bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydroxyurea Optimization through Precision Study (HOPS): study protocol for a randomized, multicenter trial in children with sickle cell anemia
Authors: Meier Emily R. , Creary Susan E. , Heeney Matthew M. , Dong Min , Appiah‐Kubi Abena O , Nelson Stephen C. , Niss Omar , Piccone Connie , Quarmyne Maa-Ohui , Quinn Charles T. , Saving Kay L. , Scott John P. , Talati Ravi , Latham Teresa S. , Pfeiffer Amanda , Shook Lisa M. , Vinks Alexander A. , Lane Adam , McGann Patrick
Published: October 2020

Background : Sickle cell disease (SCD) is a severe and devastating hematological disorder that affects over 100,000 persons in the United States and millions worldwide. Hydroxyurea is the primary disease-modifying therapy for the SCD, with proven benefits to reduce both short-term and long-term complications. Despite the well-described inter-patient variability in pharmacokinetics (PK), pharmacodynamics and optimal dose, hydroxyurea is traditionally initiated at a weight-based dose with a subsequent conservative dose escalation strategy to avoid myelosuppression. Because the dose escalation process is time consuming and requires frequent laboratory checks, many providers default to a fixed dose, resulting in inadequate hydroxyurea exposure and suboptimal benefits for many patients. Results from a single-center trial of individualized, PK-guided dosing of hydroxyurea for children with SCD suggest that individualized dosing achieves the optimal dose more rapidly and provides superior clinical and laboratory benefits than traditional dosing strategies. However, it is not clear whether these results were due to individualized dosing, the young age that hydroxyurea treatment was initiated in the study, or both. The Hydroxyurea Optimization through Precision Study (HOPS) aims to validate the feasibility and benefits of this PK-guided dosing approach in a multi-center trial. Methods : HOPS is a randomized, multicenter trial comparing standard vs. PK-guided dosing for children with SCD as they initiate hydroxyurea therapy. Participants (ages 6 months through 21 years), recruited from 11 pediatric sickle cell centers across the United States, are randomized to receive hydroxyurea either using a starting dose of 20 mg/kg/day (Standard Arm) or a PK-guided dose (Alternative Arm). PK data will be collected using a novel sparse microsampling approach requiring only 10μL of blood collected at 3 time-points over 3 hours. A protocol-guided strategy more aggressive protocols is then used to guide dose escalations and reductions in both arms following initiation of hydroxyurea. The primary endpoint is the mean %HbF after 6 months of hydroxyurea. Discussion: HOPS will answer important questions about the clinical feasibility, benefits, and safety of PK-guided dosing of hydroxyurea for children with SCD with potential to change the treatment paradigm from a standard weight-based approach to one that safely and effectively optimize the laboratory and clinical response. Trial registration: ClinicalTrials.gov, NCT03789591. Registered on December 28, 2018.
Influence of diabetes on short-term outcome after major hepatectomy – an underestimated risk?
Authors: Fischer Alexander , Fuchs Juri , Stravodimos Christos , Hinz Ulf , Billeter Adrian , Büchler Markus W. , Mehrabi Arianeb , Hoffmann Katrin
Published: October 2020

Background: Patient-related risk factors such as diabetes mellitus and obesity are increasing in western countries. At the same time the indications for liver resection in both benign and malignant diseases have been significantly extended in recent years. Major liver resection is performed more frequently in a patient population of old age, comorbidity and high rates of neoadjuvant chemotherapy. The aim of this study was to evaluate whether diabetes mellitus, obesity and overweight are risk factors for the short-term post-operative outcome after major liver resection. Methods: Four hundred seventeen major liver resections (≥3 segments) were selected from a prospective database. Exclusion criteria were prior liver resection in patient’s history and synchronous major intra-abdominal procedures. Overweight was defined as BMI ≥ 25 kg/m 2 and < 30 kg/m 2 and obesity as BMI ≥ 30 kg/m 2 . Primary end point was 90-day mortality and logistic regression was used for multivariate analysis. Secondary end points included morbidity, complications according to Clavien-Dindo classification, unplanned readmission, bile leakage, and liver failure. Morbidity was defined as occurrence of a post-operative complication during hospital stay or within 90 days postoperatively. Results: Fifty-nine patients had diabetes mellitus (14.1%), 48 were obese (11.6%) and 147 were overweight (35.5%). There were no statistically significant differences in mortality rates between the groups. In the multivariate analysis, diabetes was an independent predictor of morbidity (OR = 2.44, p = 0.02), Clavien-Dindo grade IV complications (OR = 3.6, p = 0.004), unplanned readmission (OR = 2.44, p = 0.04) and bile leakage (OR = 2.06, p = 0.046). Obese and overweight patients did not have an impaired post-operative outcome compared patients with normal weight. Conclusions: Diabetes has direct influence on the short-term postoperative outcome with an increased risk of morbidity but not mortality. Preoperative identification of high-risk patients will potentially decrease complication rates and allow for individual patient counseling as part of a shared decision-making process. For obese and overweight patients, major liver resection is a safe procedure.
Cell-specific Characterization of the Placental Methylome
Authors: Yuan Victor , Hui Desmond , Yin Yifan , Peñaherrera Maria , Beristain Alexander , Robinson Wendy
Published: October 2020

Background: DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n=9) and term (n=19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at >850,000 CpGs.Results: The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare fetal-derived macrophage population. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation.Conclusions: Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from GEO (GSE159526), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.
Developing a complex intervention to support pregnant women with mild to moderate anxiety: application of the Medical Research Council framework
Authors: Evans Kerry , Spiby Helen , Morrell Jane C
Published: October 2020

Aim: To design and develop an intervention to support women with symptoms of mild to moderate anxiety in pregnancy.Methods: The development followed the MRC framework for complex interventions, utilising psychological theory, review level evidence and professional and public involvement. Two systematic reviews were completed which helped identify potentially beneficial intervention components. The theory underpinning the components was explored to consider the potential benefit for women with mild to moderate anxiety symptoms in pregnancy. Methods of delivering the intervention within maternity services were explored. The intervention comprised: group discussions, one to one support and assisted self-help resources. Midwives were identified as ideally placed to facilitate the intervention supported by midwifery support workers. A bespoke training package was provided by subject experts to prepare the facilitators. Discussion: The absence of established interventions and a paucity of evidence based approaches for pregnant women with symptoms of mild to moderate anxiety indicated the need for a rigorous and systematic approach to the intervention design. This approach led to the development of an intervention feasible for implementation in maternity care systems tailored to the needs of pregnant women. The involvement of a multi-professional advisory team and active engagement of service users helped to consider the acceptability of the intervention for women and the feasibility of delivering the intervention in the context of maternity care. Conclusion: The MRC Framework provided useful overarching guidance to develop a midwife facilitated intervention for women with symptoms of anxiety in pregnancy. The framework assisted the development of a robust rationale for each intervention component and considered the processes of evaluation and implementation into maternity care systems.
Implementation and factors affecting the nursing process among nurses working in selected government hospital in southwest Ethiopia
Authors: Adasho Zerihun Adraro , Bekele Daniel Mengistu
Published: October 2020

Background: The nursing process was initially adopted from the general system theory, and was developed and implemented in the field of education in the early years.Objective: The purpose of this study was to assess implementation and factors affecting the nursing process among nurses working in selected government hospitals in Southwest Ethiopia.Methods: An institution-based cross-sectional descriptive study was conducted from March 10 to April 1, 2015 in three hospitals in southwest Ethiopia using self-administered questionnaires. This study included a total of 138 nurses using simple random sampling. Data were classified, coded and entered into epidemiological information version 3.5.3, and exported to the statistical package for social science version 20 for analysis, descriptive statistics were used to describe the variables, bivariable and multivariable logistic regression were used to see the effect of each variable on the dependent variable.Result: The nursing process was found to be 73.9 percent implemented. Compared to a Bachelor of Science nurses’, the likelihood of implementing the nursing process was less likely among diploma nurses. Nurses working in administratively supported hospitals implemented the nursing process more compared to those without administrative support. The nursing process had been implemented higher by trained nurses compared to untrained nurses.Conclusion: The implementation of nursing process was good where; nearly seven in every ten nurses implemented the nursing process. Low educational qualification, lack of training, and non-supportive hospital administration were predictors of the nursing process implementation.
Women’s appraisal, interpretation and help-seeking for possible symptoms of breast and cervical cancer in South Africa: a qualitative study 
Authors: Harries Jane , Scott Suzanne E , Walter Fiona M , Mwaka Amos D , Moodley Jennifer
Published: October 2020

Background: In South Africa, breast cancer is the most commonly diagnosed cancer and cervical cancer the leading cause of cancer mortality. Most cancers are diagnosed at a late-stage and following symptomatic presentation. The overall purpose of the study was to inform interventions aimed at improving timely diagnosis of breast and cervical cancer.Methods: In-depth interviews were conducted with women with potential breast or cervical cancer symptoms from urban and rural South Africa. Participants were recruited from a community-based cross-sectional study on breast and cervical cancer awareness. Data were analysed using a thematic analysis approach. Results: Eighteen women were interviewed (10 urban, 8 rural): the median age was 34.5 years (range 22-58). Most were unemployed, and five were HIV positive. Themes included impact and attribution of bodily changes; influence of social networks and health messaging in help-seeking; management of symptoms and help-seeking barriers. Breast changes were often attributed to manual activities or possible cancer. Women were often unsure how to interpret vaginal symptoms, attributing them to HIV, hormonal contraceptives, or partner infidelity. Concerns about cancer were based on health information from the radio, social networks, or from primary care providers. Prompt care seeking was triggered by impact of symptoms on personal lives. Rural women, especially with possible symptoms of cervical cancer, experienced challenges during help-seeking including judgmental attitudes of clinic staff. Most participants were skeptical of traditional medicine. Conclusions: This is the first study exploring interpretation of possible breast and cervical cancer symptoms at a community level in South Africa. The process of interpreting bodily changes, symptom attribution and help-seeking is complex and influenced by women’s everyday life experiences. Timely diagnosis interventions should not only include cancer symptom awareness but also address individual, structural and health systems related barriers to care.
Association of gestational diabetes mellitus with offspring weight status across infancy: a prospective birth cohort study in China
Authors: Hu Jiajin , Liu Yilin , Wei Xiaotong , Li Lin , Gao Ming , Liu Yang , Ma Yanan , Wen Deliang
Published: October 2020

Background: The association between gestational diabetes mellitus (GDM) and childhood body weight remains controversial, and additional study is needed, especially in Asian populations.Methods: This prospective study investigated the association between maternal glucose concentration, and GDM status and infant body weight from birth to 12 months of age. Linear mixed effects (LME) models and multiple linear regression were used to assess the longitudinal association of GDM with infant growth measured by weight-for-length (WFLZ), weight-for-age (WFAZ), and length-for-age (LFAZ) z-scores at birth, 1, 3, 6, 8, and 12 months of age.Results: Offspring born to mothers with GDM had higher WFLZ [β: 0.26 SD units (95% CI: 0.13–0.40)] across infancy than those of mothers without GDM. The association was more pronounced in normal-weight and overweight/obese women (P for interaction< 0.05). Multiple linear regression found that the effect estimate of GDM on infant WFLZ was highest at birth [β: 0.32 SD units (95% CI: 0.07– 0.57)], remained significant at 1 [β: 0.24 SD units (95% CI: 0.05–0.43)] and 3 [β:0.20 SD units (95% CI: 0.01–0.39)] months of age and decreased across infancy. Maternal GDM status was not associated with infant WFAZ or LFAZ.Conclusions: Maternal GDM status was associated with infant WFLZ, but not WFAZ or LFAZ. The association of GDM status with offspring WFLZ was more pronounced in early infancy or in normal-weight and overweight/obese women. The results may help to identify the critical period and specific GDM-risk groups for childhood weight status.
Comparison of deep learning with regression analysis in creating predictive models for SARS-CoV-2 outcomes
Authors: Abdulaal Ahmed , Patel Aatish , Charani Esmita , Denny Sarah , Alqahtani Saleh A , Davies Gary W , Mughal Nabeela , Moore Luke SP
Published: October 2020

Background: Accurately predicting patient outcomes in SARS-CoV-2 could aid patient management and allocation of healthcare resources. There are a variety of methods which can be used to develop prognostic models, ranging from logistic regression and survival analysis to more complex machine learning algorithms and deep learning. Despite several models having been created for SARS-CoV-2, most of these have been found to be highly susceptible to bias. We aimed to develop and compare two separate predictive models for death during admission with SARS-CoV-2. Method: Between March 1 - April 24, 2020, 398 patients were identified with laboratory confirmed SARS-CoV-2 in a London teaching hospital. Data from electronic health records were extracted and used to create two predictive models using: 1) a Cox regression model and 2) an artificial neural network (ANN). Model performance profiles were assessed by validation, discrimination, and calibration. Results: Both the Cox regression and ANN models achieved high accuracy (83.8%, 95% confidence interval (CI): 73.8 - 91.1 and 90.0%, 95% CI: 81.2 - 95.6, respectively). The area under the receiver operator curve (AUROC) for the ANN (92.6%, 95% CI: 91.1 - 94.1) was significantly greater than that of the Cox regression model (86.9%, 95% CI: 85.7 - 88.2), p=0.0136. Both models achieved acceptable calibration with Brier scores of 0.13 and 0.11 for the Cox model and ANN, respectively. Conclusion: We demonstrate an ANN which is non-inferior to a Cox regression model but with potential for further development such that it can learn as new data becomes available. Deep learning techniques are particularly suited to complex datasets with non-linear solutions, which make them appropriate for use in conditions with a paucity of prior knowledge. Accurate prognostic models for SARS-CoV-2 can provide benefits at the patient, departmental and organisational level.
Preparing Lifelong Learners for Delivering Pharmaceutical Care in an Ever-Changing World: A Study of Pharmacy Students
Authors: Khamis Sarah , Abdi Abdikarim Mohamed , Basgut Bilgen
Published: October 2020

Background Continuing professional development (CPD) continues to gain acceptance as a model for health care professionals to engage in lifelong learning (LLL). Many pharmacy schools have not adopted yet specific programs targeting the development of LLL skills , though LLL is widely accepted as an essential competence. This paper examines the effectiveness and utility of a longitudinal CPD training program.

Methods

A CPD simulation course was introduced to a cohort of fifth year students in Northern Cyprus in the 2018-2019 academic year. The program was delivered as an interactive orientation course in one semester; meanwhile, in the second semester, the students applied the CPD cycle and completed their portfolios during their final experiential practice. A mixed-methods approach was used to evaluate the outcomes of the intervention using students’ preparedness for lifelong learning (SPLLL) self-administered questionnaire delivered pre-post program, focus group sessions for students to reflect on the course experience, and instructors’ evaluations of portfolios.

Results

Following the implementation of the course, students’ assessment scores were significantly higher overall and for all scale domains, including “knowledge, skills, attitude and practice”, compared to the baseline assessment. Additionally, compared to fifth year students who responded to the second SPLLL questionnaire, the intervention group students’ assessment was significantly higher in knowledge, skills, and practice. The qualitative analysis reported high student satisfaction and achievement of the course objectives. Nineteen of the students scored high on their portfolios.

Conclusion

The CPD simulation course provided students with opportunities to practice and develop self-assessment and self-management skills that are all desirable for lifelong learning and prepared them for CPD.
Fluoroquinolone resistance of Staphylococcus epidermidis isolated from healthy conjunctiva and analysis of their mutations in quinolone-resistance determining region
Authors: Kang Jung Youb , Lee Woonhyoung , Noh Gwang Myeong , Jeong Bo Hyun , Park Indal , Lee Sang Joon
Published: October 2020

Background: S. epidermidis is the most common pathogen in postoperative endophthalmitis and causes various infectious eye diseases. However, there is very little information on fluoroquinolone antibiotic resistance to S. epidermidis identified in conjunctival microbe and analysis of related genes. Here, the authors investigated the rate of resistance to fluoroquinolones of Staphylococcus epidermidis isolated from normal conjunctival microbes and mutations in the quinolone-resistance determining region (QRDR).Methods: 377 eye samples from 187 patients who underwent intravitreal injection and cataract surgery were included. Specimens were taken from the bilateral lower conjunctival sacs using a cotton swab and cultured. The cultures were identified using MALDI-TOP MS and gyrA, gyrB, parC, and parE gene mutations of QRDR were confirmed by DNA extraction from resistant strains of S. epidermidis with a micro-dilution method using ciprofloxacin, levofloxacin, and moxifloxacin.Results: The culture positive rate was 61.8% (231) for 374 eye samples. Of the 303 total strains cultured, S. epidermidis was the most common with 33.7% (102). Ten types of gene mutations were observed in the resistant S. epidermidis of 21 strains. One-point mutation was observed mainly in gyrA and parC, and a small number of mutations were observed in parE in the form of a double point mutations. When there were multiple point mutations in both gyrA and parC, the highest minimum inhibitory concentration (MIC) was observed.Conclusions: The quinolone resistance rate of S. epidermidis increased in comparison with previous studies, and resistant S. epidermidis showed mostly QRDR mutations, which were mainly found in gyrA and parC, and showed strong resistance when mutated in both genes.
Increasing newly diagnosed inflammatory bowel disease and improving prognosis in China: a 30-year retrospective study from a single center
Authors: Lv Hong , Jin Meng , Zhang Huimin , Chen Xuanfu , Wu Meixu , Guo Mingyue , Zhou Runing , Wang Zheng , Yang Hong , Qian Jiaming
Published: October 2020

Background: We aimed to characterize the trends of prognosis in ulcerative colitis (UC) and Crohn’s disease (CD) in a Chinese tertiary hospital. Methods: A 30-year retrospective cohort analysis was conducted at Peking Union Medical College Hospital. Consecutive patients newly diagnosed with UC or CD from 1985 to 2014 were included. The primary outcome was in-hospital mortality. The secondary outcomes included surgery and length of stay in hospital. The Pearson correlation coefficient was applied to determine the relationship between time and prognosis. Multivariable logistic regression analysis was performed to determine the risk factors for in-hospital mortality and surgery. Results: In total, 1467 patients were included in this study (898 cases with UC and 569 cases with CD). Annual admissions for UC and CD have increased significantly over the last 30 years (UC, r=0.918, P<0.05; CD, r=0.898, P<0.05). Decreased in-hospital mortality was observed both in patients with UC and CD (UC, from 2.44% to 0.27%, r=-0.827, P<0.05; CD, from 12.50% to 0.00%, r=-0.978, P<0.05). A decreasing surgery rate was observed in patients with CD (r=-0.847, P<0.05), while an increasing surgery rate was observed in patients with UC (r=0.956, P<0.05). Shortened average lengths of hospital stay were observed in both UC and CD patients (UC, from 47.83±34.35 days to 23.58±20.05 days, r=-0.970, P<0.05; CD, from 65.50±50.57 days to 26.41±18.43 days, r=-0.913, P<0.05). Toxic megacolon and septic shock were independent risk factors for in-hospital mortality in patients with UC. Intestinal fistula and intestinal perforation were independent risk factors for in-hospital mortality in patients with CD. Conclusions: In this cohort, the admissions of patients with UC and CD were increased, with significantly improved prognoses during the past 30 years.
Association between nontraditional lipid profiles and peripheral arterial disease in Chinese adults with hypertension
Authors: Ding Congcong , Chen Yang , Shi Yumeng , Li Minghui , Hu Lihua , Zhou Wei , Wang Tao , Zhu Lingjuan , Huang Xiao , Bao Huihui , Cheng Xiaoshu
Published: October 2020

Background: Data on the relationship between nontraditional lipid profiles [total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)/HDL-C ratio, low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio, non-high-density lipoprotein cholesterol (non-HDL-C)] and the risk of peripheral artery disease (PAD) are limited. The present study investigated the relationship of nontraditional lipid indices with PAD in hypertensive patients. Methods: This cross-sectional study was performed among 10,900 adults with hypertension. Participants were diagnosed with PAD when their ankle-brachial index (ABI) was < 0.9. The association between nontraditional lipid profiles and PAD was examined using multivariate logistic regression analysis and the restricted cubic spline. Results: All nontraditional lipid indices were independently and positively associated with PAD in a dose-response fashion. After multivariable adjustment, the per SD increments of the TC/HDL-C, TG/HDL-C, LDL-C/HDL-C ratios and non-HDL-C were all significantly associated with 37%, 14%, 40%, and 24% higher risk for PAD, respectively. The adjusted ORs (95% CI) for PAD were 1.77 (1.31, 2.40), 1.71 (1.25, 2.34), 2.03 (1.50, 2.74), and 1.70 (1.25, 2.31) when comparing the highest tertile to the lowest tertile of the TC/HDL-C, TG/HDL-C, LDL-C/HDL-C ratios and non-HDL-C, respectively. Conclusions: Among Chinese hypertensive adults, all nontraditional lipid indices were positively associated with PAD, and the LDL-C/HDL-C and TC/HDL-C ratios were better than the other nontraditional lipid indices for predicting PAD. These findings may improve the risk stratification of cardiovascular disease and dyslipidemia management.
A comparison between manual and artificial intelligence-based automatic positioning in CT imaging for COVID-19 patients
Authors: Gang Yadong , Chen Xiongfeng , Li Huan , Wang Hanlun , Li Jianying , Guo Ying , Zeng Junjie , Hu Qiang , Hu Jinxiang , Xu Haibo
Published: October 2020

Objective: To analyze and compare the imaging workflow, radiation dose and image quality for COVID-19 patients examined using either the conventional manual positioning (MP) method or an AI-based automatic positioning (AP) method. Materials and Methods: 127 adult COVID-19 patients underwent chest CT scans on a CT scanner using the same scan protocol except with the manual positioning (MP group) for the initial scan and an AI-based automatic positioning method (AP group) for the follow-up scan. Radiation dose, patient positioning time and off-center distance, of the two groups were recorded and compared. Image noise and signal-to-noise ratio (SNR) were assessed by three experienced radiologists and were compared between the two groups.Results: The AP operation was successful for all patients in the AP group and reduced the total positioning time by 28% compared with the MP group. Compared with the MP group, the AP group had significantly less patient off-center distance (AP:1.56cm±0.83 vs. MP: 4.05cm±2.40, p<0.001) and higher proportion of positioning accuracy (AP: 99% vs. MP: 92%), resulted in 16% radiation dose reduction (AP: 6.1mSv±1.3 vs. MP: 7.3mSv±1.2, p<0.001) and 9% image noise reduction in erector spinae and lower noise and higher SNR for lesions in the pulmonary peripheral areas.Conclusion: The AI-based automatic positioning and centering in CT imaging is a promising new technique for reducing radiation dose, optimizing imaging workflow and image quality in imaging the chest. This technique has important added clinical value in imaging COVID-19 patients to reduce the cross-infection risks.
Evolutionary history of Ku proteins: evidence of horizontal gene transfer from archaea to eukarya
Authors: Mainali Ashmita , Rijal Sadikshya , Bhattarai Hitesh Kumar
Published: October 2020

Background

The DNA end joining protein, Ku, is essential in Non-Homologous End Joining in prokaryotes and eukaryotes. It was first discovered in eukaryotes and later by PSI blast, was discovered in prokaryotes. While Ku in eukaryotes is often a multi domain protein functioning in DNA repair of physiological and pathological DNA double stranded breaks, Ku in prokaryotes is a single domain protein functioning in pathological DNA repair in spores or late stationary phase. In this paper we have attempted to systematically search for Ku protein in different phyla of bacteria and archaea as well as in different kingdoms of eukarya.
Result

From our search of 116 sequenced bacterial genomes, only 25 genomes yielded at least one Ku sequence. From a comprehensive search of all NCBI archaeal genomes, we received a positive hit in 7 specific archaea that possessed Ku. In eukarya, we found Ku protein in 27 out of 59 species. Since the entire genome of all eukaryotic species is not fully sequenced this number could go up. We then drew a phylogenetic maximum likelihood tree to determine the ancestral relationship between Ku70 and Ku80 in eukaryotes and Ku in prokaryotes. Out tree revealed a common node for some archaeal Ku, Ku70 and Ku80.
Conclusion

This led us to hypothesize that Ku from archaea transferred through horizontal gene transfer onto neozoa and then duplicated to form Ku70 and Ku80. Additionally, we analyzed the domains of the different eukaryotic species to demonstrate that fusion, fission, terminal addition, terminal deletion, single domain loss, single domain emergence events during evolution.
Longitudinal Analysis of Socioecological Obesogenic Factors in a National Sample of U.S. Children
Authors: Kim Taeeung , KWON JUNHYE , Lee Chung Gun , Jang Chang-Yong
Published: October 2020

Background: Childhood obesity is a serious public health threat. Although many researchers conducted research on socioecological determinants of childhood obesity, their longitudinal effects remain inconclusive especially among young children. This study examined socioecological factors and associated transitions of children’s body mass index (BMI) status throughout children’s kindergarten to elementary school years, using data from a national longitudinal sample.Methods: The baseline sample of this study included 1,264 children (weighted N=379,297) extracted from the Early Childhood Longitudinal Study (baseline mean age: 5.24 years). The socioecological framework guided selection of socioecological obesogenic variables (e.g., family activity and parental involvement). Longitudinal ordered logistic regressions were performed to determine the associations between socioecological obesogenic variables and unhealthy/healthy changes in BMI status that captured transitions between healthy and unhealthy weight status (i.e., overweight, obesity, and severe obesity).Results: Children with Hispanic ethnicity and nonwhite, less socioeconomic and environmental support, and living in households with fewer family members were more likely than their counterparts to have unhealthy BMI status changes over time (all ps<0.05). Over the study period, girls were less likely than boys to experience transitions to unhealthy BMI status (all ps<0.05).Conclusion: As hypothesized a priori, the findings of the current affirmed multiple dimensions of how sociological obesogenic factors may influence children’s BMI status changes in a longitudinal setting. In order to maintain children’s long-term healthy weight, more attention should be paid to socioeconomic obesogenic factors surrounding children as well as individual determinants of obesity (e.g., being physically active and having well-balanced nutrition).
Transcriptional expression of secondary resistance genes ccdB and repA2 is enhanced in presence of cephalosporin and carabapenem in Escherichia coli
Authors: Baishya Somorita , Deshamukhya Chandrayee , Wangkheimayum Jayalaxmi , Das Bhaskar Jyoti , Anbarasu Anand , Talukdar Anupam Das , Bhattacharjee Amitabha , Choudhury Manabendra Dutta
Published: October 2020

Background: The issue of carbapenem resistance in E.coli is very concerning and it is speculated that cumulative effect of both primary resistance genes and secondary resistance genes that act as helper to the primary resistance genes are the reason behind their aggravation. Therefore, here we attempted to find the role of two secondary resistance genes (SRG) ccdB and repA2 in carbapenem resistance in E. coli (CRE).Methods: Influential genes belonging to secondary resistome that act as helper to the primary resistance genes like blaNDM and blaCTX-M in aggravating β-lactam resistance were selected from an earlier reported in silico study. Transcriptional expression of the selected genes in clinical isolates of E.coli that were discretely harboring blaNDM-1, blaNDM-4, blaNDM-5, blaNDM-7 and blaCTX-M-15 with and without carbapenem and cephalosporin stress (2µg/ml) was determined by real time PCR. Cured mutants sets that were lacking (i) primary resistance genes, (ii) secondary resistance genes and (iii) both primary and secondary resistance genes were prepared by SDS treatment. These sets were then subjected to antibiotic susceptibility testing by Kirby Bauer disc diffusion method.Results: Out of the 21 genes reported in the in silico study, 2 genes viz. repA2 and ccdB were selected for transcriptional expression analysis. repA2, coding replication regulatory protein, was downregulated in response to carbapenems and cephalosporins. ccdB, coding for plasmid maintenance protein, was also downregulated in response to carbapenems except imipenem and cephalosporins. Following plasmid elimination assay increase in diameter of zone of inhibition under stress of both antibiotics was observed as compared to uncured control hinting at the reversion of antibiotic susceptibility by the-then resistant bacteria. Conclusion: SRGs repA2 and ccdB help sustenance of blaNDM and blaCTX-M under carbapenem and cephalosporin stress.
Encephalitis Associated with COVID-19 in a Patient with Multiple Sclerosis
Authors: Moghadasi Abdorreza Naser
Published: October 2020

From the beginning of COVID-19 pandemics, the involvement of patient’s nervous system with this virus is increasingly reporting. Although various reports are published on affliction of multiple sclerosis (MS) patients with SARS-CoV-2, no report has been published on brain involvement by this virus in MS patients so far. Herein, a 34-year-old patient with MS who experienced the decreased level of consciousness and encephalopathy following COVID-19 involvement has been reported.
Targeted suppression of microRNA-33 in lesional macrophages using pH low-insertion peptides (pHLIP) improves atherosclerotic plaque regression
Authors: Zhang Xinbo , Rotllan Noemi , Canfrán-Duque Alberto , Toczek Jakub , Moshnikova Anna , Malik Shipra , Price Nathan , Araldi Elisa , Zhong Wen , Sadeghi Mehran , Andreev Oleg , Bahal Raman , Reshetnyak Yana , Suarez Yajaira , Fernandez-Hernando Carlos
Published: October 2020

Hypoxia and tissue acidification occur in the macrophage-rich regions of advanced atherosclerotic lesions due to the higher oxygen demand of activated immune cells and insufficient oxygen supply. Our group and others originally identified microRNA-33 (miR-33) as critical regulator of cellular lipid homeostasis and lipoprotein metabolism controlling the development of atherosclerosis. Our prior work has demonstrated that pH Low-Insertion Peptides (pHLIP) can be used to direct miR-33 inhibitors to acidic microenvironments and protect against kidney fibrosis. Here we utilize anti-miR-33 conjugated pHLIP constructs to target macrophages located in atherosclerosis plaques. The inhibition of miR-33 using pHLIP-directed targeting increased collagen content and decreased lesional lipid accumulation within atherosclerotic plaques in a murine model of atherosclerosis regression. Single cell RNA sequencing analysis revealed higher expression of fibrotic genes (Col2a1, Col3a1, Fn1, Dcn, etc) and tissue inhibitor of metalloproteinase 3 (Timp3), and downregulation of matrix metallopeptidase 12 (Mmp12) in macrophages from atherosclerotic lesions targeted by pHLIP- anti-miR-33. These results suggest a potential application of pHLIP for treating advanced atherosclerosis via pharmacological inhibition of miR-33.
WITHDRAWN: The Drone delivery problem in disaster and pandemics
Authors: Hammouti Issam El , Lajjam Azza , Merouani Mohamed El
Published: October 2020

Recently, the use of drone is growing in importance in several fields. Their capacity toavoid traffic jam and operate without a human pilot, make it the perfect method tohome delivery in natural disasters and pandemics. This paper addresses the dronedelivery problem inside Covid-19 outbreak area where quarantine status has beenapplied. This problem aims to minimize the time spent by a drone to complete thehome delivery of pharmaceutical products and other indispensable goods to a set ofresidents inside the quarantine area. We propose a new mathematical formulation forthe problem, and we develop a simulated annealing algorithm to solve large sizedinstances. To show the performance of our metaheuristic; extensive computationalexperience inspired by a real case of study in Morocco (Nador) are realized. Ourresults confirm that the proposed metaheuristic is a better alternative to solve the dronedelivery problem in disaster and pandemics than the commercial solver (CPLEX 12.7)
The ratio of negative lymph nodes count inside the thoracic cavity to the positive lymph count is a prognostic factor in esophageal squamous cell carcinoma
Authors: Zhang jinling , Liu yan , Li hongyan , Li xinglan , Li luning , Yu lianling , Che fengyuan , Heng xueyuan
Published: October 2020

BACKROUND: It was reported that the number of positive lymph nodes (PLN) and negative lymph nodes (NLN) resected in lymphadenectomy were both independent prognostic factors in esophageal squamous cell carcinoma (ESCC). However, it is unclear which kind of combination of them would have a stronger impact on the prognosis of the ESCC patients. METHODS: A total of 229 patients with ESCC were retrospectively investigated. The Cox Proportional Hazards Model was used to investigate the relationship between the PLN or NLN and the overall survival of patients. Survival analysis was performed using the Kaplan-Meier method, and the survival difference between sub-groups were explored with log-rank tests. The cut-off number of the ratio of NLN count to PLN count resulted in an improved outcome for patients was investigated by a series of log-rank tests. RESULTSs: The numbers of PLN and NLN were both independent prognostic factors, supported by the results of Cox regression model analysis (hazard ratio [HR], 1.12, P<0.001 and HR, 0.97, P=0.024, respectively).The survival differences among sub-groups from N0 to N3 stage were statistically significant (P<0.001). Analysis using a Cox regression model revealed that the number of NLN inside the thoracic cavity had a stronger impact on the prognosis compared to the number of NLN outside the thoracic cavity (HR,0.959, P=0.042 vs.HR, 0.973, P=0.179). As a combination analysis consisting of the number of PLN and NLN, the log-rank test result demonstrated that patients with the ratio of NLN count inside thoracic cavity to the PLN count less than 8 could achieve a better survival.CONCLUSIONS: The ratio of NLN count inside thoracic cavity to the PLN count was a independent prognostic factor.
Needs and Resources of People With Type 2 Diabetes in Peri-urban Cochabamba, Bolivia: a People-centred Perspective
Authors: Leyns Christine , Couvreur Niek , Willems Sara , Hecke Ann Van
Published: October 2020

Background: The rising prevalence of type 2 diabetes results in a worldwide public healthcare crisis, especially in low- and middle-income countries (LMICs) with unprepared and overburdened health systems mainly focused on infectious diseases and maternal and child health. Studies regarding type 2 diabetes in LMICs describe specific interventions ignoring a comprehensive analysis of the local factors people see influential to their health. This study aims to meet this research gap by exploring what people with type 2 diabetes in Bolivia need to maintain or improve their health, how important they perceive those identified needs and to what extent these needs are met.Methods: From March until May 2019, 33 persons with type 2 diabetes from three periurban municipalities of the department of Cochabamba participated in this study. The concept mapping methodology by Trochim, a highly structured qualitative brainstorming method, was used to generate and structure a broad range of perspectives on what the participants consider instrumental for their health.Results: The brainstorming resulted in 156 original statements condensed into 72 conceptually different needs and resources, structured under nine conceptual clusters and four action domains. These domains illustrated with vital needs were: (1) self-management with use of plants and the possibility to measure sugar levels periodically; (2) healthcare providers with the need to trust and receive an uniform diagnose and treatment plan; (3) health system with opportune access to care and (4) community with community participation in health and safety, including removal of stray dogs.Conclusions: This study identifies mostly contextual factors like low literacy levels, linguistic problems in care, the need to articulate people's worldview and traditional use of natural remedies with the Bolivian health system and the lack of expertise on type 2 diabetes by primary health care providers. Understanding the needs and structuring them in different areas wherein action is required serves as a foundation for the planning and evaluation of an integrated people centred care program for people with type 2 diabetes. This participative method serves as a tool to implement the often theoretical concept of integrated people centred health care in health policy and program development.
Identification of Androgen Receptor Variant 7-related RNAs Affecting Abiraterone Efficacy in Castration-resistant Prostate Cancer Treatment by RNA-sequencing
Authors: Wang Shuo , Cao Yudong , Tang Xingxing , Yang Yong , Du Peng
Published: October 2020

Background: This study aimed to identify androgen receptor variant 7 (AR-V7)-related RNAs affecting Abiraterone treatment of castration-resistant prostate cancer (CRPC) using RNA-sequencing. Methods: To identify AR-V7-related RNAs affecting Abiraterone treatment of CRPC, a series of in vitro experiments were employed, including cell proliferation assay, cell apoptosis assay, Western blot analysis, and Real-time quantitative reverse transcription PCR (qRT-PCR). After RNA-sequencing, the differentially expressed (DE) mRNAs and DE long non-coding RNAs (lncRNAs) were screened and the lncRNA-mRNA pairs were identified. In addition, enrichment and Protein-protein interaction (PPI) network analyses were performed. Finally, the mRNA-miRNA-lncRNA competing endogenous RNAs (ceRNA) network was built, along with survival analysis. Results: A total of 1,387 AR-V7-related RNAs affecting Abiraterone treatment of CRPC were identified. The enrichment analysis showed that the target genes of DEmRNAs and DElncRNAs were primarily involved in cancer-related pathways, including the ErbB signaling pathway, pathways in cancer, and basal cell carcinoma. In addition, notch receptor 1 (NOTCH1), ionotropic NMDA glutamate receptor type subunit 1 (GRIN1), U-box containing protein 1 (STUB1), and mitogen-activated protein kinase 7 (MAP2K7) with high degrees in the PPI network. Moreover, MAP2K7 was regulated by hsa-miR-6825-5p, which in turn was regulated by MAFG-AS1 lncRNA in the ceRNA network. The survival analysis revealed that a total of four lncRNAs, including MAFG-AS1, and 17 mRNAs, including high muscle blind-like splicing regulator 2 (MBNL2), were associated with disease-free survival (RFS). Among them, only MBNL2 overexpression correlated with good survival outcome. The NOTCH1, GRIN1, STUB1, MBNL2, and ErbB signaling pathways are likely related to the efficacy of Abiraterone in CRPC treatment. Moreover, the MAFG-AS1-hsa-miR-6825-5p-MAP2K7 axis could be a therapeutic target for Abiraterone in CRPC treatment.Conclusions: NOTCH1, GRIN1, STUB1, MBNL2, and the ErbB signaling pathway may relate to the progression of CRPC. MAFG-AS1-hsa-miR-6825-5p-MAP2K7 axis might be a potential therapeutic target for Abiraterone in CRPC.
A Prediction Model Based on DNA Methylation Biomarkers and Radiological Characteristics for Identifying Malignant From Benign Pulmonary Nodules
Authors: Xing Wenqun , Sun Haibo , Yan Chi , Zhao Chengzhi , Wang Dongqing , Li Mingming , Ma Jie
Published: October 2020

BackgroundLung cancer remains the leading cause of cancer deaths across the world. Early detection of lung cancer by low-dose computed tomography (LDCT) can reduce the mortality rate. However, making a definitive preoperative diagnosis of malignant pulmonary nodules (PNs) found by LDCT is a clinical challenge. This study aimed to develop a prediction model based on DNA methylation biomarkers and radiological characteristics for identifying malignant pulmonary nodules from benign PNs. MethodsWe assessed three DNA methylation biomarkers (PTGER4, RASSF1A, and SHOX2) in a training cohort of 110 individuals with PNs. Using univariate and multivariate logistic regression analysis, we developed a prediction model based on the three DNA methylation biomarkers and one radiological characteristic for identifying malignant from benign PNs. The performance of the prediction model with that of the methylation biomarkers and the Mayo Clinic model were compared using the non-parametric approach of DeLong et al. with the area under a receiver operator characteristic curve (AUC) analysis. ResultsThe developed prediction model achieved a sensitivity of 87.3% and a specificity of 95.7% with an AUC value of 0.951 in malignant PNs diagnosis, being significantly higher than the three DNA methylation biomarkers (84.1% sensitivity and 89.4% specificity, p=0.013) or clinical/radiological characteristics (76.2% sensitivity and 87.2% specificity, p=0.001) alone. Validation of the prediction model in the testing cohort of 100 subjects with PNs confirmed the diagnostic value.ConclusionWe have shown that integrating DNA methylation biomarkers and radiological characteristics could more accurately identify lung cancer in subjects with CT-found PNs. The prediction model developed in our study may provide clinical utility in combination with LDCT to improve the over-all diagnosis of lung cancer.