bluuebunny/crossref_metadata_2025_split huggingface dataset:
LipF increases rifampicin and streptomycin sensitivity in a Mycobacterium tuberculosis surrogate
Authors: Arriaga-Guerrero Ana Leticia , Hernández-Luna Carlos E. , Rigal-Leal Joyce , Robles-González Rene J. , González-Escalante Laura Adiene , Silva-Ramírez Beatriz , Mercado-Hernández Roberto , Vargas-Villarreal Javier , Bermúdez de León Mario , Peñuelas-Urquides Katia 
Published: May 2020

Abstract
Background
Mortality due to tuberculosis (TB) has increased due to the development of drug resistance, the mechanisms of which have not been fully elucidated. Our research group identified a low expression of lipF gene in Mycobacterium tuberculosis clinical isolates with drug resistance. The aim of this work was to evaluate the effect of lipase F (LipF) expression on mycobacterial drug resistance.

Results
The effects of expressing lipF from Mycobacterium tuberculosis in Mycobacterium smegmatis on resistance to antituberculosis drugs were determined with resazurin microtiter assay plate and growth kinetics. Functionality of ectopic LipF was confirmed. LipF expression reduced the rifampicin (RIF) and streptomycin (STR) minimum inhibitory concentration (MIC) from 3.12 μg/mL to 1.6 μg/mL and 0.25 μg/mL to 0.06 μg/mL respectively, moreover a reduced M. smegmatis growth in presence of RIF and STR compared with that of a control strain without LipF expression (p < 0.05 and p < 0.01) was shown.

Conclusions
LipF expression was associated with increased RIF and STR sensitivity in mycobacteria. Reduced LipF expression may contribute to the development of RIF and STR resistance in Mycobacterium species. Our findings provide information pertinent to understanding mycobacterial drug resistance mechanisms.
Precision genome editing in plants: state-of-the-art in CRISPR/Cas9-based genome engineering
Authors: Wada Naoki , Ueta Risa , Osakabe Yuriko , Osakabe Keishi 
Published: May 2020

AbstractTraditionally, generation of new plants with improved or desirable features has relied on laborious and time-consuming breeding techniques. Genome-editing technologies have led to a new era of genome engineering, enabling an effective, precise, and rapid engineering of the plant genomes. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) has emerged as a new genome-editing tool, extensively applied in various organisms, including plants. The use of CRISPR/Cas9 allows generating transgene-free genome-edited plants (“null segregants”) in a short period of time. In this review, we provide a critical overview of the recent advances in CRISPR/Cas9 derived technologies for inducing mutations at target sites in the genome and controlling the expression of target genes. We highlight the major breakthroughs in applying CRISPR/Cas9 to plant engineering, and challenges toward the production of null segregants. We also provide an update on the efforts of engineering Cas9 proteins, newly discovered Cas9 variants, and novel CRISPR/Cas systems for use in plants. The application of CRISPR/Cas9 and related technologies in plant engineering will not only facilitate molecular breeding of crop plants but also accelerate progress in basic research.
Differential effects and mechanisms of local anesthetics on esophageal carcinoma cell migration, growth, survival and chemosensitivity
Authors: Zhu Guanhua , Zhang Ling , Dan Jiapeng , Zhu Qiong 
Published: May 2020

Abstract
Background
Retrospective analysis and pre-clinical studies suggest that local anesthetics have anti-tumoral effects. However, the association between cancer recurrence and the use of local anesthesia is inconclusive and most reports are based on single local anesthetic results.

Methods
The biological effects (growth, migration and survival) of four common local anesthetics on esophageal carcinoma cells were compared. Biochemical assays on molecules involved in cell migration and proliferation were analyzed.

Results
Ropivacaine and bupivacaine significantly inhibited esophageal carcinoma cell migration, at clinically relevant micromolar concentrations. Mepivacaine and lidocaine showed less potent cell migration inhibition than ropivacaine or bupivacaine. All four local anesthetics inhibited cell proliferation. Of note, the effective concentration of anti-proliferative activities requires higher doses. At millimolar concentrations of these local anesthetics, cell apoptosis was moderately affected. Drug combination analysis demonstrated that two of four local anesthetics augmented chemotherapeutic drugs in inhibiting migration. However, all four local anesthetics significantly augmented chemotherapeutic drugs in inhibiting growth and inducing apoptosis. The anti-growth and anti-survival effects of four local anesthetics were attributed to mitochondrial dysfunction and oxidative damage. The anti-migratory effect of local anesthetics is likely through decreasing Rac1 activity.

Conclusions
Our work demonstrates the differential effects and proposes the mechanisms of local anesthetics on esophageal carcinoma cell migration, growth, survival and chemosensitivity.
Awake intubation and extraluminal use of Uniblocker for one-lung ventilation in a patient with a large mediastinal mass a case report
Authors: Liu Zhuo , Jia Qianqian , Yang Xiaochun 
Published: May 2020

Abstract
Background
The anesthesia of patients with large mediastinal mass is at high-risk. Avoidance of general anesthesia in these patients is the safest option, if this is unavoidable, maintenance of spontaneous ventilation is the next safest technique. In these types of patients, it is not applicable to use double-lumen tube (DLT) to achieve one-lung ventilation (OLV) because the DLT has a larger diameter and is more rigid than single-lumen tube (SLT), so the mass may rupture and bleed during intubation. Even using a bronchial blocker, a small size of SLT is required for once the trachea collapses the SLT can pass through the narrowest part of trachea. However, it is difficult to control the fiberoptic bronchoscopy (FOB) and the bronchial blocker simultaneously within the lumen of a small size SLT with traditional intubation methods.

Case presentation
The current study presented a 66 years old female patient with a large mediastinal mass that presented with difficulty breathing when lying flat. In this case, we combined use of dexmedetomidine and remifentanil to preserve the patient’s spontaneous ventilation during intubation and achieved one-lung ventilation with extraluminal use of Uniblocker.

Conclusions
Extraluminal use of Uniblocker and maintenance of spontaneous ventilation during intubation may be an alternative to traditional methods of lung isolation in such patients with a large mediastinal mass.
The Peacock study: feasibility of the dynamic characterisation of the paediatric hypothalamic-pituitary-adrenal function during and after cardiac surgery
Authors: Fudulu Daniel Paul , Angelini Gianni Davide , Papadopoulou Fani Fanoula , Evans Jonathan , Walker-Smith Terrie , Kema Ido , van Faassen Martijn , Stoica Serban , Caputo Massimo , Lightman Stafford , Gibbison Benjamin 
Published: May 2020

Abstract
Background
Cortisol is the main stress hormone mobilised during surgery to establish homeostasis. Our current understanding of the hypothalamic-pituitary-adrenal axis physiology in children undergoing cardiopulmonary bypass is very limited due to: (1) very few cortisol time point measurements over long periods (2) difficulties of sampling in low weight babies and (3) the concomitant use of glucocorticoids at anaesthesia induction. This lack of understanding is reflected in a lack of consensus on the utility of glucocorticoids perioperatively in cardiac surgery with the use of cardiopulmonary bypass.

Methods
The Peacock Study is a prospective, two-centre, observational cohort study of 78 children (undergoing cardiopulmonary bypass procedures and non-surgical procedures - split by age/cyanosis) that aims to characterise in detail the hypothalamic-pituitary-adrenal axis physiology of children using the stress model of paediatric cardiac surgery. Also, we aim to correlate cortisol profiles with clinical outcome data. We herein describe the main study design and report the full cortisol profile of one child undergoing heart surgery, thus proving the feasibility of the method.

Results
We used an automated, 24-h tissue microdialysis system to measure cortisol and cortisone, every 20 min. We herein report one cortisol profile of a child undergoing heart surgery. Besides, we measured serum cortisol and adrenocorticotrophic hormone at seven-time points for correlation. Tissue concentrations of cortisol increased markedly several hours after the end of surgery. We also noted an increase in the tissue cortisol/cortisone ratio during this response.

Conclusion
We report for the first time, the use of an automated microdialysis sampling system to evaluate the paediatric adrenal response in children. Changes in cortisol and cortisone could be measured, and the concentration of cortisol in the tissues increased after the end of cardiac surgery. The method has wide application to measure other hormones dynamically and frequently without the limitation of the circulating blood volume. The data from the main study will clarify how these cortisol profiles vary with age, pathology, type of procedure and correlation to clinical outcomes.

Trial registration
ISCRTN registry, number: 982586.
Reliability of prehospital patient classification in helicopter emergency medical service missions
Authors: Heino A. , Laukkanen-Nevala P. , Raatiniemi L. , Tommila M. , Nurmi J. , Olkinuora A. , Virkkunen I. , Iirola T. 
Published: May 2020

Abstract
Background
Several scores and codes are used in prehospital clinical quality registries but little is known of their reliability. The aim of this study is to evaluate the inter-rater reliability of the American Society of Anesthesiologists physical status (ASA-PS) classification system, HEMS benefit score (HBS), International Classification of Primary Care, second edition (ICPC-2) and Eastern Cooperative Oncology Group (ECOG) performance status in a helicopter emergency medical service (HEMS) clinical quality registry (CQR).

Methods
All physicians and paramedics working in HEMS in Finland and responsible for patient registration were asked to participate in this study. The participants entered data of six written fictional missions in the national CQR. The inter-rater reliability of the ASA-PS, HBS, ICPC-2 and ECOG were evaluated using an overall agreement and free-marginal multi-rater kappa (Κfree).

Results
All 59 Finnish HEMS physicians and paramedics were invited to participate in this study, of which 43 responded and 16 did not answer. One participant was excluded due to unfinished data entering. ASA-PS had an overall agreement of 40.2% and Κfree of 0.28 in this study. HBS had an overall agreement of 44.7% and Κfree of 0.39. ICPC-2 coding had an overall agreement of 51.5% and Κfree of 0.47. ECOG had an overall agreement of 49.6% and Κfree of 0.40.

Conclusion
This study suggests a marked inter-rater unreliability in prehospital patient scoring and coding even in a relatively uniform group of practitioners working in a highly focused environment. This indicates that the scores and codes should be specifically designed or adapted for prehospital use, and the users should be provided with clear and thorough instructions on how to use them.
Genetic variation in toll like receptors 2, 7, 9 and interleukin-6 is associated with cytomegalovirus infection in late pregnancy
Authors: Mhandire Doreen Z. , Mhandire Kudakwashe , Magadze Mulalo , Wonkam Ambroise , Kengne Andre P. , Dandara Collet 
Published: May 2020

AbstractBackgroundMaternal cytomegalovirus (CMV) infection and/or reactivation in pregnancy is associated with a myriad of adverse infant outcomes. However, the role of host genetic polymorphisms in modulating maternal CMV status is inconclusive. This study investigated the possible association of single nucleotide polymorphisms in toll-like receptor (TLR) and cytokine genes with maternal plasma CMV DNA status in black Zimbabweans.MethodsIn a cross-sectional study, 110 women in late gestation who included 36 CMV infected cases and 74 CMV uninfected, age and HIV status matched controls were enrolled. Twenty single nucleotide polymorphisms in 10 genes which code for proteins involved in immunity against CMV were genotyped using Iplex GOLD SNP genotyping protocol on the Agena MassARRAY® system. Statistical analyses were performed using Stata SE and the ‘Genetics’ and ‘SNPassoc’ packages of the statistical package R.ResultsTheTLR7rs179008A > T (p < 0.001) polymorphism was associated while theTLR9rs352139T > C (p = 0.049) polymorphism was on the borderline for association with CMV positive (CMV+) status. In contrast, the interleukin (IL)-6rs10499563T > C (p < 0.001) andTLR2rs1816702C > T (p = 0.001) polymorphisms were associated with CMV negative (CMV-) status. Furthermore, allele frequencies of SNPs inTLR2, TLR4, TLR9, TLR7,IL-6,IL-10,IL-28B,IL-1Aand interferon AR1 (IFNAR1) genes are being reported here for the first time in a Zimbabwean population. The allele frequencies in the Zimbabwean population are generally comparable to other African populations but different when compared to European and Asian populations.ConclusionsToll-like receptor and interleukin genetic polymorphisms influence CMV status in late gestation among black Zimbabweans. This is attributable to possible modulation of immune responses to CMV reactivation in a population previously exposed to CMV infection.
Chronic kidney disease in Russia: the Ural eye and medical study
Authors: Bikbov Mukharram M. , Zainullin Rinat M. , Kazakbaeva Gyulli M. , Gilmanshin Timur R. , Rakhimova Ellina M. , Rusakova Iulia A. , Bolshakova Natalia I. , Safiullina Kamila R. , Panda-Jonas Songhomitra , Yakupova Dilya F. , Nikitin Nikolai A. , Jonas Jost B. 
Published: May 2020

Abstract
Background
To examine the prevalence of chronic kidney disease (CKD) and its associations in a Russian population.

Methods
Out of 7328 eligible individuals, the population-based cross-sectional Ural Eye and Medical Study included 5899 (80.5%) individuals aged 40+ years and undergoing a detailed medical examination. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic-Kidney-Disease-Epidemiology-Collaboration (CKD-EPI) equation.

Results
The mean eGFR was 72.3 ± 19.1 mL/min/1.73m2 (median:70.3 mL/min/1.73m2). Prevalence of CKD stage 3a (eGFR< 60 mL/min/1.73m2 and > 45 mL/min/1.73m2), CKD stage 3b (eGFR< 45 mL/min/1.73m2 and > 30 mL/min/1.73m2) and CKD stage 4+ (eGFR< 30 mL/min/1.73m2) were 1351/5841 (23.1%;95% confidence interval (CI):22.1,24.2), 294/5841 (5.0%;95%CI:4.5,5.6), and 29/5841 (0.5%;95%CI:0.3,0.7), respectively. The CKD stage 3+ prevalence increased (P < 0.001) from 11.1% (95%CI:8.4,13.9) in 40–44-year-olds to 56.8% (95%CI:52.8,60.8) in 75 + year-olds. In univariate analysis, CKD stage 3a + prevalence increased with higher systolic blood pressure (P < 0.001). In multivariable analysis, higher prevalence of CKD stage 3a + was associated with older age (P < 0.001;odds ratio (OR):1.06;95%CI:1.05,1.07), female sex (P < 0.001;OR:2.29;95%CI:1.94,2.69), rural region of habitation (P = 0.001;OR:1.29;95%CI:1.11,1.50), higher body mass index (P = 0.03;OR:1.02;95%CI:1.002,1.03), lower prevalence of house ownership (P = 0.02;OR:0.57;95%CI:0.35,0.92), higher prevalence of mostly sitting or standing during work (P < 0.001;OR:1.40;95%CI:1.20,1.64), higher serum concentration of triglycerides (P < 0.001;OR:1.23;95%CI:1.12,1.35) and blood urea nitrogen (P < 0.001;OR:1.33;95%CI:1.27,1.40), lower serum concentration of hemoglobin (P = 0.03;OR:0.99;95%CI:0.99,0.999), and lower prevalence of chronic obstructive pulmonary disease (P < 0.001;OR:0.57;95%CI:0.42,0.78).

Conclusions
In this population from Russia aged 40+ years, prevalence of CKD stage 3+ (28.7%;95%CI:27.5,29.8) was relatively high as compared to populations from other countries. Associated factors were older age, female sex, rural region, higher body mass index, a sedentary lifestyle, and lower socioeconomic background.
Percutaneous insertion of peritoneal dialysis catheter is a safe and effective technique irrespective of BMI
Authors: Xie Dayang , Zhou Jianhui , Cao Xueying , Zhang Qingtao , Sun Yanli , Tang Li , Huang Jing , Zheng Juanli , Lin Li , Li Zhenzhen , Cai Guangyan , Chen Xiangmei 
Published: May 2020

Abstract
Background
A large body mass index (BMI) has been considered as a relative contraindication for percutaneous catheter insertion, although this technique has many advantages. Up to now, there are few studies on peritoneal catheter placement and obesity. The aim of this study was to determine whether patients with large BMI can also choose the percutaneous technique for peritoneal dialysis catheter insertion.

Methods
One hundred eighty seven consecutive patients underwent peritoneal catheter insertions in the Chinese PLA General Hospital between January 1, 2015 and December 31, 2016, with 178 eligible cases being included in the analysis. Two groups were created based on the catheter insertion techniques, the percutaneous group (group P) and the surgical group (group S). Subgroups were created according to BMI > 28 or ≤ 28. The outcomes included catheter related complications and catheter survival.

Results
Total infectious complication rates were significantly lower in group P than in group S. There were no significant differences in peritonitis rate between group P and group S (1.20% vs. 3.16% with P = 0.71 in early stage, and 4.82% vs. 11.58% with P = 0.11 in late stage). All other measured complications were similar between the two groups. Though the one-year infection-free catheter survival in group P was 7.5% higher than group S, the difference was not significant. The one-year dysfunction-free catheter survival, one-year dysfunction-and-infection-free catheter survival, and overall catheter survival were similar between the two groups. Subgroup analyses showed a superior one-year infection-free catheter survival of percutaneous technique in patients with BMI > 28, which was confirmed by Kaplan-Meier analysis.

Conclusions
Despite the challenges that may be encountered with patients who have a large BMI, the percutaneous technique seems to be a safe and effective approach to placing a peritoneal dialysis catheter.
CT-based radiomics scores predict response to neoadjuvant chemotherapy and survival in patients with gastric cancer
Authors: Sun Kai-Yu , Hu Hang-Tong , Chen Shu-Ling , Ye Jin-Ning , Li Guang-Hua , Chen Li-Da , Peng Jian-Jun , Feng Shi-Ting , Yuan Yu-Jie , Hou Xun , Wu Hui , Li Xin , Wu Ting-Fan , Wang Wei , Xu Jian-Bo 
Published: May 2020

Abstract
Background
Neoadjuvant chemotherapy is a promising treatment option for potential resectable gastric cancer, but patients’ responses vary. We aimed to develop and validate a radiomics score (rad_score) to predict treatment response to neoadjuvant chemotherapy and to investigate its efficacy in survival stratification.

Methods
A total of 106 patients with neoadjuvant chemotherapy before gastrectomy were included (training cohort: n = 74; validation cohort: n = 32). Radiomics features were extracted from the pre-treatment portal venous-phase CT. After feature reduction, a rad_score was established by Randomised Tree algorithm. A rad_clinical_score was constructed by integrating the rad_score with clinical variables, so was a clinical score by clinical variables only. The three scores were validated regarding their discrimination and clinical usefulness. The patients were stratified into two groups according to the score thresholds (updated with post-operative clinical variables), and their survivals were compared.

Results
In the validation cohort, the rad_score demonstrated a good predicting performance in treatment response to the neoadjuvant chemotherapy (AUC [95% CI] =0.82 [0.67, 0.98]), which was better than the clinical score (based on pre-operative clinical variables) without significant difference (0.62 [0.42, 0.83], P = 0.09). The rad_clinical_score could not further improve the performance of the rad_score (0.70 [0.51, 0.88], P = 0.16). Based on the thresholds of these scores, the high-score groups all achieved better survivals than the low-score groups in the whole cohort (all P < 0.001).

Conclusion
The rad_score that we developed was effective in predicting treatment response to neoadjuvant chemotherapy and in stratifying patients with gastric cancer into different survival groups. Our proposed strategy is useful for individualised treatment planning.
Anxiety related disorders in adolescents in the United Arab Emirates: a population based cross-sectional study
Authors: Al-Yateem Nabeel , Bani issa Wegdan , Rossiter Rachel C. , Al-Shujairi Arwa , Radwan Hadia , Awad Manal , Fakhry Randa , Mahmoud Ibrahim 
Published: May 2020

Abstract
Background
Anxiety disorders are common among children and adolescents. However, there is a paucity of up-to-date data on the prevalence and correlates of anxiety-related disorders among children and adolescents in the United Arab Emirates (UAE).

Methods
We conducted a cross sectional study to determine the prevalence of specific anxiety-related disorders (e.g., generalized anxiety disorder, panic disorder, separation anxiety, social anxiety) in the UAE, and identify correlations between these disorders and adolescents’ demographic variables. Participants were 968 adolescents aged 13–18 years attending secondary schools across the UAE. Convenience sampling was used to recruit participants. We collected demographic information and data about participants’ anxiety levels. Anxiety was assessed using the Arabic and English versions of the Screen for Child Anxiety Related Disorders scale. Univariate analyses (independent sample t-tests and analysis of variance) were performed to evaluate factors affecting participants’ anxiety scores. Chi-square tests were used to compare factors associated with anxiety disorders.

Results
Participants’ mean age was 16 ± 1.8 years, and 65.8% were female. The overall prevalence of anxiety disorders was 28%, with this being significantly higher in girls (33.6%) than boys (17.2%) (p < 0.0001). Participants aged < 16 years had higher generalized anxiety, separation anxiety, and social anxiety scores compared with those aged ≥16 years (p ≤ 0.05). Those from households with a maid had significantly higher generalized anxiety, panic disorder, separation anxiety, and significant school avoidance scores than those without a maid (p ≤ 0.05). In addition, participants from middle and low economic backgrounds had higher separation anxiety scores compared with children from high economic backgrounds (p ≤ 0.05). The multivariate analysis showed the main associated factors with anxiety were gender (being female, p < 0.001) and caregiver (other than mother and father together, p < 0.001).

Conclusions
We found a high incidence of anxiety-related disorders among school-aged adolescents in the UAE, with girls being more affected than boys. This suggests that age-appropriate initiatives are urgently needed to reduce the high rate of anxiety-related disorders. It may also be necessary to further investigate the two main associated factors with anxiety identified in this study (being female and non-parental caregivers).