bluuebunny/crossref_metadata_2025 huggingface dataset:
Single Nucleotide Polymorphisms Associated With Prostate Cancer Development in Saudi Males
Authors: Osman Awad , Ahmed Atif Ali , Elbagir Asim Ali
Published: May 2020

Background: Genome-wide association studies have demonstrated that single nucleotide polymorphisms (SNPs) are important risk factors for the development of prostate cancer (PC). In this study, we investigated a group of SNPs in Saudi individuals and compared their frequency in patients and healthy normal controls. Methods: A total of 320 individuals were included in the study: 85 with PC, 120 with benign nodular hyperplasia, and 115 healthy normal controls. DNA was extracted from paraffin-embedded formalin-fixed tissue from PC and nodular hyperplasia patients and from whole blood of healthy controls. A total of thirteen SNPs were genotyped using the TaqMan® MGB PCR assay. Results: The rs16901979A, s629242T and rs1447295A alleles were found at significantly higher frequencies in PC patients than in controls (p < 0.05). The C/A genotype of the rs16901979 SNP was observed significantly more frequently in PC patients than in controls (43% vs 14%, OR = 0.2, p value = 0.0001) and more frequently in PC patients than in the benign hyperplasia group (43% vs 25%, OR = 2.3, p value = 0.03). Conclusion: Our study highlighted several SNP genotypes associated with PC development in Saudi males. These findings have important implications for diagnosing PC and screening unaffected family members of Saudi patients.
Association of Schistosoma haematobium Infection Morbidity and Severity on Co-infections status in Pre-school Age Children Living in a Rural Endemic Area in Zimbabwe
Authors: Mduluza-Joko Tariro Lavender , Naicker Thajasvarie , Jokonya Luxwell , Midzi Herald , Vengesai Arthur , Kasambala Maritha , Choto Emelia , Rusakaniko Simbarashe , Sibanda Elopy , Mutapi Francisca , Mdul Takafira
Published: May 2020

Background: Individuals living in Schistosoma haematobium endemic areas are often at risk of having other communicable diseases, simultaneously. This usually creates diagnostic difficulties leading to misdiagnosis and overlooking schistosomiasis infection. In this study we investigated the prevalence and effects of coinfections in pre-school age children and further investigated association between S. haematobium prevalence and under 5 mortality.Methods: Four hundred and sixty five Preschool age children (1-5 years old) with 51% being male were clinically examined for the following top morbidity causing conditions: respiratory tract infections, dermatophytosis, malaria and fever of unknown origin. The conditions were diagnosed as per approved WHO standards. S. haematobium infection was diagnosed by urine filtration and the children were screened for conditions common in the study area which included HIV, tuberculosis, malnutrition and typhoid. Results: Prevalence of S. haematobium was 35% (145). The clinical conditions assessed had the following prevalence in the study population: upper respiratory tract infection 40% (229), fever of unknown origin 45% (189), dermatophytosis and malaria both had 18% (75), The odds of co-infections observed with S. haematobium infection were: upper respiratory tract infection AOR = 1.22 (95% CI 0.80 to 1.87), dermatophytosis AOR = 4.79 ( 95% CI 2.78 to 8.25), fever of unknown origin AOR = 10.63 ( 95% CI 6.48-17.45) and malaria AOR = 0.91 ( 95% CI 0.51 to1.58). Relative risks of the severe sequels when coinfected were: Severe pneumonia RR=7.5 (95% CI 2.92-19.23), p<0.0001, complicated malaria RR=12 (95%CI 11.53-94.53), p=0.02, severe dermatophytosis RR=8.5 (95% CI 1.2-60.2):p=0.03, and fever of unknown origin RR=2.32 (95% CI 1.12-4.80), p=0.02.Conclusion: This study is novel as it identifies a possible association relationship between S. haematobium infection and top morbidity conditions in children under five years. There is need to alert policy makers so as to initiate early treatment of schistosomiasis in pre-school age children.
Significance of calorie-restricted ketogenic diet for lung cancer with brain metastases and hepatoma with pulmonary metastases: report of two cases
Authors: Tan Dong , Zhao Jing , Liu Xiao-jing , Yang Wen-ru , Yuan Fang
Published: May 2020

Cancer cells have altered metabolism that is characterized by an enhanced uptake and utilization of glucose. These increased glucose dependence alterations, present potential vulnerabilities that could be targeted for cancer therapy. The calorie-restricted ketogenic diet (KD) may meet the requirement. In this study, we explore the feasibility of the ketogenic diet as adjuvant therapy for cancer treatment. We present two cases of patients diagnosed with aggressive forms of cancer, lung cancer with brain metastatic tomours and primary liver cancer with pulmonary metastases. The patients began KD intervention after exhausting the other treatment options. Both of them responded to KD and demonstrated a beneficial effect. The tomour size from serial imaging and serum tumour markers were significantly reduced after KD in both subjects without any adverse effects. Both patients had tumour remission even after stopping the ketogenic diet, indicating that KD is a safe, effective treatment to aggressive cancers with metastases when used with conventional therapies.
Substitution mapping of the major quantitative trait loci controlling stigma exsertion rate from Oryza glumaepatula
Authors: Tan Quanya , Zou Tuo , Zheng Mingmin , Ni Yuerong , Luan Xin , Li Xiaohui , Yang Weifeng , Yang Zifeng , Zhu Haitao , Zeng Ruizhen , Liu Guifu , Wang Shaokui , Fu Xuelin , Zhang Guiquan
Published: May 2020

Background: Stigma exsertion rate (SER) is a key determinant for the outcrossing ability of male sterility lines (MSLs) in hybrid rice seed production. In the process of domestication, the outcrossing ability of cultivated rice varieties decreased, while that of wild Oryza species kept strong. Here, we detected the quantitative trait loci (QTLs) controlling SER using a set of single-segment substitution lines (SSSLs) derived from O. glumaepatula , a wild Oryza species. Results: Seven QTLs for SER were located on 5 chromosomes. qSER-1a and qSER-1b were located on chromosome 1. qSER-3a and qSER-3b were mapped on chromosome 3, and qSER-3b was further located at an estimated interval of 898.8kb by secondary substitution mapping. qSER-5 , qSER-9 and qSER-10 were identified on chromosomes 5, 9 and 10, respectively, and qSER-9 was delimited to an estimated region of 551.9kb by secondary substitution mapping. The additive effects of the 7 QTLs ranged from 10.6% to 14.8%, which were higher than those of most loci for SER reported previously. Conclusions: qSER-1a and qSER-1b are novel loci for SER on chromosome 1. All of the 7 QTLs have major effects on SER. The major QTLs of SER will help to develop MSLs with strong outcrossing ability.
Surgical management of sarcoma in adolescent and young adult patients
Authors: Hashimoto Kazuhiko , Nishimura Shunji , Oka Naohiro , Akagi Masao
Published: May 2020

Objective: To examine the clinical features and outcomes of adolescent and young adult sarcoma patients who underwent surgical management and clarify important factors associated with prognosis. We reviewed 18 young adult sarcoma patients sarcoma patients treated surgically in our hospital. The tumor site, histology, grade, stage, and American Society of Anesthesiologists-Physical Status before surgery, operation time, intraoperative blood loss, complications, surgical margin, local recurrence, metastasis, and outcomes were investigated. The 3-year survival rate was also calculated. We compared survival based on age, grade, and surveyed features of poor outcome cases.Results: The 3-year survival rate was 61.3%. There was no significant difference in survival based on age, grade, operation time, or intraoperative blood loss. Three of five patients who died of the disease had stage ≥ IV at diagnosis. All patients with R1 surgical margins developed recurrence and all those with an American Society of Anesthesiologists-Physical Status ≥ 2 died. Patients with late-stage sarcomas, R1 tumor margin, or high American Society of Anesthesiologists-Physical Status score had poor prognoses. To achieve a favorable outcome in adolescent and young adult sarcoma patients, early detection and obtaining R0≥ surgical margin are essential.
Pleiotropic function of SQUAMOSA PROMOTER-BINDING PROTEIN-BOX gene TaSPL14 on plant architecture of wheat
Authors: Cao Jie , Liu Kaiye , Song Wanjun , Zhang Jianing , Yao Yingyin , Xin Mingming , Hu Zhaorong , Peng Huiru , Ni Zhongfu , Sun Qixin , Du Jinkun
Published: May 2020

Background

SQUAMOSA PROMOTER-BINDING PROTEIN-BOX gene OsSPL14 from rice is evaluated as the major gene for ideal plant architecture consisting of few unproductive tillers, more grains per spike and high lodging resistance stems. However, the function of its orthologous gene TaSPL14 in wheat is still unknown.
Results

Here, we reported the similarity and variation between TaSPL14 and OsSPL14. Similar to OsSPL14, TaSPL14 knock-out mutants exhibited decreased plant height, spike length, spikelet number, thousand-grain weight. Different from OsSPL14, TaSPL14 had no effect on tiller number. Transcriptome analysis genes related to ethylene response were significantly decreased in young spikes of TaSPL14 knockout mutants, compared with wild type. TaSPL14 directly binds to the promoters of the ethylene response gene TaEIL1 (EIN3-LIKE 1), TaRAP2.11 (ETHYLENE-RESPNSIVE TRANSCRIPTION FACTOR 2.11) and TaERF1 (ETHYLENE-RESPNSIVE TRANSCRIPTION FACTOR 1) and activities their expression, suggesting that TaSPL14 might regulate wheat spike development through ethylene response pathway.
Conclusions

TaSPL14 had similar function with OsSPL14 in regulating plant height, spike length, spikelet number and thousand-grain weight of wheat, and had different function in tiller development. TaSPL14 might regulate spike development through TaEIL1, TaRAP2.11 and TaERF1, not TaDEP1.The elucidation of TaSPL14 will contribute to exploring the molecular mechanisms underlying plant architecture of wheat.
Identification and validation of aberrant regulation of miR-445-3p /TTK , miR-140-5p/TTK and miR-133b/CDCA8 in small-cell lung cancer via bioinformatics analysis
Authors: Tang Ming-bo , Gao Xin-liang , Xin Zhuo-yuan , Fang Li-nan , Liu Wei
Published: May 2020

Background: Small-cell lung cancer (SCLC) remains the leading form of malignant lung cancer, but little bioinformation on SCLC is available. This study explored the molecular targets of SCLC by evaluating differentially expressed genes (DEGs) and differentially expressed microRNAs (miRNAs) (DEMs).Methods: Five mRNA expression profiles and two miRNAs expression profiles from Gene Expression Omnibus (GEO) were downloaded. R software was utilized to analyze the DEGs and DEMs between SCLC and normal samples. The DEGs were analyzed via functional enrichment analyses and were used to construct protein-protein interaction (PPI) networks. DEM targets were then predicted and intersected with the DEGs. Furthermore, the hub genes of SCLC in the overlapping DEGs were analyzed in Oncomine. Finally, the expression of DEM-hub gene pairs were verified in tissues by RT-qPCR and Western blotting.Results: In total, 236 common DEGs and 104 common DEMs were identified. Functional enrichment analysis showed the DEGs were primarily enriched in ‘cell cycle’, ‘DNA replication’ and ‘oocyte meiosis’. Twenty hub genes and five modules were identified from the PPI network. Furthermore, 6732 targeted genes of the DEMs were predicted. After intersecting with DEGs, 54 genes and 153 miRNA-mRNA pairs were eventually identified aberrant regulation in SCLC. MiR-445-3p/TTK, miR-140-5p/TTK and miR-133b/CDCA8 were identified as DEM-hub gene pairs. Oncomine analysis confirmed the overexpression of TTK and CDCA8 in SCLC. Further validation demonstrated that TTK and CDCA8 levels in SCLC tissue samples were markedly increased relative to normal controls, while miR-445-3p, miR-140-5p, and miR-133b levels were lower in SCLC samples than in controls.Conclusions: Our results revealed key miRNA-mRNA pairs associated with SCLC, providing new insights into potential disease targets.
Analysis of the heterogeneity of the BCR H-CDR3 repertoire in the bone marrow and spleen of 3-,12-,and20-month old mice
Authors: Ma Lina , Yao Xinsheng
Published: May 2020

The number of central and peripheral B cells and their responsiveness are decreased in agedmice. The diversity of mouse central and peripheral B cell repertoires with increasing age has notbeen elucidated. In this study, we demonstrated that there were significant differences in theusage of some V, D, and J genes in the BCR H-CDR3 repertoire of bone marrow B cells, spleen Bcells and spleen memory B cells in 3-, 12-, and 20-month-old mice. In the productive, pseudogene,and out-of-frame sequences, bone marrow B cells had significant differences in 5′J trimmingwith age; peripheral spleen B cells and memory B cells had significant differences in N1 insertion,N2 insertion, P5'D insertion, and 5'D trimming with age. The BCR H-CDR3 repertoire diversityof mouse bone marrow B cells, spleen B cells and spleen memory B cells decreased withincreasing age. The proportion of overlap in bone marrow and spleen B cells, but not spleenmemory B cells, of mice at different ages was lower at 3 months than at 12 and 20 months.Thisstudy is the first to report the homogeneity and heterogeneity of the CDR3 repertoire of centraland peripheral B cells change as mice age , to further investigation of the decline and response ofB cell immunity in young/middle/old-aged mice.
Joint effects of WT1, CA10 methylation in peripheral blood leukocyte and dietary zinc on breast cancer risk: a case-control study
Authors: Ge Anqi , Gao Song , Liu Yupeng , Zhang Hui , Wang Xuan , Zhang Lei , Pang Da , Zhao Yashuang
Published: May 2020

Background
Studies have shown that abnormal changes of specific-gene DNA methylation in leukocytes may be associated with elevated risk of cancer. However, associations between the methylation of zinc-related genes, WT1 and CA10, and breast cancer risk, and interactions between WT1, CA10 methylation and dietary zinc intake on breast cancer risk remain unknown.
Methods
The methylation of WT1, CA10 was analyzed by methylation-sensitive high-resolution-melting (MS-HRM) in a case-control study with female subjects (N = 959). Logistic regression was used to analyze the associations and propensity score (PS) method was used to adjust confounders.
Results
The results showed that WT1 hypermethylation was associated with an increased risk of breast cancer with an odds ratio (OR) of 3.069 [95% confidence interval (CI): 1.669–5.643, P < 0.001]. Subgroup analyses showed that WT1 hypermethylation was specifically associated with an elevated risk of Luminal A subtype (OR = 2.620, 95%CI: 1.107-6.200, P = 0.029) and Luminal B subtype (OR = 3.231, 95%CI: 1.339–7.796, P = 0.009). CA10 hypermethylation was associated with an increased risk of Luminal B subtype (OR = 1.798, 95%CI: 1.085–2.982, P = 0.023). Furthermore, the joint effects of methylation of WT1, CA10 and lower dietary zinc intake were associated a strongly elevated risk of breast cancer with ORs of 11.220 (95%CI: 4.057–31.032, P < 0.001) and 4.145 (95%CI: 2.717–6.324, P < 0.001), respectively.
Conclusion
The study suggested the hypermethylation of WT1 methylation in leukocytes was significantly associated with an increased risk of breast cancer. Notably, the joint effects of WT1, CA10 methylation and lower dietary zinc intake might significantly associate with breast cancer risk.
Three-year outcome after transanal versus laparoscopic total mesorectal excision in locally advanced rectal cancer: a multicenter comparative analysis
Authors: de Lacy F. Borja , Roodbeen Sapho X. , Ríos Jose , Laarhoven Jacqueline van , Otero-Piñeiro Ana , Bravo Raquel , Visser Tjaakje , Poppel Roy van , Valverde Silvia , Hompes Roel , Sietses Colin , Castells Antoni , Bemelman Willem A. , Tanis Pieter J. , Lacy Antonio M.
Published: May 2020

Background
For patients with mid and distal rectal cancer, robust evidence on long-term outcome and causal treatment effects of transanal total mesorectal excision (TaTME) is lacking. This multicentre retrospective cohort study aimed to assess whether TaTME reduces locoregional recurrence rate compared to laparoscopic total mesorectal excision (LapTME).
Methods
Consecutive patients with rectal cancer within 12 centimetres from the anal verge and clinical stage II-III were selected from three institutional databases. Outcome after TaTME (Nov 2011 - Feb 2018) was compared to a historical cohort of patients treated with LapTME (Jan 2000 - Feb 2018) using the inverse probability of treatment weights method. The primary endpoint was three-year locoregional recurrence.
Results
A total of 710 patients were analysed, 344 in the TaTME group and 366 in the LapTME group. At three years, cumulative locoregional recurrence rates were 3.6% (95% CI, 1.1–6.1) in the TaTME group and 9.6% (95% CI, 6.5–12.7) in the LapTME group (HR = 0.4; 95% CI, 0.23–0.69; p = 0.001). Three-year cumulative disease-free survival rates were 74.3% (95% CI, 68.8–79.8) and 68.6% (95% CI, 63.7–73.5) (HR = 0.82; 95% CI, 0.65–1.02; p = 0.078) and three-year overall survival 87.2% (95% CI, 82.7–91.7) and 82.2% (95% CI, 78.0-86.2) (HR = 0.74; 95% CI, 0.53–1.03; p = 0.077), respectively. In patients who underwent sphincter preservation procedures, TaTME was associated with a significantly better disease-free survival (HR = 0.78; 95% CI, 0.62–0.98; p = 0.033).
Conclusions
These findings suggest that TaTME may improve locoregional recurrence and disease-free survival rates among patients with mid and distal locally advanced rectal cancer.
Effect of capsular tension ring implantation on capsular stability after phacoemulsification in patients with weak zonules:a randomized controlled trail. CTR implantation in cataract patients with weak zonules
Authors: Yang Shangfei , Jiang Hui , Nie Kailai , Feng Liwen , Fan Wei
Published: May 2020

Background
Patients who had previously undergone pars plana vitrectomy (PPV) or who had severe myopia may have weaker zonules, for which a capsular tension ring (CTR) implantation is still controversial. This study is to test the effect of CTR implantation on capsular stability after phacoemulsification in those patients.
Methods
A total of 42 patients who underwent phacoemulsification and received an intraocular lens (IOL) were randomized to undergo CTR implantation or not. The primary outcomes were uncorrected distant visual acuity (UDVA), best corrected distant visual acuity (BCDVA), refractive prediction error, the area of anterior capsulorhexis, and IOL inclination angle. Follow-up visits were conducted postoperatively at 1 day, 1 week, 1 month and 3 months. Outcomes were compared between all CTR and control patients, as well as between subgroups who had previously undergone PPV or who had severe myopia.
Results
Surgery significantly improved UDVA and BCDVA to similar extents in CTR and control patients, and refraction prediction error was similar between the two groups at all follow-up times. At 3 months after surgery, the area of anterior capsulorhexis was significantly larger in CTR patients than in controls (p = 0.0199). These differences were also significant between the subgroups of patients with strong myopia. Vertical IOL inclination was less within CTR groups at 3 months after surgery, especially in patients with severe myopia(P = 0.0286). At 1 week postoperatively, the proportion of individuals whose posterior lens capsule that had completely adhered to the posterior IOL surface was significantly higher among CTR patients (p = 0.023). No serious surgical complications were observed.
Conclusion
CTR implantation can benefit cataract patients with weak zonules by maintaining the shape of the capsular bag, reducing capsule shrinkage and stabilizing IOL inclination.
Trail Registration:
This study was registered at the Chinese Clinical Trial Registry (ChiCTR-INR-17011217).
­­­An Integrated Autophagy-Related Gene Signature Predicts Prognosis in Human Endometrial Cancer
Authors: Zhang Jun , Wang Ziwei , Zhao Rong , An Lanfen , Zhou Xing , Zhao Yingchao , Wang Hongbo
Published: May 2020

Background Globally, endometrial cancer is the fourth most common malignant tumor in women and the number of women being diagnosed is increasing. Tumor progression is strongly related to the cell survival-promoting functions of autophagy. We explored the relationship between endometrial cancer prognoses and the expression of autophagy genes using human autophagy databases.Methods The Cancer Genome Atlas was used to identify autophagy related genes (ARGs) that were differentially expressed in endometrial cancer tissue compared to healthy endometrial tissue. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were referenced to identify important biological functions and signaling pathways related to these differentially expressed ARGs. A prognostic model for endometrial cancer was constructed using univariate and multivariate Cox, and Least Absolute Shrinkage and Selection Operator regression analysis. Endometrial cancer patients were divided into high- and low-risk groups according to risk scores. Survival and receiver operating characteristic (ROC) curves were plotted for these patients to assess the accuracy of the prognostic model. Using immunohistochemistry the protein levels of the genes associated with risk were assessed.Results We determined 37 ARGs were differentially expressed between endometrial cancer and healthy tissues. These genes were enriched in the biological processes and signaling pathways related to autophagy. Four ARGs (CDKN2A, PTK6, ERBB2and BIRC5) were selected to establish a prognostic model of endometrial cancer. Kaplan–Meier survival analysis suggested that high-risk groups have significantly shorter survival times than low-risk groups. The area under the ROC curve indicated that the prognostic model for survival prediction was relatively accurate. Immunohistochemistry suggested that among the four ARGs the protein levels of CDKN2A, PTK6, ERBB2 and BIRC5 were higher in endometrial cancer than healthy endometrial tissue.Conclusions Our prognostic model assessing four ARGs (CDKN2A, PTK6, ERBB2, and BIRC5) suggested their potential as independent predictive biomarkers and therapeutic targets for endometrial cancer.
A Comparative Study of Target Reconstruction of Ultra-High-Resolution CT for Patients with Corona-Virus Disease 2019 (COVID-19)
Authors: Lv Shaomao , Lin Yu , Kang Jianghe , Duan Shaoyin , Zhang Weiguo , Wang Jinan
Published: May 2020

Background: The corona-virus disease 2019 (COVID-19) pandemic has caused a serious public health risk. Compared with conventional high-resolution CT (C-HRCT, matrix 512), ultra-high resolution CT (U-HRCT, matrix 1024) can increase the effective pixel per unit volume by about 4 times. Our study is to evaluate the value of target reconstruction of U-HRCT in the accurate diagnosis of COVID-19. Methods: A total of 13 COVID-19 cases, 44 cases of other pneumonias, and 6 cases of ground-glass nodules were retrospectively analyzed. The data were categorized into groups A (C-HRCT) and B (U-HRCT), following which iDose4-3 and iDose4-5 were used for target reconstruction, respectively. CT value, noise, and signal-to-noise ratio (SNR) in different reconstructed images were measured. Two senior imaging doctors scored the image quality and the structure of the lesions on a 5-point scale. Chi-square test, variance analysis, and binary logistic regression analysis were used for statistical analysis. Results: U-HRCT image can reduce noise and improve SNR with an increase of the iterative reconstruction level. The SNR of U-HRCT image was lower than that of the C-HRCT image of the same iDose4 level, and the noise of U-HRCT was higher than that of C-HRCT image; the difference was statistically significant (P < 0.05). Logistic regression analysis showed that peripleural distribution, thickening of blood vessels and interlobular septum, and crazy-paving pattern were independent indictors of the COVID-19 on U-HRCT. U-HRCT was superior to C-HRCT in showing the blood vessels, bronchial wall, and interlobular septum in the ground-glass opacities; the difference was statistically significant (P < 0.05). Conclusions: Peripleural distribution, thickening of blood vessels and interlobular septum, and crazy-paving pattern on U-HRCT are favorable signs for COVID-19. U-HRCT is superior to C-HRCT in displaying the blood vessels, bronchial walls, and interlobular septum for evaluating COVID-19.
Perception, Knowledge and Attitudes Towards Molar Incisor Hypomineralization Among Spanish Dentists: A Cross-sectional Study.
Authors: Serna-Muñoz Clara , Martinez-Beneyto Yolanda , Pérez-Silva Amparo , Poza-Pascual Andrea , Ibáñez-López Francisco Javier , Ortiz-Ruiz Antonio J.
Published: May 2020

Background: Molar Incisor Hypomineralization (MIH) is a growing problem, and its treatment is a challenge. The purpose was to evaluate and compare the perceptions, knowledge and clinical experiences of MIH between general dental practitioners (GDPs) and pediatric dentists (PDs) in Spain. Methods: All dentists belonging to the College of Dentists of the Region of Murcia, in the South-East of Spain, were invited to participate in a cross-sectional survey. They were asked to complete a 2-section questionnaire including socio-demographic profiles and knowledge, experience, and perceptions of MIH. Data were analyzed using the Pearson chi-square test, Fisher´s exact test and Cramer´s V test.Results: The overall response rate was 18.6% (214/1147). Most respondents were aged 31-40 years (44.86%), with more than 15 years of professional experience (39.72%). They worked mainly in the private sector (84.58%) and were licensed in Dentistry (74.30%): 95.45% of pediatric dentists had detected an increase in the incidence of MIH in recent years (p<0.001). Only 23.80% of GDPs claimed to have had some training course in MIH. With respect to the etiology, chronic medical conditions (p<0.05) and environmental pollutants (p<0.001) were the only factors that showed significant between-group differences. Durability (p<0.01) and remineralization potential (p<0.05) were the factors where there was a between-group difference when choosing the material for restoration. In the case of post-eruptive fractures and opacities the preferred material for both groups was resin-modified glass ionomer (RMGIC). However, in incisor lesions, composite was the material of choice for both groups, with significant differences (p<0.05) in the use of glass ionomer. Most respondents expressed a need for continuing education on MIH. Conclusion: Spanish dentists perceived an increase in the incidence of MIH. The material of choice is RMGIC for non-aesthetic sectors and composite for incisors. Both GDPs and PDs believe they need more training on the etiology, diagnosis and treatment of MIH.
Promoter methylation, transcription, and retrotransposition of LINE-1 in colorectal adenomas and adenocarcinomas
Authors: SHADEMAN Milad , ZARE Khadijeh , ZAHEDI Morteza , MOZAFFARI Hooman MOSANNEN , HOSSEINI Hadi BAGHERI , GHAFFARZADEGAN Kamran , Goshayeshi Ladan , Dehghani Hesam
Published: May 2020

Background: LINE-1, Alu, and SVA elements are non-LTR retrotransposons that create approximately one-third of the human genome. The loss of tight control mechanisms on the function of mobile elements has been implicated in many human diseases. The methylation of the CpG islands of the LINE-1 promoter is one of these mechanisms. In this study, we determined the promoter methylation and the expression of LINE-1 in three stages of colorectal non-advanced adenoma, advanced adenoma, and adenocarcinoma. In addition, we analyzed the insertion of LINE-1, Alu, and SVA elements in the genome of colorectal advanced adenomas.Results: We found that the LINE-1 hypomethylation index in advanced adenoma and adenocarcinoma were significantly higher than that in non-advanced adenomas. The copy number of LINE-1 transcripts in advanced adenoma was significantly higher than that in non-advanced adenomas, and in adenocarcinomas was significantly higher than that in the advanced adenomas. Analysis of the genome of colorectal advanced adenomas revealed that at this stage de novo insertions of LINE-1, Alu, and SVA were approximately 16%, 51%, and 74%, respectively.Conclusions: Our findings showing a decreased methylation of LINE-1 promoter accompanied by the higher level of LINE-1 transcription, and de novo genomic insertions in advanced (high-grade) adenoma, a precancerous stage before colorectal carcinoma, suggests that the early and advanced polyp stages may host very important pathogenic processes concluding to cancer.
Leadership, governance and management for improving district capacity and performance: the case of USAID Transform: Primary Health Care
Authors: Desta Binyam Fekadu , Azeb Abitew , Ismael Beshir Ali , Mesele Argaw Damite , Sualiha Abdlkader
Published: May 2020

Primary health care (PHC) in Ethiopia serves as the main entry point for preventive, promotive and curative health services. The district health office is responsible for the planning, implementation and evaluation of all district health activities. In addition, district health offices manage service delivery facilities working on provision of PHC – primary hospitals, health centers and health posts. As the leader of the health care system tier, district health management must ensure direction, alignment and commitment within teams and organizations and make sure that achievements are consistent with the vision, values and strategy of the organization. USAID Transform: Primary Health Care provides diverse support to improve district health manager competencies including in-service trainings followed by planning and implementation of performance improvement projects and on-the-job mentoring and support. This study was conducted to compare district level capacity and performances between leadership, management and governance (LMG) and non-LMG districts. Project outcome monitoring data that shows the performance of districts was collected from 284 districts from January to December 2019. The study was carried out using a comparative-cross sectional study design, which assessed and compared district health office level indicators. Districts were classified into two categories: LMG and non-LMG districts. The study compared data from 94 LMG and 190 non-LMG districts. Results of the independent samples t-test revealed that LMG districts scored better average performances of 61.8 ± 12.4 standard deviation (SD) compared to non-LMG districts at 56.8 ± 11.3 SD, with t (282) = 3.407 and p < 0.001, two-tailed. The difference of 5.02 percentage unit in the average performance indicated a statistically significant difference between the LMG and non-LMG districts. The data analysis illustrated changes observed in management practices, district administrative capacity, capacity of districts in resource mobilization and use, service availability and quality in project implementation sites.
Lived experience of women who underwent early removal of long-acting Contraceptive Methods in Bedesa town, Wolaita Zone, Southern Ethiopia: A phenomenological study
Authors: Obsa Mohammed Suleiman , Takiso Kassahun Tekle , Ayele Tamiru Tilahun , Koyra Hailu Chare , Hidota Kasahun Tafesse , Shanka Getahun Molla , Hanfore Lolemo Kelbiso , Arba Mihiretu Alemeyehu , Anjulo Antehun Alemeyehu , kanche Zewde Zema , kercho Melkamu Worku
Published: May 2020

Background

Long-acting contraceptive methods can play a pivotal role in ining reducing maternal mortality. In The total fertility rate of Ethiopia is as high as 4.6 children per woman, which is manifested by short birth-interval. However, this rapid population growth is not in line with the weak economic growth of the country. Therefore, this study was done to explore the lived experiences of women who underwent early removal of long-acting contraceptive methods in Bedesa town, Southern Ethiopia.
Methods

A phenomenological study design was employed from April 16–22, 2020 to conduct this qualitative study among Bedessa town community. Individual In-depth interviews were used to collect data from a sampled study participants recruited through criterion sampling method. Based on the theoretical saturation of data, this study included a total of 10 in-depth interviews of sampled women.. Open code version 4.03 was used to code and facilitate analysis. The study used thematic analysis technique after the transcripts were read and re-read separately by the investigators to identify emerging themes.
Results

This study revealed that the majority of participants were able to mention at least three types of contraceptive methods. Participants frequently said that the side effect of the long-acting family planning methods as the main reason for early removal. Furthermore, heavy and irregular menses were mentioned as the most frequently occurring side effects. Delayed fertility after removal of long-acting contraceptive was one of frequently stated fear by the clients. Some of the participants indicated that counseling provided by health professionals was not adequate.
Conclusion

The majority of our study participants taught that the side effects of long-acting family planning methods outweigh than benefits. Besides, the counseling service provided by health care providers was not adequate. Therefore, proper counseling services should be given to mothers who are taking long-acting family planning methods.
Impact of Doxycycline on Covid-19 Patients With Risk Factors of Disease Degradation: Dynamic, A Randomised Controlled Double-blind Trial
Authors: Poinas Alexandra , Boutoille David , Vrignaud Florence , Nguyen Jean-Michel , Bonnet Fabrice , Rat Cédric , Garcia Gilles , Dompmartin Anne , Leccia Marie-Thérèse , Piroth Lionel , Maubec Eve , Gandon Pierre , Jobert Alexandra , Boinet Soizic , Cassecuel Julie , Flet Laurent , Khammari Amir , Dréno Brigitte
Published: May 2020

Background: The DYNAMIC study is based on three properties of tetracyclines. (1) Tetracyclines are known to chelate zinc from metalloproteases (MMPs). It is possible that their chelating activity may help to inhibit COVID-19 infection by limiting its ability to replicate in the host. (2) As seen with dengue virus, tetracyclines may also be able to inhibit the replication of positive polarity single-stranded RNA viruses, such as COVID-19. (3) In addition, tetracyclines are modulators of innate immunity (anti-inflammatory activity), a property that has been used to treat inflammatory skin diseases for many years. They could therefore participate in limiting the cytokine storm induced by COVID-19. The lipophilic nature of tetracyclines and their strong pulmonary penetration could allow them to inhibit viral replication at this level. Among tetracyclines, the advantages of doxycycline are triple: its long history of safety (infrequent side effects with no notable risks), the short duration of treatment and its low cost.Methods: By estimating the rate of patients presenting pulmonary signs requiring hospitalisation in at-risk patients infected with COVID-19 at 25%, we hypothesise that on doxycycline, this rate would decrease to 12%. The main objective involves 2 embedded hypotheses tested successively in case of rejection of the previous one: (i) Decrease the rate of patients requiring hospitalisation, (ii) Decrease the use of mechanical ventilatory assistance.Discussion: This study could have an impact on the management of COVID-19 risk factor patientsupstream of hospitals by general practitioners. These patients,if kept at home under experimental treatment, would participate in reducing the risk of dissemination of SAR-CoV-2in the population.Thus, this treatment would contribute to supporting the deconfinement strategy through blocking the viral infection early and reducing the contagious period.Trial Registration: On ClinicalTrials.gov, registration number NCT04371952, first published on 30 April 2020.
Graphene-Modified CePO4 Nanorods Effectively Treat Breast Cancer-Induced Bone Metastases and Regulate Macrophage Polarization to Improve Osteo-Inductive Ability
Authors: Ge Yuwei , Liu Xiao-Liang , Yu De-gang , Zhu Zhen-An , Ke Qin-Fei , Mao Yuan-Qing , Guo Ya-Ping , Zhang Jing-Wei
Published: May 2020

Background Breast cancer bone metastasis has become one of the most common complications; however, it may cause cancer recurrence and bone nonunion and local bone defects.Methods Herein, In vitro, we verified the effect of bioscaffold materials on cell proliferation and apoptosis through CCK8 experiment, staining of living dead cells, and flow cytometry. We used immunofluorescence technology and flow cytometry to verified whether bioscaffold materials regulated the polarization of macrophages, and we use ALP staining, alizarin red staining and PCR to verify whether the bioscaffold material promotes bone regeneration. In vivo, we once again studied the effect of bioscaffold materials on tumors by measuring tumor volume in mice, Tunel staining, and caspase-3 immunofluorescence. We also constructed a mouse skull ultimate defect model to verify the effect on bone regeneration.Results Graphene oxide (GO) nanoparticles, hydrated CePO4 nanorods and bioactive chitosan (CS) are combined to form a bioactive multifunctional CePO4/CS/GO scaffolds, which has the following characteristics such as photothermal therapy to kill tumors, macrophage polarization promotes blood vessel formation and induces bone formation. The CePO4/CS/GO scaffold activates the caspase-3 proteasein local tumor cells, thereby lysing DNA between nucleosomes and causing apoptosis. On the one hand, the as-released Ce3+ ions promote the M2 polarization of macrophages, which secretes vascular endothelial growth factor (VEGF) and Arginase-1 (Arg-1), which promotes angiogenesis. On the other hand, the as-released Ce3+ ions also activated BMP-2/Smad signaling pathway that facilitated bone tissue regeneration.Conclusion the multifunctional CePO4/CS/GO scaffolds may become a promising platform for therapy of breast cancer bone metastases.
Characteristics of Circular RNA Expression in Ishikawa Human Endometrial Carcinoma Cells with Progesterone Treatment
Authors: Wang Lihua , Zheng Panchan , Cao Wenjiao , Sun Xiao , Gao Wuyuan , Wang Yudong
Published: May 2020

Background

Progestins are commonly used as the conservative endocrine treatment of young early endometrial cancer (EC) patients. Circular RNAs (circRNAs) are new group players in multiple cellular functions. This study aims to identify the differentially expressed circular RNAs (DE-circRNAs) in endometrial cancer (EC) cells upon the progesterone treatment, aiding in the understanding of the impact of circRNAs in progestin therapy.
Methods

RNA-seq analysis was used to identify the DE-circRNAs between MPA-treated and -non-treated Ishikawa cell lines. Functional enrichment analysis and circRNA-miRNA interaction network analysis were applied to these DE-circRNAs, validated by qRT-PCR analyses. Moreover, shRNA knockdown was utilized to explore the circRNA function.
Results

A total of 87 circRNAs were differentially expressed in Ishikawa cell lines with MPA treatment compared with that of control cells (|fold change| ≥2.0, p < 0.05). Besides, these circRNAs were mainly enriched in cancer-related pathways, including response to cholesterol, epithelial to mesenchymal transition, and base-excision repair. The competing endogenous RNA (ceRNA) network showed that miR-296-3p, miR-1236-3p, and miR-144-5p were related to cancer. Furthermore, the qPCR results were coincident with the RNA-seq data. Of note, hsa_circ_0001860 was significantly induced upon MPA treatment. Knockdown of hsa_circ_0001860 can partially rescue the MPA-inhibited cell proliferation and invasion and regulate the expression of its interacting miRNAs.
Conclusions

This is the first time to evaluate the circRNA expression profile in progesterone treatment for EC. These circRNAs (e.g., hsa_circ_0001860) may be used as potential diagnostic biomarkers and treatment targets for the evaluation of EC progesterone treatment.
The characteristics of overseas imported COVID-19 cases and the effectiveness of screening strategy in Beijing, China
Authors: Li Li , Ma Cheng-Jie , Chang Yu-Fei , Yang Si-Yuan , Tang Yun-Xia , Jiang Rong-Meng
Published: May 2020

Background
While great success in the coronavirus disease 2019 (COVID-19) control has been achieved in China, imported cases have become a major challenge. This study aimed to describe the epidemiological and clinical characteristics of imported COVID-19 cases and to assess the effectiveness of screening strategy in Beijing, China.
Methods
This retrospective study included all imported COVID-19 cases from Beijing Ditan Hospital from 29 February to 20 March 2020, who were screened by both chest computed tomography (CT) and reverse-transcriptase-polymerase chain reaction (RT-PCR) at initial presentation. Demographic, clinical and laboratory data, in addition to chest CT imaging were were collected and analyzed.
Results
A total of 71 imported cases were finally diagnosed with laboratory-confirmed COVID-19. The cases were mainly acquired from Europe (63 cases, 88.73%). The main clinical manifestations were fever and cough, which accounted for 30 cases (42.25%) and 35 cases (49.30%), respectively. Only 4 cases (5.63%) had lymphocytopenia and 13 (18.31%) cases demonstrated elevated levels of C-reactive protein (CRP). All cases had normal serum levels of procalcitonin (PCT). 35 cases (49.30%) had abnormal CT findings at initial presentation, whereas 36 cases (50.70%) had a normal CT. Using RT-PCR, 59 cases (83.10%) were tested positive at initial presentation.
Conclusions
The number of overseas imported COVID-19 cases continues to rise in China. The combination of screening tools, particularly CT and RT-PCR, can detect imported COVID-19 cases efficiently.
Lifestyle, exercise and activity package for people living with progressive multiple sclerosis (LEAP-MS): Protocol for a Single-Arm Feasibility Study.
Authors: Latchem-Hastings Julie , Randell Elizabeth , Button Kate , Jones Fiona , Lowe Rachel , Dawes Helen , Wood Fiona , Davies Freya , Poile Vincent , O’Halloran Rhian , Stensland Barbara , Tallantyre Emma , Playle Rebecca , Edwards Adrian , Busse Monica
Published: May 2020

Background. We have co-designed a tailored blended physiotherapy intervention for people with Progressive Multiple Sclerosis (MS) who often struggle to access support for physical activity. Underpinned by self-management principles, the Lifestyle, Exercise and Activity Package for people with MS intervention, which we call the LEAP-MS intervention, incorporates face-to-face or online physiotherapy coaching sessions with an accompanying online physical activity platform. The LEAP-MS platform is a multi-user system enabling user and physiotherapist to co-create activity plans. The LEAP-MS platform consists of an information and activity suite, interactive components enabling selection of exercises into an activity programme, goal setting, and activity logging. The platform also facilitates online remote support from a physiotherapist through an embedded online messaging function. We aim to evaluate the LEAP-MS platform in a feasibility trial. Methods. LEAP-MS will be evaluated within a single arm feasibility study with embedded process evaluation. After registration and initial eligible screening, 21 participants will be required to complete baseline self-completion measures. This will be followed by an initial home-based or online coaching session with a physiotherapist (who has received tailored self-management and digital resource training) and access to the online intervention for an initial three-month period. During this period participants are given the option to request up to five further home-based or online physiotherapy coaching sessions. Follow-up questionnaires and semi-structured interviews will be administered three months after baseline with participants and intervention physiotherapists. The LEAP-MS platform will be available to participants for a further three months. Usage of the LEAP-MS platform will be tracked during the full six-month period and final follow up will be conducted six months after baseline. Discussion. Feasibility outcomes (recruitment, retention, intervention uptake and safety) will be reported. The process evaluation will be undertaken to identify possible mechanisms for any observed effects. The data here will inform full scale evaluations of this co-produced, blended physiotherapy intervention. Trial registration: ClinicalTrials.gov NCT03951181. Registered 15th May 2019 https://clinicaltrials.gov/ct2/show/NCT03951181
LncRNA BANCR Attenuates the Killing Capacity of Cisplatin on Gastric Cancer Cell through the ERK1/2 Pathway
Authors: Miao Xiang , Liu Yixiang , Fan Yuzhu , Wang Guoqiang , zhu Hongbo
Published: May 2020

Background
Chemotherapy-based comprehensive treatment is the most important therapeutic method for patients with advanced gastric cancer, but chemoresistance often causes treatment failure. Long non-coding RNA (LncRNA) BRAF-activated non-coding RNA (BANCR) has been shown to participate in many biological behaviors of multiple cancers. However, the biological roles of LncRNA BANCR in chemoresistance of gastric cancer remain unclear. Here, we aimed to evaluate the functions of LncRNA BANCR in the therapy of gastric cancer.
Methods
In this study, LncRNA BANCR expression was detected in GC patient samples and cell lines by quantity polymerase chain reaction (qPCR). Cell proliferation and viability in cisplatin treated cells were measured using clonogenic survival assay and cell counting kit-8. The levels of ERK1/2 pathway molecules were tested with western blot. Ly3214996, an inhibitor of ERK signal pathway, administration was used to assess the effects of BANCR overexpression on GC cell cisplatin-treated resistance. Moreover, the role of BANCR in cisplatin resistance of GC was certified in xenograft mouse models in vivo.
Results
our study showed that LncRNA BANCR expression was also significantly increased in GC tissues compared with adjacent normal tissues. Furthermore, we found that BANCR overexpression promoted, while BANCR inhibited, GC cell resistance to cisplatin in vitro. Ly3214996 treatment abolished the BANCR overexpression-mediated GC cell cisplatin resistance via regulating the phosphorylation of ERK protein. Knock-down of BANCR delayed significantly tumor growth in xenograft mouse models.
Conclusion
BANCR promoted cisplatin resistance of GC cells by activating ERK1/2 pathway. Inhibition of BANCR was markedly suppressed the growth of gastric cancer cells in vitro as well as in vivo. This result provided a new strategy for gastric cancer via targeting BANCR