bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring in practice – How are UK academic clinical trials monitored? A survey
Authors: Love Sharon , Yorke-Edwards Victoria , Lensen Sarah , Sydes Matthew R
Published: December 2019

Despite the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) encouraging the use of risk-based monitoring for trials in 2013, there remains a lack of evidence-based guidelines on how to monitor. We surveyed the academic United Kingdom Clinical Research Collaboration (UKCRC) registered clinical trials units (CTUs) to find out their policy on monitoring of phase III randomised clinical trials of an investigational medicinal product (CTIMPs).
Methods
An online survey of monitoring policy with sections on the CTU, central monitoring and on-site monitoring was sent to all 50 UKCRC registered CTUs in November 2018.
Descriptive data analysis and tabulations are reported using the total number answering each question.
Results
43/50 (86%) of CTUs responded with 38 conducting phase III randomised CTIMP trials. Of these 38 CTUs, 34 finished the survey. Most CTUs (36/37, 97%) use a central monitoring process to guide, target or supplement site visits. More than half (19/36, 53%) of CTUs do not use an automated monitoring report when centrally monitoring trials and all units use trial team knowledge to make a final decision on whether an on-site visit is required.
31/34 (91%) CTUs used triggers to decide whether or not to conduct an on-site monitoring visit. On-site, a mixture of source data verification and checking of processes was carried out.
The CTUs overwhelmingly (27/34, 79%) selected optimising central monitoring as their most pressing concern.

Conclusion
The survey showed a wide variation in Phase III randomised CTIMP trial monitoring practices by academic clinical trials units within a single research-active country. We urgently need to develop evidence-based regulator agreed guidance for CTUs on best practice for both central and on-site monitoring and to develop tools for all CTUs to use.
The ultrastructural damage of Eugenia zeyheri and Syzygium legatii acetone leaf extracts on pathogenic Escherichia coli
Authors: Famuyide Ibukun M. , Fasina Folorunso O. , Eloff Jacobus , McGaw Lyndy J.
Published: December 2019

Background Antibiotics are commonly added to livestock feeds in sub-therapeutic doses as growth promoters and for prophylaxis against pathogenic microbes, especially those implicated in diarrhoea. While this practice has improved livestock production, it is a major cause of antimicrobial resistance in microbes against livestock and humans. This has led to the banning of prophylactic antibiotic use in animals in many countries. To compensate for this, alternatives have been sought from natural sources such as plants. While many studies have reported the antimicrobial activity of medicinal plants with potential for use as phytogenic/botanical feed additives, little information exists on their mode of action. This study is based on our earlier work and describes ultrastructural damage induced by acetone crude leaf extracts of Syzygium legatii and Eugenia zeyheri (Myrtaceae) active against diarrhoeagenic E. coli of swine origin using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and fluorescent microscopy (FM). Gas chromatography/mass spectrometry (GC-MS) was used to investigate the chemical composition of plant extracts.Results The extracts damaged the internal and external anatomy of the cytoplasmic membrane and inner structure at a concentration of 0.04 mg/mL. Extracts also led to an increased influx of propidium iodide into treated bacterial cells suggesting compromised cellular integrity and cellular damage. Non-polar compounds such as α-amyrin, friedelan-3-one, lupeol, and β-sitosterol were abundant in the extracts.Conclusions The extracts of S. legatii and E. zeyheri caused ultrastructural damage to E. coli cells characterized by altered external and internal morphology. These observations may assist in elucidating the mode of action of the extracts
Familial autosomal recessive bestrophinopathy: identification of a novel variant in BEST1 gene and the specific metabolomic profile
Authors: Ye Panpan , Xu Jia , Luo Yueqiu , Su Zhitao , yao ke
Published: December 2019

BackgroundAutosomal recessive bestrophinopathy (ARB) is a retinal degenerative disorder caused by BEST1 mutations with autosomal recessive inheritance. We aim to map a comprehensive genomic and metabolomic profile of a consanguineous Chinese family with ARB.MethodsOphthalmic examinations were performed on the affected patients with ARB. The proband was screened for potential causative mutations in a panel with 256 known retinal disease genes by using target capture sequencing. The related mutation was further validated and segregated in the family members by Sanger sequencing. In silico prediction tools were used for pathogenicity assessment. A UHPLC-MS/MS metabolomic analysis was performed to explore the disease-associated metabolic feature.ResultsThe affected patients from this family were characterized by low vision, the presence of subretinal fluid, macular edema, and hyperopia with coincidental angle closure. DNA sequencing identified a novel missense mutation in the BEST1 gene c.646G>A (p.Val216Ile) of the proband. Sanger sequencing further confirmed the mutation. The missense mutation was co-segregation across the pedigree and predicted to be deleterious by SIFT (0.017). The blood metabolic profiles were highly similar among all family members probably because of the same lifestyle, habitat and genomic background. However, ARB patients presented a significant deregulation of metabolites, such as citric acid, L-Threonic acid, and eicosapentaenoic acid.ConclusionsWe identified a novel disease-associated variant in the BEST1 gene as well as a disease-specific metabolic feature in familial ARB. Our findings helped improve the understanding of ARB mechanisms.
The Oxidoreductase DsbA1 negatively influences 2,4-diacetylphloroglucinol biosynthesis by interfering the function of Gcd in Pseudomonas fluorescens 2P24
Authors: Zhang Bo , Zhao Hui , Wu Xiaogang , Zhang Li-Qun
Published: December 2019

The polyketide antibiotic 2,4-diacetylphloroglucinol (2,4-DAPG), produced by Pseudomonas fluorescens 2P24, is positively regulated by the GacS-GacA two-component system. Here we reported on the characterization of DsbA1 (disulfide oxidoreductase) as novel regulator of biocontrol activity in P. fluorescens . Our data showed that mutation of dsbA1 caused the accumulation of 2,4-DAPG in a GacA-independent manner. Further analysis indicated that DsbA1 interacts with membrane-bound glucose dehydrogenase Gcd, which positively regulates the production of 2,4-DAPG. Mutation of cysteine (C)-235, C275, and C578 of Gcd, significantly reduced the interaction with DsbA1, enhanced the activity of Gcd and increased 2,4-DAPG production. Taken together, our results suggest that DsbA1 regulates the 2,4-DAPG concentration via fine-tuning the function of Gcd in P. fluorescens 2P24.
Association Between Dietary Consumption, Anthropometric Measures And Body Composition Of Rural And Urban Ghanaian Adults; A Comparative Cross Sectional Study.
Authors: Agyapong Nana Ama Frimpomaa , Annan Reginald Adjetey , Apprey Charles , Aduku Linda Nana Esi , Swart Catherina Elizabeth
Published: December 2019

Background: Overweight and obesity have become threats to public health in all regions across the globe. Policies to regulate the food environment and promote healthy food consumption can reduce the prevalence obesity but in Ghana there is not enough data to elicit a policy response. This study assessed the association between dietary consumption, anthropometric measures, body composition and physical activity among rural and urban Ghanaian adults. Methods: This was a cross-sectional study involving 565 Ghanaian adults. Structured questionnaires were used to collect socio-demographic information. Dietary consumption was assessed using household food frequency questionnaire and 24-hour recall. Height, weight, BMI, waist circumference and body composition of all participants were also measured. The World Health Organization’s Global Physical Activity Questionnaire (GPAQ) was used to assess physical activity levels. Mann Whitney U test was used to analyze differences in anthropometric measurements, body composition and dietary consumption among rural and urban participants. Principal component analysis was used to analyze household food frequency data and nutrient analysis template was used to analyze 24-hour recall. Chi-square was used to measure differences in obesity prevalence by community and gender. Multinomial logistic regression was used to model the risk factors associated with obesity. Results: The prevalence of overweight and obesity using BMI were 29.9 and 22.9 respectively. The use of waist circumference measurement resulted in the highest overall obesity prevalence of 41.5%. Prevalence of obesity was higher among females compared to males across all measures with the exception of visceral fat that showed no significant difference. Four different patterns were derived from principal component analysis. Among urban participants, component 3 (staple pattern) showed a significant negative correlation with visceral fat (r -0.186, p-value 0.013) and BMI (r -0.163, p-value 0.029). Multinomial logistic regression showed that males (AOR 19.715, CI 9.723-39.978, p-value < 0.001) had higher odds of being of normal weight compared to females. Conclusion: Prevalence of overweight and obesity continue to rise in Ghana, especially among females. Public education and screening as well as interventions that regulate the food environment and make affordable and available healthy food options are needed to control the rise in obesity prevalence.
Cytological evidence of BSD2 functioning in both chloroplast division and dimorphic chloroplast formation in maize leave
Authors: Li Heying , Bai Mei , Jiang Xingshan , Shen Rongxin , Wang Huina , Wang Haiyang , Wu Hong
Published: December 2019

Background: Maize bsd2 (bundle sheath defective2) is a classical C4 mutant with defective C4 photosynthesis, accompanied with reduced accumulation of Rubisco (ribulose bisphosphate carboxylase oxygenase) and aberrant mature chloroplast morphology in the bundle sheath (BS) cells. However, as a hypothetical chloroplast chaperone, the effects of BSD2 on C4 chloroplast development have not been fully examined yet, which precludes a full appreciation of BSD2 function in C4 photosynthesis. The aims of our study are to find out the role of BSD2 in regulating chloroplasts development in maize leaves, and to add new insights into our understanding of C4 biology.
Results: We found that at the chloroplast maturation stage, the thylakoid membranes of chloroplasts in the BS and mesophyll (M) cells became significantly looser, and the grana of chloroplasts in the M cells became thinner stacking in the bsd2 mutant when compared with the wild type plant. Moreover, at the early chloroplast development stage, the number of dividing chloroplasts and the chloroplast division rate are both reduced in the bsd2 mutant, compared with wild type. Quantitative reverse transcriptase-PCR analysis revealed that the expression of both thylakoid formation-related genes and chloroplast division-related genes is significantly reduced in the bsd2 mutants. Further, we showed that BSD2 interacts physically with the large submit of Rubisco (LS) in Bimolecular Fluorescence Complementation assay.

Conclusions: Our combined results suggest that BSD2 plays an essential role in regulating the division and differentiation of the dimorphic BS and M chloroplasts, and that it acts at a post-transcriptional level to regulate LS stability or assembly of Rubisco.
Trabecular bone scores in young HIV-infected men: a matched case-control study
Authors: Kim Youn Jeong , Kang Kwi Young , Shin Juyoung , Jun Yoonhee , Kim Sang Il , Ree Kim Yang
Published: December 2019

Background Screening for osteoporosis with dual-energy X-ray absorptiometry (DXA) is recommended for male HIV-infected patients only above the age of 50. Recently, trabecular bone score (TBS) has been introduced as a novel tool to assess bone microarchitecture using DXA of the lumbar spine. Few studies have reported TBS values in HIV-infected individuals younger than 50 years of age. This study compared TBS values in young males infected with HIV and matched controls, and investigated the associations between TBS and demographic parameters, clinical parameters, and bone mineral density (BMD) scores. Methods A cross-sectional study of BMD and TBS in HIV-infected men (n = 80) aged between 18 and 50 years and age- and sex-matched controls (n = 80) was conducted. Results The proportion of patients with low BMD (Z-score ≤−2) was significantly greater among HIV-infected patients than among matched controls (21.3% [17/80] vs. 8.8% [7/80], p = 0.027). Mean TBS values were significantly lower in HIV-infected patients than in controls (1.41 ± 0.07 vs. 1.45 ± 0.07, p = 0.008). In both groups, TBS values were positively correlated with BMD at the lumbar spine, femoral neck, and total hip (p < 0.001); however, TBS was not correlated with body mass index. In the HIV group, TBS was negatively correlated with the duration of tenofovir disoproxil fumarate(TDF) exposure (p = 0.04). Conclusion Young men infected with HIV had abnormal bone trabecular microarchitecture, as assessed by both TBS and BMD. TBS values were correlated with both BMD and the duration of TDF exposure.
Semi-constrained posterior stabilized total knee arthroplasty reproduces natural deep knee bending kinematics
Authors: Sumino Takanobu , Tomita Tetsuya , Sugamoto Kazuomi , Yamazaki Takaharu , Okazaki Ken
Published: December 2019

Background: The Flexible Nichidai Knee Posterior Stabilized (FNK-PS) system was designed to provide relatively high varus-valgus stabilities without the stem extensions to patients with severe knee joint disorders. This is a combination of a large tibial post and high femoral cam adapted to a PS system. The aim of our study was to analyze the in vivo two-dimensional/three-dimensional registration kinematics of the FNK PS-total knee arthroplasty (TKA) system during deep knee bending.
Methods: Nineteen knees from 15 total knee arthroplasty (TKA) patients who were able to squat with enough knee flexion were selected. During deep knee bending under weight bearing (WB) and non-weight bearing (NWB) conditions, we quantified range of motion, axial rotation, femoral anteroposterior translation, and post-cam engagement angle.
Results: The maximum-flexion was significantly different between the two conditions. The mean axial femoral external rotation was 4.8° and 6.2° under WB and NWB conditions, respectively, at 120° flexion. Anteroposterior translation based on bicondylar posterior roll-back patterns was noted with increasing knee flexion. Both the medial and lateral femoral aspects were significantly more posterior during early to mid-flexion. Initial post-cam engagement occurred significantly earlier during flexion under NWB than under WB conditions. Under WB, the timing of the post-cam engagement correlated with the maximum flexion .
Conclusions: The kinematics of the semi-constrained PS system reproducibly exhibited a mild external rotation with smooth posterior roll-back. This was assisted by the engagement of the large tibial post and high femoral cam during the early phase of flexion.
Potential consequences of expanded MUAC-only programs on targeting of acutely malnourished children and ready-to-use-therapeutic-food allocation: lessons from cross-sectional surveys
Authors: Guesdon Benjamin , Couture Alexia , Pantchova Danka , Bilukha Oleg
Published: December 2019

Background: Some of the recently piloted innovative approaches for the management of acute malnutrition in children use the “expanded MUAC-only” approach, with Mid Upper Arm Circumference (MUAC) <125mm as the sole anthropometric criterion for screening and admission, classification of cases as severe using the 115mm cut-off, and use Ready-to-Use-Therapeutic-Food (RUTF) for the management of both moderate (MAM) and severe (SAM) cases of acute malnutrition. Our study aimed at exploring the potential consequences of this “expanded MUAC-only” program scenario on the eligibility for treatment and RUTF allocation, as compared with the existing WHO normative guidance.

Methods: We analyzed data from 550 population representative cross-sectional cluster surveys conducted since 2007. We retrieved all children classified as SAM and MAM according to currently used case definitions, and calculated the proportions of SAM children who would be excluded from treatment, misclassified as MAM, or whose specific risks (because of having both MUAC and weight-for height deficits) would be ignored. We also analyzed the expected changes in the number and demographics (sex, age) of children meant to receive RUTF according to the new approach.

Results: We found that approximately one quarter of SAM children would not be detected and eligible for treatment under the “expanded MUAC-only” scenario, and another 20% would be classified as MAM. A further 17% of the total SAM children would be admitted and followed only according to their MUAC or oedema status, while they also present with a severe weight-for height deficit on admission. Considering MAM targeting, about half of the MAM children would be left undetected. This scenario also shows a 2.5 time increase in the number of children targeted with RUTF, with approximately 70% of MAM and 30% of SAM cases among this new RUTF target.

Conclusions: This empirical evidence suggests that adoption of “expanded MUAC-only” programs would likely lead to a priori exclusion from treatment or misclassifying as MAM a large proportion of SAM cases, while redirecting programmatic costs in favor of those less in need. It underscores the need to explore other options for improving the impact of programs addressing the needs of acutely malnourished children.
Hospitalizations for viral respiratory infections in children under 2 years of age: epidemiology and in-hospital complications
Authors: Zurita-Cruz Jessie , Gutierrez-Gonzalez Alejandro , Manuel-Apolinar Leticia , Fernández-Gárate José Esteban , Arellano-Flores María Luisa , Eng Roberto Alejandro Correa Gonzalez , Vazquez-Rosales Guillermo , Sanchez-Armas Rocio , Cisneros Nelly
Published: December 2019

Background Viral respiratory infection (VRI) is a frequent cause of hospitalization in children under 24 months of age. Prematurity or heart disease histories may be risk factors for complications in patients hospitalized for VRI.Objective To describe the epidemiological data of pediatric patients 1 to 24 months of age who were hospitalized for VRI and identify risk factors for the presence of in-hospital complications over a period of 5 years.Methods This was a cross-sectional study. The database was compiled by doctors, electronically validated by engineers and analyzed by statisticians. Patients with VRI (based on International Classification of Diseases [ICD-10] codes B974, J12, J120-J129X, J168, J17, J171, J178, J20, J203-J209, J21, J210, J211, J218, J219, J22X, and J189) from 2013 to 2017 were registered. The patients were classified into 2 groups according to the absence or presence of a history of prematurity (P070, P072, P073), bronchopulmonary dysplasia (BPD) (P271) and congenital heart disease (CHD) (Q20-Q26). Length of hospital stay, in-hospital complications, surgical procedures and mortality were analyzed.Statistical analysis The prevalence of hospitalization for VRI was described. For comparisons between the groups, Student's t-tests and chi 2 tests were applied. To identify the factors related to in-hospital complications and mortality, a logistic regression model was constructed.Results A total of 69,093 hospitalizations were reported. The average age of patients was 14.17 weeks. The number of hospitalization events in winter was the highest (38.9%), followed by autumn (27.3%). A total of 408 (0.59%) patients died. A total of 7,496 hospitalized patients with comorbidities were identified. Surgical procedures (OR = 16.66 & 16.64) and comorbidities (OR = 4.29 & 4.58) were risk factors for in-hospital complications and mortality.Conclusions The risk factors for morbidity and mortality in patients hospitalized for VRI were a history of prematurity, BPD and CHD, as well as some type of surgical procedure during hospitalization.
CircRNA_0058063 functions as a ceRNA in bladder cancer progression via targeting miR-486-3p/FOXP4 axis
Authors: Liang Haote , Huang Hang , Li Yeping , Lu Yongyong , Ye Tingyu
Published: December 2019

Emerging evidences have uncovered critical regulatory roles of circular RNAs (circRNAs) function as dynamic scaffolding molecules in tumorigenesis and progression. However, the aberrant expression and clinical significance of hsa_circ_0058063 (circRNA_0058063) in bladder cancer (BC) remain poorly understood. circRNA expression was analyzed via a microarray in cancerous tissue and non-carcinoma tissues. Luciferase reporter assays and RNA immunoprecipitation (RIP) were both conducted to uncover the function of circRNA_0058063 in BC. circRNA_0058063 was overexpressed in BC tissues compared to adjacent normal tissues. Knockdown of circRNA_0058063 dramatically decreased cell proliferation and invasion, and promoted apoptosis in 5637 and BIU-87 cell lines. Furthermore, mechanistic investigations showed that circRNA_0058063 and FOXP4 could directly bind to miR-486-3p, demonstrating that circRNA_0058063 regulated FOXP4 expression by competitively binding to miR-486-3p. Taken together, circRNA_0058063 functions by sponging miR-486-3p in BC progression, which could be act as a new biomarker and further developed to be a therapeutic target in BC.
Value of digital mammography in predicting lymphovascular invasion of breast cancer
Authors: Liu Zhuangsheng , Li Ruqiong , Liang Keming , Chen Junhao , Chen Xiangmeng , Li Xiaoping , Li Ronggang , Zhang Xin , Yi Lilei , Long Wansheng
Published: December 2019

Background: To use digital mammography, a more popular imaging tool, for predicting lymphovascular invasion(LVI) in breast cancer patients preoperatively.
Methods: 122 cases of invasive ductal carcinoma diagnosed between May 2017 and September 2018 were collected, which were divided into positive group (n=42) and negative group (n=80) according to the presence or absence of LVI.
Results: The differences of these variables(childbearing history, miscarriage history, other breast diseases history, nipple discharge, breast cancer marker CA153, age, ER, PR, HER-2, E-CAD, P53, Ki-67) between LVI positive group and the LVI negative group were not statistically significant, except that of Ki-67 (P=0.012). For the image features of digital mammography, the differences of interstitial edema (P=0.013) and skin thickening (P=0.000) between LVI positive group and negative groups were statistically significant. The differences of other imaging patterns, that is, fibroglandular tissue density, size , solitary/multiple, mass shape, mass margin , subcutaneous fat, axillary adenopathy and so on, between the two groups were not statistically significant. Multiple factor analysis shows that, there are three independent risk factors for predicting LVI occurrence: interstitial edema (OR = 12.610, 95% confidence interval CI: 1.061, 149.922, P=0.045), subcutaneous fat (OR=0.081, 95% confidence interval CI: 0.012, 0.645, P =0.017) and skin thickening (OR=9.041, 95% confidence interval CI: 2.553, 32.022, P=0.001).
Conclusion: Interstitial edema, blurring of subcutaneous fat layer, and skin thickening were independent risk factors for predicting LVI occurrence. When applying these three imaging patterns together, the specificity of LVI prediction was as high as 98.8%.
Epidemiology and clinico-pathological characteristics of current goat pox outbreak in North Vietnam
Authors: Hong Trang Pham , Lila Mohd Azmi Mohd , Rahaman Nor Yasmin Abd. , Lan Huong Lai Thi , Thi Lan Nguyen , Van Khien Do , Noordin Mohamed Mustapha
Published: December 2019

Background In view of the current swine fever outbreak and the government aspiration to increase the goat population, a need arises to control and prevent industry decimating outbreaks goat pox. Despite North Vietnam facing sporadic cases of goat pox, this most recent outbreak had the highest recorded morbidity, mortality and case fatality rate. Thus, owing to the fear that such outbreak may recur and become widespread, an analysis of that outbreak was done based on selected signalment, management and disease pattern (signs and pathology) parameters.Results It was found that the susceptible age group were between 3-6 months old kids while higher infection rate occurred in those under the free-range rearing system. The clinical signs and lesions were not restricted to the skin but have extended into the lung and intestine. The pathogen had been confirmed in positive cases via PCR as goat pox with prevalence of almost 80%.Conclusions The current outbreak of goat pox in North Vietnam denotes its significance to the industry and signals the importance of a prompt identification which will lead to an effective control of the disease.
Suicide among people treated for drug use disorders: a Danish national record-linkage study
Authors: Hesse Morten , Thylstrup Birgitte , Seid Abdu Kedir , Skogen Jens Christoffer
Published: December 2019

Background: Substance use disorders are a major risk factor for suicide. However, less is known about specific risk factors for suicide in people with substance use disorders.
Methods: This population cohort study assessed suicide among people treated for drug use disorders in Denmark 2000-2010, and described risk factors for completed suicide. Data from 27,942 individuals enrolled in treatment were linked to national registers and matched with controls without drug use disorder and with (n=138,136) or without psychiatric history (n=1,574). Competing risk regression was used to identify risk factors of completed suicide.
Results: There were 163 suicides among patients with a history of drug treatment (0.6% of patients). Increased risk was associated with younger age at enrolment (hazard ratio [HR] = 0.97, 95% confidence interval (CI): 0.95, 0.98), history of psychiatric care (HR=1.96, CI 95%: 1.39, 2.77), opioid use (HR=1.81, 95% CI: 1.23, 2.68), and alcohol use (HR=1.56, 95% CI: 1.09, 2.23). Lower risk was associated with cannabis use (HR=0.69, 95% CI: 0.50, 0.96). Compared with age- and gender-matched controls without a history of treatment for substance use disorders or recent psychiatric care, the standardized mortality ratio due to suicide was 7.13 for people with drug use disorder without a history of psychiatric care (95% CI: 5.81, 8.44), 13.48 for people with drug use disorder and psychiatric history (95% CI: 9.75, 17.22), and 13.61 for people with psychiatric history only (95% CI: 6.72, 20.50).
Conclusions: Risk of suicide is increased among people with drug use disorders. Access to treatment for co-morbid mental health problems for people with drug use disorders could potentially reduce risk of suicide.
Clinical audit in the Pediatric primary care office setting: a tool for improvement of overweight prevention in preschool age.
Authors: Limauro Raffaele , Gallo Patrizia , Cioffi Luigi , Antignani Angelo , Cioffi Valentina , Calella Patrizia , Valerio Giuliana
Published: December 2019

Background: Clinical audit is a process by which physicians or other health care professionals perform a regular and systematic review of their clinical practice and amend it, when necessary. An internal audit allows to review the activities carried out by professionals, in order to assess the appropriateness, effectiveness, efficiency and safety of the services provided. Aim of this study was to apply the process of clinical audit to the obesity/overweight care in young children. After the correction of the nutritional errors that were considered potentially responsible for the excess weight gain, the effect of the changes of dietary advices on the frequency of overweight/obesity was assessed in a cohort of children aged 24-36 months. Methods: Three Italian primary care pediatricians have applied the audit strategy by recognizing the high prevalence of overweight and obesity in the entire cohort of children born in 2005, 2006 and 2007 (Pre-Audit group, age 24-36 months old) under their care. By reviewing their clinical practice, they changed the protocol of weaning and feeding up to 36 months, mainly reducing the protein intake. The change involved the cohorts of children born in the years 2010, 2011 and 2012 (Post-Audit group). Results: Changes in children’s diet yielded a reduction of the frequency of overweight and obesity between 24 and 36 months of life in the Post-Audit group. Conclusion: Clinical audit can be an effective tool in identifying inaccuracies in medical procedures and helpful in revising them.
Risky Sexual Behavior and Associated Factors Among Sexually-Active Unmarried Young Female Internal Migrants Working in Burayu Town, Ethiopia
Authors: Baru Ararso , Adeoye Ikeola A. , Adekunle Adeyemi O.
Published: December 2019

Background Young female internal migrants are highly vulnerable to risky sexual behaviors (RSB) which may result in serious health problems such as unintended pregnancy, abortion and sexually transmitted infections including HIV. RSB include early sexual debut (before 18 years), having multiple sexual partners, sex without condom or inconsistent use of condom and sex under influence of substance use. This study aimed to assess the magnitude and the factors associated with RSB among sexually-active unmarried young female internal migrants in Burayu Town, Ethiopia.Methods A cross sectional study design was used for the study. A total of 267 respondents were recruited in to the study using simple random sampling technique. A semi-structured interviewer administered questionnaire was used to obtain information from the study participants. The collected data were cleaned, coded and entered into Epi data version 3.1 and then exported to SPSS Ver.21 for analysis. Multiple logistic regression models were used to indicate the association between dependent and independent variables.Results About 35% of the young female internal migrants had sexual debut before age of 18 years; 64.4% had sex without condom or inconsistently used condom; nearly one quarter of the participants had multiple sexual partners and 29.6% had sex under influence of substance uses. The magnitude of RSB among the study participants was (79.1%). Sexting [AOR 3.47(95%; CI;1.10-11.94)], frequent indulgence of social media [AOR 10.9(95%;CI;2.31-51.89)], feeling of embarrassment to buy condom [AOR 8.28(95%; CI; 2.10-32.62)], unfavorable attitude toward using condom for steady and loving relationship [AOR 5.72(95%; CI; 1.47-22.24)] were related with RSB while self-efficacy [AOR 0.15(95%: CI; 0.04-0.57)] to use condom and perceived risks of getting pregnant [AOR 0.05(95%; CI; 0.01-0.23)] were found to be protective factors.Conclusion The study found high levels of RSB among sexually-active unmarried young female internal migrants. This finding suggests an urgent need of intervention to promote safe sex among this group. Special attention and prompt interventions are needed to promote the use of condom. Moreover, intense efforts should be made to improve awareness on the seriousness of exposure to sexting and judicious use of social media among unmarried female internal migrants.
Factors influencing malaria infection in Rwanda 2010: a cross-sectional survey study using generalized structural equation modeling
Authors: Bakar Muhammad Abu , Fiaz Rahma , Musenge Eustasius
Published: December 2019

BackgroundMalaria is one of the primary public health concerns in the world and an important cause of morbidity and mortality in sub-Saharan Africa. Malaria morbidity is associated with poverty and vulnerability as it is not easy for the poor people to access preventive treatment and protective measures. In Rwanda, malaria prevention has become a major problem against the double-barreled burden of an overstretched health system and strained financial resources.MethodsThis work was a cross-sectional survey study design based on data from Rwanda collected in 2010 through the Malaria Indicator Survey as part of the Demographic and Health Survey. The primary outcome variable was an ordinal variable with three categories; no malaria, probable malaria, and confirmed malaria cases. The outcome variable was formulated by combining rapid malaria test and confirmatory blood smear laboratory test. Statistical analysis was done using survey ordinal logistic regression modelling adjusting for random effects for direct effects and generalised structural equation modelling (G-SEM) to obtain total (direct and indirect) effects of malaria morbidity. ResultsThe 11,865 participants had a mean age of 22 years, and two-thirds of the participants were females (67%). Household related variables (socio-economic status, health insurance, age in years) showed a significant total effect on malaria infection. Socioeconomic status had the greatest total effect which was a sum of the direct and indirect effects influenced indirectly by education, health insurance and the number of rooms for sleeping. Conclusion Poverty is still the core issue to the morbidity patterns driving the malaria epidemic in Rwanda. Access to health insurance has a high positive impact on decreasing disease as such a special focus on some regions can be an effective intervention strategy. A better understanding of the drivers of morbidity directly and/or indirectly can better target interventions to be more efficient in those affected areas.
Development and outcomes of a comprehensive multidisciplinary incidental lung nodule and lung cancer screening program
Authors: LeMense Gregory , Waller Ernest A. , Campbell Cheryl , Bowen Tyler
Published: December 2019

BackgroundAppropriate management of lung nodules detected incidentally or through lung cancer screening can increase the rate of early-stage diagnoses and potentially improve treatment outcomes. However, the implementation and management of comprehensive lung nodule programs is challenging. MethodsA single-center, retrospective study was conducted to describe the development and outcomes of a lung nodule program at a community practice in Tennessee.ResultsThe number of patients with lung nodules referred to the program increased over 2 years, with 665 patients in Year 1 and 745 patients in Year 2. Most nodules were incidental (60% Year 1, 65% Year 2). In Year 1, 17% of nodules were symptomatic and 12% were identified through screening. Of the 665 nodules in Year 1, 182 underwent a diagnostic intervention and 121 (18%) received a cancer diagnosis. Most diagnostic interventions were image-guided bronchoscopy (88%) or percutaneous biopsy (9%). The proportion of Stage I-II cancer diagnoses increased from 23% prior to program implementation to 36% in Year 1 and 38% in Year 2. Among screening cases, follow-up scans were conducted within 18 months in 71%. Only 2% of patients under watchful waiting required a diagnostic intervention, of which 1% received a cancer diagnosis.ConclusionsThe current study reports outcomes over the first two years of a lung cancer screening and incidental nodule program. The program was successful and manageable, given the appropriate level of data management and oversight. Comprehensive lung nodule programs have the potential to benefit the patient, physician, and hospital system.
Prognosis of patients with acute exacerbation of combined pulmonary fibrosis and emphysema: A retrospective single-center study
Authors: Ikuyama Yuichi , Ushiki Atsuhito , Kosaka Makoto , Akahane Jumpei , Mukai Yuichi , Araki Taisuke , Kitaguchi Yoshiaki , Tateishi Kazunari , Urushihata Kazuhisa , Yasuo Masanori , Yamamoto Hiroshi , Hanaoka Masayuki
Published: December 2019

BackgroundPrevious analyses of combined pulmonary fibrosis and emphysema (CPFE) cohorts have provided conflicting data on the survival of patients with CPFE. Therefore, the aim of this study was to investigate the clinical prognosis of acute exacerbation (AE) of CPFE.MethodsWe retrospectively reviewed the medical records of patients who had been treated at Shinshu University Hospital (Matsumoto, Japan) between 2003 and 2017. We identified 21 patients with AE of CPFE and 41 patients with AE of idiopathic pulmonary fibrosis (IPF) and estimated their prognoses using the Kaplan–Meier method.ResultsTreatment content and respiratory management were not significantly different between the two groups before and after exacerbation. At the time of AE, the median serum Krebs von den Lungen-6 level was significantly lower in the CPFE group (Krebs von den Lungen-6: 966 U/µL; white blood cell count: 8810 /µL) than that in the IPF group (Krebs von den Lungen-6: 2130 U/µL, p < 0.001; white blood cells: 10809/µL, p = 0.0096). The baseline Gender-Age-Physiology score was not significantly different between the two groups (CPFE, 4.5 points; IPF, 4.7 points; p = 0.58). Kaplan–Meier curves revealed that the survival time after AE for patients with CPFE was longer than that for patients with IPF (p < 0.001, log-rank test).ConclusionsSurvival prognoses after AE were significantly better for patients with CPFE than that for patients with IPF. Our findings may improve the medical treatment and respiratory management of patients with AE-CPFE.
Lipase immobilized on functionalized superparamagnetic few-layer graphene oxide as an efficient nanobiocatalyst for biodiesel production from chlorella vulgarise bio-oil
Authors: Nematian Tahereh , Shakeri Alireza , Salehi Zeinab , Saboury Ali Aakbar
Published: December 2019

Background Microalgae, due to its well-recognized advantages have been gained renewed interest as potentially good feedstock for biodiesel. Production of fatty acid methyl esters (FAMEs) as a type of biodiesel was carried out from Chlorella vulgaris bio oil. Biodiesel was produced in the presence of nano-biocatalysts composed of immobilized lipase on functionalized superparamagnetic few-layer graphene oxide via a transesterification reaction. A hybrid of few-layer graphene oxide and Fe3O4 (MGO) was prepared and characterized. The MGO was functionalized with 3-aminopropyl triethoxysilane (MGO-AP) as well as with a couple of AP and glutaraldehyde (MGO-AP-GA). The Rhizopus oryzae lipase (ROL) was immobilized on MGO and MGO-AP using electrostatic interactions as well as on MGO-AP-GA using covalent bonding. The supports, MGO, MGO-AP, and MGO-AP-GA, as well as Nano-biocatalyst, ROL/MGO, ROL/MGO-AP, and ROL/MGO-AP-GA, were characterized using FESEM, VSM, FTIR, and XRD. The few-layer graphene oxide was characterized using AFM and the surface charge of supports was evaluated with the zeta potential technique. The nano-biocatalysts assay was performed with an evaluation of kinetic parameters, loading capacity, relative activity, time-course thermal stability, and storage stability. Biodiesel production was carried out in the presence of nano-biocatalysts and their reusability was evaluated in 5 cycles of transesterification reaction. Results: The AFM analysis confirmed the few-layer structure of graphene oxide and VSM also confirmed that all supports were superparamagnetic. The maximum loading of ROL (70.2%) was related to MGO-AP-GA. The highest biodiesel conversion of 71.19% achieved in the presence of ROL/MGO-AP-GA. Furthermore, this nano-biocatalyst could maintain 58.77% of its catalytic performance after 5 cycles of the transesterification reaction and was the best catalyst in the case of reusability. Conclusions: In this study, the synthesized nano-biocatalyst based on bare and functionalized magnetic graphene oxide was applied and optimized in the process of converting microalgae bio-oil to biodiesel for the first time and compared with bare lipase immobilized on magnetic nanoparticles. Results showed that the loading capacity, kinetic parameters, thermal stability, and storage stability improved by the functionalization of MGO. The biocatalysts, which were prepared via covalent bonding immobilization of enzyme generally, showed better characteristics. Keywords Few-layer graphene oxide; Biodiesel; Chlorella vulgaris; Bio-oil; Superparamagnetic; Nano-biocatalyst.
New insights from the biogas microbiome by comprehensive genome-resolved metagenomics of nearly 1600 species originating from multiple anaerobic digesters
Authors: Campanaro Stefano , Treu Laura , Rodriguez-Rojas Luis M , Kovalovszki Adam , Ziels Ryan M , Maus Irena , Zhu Xinyu , Kougias Panagiotis G. , Basile Arianna , Luo Gang , Schlüter Andreas , Konstantinidis Konstantinos T. , Angelidaki Irini
Published: December 2019

Background
Microorganisms in biogas reactors are essential for degradation of organic matter and methane production. However, a comprehensive genome-centric comparison, including relevant metadata for each sample, is still needed to identify the globally distributed biogas community members and serve as a reliable repository.
Results
Here, 134 publicly available metagenomes derived from different biogas reactors were used to recover 1,635 metagenome-assembled genomes (MAGs) representing different biogas bacterial and archaeal species. All genomes were estimated to be >50% complete and nearly half ≥90% complete with ≤5% contamination. In most samples, specialized microbial communities were established, while only a few taxa were widespread among the different reactor systems. Metabolic reconstruction of the MAGs enabled the prediction of functional traits related to biomass degradation and methane production from waste biomass. An extensive evaluation of the replication index provided an estimation of the growth rate for microbes involved in different steps of the food chain. The recovery of many MAGs belonging to Candidate Phyla Radiation and other underexplored taxa suggests their specific involvement in the anaerobic degradation of organic matter.
Conclusions
The outcome of this study highlights a high flexibility of the biogas microbiome, allowing it to modify its composition and to adapt to the environmental conditions, including temperatures and a wide range of substrates. Our findings enhance our mechanistic understanding of the AD microbiome and substantially extend the existing repository of genomes. The established database represents a relevant resource for future studies related to this engineered ecosystem.
Keywords
Anaerobic digestion, Metagenome-Assembled Genomes, Biogas, Microbial community structure, Functional reconstruction
Transcriptome analysis of the regulation of natamycin biosynthesis in Streptomyces natalensis HW-2 by fungal elicitor
Authors: Wang Dahong , Shen Wenhao , Yuan Jiangfeng , Wei Lanlan , Zhang Ying
Published: December 2019

Background

Natamycin is a polyene macrolide polyketide antibiotics and used in 150 countries as a natural food preservative. Streptomyces natalensis is an important producer. Elicitation had been approved to be an effective method to improve the biosynthesis of secondary metabolites. Fungal elicitor from Penicillium chrysogenum AS 3.5163 showed inductive effect on the biosynthesis of natamycin in S. natalensis HW-2 fermentation. However, regarding the global gene expression of natamycin in response to fungal elicitor is not still reported.

Results

RNA-Seq analysis showed that there were 1265 differential expression genes (DEGs) at 40 h and 2196 DEGs at 80 h. The fungal elicitor had stronger effects on the transcription level of S. natalensis HW-2 at 80 h than that at 40 h. Gene Ontology (GO) enrichment analysis of DEGs showed significant enrichment in biological processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the fungal elicitor mainly affected the expression levels of some genes about cellular process, metabolism and genetic information, especially in pentose phosphate pathway (PPP), glycolytic pathway (EMP) and tricarboxylic acid cycle (TCA). KEGG pathway showed that fungal elicitor had a greater influence on the metabolism of branched-chain amino acids (BCAAs). Among them, 23 DEGs associated with BCAAs metabolism were up-regulated or down-regulated. The supplementation experiment with BCAAs confirmed that 0.2 g/L of L-Ile and 0.5 g/L of L-Val increased natamycin yield by 17.6% and 37.8%, respectively. Fungal elicitor also up-regulated the transcriptional levels of most of the enzymes associated with the biosynthesis of natamycin and two important transcription regulators ( pimR and pimM ). To confirm the accuracy of RNA-Seq, the results of qPCR showed that these gene expression levels were in agreement with the transcription changes by RNA-Seq.

Conclusion

In this study, the change of transcriptional levels in S. natalensis HW-2 under treated with the fungal elicitor was firstly reported. The major finding of our comparative transcriptome analysis is that the fungal elicitor improves the supply of precursor, and alters the expression of natamycin related genes and regulator of secondary metabolism. From our results, we conclude that regulatory alterations are important factors for the enhancement of natamycin.
TB-diabetes comorbidity and associated factors in Maekel Zone, Eritrea: A cross sectional study.
Authors: Araia Zenawi Zeramariam , Mebrahtu Amanuel Hadgu , Tewelde Adiam Ghebreyohanns , Mesfun Araia Berhane , Saleh Randa Osma , Tuumzghi Hagos Andom
Published: December 2019

Background : In Eritrea, no study document the true burden of TB-diabetes comorbidity. However, diabetes has been constantly increasing with a prevalence of 3.4 %. Similarly, even though TB notification is showing a declining trend the prevalence is 123/100,000 population. With an increasing diabetes trend, the country is at higher risk of rising TB-diabetes comorbidity which can further complicate TB care, control and prevention activities. Thus, this study was conducted to assess the prevalence of diabetes among pulmonary positive TB patients and its influencing factors in Maekel zone, Eritrea. Methods: This study was a cross sectional study conducted in all (11) TB diagnostic and treatment sites of Maekel zone. All consecutive pulmonary positive TB cases who were registered during the period of 2015-2018 in the national TB treatment register and were eligible included in the analysis. Pretested data extraction tool was used to collect the required information. Data analysis was done by SPSS version 23. Simple frequencies, percentages and means were used to describe the data. Chi-square test and logistic regression analysis was also performed. Results: A total of 490 pulmonary positive TB cases were eligible for the study and the overall prevalence of diabetes among pulmonary positive TB cases was 4.3%. Univariate logistic regression showed that participants with an older age (45-90) were more likely to have TB-diabetes comorbidity (COR: 4.397[CI: 1.675-11.545], p<0.01) than those aged 10-44 years old. In addition, subjects whose weight was 65kg and above were more likely (COR: 7.647[CI: 1.965-29.758], p<0.01) to have TB- diabetes comorbidity than those with lower body weight. Conclusion: TB-diabetes comorbidity observed in this study is low but given the growing diabetes trend in the country, an integrated TB-DM services should be given regularly on full scale at all health facilities.