinical problems. Methods ： From October 2014 to December 2018, 364 patients with distal femur fractures were treated with ORIF and followed for complete data within one year. Receiver operating characteristic (ROC) analyses, univariate Chi-square analyses, and multiple logistic regression analyses were used to screen the adjusted predictors of SSI. Results : The incidence of SSI was 6% (22/364): 2.4% for superficial SSIs and 3.6% for deep SSIs. Staphylococcus aureus (methicillin-resistant S. aureus in 2 cases) was the most common pathogenic bacteria (7, 36.8%). In multivariate analysis, parameters independently associated with SSI were: Open fracture (OR: 7.27, p = 0.003), drain use (OR: 4.11, p = 0.037), and incision cleanliness (OR: 3.53, p = 0.002). An albumin/globulin (A/G) level ≥ 1.35 (OR: 0.23, p = 0.042) was an adjusted protective factor for SSI. Conclusions : The SSI after ORIF affected approximately one in 15 patients with distal femur fractures. We recommend that maintaining A/G levels higher than 1.35 is introduced during hospitalization and elaborative evaluation of drain use is conducted for reducing the risk of post-operative SSI. Trial registration: NO 2014-015-1, October 15, 2014. We registered our trial prospectively in October 15, 2014 before the first participant was enrolled. This study protocol was conducted according to the Declaration of Helsinki and approved by the Institutional Review Board. The ethics committee approved the Surgical Site Infection in Orthopaedic Surgery (NO 2014-015-1). Data used in this study were obtained from the patients who underwent orthopaedic surgeries between October 2014 to December 2018.
How Professionals Tinker With Ethical Tensions Collectively When Fostering Service User Autonomy: An Ethnographic Study In Long-term Care
Authors: Heerings Marjolijn , Bovenkamp Hester van de , Cardol Mieke , Bal Roland
Published: August 2020

The authors have withdrawn this preprint due to a need to make corrections.
Comparative study of preoperative prediction scores for lymph node metastasis in gastric and colon cancer patients
Authors: Zheng Xiangjian , Chen Xiaodong , Li Min , Li Chunmeng , Shen Xian
Published: August 2020

Background: Surgery combined with chemo-radiotherapy is a recognized model for the treatment of gastric and colon cancers. Lymph node metastasis determines the patient's surgical or comprehensive treatment plan. This analytical study aims to compare preoperative prediction scores to better predict lymph node metastasis in gastric and colon cancer patients.Methods: This study comprised 768 patients, which included 312 patients with gastric cancer and 462 with colon cancer. Preoperative clinical tumor characteristics, serum markers, and immune indices were evaluated using single-factor analysis. Logistic analysis was designed to recognize independent predictors of lymph node metastasis in these patients. The independent risk factors were integrated into preoperative prediction scores, which were accurately assessed using receiver operating characteristic (ROC) curves.Results: Results showed that serum markers (CA125, hemoglobin, albumin), immune indices (S100, CD31, d2–40), and tumor characteristics (pathological type, size) were independent risk factors for lymph node metastasis in patients with gastric and colon cancer. The preoperative prediction scores reliably predicted lymph node metastasis in gastric and colon cancer patients with a higher area under the ROC curve (0.901). The area was 0.923 and 0.870 in gastric cancer and colon cancer, respectively. Based on the ROC curve, the ideal cutoff value of preoperative prediction scores to predict lymph node metastasis was established to be 287. Conclusion: The preoperative prediction scores is a useful indicator that can be applied to predict lymph node metastasis in gastric and colon cancer patients.
A clinical prediction model for complicated appendicitis in children younger than five years of age
Authors: Feng Wei , Zhao Xu-Feng , Li Miao-Miao , Cui Hua-Lei
Published: August 2020

Background: No reliably specific method for complicated appendicitis has been identified in children younger than five years of age. This study aimed to analyze the independent factors for complicated appendicitis in children younger than five years of age, develop and validate a prediction model for the differentiation of simple and complicated appendicitis. Methods: A retrospective study of 382 children younger than five years of age with acute appendicitis from January 2007 to December 2016 was conducted with assessments of demographic data, clinical symptoms and signs, and pre-operative laboratory results. According to intraoperative findings and postoperative pathological results, acute appendicitis were divided into simple and complicated appendicitis. Univariate and multivariate analyses were used to screen out the independent factors of complicated appendicitis, and develop a prediction model for complicated appendicitis. Then 156 such patients from January 2017 to December 2019 were collected as validation sample to validate the prediction model. Test performance of the prediction model was compared with the ALVARADO score and Pediatric Appendicitis Score (PAS). Results: Of the 382 patients, 244 (63.9 %) had complicated appendicitis. Age, white blood cell count, and duration of symptoms were the independent factors for complicated appendicitis in children younger than five years of age. The final predication model for complicated appendicitis included factors above. In validation sample, the prediction model exhibited a high degree of discrimination (area under the curve [AUC]: 0.830; 95% confidence interval [CI]: 0.762 - 0.885) corresponding to a optimal cutoff value of 0.62, and outperformed the PAS (AUC: 0.735; 95% CI: 0.658 - 0.802), ALVARADO score (AUC: 0.733; 95% CI: 0.657 - 0.801). Conclusion : Age, white blood cell count, and duration of symptoms could be used to predict complicated appendicitis in children younger than five years of age with acute appendicitis. The prediction model is a novel but promising method that aids in the differentiation of acute simple and complicated appendicitis.