bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a membrane‐separated and a membrane‐less electrobioreactor for bioelectrochemical syntheses
Authors: Krieg Thomas , Phan Linh M. P. , Wood Jeffery A. , Sydow Anne , Vassilev Igor , Krömer Jens O. , Mangold Klaus‐Michael , Holtmann Dirk 
Published: March 2018

AbstractBioelectrochemical systems (BESs) have the potential to contribute to the energy revolution driven by the new bio‐economy. Until recently, simple reactor designs with minimal process analytics have been used. In recent years, assemblies to host electrodes in bioreactors have been developed resulting in so‐called “electrobioreactors.” Bioreactors are scalable, well‐mixed, controlled, and therefore widely used in biotechnology and adding an electrode extends the possibilities to investigate bioelectrochemical production processes in a standard system. In this work, two assemblies enabling a separated and non‐separated electrochemical operation, respectively, are designed and extensively characterized. Electrochemical losses over the electrolyte and the membrane were comparable to H‐cells, the bioelectrochemical standard reaction system. An effect of the electrochemical measurements on pH measurements was observed if the potential is outside the range of −1,000 to +600 mV versus Ag/AgCl. Electrobiotechnological characterization of the two assemblies was done using Shewanella oneidensis as an electroactive model organism. Current production over time was improved by a separation of anodic and cathodic chamber by a Nafion® membrane. The developed electrobioreactor was used for a scale‐up of the anaerobic bioelectrochemical production of organic acids and lysine from glucose using an engineered Corynebacterium glutamicum. Comparison to a small‐scale custom‐made electrobioreactor indicates that anodic electro‐fermentation of lysine and organic acids might not be limited by the BES setup but by the biocatalysis of the cells.
Hollow microcarriers for large‐scale expansion of anchorage‐dependent cells in a stirred bioreactor
Authors: YekrangSafakar Ashkan , Acun Aylin , Choi Jin‐Woo , Song Edward , Zorlutuna Pinar , Park Kidong 
Published: March 2018

AbstractWith recent advances in biotechnology, mammalian cells are used in biopharmaceutical industries to produce valuable protein therapeutics and investigated as effective therapeutic agents to permanently degenerative diseases in cell based therapy. In these exciting and actively expanding fields, a reliable, efficient, and affordable platform to culture mammalian cells on a large scale is one of the most vital necessities. To produce and maintain a very large population of anchorage‐dependent cells, a microcarrier‐based stirred tank bioreactor is commonly used. In this approach, the cells are exposed to harmful hydrodynamic shear stress in the bioreactor and the mass transfer rates of nutrients and gases in the bioreactor are often kept below an optimal level to prevent cellular damages from the shear stress. In this paper, a hollow microcarrier (HMC) is presented as a novel solution to protect cells from shear stress in stirred bioreactors, while ensuring sufficient and uniform mass transfer rate of gases and nutrients. HMC is a hollow microsphere and cells are cultured on its inner surface to be protected, while openings on the HMC provide sufficient exchange of media inside the HMC. As a proof of concept, we demonstrated the expansion of fibroblasts, NIH/3T3 and the expansion and cardiac differentiation of human induced pluripotent stem cells, along with detailed numerical analysis. We believe that the developed HMC can be a practical solution to enable large‐scale expansion of shear‐sensitive anchorage‐dependent cells in an industrial scale with stirred bioreactors.
Risk profile analysis and complications after surgery for autoimmune thyroid disease
Authors: Thomusch O , Sekulla C , Billmann F , Seifert G , Dralle H , Lorenz K , Vorländer C , Dralle H , Freitag M , Jähne J , Steinmüller T , Trupka A , Steinert F , Schabram J , Heinzmann B , Lang H , Cotte J , Hoffmann T F , Dette K , Gellert K , Henne-Bruns D , Boese-Landgraf J , Simon Evangelisches D , Kube R , Lorenz E P M , Pross M , Hartel M , Thomschke D , Pistorius G , Hopt U T , Franke C , Rose U , Steuer W , Schwenk W , Ebert K-H , Kelm C , Witzigmann H , Rampf W , Ridwelski K , Knoefel W T , Bechstein W O , Grothe D , Anthuber M , Mirow L , Probst W , Thews A , Fleck U , Kärgel W , Schimmelpenning H , Fielitz J , Rose U , Schöffauer T , Asperger W , Zaage J , Dorn H-U , Weitz J , Neubauer M , Klar E , Lautermann J , Senkal M , Lippert H , Lück R , Ziesche M , Kröll K-P , Skrobisz J , Lorenc Z , Dudesek B , Smutny S , Brauckhoff M , Längle F , Wenzl E 
Published: March 2018

Abstract

Background
Surgical approaches to autoimmune thyroid disease are currently hampered by concerns over postoperative complications. Risk profiles and incidences of postoperative complications have not been investigated systematically, and studies with sufficient power to show valid data have not been performed.

Methods
A prospective multicentre European study was conducted between July 2010 and December 2012. Questionnaires were used to collect data prospectively on patients who had surgery for autoimmune thyroid disease and the findings were compared with those of patients undergoing surgery for multinodular goitre. Logistic regression analysis was used to evaluate risk factors for thyroid surgery-specific complications, transient and permanent recurrent laryngeal nerve (RLN) palsy and hypoparathyroidism.

Results
Data were available for 22 011 patients, of whom 18 955 were eligible for analysis (2488 who had surgery for autoimmune thyroid disease and 16 467 for multinodular goitre). Surgery for multinodular goitre and that for autoimmune thyroid disease did not differ significantly with regard to general complications. With regard to thyroid surgery-specific complications, the rate of temporary and permanent vocal cord palsy ranged from 2·7 to 6·7 per cent (P = 0·623) and from 0·0 to 1·4 per cent (P = 0·600) respectively, whereas the range for temporary and permanent hypoparathyroidism was 12·9 to 20·0 per cent (P &lt; 0·001) and 0·0 to 7·0 per cent (P &lt; 0·001) respectively. In logistic regression analysis of transient and permanent vocal cord palsy, autoimmune thyroid disease was not an independent risk factor. Autoimmune thyroid disease, extent of thyroid resection, number of identified parathyroid glands and no autotransplantation were identified as independent risk factors for both transient and permanent hypoparathyroidism.

Conclusion
Surgery for autoimmune thyroid disease is safe in comparison with surgery for multinodular goitre in terms of general complications and RLN palsy. To avoid the increased risk of postoperative hypoparathyroidism, special attention needs to be paid to the parathyroid glands.
Quantification of metronidazole in human plasma using a highly sensitive and rugged LC–MS/MS method for a bioequivalence study
Authors: Vanol Pravin G. , Sanyal Mallika , Shah Priyanka A. , Shrivastav Pranav S. 
Published: March 2018

AbstractA highly sensitive, selective and rugged method has been described for the quantification of metronidazole (MTZ) in human plasma by liquid chromatography–tandem mass spectrometry using metronidazole‐d4 as the internal standard (IS). The analyte and the IS were extracted from 100 μL plasma by liquid–liquid extraction. The clear samples obtained were chromatographed on an ACE C18 (100 × 4.6 mm, 5 μm) column using acetonitrile and 10.0 mm ammonium formate in water, pH 4.00 (80:20, v/v) as the mobile phase. A triple quadrupole mass spectrometer system equipped with turbo ion spray source and operated in multiple reaction monitoring mode was used for the detection and quantification of MTZ. The calibration range was established from 0.01 to 10.0 μg/mL. The results of validation testing for precision and accuracy, selectivity, matrix effects, recovery and stability complied with current bioanalytical guidelines. A run time of 3.0 min permitted analysis of more than 300 samples in a day. The method was applied to a bioequivalence study with 250 mg MTZ tablet formulation in 24 healthy Indian males.
Simultaneous determination of zidebactam and cefepime in dog plasma by LC–MS/MS and its application to pre‐clinical pharmacokinetic study
Authors: Patil Kiran , Tambe Harshad , Zope Vineet , Chavan Rajesh , Yeole Ravindra , Patel Mahesh 
Published: March 2018

AbstractA precise and accurate liquid chromatography–tandem mass spectrometric (LC–MS/MS) bioanalytical method has been developed and validated for the simultaneous quantification of zidebactam (ZID) and cefepime (FEP) in dog plasma. Ceftazidime was used as an internal standard. Protein precipitation method was used as sample preparation approach. The calibration curve obtained was linear (r ≥ 0.99) over the concentration range 0.156–80 μg/mL for ZID and 0.312–160 μg/mL for FEP. The method was validated as per US Food and Drug Administration guidelines and the results met the acceptance criteria. A run time of 3.5 min for each sample made it possible to analyze the maximum number of samples per day. The proposed method was successfully applied for pharmacokinetic study in beagle dogs.
Inhibitory effects of Danhong Injection and its major constituents on human cytochrome P450 enzymes in vitro
Authors: Ye Lin‐Hu , Zhao Xin‐Qian , Kong Ling‐Ti , Wang Li‐Sha , Tao Xue , Wu Hui , He Mei , Chang Qi 
Published: March 2018

AbstractDanhong Injection (DHI) as a Chinese patent medicine is mainly used to treat ischemic encephalopathy and coronary heart disease in combination with other chemotherapy. However, the information on DHI's potential drug interactions is limited. The goal of this work was to examine the potential P450‐mediated metabolism drug interaction arising from DHI and its active components. The results showed that DHI inhibited CYP2C19, CYP2D6, CYP3A4, CYP2E1 and CYP2C9 with IC50 values of 1.26, 1.42, 1.63, 1.10 and 1.67% (v/v), respectively. Danshensu and rosmarinic acid inhibited CYP2E1 and CYP2C9 with IC50 values of 36.63 and 75.76 μm, and 34.42 and 76.89 μm, respectively. Salvianolic acid A and B inhibited CYP2D6, CYP2E1 and CYP2C9 with IC50 values of 33.79, 21.64 and 31.94 μm, and 45.47, 13.52 and 24.15 μm, respectively. The study provides some useful information for safe and effective use of DHI in clinical practice.
Sodium valproate compared to phenytoin in treatment of status epilepticus
Authors: Amiri‐Nikpour Mohammad Reza , Nazarbaghi Surena , Eftekhari Parisa , Mohammadi Sedra , Dindarian Sina , Bagheri Mahdi , Mohammadi Hozan 
Published: March 2018

AbstractBackgroundStatus epilepticus (SE) is a neurological emergency which can be life‐threatening. Several medical regimens are used in order to control it. In this study, we intended to evaluate the clinical efficacy and tolerability of sodium valproate and intravenous phenytoin (IV PHT) in the control of SE.MethodsOne hundred and ten consecutive patients suffering from benzodiazepine refractory SE who were referred to the emergency ward from March 2014 to March 2015 were randomly divided into two groups. The first group received intravenous sodium valproate, 30 mg/kg as loading dose and then 4–8 mg/kg every 8 hr as maintenance regimen. The second group received IV PHT 20 mg/kg as loading dose and then 1.5 mg/kg for 8 hr as maintenance therapy. All patients were monitored for vital signs every 2 hr up to 12 hr. The patients were also followed up for 7 days regarding drug response and adverse effects.ResultsThe administration of sodium valproate and phenytoin respectively resulted in seizure control in 43 (78.18%) and 39 (70.90%) of the patients within 7 days of drug administration (p = .428). Seven‐day mortality rate was similar in both groups (12.73% vs. 12.73%; p = .612). There was no significant difference in adverse effects between two groups.ConclusionSodium valproate is preferred to IV PHT for treatment and control of SE due to its higher tolerability and lower hemodynamic instability.
Effects of oral metaphors and allegories on programming problem solving
Authors: Hidalgo‐Céspedes Jeisson , Marín‐Raventós Gabriela , Lara‐Villagrán Vladimir , Villalobos‐Fernández Luis 
Published: March 2018

AbstractMetaphors of ordinary concepts are intensively used in computer science for naming abstract concepts and for designing users interfaces. Metaphors are mappings from a source domain (e.g., a stream) to a target domain (e.g., a sequence of bytes). Typically computing phenomena are explained using incoherent discourses at the source domain, formed by metaphors taken from a diversity of origins. Nonetheless, versatility of metaphors allows for the creation of coherent discourses in the origin domain that map the target computing discourse, and we call themallegories. The limited number of existing studies about this topic has compared only textual allegories, visual allegories, and the traditional unconnected metaphors. Although their findings are heterogeneous, equal effectiveness is the most frequent empirical result between these three types of metaphors. Furthermore, we have not found any study about oral allegories, in spite of oral being the most used modality for metaphors in computer science education. This article experimentally compares the effects of oral allegories and oral metaphors on a complex problem‐solving task. As in previous studies, our results did not find any significant differences on support or detriment of oral allegories. Our results support new metaphor theories posing that the context significantly influences the metaphors’ efficacy, and encourages future research about the interaction between context and allegories.
The benefit and risk of nivolumab in non‐small‐cell lung cancer: a single‐arm meta‐analysis of noncomparative clinical studies and randomized controlled trials
Authors: Zhao Binghao , Zhang Wenxiong , Yu Dongliang , Xu Jianjun , Wei Yiping 
Published: March 2018

AbstractNivolumab is a programmed cell death 1 (PD‐1) receptor inhibitor antibody that enhances immune system antitumor activity. Although it is used for treating advanced non‐small‐cell lung cancer (NSCLC), its actual efficacy has not been determined. We searched PubMed, the Cochrane Library, Embase,MEDLINE, and Web of Science for related noncomparative clinical studies and randomized controlled trials (RCTs) to assess nivolumab benefit and risk inNSCLC. The main outcomes were objective response rate (ORR), 1‐year overall survival rate (1‐yOSrate), and progression‐free survival rate at 24 weeks (PFSat 24 weeks rate), any‐grade adverse effects rate (any‐gradeAEs%), and grade 3–4AErate (grade 3–4AEs%). Relative risk (RR) was used to compareORRin patients with positive and negative programmed cell death ligand 1 (PD‐L1) expression. Random‐effects models were used to determine pooled effect size and two‐sided 95% confidence intervals (95%CI). We included 20 studies (17 noncomparative open‐label cohort studies, threeRCTs) involving 3404 patients in our meta‐analysis. The modified nivolumabORRwas 18% (95%CI: 15–20%), the 1‐yOSrate was 45% (95%CI: 40–50%),PFSat 24 weeks rate was 42% (95%CI: 37–48%), any‐gradeAEs% was 61% (95%CI: 50–73%), and grade 3–4AEs% was 12% (95%CI: 9–16%).PD‐L1 expression was related with the nivolumabORR. Nivolumab potentially causes ongoing response, long‐termPFS, and reduced treatment‐relatedAEs.PD‐L1 expression predicts the outcome of nivolumab immunotherapy. More high‐quality and well‐designedRCTs with large sample sizes are warranted to prove our findings.
NOTCH1 mutation and its prognostic significance in Chinese chronic lymphocytic leukemia: a retrospective study of 317 cases
Authors: Zou Yixin , Fan Lei , Xia Yi , Miao Yi , Wu Wei , Cao Lei , Wu Jiazhu , Zhu Huayuan , Qiao Chun , Wang Li , Xu Wei , Li Jianyong 
Published: March 2018

AbstractThe proto‐oncogene NOTCH1 is frequently mutated in around 10% of patients with chronic lymphocytic leukemia (CLL). This study analyzed NOTCH1 mutation status of 317 Chinese patients with CLL by Sanger sequencing. The frequencies of NOTCH1 mutation in the PEST (proline (P), glutamic acid (E), serine (S), threonine (T)‐rich protein sequence) domain and the 3′ untranslated regions (UTR) were 8.2% and 0.9%, with the most frequent mutation being c.7541_7542delCT and c.*371A>G, respectively. Clinical and biological associations were determined including NOTCH1 mutations with advanced stage (Binet stage, P = 0.010), unmutated immunoglobulin heavy‐chain variable region (IGHV) gene (P < 0.001) and trisomy 12 (+12) (P = 0.014). NOTCH1‐mutated patients had lower CD20 expression intensity than NOTCH1‐unmutated patients (P = 0.029). In addition, NOTCH1‐mutated patients had shorter overall survival (OS) (P = 0.002) and treatment‐free survival (TFS) (P = 0.002) than NOTCH1‐unmutated patients, especially for patients with NOTCH1 c.7541_7542delCT and/or c.*371A>G mutations. Patients with both mutated NOTCH1 and unmutated IGHV had shorter OS (P < 0.001) and TFS (P < 0.001) than those with unmutated NOTCH1 or mutated IGHV. These data provide a comprehensive view of the clinical relevance and prognostic impact of NOTCH1 mutations on Chinese patients with CLL.
Plasma miRNA can detect colorectal cancer, but how early?
Authors: Wikberg Maria L. , Myte Robin , Palmqvist Richard , van Guelpen Bethany , Ljuslinder Ingrid 
Published: March 2018

AbstractColorectal cancer (CRC) is a major cause of deaths worldwide but has a good prognosis if detected early. The need for efficient, preferable non‐ or minimally invasive, inexpensive screening tools is therefore critical. We analyzed 12 miRNAs in pre‐ and postdiagnostic plasma samples to evaluate their potential as CRC screening markers. We used a unique study design with two overlapping cohorts, allowing analysis of pre‐ and postdiagnostic samples from 58 patients with CRC and matched healthy controls. Plasma concentrations of miR‐15b, ‐16, ‐18a, ‐19a, 21, ‐22, ‐25, ‐26a, ‐29c, ‐142‐5p, ‐150, and ‐192 were measured by semi‐quantitative real‐time PCR. Concentrations of miR‐18a, ‐21, ‐22, and ‐25 in plasma from patients with CRC were significantly altered compared to healthy controls. Combined as a multimarker panel, they detected CRC with an AUC of 0.93. Furthermore, levels of these three miRNAs also showed different levels in the prediagnostic case samples close to diagnosis. Only miR‐21‐levels were elevated several years before diagnosis. Plasma levels of miR‐18a, ‐21, ‐22, and ‐25 show promise as screening biomarkers for CRC. However, based on our unique analysis of prediagnostic and postdiagnostic samples from the same patients, we conclude that circulating miRNAs elevated at diagnosis may not automatically be suitable for CRC screening, if the increase occurs too close to clinical diagnosis.
Liquid biopsy by NGS: differential presence of exons (DPE) in cell‐free DNA reveals different patterns in metastatic and nonmetastatic colorectal cancer
Authors: Olmedillas‐López Susana , García‐Olmo Dolores C. , García‐Arranz Mariano , Peiró‐Pastor Ramón , Aguado Begoña , García‐Olmo Damián 
Published: March 2018

AbstractNext‐generation sequencing (NGS) has been proposed as a suitable tool for liquid biopsy in colorectal cancer (CRC), although most studies to date have focused almost exclusively on sequencing of panels of potential clinically actionable genes. We evaluated the clinical value of whole‐exome sequencing (WES) of cell‐free DNA (cfDNA) circulating in plasma, with the goal of identifying differential clinical profiles in patients with CRC. To this end, we applied an original concept, “differential presence of exons” (DPE). We determined differences in levels of 379 exons in plasma cfDNA and used DPE analysis to cluster and classify patients with disseminated and localized disease. The resultant bioinformatics analysis pipeline allowed us to design a predictive DPE algorithm in a small subset of patients that could not be initially classified based on the selection criteria. This DPE suggests that these nucleic acids could be actively released by both tumor and nontumor cells as a means of intercellular communication and might thus play a role in the process of malignant transformation. DPE is a new technique for the study of plasma cfDNA by WES that might have predictive and prognostic value in patients with CRC.
Prognostic significance of the infiltration of CD163+ macrophages combined with CD66b+ neutrophils in gastric cancer
Authors: Huang Xiaopei , Pan Yamin , Ma Jun , Kang Zhengchun , Xu Xiaowen , Zhu Yan , Chen Jikuai , Zhang Wei , Chang Wenjun , Zhu Jiangbo 
Published: March 2018

AbstractThe polarization of tumor‐associated macrophages (TAMs) and tumor‐associated neutrophils (TANs), especially from the antitumoral phenotype to the protumoral phenotype under certain conditions, has an important influence on the progression of tumors. However, the interactions and combined prognosis of these cells are poorly known. Here, we detected the infiltration of CD68+ TAMs, CD163+ TAMs, and CD66b+ TANs in the specimens from 662 patients with GC by immunohistochemistry. The results showed that the infiltration of each of CD163+, CD68+, and CD66b+ cells in GC tissue was significantly increased and independently associated with GC prognosis. Strong collinearity (r = 0.690, P < 0.001) was found between the infiltration of CD163+ and CD68+ cells in GC, and multivariate Cox analysis confirmed the infiltration of CD163+ cells was a better predictor for prognosis than that of CD68+ cells. The combination of the infiltration of CD163+ and CD66b+ cells provided more accurate survival prediction than any individual marker. Patient subgroups with CD66blowCD163low (hazard ratio (HR) = 2.161; 95% confidence interval (CI) = 1.266–3.688; P < 0.001), CD66bhighCD163high (HR = 3.575; 95% CI = 2.155–5.933; P < 0.001), and CD66blowCD163high (HR = 7.514; 95% CI = 4.583–12.312; P < 0.001) were gradually associated with shorter DFS when compared with the subgroup with CD66bhighCD163low. The similar result was also for DSS among the subgroups. Moreover, the two‐marker model could more effectively discriminate the prognosis among the patients with chemotherapy than that among those without chemotherapy. We concluded that CD163+ TAMs were a more valuable prognostic marker than CD68+ TAMs, and CD163+ TAMs combined with CD66b+ TANs could more precisely predict the prognosis of patients with GC.
Intake of bean fiber, beans, and grains and reduced risk of hormone receptor‐negative breast cancer: the San Francisco Bay Area Breast Cancer Study
Authors: Sangaramoorthy Meera , Koo Jocelyn , John Esther M. 
Published: March 2018

AbstractHigh dietary fiber intake has been associated with reduced breast cancer risk, but few studies considered tumor subtypes defined by estrogen receptor (ER) and progesterone receptor (PR) status or included racial/ethnic minority populations who vary in their fiber intake. We analyzed food frequency data from a population‐based case–control study, including 2135 breast cancer cases (1070 Hispanics, 493 African Americans, and 572 non‐Hispanic Whites (NHWs)) and 2571 controls (1391 Hispanics, 557 African Americans, and 623 NHWs). Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer associated with fiber intake were calculated using unconditional logistic regression. Breast cancer risk associated with high intake (high vs. low quartile) of bean fiber (p‐trend = 0.01), total beans (p‐trend = 0.03), or total grains (p‐trend = 0.05) was reduced by 20%. Inverse associations were strongest for ER‐PR‐ breast cancer, with risk reductions associated with high intake ranging from 28 to 36%. For bean fiber, risk was reduced among foreign‐born Hispanics only, who had the highest fiber intake, whereas for grain intake, inverse associations were found among NHWs only. There was no evidence of association with fiber intake from vegetables and fruits or total intake of vegetables and fruits. A high dietary intake of bean fiber and fiber‐rich foods such as beans and grains may lower the risk of ER‐PR‐ breast cancer, an aggressive breast cancer subtype for which few risk factors have been identified.