bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of autophagy triggers melatonin-induced apoptosis in glioblastoma cells
Authors: Zhou Nan , Wei Zixuan , Qi Zengxin
Published: December 2019

Background: Autophagy is considered to be another restorative focus for the treatment of brain tumors. Although several research have demonstrated that melatonin induces autophagy in colon cancer and hepatoma cells, there has not been any direct evidence of whether melatonin is capable of inducing autophagy in human glioma cells.
Results: In the present research, we report that melatonin or its agonist, agomelatine, induced autophagy in A172 and U87-MG glioblastoma cells for a concentration-and time-dependent way, which was significantly attenuated by treatment with luzindole, a melatonin receptor antagonist. Furthermore, by suppressing autophagy at the late-stage with bafilomycin A1 and early stage with 3-MA, we found that the melatonin-induced autophagy was activated early, and the autophagic flux was complete. Melatonin treatment alone did not induce any apoptotic changes in the glioblastoma cells, as measured by flow cytometry. Western blot studies confirmed that melatonin alone prominently upregulated the levels of Beclin 1 and LC3 II, which was accompanied by an increase in the expression of Bcl-2, whereas it had no effect on the expression of Bax in the glioblastoma cells. Remarkably, co-treatment with 3-MA and melatonin significantly enhanced the apoptotic cell population in the glioblastoma cells, along with a prominent decrease in the expression of bcl-2 and increase in the Bax expression levels, which collectively indicated that the disruption of autophagy triggers the melatonin-induced apoptosis in glioblastoma cells.
Conclusions: These results provide information indicating that melatonin may act as a common upstream signal between autophagy and apoptosis, which may lead to the development of new therapeutic strategies for glioma.
The Smoking Cessation in Pregnancy Incentives Trial (CPIT): study protocol for a phase III randomised controlled trial
Authors: Sinclair Lesley , McFadden Margaret , Tilbrook Helen , Mitchell Alex , Keding Ada , Watson Judith , Bauld Linda , Kee Frank , Torgerson David , Hewitt Catherine , McKell Jennifer , Hoddinott Pat , Harris Fiona M , Uny Isabelle , Boyd Kathleen , Mcmeekin Nicola , Ussher Michael , Tappin David
Published: December 2019

Background
Eighty percent of UK women have at least one baby, making pregnancy an opportunity to help women to stop smoking before their health is irreparably compromised. Smoking cessation during pregnancy helps protect infants from miscarriage, still birth, low birth weight, asthma, attention deficit disorder and adult cardiovascular disease. UK national guidelines highlight lack of evidence for effectiveness of financial incentives to help pregnant smokers quit. This includes a research recommendation: Within a UK context, are incentives an acceptable, effective and cost-effective way to help pregnant women who smoke to quit?
Methods
CPIT III is a pragmatic, 39-month, multi-centre, parallel group, individually randomised controlled superiority trial of the effect on smoking status of adding to usual smoking cessation support the offer of up to £400 of financial voucher incentives, compared with usual support alone, to quit smoking during pregnancy.
Participants (n = 940) are pregnant smokers (age > 16, <24 weeks pregnant, English speaking), who consent via telephone to take part and are willing to be followed-up in late pregnancy and 6 months after birth.
The primary outcome is cotinine/anabasine validated abstinence from smoking in late pregnancy. Secondary outcomes include engagement with cessation services, quit rates at four weeks from agreed quit date and 6 months after birth, and birth weight. Outcomes will be analysed by intention-to-treat, and regression models will be used to compare treatment effects on outcomes. A meta-analysis will include data from the feasibility study in Glasgow. An economic evaluation will assess cost-effectiveness from a UK NHS perspective. Process evaluation using a case study approach will identify opportunities to improve recruitment and learning for future implementation.
Research questions: What is the therapeutic efficacy of incentives? Are incentives cost-effective? What are the potential facilitators and barriers to implementing incentives in different parts of the UK?
Discussion
This phase III trial in Scotland, England and Northern Ireland, follows a successful phase II trial in Glasgow UK. The participating sites have diverse smoking cessation services, that represent most cessation services in the UK and serve demographically varied populations. If found to be acceptable and cost-effective this trial could demonstrate that financial incentives are effective and transferable to most UK cessation services for pregnant women.
Identity Matters- Perceptions of Inter-Professional Feedback in the Context of Workplace-based Assessment in Diabetology Training: A Qualitative Study
Authors: Feller Katrin , Berendonk Christoph
Published: December 2019

Background:
Inter-professional collaboration is acknowledged as essential for quality patient-care. However, little is known about receptiveness to inter-professional feedback in the postgraduate training. This study explores, in light of social identity theory, the perceptions of residents, supervising physicians and allied health care professionals regarding inter-professional feedback in the context of workplace-based assessment.
Methods:
For six months, residents in diabetology at the University Hospital of Bern performed formative workplace-based assessments under direct observation of a supervising physician and an allied health care professional. Feedback from both observers was given to the resident after every assessment. Subsequently, focus group discussions were conducted to collect the participants’ perceptions of inter- and intra-professional feedback. Transcripts were analyzed qualitatively using a thematic analysis approach.
Results:
We identified four main themes: (1) Identity and hierarchy; (2) Interdependence of feedback source and feedback content; (3) Impact on collaboration and patient-care; (4) Logistical and organizational requirements. While different social identities are the source of inter-professional hierarchies, they did not impede the receptiveness to feedback. Perceived trustworthiness of the feedback was attributed with more importance than professional affiliations, whereas intra-professional hierarchies between physicians led to the perception of a more summative nature of the feedback and rather impeded receptiveness. According to the participants, inter-professional feedback raised awareness of the working reality of other team members and had a positive impact on communication between the different professional groups. Moreover, participants reported positive response from patients regarding the inter-professional collaboration they experienced. Considerable organizational effort is required to enable the parallel observation of a resident’s consultation by a supervising physician and an allied health care professional.
Conclusions:
Feedback from allied health care professionals can be a valuable learning resource for residents, given its role outside the sometimes conflicting area of intra-professional hierarchies. Inter-professional feedback in the context of workplace-based assessment carries the potential to strengthen collaboration between the different professional groups.
Confirmatory Factor Analysis of Adverse Childhood Experiences (ACEs) among a Community-Based Sample of Parents and Adolescents
Authors: Afifi Tracie , Salmon Samantha , Davila Isabel Garcés , Struck Shannon , Fortier Janique , Taillieu Tamara , Stewart-Tufescu Ashley , Asmundson Gordon J.G. , Sareen Jitender , MacMillan Harriet L.
Published: December 2019

The authors have withdrawn this preprint from Research Square
Correlation between the efficacy of stem cell therapy for osteonecrosis of the femoral head and cell viability
Authors: Wu ZhanYu , Sun Qi , Liu Ming , Grottkau Brian , He ZhiXu , Zou Qiang , Ye Chuan
Published: December 2019

Background: Osteonecrosis of the femoral head (ONFH) is a common disease that greatly affects the quality of life of patients. Repair of the necrotic area is key to successful treatment. Currently, the combination of stem cell transplantation and decompression is used clinically to promote the repair of necrotic areas based on the characteristics of stem cells. However, a considerable number of patients do not achieve a satisfactory outcome in terms of repair of the femoral head necrotic area, and it is very important to determine the reasons for the poor curative effect. The aim of this study was to investigate the correlation between stem cell viability and the repair efficacy of stem cell therapy combined with core decompression for early-stage ONFH. Methods: A total of 30 patients with idiopathic ONFH underwent core decompression combined with autologous stem cell transplantation. The Harris hip score (HHS) and difference in necrosis area before and after surgery were measured. The mean repair ratio was set as the threshold to divide the patients into group A (ratio above the mean) and group B (ratio below the mean). The ultrastructure, proliferative capacity, and multidirectional differentiation ability were compared between the groups. Results : At 9 months after surgery, the HHS and magnetic resonance imaging (MRI) findings improved by varying degrees. Based on the mean repair ratio of (62.2 ± 27.0)%, the threshold for dividing the patients into groups A and B was set to 62.2%. Better repair (group A) was associated with more rapid proliferation and a healthier ultrastructure. The cells in group A showed stronger specific staining signifying osteogenic and chondrogenic differentiation; alkaline phosphatase (ALP) activity, an indicator of osteogenic differentiation, was higher in group A than in group B (OD, 2.39 ± 0.44 and 1.85 ± 0.52; p < 0.05). Conclusions: The quality of implanted stem cells is closely related to treatment efficacy and determines whether the defective self-repair in the necrotic area can be corrected to enhance repair and thus achieve the desired therapeutic outcome.
Safety and Efficacy of Rituximab in Systemic Sclerosis: A Systematic Review and Meta-analysis
Authors: Tang Rui , Yu Jiangfan , Shi Yaqian , Zou Puyu , Zeng Zhuotong , Wang Yaoyao , Ling Guanghui , Luo Mei , Xiao Rong
Published: December 2019

Background: Rituximab has been widely proposed to treat systemic sclerosis (SSc) by depletion of pathogenic B cells. Nonetheless, the clinical benefit of Rituximab in SSc remains contentious. Objective: This meta-analysis was conducted to systematically evaluate the safety and efficacy profile of Rituximab in SSc patients. Methods: We performed a systematic online query in PubMed, Cochrane, and Web of science. Available studies about the assessment of Rituximab in SSc patients were comprehensively reviewed and investigated. Results: In total, 14 studies comprising 597 participants were enrolled in our analysis. Pooled results showed the durable improvement of mRSS for skin involvement (∆mRSS: 7.00 at 6-month, 9.70 at 12-month, and 10.93 at 24-month), while FVC (∆FVC: -0.69 at 6-month, -2.62 at 12-month, -0.67 at 24-month) and DLCO (∆DLCO -2.39 at 6-month, -3.28 at 12-month, -0.79 at 24-month) for lung involvement remain stable in SSc patients after Rituximab treatment. And safety profile of Rituximab-related adverse events rate was 12% in the pooled result. Conclusion: The pooled results of this meta-analysis indicated that Rituximab was well-tolerated, and it was able to generate improvement of cutaneous function and stabilization of pulmonary function in SSc patients.
Inhibition of Carrageenin-induced Dental Inflammatory Responses Owing to Decreasing TRPV1 Activity by Dexmedetomidine
Authors: Lu Gang , Zhu Guanhua , Xu Maohua , Ping Xinggao , Xiao Qingfeng
Published: December 2019

Background : Dexmedetomidine (Dex) is a highly selective agonist of the α2 adrenergic receptor and a common sedative; however, its anti-inflammatory effect has been studied. In this study, the inhibitory effect of Dex on inflammation in dental pulp cells was assessed. To solve this problem, the effect of Dex on inflammation induced by carrageenan (Car) in human dental pulp cells (hDPCs) was studied. Car incubation induced a robust inflammatory response in the hDPCs as well as activation of PKA–STAT3 and PKC–nuclear factor kappa B (NFκB) signaling pathways. Results : Dex could reduce the expression of inflammatory cytokines in a dose-dependent manner. Meanwhile, the phosphorylation of PKA, PKC, STAT3, and NFκB as well as the nuclear accumulation of STAT3 and NFκB were significantly increased in Dex-treated Car-induced hDPCs. Western blotting results also showed that the phosphorylation level of transient receptor potential cation channel subfamily V member 1 (TRPV1) was downregulated owing to Dex treatment. Further, we found that the administration of the TRPV1 agonist capsaicin (Cap) reversed the effects of Dex on proinflammatory cytokines; however, the expression and activation of PKA–STAT3 and PKC–NFκB signals were not altered owing to Cap administration. Conclusions : These results indicate that Dex exerts a defensive role in dental pulp inflammation by regulating the TRPV1 channel and can be used as a potential target for human dental pulp inflammation intervention.
Epidemiology of neonatal infections in hospitals of Nepal: Evidence from a large- scale study
Authors: Budhathoki Shyam Sundar , Sunny Avinash K , Paudel Pragya Gautam , Thapa Jeevan , Basnet Lila Bahadur , Karki Sandeepa , Gurung Rejina , Paudel Prajwal , Kc Ashish
Published: December 2019

Introduction Every year, neonatal infections account for approximately 750,000 neonatal deaths globally. It is the third major cause of neonatal death, globally and in Nepal. There is a paucity of data on clinical aetiology and outcomes of neonatal infection in Nepal. This paper aims to assess the incidence and risk factors of neonatal infection in babies born in public hospitals of Nepal.Methods This is a prospective cohort study conducted for a period of 14 months, nested within a large-scale cluster randomized control trial which evaluated the Helping Babies Breathe Quality Improvement package in 12 public hospitals in Nepal. All the mothers who consented to participate within the study and delivered in these hospitals were included in the analysis. All neonates admitted into the sick newborn care unit weighing >1500 gram or/and 32 weeks or more gestation with clinical signs of infection or positive septic screening were taken as cases and those that did not have an infection were the comparison group. Bivariate and multi-variate analysis of socio-demographic, maternal, obstetric and neonatal characteristics of case and comparison group were conducted to assess risk factors associated with neonatal infection.Results The overall incidence of neonatal infection was 7.3 per 1000 live births. Babies who were born to first time mothers were at 59% higher risk of having infection (aOR-1.64, 95% CI, 1.30-2.06, p-value<0.001). Babies born to mothers who had no antenatal check-up had more than three-fold risk of infection (aOR-3.45, 95% CI, 1.82-6.56, p-value<0.001). Babies born through caesarean section had more than two-fold risk (aOR-2.06, 95% CI, 1.48-2.87, p-value<0.00) and babies with birth asphyxia had more than three-fold risk for infection (aOR-3.51, 95% CI, 1.71-7.20, p-value=0.001).Conclusion Antepartum factors, such as antenatal care attendance, and intrapartum factors such as mode of delivery and birth asphyxia, were risk factors for neonatal infections. These findings highlight the importance of ANC visits and the need for proper care during resuscitation in babies with birth asphyxia.
First Isolation and Molecular Characterization of blaCTX-M-121-producting Escherichia coli O157:H7 from China Cattle
Authors: Su Zhanqiang , Tong Panpan , Zhang Ling , Zhang Mengmeng , Wang Dong , Ma Kaiqi , Zhang Yi , Liu Yingyu , Xia Lining , Xie Jinxin
Published: December 2019

Background: To study antibiotic resistance and the molecular epidemiology of bovine Escherichia coli (E.coli) O157:H7 and to explore the intrinsic relationship among different isolates, we collected 27 strains of bovine E. coli O157:H7 in Xinjiang from 2012 to 2017 and assessed virulence genes, antibiotic resistance and pulsed-field gel electrophoresis (PFGE) molecular typing. Results: In this study, 21 strains carried at least one virulence gene, and 19 strains carried eae gene (70.4%) including 8 carrying stx1+stx2+eae +hly+tccP. Most strains were sensitive to all antibiotics tested, 4 strains were bacteria-resistant, and 2 strains possessed multi-drug resistance, including one ESBL-producing strain. This is the first report of a blaCTX-M-121 gene in bovine E. coli O157:H7. Moreover, blaCTX-M-121 gene can be transmitted horizontally by plasmid between strains. The PFGE spectral similarity of the 27 strains was between 65.8% and 100%. Two PFGE types including clusters Ⅰ and Ⅱ were obtained through cluster analysis. Conclusions: E. coli O157:H7 may have undergone clonal propagation in cattle farms as well as cross-regional transmission. A horizontal transmission path with E. coli O157:H7 appeared in different areas.
Results of Caring and Reaching for Health (CARE): A Cluster-Randomized Controlled Trial Assessing a Worksite Wellness Intervention for Child Care Staff
Authors: Linnan Laura A , Vaughn Amber E , Smith Falon , Westgate Philip , Hales Derek , Arandia Gabriela , Neshteruk Cody , Willis Erik , Ward Dianne S.
Published: December 2019

BackgroundChild care workers are among the lowest paid US workers and experience a wide array of health concerns. The physical and mental demands of their job and the lack of employer-provided health-insurance increase health risks. The Caring and Reaching for Health (CARE) study evaluated a 6-month Healthy Lifestyles intervention targeting child care workers’ physical activity (primary outcome), other health behaviors, and their workplace health environment.MethodsEligible child care centers, defined as being in operation for at least two years and employing a least four staff, were enrolled into CARE’s cluster-randomized trial. Centers and their child care staff were randomly assigned to either the Healthy Lifestyles (HL) intervention arm or the Healthy Finances (HF) attention control arm using a block randomization approach. Outcome measures were collected during center visits at baseline and immediately post-intervention by trained data collectors blinded to center arm assignment. Workers’ physical activity was assessed with accelerometers, worn for seven days. Secondary outcome measures included biometric assessments of health and fitness, web-based surveys about health behaviors, and an environmental audit of workplace supports for health. Multi-level linear mixed models assessed worker- and center-level changes in these outcomes.ResultsParticipants included 553 child care workers representing 56 centers (HL=250 staff/28 centers, HF=303 staff/28 centers). At six months, moderate-to-vigorous physical activity declined slightly in both arms (-1.3 minutes/day, 95% CI: -3.0, 0.3 in HL; -1.9 minutes/day, 95% CI: -3.3, -0.5 in HF), but there was no significant group by time interaction. Several secondary outcomes for other health behaviors and workplace health environment showed improvements in favor of the intervention arm, yet differences did not remain statistically significant after adjustment for multiple comparisons.ConclusionsWhile the Healthy Lifestyles intervention did not improve health behaviors or the workplace health environment, results confirmed the pressing need to focus on the health of child care workers. Future interventions should focus on prevalent health issues (e.g., weight, stress), include both high-tech and high-touch intervention strategies, and address work conditions or other social determinants of health (e.g. wages) as a means of improving the health of these important workers.
Associations of CXCL1 gene 5’UTR variations with ovarian cancer
Authors: Guo Man , Xu Chao , Chen Yan-Zhe , Sun Qi-Wen , Zhao Xin-Ying , Liu Xin , Yang Yi , Hu Yi-Yan , Li Fei-Feng , Liu Shu-Lin
Published: December 2019

Background: There are about 2.4 hundred thousand new cases and 1.5 hundred thousand deaths of ovarian cancer (OC) annually in the world. Chronic inflammation is a risk factor for OC. C-X-C motif chemokine ligand 1 (CXCL1) defects may facilitate inflammation and transactivate EGFR in ovarian cancer, but the precise haplotypes associated with the potential diseases remained largely unknown. In this work, we characterized CXCL1 gene variations to elucidate their possible associations with OC. Methods: We analyzed the the CXCL1 gene for 300 OC patients with 400 healthy participants as controls. The statistical analyses and Hardy-Weinberg equilibrium tests of the patients and control populations were conducted using the SPSS software (version 19.0) and Plink (version 1.9). Results: The variants rs11547681, rs201090116, rs199791199, rs181868085, rs4074 and rs1814092 within or near the CXCL1 gene were characterized. The genetic heterozygosity of rs11547681 and rs4074 was very high. Statistical analysis showed that the variant rs11547681 in the gene was closely associated with the risk of OC in the Chinese Han population, although this variant was not associated with FIGO stages or pathological grades of the patients.Conclusions: rs11547681 in CXCL1 was associated with the risk of OC in the Chinese Han population.
Equilibrium, kinetic and thermodynamic studies on the adsorption of atrazine in soils of the water fluctuation zone in the Three-Gorges Reservoir
Authors: Yu Haiyan , Shu Xingquan , Liu Yongfeng , Fang Han , Sun Xiaojing , Pan Yuwei , Ma Limin
Published: December 2019

Background: Environmental behavior of pesticide in soils is a key current research focus. Studying the adsorption characteristics of pesticides in soils as a parameter for evaluating the risk of groundwater pollution by pesticides, is commonly applied in agriculture. Results: In order to provide a theoretical basis for environment risk assessment and pollution remediation, the thermodynamics and kinetics of the equilibrium of atrazine adsorption in the Three Gorges Reservoir area were assessed and analyzed via batch experiments. Results showed that the sorption of atrazine was exothermic and spontaneous process at the temperatures (298–318K), and the atrazine was more easily adsorbed by soils at a concentration of 0–30 mg L -1 , with low temperature adsorption effects better than high temperature adsorption. The adsorption of atrazine to the two assessed soils was well fitted by Freundlich and Langmuir models. The adsorption kinetics of atrazine on soils were consistent with the quasi-second order kinetic model and intraparticle diffusion was found not to be the only control step. Results showed that monolayer adsorption occurred with non-uniform energy distribution on the soil surface, indicating that the adsorption of atrazine on the two kinds of soil was controlled by internal diffusion surface adsorption and liquid film diffusion, leading to the complexity of its adsorption kinetics. The values of standard free energy <0, indicating that the adsorption of atrazine in the soils was spontaneous and dominated by physical adsorption. Changes in standard enthalpy ( ) indicated that the adsorption was exothermic. Conclusion: Atrazine exhibited a weak adsorption capacity in both soils, indicating it is highly mobile in the soil-water environment and could easily cause groundwater pollution. Therefore, much attention should be paid to the environmental behavior of pesticide soil moisture fluctuations, leading to broad spreading of pollution.
Changes in Bone Turnover, Inflammatory, Oxidative Stress, and Metabolic Markers in Women Consuming Iron plus Vitamin D Supplements: A Randomized Clinical Trial
Authors: Abiri Behnaz , Azizi-Soleiman Fatemeh , Vafa Mohammadreza , Safavi Morteza , Kazemi Seyyed Morteza , Salehi Masood , Zaeri Farid , Sadeghi Homa
Published: December 2019

Background We aimed to investigate whether combination of vitamin D and iron supplementation, comparing vitamin D alone, could modify bone turnover, inflammatory, oxidative stress, and metabolic markers. Methods Women with hemoglobin (Hb)≤12.7 g/dL and 25OHD≤29 ng/mL vitamin D deficiency/insufficiency aged 18-45 years (n=100) were recruited into a trial to receive either 1000 IU/d vitamin D3 plus 27 mg/d iron (D-Fe) or vitamin D3 plus placebo supplements (D-P) for 12 weeks. Results In D-Fe group, significant decreases in red blood cells (RBC) (P=0.001), hematocrit (Hct) (P=0.004) and increases in mean corpuscular hemoglobin concentration (MCHC)(P=0.001), 25OHD (P<0.001), osteocalcin (P<0.001), high-density cholesterol (HDL) (P=0.041), and fasting blood sugar (FBS) (P<0.001) were observed. D-P group showed significant decreases of RBC (P<0.001), Hb (P<0.001), Hct (P<0.001), mean corpuscular volume (MCV) (P=0.004), mean corpuscular hemoglobin (MCH) (P<0.001), MCHC (P=0.005), serum ferritin (P<0.001), and low-density cholesterol (LDL) (P=0.016) and increases of 25OHD (P<0.001), osteocalcin (P<0.001), C-terminal telopeptide (CTX) (P=0.025), triglyceride (TG) (P=0.004), FBS (P<0.001), and interleukin-6 (IL-6) (P=0.001) at week 12. After the intervention, the D-P group had between-group increases in mean change in the osteocalcin (P=0.007) and IL-6 (P=0.033), and decreases in the RBC (P<0.001), Hb (P<0.001), Hct (P<0.001), MCV (P=0.001), compared to the D-Fe group. There were significant between-group changes in MCH (P<0.001), MCHC (P<0.001), ferritin (P<0.001), and serum iron (P=0.018). Conclusions Iron-vitamin D co-supplementation does not yield added benefits for improvement of bone turnover, inflammatory, oxidative stress, and metabolic markers; whereas, vitamin D alone may have some detrimental effects on inflammatory and metabolic markers.
Hidden analyses: A review of current reporting practice and recommendations for more transparent reporting of initial data analyses
Authors: Huebner Marianne , Vach Werner , Cessie Saskia le , Schmidt Carsten Oliver , Lusa Lara
Published: December 2019

Background: In the data pipeline from the data collection process to the planned statistical analyses, initial data analysis (IDA) typically takes place between the end of the data collection and do not touch the research questions. A systematic process for IDA and clear reporting of the findings would help to understand the potential shortcomings of a dataset, such as missing values, or subgroups with small sample sizes, or shortcomings in the collection process, and to evaluate the impact of these shortcomings on the research results. A clear reporting of findings is also relevant when making datasets available to other researchers. Initial data analyses can provide valuable insights into the suitability of a data set for a future research study. Our aim was to describe the current practice of reporting of initial data analyses in observational studies in five highly ranked medical journals with focus on data cleaning, screening, and reporting of findings which led to a potential change in the analysis plan.Methods: This review was carried out using systematic search strategies with eligibility criteria for articles to be reviewed. A total of 25 papers about observational studies were selected from five medical journals. Each paper was reviewed by two reviewers and IDA statements were further discussed by all authors. The consensus was reported.Results: IDA statements were reported in the methods, results, discussion, and supplement of papers. Ten out of 25 papers (40%) included a statement about data cleaning. Data screening statements were included in all articles, and 18 (72%) indicated the methods used to describe them. Item missingness was reported in 11 papers (44%), unit missingness in 15 papers (60%). Eleven papers (44%) mentioned some changes in the analysis plan. Reported changes referred to missing data treatment, unexpected values, population heterogeneity and aspects related to variable distributions or data properties. Conclusion: Reporting of initial data analyses were sparse, and statements on IDA were located throughout the research articles. There is a lack of systematic reporting of IDA. We conclude the article with recommendations on how to overcome shortcomings in the current practice of IDA reporting in observational studies.
Distribution of blaOXA, blaSHV, and blaTEM type extended-spectrum β-lactamase genes in multi-drug resistant Gram-negative isolates from burn patients of Lahore, Pakistan
Authors: Haider Muhammad Hayat , Ain Noor Ul , Abrar Samyyia , Riaz Saba
Published: December 2019

Background Multidrug resistant Gram-negative bacterial pathogens are becoming a lethal source of infections and associated complications of sepsis and multiple organ failure following burn injuries. Genotypic variants of bla OXA , bla SHV and bla TEM type extended-spectrum-β-lactamases (ESBLs) have been detected in Pseudomonas aeruginosa , Enterobacteriaceae and other type of bacteria. These hydrolytic enzymes are responsible for the degradation of broad-spectrum antimicrobials including third generation cephalosporins. We aimed to determine the distribution of ESBLs gene variants among MDR pathogens from post burn infections.Methods A total of 358 specimens were collected during the period from 15 th August 2017 to 15 th August 2018 from burnt patients at Jinnah Burn and Reconstructive Surgery Centre (JB&RSC).Results 53.57% cephalosporins resistant isolates were found to be associated with a slightly higher frequency of 50.7% community-acquired and 49.30% nosocomial infections. 72% of these infections was found to be associated with males (p-value = 0.919, OR = 1.038). The age of burn victims ranged from 4 to 85 years (Mean=28.95, SD=±15.65). Pseudomonas spp., were the predominant as 49.33% followed by 22.67% Klebsiella spp., 20% Acinetobacter spp., and 8% Proteus spp., strains. There were 83.33% multidrug resistant isolates and meropenem, imipenem, and amikacin were found to be effective against 28.70%, 25.30%, and 26.00% of cephalosporins resistant strains respectively. Lowest sensitivity of phenotypic tests was observed as 16% ESBLs were detected by double disk synergism test (DDST) and 14% were confirmed by combination disk test (CDT). Molecular detection proved to be effective for the detection of 79.71% bla TEM , 37.68% bla OXA , and 18.84% bla SHV isolates. bla TEM genes were confirmed in 18.18% CDT positive isolates with 62.67% diagnostic accuracy (95% CI = 54.70, 70.00) and 88.42% specificity (95% CI = 80.45, 93.41). All of the bla TEM positive isolates were resistant to cefuroxime and 98.18% were resistant to cephradine, and piperacillin.Conclusion The antimicrobial resistance associated with the ESBLs producing Pseudomonas spp., and Enterobacteriaceae is becoming a challenge for the treatment and survival of burn patients. The higher frequency of MDR isolates and detection of bla TEM , bla OXA , and bla SHV genes confirms that management of burn patients should be improved to prevent the infections.
Machine Learning Algorithms to Predict the Mortality of Carbapenem Resistant Klebsiella Pneumoniae bacteremia
Authors: Liang Qiqiang , Qian Fang , Chen Yibing , Xu Zhijun , Xu Zhijiang , Huang Man
Published: December 2019

Purpose To establish mortality prediction models in 14 days of Carbapenem-Resistant Klebsiella Pneumoniae bacteremia using Machine learning.Materials and Methods It is a single-center retrospective study. We collect the relevant clinical information of all patients with Carbapenem-Resistant Klebsiella Pneumoniae (CRKP) bacteremia in the past 5 years using the local database. Data analysis and verification are carried out by multiple logical regression, decision tree, random forest, support vector machine (SVM), and XGBoost.Result This study includes 187 patients with 40 related variables. In multiple logical regression, acute renal injury (P=0.003), Apache II score (P=0.036), immunodeficiency (P=0.025), severe thrombocytopenia (P=0.025) and septic shock (P=0.044) are the high-risk factors for 14 days mortality of CRKP bloodstream infections. According to the importance of those parameters, risk scoring is established to predict the survival rate of CRKP bacteremia. The analysis of the five models, with 70% training set and 30% test set, show the comprehensive performance of random forest (AUROC=0.953, precision=91.85%) is slightly better than that of XGBoost (AUROC=0.912, precision=86.41%) and SVM (AUROC=0.936, precision=79.89%) in predicting 14-day mortality of CRKP bacteremia. The multiple logical regression model (AUROC=0.825, precision=81.52%) is the second, and the decision tree model (AUROC=0.712, precision=79.89%) is not very ideal.Conclusion Machine learning has good performances in predicting 14-day mortality of CRKP bacteremia than multiple logical regression. Acute renal injury, severe thrombocytopenia, and septic shock are the high-risk factors of CRKP bacteremia mortality.
New insights on the function of plant acyl carrier proteins from comparative and evolutionary analysis
Authors: Yang Xuezhen , Liu Xiaoxue , Zhou Yanchen , Zhang Fan , Huang Lan , Wang Jun , Song Jian , Qiu Lijuan
Published: December 2019

BackgroundAcyl carrier proteins (ACPs) play a central role in both plastidial and mitochondrial Type II fatty acid synthesis in plant cells. However, a large proportion of plant ACPs remain functionally uncharacterized, and their evolutionary history remains elusive. ResultsIn present study, 97 putative ACPs were identified from ten angiosperm species examined. Based on phylogenetic analysis, ACP genes were grouped into plastidial (cpACP: ACP1/2/3/4/5) and mitochondrial (mtACP: mtACP1/mtACP2/mtACP3) ACPs. Protein sequence (motifs and length), tertiary structure, and gene structure (exon number, average intron length, and intron phase) were highly conserved in different ACP subclades. The differentiation of ACPs into distinct types occurred 85–98 and 45–57 million years ago. A limited proportion of ACP genes experience tandem or segmental duplication, corresponding to two rounds of whole genome duplication. Ka/Ks ratios revealed that duplicated ACP genes underwent a purifying selection. Regarding expression patterns, most ACPs were expressed constitutively and tissue-specifically. Notably, the average expression levels of ACP1, mtACP3, and mtACP1 were positively correlated with those of ACP3, ACP4, and mtACP2, respectively. Analysis of cis-elements showed that seven motifs (CACTFTPPCA1, DOFCOREZM, GT1CONSENSUS, CAATBOX1, ARR1AT, POLLEN1LELAT52, and GATABOX) related to tissue-specific, ABA, and light-mediated gene regulation were ubiquitous in all ACPs investigated, which shed new light on the regulation patterns of these central enzymatic partners of the FAS system. ConclusionsThis study presents a thorough overview of angiosperm ACP gene families and provides informative clues for the functional characterization of plant ACPs in the future.
Efficacy of the erector spinae plane block in lumbar spinal surgery patients: a systematic review
Authors: Qiu Yong , Zhang Teng-jiao , Meng Ling-bing , Hua Zhen
Published: December 2019

Background: Erector spinae palne block (ESPB) as a new trunk fascia block technique was proposed in 2016. Because of its clear analgesic effect and simple operation, it has aroused the interest of many nerve block experts. However, there are few clinical studies on ESPB for lumbar surgery, and its benefits are controversial. The goal of this review paper is to summarize the use of ESPB for lumbar spine surgery in order to better understand and promote this technique.Methods: Pubmed, EMBASE, Cochrane library, ClinicalTrial.gov databases were searched up to July 30, 2019. According to the inclusion and exclusion criteria established in advance, “lumbar spine surgery” and “ESPB” related MesH terms, free-text words were used. Data on pain scores, analgesic consumptions and adverse effects were reported. All processes follow PRISMA statement guidelines.Results: A total of 171 participants from 11 publications were identified, including two randomized controlled trials, one retrospective cohort study, four case report, four cases series. Block operation plane from T8 to L4. The main anesthetics used in block are bupivacaine, ropivacaine and lidocaine. There was evidence for reducing postoperative pain scores and analgesic consumptions.Conclusion: ESPB in lumbar spine surgery have the potential to relieve lumbar postoperative pain and reduce the use of analgesic drugs. Randomized controlled trials of high quality and large samples are needed to further clarify the benefits of ESPB in lumbar surgery patients.
Fluid Overload After Coronary Artery Bypass Graft in Patients on Maintenance Hemodialysis is Associated with Prolonged Time on Mechanical Ventilation
Authors: silva sirlei , Consolim-Colombo Fernanda Marciano , Rodrigues Renata Gomes , Gaiotto Fábio Antonio , Hajjar Ludhmila Abrahão , Moysés Rosa Maria Affonso , Elias Rosilene Motta
Published: December 2019

Background: Fluid overload is a risk factor for morbidity, mortality, and prolonged ventilation time after surgery. Patients on maintenance hemodialysis might be at higher risk. We hypothesized that fluid accumulation would be directly associated with extended ventilation time in patients on hemodialysis, as compared to patients with chronic kidney disease not on dialysis (CKD3-4) and patients with normal renal function (reference group).Methods: this is a prospective observational study that included patients submitted to isolated and elective coronary artery bypass surgery, divided in 3 groups: reference (N=167, normal renal function), CKD3-4 (N=84, estimated glomerular filtration rate 30-60ml/min/1.73m2), and hemodialysis (N=31, maintenance hemodialysis). The same observer followed patients daily from the surgery to the hospital discharge. Results: Fluid accumulation correlated with time on mechanical ventilation in patients on hemodialysis (r=0.627, p=0.003), but not in the CKD3-4 group (r=-0.068, p=0.652) and in the reference group (r=-0.085, p=0.363). Multivariate analysis revealed that the fluid accumulation, scores of sequential organ failure assessment (SOFA) in the day following surgery, and the study group were independently associated with time in mechanical ventilation. Among patients on hemodialysis, the time from the surgery to the first hemodialysis session also accounted for the time on mechanical ventilation. Conclusions: Fluid accumulation is an important risk factor for lengthening mechanical ventilation, particularly in patients on hemodialysis. Future studies are warranted to address the ideal timing for initiating dialysis in this scenario in an attempt to reduce fluid accumulation and avoid prolonged ventilation time and hospital stay.
Full-length transcriptome sequencing and comparative transcriptomic analysis to uncover genes involved in early gametogenesis in the gonads of Amur sturgeon (Acipenser schrenckii)
Authors: Zhang Xiujuan , Zhou Jiabin , Li Linmiao , Huang Wenzhong , Ahmad Hafiz Ishfaq , Li Huiming , Jiang Haiying , Chen Jinping
Published: December 2019

Background Sturgeons (Acipenseriformes) are polyploid chondrostean fish that constitute an important model species for studying development and evolution in vertebrates. To better understand the mechanisms of reproduction regulation in sturgeon, this study combined PacBio isoform sequencing (Iso-Seq) with Illumina short-read RNA-seq methods to discover full-length genes involved in early gametogenesis of the Amur sturgeon, Acipenser schrenckii .Results A total of 50.04 G subread bases were generated from two SMRT cells, and herein 164,618 nonredundant full-length transcripts (unigenes) were produced with an average length of 2,782 bp from gonad tissues (three testes and four ovaries) from seven 3-year-old A. schrenckii individuals. The number of ovary-specific expressed unigenes was greater than those of testis (19,716 vs. 3,028), and functional assignment indicated that 6 of 14 annotated KEGG pathways were directly ovary-related and had abundant transcripts and differential expression genes. Importantly, 60 early gametogenesis-related genes (involving 755 unigenes) were successfully identified, and exactly 50 percent (30/60) of those showed differential expression in testes and ovaries. The Amh and Gsdf with testis-biased expression, and Foxl2 and Cyp19a with ovary-biased expression strongly suggested the important regulatory roles in spermatogenesis and oogenesis of A. schrenckii , respectively. We also found the four novel Sox9 transcript variants, which increase the numbers of regulatory genes and imply function complexity of early gametogenesis. Finally, a total of 236,672 AS events (involving 36,522 unigenes) were detected, and 10,556 putative long noncoding RNAs (lncRNAs) and 4,339 predicted transcript factors (TFs) were also respectively identified, which all significantly associated with the early gametogenesis of A. schrenckii .Conclusions Overall, our results provide new genetic resources of full-length transcription data and information as a genomic-level reference for sturgeon. Crucially, we explored the comprehensive genetic characteristics that differ between the testes and ovaries of A. schrenckii in the early gametogenesis stage. These provide candidate genes and theoretical basis for further the mechanisms of reproduction regulation of sturgeon.
Efficient Biosynthesis of R-(-)-linalool through Adjusting Expression Strategy and Increasing GPP Supply in Escherichia coli
Authors: Wang Xun , Wu Jing , Chen Jiaming , Xiao Longjie , Li Xun
Published: December 2019

Background: R-(-)-linalool is a versatile acyclic monoterpene alcohol with applications in the flavor and fragrance, pharmaceutical, and agrochemical industries. However, plant extraction furnishes only limited and unstable R-(-)-linalool yields that do not satisfy market demand. Therefore, a sustainable yet efficient and productive method of R-(-)-linalool synthesis is urgently needed. Results: To induce the R-(-)-linalool biosynthesis pathway in E. coli , we expressed heterologous (3R)-linalool synthase (LIS) from Lavandula angustifolia (laLIS). We then enhanced R-(-)-linalool production in the cells using a suitable LIS from Streptomyces clavuligerus (bLIS). The bLIS expression was markedly elevated by using optimized ribosomal binding sites (RBSs) and protein fusion tags. R-(-)-linalool output rose from 4.8 mg L -1 to 33.4 mg L -1 . To increase the geranyl diphosphate (GPP) content in E. coli , we tested various alterations in geranyl diphosphate synthases (GPPSs) and their mutants. The final E. coli strain harboring GPPS from Abies grandis ( Ag GPPS) accumulated ≤ 100.1 mg L -1 R-(-)-linalool after 72 h shake-flask fermentation. This yield gain constitutes a 60.7-fold improvement in R-(-)-linalool biosynthesis over the parent strain. Fed-batch cultivation of the engineered strain in a 1.3-L fermenter yielded 1,027.3 mg L -1 R-(-)-linalool. Conclusions: In this study, an efficient R-(-)-linalool production pathway was induced in E. coli via the heterologous MVA pathway, AgGPPS, and (3R)-linalool synthase (bLIS). By overexpressing the key enzyme in the engineered E. coli strain, R-(-)-linalool production reached 100.1 mg L -1 and 1,027.3 mg L -1 under shake flask- and fed-batch fermentation conditions, respectively. The latter is the highest reported R-(-)-linalool yield to date using an engineered E. coli strain. The strategies of key enzyme overexpression and mutation could lay theoretical and empirical foundations for engineering terpenoid pathways and optimizing other metabolic pathways.
Camelina sativa meal hydrolysate as sustainable biomass for the production of carotenoids by Rhodosporidium toruloides
Authors: Bertacchi Stefano , Bettiga Maurizio , Porro Danilo , Branduardi Paola
Published: December 2019

Background: The sustainability of biorefineries is strongly related to the origin, the availability and the market of the biomass used as feedstock. Moreover, one of the pillars of circular economy aims at reducing waste, ideally to zero. These considerations well justify the increasing industrial interest in exploiting many and diverse residual biomasses. This work focuses on the valorization of the leftover from Camelina sativa oil extraction, named Camelina meal. Despite Camelina meal is used as animal feed, there is an increasing interest in further valorizing its macromolecular content or its nutritional value. Results: Here we valorized Camelina meal hydrolysates by using them as nutrient and energy source for shake-flask fermentations where Rhodosporidium toruloides , a yeast natural producer of carotenoids, accumulated these pigments as desired product. Initially, by total acid hydrolysis we determined that in Camelina meal carbohydrates account for a maximum of 30.8 ± 1.0 %. However, since the acid hydrolysis is not optimal for subsequent microbial fermentation, an enzymatic hydrolysis protocol was assessed, obtaining a maximum sugar recovery of 53.3%. Having stated that, by Separate Hydrolysis and Fermentation, with or without water insoluble solids (SHF, SHF+WIS), or Simultaneous Saccharification and Fermentation (SSF) we obtained 5.51 ± 0.67, 12.64 ± 2.57, and 15.97 ± 0.67 mg/L of carotenoids, respectively, from Camelina meal hydrolysate. Significantly, the presence of WIS, possibly containing microbial inhibitors, correlates with a higher titer of carotenoids, which can be seen as scavengers. Conclusions: The proposed study paves the way for the development of bioprocesses based on the exploitation of Camelina meal, scarcely investigated in the field before, as feedstock. The processes depicted provide an example of how different final products of industrial interests can be obtained from this leftover, such as pure carotenoids and carotenoid-enriched Camelina meal for the feed industry, without diminishing but possibly increasing its initial value. These data provide valuable basis for the economic evaluations necessary to assess the feasibility of a bioprocess based on Camelina meal to obtain high-value added products.
Study On The Biomechanical Properties Of Rabbit Venous Arterialization
Authors: Zhang Yuhao , Niu Pei , Zhang Zhimin , Niu Xiaolong , Shen Wenzeng , Hao Liangchao , Zhou Yujuan , Liu Fulin
Published: December 2019

Objective : To investigate the mechanisms underlying restenosis following coronary artery bypass grafting using bridging veins.Method : We established a rabbit model of venous arterialisation, by transplanting veins into the arterial system as bridging vessels and investigated vessel tensile mechanical and histomorphological properties. Result : Control vein elasticity (k = 16.20) was less than that of the control artery (k = 58.04; P < 0.05), and vein walls were thinner. Following venous arterialisation, proliferating cell nuclear antigen and alpha-actin were upregulated and vein walls thickened (P < 0.05), with elasticity after venous arterialisation (k = 86.26) significantly higher than that of control veins (P < 0.05). Conclusion : This indicates that venous intima is damaged by high pressure following arterialisation, resulting in gradual restenosis, with thickening of the venous intima and an increase in vessel elasticity. Clinically, there is potential to repeat these experiments to determine the elastic extremum of the great saphenous vein and control the pressure in the lumen of this vessel, to ensure minimal damage to the intima before anastomosis, thereby facilitating improvement of long-term patency rates following vein bridge surgery. Whether the increase in venous bridge elasticity after venous arterialisation can be controlled, with the aim of preventing early-stage restenosis, warrants investigation.