bluuebunny/crossref_metadata_2025 huggingface dataset:
Personalising screening of sight-threatening diabetic retinopathy - qualitative evidence to inform effective implementation
Authors: Byrne Paula , Thetford Clare , Gabbay Mark , Clarke Pam , Doncaster Emily , Harding Simon
Published: June 2020

Background

Internationally, systematic screening for sight-threatening diabetic retinopathy (STDR) usually includes annual recall. Researchers and policy-makers support extending screening intervals, citing evidence from observational studies with low incidence rates. However, there is little research around the acceptability to people with diabetes (PWD) and health care professionals (HCP) about changing eye screening intervals.

Methods

We conducted a qualitative study to explore issues surrounding acceptability and the barriers and enablers for changing from annual screening, using in-depth, semi-structured interviews analysed using the constant comparative method. PWD were recruited from general practices and HCPs from eye screening networks and related specialties in North West England using purposive sampling. Interviews were conducted prior to the commencement of and during a randomised controlled trial (RCT) comparing fixed annual with variable (6, 12 or 24 month) interval risk-based screening.

Results

Thirty PWD and 21 HCP participants were interviewed prior to and 30 PWD during the parallel RCT. The data suggests that a move to variable screening intervals was generally acceptable in principle, though highlighted significant concerns and challenges to successful implementation. The current annual interval was recognised as unsustainable against a backdrop of increasing diabetes prevalence. There were important caveats attached to acceptability and a need for clear safeguards around: the safety and reliability of calculating screening intervals, capturing all PWDs, referral into screening of PWDs with diabetic changes regardless of planned interval. For PWDs the 6-month interval was perceived positively as medical reassurance, and the 12-month seen as usual treatment. Concerns were expressed by many HCPs and PWDs that a 2-year interval was too lengthy and was risky for detecting STDR. There were also concerns about a negative effect upon PWD care and increasing non-attendance rates. Amongst PWDs, there was considerable conflation and misunderstanding about different eye-related appointments within the health care system.

Conclusions

Implementing variable-interval screening into clinical practice is generally acceptable to PWD and HCP with important caveats, and misconceptions must be addressed. Clear safeguards against increasing non-attendance, loss of diabetes control and alternative referral pathways are required. For risk calculation systems to be safe, reliable monitoring and clear communication is required.
Quantifying flight aptitude variation in wild An. gambiae s.l. in order to identify long-distance migrants
Authors: Faiman Roy , YARO Alpha Seydou , Diallo Moussa , Dao Adama , Samake Djibril , Sanoga Zana Lamissa , Sullivan Margery , Krishna Asha , Krajacich Benjamin J , Lehmann Tovi
Published: June 2020

Background In the West African Sahel, mosquito reproduction is halted during the 5-7 month-long dry season, due to the absence of surface waters required for larval development. However, recent studies have suggested that both Anopheles gambiae s.s and An. arabiensis repopulate this region via migration from distant locations where larval sites are perennial. An. coluzzii engages in more regional migration, presumably within the Sahel, following shifting resources correlating with the ever-changing patterns of Sahelian rainfall. Understanding mosquito migration is key to controlling malaria—a disease that continues to claim more than 400,000 lives annually, especially those of African children. Using tethered flight data of wild mosquitoes, we evaluated the distribution of flight parameters as indicators of long-range migrants vs. appetitive flyers, compared species specific seasonal differences and gonotrophic states on flight activity. We also evaluated morphometrical differences in the wings of mosquitoes exhibiting high flight activity (HFA) vs. low flight activity (LFA). Methods We used a novel tethered-flight assay to characterize flight in the three primary malaria vectors- An. arabiensis, An. coluzzii and An. gambiae s.s. The flights of tethered wild mosquitoes were audio-recorded from 21:00h to 05:00h in the following morning and three flight aptitude indices were examined: total flight duration, longest flight bout, and the number of flight bouts during the assay. Results The distributions of all flight indices were strongly skewed to the right, indicating that the population consisted of a majority of low-flight activity (LFA) mosquitoes and a minority of high-flight activity (HFA) mosquitoes. The median total flight was 586 seconds and the maximum value was 16,110 seconds (~4.5 h). In accordance with recent results, flight aptitude peaked in the wet season, and was higher in gravid females than in non-bloodfed females. Flight aptitude was also found to be higher in An. coluzzii compared to An. arabiensis, with intermediate values in An. gambiae s.s., but displaying no statistical difference. Evaluating differences in wing size and shape between LFA individuals and HFA ones, the wing size of HFA An. coluzzii was larger than that of LFAs during the wet season—its length was wider than predicted by allometry alone, indicating a change in wing shape. No statistically significant differences were found in the wing size/shape of An. gambiae s.s. or An. arabiensis. Conclusions The partial agreement between the tethered flight results and recent results based on aerial sampling of these species suggest a degree of discrimination between appetitive flyers and long-distance migrants although identifying HFAs as long-distance migrants is not recommended without further investigation.
Biospeckle optical coherence tomography in speedy visualizing effects of foliar application of plant growth hormone to Chinese chives leaves
Authors: RAJAGOPALAN UMAMAHESWARI , Kabir Mahjabin , Lim Yiheng , Kadono Hirofumi
Published: June 2020

Objective: The aim of this study is to demonstrate the potential of applying the contrast of the speckles obtained as noise in optical coherence tomography (OCT) images to monitor short term activity changes during foliar application of phytohormones to a plant leaf. Plant growth hormone, gibberellic acid (GA3) was sprayed onto the leaf of Chinese chives and after 60 minutes, OCT images (1frame:512x2048pixles) were recorded at ten frames per second for a few tens of seconds. Results: Contrast across the temporal axis was calculated for each pixel of the structural images and biospeckle OCT contrast images were obtained under the conditions of before and after application of GA3 for different concentrations 0, 40, and 100 mM. Application of 40 mM GA3 failed to show any differences in the OCT structural images. However, bOCT contrast image was clearly different. Changes were found to be statistically significant.Although the mechanism for the contrast difference is not clear, it can be said there is a large change across the temporal scale with the application of GA3. Demonstration of OCT utilizing the speckle contrast is believed to have the potential as a promising tool in plant physiology.
“Universal test and treat” program reduced TB incidence by 75% among a cohort of adults taking antiretroviral therapy (ART) in Gurage zone, South Ethiopia
Authors: Girum Tadele , Yasin Fedila , Dessu Samuel , Zeleke Bereket , Geremew Mulugeta
Published: June 2020

Background: Tuberculosis (TB) remains the leading cause of morbidity and mortality in peoples living with HIV and at least 25% of deaths are attributed to TB. Many countries implement the Universal Test and Treat (UTT) program for HIV, which is believed to reduce the incidence of TB. However, there are limited studies that evaluate the impact of UTT on TB incidence. Therefore, by recruiting a cohort of ART users in the “UTT” and “differed treatment” programs, we aim to measure the effect of the UTT program on TB incidence.Objective: To measure the effect of “UTT” program on TB incidence among a cohort of adults taking antiretroviral therapy (ART) in Gurage Zone, South Ethiopia.Methods: A retrospective cohort study was conducted through record review over 5 years (2014-2019) in public health facilities in Gurage Zone. 384 records were randomly selected and reviewed using a standardized structured checklist. Data was entered using Epi InfoTM Version 7 and analyzed by STATA. A generalized linear model with binomial link function was fitted to measure the adjusted incidence density/incidence rate ratio and to identify predictors of incidence difference between the two programs.Results: During the follow up period, 39 incident TB cases were identified with an overall incidence rate of 4.79/100 person-year (PY). TB incidence was significantly lower in the UTT cohort (IR=2.10/100 PY) in comparison to the differed program cohort (IR=6.23/100 PY). The adjusted incidence rate ratio (AIRR) of TB among patients enrolled in the UTT program was; 0.25 (95% CI=0.08-0.70). Thus, there was a reduction of TB incidence by 75% in the UTT program compared to differed program. In addition, IPT (isoniazid preventive therapy) use (AIRR= 0.35 (95% CI=0.22-0.48)), WHO Stage I and II (AIRR=0.70 (95% CI=0.61-0.94)) and higher base line CD4 count (AIRR=0.96 (95% CI=.94-0.99)) significantly reduced the incidence of TB. However, treatment failure increase the incidence (AIRR=5.8 (95% CI=1.93-8.46)). Conclusion: TB incidence was significantly reduced by 75% after UTT. Therefore, intervention to further reduce the incidence has to focus on strengthening UTT program and IPT.
Validation of Family Planning tool in the Pastoralist Community
Authors: Alemayehu Mussie , Medhanyie Araya Abrha , Reed Elizabeth , Bezabih Afework Mulugeta
Published: June 2020

Background: Pastoralist community, Afar, women felt that they are embedded in strong cultural and religious perspectives which promotes a high number of children, and discourages family planning (FP) use. They are multifaced factors which hinder women not to use FP and it is time to develop a context-based tool to understand the situation at the ground. However, we have a dearth of evidence on a reliable and valid tool. Therefore, this study aims in developing a reliable and valid tool that considers the women's knowledge, male involvement, attitude, and belief about whether most people approve or disapprove of the behavior to use or not use of FP. Methods: A total of 891 married women participated in the study. Reviewing the literature, piloting, pretesting, and collecting the actual data were the steps we used to develop a reliable and valid tool. We used the integrated behavioral model (IBM) as a conceptual framework for developing the tool. The developing tool consists of 1) knowledge 2) perceived male involvement and 3) constructs of integrated behavioral model (IBM); expressional and instrumental attitude, subjective norm, self-efficacy, perceived control and intention to use of FP. The IBM items composed of direct and indirect measurement. In the analysis of the data, exploratory and confirmatory factor analysis was done. Independent t. test with cohen’s d was used to calculate the effect size. The correlation coefficient was carried between the direct and indirect measurements of the items of the integrated behavioral model (IBM). Results: A total of 891 pastoralist married women were included in the analysis of the reliability and validity of the tool. The mean age of the participants was 26.74(±6.45). The KMO value for all items was greater than 0.83 with a Bartlett test of sphericity of (p<0.00). Thirteen items were used to measure the knowledge of the respondent towards FP use. The tool had 64.92 variances explained and Cronbach alpha of 0.85. Acceptable values of the fitness indices were obtained in the confirmatory factor analysis (CFA) The items of knowledge towards FP had normed chi-square of 4.5, RMSEA with 90% CI of 0.064(0.056,.0.071), SRMR of 0.039, CFI of 0.969 and TLI of 0961. All the developed items had a Cohen’s d ranges from 0.5 to 2. Moreover, the correlation test of the IBM ranges from 0.6 to 0.7 which shows a higher correlation between the measurement direct and indirect items.Conclusion: The pastoralist community version of the FP questionnaire is a valid and reliable tool and can be used to measure future family planning use. The indirect measurement of the IBM constructs was a good item to measure FP. However, as a limitation of the study respondents may face difficulty in realizing the difference one item to another especially when items on the scale look so similar to her.
Cyclin H predicts the poor prognosis and promotes the proliferation of ovarian cancer
Authors: Peng Chen , Yang Yansong , Ji Li , Yang Panpan , Yang Xiaoqing , Zhang Yuquan
Published: June 2020

Background: Cell cycle dysregulation plays a key role in the pathogenesis of malignant tumors. As a part of the CDK-activating kinase (CAK) trimeric complex, cyclin H is necessary to regulate the cell cycle and proliferation. This investigation aims to characterize the clinical significance and the biological functions of cyclin H in ovarian cancer. Methods: Immunohistochemical staining was performed on 60 ovarian cancer cases, and a correlation between cyclin H expression and the clinical characteristics of ovarian cancer was analyzed. The function of cyclin H in ovarian cancer was further explored using HO8910 cells and a subcutaneous xenograft model of nude mice. Result: Cyclin H was slightly expressed in grade 1 ovarian cancer but highly expressed in grade 2 and grade 3 cancerous tissues. The Spearman’s rank correlation analysis showed that the expression of cyclin H is positively correlated with the tumor grade, the FIGO stage, histological grade, and the peritoneal metastasis of ovarian cancer and is also positively correlated with the Ki67 and p-CDK2 in ovarian cancer. Additionally, we found that the five-year survival rate was higher in patients expressing low cyclin H than those expressing high cyclin H . Further, knockdown of cyclin H was achieved using an shRNA in HO8910 ovarian cancer cell line. Silencing cyclin H resulted in a G1/S cell cycle arrest in ovarian cancer cells suppressing its growth. The Ki67 expression was also decreased in cyclin H silenced ovarian cancer. Conclusion: These results suggest that high expression of cyclin H predicts the poor prognosis and promotes the growth of ovarian cancer by regulating the cell cycle.
Patterns of food parenting practices regarding junk food and sugary drinks among parent-child dyads
Authors: Thomson Jessica , Hennessy Erin , Landry Alicia , Goodman Melissa
Published: June 2020

Background: Children’s food preference and intake patterns are affected by parental child feeding practices. The objective was to determine patterns of food parenting practices regarding junk food and sugary drinks (JS) and investigate their associations with demographic characteristics and dietary intake in a large cohort of parents and their children (12-17 years).Methods: Dyadic survey data from the cross-sectional, internet-based Family Life, Activity, Sun, Health, and Eating Study, conducted in 2014, were analyzed using latent class analysis to identify patterns of use for six JS parenting practices – negative emotions, restriction, monitoring, availability, modeling, and child involvement – based on both parent and child report. Model covariates included self-reported parent sex, body mass index, added sugars intake, and legitimacy of parental authority; and self-reported child age, sex, body mass index percentile, added sugars intake, and legitimacy of parental authority. Results: Based on 1,657 parent-child dyads, five parenting practice patterns were identified – Complete Influencers (28%; reference class), Indifferent Influencers (21%), Negative Influencers (20%), Minimal Influencers (18%), and Disagreeing Influencers (13%). Compared to older child dyads, younger child dyads were less likely to belong to Indifferent and Minimal Influencers (79% and 63% lower odds, respectively). Greater parent added sugars intake increased the odds of belonging to Indifferent and Negative Influencers (4% and 5% higher for every teaspoon increase, respectively) while greater child added sugars intake decreased the odds of belonging to Minimal Influencers (6% lower for every teaspoon increase). Compared to dyads with high agreement, dyads with low parental and child agreement with legitimacy of parental authority regarding JS were 2 to 26 times as likely to belong to one of the other four classes. Conclusions: The study findings suggest that parents utilize distinct patterns of feeding practices regarding JS ranging from use of many practices, use of some practices, to low use of any practice, with differential associations with parent and child intakes of added sugars. Counseling or intervening with parents to use a mix of structure practices to positively influence their child’s and possibly their own intake of sugary snacks and drinks may prove more efficacious than use of coercive control practices.
Phylogenetic analysis of Anguilla marmorata population in Thua Thien Hue, Vietnam based on the cytochrome c oxidase I (COI) gene fragments
Authors: Linh Nguyen Quang , Huyen Kieu Thi
Published: June 2020

The giant mottled eel is a species with high commercial value so overfishing, river management, and water pollution have negatively affected its movement and population numbers. Anguilla marmorata (eel) was listed in the Vietnam Red Data Book 2007 with a description of Vulnerability. This study used a barcode technique to analyze molecular characteristics and build genetic plants based on the cytochrome c oxidase I gene segment isolated from the mitochondrial genome of 48 individuals of A. marmorata collected in five different ecological regions of Thua Thien Hue, Vietnam. The isolated the cytochrome c oxidase I sequence has a length of 843 nucleotides, four base nucleotides of 30.03% Thymine, 25.15% Cytosine, 27.49% Adenine, and 17.43% Guanine. The percentage of Guanine + Cytosine content (42.58%) is acceptable, lower than the Adenine + Thymine content. The replacement capacity of Adenine and Guanine is 22.45% highest, the ratio between Thymine and Guanine; Cytosine and Guanine are the lowest at 2.72%. The establishment of genetically modified plants has shown the high genetic similarity of individuals in eel populations in Thua Thien Hue. The population of Anguilla marmorata eels in Thua Thien Hue, Vietnam is divided into two separate groups that are guided by the migration process and specific ecological. This is particularly important in building strategies to conserve and develop the gene for eel in Vietnam and Thua Thien Hue.
Investigation of the effects of P1 on HC-Pro-mediated gene silencing suppression through genetics and omics approaches
Authors: Hu Sin-Fen , Wei Wei-Lun , Hong Syuan-Fei , Fang Ru-Ying , Wu Hsin-Yi , Lin Pin-Chun , Sanobar Neda , Wang Hsin-Ping , Sulistio Margo , Wu Chun-Ta , Lo Hsiao-Feng , Lin Shih-Shun
Published: June 2020

Background: Posttranscriptional gene silencing (PTGS) is one of the most important mechanisms for plants during viral infection. However, viruses have also developed viral suppressors to negatively control PTGS by inhibiting microRNA (miRNA) and short-interfering RNA (siRNA) regulation in plants. The first identified viral suppressor, P1/HC-Pro, is a fusion protein. Upon infecting plants, the P1 protein itself is released from HC-Pro by the self-cleaving activity of P1. P1 has an unknown function in enhancing HC-Pro-mediated PTGS suppression. We performed proteomics to identify P1-interacting proteins. We also performed transcriptomics that were generated from Col-0 and various P1/HC-Pro-related transgenic plants to identify novel genes. The results showed several novel genes were identified through the comparative network analysis that might be involved in P1/HC-Pro-mediated PTGS suppression. Results: First, we demonstrated that P1 enhances HC-Pro function and that the mechanism might work through P1 binding to VERNALIZATION INDEPENDENCE 3/SUPERKILLER 8 (VIP3/SKI8), a subunit of the exosome, to interfere with the 5'-fragment of the PTGS-cleaved RNA degradation product. Second, specifically the AGO1 was specifically posttranslationally degraded in transgenic Arabidopsis expressing P1/HC-Pro of turnip mosaic virus (TuMV) (P1/HCTu plant). Third, the comparative network highlighted potentially critical genes in PTGS, including miRNA targets, calcium signaling, hormone (JA, ET, and ABA) signaling, and defense response. Conclusion: Through these genetic and omics approaches, we revealed an overall perspective to identify many critical genes involved in PTGS. These new findings significantly impact in our understanding of P1/HC-Pro-mediated PTGS suppression.
Plasmodium falciparum genetic factors rather than host factors are likely to drive resistance to ACT in Ghana
Authors: Hodoameda Peter , Duah-Quashie Nancy Odurowah , Hagan Charles Oheneba , Matrevi Sena , Abuaku Benjamin , Koram Kwadwo A , Quashie Neils B
Published: June 2020

Background Artemisinin-based combination therapy (ACT) partner drugs, currently used in Ghana are lumefantrine, amodiaquine and piperaquine. Plasmodium falciparum isolates with reduced susceptibility to these partner drugs may affect treatment outcome. Mutations in pfmdr1 gene is linked to reduced parasite susceptibility to amodiaquine and lumefantrine. In addition, the potency of the partner drugs in vivo depends on the metabolism by the cytochrome P450 (CYP) enzyme in the host. Mutations in the CYP2C8 and CYP3A4 genes are linked to reduced metabolism of amodiaquine and lumefantrine in vitro, respectively. This study investigated the host and parasite genetic factors affecting the susceptibility of the malaria parasite to ACT partner drugs.Methods Archived samples from 240 patients age ≤9 years participating in anti-malarial drug resistance survey in Ghana, and given artemether with lumefantrine (AL) or artesunate with amodiaquine (AA), were selected and analysed. Polymerase chain reaction (PCR) followed by Sanger sequencing was used to determine the polymorphisms in CYP2C8, CYP3A4 and pfmdr1 genes. Results For CYP3A4, all had wild type alleles, suggesting that the hosts are good metabolizers of lumefantrine. For CYP2C8 60% had wild type alleles, 35% heterozygous and 5% homozygous recessive alleles suggesting efficient metabolism of amodiaquine by the hosts. For pfmdr1 gene, at codon 86, 95% were wild type (N86) and 5% mutant (Y86). For codon 184, 36% were wild type (Y184) and 64% mutant (F184) while for codons 1034, 1042 and 1246, 100% (all) were wild type. The high prevalence of N86-F184-D1246 haplotype (NFD) suggest presence of parasites with reduced susceptibility to lumefantrine and not amodiaquine. Delayed clearance was observed in individuals with mutations in the pfmdr1 gene and not cytochrome 450 gene. Both synonymous and non-synonymous mutations were observed in the Pfmdr1 at low prevalence. Conclusion The outcome of this study indicates that the parasite's genetic factors rather than the host’s are likely to drive resistance to ACT in Ghana.
A Cohort Study Evaluating the Association Between Concurrent Mental Disorders, Mortality, Morbidity, and Continuous Treatment Retention for Patients in Opioid Agonist Treatment (OAT) Across Ontario, Canada Using Administrative Health Data
Authors: Morin Kristen , Eibl Joseph K , Gauthier Graham , Rush Brian , Mushquash Christopher , Lightfoot Nancy E , Marsh David
Published: June 2020

Background: Due to the high prevalence of mental disorders among people with opioid use disorder, the objective of this study was to determine the association between concurrent mental disorders, mortality, morbidity and continuous treatment retention for patients in opioid agonist treatment in Ontario, Canada. Methods: We conducted a retrospective cohort study of patients enrolled in opioid agonist treatment between January 1, 2011, and December 31, 2015. Patients were stratified into two groups: those diagnosed with concurrent mental disorders and opioid use disorder and those with opioid use disorder only, using data from the Ontario Health Insurance Plan Database, Ontario Drug Benefit Plan Database. The primary outcome studied was all-cause mortality using data from the Registered Persons Database. Emergency Department visits from the National Ambulatory Care Database, hospitalizations Discharge Abstract Database, and continuous retention in treatment, defined as one year of uninterrupted opioid agonist treatment using data from the Ontario Drug Benefit Plan Database, were measured as secondary outcomes. Encrypted patient identifiers were used to link information across databases.Results: We identified 55,924 individuals enrolled in opioid agonist treatment, and 87% had a concurrent mental disorder diagnosis during this period. We observed that having a mental disorder was associated with an increased likelihood of all-cause mortality (Odds Ratio (OR) 1.4; 95% Confidence Interval (CI) 1.2-1.5. For patients who had been diagnosed with mental disorders, the number of ED visits per year 2.25 times higher, and the number of hospitalizations per year was 1.67 times higher than for patients with no mental disorders. However, there was no association between having a diagnosis of a mental disorder and one-year treatment retention in OAT adjusted Hazzard Ratio (HR) = 1.0; 95%CI 0.9 to 1.1).Conclusion: Our findings highlight the consequences of the high prevalence of mental disorders for individuals with opioid use disorder in Ontario, Canada
Overexpression of ANP32E is associated with poor prognosis of pancreatic cancer and promotes cell proliferation and migration through regulating β-catenin
Authors: Zhang Jianwei , Lan Zhongmin , Qiu Guotong , Ren Hu , Zhao Yajie , Gu Zongting , Li Zongze , Feng Lin , He Jin , Wang Chengfeng
Published: June 2020

Background: Pancreatic cancer is a malignant tumor with high lethality. Acidic nuclear phosphoprotein 32 family member E (ANP32E) is a specific H2A.Z chaperone. The role of ANP32E in pancreatic cancer is poorly understood. This study aimed to investigate the clinical relevance and function of ANP32E in pancreatic cancer.Methods: The expression of ANP32E in 179 pancreatic cancer tissues and 171 normal tissues, and its correlation with patients’ survival were analyzed from the TCGA database. ANP32E was overexpressed and silenced using lentivirus. siRNA was used to knock down β-catenin. CCK8, colony formation, cell cycle detection and Transwell assays were performed to determine cell proliferation and migration. qRT-PCR and Western blot were conducted to detect mRNA and protein expression.Results: ANP32E was an oncogene in pancreatic cancer. ANP32E was up-regulated in pancreatic cancer tissues and cells. Up-regulation of ANP32E predicted poor survival in patients. Lentivirus-mediated knockdown of ANP32E suppressed the proliferation, colony growth and migration of PANC1 and MIA cells. By contrast, ANP32E overexpression promoted the proliferation and migration capacity of the cells. In addition, ANP32E overexpression accelerated the cell cycle progression in PANC1 and MIA cells. Molecular experiments showed that ANP32E activated β-catenin/cyclin D1 signaling. Silencing of β-catenin reduced cell proliferation and migration in ANP32E over-expressed cells.Conclusion: Our results reveal that ANP32E functions as an oncogene in pancreatic cancer via activating β-catenin.
Autonomous replication sequences from the Amaranthus palmeri eccDNA replicon enable replication in yeast
Authors: Molin William T. , Yaguchi Allison , Blenner Mark , Saski Christopher
Published: June 2020

Objective: The objective of the research presented here was to determine whether autonomous replication sequences (ARS) discovered in the eccDNA replicon of glyphosate resistant Amaranthus palmeri enable self-replication in a yeast system. Results: Sequence analysis of the eccDNA replicon revealed a region of sharp changes in A+T/G+C content with characteristic bending indicative of an autonomous replication sequence. Further sequence analysis revealed an extended autonomous replication sequence (EACS) in close proximity to multiple DNA unwinding element (DUE) sequences. This region of the eccDNA replicon enabled autonomous replication of an ARS-less yeast plasmid.
Clinical Features, Prognostic Factors, and Treatment Strategy of Osteoblastoma-like Osteosarcoma: A Case Report and Review of the Literature
Authors: Huo Xu-Lei , Ma Jun-Peng , Song Lai-Rong , Tian Kai-Bing , Du Jiang , Wu Zhen , Li Da
Published: June 2020

Background： Osteoblastoma-like osteosarcoma is a very rare tumor and the diagnosis and the treatment can be challenging and controversial. Herein, we presented a case occurring in the occipital bone firstly and summarized all of the previously published cases to delineate the clinical characteristics, prognostic factors and treatment strategy of osteoblastoma-like osteosarcoma. Case presentation: A 34-year-old man presented with a headache with bitter and dull for 6 months, underwent a suboccipital posterior median approach to remove the lesion without intra-operative complications. Computerized tomography revealed osteogenic bone destruction on the occipital protuberance involving inner and outer table of the skull. Preoperative Magnetic Resonance Venogram revealed that the tumor invades sinus convergence, disappeared sinus convergence, narrowed bilateral transverse sinus, and abundant tumor blood vessels. Re-examination on the day after operation revealed that the post-operative changes of the occipital bone and the tumor were resected completely. The pathologic examination identified the Osteoblastoma-like osteosarcoma. The postoperative course was uneventful. Patient was discharged home 7 days after operation. By four months, re-examination Magnetic Resonance Imaging scan revealed that there was no evidence of recurrence and was not leaded to any problem. Conclusion: For patients with presumed osteoblastoma-like osteosarcoma, gross total resection should be recommended. If tolerable, radiotherapy or chemotherapy could be an alternative treatment modality. Patients with areas of conventional osteosarcoma had poor progression-free survival and tumors with metastasis had a poor overall survival. The lung was the most frequently involved regions of metastasis. Trial registration: CRD, CRD42019121880. Registered 13 February 2019, https://www.crd.york.ac.uk/PROSPERO
A comparative study of transscrotal, transinguinal and laparoscopic orchidopexy for inguinal cryptorchidism
Authors: Wang Yun-jin , Zhang Qi-liang , Chen Liu , Cui Xu , Zhou Chao-ming , Zhou Qing , zhang zhengmian
Published: June 2020

Background
A retrospective comparative study was performed on scrotal incision, inguinal incision and laparoscopic orchidopexy. The characteristics of the different surgical methods were analysed.
Methods
Clinical data of 158 patients with inguinal cryptorchidism admitted to our hospital from January 2017 to January 2018 were retrospectively analysed.
Results
The operation time in the scrotal incision group was significantly less than that in the inguinal incision group and laparoscopic group (P < 0.05). The length of the operative incision in the scrotal incision group and laparoscopic incision group was shorter than that in the inguinal incision group. There was no significant difference in the postoperative hospitalisation time or hospitalisation cost among the three groups (P > 0.05). The incidence of scrotal haematoma in the scrotal incision group was significantly higher than that in the inguinal incision group and laparoscopic group. There were no complications, such as testicular atrophy, testicular retraction, indirect inguinal hernia, or hydrocele.
Conclusions
Transscrotal incision, transinguinal incision and laparoscopic orchidopexy are safe for the treatment of inguinal cryptorchidism. Satisfactory early clinical results can be achieved. Rational use of scrotal incision surgery and laparoscopic surgery for cryptorchidism may replace transinguinal surgery and can provide a good cosmetic effect for children.
Bioinformatics Approach to Investigate the Genes Manifesting Alopecia Areata
Authors: Kaushal Shruti , Puri Veena
Published: June 2020

The authors have withdrawn this preprint due to author disagreement.
VALD-3, a Schiff base ligand synthesized from o-vanillin derivatives, induces cell cycle arrest and apoptosis in breast cancer cells by inhibiting the Wnt/β-catenin pathway
Authors: Li Hongling , Dang Chunyan , Tai Xiaohui , Xue Li , Meng Yuna , Ma Shuping , Zhang Jing
Published: June 2020

Background: Schiff base compounds and their metal complexes have become important synthetic organic drugs due to their extensive biological activities, which include anticancer, antibacterial and antiviral effects. In this study, we investigated the cytotoxic and apoptotic effects of VALD-3, a Schiff base ligand synthesized from o-vanillin derivatives, on human breast cancer cells and the possible underlying mechanisms.Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-test was used to observe the proliferation of human breast cancer MCF-7 and MDA-MB-231 cells induced on VALD-3. The effects of VALD-3 on the cell cycle were analyzed in MCF-7 and MDA-MB-231 cells by PI single staining. Hoechst 33258 staining was performed to determine if VALD-3 induced apoptosis of MCF-7 and MDA-MB-231 cells and Annexin V/PI staining was performed to quantify the percentages of apoptosis. The expression of pro-apoptotic proteins and anti-apoptotic proteins in MCF-7 and MDA-MB-231 cells was investigated by Western blotting. Wnt/β-catenin signaling pathways were also examined. The antitumor activity and survival analysis of VALD-3 in vivo was determined by the nude mice xenograft assay.Results: Flow cytometry analysis showed that VALD-3 triggered cell cycle arrest and induced apoptosis of breast cancer cells. Western blot analysis revealed that VALD-3 upregulated pro-apoptotic proteins (Bad and Bax), downregulated anti-apoptotic proteins (Bcl-2, Bcl-xl, survivin and XIAP) and increased the expression of cleaved caspase-3, cleaved caspase-8, Cyto-c and cleaved PARP. VALD-3 also regulated the Wnt/β-catenin signaling pathway in breast cancer cells, inhibiting the activation of downstream molecules. By xenografting human breast cancer cells into nude mice, we found that VALD-3 significantly suppressed tumor cell growth while showing low toxicity against major organs. In addition, survival analysis results showed that VALD-3 can significantly prolong the survival time of mice (P=0.036).Conclusion: This study is the first to show that VALD-3 induces apoptosis and cell cycle arrest in human breast cancer cells by suppressing Wnt/β-catenin signaling, indicating that it could be a potential drug for the treatment of breast cancer.
Frequency distribution of IL-17A G197A (rs2275913) and IL-17F A7488G (rs763780) polymorphisms among healthy Sudanese population
Authors: Mohamed Nouh Saad , Siddig Emmanuel E. , Ahmed Abdallah E. , Albsheer Musab MA. , Abdelbagi Hanadi , Ali Eman T. , Alsubki Anadel A. , Abdalaziz Sabah A. , Mustafa Madinna , Muneer Mohamed S. , Osman Hussam A. , Osman Maha M. , Ali Mohamed S. , Edris Ali MM. , Ahmed Ayman , Omer Rihab A.
Published: June 2020

Objectives: IL-17A G197A and IL-17F A7488G polymorphisms has been identified to be associated with the susceptibility to many diseases. This study aimed to investigate the frequency distribution of IL-17A G197A and IL-17F A7488G polymorphisms among healthy Sudanese population. A descriptive cross-sectional hospital-based molecular study conducted in different sites throughout Sudan. Two ml blood samples were collected from 717 healthy participants. Demographic data and the medical history of the participants were collected.Results: Of the 717 participants, 355 (49.5%) were males and 362 (50.5%) were females, their mean age was 30.2±17.2 and 32.2±16.5, respectively. For IL-17A, the most frequent genotype detected among males and females was IL-17A heterozygote allele (AG); 215 (60.6%) and 194 (53.6%), respectively. Whereas, for IL-17F, the most frequent allele among males and females was the homozygote allele (AA); 298 (83.9%) for males and 322 (89.0%) for females. HWE for genotype distributions of IL-17A was showing statistical insignificance for IL-17A among males and females, P value 0.614. While HWE for IL-17F reached the equilibrium level, P value 0.048. The most frequent age group was those aged between 21 to 40 years; 281 (39.2%). Arab constituted the major ethnicity of the study participants; 418 (58.3%), P value 0.034.
The Social Risk Factors for Internet Addiction in College Undergraduate Students
Authors: Lin Xia , Gu Jingyan , Guo Wan-jun , Meng Ya-jing , Wang Hui-yao , Li Xiao-jing , Deng Wei , Zhao Lian-sheng , Ma Xiao-hong , Li Ming-li , Chen Ting , Cheng Andy S.K. , Li Tao
Published: June 2020

Objective: The current study aims to explore precipitating and risk factors for internet addiction (IA) in university undergraduate students, and to provide evidence for interventions and the early prevention of IA in this population.Method: Four thousand eight hundred and fifty-eight college sophomores completed an online survey on their internet use-related behaviours and social risk factors.Result: Compared to female students (5.4%), more male students (8.3%) were in the moderate and severe IA groups. Male and female students tend to engage in different types of online entertainment. There are some shared and some different precipitating factors for internet use and risk factors for IA between the different gender groups.Conclusion: By understanding the differences and similarities in risk factors for IA in both gender groups of the university undergraduate students, interventions can be more precisely designed to target specific behaviours in this populations.
A validation study of the Hospital Anxiety and Depression Scale (HADS) in WLHIV
Authors: Yousuf Abdilahi , Musa Ramli , Md. Muhammad Lokman , Arifin Siti Roshaidai Mohd
Published: June 2020

Background

Hospital Anxiety and Depression Scale (HADS) is a self-assessment tool that measures anxiety and depression and is mostly used in hospital settings. The purpose of this study is to test the validity and reliability of the Somali version of HADS in selected two hospitals in eastern Ethiopia.
Method:

From the WLHIV who attend the ART service, 357 women were included in the study and assessed with this tool. The English language of HADS was translated into the Somali version and used for this study. Statistical analysis was computed to examine the validity and measure the reliability of the study.
Result

This version of HADS was found to be acceptable for people living with HIV. To test the reliability, the internal consistency was found to be 0.83 for the anxiety sub-scale and 0.84 for the depression sub-scale. The Somali version of HADS has shown good internal consistency with its metric properties similar to international literature. By two-factor analysis, the Varimax rotation has shown high factor loading in both sub-scales (Anxiety and depression).
Conclusion

Therefore, this version can be used to screen the anxiety and depression of patients living with HIV. Therefore, the findings of this validation study show that the Somali version of the HADS is a valid and reliable tool to measure depression and anxiety and can be used to screen people living with HIV.
Climatic and topographic changes since the Miocene influenced the radiation and biogeography of tent tortoises (Psammobates tentorius) species complex in southern Africa as inferred from mitochondrial and nuclear genes, microsatellite markers as well as ecological niche modelling
Authors: Zhao Zhongning , Heideman Neil , Bester Phillip , Jordaan Adriaan , Hofmeyr Margaretha D.
Published: June 2020

Background
Climatic and topographic changes function as key drivers in shaping genetic structure and cladogenic radiation in many organisms. Southern Africa has an exceptionally diverse tortoise fauna, harbouring one-third of the world’s tortoise genera. The distribution of Psammobates tentorius covers two of the 25 biodiversity hotspots of southern Africa, the Succulent Karoo and Cape Floristic Region. The highly diverged P. tentorius represents an excellent model species for exploring biogeographic and radiation patterns of reptiles in southern Africa.
Results
We investigated genetic structure, population dynamics and radiation patterns against temporal and spatial dimensions since the Miocene in the Psammobates tentorius species complex, using multiple types of DNA markers and niche modelling analyses. Cladogenesis in P. tentorius started in the late Miocene when populations dispersed from north to south to form two geographically isolated groups. The northern group diverged into a clade north of the Orange River (OR), followed by the splitting of the group south of the OR into a western and an interior clade. The latter divergence corresponded to the intensification of the cold Benguela current, which caused western aridification and rainfall seasonality. In the south, tectonic uplift and subsequent exhumation, together with climatic fluctuations seemed responsible for radiations among the four southern clades since the late Miocene. We found that each clade occurred in a habitat shaped by different climatic parameters, and that the niches differed substantially among the clades of the northern group but were similar among clades of the southern group.
Conclusion
Climatic shifts, and biome and geographic changes possibly functioned as major driving forces in shaping cladogenesis, population dynamics and genetic structure in southern African tortoise species. Our results revealed that the cryptic cladogenic radiation of the P. tentorius species complex was probably shaped by environmental cooling, biome shifts and topographic uplift in southern Africa since the late Miocene. The Last Glacial Maximum may have impacted the population dynamics of P. tentorius substantially. We found the taxonomic diversify of the P. tentorius species complex to be highest in the Greater Cape Floristic Region. All seven clades discovered warrant conservation attention, particularly C1- C3, C5 and C6.
Effect of Eight-Month Exercise Intervention on Bone Outcomes of Young Opioid-Dependent Women
Authors: Xu Yubing , Ding Zenghui , Chen Yanyan , Wang Mu , He Zijun , Wang Yuan , Sun Yining , Li Huazhi , Ma Zuchang
Published: June 2020

Background: The purpose of this study was to evaluate bone response to an 8-month aerobic gymnastics training program in young opioid addicted women. Method: One hundred and two young women with previous opioid addiction were divided into two groups: (a) low bone quality intervention experimental group (n=55); (b) low bone quality observed control group (observation group) (n=47). Intervention group took aerobic gymnastics regularly for 120 min·d-1, 5d·wk-1 for 8 months and completed follow-up testing. Substance use history and other life habit affecting bone quality were assessed by questionnaire-based interviews. Bone quality (stiffness-index, T-score, Z-score) was examined with quantitative ultrasound. Anthropometric characteristics (body weight, fat free mass, fat mass) were obtained by bioelectrical impedance analysis. Results: After 8-month intervention, the stiffness-index of bone quality increased significantly (before: 82±6, after: 108±14, p<0.05) in the experimental groups. However, the bone quality did not change significantly in the controls (observation group: before: 79±10, after: 77±13, p>0.05). Fat mass decreased in experimental group (Experimental group: before: 19.6±3.7kg, after: 18.8±4.0kg, p<0.05). Meanwhile, change of fat-free mass was the determination of change of bone quality in the experimental group. Conclusions: Our results suggested that aerobic gymnastics intervention can be an effective strategy for the prevention and treatment of drug-induced osteoporosis in detoxification addicts.
Case report: New clinical clue of hyper-endogenous heparinization provides an imperative guideline for Treatment of Postpartum Hemorrhage with DIC via TEG guides and protamine intervention
Authors: Yan Tian , Fei He , Dong Lai , Changfu Ji
Published: June 2020

BackgroundPostpartum hemorrhage (PPH) is a leading cause of maternal mortality and severe maternal morbidity worldwide and involves disseminated intravascular coagulation (DIC) secondary to cause massive blood loss. The coagulation abnormality in response to severe trauma or infection is a latent cause that may aggravate PPH.Case presentationA 26-year-old puerpera with 39 weeks of menolipsis case lacks amniotic fluid and uterus infection was examined. During the cesarean section, the patient presented fever and massive hemorrhage that she became the DIC and shock. The low coagulation of this PPH patient was diagnosed by Thromboelastography (TEG) guiding with heparinase (type I). The patient appeared a critical condition admitted in emergency room. According the continuous detection via TEG guides assay, she was observed in coagulopathy and hyper-heparinization. And subsequently the protamine correction for the patient's coagulation abnormality, the patient who became a stable condition after 4 hours of urgent treatment.ConclusionTEG-guided determination of endogenous heparin and subsequent infusion of protamine effectively reversed the syndrome of PPH with DIC. This is the first case report that infection and bleeding might be major causes of hyper-endogenous heparinization without exogenous heparin intervention. The hyper-endogenous heparinization is clinically taken into consideration for the syndrome of PPH with low coagulation.
EML4-ALK induces cellular senescence in mortal normal human cells and promotes anchorage-independent growth in immortalized normal human cells
Authors: Miyanaga Akihiko , Matsumoto Masaru , Beck Jessica A. , Horikawa Izumi , Oike Takahiro , Okayama Hirokazu , Tanaka Hiromi , Burkett Sandra S. , Robles Ana I. , Khan Mohammed , Lissa Delphine , Seike Masahiro , Gemma Akihiko , Mano Hiroyuki , Harris Curtis C.
Published: June 2020

Background: Chromosomal inversions involving anaplastic lymphoma kinase (ALK) and echinoderm microtubule associated protein like 4 (EML4) generate a fusion protein EML4-ALK in non-small cell lung cancer (NSCLC). The understanding of EML4-ALK function can be improved by a functional study using normal human cells.Methods: Here we for the first time conduct such study to examine the effects of EML4-ALK on cell proliferation, cellular senescence, DNA damage, gene expression profiles and transformed phenotypes.Results: The lentiviral expression of EML4-ALK in mortal, normal human fibroblasts caused, through its constitutive ALK kinase activity, an early induction of cellular senescence with senescence-associated b-galactosidase activity, upregulation of p16INK4A and p21WAF1, and accumulated DNA damage. In contrast, when EML4-ALK was expressed in normal human fibroblasts immortalized by telomerase reverse transcriptase (hTERT), which is activated in the vast majority of NSCLC, the cells showed accelerated proliferation and acquired anchorage-independent growth ability in soft-agar medium, without accumulated DNA damage, chromosome aberration, nor p53 mutation. EML4-ALK induced the phosphorylation of STAT3 in both mortal and immortalized cells, but RNA sequencing analysis suggested that the different STAT3-regulated signaling pathways contributed to the different phenotypic outcomes in these cells. While EML4-ALK also induced anchorage-independent growth in hTERT-immortalized human bronchial epithelial cells in vitro, the expression of EML4-ALK alone did not cause detectable in vivo tumorigenicity in immunodeficient mice.Conclusions: Our data indicate that the immortalized state is critical for EML4-ALK to manifest its in vitro transforming activity in human cells. This study provides the isogenic pairs of human cells with and without EML4-ALK expression.