bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient production of (S)-1-phenyl-1, 2-ethanediol using xylan as co-substrate by a coupled multi-enzyme Escherichia coli system
Authors: Rao Junchao , Zhang Rongzhen , Xu Guanyu , Li Lihong , Xu Yan 
Published: March 2020

Abstract
Background: ( S )-1-phenyl-1,2-ethanediol is an important chiral intermediate in the synthesis of liquid crystals and chiral biphosphines.(S)-carbonyl reductase II from Candida parapsilosis catalyzes the conversion of 2-hydroxyacetophenone to ( S )-1-phenyl-1,2-ethanediol with NADPH as a cofactor. Glucose dehydrogenase with a Ala258Phe mutation is able to catalyze the oxidation of xylose with concomitant reduction of NADP + to NADPH, while endo-β-1,4-xylanase 2 catalyzes the conversion of xylan to xylose. In the present work, the Ala258Phe glucose dehydrogenase mutant and endo-β-1,4-xylanase 2 were introduced into the ( S )-carbonyl reductase II-mediated chiral pathway to strengthen cofactor regeneration by using xylan as a naturally abundant co-substrate.
Results: We constructed several coupled multi-enzyme systems by introducing ( S )-carbonyl reductase II, the A258F glucose dehydrogenase mutant and endo-β-1,4-xylanase 2 into Escherichia coli . Different strains were produced by altering the location of the encoding genes on the plasmid. Only recombinant E. coli /pET-G-S-2 expressed all three enzymes, and this strain produced ( S )-1-phenyl-1,2-ethanediol from 2-hydroxyacetophenone as a substrate and xylan as a co-substrate. The optical purity was 100% and the yield was 98.3% (6 g/L 2-HAP) under optimal conditions of 35°C, pH 6.5 and a 2:1 substrate-co-substrate ratio. The introduction of A258F glucose dehydrogenase and endo-β-1,4-xylanase 2 into the ( S )-carbonyl reductase II-mediated chiral pathway caused a 54.6% increase in yield, and simultaneously reduced the reaction time from 48 h to 28 h.
Conclusions: This study demonstrates efficient chiral synthesis using a pentose as a co-substrate to enhance cofactor regeneration. This provides a new approach for enantiomeric catalysis through the inclusion of naturally abundant materials.
Impacts of skull stripping on construction of three-dimensional T1-weighted imaging-based brain structural network in full-term neonates
Authors: Wang Geliang , Hu Yajie , Li Xianjun , Wang Miaomiao , Liu Congcong , Yang Jian , Jin Chao 
Published: March 2020

Abstract
Background: Skull stripping remains a challenge for neonatal brain MR image analysis. However, little is known about how accuracy of the skull stripping affects the neonatal brain tissue segmentation and subsequent network construction. This paper therefore aimed to clarify this issue by comparing two automatic (FMRIB Software Library's Brain Extraction Tool, BET; Infant Brain Extraction and Analysis Toolbox, iBEAT) and a semiautomatic (iBEAT with manual correction) processes in constructing 3D T1-Weighted Imaging (T1WI)-based brain structural network. Methods: Twenty-two full-term neonates (gestational age, 37-42 weeks; boys/girls, 13/9) without abnormalities on MRI who underwent brain 3D T1WI were retrospectively recruited. Two automatic (BET and iBEAT) and a semiautomatic preprocessing (iBEAT with manual correction) workflows were separately used to perform the skull stripping. Brain tissue segmentation and volume calculation were performed by a John Hopkins atlas-based method. Sixty-four gray matter regions were selected as nodes; volume covariance network and its properties (clustering coefficient, C p ; characteristic path length, L p ; local efficiency, E local ; global efficiency, E global ) were calculated by GRETNA. Analysis of variance (ANOVA) was used to compare the differences in the calculated volume between three workflows. Results: There were significant differences in volumes of 50 brain regions between three workflows ( P <0.05). Three neonatal brain structural networks presented small-world topology. The semiautomatic workflow showed remarkably decreased C p , increased L p , decreased E local , and decreased E global , in contrast to two automatic ones. Conclusions: Imperfect skull stripping indeed affected the accuracy of brain structural network in full-term neonates.
Nosocomial Infections Due to Multidrug-Resistant Bacteria in Cancer Patients: A Six-Year Experience of an Oncology Center of Western China
Authors: Jiang Ai-Min , Shi Xin , Liu Na , Gao Huan , Ren Meng-Di , Zheng Xiao-Qiang , Fu Xiao , Liang Xuan , Ruan Zhi-Ping , Yao Yu , Tian Tao 
Published: March 2020

Abstract
Background: Bacterial infections are the most frequent complications in patients with malignancy, and the epidemiology of nosocomial infections among cancer patients has changed over time. This study aimed to evaluate characteristics, antibiotic-resistant patterns, and prognosis of nosocomial infections caused by multidrug-resistant (MDR) bacteria in cancer patients. Methods: This retrospective observational study analyzed cancer patients with MDR bacteria caused nosocomial infections from August 2013 to May 2019. The extracted clinical data were recorded in a standardized form and compared based on the patient’s survival status after infection during hospitalization. Data were analyzed by using independent samples t-test, Chi-square test, and binary logistic regression. P -values < 0.05 were considered statistically significant. Results: Overall, 257 cancer patients developed nosocomial infections caused by MDR bacteria. Extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL-PE) was the most frequently isolated multidrug-resistant Gram-negative bacteria (MDRGNB), followed by Acinetobacter baumannii , and Stenotrophomonas maltophilia . Smoking history, cancer patients who received intrapleural/abdominal infusion within 30 days, presence of indwelling urinary catheter, and haemoglobin were independent factors for in-hospital mortality in the study population. The isolated MDR bacteria were mainly sensitive to amikacin, meropenem, imipenem, tigecycline, and piperacillin/tazobactam. Conclusions: This study confirms that MDR bacteria caused nosocomial infections were widely prevalent in cancer patients. ESBL-PE was the most commonly MDR bacteria, and the isolated MDR strains were mainly sensitive to amikacin, meropenem, imipenem, tigecycline, and piperacillin/tazobactam. Former smokers, cancer patients who received intrapleural/abdominal infusion within 30 days, presence of indwelling urinary catheter, and anemia were associated with increased in-hospital mortality. Our findings suggest that clinicians should think highly of nosocomial infections caused by MDR in cancer patients and advise policymakers to develop a guideline.
Plasma neurofilament light chain and glial fibrillary acidic protein predict stroke in CADASIL
Authors: Chen Chih-Hao , Cheng Yu-Wen , Chen Ya-Fang , Tang Sung-Chun , Jeng Jiann-Shing 
Published: March 2020

Abstract
Background

Stroke remains the most cumbersome disease burden in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This study aimed to investigate whether plasma biomarkers can reflect disease severity and predict stroke recurrence in CADASIL patients.

Methods

Sixty-three CADASIL patients (mean age 58.9±9.3 years old, male 63%) from a multicenter registry and 17 controls were recruited. Plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), were measured using an ultra-sensitive single molecule array at baseline. Neuroimaging markers assessed included the Fazekas scale of white matter hyperintensity, numbers of lacunes and cerebral microbleeds (CMBs). Cox proportional hazards regression models were applied to calculate the hazard ratio (HR) of plasma biomarkers at baseline for predicting incident stroke during follow-up.

Results

Plasma NfL, GFAP, and UCHL1 levels were significantly elevated in the CADASIL patients than in the controls. Among the CADASIL patients, both plasma NfL and GFAP levels positively correlated with the numbers of CMBs (r = 0.32 and r = 0.37, respectively; both p < 0.05). Higher plasma levels of NfL and GFAP were associated with any stroke (odds ratio 2.02, 95% confidence interval [CI] 1.06–3.87) and ICH (odds ratio 2.06, 95% CI 1.26–3.35) at baseline, respectively. Within a mean follow-up period of 3.1 Common.EditSubmissionSteps.Transform.EquationText 2.1 years, 10 patients (16%) had incident stroke and 6 of them were ICH. Higher baseline NfL (HR 1.93, 95% CI 1.19–3.13) predicted any incident stroke, whereas higher GFAP (HR 2.80, 95% CI 1.21–6.53) predicted incident ICH.

Conclusions

In CADASIL patients, plasma NfL can be a promising biomarker for monitoring incident stroke, whereas GFAP may have a role in cerebral hemorrhage.
Cross-cultural validation of the Motivation to Change Lifestyle and Health Behaviours for Dementia Risk Reduction scale in the Dutch general population
Authors: Joxhorst Tessa , Vrijsen Joyce , Niebuur Jacobien , Smidt Nynke 
Published: March 2020

Abstract
BACKGROUND: This study aims to translate and validate the Motivation to Change Lifestyle and Health Behaviours for Dementia Risk Reduction (MCLHB-DRR) scale in the Dutch general population.

METHODS: A random sample of Dutch residents aged between 30 and 80 years old were invited to complete an online questionnaire including the translated MCLHB-DRR scale. Exploratory and confirmatory factor analyses (EFA and CFA) were conducted to assess construct validity. Cronbach’s alpha was calculated to assess internal consistency.

RESULTS: 618 participants completed the questionnaire. EFA and Cronbach’s alpha showed that four items were candidate for deletion. CFA confirmed that deleting these items led to an excellent fit (RMSEA = 0.043, CFI = 0.960, TLI = 0.951, χ²/df = 2.130). Cronbach’s alpha ranged from 0.69 to 0.93, indicating good internal consistency.

CONCLUSION: The current study demonstrated that the Dutch MCLHB-DRR scale is a valid scale for assessing health beliefs and attitudes towards dementia risk reduction among Dutch adults aged between 30 and 80 years old.
Diagnostic value of macrophage inhibitory cytokine 1 as a novel prognostic biomarkers for early gastric cancer screening
Authors: Ge Xin , Zhang Xiaolei , Ma Yanling , Chen Shaohua , Chen Zhaowu , Li Ming 
Published: March 2020

Abstract
BACKGROUND Early diagnosis is very important to improve the survival rate of patients with gastric cancer, especially in asymptomatic participants. However, low sensitivity of common biomarkers has caused difficulties in early screening of gastric cancer. In this study, we explored whether MIC-1 can improve the detection rate of early gastric cancer.METHODS We screened 8,257 participants based on risk factors such as age, gender, and family history for physical examination including gastroscopy. Participant blood samples were taken for measure MIC-1, CA-199, CA72-4 and PG1/PG2 levels. The diagnostic performance of MIC-1 was assessed and compared with CA-199, CA72-4 and PG1/PG2, and its role in early gastric cancer diagnosis and the assessment of the risk of precancerous lesions have also been studied.RESULTS Based on endoscopic and histopathological findings, 55 participants had gastric cancer, 566 participants had low-grade neoplasia, 2605 participants had chronic gastritis. MIC-1 levels were significantly elevated in gastric cancer serum samples as compared to controls (p<0.001). The sensitivity of serum MIC-1 for gastric cancer diagnosis was much higher than that of CA-199 (49.1% vs. 20.0%) with similar specificities. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MIC-1 had a better performance compared with CA-199, CA72-4 and PG1/PG2 in distinguishing early-stage gastric cancer (AUC: 72.9% vs. 69.5%, 67.5%, 44.0% respectively).CONCLUSIONS Serum MIC-1 is significantly elevated in most patients with early gastric cancer. MIC-1 can serve as a novel diagnostic marker of early gastric cancer and value the risk of gastric cancer.
Particle characterization and toxicity in C57BL/6 mice following instillation of five different diesel exhaust particles designed to differ in physicochemical properties
Authors: Bendtsen Katja Maria , Gren Louise , Malmborg Vilhelm Berg , Shukla Pravesh Chandra , Tunér Martin , Essig Yona J , Krais Annette M , Clausen Per Axel , Berthing Trine , Loeschner Katrin , Jacobsen Nicklas Raun , Wolff Henrik , Pagels Joakim , Vogel Ulla B 
Published: March 2020

Abstract
Background Diesel exhaust is carcinogenic and exposure to diesel particles cause health effects. We investigated the toxicity of diesel exhaust particles designed to have varying physicochemical properties in order to attribute health effects to specific particle characteristics. Particles from three fuel types were compared at 13% engine intake O 2 concentration: MK1 ultra low sulfur diesel (DEP13) and the two renewable diesel fuels hydrotreated vegetable oil (HVO13) and rapeseed methyl ester (RME13). Additionally, diesel particles from MK1 ultra low sulfur diesel were generated at 9.7% (DEP9.7) and 17% (DEP17) intake O 2 concentration. We evaluated physicochemical properties and histopathological, inflammatory and genotoxic responses on day 1, 28 and 90 after single intratracheal instillation in mice compared to reference diesel particles and carbon black.Results Moderate variations were seen in physical properties for the five particles: primary particle diameter: 15-22 nm, specific surface area: 152-222 m 2 /g, and count median mobility diameter: 55-103 nm. Larger differences were found in chemical composition: organic carbon/total carbon ratio (0.12-0.60), polycyclic aromatic hydrocarbon content (1-27 mg/mg) and acid-extractable metal content (0.9-16 mg/mg). Intratracheal exposure to all five particles induced similar toxicological responses, with different potency. Lung particle retention was observed in DEP13 and HVO13 exposed mice on day 28, with less retention for the other fuel types. RME exposure induced limited response whereas the remaining particles induced dose-dependent inflammation and acute phase response on day 1. DEP13 induced acute phase response on day 28 and inflammation on day 90. DNA strand break levels were not increased as compared to vehicle, but were increased in lung and liver compared to blank filter extraction control. Neutrophil influx on day 1 correlated best with estimated deposited surface area, but also with elemental carbon, organic carbon and PAHs. DNA strand break levels in liver on day 90 correlated with acellular particle-induced ROS.Conclusions We studied diesel exhaust particles designed to differ in physicochemical properties. Our study highlights particle size, elemental carbon content, PAHs and ROS-generating potential as physicochemical predictors of diesel particle toxicity.
Non–anti-TNF biologic agents not associated with a worsening of lung disease secondary to rheumatoid arthritis.
Authors: Vázquez Natalia Mena , Godoy-Navarrete Francisco Javier , Manrique-Arija Sara , Aguilar-Hurtado Maria Carmen , Romero-Barco Carmen María , Ureña-Garnica Inmaculada , Añón-Oñate Isabel , Pérez-Albaladejo Lorena , Gomez-Cano Carmen , Jimenez-Núñez Francisco Gabriel , Padin-Martín Maria Isabel , Fernández-Nebro Antonio 
Published: March 2020

Abstract
Objectives To analyze the effect of disease-modifying antirheumatic drugs (DMARDs) on the outcome of interstitial lung disease secondary to rheumatoid arthritis (RA-ILD). Patients and methods We performed a multicenter, prospective, observational study of patients with RA-ILD receiving DMARDs between 2015 and 2017. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 24 months. The radiological assessment was centralized. The main outcome measure at 24 months was change in lung function (improvement, stabilization, worsening, or death). We recorded the 28-joint Disease Activity Score 28 (DAS28) and adverse events. A logistic regression analysis was performed to identify factors associated with worsening of ILD. Results After 24 months, lung disease was stabilized in 40 patients (57.1%), improved in 8 (11.4%), and worse in 21 (30.0%). One patient (1.4%) died. The factors associated with worsening of ILD in the multivariate analysis were treatment with abatacept, tocilizumab, or rituximab (OR, 0.102 [95%CI, 0.015-0.686]), DAS28 (OR, 1.969 [95%CI, 1.005-3.857]), and smoking (OR, 6.937 [95%CI, 1.378-4.900]). During follow-up, 30 patients (42.9%) experienced an adverse event, which was severe in 12 cases (17.1%). Conclusions Lung function is stable and inflammatory activity well controlled in most patients with RA-ILD receiving treatment with DMARDs. Non–anti-TNF DMARDs reduce the risk of worsening of lung disease in 90% of patients. The inflammatory activity of RA and smoking, on the other hand, are associated with worsening.
Persistence of Pregabalin Treatment in Taiwan: a Nation-Wide Population-Based Study
Authors: Wang Yen-Feng , Chen Yung-Tai , Tsai Ching-Wen , Yen Yu-Chun , Chen Yi-Chun , Hsia Ben-Chang , Wang Shuu-Jiun 
Published: March 2020

Abstract
Background Pregabalin is approved for the treatment of neuropathic pain, fibromyalgia, and seizure disorders, although the pivotal trials were mostly carried out in Europe or North America. The prescribing patterns among different indications in Asia have rarely been explored. Methods This was a population-based retrospective cohort study based on the National Health Insurance Research Database in Taiwan. Prescriptions of pregabalin were identified, and data regarding demographics, indications, co-existing diagnoses, and concomitant medications were extracted. Pregabalin users were followed for at least one year, and factors associated with persistence at one year were determined by using multivariate logistic regression analysis. Results Between June 2012 and December 2016, 114,437 pregabalin users (mean age 60.7±15.4 years, 57.8% female) were identified. The indications included post-herpetic neuralgia (PHN) (30.5%), musculoskeletal diseases other than fibromyalgia (21.2%), fibromyalgia (18.4%), diabetic peripheral neuropathic pain (DPNP) (11.7%) and epilepsy (2.9%). Overall, 62.5% and 6.4% of patients achieved a maximum dose of ≥150 and ≥300 mg/day, respectively. The median duration of persistent pregabalin use was 28 days (interquartile range 14-118 days). The one-year persistence rate was 12.1%, and the indications associated with the highest and lowest persistence rates were epilepsy (42.4%) and PHN (6.1%), respectively. Male gender (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.09-1.18), older age (OR 1.01 per year, 95% CI 1.01-1.01), indications other than PNH, especially epilepsy (OR 8.04, 95% CI 7.33-8.81, PHN as reference), and a higher initial dose (OR 1.12 per 75 mg, 95% CI=1.10-1.15) were associated with persistence at one year, whereas the initial concomitant use of antiviral agents decreased the likelihood (OR 0.41, 95% CI 0.35-0.47). Conclusions Pregabalin prescriptions for pain disorders were limited to short-term use, which is consistent around the world. However, the average prescribed dose in Taiwan was lower than those in Western countries, and was typically below the recommended ranges. Potential causes included off-label prescriptions for pain in acute herpes zoster, rather than PNH, as well as intolerance to the side effects. Keywords pregabalin, pain, persistence
Association of serum levels of antibodies against ALDOA and FH4 with transient ischemic attack and cerebral infarction
Authors: Wang Hao Hao , Lu Hao Hao , Zhang Xiao-Meng Xiao-Meng , Goto Ken-ichiro Ken-ichiro , Kobayashi Eiichi Eiichi , Yoshida Yoichi Yoichi , Adachi Akihiko Akihiko , Matsutani Tomoo Tomoo , Iwadate Yasuo Yasuo , Min Seiichiro Seiichiro , Machida Toshio Toshio , Sata Mizuki Mizuki , Yamagishi Kazumasa Kazumasa , Iso Hiroyasu Hiroyasu , Sawada Norie Norie , Tsugane Shoichiro Shoichiro , Kamitsukasa Ikuo Ikuo , Wada Takeshi Takeshi , Aotsuka Akiyo Akiyo , Sugimoto Kazuo Kazuo , Takizawa Hirotaka Hirotaka , Kashiwado Koichi Koichi , Shin Hideo Hideo , Tomiyoshi Go Go , Nakamura Rika Rika , Shinmen Natsuko Natsuko , Kuroda Hideyuki Hideyuki , Xu Anding Anding , Hiwasa Takaki 
Published: March 2020

Abstract
Background and Purpose: Ischemic stroke, such as Transient ischemic attack (TIA) and cerebral infarction (CI) , are the serious problems in the aging society. Therefore, development of biomarkers for TIA and CI is attempted.Methods: Candidate antigens recognized by IgG autoantibodies in the sera of nineteen TIA patients were screened by a human aortic endothelial cell cDNA library. Serum antibody levels against the antigens were examined by amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in healthy donor (HD), TIA, and CI cohorts (n = 285, 92 and 529). A case-control study nested within the Japan Public Health Center-based Prospective Cohort Study (JPHC) was performed.Results: Aldolase A, fructose-bisphosphate (ALDOA) and fumarate hydratase (FH) were identified as the candidate antigens. AlphaLISA revealed that anti-ALDOA and anti-FH antibody levels were both higher in TIA or CI patients than in HDs ( P < 0.0001). The levels of anti-ALDOA [Odds ratio (OR): 2.46, P = 0.005] and anti-FH (OR: 2.49, P = 0.0037) were independent predictors of TIA by multivariate logistic regression analysis, similar results were found in CI. The case-control study showed the levels of anti-ALDOA (OR: 2.50, P < 0.01) and anti-FH (OR: 2.60, P < 0.01) were associated with risk of CI. Spearman’s correlation analysis demonstrated an association between the anti-ALDOA and anti-FH levels and risk factors of ischemic stroke, such as age, smoking habit, coronary heart disease, and hypertension.Conclusions: Anti-ALDOA and anti-FH antibodies can serve as novel potential biomarkers for prediction of TIA and CI.