bluuebunny/crossref_metadata_2025 huggingface dataset:
SOX2 heterozygous mutation causes multiple extra-ocular phenotypes in boys
Authors: Wang Yi , Fan LiJun , Ren Xiaoya , Song Yanning , Zhang Beibei , Gong Chunxiu
Published: May 2020

Background The SOX2 gene is widely expressed in the eyes and the central nervous system. Heterozygous mutations could cause eye malformations and hypopituitarism, and serve as the causative gene for syndromic and non-syndromic hypogonadotropic hypogonadism (HH). Our study reports three children with chromosome 46, XY, SRY (+), but SOX2 mutations.Methods Three children visited our endocrine clinic because of micropenis and/or cryptorchidism. Clinical data were collected, and one took PANEL sequencing and the others for whole exome sequencing. Then we summarized characteristics of the patients and compared with those mentioned in literature.Results Patient 1 manifested with micropenis, patient 2 with bilateral cryptorchidism and craniofacial deformities, both carrying the same reported SOX2 gene mutation (T232N), and both mutations from mothers with delayed puberty only. Patient 3 showed micropenis, mental retardation and craniofacial deformities, and the child carried a spontaneous truncation mutation (Y110X) of the SOX2 gene. This site has reported that a missense mutation caused adolescent adolescence without major eye signs. All three patients carried another gene mutations that affected hypothalamic-pituitary function: Patient 1, FGFR1: c.238C>T/p.R80C (uncertain) from father; Patient 2, CHD7: c.2656C>T/p.R886W (pathogenic) de novo; Patient 3, SEMA3A: c.1432G> A/p.E478K (uncertain) from mother. None had major ocular malformations, and all showed genitourinary tract malformations. Two patients had craniofacial deformities, and one patient had muscle anomality and intellectual disability. We summarized previous studies with SOX2 gene mutations and it showed: 71.2% of mutations are de novo, all patients reported whose variants inherit from parents, 15.1% parents (including mother 11.0% and father 4.1%) show completely normal phenotypes, 4.1% (3/73) variants inherit from mother with germinal mosaicism. Except for major ocular malformations (91.1%), the most common phenotype is developmental delay/mental retardation (DD/MR), accounting for 40.7%, followed by brain anomely (BA), accounting for 28.5%, male genital abnormalities (GA) for 20.3%, non-syndromic HH accounted for 4.9%, the younger the patients visit the doctor, the more common the retardation are. Conclusion SOX2 mutations could cause a broad phenotype spectrum from completely normal to severe ocular malformations, retardation and most mutations are de novo. Except for major ocular malformations and retardation, GA/HH is another common symptom. GA/HH may be the only symptom, and SOX2 may cooperate with another HH pathogenic genes to cause non-syndromic HH.
Relationship between caffeine intake and infertility: a systematic review of controlled clinical studies
Authors: Fanlong Bu , Feng Xue , Yang Xiao-Ying , Ren Jun , Cao Hui-juan
Published: May 2020

Background: Previous studies showed that high dose of caffeine intake may induce some specific human reproductive system diseases, even lead to infertility. This review is aimed to systematically review the evidence from all controlled clinical studies of caffeine intake for infertility.Methods: Relevant randomized/quasi-randomized controlled trials, non-randomized clinical studies, cohort studies, and case-control studies were included. Participants were either those without a history of infertility who are willing to have a baby (for prospective studies) or infertile patients with confirmed diagnosis (for retrospective studies). Caffeine or caffeine-containing beverage was observed as the exposure factor. The key outcome was the diagnosis of infertility.Results: Four studies (one cohort study and three case-control studies) involving 12912 participants were included. According Newcastle - Ottawa Scale (NOS), the average score of case-control studies was 6, and the cohort study achieved 9. Meta-analysis and subgroup analysis were conducted. The results showed that low (OR 0.95, 95%CI 0.78-1.16), medium (OR 1.14, 95%CI 0.69-1.86) and high doses (OR 1.86, 95%CI 0.28-12.22) of caffeine intake may not increase the risk of infertility. The GRADE method was used to assess the certainty of the evidence and the results showed that the quality of the three evidence bodies were all low.Conclusion: Our study provides low quality evidence that regardless of low, medium and high doses of caffeine intake do not appear increase the risk of infertility. But the conclusion should be treated with caution. Systematic review registration: PROSPERO CRD42015015714
Trends and sex disparities in school bullying victimization among U.S. youth, 2011–2017
Authors: Li Ruili , Lian Qiguo , Su Qiru , Li Luhai , Xie Meixian , Hu Jun
Published: May 2020

Objectives The prevalence of being bullied traditionally among U.S. high school students is expected to reduce to 17.9%, according to Healthy People 2020 Initiatives. We examined trends in traditional and cyberbullying victimization with the latest large-scale time-series data in the United States. Methods We analyzed the data from the 2011-2017 national Youth Risk Behavior Survey (YRBS) to access the trends in traditional and cyberbullying among U.S. high school students. We identified the temporal trends using multivariate logistic regression analyses, accounting for survey design features of YRBS. Results The overall prevalence of victimization was 19.74% for traditional bullying and 15.38% for cyberbullying, suggesting that cyberbullying is not a low frequent phenomenon. The prevalence of victimization ranged from 20.19% to 19.04% for traditional bullying and 16.23% to 14.77% for cyberbullying, and the declined trends for the two kinds of bullying victimization were both statistically non-significant. The degree of overlap between the two kinds of bullying victimization was about 60%. Besides, female students experienced more traditional and cyberbullying than male peers within each survey cycle. Conclusions No declined trends in traditional and cyberbullying victimization were observed during 2011-2017. Female students are more likely to experience bullying. To achieve the Healthy People 2020 goal on bullying, more work is needed.
Aboriginal Community Controlled Health Organisations address health equity through action on the social determinants of health of Aboriginal and Torres Strait Islander peoples in Australia.
Authors: Pearson Odette , Schwartzkopff Kate , Dawson Anna , Hagger Christina , Karagi Agape , Davy Carol , Brown Alex , Braunack-Mayer Annette
Published: May 2020

Background Indigenous populations globally are continually striving for better health and wellbeing due to experiencing significant health and social inequities. The social determinants of health are important contributors to health outcomes. Comprehensive primary health care that is governed and delivered by Indigenous people extends beyond the biomedical model of care to address the social determinants of health. Aboriginal Community Controlled Health Organisations (ACCHOs) are known to provide culturally informed, holistic health services that directly and indirectly address the social determinants of health. The range and extent of their activities in addressing the social determinants of health, however, is not well documented.Methods The most recent ACCHO annual reports were retrieved online or by direct correspondence. For coding consistency, a dictionary informed by the World Health Organization’s Conceptual Framework for Action on the Social Determinants of Health was developed. A document and textual analysis of reports coded ACCHO activities and the determinants of health they addressed, including intermediary determinants, socio-economic position and/or socio-political context. Summary statistics were reported. Representative quotes illustrating the unique nature of ACCHO service provision in addressing the social determinants of health were used to contextualise the quantitative findings.Results Sixty-seven annual reports were collected between 2017 and 2018. Programs were delivered to population groups across the life span. Fifty three percent of reports identified programs that included work at the socio-political level and all annual reports described working to improve socioeconomic position and intermediary determinants of health through their activities. Culture had a strong presence in program delivery and building social cohesion and social capital emerged as themes.Conclusions This study provides evidence of the considerable efforts of the ACCHO sector, as a primary health care provider, in addressing the social determinants of health and health inequity experienced by Indigenous communities. For the Aboriginal and Torres Strait Islander population, ACCHOs not only have an essential role in addressing immediate healthcare needs but also invest in driving change in the more entrenched structural determinants of health. These are important actions that are likely to have an accumulative positive effect in closing the gap towards health equity.
Physiological and transcriptome analysis of Poa pratensis var. anceps cv. Qinghai in response to cold stress
Authors: Dong Wenke , Ma Xiang , Jiang Hanyu , Zhao Chunxu , Ma Huiling
Published: May 2020

Background
Low temperature limits the growth and geographical distribution of plants. Poa pratensis is a cool-season turfgrass mainly grown in urban areas. However, low winter temperature or cold events in spring and autumn may cause P.pratensis mortality, affecting the appearance of lawns. P.pratensis var. anceps cv. Qinghai (PQ) is widely distributed in the Qinghai-Tibet Plateau above 3000 m. PQ has greater cold resistance than the commercially cultivated P.pratensis varieties. However, existing studies on the response mechanism of PQ to low temperatures have mainly focused on physiological and biochemical perspectives, while changes in the PQ transcriptome during the response to cold stress have not been reported.
Results
To investigate the molecular mechanism of the PQ cold response and identify genes to improve the low-temperature resistance of P.pratensis, we analyzed and compared the transcriptomes of PQ and the cold-sensitive P.pratensis cv. ‘Baron’ (PB) under cold stress using RNA sequencing. We identified 4878 and 1871 differentially expressed genes (DEGs) between the treatment vs control comparison of PQ and PB, respectively, with 4494 DEGs specific to PQ. Based on the DEGs, important Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as “starch and sucrose metabolism”, “protein processing in endoplasmic reticulum”, “phenylalanine metabolism” and “glycolysis/gluconeogenesis” were significantly enriched in PQ, and “starch and sucrose metabolism”, “phenylpropanoid biosynthesis”, “galactose metabolism” and “glutathione metabolism” were significantly enriched in PB. In addition, the “glycolysis” and “citrate cycle (TCA cycle)” pathways were identified as involved in cold resistance of P.pratensis.
Conclusions
As we know, this is the first study to explore the transcriptome of P.pratensis var. anceps cv. Qinghai. Our study not noly provides important insights into the molecular mechanisms of P.pratensis var. anceps cv. Qinghai responds to cold stress, but also systematically reveals the changes of key genes and products of glycolysis and TCA cycle in response to cold stress, which is conductive to the breeding of cold-resistant P.pratensis genotype.
One-step percutaneous transhepatic cholangioscopy combined with high-frequency needle-knife electrotomy in biliary strictures after liver transplantation
Authors: Tao Haisu , Wang Ping , Sun Beiwang , Zhou Xinghua , Xie Jiafen
Published: May 2020

Background
Endoscopic management is the mainstay for biliary strictures after liver transplantation. However, this method is often failed in cases associated with hepatolithiasis or refractory strictures. The aim of this study is to investigate whether one-step PTC combined with high-frequency needle-knife electrotomy can be an alternative method in biliary strictures after liver transplantation that could not be treated by endoscopic management.
Methods
Clinical data of 14 patients suffering from biliary strictures after liver transplantation from June 2014 to January 2018 were retrospectively analyzed. One-step PTC combined with high-frequency needle-knife electrotomy was used to resolve the strictures.
Results
One-step PTC was successfully performed in all 14 patients. In 10 of 12 (83.3%) patients with hepatolithiasis, the stones were removed completely. The stricture resolution was achieved in 13 of 14 (92.9%) patients at supporting catheter removal. Three mild adverse events occurred (cholangitis, 2 patient; delayed hemobilia, 1 patient), but were resolved with conservative treatment. The follow up after supporting catheter removal was 15.7 ± 4.5 months. Only 1 patient (8.3%) had stone recurrence and no stenosis occurred during supporting-free follow-up.
Conclusion
One-step PTC combined with high-frequency needle-knife electrotomy appears to be a useful for treating biliary strictures after liver transplantation.
Association mapping of Iranian wheat genotypes to detect QTLs conferring resistance to stem rust at seedling stage
Authors: Saremirad Ali , Bihamta Mohammad , Malihipour Ali , Mostafavi Khodadad , Alipour Hadi
Published: May 2020

Background

Stem rust caused by Puccinia graminis f. sp. tritici (Pgt) is an important disease of wheat in the world. Pgt pathogen is constantly evolving and creating more virulent races that break down stem rust (Sr) resistance genes. As a result, many of Sr genes have become ineffective against new Pgt races. Exploring new sources of resistance to detect new Sr genes/QTLs is very important in order to introducing them into wheat breeding programs and developing resistant wheat cultivars. The objective of the present study was to evaluate 297 Iranian wheat genotypes for resistance to stem rust at seedling stage and to detect Sr resistance genes/QTLs through association mapping (AM).
Results

A set of 297 Iran bread wheat cultivars and landraces were evaluated for infection type and latent period in four race of Pgt. Genotypic data of 282 genotypes were available, so AM was performed based on 282 genotypes. The results of population structure analysis showed that 277 genotypes clearly were distinguished in the three subpopulations and the other five genotypes were classified in the mixed group. The mean linkage disequilibrium decreased with increasing genetic distance. The markers did not have a uniform distribution on the genomes, so the share of each of the A, B and D genomes in commercial cultivars and landraces was approximately 37, 46 and 17%, respectively. Collectively, 69 QTLs for infection type and 62 QTLs for latent period of studied Pgt races were identified in the original dataset (P ≤ 0.001). In the imputed SNPs dataset, the number of QTLs for infection type increased to 504 QTL and for latent period increased to 454 QTLs (P ≤ 0.001).
Conclusion

Based on the results of this study, it can be concluded that the Iranian wheat genotypes are valuable source resistance to stem rust. By incorporating these genotypes into wheat breeding programs and optimizing effective resistance genes, an important step can be taken to prevent the threat of and the disease to ensure food security. This study provides additional useful information for selection of resistant genotypes against the disease by improving marker-assisted selection efficiency.
Literature Analysis of Blastocystis sp. from 1990 to 2019 in China
Authors: Ning Chao-qun , Ai Lin , Tian Li-Guang
Published: May 2020

Background
Blastocystis sp. is ubiquitous presence in animals and humans worldwide and a broad diversity genetically. The aim of this study was to find out the main research progress and research status of Blastocystis sp. in China in the past thirty years.
Methods
On the Chinese mainstream database China National Knowledge Infrastructure (CNKI), Wanfang database and PubMed database, the research literatures of Chinese Blastocystis sp. were searched and analyzed.
Results
285 articles related to Blastocystis sp. were retrieved, including 244 published in Chinese and 41 English on pathogen morphology, epidemiological investigation, laboratory detection and diagnosis, clinical case reports, drug treatment, animal model establishment as well as pathogenicity studies. There were the most epidemiological investigations and researches on pathogenic morphology decreasing recently Surveys of Blastocystis sp. of human has been carried out among a total of 18 provinces, with infection rates ranging from 0.007–48.6%. Infants and young children, school students, hospitalized diarrhea patients, human immunodeficiency virus (HIV) patients, tuberculosis patients, and cancer patients as respondents had been included. ST1-ST7 and ST12 were the main subtypes in Chinese population. Moreover, surveys of Blastocystis sp. of animal were also conducted in 12 provinces, with infection rates ranging from 2.54–79.41%. A variety of animals were investigated including pigs, cattle, sheep, yak, giant panda, and Crested Ibis et al., with the main subtypes of ST1-ST8, ST10, ST12-ST14. In vitro culture and Polymerase chain reaction (PCR) were commonly used to detect Blastocystis sp. in research and less in clinical application. Traditional Chinese medicine and western medicine for clinical drug treatment appeared curative effects. However, there were few reports on the application of traditional Chinese medicine in clinical treatment. The pathogenicity of Blastocystis sp. remains controversial and needs further exploration.
Conclusion
various researches on Blastocystis sp. had been carried out in China, especially in epidemiology. However, there is no report on the relationship between human Blastocystis sp. and animal infection. Furthermore, the relationship between infant diarrhea and its impact on the intestinal microecology have not received much attention from clinicians. The research on Blastocystis sp. still needs to be strengthened to provide effective data for the prevention and control and improve the quality of life of the population.
Design and validation of Brucellosis prevention questionnaire focused on animal vaccination
Authors: Ghofranipour Fazlollah , Bahadori Farhad , Ghaﬀarifar Saeideh , Ziaei Reza
Published: May 2020

Background Animal breeders' inadequate awareness about the transmission of brucellosis and their improper knowledge about prevention of brucellosis are among important barriers to vaccinate animals against brucellosis. The aim of this study is design, implementation and evaluation of a theory-driven and vaccination-focused training program for brucellosis prevention.Methods In this exploratory psychometric study, a brucellosis prevention questionnaire (BPQ) was developed. Face-to-face interviews were conducted to develop the initial items of BPQ. The findings from interviews were merged with those of literature review. Face, content and construct validity of BPQ were assessed by participation of animal breeders, veterinarians and health educationists. Impact Score (IS), Content Validity Ratio (CVR) and Content Validity Index (CVI) of the items were calculated. Construct validity of BPQ was evaluated through factor analyses. Cronbach’s alpha, Intra-class correlation coefficient (ICC), composite reliability and standard error of measurement (SEM) were measured to assess the reliability of the findings by BPQ.Results BPQ was finalized by 53 items. Its validity was confirmed by CVI, CVR, and IS of 0.90, 0.74 and 4.30, respectively. The items were loaded into three constructs of awareness, attitude and practice. The predictive power of the awareness, attitude and practice was 43.43%, 15.81% and 15.78%, respectively. The fitness of the proposed model among those constructs was confirmed by RMSEA < 0.08, Normed Chi2 < 5, CFI > .90, TLI > .90.Conclusion The brucellosis prevention questionnaire has acceptable psychometric properties. Applying BPQ, veterinarians and educational planners can identify factors influencing animal breeders' preventive behavior.
Trends of alcohol use, dietary behaviour, interpersonal violence, mental health, oral and hand hygiene behaviour among adolescents in Lebanon: cross-sectional national school surveys from 2005, 2011 and 2017
Authors: Pengpid Pengpid , Peltzer Karl
Published: May 2020

Background This investigation aimed to report the trends in the prevalence of various health risk behaviours among adolescents in Lebanon.Methods Cross-sectional nationally representative data were analysed from 13,109 adolescents (14 years median age) that participated in three waves (2005, 2011 and 2017) of the “Lebanon Global School-Based Student Health Survey (GSHS)”.Results Significant improvements were found among both boys and girls in the decline of interpersonal violence (bulling victimization, being physically attack and involvement in physical fighting), poor washing of hands after using the toilet, and among girls only suicidal ideation and suicide plan. Significant increases were found among both boys and girls in the prevalence of inadequate fruit consumption, unintentional injury and among boys only poor washing of hands prior to eating and among girls only having no close friends and school truancy.Conclusion Several decreases but also increases of health risk behaviours were found over three assessment points during a period of 12 years calling for continued health enhancing activities in this adolescent population.
Level and Determinants of Willingness to Donate Organs Among the General Public: A Cross-Sectional Survey in China
Authors: Fan Xiaojing , Zheng Sirui , Li Meng , Wang Duolao , Li Enchang , Zhou Zhongliang , Zheng Weirong , Wang Lingling , Zhang Qing , Li Yingying , Lin Jianfeng
Published: May 2020

Background: This study aims to assess the level and determinants of the general public’s willingness to organ donation. Methods: We conducted a population-based cross-sectional study of 4261 participants in China. The primary outcome was the willingness to donate organs. Logistic regression modelling was used to determine the factors that affect willingness to donate organs. Results: Overall, the proportion of participants who showed a willingness to donate organs was 47.45% (95%CI: 0.46, 0.49) in this study. Logistic regression modelling showed participants from Western (OR=1.35, 95%CI=1.13-1.62) and Eastern China (OR=1.54, 95%CI=1.20-1.66) were more willing to donate organs compared with those from Central China. The odds of being willing to donate organs was higher in females than males (OR=1.34, 95%CI=1.17-1.55); and was higher in those participants with experience of organ donation (OR=1.57, 95%CI=1.12-2.20), experience of caring for organ transplant patients (OR=1.47, 95%CI=1.03-2.10), and those undertaking related voluntary activities (OR=1.68, 95%CI=1.45-1.94), than those without. Conclusion: The general public’s level of willingness to organ donation was not high in China. Geographical region, gender, experience of organ donation related activities, taking care of organ transplant patients and volunteering in related activities were independently associated with participants’ willingness to donate organs.
Genome-wide association study for yield and yield related traits under reproductive stage drought in a diverse indica-aus rice panel
Authors: Bhandari Aditi , Sandhu Nitika , Bartholome Jérôme , Cao-Hamadoun Tuong-Vi , Ahmadi Nourollah , Kumari Nilima , Kumar Arvind
Published: May 2020

Background Reproductive-stage drought stress is a major impediment to rice production in rainfed areas. Conventional and marker-assisted breeding strategies for developing drought-tolerant rice varieties are being optimized by mining and exploiting adaptive traits, genetic diversity; identifying the alleles, and understanding their interactions with genetic backgrounds for their increased contribution to drought tolerance. Field experiments were conducted in this study to identify marker-trait associations (MTAs) involved in response to yield under reproductive-stage (RS) drought. A diverse set of 280 indica-aus accessions was phenotyped for grain yield and nine yield-related traits under normal irrigated condition and under two managed reproductive-stage drought environments. The accessions were genotyped with 215,250 single nucleotide polymorphism markers. Results The study identified a total of 220 significant MTAs for 10 traits and candidate gene analysis within a 200kb window centered from GWAS identified SNP peaks detected these MTAs within/ in close proximity to 38 genes, 4 earlier reported major grain yield QTLs and 6 novel QTLs for 7 traits out of the 10. The significant MTAs were mainly located on chromosomes 1, 2, 5, 6, 9, 11 and 12 and the percent phenotypic variance captured for these traits ranged from 5 to 88%. The significant positive correlation of grain yield with yield-related traits, except flowering time, observed under different environments point towards their contribution in improving rice yield under drought. Seven promising accessions were identified for use in future genomics-assisted breeding programs targeting grain yield improvement under drought. Conclusion These results provide a promising insight into the complex genetic architecture of grain yield under reproductive-stage drought in different environments. Validation of major genomic regions reported in the study will enable their effectiveness to develop drought-tolerant varieties following marker-assisted selection as well as to identify genes and understanding the associated physiological mechanisms.
Comparisons of chest computed tomography patterns between survivors and non-survivors with Coronavirus Disease 2019 (COVID-19): a case-control study
Authors: Pan Feng , Zheng Chuansheng , Ye Tianhe , Li Lingli , Liu Dehan , Li Lin , Hesketh Richard L. , Yang Lian
Published: May 2020

Objectives To compare the chest computed tomography (CT) findings between survivors and non-survivors with Coronavirus Disease 2019 (COVID-19).Materials and Methods Between 12 January 2020 to 20 February 2020, the records of 124 consecutive patients diagnosed with COVID-19 were retrospectively reviewed and divided into survivor (83/124) and non-survivor (41/124) groups. Chest CT findings were qualitatively compared on admission and serial chest CT scans were semi-quantitively evaluated between two groups using curve estimations.Results Elder age (median: 69 vs. 43y, p<0.001), higher male ratio (31/41 vs. 32/83, p<0.001), and more comorbidities were observed in non-survivor group. On admission, significantly more bilateral (97.6% vs. 73.5%, p=0.005) and diffuse lesions (39.0% vs. 8.4%, p<0.001) with higher total CT score (median: 10 vs. 4) were observed in non-survivor group compared with survivor group. Besides, crazy-paving pattern was more predominant in non- survivor group than survivor group (39.0% vs. 12.0%, p=0.004). From the prediction of curve estimation, in survivor group total CT score increased in the first 20 days reaching the peak of 6 points and then gradual decreased for more than other 40 days (R2=0.545, p<0.001). In non- survivor group, total CT score rapidly increased over 10 points in the first 10 days and gradually increased afterwards until ARDS occurred with following death events (R2=0.711, p<0.001).Conclusions Persistent progression with predominant crazy-paving pattern was the major manifestation of COVID-19 in non-survivors. Understanding this CT feature could help the clinical physician to predict the prognosis of the patients.
Pulp and Papermaking Characteristics of South Sudanese Cordia Africana (Gambil) Wood
Authors: Elzaki Osman Taha , Tuphach Selim Otuk , Khider Tarig
Published: May 2020

The wood of an important indigenous Sudanese hardwood species, Cordia africana lam, was examined to determine its suitability for pulp and papermaking. Basic density, bark-to-wood ratio, fiber dimensions and chemical composition were studied. Pulps were evaluated and papermaking characteristics were tested. C. africana wood showed medium basic density (410 kg m-1). The average bark-to wood ratio by mass (6.82%) and volume (11.67%) were in the normal average for pulpwood and could be used for production of high grade pulp.The fibers of C. africana were long with an average fiber length of 1.13 mm, average fiber diameter was 30 µm with an average lumen diameter 20 µm and cell wall thickness of 5 µm. the wood showed high ash content (2.7%), high pentosans (25%), relatively medium lignin content (23.9%).C. africana pulped with 12-15% alkali charge as Na2O for two hours at 170 0C gave good Kappa numbers with normal and relatively high yield with very low rejects. The addition of 0.13% anthraquinone (AQ) in cooking liquor reduced the active alkali consumption by 2-2.3%, increased the pulp yield and reduced bleachable Kappa numbers. The pulp produced suitable for wrapping paper and paperboard.
SARS-CoV-2 Seroprevalence Among Parturient Women
Authors: Flannery Dustin D. , Gouma Sigrid , Dhudasia Miren B. , Mukhopadhyay Sagori , Pfeifer Madeline R. , Woodford Emily C. , Gerber Jeffrey S. , Arevalo Claudia P. , Bolton Marcus J. , Weirick Madison E. , Goodwin Eileen C. , Anderson Elizabeth M. , Greenplate Allison R. , Kim Justin , Han Nicholas , Pattekar Ajinkya , Dougherty Jeanette , Kuthuru Oliva , Mathew Divij , Baxter Amy E. , Vella Laura A. , Weaver JoEllen , Verma Anurag , Leite Rita , Morris Jeffrey S. , Rader Daniel J. , Elovitz Michal A. , Wherry E. John , Puopolo Karen M. , Hensley Scott E.
Published: May 2020

SARS-CoV-2 has led to a pandemic of respiratory and multisystem disease, named COVID-19.1 Limited data are available for pregnant women affected by COVID-19.2 Serological tests, particularly those that provide quantitative information, are critically important to determine exposure and immunity to SARS-CoV-2 within both individuals and populations.3 Here, we completed SARS-CoV-2 serological testing of 237 parturient women at two centers in Philadelphia from April 4 to April 15, 2020. Using an assay with a 1.0% false positive rate, we show that 14/237 (5.9%) of parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies. We found significant racial differences, with an 11.2% seropositive rate in black women and a 1.5% seropositive rate in women of other races. Seropositive women who received nasopharyngeal (NP) SARS-CoV-2 PCR (polymerase chain reaction) testing were all found to be positive. Continued serologic surveillance among pregnant women may inform perinatal clinical practices and can potentially be used to estimate seroprevalence within the community.Authors Dustin D. Flannery and Sigrid Gouma contributed equally to this work.
Effect of Antithrombotic Therapy on Secondary Bleeding After Proctological Surgery
Authors: Maemoto Ryo , Tsujinaka Shingo , Miyakura Yasuyuki , Machida Erika , Kakizawa Nao , Takahashi Jun , Tamaki Sawako , Ishikawa Hideki , Rikiyama Toshiki
Published: May 2020

Background: The purpose of this study was to identify the incidence and severity of secondary bleeding after proctological surgery for patients with or without antithrombotic therapy.Methods: We retrospectively identified 113 patients who underwent proctological surgery in our hospital from March 2009 to February 2019. In general, antiplatelet drugs were continued and anticoagulant drugs were either substituted or withdrawn prior to the surgery. The severity of secondary bleeding was classified as mild, moderate, severe.Results: Eighteen patients underwent antiplatelet therapy (A group) and 95 patients did not undergo antithrombotic therapy (N group). Secondary bleeding was observed in nine patients (8.0%) and patients in the A group exhibited significantly higher rate of secondary bleeding rate than patients in the N group (39% vs. 2.4%, P < 0.01). The median interval from surgery to the onset of secondary bleeding was 5 (range: 0-11days). The severity of bleeding was the highest in patients administered direct oral anticoagulants (DOAC) and was the lowest in those administered aspirin. There was no mortality or cardiovascular event.Conclusions: Antithrombotic therapy is associated with high risk of secondary bleeding after proctological surgery, particularly in patients who undergo anticoagulant therapy. Delaying of postoperative resumption of anticoagulants may be considered in balancing the individual risk of postoperative thromboembolic complications against the risk of secondary bleeding. Future prospective studies with larger number of patients are needed to determine the appropriate timing of resuming antithrombotic therapy.
Point-of-care serological assays for SARS-CoV-2 in a UK hospital population: potential for enhanced case finding
Authors: Pallett Scott , Denny Sarah , Patel Aatish , Charani Esmita , Mughal Nabeela , Stebbing Justin , Davies Gary , Moore Luke
Published: May 2020

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Case identification is currently made by real-time polymerase chain reaction (PCR) during the acute phase and largely restricted to healthcare laboratories. Serological assays are emerging but independent validation is urgently required to assess their utility.We evaluated five different point-of-care (POC) SARS-CoV-2 antibody test kits against PCR, finding concordance across the assays (n=15). We subsequently tested 200 patients using the OrientGene COVID-19 IgG/IgM Rapid Test Cassette and find a sensitivity of 74% in the early infection period (day 5-9 post symptom onset), with 100% sensitivity not seen until day 13. Specificity was 96%, but in validating the serological tests uncovered potential false-negatives from PCR testing late-presenting cases. A positive predictive value (PPV) of 37% in the general population precludes any use for general screening. Where a case definition is applied however, the PPV is substantially improved (95·4%), supporting use of serology testing in carefully targeted populations. Larger studies in specific patient cohorts, including those with mild infection are urgently required to inform on the applicability of POC serological assays to help control the spread of SARS-CoV-2 and improve case finding of patients that may experience late complications.
EPDR1 correlates with immune cell infiltration in hepatocellular carcinoma and can be used as a prognostic biomarker
Authors: Chen Ruochan , Zhang Yiya
Published: May 2020

Background: Hepatocellular carcinoma (HCC) has high mortality rate and is a serious disease burden globally. Hence, identification and characterization of novel biomarkers for the diagnosis and prognosis of HCC are critically important. The protein EPDR1 (ependymin related 1) is a member of piscine brain glycoproteins and is involved in cell adhesion. This is the first study to report the expression of EPDR1 and its prognostic significance, pathological role, and association with cancer immunity in HCC.Methods: The gene expression, prognostic, and clinicopathological analyses were performed based on the data obtained from multiple transcriptome databases. Protein expression of EPDR1 in HCC was verified using human protein atlas and CPTAC databases. Co-expression network analysis using the LinkedOmics database was performed to identify genes co-expressed with EPDR1 expression. Functional analysis of the co-expressed genes, including gene set enrichment analysis was performed to identify the functional role of EPDR1. The statistical analysis was conducted in R, and the relationship between EPDR1 expression and immune cell infiltration was analyzed using TIMER and CIBERSORT resources. Results: The expression of EPDR1 was found to be significantly higher in HCC tissues than in the normal tissues and is an independent prognostic factor for the overall survival of HCC patients. Further, a high level of EPDR1 was shown to be correlated with advanced stage of HCC. Functional analysis revealed that EPDR1 is associated with multiple signaling pathways as well as pathways related to cancer and apoptosis. Notably, EPDR1 expression significantly correlated with purity and the infiltration levels of B cells, CD8+ and CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC. Further, the EPDR1 expression significantly correlated with the expression of immune signatures, such as KIR2DL4, ITGAM, GATA3, STAT6, STAT5A, BCL6, STAT3, and HAVCR2.Conclusions: Our study identified EPDR1 as a novel prognostic biomarker in HCC. The expression of EPDR1 was shown to be associated with immune cell infiltration as well as the signature molecules that potentially regulate these processes during the carcinogenesis of HCC. With better understanding of its biological function, EPDR1 could become an effective target for HCC diagnosis and treatment in the future.
To procrastinate or not to procrastinate: the optimal timing of containing the global COVID-19 pandemic spread
Authors: Li Jun , Zhou Yimin , Ye Lingjian , Zhang Joy Y , Chen Zhuo
Published: May 2020

As global public health is under threat by the 2019-nCoV, an urgent question to ask is what the optimal strategy of epidemic prevention and control (P&C) measures would be, especially in terms of the timing of enforcing aggressive policy response so as to maximise health efficacy and to contain pandemic spread. Here, we developed a logistic probability function configured SEIR model to analyse the COVID-19 outbreak and estimate its transmission pattern under different “anticipate- or delay-to-activate” policy response scenarios in containing the pandemic. We wound that the potential positive effects of stringent P&C measures would be cancelled out in case of significantly delayed action, whereas a partially procastinatory wait-and-see control policy may still be able to contribute to containing the degree of epidemic spread although its effectiveness may be significantly compromised compared to a scenario of early intervention coupled with stringent P&C measures. A laissez faire policy adopted by the government and health authority to tackling the uncertainly of COVID19-type pandemic development during the early stage of the outbreak turns out to be a very bad strategy from optimal control perspective, as significant damages would be produced in that case. Authors Jun Li and Yimin Zhou contributed equally to this work.
Drug repurposing: Dipeptidyl peptidase IV (DPP4) inhibitors as potential agents to treat SARS-CoV-2 (2019-nCov) infection
Authors: Rao Praveen P. N. , Pham Amy Trinh , Shakeri Arash , Shatshat Amna El , Zhao Yusheng , Karuturi Rahul C. , Hefny Ahmed A.
Published: May 2020

The current outbreak of severe acute respiratory distress syndrome (SARS) or nCOVID-19 pandemic, caused by the coronavirus-2 (CoV-2), continues to wreak havoc globally. Unfortunately, there are no concrete treatment options available which has severely hampered the pharmacotherapy of this devastating infection. This calls for an urgent need to consider alternative strategies which can be employed quickly, as discovering new drugs for SARS-CoV-2 infections is a time consuming and expensive proposition. In this regard, drug repurposing is an appealing approach which can provide rapid access to therapeutics with proven record of safety and efficacy. Accordingly, we investigated the drug repurposing potential of a library of dipeptidyl peptidase 4 (DPP4) inhibitors which are currently marketed for type-2 diabetes, to treat SARS-CoV-2 infections. Computational studies were conducted in the crystal structure of the substrate binding site of viral protease, the SARS-CoV-2 Mpro dimer, which led to the identification of three marketed DPP4 inhibitors; gemigliptin, linagliptin and evogliptin exhibiting favorable binding, in the SARS-CoV-2 Mpro dimer, viral protease. These studies support the repurposing of DPP4 class of inhibitors in treating SARS-CoV-2 infections, especially in elderly patients with type-2 diabetes, who are at a greater risk of suffering from increased disease severity and mortality.
Analysis of the full genome sequences of SARS-CoV-2 isolates to determine antigenic proteins and epitopes to be used for the development of a vaccine or a diagnostic approach for COVID-19
Authors: Can Hüseyin , Köseoğlu Ahmet Efe , Alak Sedef Erkunt , Güvendi Mervenur , Döşkaya Mert , Karakavuk Muhammet , Gürüz Adnan Yüksel , Ün Cemal
Published: May 2020

In genome of SARS-CoV-2, the 5’-terminus encodes a polyprotein (pp1ab), which is further cleaved into 15 non-structural proteins (nsp-1 to nsp-10 and nsp-12 to nsp-16) whereas the 3’ terminus encodes four structural proteins (spike, envelope, membrane, and nucleocapsid) and eight accessory proteins (3a, 3b, p6, 7a, 7b, 8b, 9b, and orf14). Among these 27 proteins, the present study aimed to discover likely antigenic proteins and epitopes to be used for during the development of a vaccine or serodiagnostic assay using a reverse vaccinology in silico approach. For this purpose, after the full genome analyses of SARS-CoV-2 isolates, viral surface proteins including spike, envelope and membrane proteins as well as proteins with predicted signal peptide were determined as probable vaccine candidates whereas the remaining were considered as possible antigens to be used during development of serodiagnostic assays. According to results, the phylogenetic analysis of SARS-CoV-2 isolates from 31 different countries showed two significant clusters in which one was clustered with China-Wuhan and the other one with China-Yunnan isolates. During the analyses, 105 SNPs were identified that resulted in change in 70 amino acid positions. Among the 27 proteins, 26 of them were predicted as probable antigen, except nsp-16. In 26 proteins, spike protein was selected as the best vaccine candidate because of having a signal peptide, negative grand average of hydropathicity value, one transmembrane helix, moderate aliphatic index, a big molecular weight, a long-estimated half-life, beta wrap motifs as well as having a stable, soluble and non-allergic features. In addition, orf7a, orf8 and nsp-10 proteins were considered as potential vaccine candidates because of having signal peptides. Nucleocapsid protein and a highly antigenic GGDGKMKD epitope of nucleocapsid protein were identified as ideal antigens to be used in development of serodiagnostic assays. Moreover, considering MHC-I alleles, highly antigenic KLNDLCFTNV and ITLCFTLKRK epitopes belonging to spike and orf7a proteins can be used to develop an epitope-based peptide vaccine or used as antigen for development of serodiagnostic assay.
Complete Genome Analysis of A Virulent Vibrio Scophthalmi Strain VSc190401 Isolated form Diseased Marine Fish Half-Smooth Tongue Sole, Cynoglossus Semilaevis
Authors: Zhang Zheng , Yu Yong-xiang , Wang Yin-geng , Liu Xiao , Wang Lifang , Zhang Hao , Liao Mei-jie , Li Bin
Published: May 2020

Background: Vibrio scophthalmi is an opportunistic bacterial pathogen, which is widely distributed in marine environment. Earlier studies have suggested that it is a normal microorganism in turbot gut. However, recent studies have confirmed that this bacterial strain can cause diseases in many different marine animals. Therefore, it is necessary to investigate its whole genome for better understanding its physiological and pathogenic mechanism.Results: In the present study, we obtained a pathogenic strain of V. scophthalmi from diseased half-smooth tongue sole (Cynoglossus semilaevis) and sequenced its whole genome. Its genome contained two circular chromosomes and two plasmids with a total size of 3,541,838 bp, which harbored 3,185 coding genes. Among these genes, 2,648, 2,298 and 1,915 genes could be found through annotation information in COG, Blast2GO and KEGG databases, respectively. Moreover, 10 genomic islands were predicted to exist in the chromosome I through IslandViewer online system. Comparison analysis in VFDB and PHI database showed that this strain had 334 potential virulence-related genes and 518 pathogen-host interaction-related genes. Although it contained genes related to four secretion systems of T1SS, T2SS, T4SS and T6SS, there was only one complete T2SS secretion system. Based on CARD database blast results, 180 drug resistance genes belonging to 27 antibiotic resistance categories were found in the whole genome of such strain. However, there were many differences between the phenotype and genotype of drug resistance.Conclusions: Based on the whole genome analysis, the pathogenic V. scophthalmi strain contained many types of genes related to pathogenicity and drug resistance. Moreover, it showed inconsistency between phenotype and genotype on drug resistance. These results suggested that the physiological mechanism might be complicated.
A Rice Promoter Protein Binding Microarray for Cis-Acting Elements for Rice Transcription Factors
Authors: KIM JOUNG SUG , Chae SongHwa , Jun Kyong Mi , Lee Gang-Seob , Jeon Jong-Seong , Kim Kyungdo , Kim Yeon-Ki
Published: May 2020

BackgroundTranscription factors (TFs) regulate the expression of genes at the transcriptional level by binding a specific DNA sequence. Thus, predicting the DNA-binding motifs of TFs is one of the most important areas for the functional analysis of TFs in the postgenomic era. Although many methods have been developed for this challenge, there are still many TFs with unknown DNA-binding motifs.FindingsIn this paper, we designed an rice (Oryza sativa)-specific protein binding microarray (RPBM), and its probes are 40 bp long with 20 bp of overlap; there are 49 probes spanning the 1 kb promoter region before the translation start site of each gene. To confirm the efficiency of RPBM technology, we selected two TFs, OsWOX13 and OsSMF1. We identified the ATTGATTG DNA-binding sequence and 635 putative target genes of OsWOX13. OsSMF1 bound to GCTGACTCA and GGATGCC sequences and bound especially strongly to CCACGTCA. A total of 932 putative target genes were identified for OsSMF1.ConclusionsRPBM can be applicable in the analysis of DNA-binding motifs for TFs where binding is evaluated in extended natural promoter regions. The analysis can also be applicable to TFs that have single or multiple binding motifs. The technology might even be expanded for application to TFs that are heterodimers or form higher-order complexes.
Construction of a Prognostic Value Model in Papillary Renal Cell Carcinoma by Immune-Related Genes
Authors: Wang Leilei , Gu Weile , Ni Huijun
Published: May 2020

Papillary renal cell carcinoma (PRCC) is the second most common type of renal carcinoma following clear cell renal cell carcinoma, and the role of immune-related genes (IRGs) in tumorigenesis and metastasis is evident; its prognostic value in PRCC remains unclear. In this study, we downloaded the gene expression profiles and clinical data of patients with PRCC from The Cancer Genome Atlas (TCGA) database and obtained IRGs from the ImmPort database. A total of 371 differentially expressed IRGs (DEIRGs) were discovered between PRCC and normal kidney tissues. Prognostic DEIRGs (PDEIRGs) were identified by univariate Cox regression analysis. Then, we screened the four most representative PDEIRGs (IL13RA2, CCL19, BIRC5, and INHBE) and used them to construct a risk model to predict the prognosis of patients with PRCC. This model precisely stratified survival outcome and accurately identified mutation burden in PRCC. Thus, our results suggest that these four PDEIRGs are available prognostic predictors for PRCC. They could be used to assess the prognosis and to guide individualized treatments for patients with PRCC.