bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 1, open‐label, dose escalation study of intravenous paricalcitol in combination with gemcitabine in patients with advanced malignancies
Authors: Fountzilas Christos , Javle Milind , Tan Wei , Ma Yingyu , Fetterly Gerald , Iyer Renuka , Johnson Candace 
Published: October 2018

AbstractBACKGROUNDCalcitriol, the active analogue of vitamin D, is antiproliferative and enhances the cytotoxicity of several anticancer agents, including gemcitabine. The vitamin D receptor (VDR) is expressed in the tumor stroma and treatment with VDR ligands results in stromal remodeling and increased intratumoral gemcitabine delivery. Furthermore, calcitriol can decrease the activity of the gemcitabine deactivating enzyme cytidine deaminase (CDD). Because hypercalcemia has been the most worrisome calcitriol‐related adverse event, the less hypercalcemic agent paricalcitol may be preferred for further investigation.METHODSThe authors undertook a phase 1 study of gemcitabine in combination with escalating doses of paricalcitol administered weekly intravenously in patients with advanced cancers. A standard 3+3 dose escalation schema was used. Pharmacokinetic assessment of gemcitabine and its metabolite 2’,2’‐difluorodeoxyuridine (dFdU) was performed. Pharmacodynamic assessment of paricalcitol was performed by measurement of CDD activity in peripheral blood mononuclear cells.RESULTSA total of 44 patients were enrolled. Somnolence was the main dose‐limiting toxicity. The highest dose of paricalcitol administered was 10.5 µg/kg. Hypercalcemia was infrequent and mild in severity. Paricalcitol did not appear to affect the pharmacokinetics of gemcitabine and dFdU. Evaluation of CDD activity was available for 9 patients; no clear trend for CDD activity after treatment with paricalcitol was established. The overall response rate was 4%; the rate of disease control was 67% in patients who were pretreated with gemcitabine. Progression‐free and overall survival were 3.4 months and 6.5 months, respectively.CONCLUSIONSParicalcitol can be administered safely in doses up to 7 µg/kg weekly with fixed dose rate gemcitabine without dose‐limiting hypercalcemia. To the best of the authors’ knowledge, the maximum tolerated dose has not been formally established to date. Preliminary clinical activity deserves further exploration.
Response to therapeutic monoclonal antibodies for multiple myeloma in African Americans versus whites
Authors: Chehab Sarah , Zhang Chao , Panjic Elyse H. , Chen Zhengjia , Kaufman Jonathan L. , Lonial Sagar , Nooka Ajay , Harvey R. Donald 
Published: October 2018

BackgroundMyeloma occurs disproportionately in African Americans, with disparities in outcomes potentially caused by access to care, cytogenetics, and immunity. A gap in knowledge of immune function dissimilarities between African Americans and whites exists. Data for other diseases suggest innate differences in immunity and inflammatory markers, with potential implications for therapeutic monoclonal antibodies reliant on secondary immune activation for activity.MethodsPatients receiving daratumumab or elotuzumab, lenalidomide, and dexamethasone were retrospectively studied with a primary endpoint of response at 2 (daratumumab) or 4 months (elotuzumab). Secondary endpoints included stable disease or better at the same points, treatment duration, time to best response, and adverse events.ResultsEighty patients were included; baseline characteristics were balanced with the exception of the stage at diagnosis, which was more advanced in African Americans. No statistically significant difference in response was seen: 37.9% in whites versus 11.8% in African Americans with daratumumab (P = .090) and 60% in whites versus 44% in African Americans with elotuzumab (P = .462). There were no differences in the duration of treatment, the time to best response, or adverse events. Common potential immune‐related adverse events in both arms were fatigue (39%), back pain (30%), and infusion reactions (40%). Anemia was significantly associated with a response to daratumumab (P = .02); no patients without anemia responded at 2 months, whereas 34.4% of patients with anemia did.ConclusionsNo significant difference in response, duration of treatment, or time to response was seen by race, although a trend toward greater early response rates in whites was observed. In these cohorts, as in other analyses, African American patients tended to present with later stage disease.
Co9S8‐Catalyzed Growth of Thin‐Walled Graphite Microtubes for Robust, Efficient Overall Water Splitting
Authors: Guo Mingrui , Liu Yi , Dong Shun , Jiao Xiuling , Wang Ting , Chen Dairong 
Published: October 2018

AbstractCo9S8 crystals can catalyze the growth of thin‐walled graphite microtubes (GMTs) through a catalytic chemical vapor deposition (CCVD) process using thiourea as the precursor. The growth of GMTs follows a tip‐growth mechanism with tube diameters up to a few micrometer. The hollow interiors of the GMTs are filled with carbon nanotubes and wrinkled graphene layers, which form a unique nanotube/graphene‐in‐microtube structure. As‐formed GMTs are N,S‐codoped with lots of Co9S8 nanoparticles encapsulated in their inner walls. These GMTs are room‐temperature ferromagnets and can be loaded on Ni foams to work as binder‐free electrocatalysts with low overpotential (310 mV at 50 mA cm−2 for the oxygen evolution reaction (OER) and 284 mV at 50 mA cm−2 for the hydrogen evolution reaction (HER)) and long‐term durability (continuous work for 120 h without loss in performance). Our research proves that metal sulfides can catalyze the growth of graphite microtubes and as‐formed GMTs may potentially be used as functional building blocks to construct new kinds of electrochemical devices for various energy‐related applications.
Microbial esterases and ester prodrugs: An unlikely marriage for combating antibiotic resistance
Authors: Larsen Erik M. , Johnson R. Jeremy 
Published: October 2018

AbstractThe rise of antibiotic resistance necessitates the search for new platforms for drug development. Prodrugs are common tools for overcoming drawbacks typically associated with drug formulation and delivery, with ester prodrugs providing a classic strategy for masking polar alcohol and carboxylic acid functionalities and improving cell permeability. Ester prodrugs are normally designed to have simple ester groups, as they are expected to be cleaved and reactivated by a wide spectrum of cellular esterases. However, a number of pathogenic and commensal microbial esterases have been found to possess significant substrate specificity and can play an unexpected role in drug metabolism. Ester protection can also introduce antimicrobial properties into previously nontoxic drugs through alterations in cell permeability or solubility. Finally, mutation to microbial esterases is a novel mechanism for the development of antibiotic resistance. In this review, we highlight the important pathogenic and xenobiotic functions of microbial esterases and discuss the development and application of ester prodrugs for targeting microbial infections and combating antibiotic resistance. Esterases are often overlooked as therapeutic targets. Yet, with the growing need to develop new antibiotics, a thorough understanding of the specificity and function of microbial esterases and their combined action with ester prodrug antibiotics will support the design of future therapeutics.
Circulating C1q/TNF‐related protein isoform 15 is a marker for the presence of metabolic syndrome
Authors: Mi Qiao , Li Yanxin , Wang Miao , Yang Gangyi , Zhao Xili , Liu Hua , Zheng Hongting , Li Ling 
Published: October 2018

AbstractBackgroundC1q/TNF‐related protein isoform 15 (CTRP15) has been reported to be related to glucose and lipid metabolism, but the results are inconsistent. Metabolic syndrome (MetS) is a cluster of metabolic disorders. The aim of this study is to determine circulating CTRP15 levels in individuals with MetS and investigate the association among circulating CTRP15 and markers for MetS as well as insulin resistance.MethodsA total of 341 individuals were recruited for this cross‐sectional study. These subjects were screened for MetS. Serum CTRP15 concentrations were measured by ELISA.ResultsSerum CTRP15 levels were significantly higher in MetS individuals relative to those of the healthy individuals. Circulating CTRP15 correlated positively with WHR, BMI, SBP, FAT %, 2 h‐BG, FIns, 2 h‐Ins, TG, FFA, HbA1c, HOMA‐IR, and AUCglucose, while negatively with HDL‐C and ISI. Multiple linear regression showed that HOMA‐IR and HDL‐C are independently related factors influencing serum CTRP15 concentrations. In addition, binary logistic regression analysis showed that serum CTRP15 concentrations were significantly related to MetS. When the mean concentrations of circulating CTRP15 in MetS subjects were stratified by the number of components of the MetS, circulating CTRP15 was found to increase progressively with increasing number of the MetS components. Finally, ROC curve analysis showed that the best cutoff values for circulating CTRP15 to predict MetS and insulin resistance were 63.6 and 64.0 μg/L.ConclusionsSerum CTRP15 concentrations were associated with the key components of MetS and insulin resistance.
Novel Calixarene/Carbon Nanotubes Based Screen Printed Sensors for Flow Injection Potentiometric Determination of Naproxen
Authors: Khaled Elmorsy , Shoukry Eman M. , Amin Mona F. , Said Basmat Amal M. 
Published: October 2018

AbstractNovel sensitive disposable sensors have been introduced for potentiometric determination of naproxen (NAP) based on single‐walled carbon nanotubes‐polyvinyl chloride (SWNTs‐PVC) composite incorporated of calix[4]arene as host‐guest molecular recognition element. The electrode matrix composition was optimized on the basis of the nature and content of the sensing element, cationic sites, plasticizer and nanomaterial. Remarkable selectivity and sensitivity towards NAP was achieved in the concentration range from 10−8 to 10−2 mol L−1 with anionic Nernstian compliance −61.0±0.0 mV decade−1. Modification with calixarene and carbon nanotubes improved the sensors performance through formation of NAP‐calixarene inclusion complex and promotion of the electron‐transfer processes which enhance the potential stability, response time, and shelf lifetime of the sensor. The proposed sensors were successfully applied for the potentiometric assay of NAP in dosage formulation and biological fluids under batch and flow injection analysis (FIA) conditions with average recoveries agreeable with the reported official methods.
An improved method for high‐efficiency coal mine methane drainage: Theoretical analysis and field verification
Authors: Liu Qingquan , Zhou Hongxing , Cheng Yuanping , Shu Longyong , Ullah Barkat 
Published: October 2018

AbstractDegassing a coal seam with in‐seam boreholes is an important method for mitigating the gas hazards in the underground coal mine. However, the low strength of the outburst‐proven coal limits the borehole sealing performance and borehole space maintaining, and thus influences the drainage performance of in‐seam boreholes. This study was conducted to seek a method to improve the sealing performance and borehole space maintaining for high‐efficiency CMM drainage. A visco‐elastic plastic model involving the plastic softening and dilatancy features for soft coal was proposed, and the deformation, shrinkage, and fracture characteristics of the coal surrounded a borehole and a roadway were analyzed. An enormous amount of connective fractures generated in the failure zone and the plastic zone, and the plastic zone develops timely for the creep behavior of coal, which aggravates the difficulties of borehole sealing. A comprehensive approach including the theoretical method and the technical method was developed to determine the proper sealing depth which can significantly influence the sealing performance. The sieve tubes made of high‐density polyethylene has been used to maintain the borehole space during the scheduled pre‐drainage period. A series of field tests were conducted in an outburst‐proven coal seam to verify the feasibility of the comprehensive approach and the borehole space maintaining method. Field tests showed that the comprehensive approach to determine the proper sealing depth and the installing of sieve tubes to protect the borehole space can provide favorable conditions for maximum CMM pre‐drainage from outburst‐prone coal and maximum utilization of the in‐seam boreholes.
Improved THINC/SW scheme for computing incompressible two‐phase flows
Authors: Qian Longgen , Wei Yanhong 
Published: October 2018

SummaryIn this paper, we propose an improved tangent of hyperbola for interface capturing with slope weighting (THINC/SW) scheme for computing incompressible two‐phase flows with surface tension on fixed Eulerian grids. The new scheme possesses the following major new properties in comparison with the original THINC/SW scheme: (i) providing a simple and accurate approach for generating a smooth level set (LS) field from the discontinuous volume‐of‐fluid field, (ii) determining the interface slope from the cogenerated LS field, and (iii) evaluating the surface tension force by the cogenerated LS field. We verified the proposed scheme with the widely used advection benchmark tests and multifluid simulations. Numerical results reveal that the new scheme can not only improve the solution quality of interface capturing but also increase the accuracy of curvature estimates and suppress the parasitic currents.
Bias in parameter estimates due to omitting gene–environment interaction terms in case‐control studies
Authors: Lobach Iryna 
Published: October 2018

AbstractGenetic studies are continuing to generate volumes and variety of data that can be used to examine the genetic effects. Often the effect of a genetic variant varies by nongenetic measures, what is traditionally defined as gene–environment interaction (G×E). If the G×E term is neglected, estimates of the main effects can be substantially biased. We derive a general and convenient approximation to the magnitude of bias in the estimates due to omitting the G×E term. We show that the approximation is reasonably accurate in finite samples. We then apply the approximation in a study of Alzheimer's disease.
Comparison of outcomes between hemithyroidectomy alone and hemithyroidectomy with elective unilateral central neck dissection in patients with papillary thyroid microcarcinoma
Authors: Son Ho Jin , Kim Jeong Kyu , Jung Young Do , Jang Gyu Ho , Seo Youn Tae , Kim Deok Su , Park Sung Hwan , Jeong Young Ju 
Published: October 2018

AbstractBackgroundThere have been arguments over the efficacy of elective unilateral central neck dissection (CND) in patients with papillary thyroid carcinoma (PTC) <1 cm who underwent hemithyroidectomy. This study was designed to investigate locoregional recurrence and postoperative complications related to elective unilateral CND for papillary thyroid microcarcinoma (PTMC).MethodsFive hundred thirty‐seven patients who underwent hemithyroidectomy, with or without CND for PTMC, were included. We compared locoregional recurrence and postoperative complication rates between 138 patients who underwent hemithyroidectomy only (CND group) and 399 patients who underwent hemithyroidectomy with elective unilateral CND (CND+ group).ResultsRecurrence was observed in 32 patients. Twenty‐two patients with recurrence were in the CND+ group and 10 were in the CND‐ group. Recurrence rate was not significantly different between the 2 groups (P = .434).ConclusionConcomitant unilateral elective CND did not enhance outcomes of hemithyroidectomy for the treatment of PTMC.
Peatland ditch blocking has no effect on dissolved organic matter (DOM) quality
Authors: Peacock Mike , Jones Tim G. , Futter Martyn N. , Freeman Chris , Gough Rachel , Baird Andrew J. , Green Sophie M. , Chapman Pippa J. , Holden Joseph , Evans Chris D. 
Published: October 2018

AbstractThe globally widespread drainage of peatlands has often been shown to lead to increased concentrations and fluxes of dissolved organic carbon (DOC) in streams and rivers. Elevated DOC concentrations have implications for carbon cycling, ecosystem functioning, and potable water treatment. Peatland rewetting, principally through ditch blocking, is often carried out with the expectation that this will reduce DOC concentrations. Uncertainty still remains as to whether drainage, or its reversal via ditch blocking, will also lead to changes in the molecular composition of DOC/dissolved organic matter (DOM), which have the potential to affect downstream processing and treatability of U.K. drinking water supplies. To investigate this question, we used a replicated experiment consisting of 12 parallel ditches on an upland bog and took samples of ditch water, pore water, and overland flow water for 4 years. After a brief preblocking baseline period, eight ditches were blocked using two methods. A complementary suite of optical metrics, chemical measurements, and analytical techniques revealed that ditch blocking had no consistent effect on DOM quality, up to 4 years after blocking. Where significant differences were found, effect size calculations demonstrated that these differences were small and would therefore have minimal impact upon water treatability. Furthermore, some differences between ditches were evident before blocking took place, highlighting the need for robust baseline monitoring before intervention. Based on our results from a hillslope‐scale experiment, we were unable to identify clear evidence that peatland ditch blocking will deliver benefits in terms of DOM treatability in potable water supplies, although we also did not find any evidence of short‐term deterioration in water quality during the restoration period. We conclude that, although peatland restoration can be expected to deliver other benefits such as reduced carbon loss and enhanced biodiversity, it is doubtful whether it will lead to improvements in drinking water treatability.
Inside Cover: In vivo photoacoustic/ultrasonic dual‐modality endoscopy with a miniaturized full field‐of‐view catheter (J. Biophotonics 10/2018)
Authors: Li Yan , Lin Riqiang , Liu Chengbo , Chen Jianhua , Liu Huadong , Zheng Rongqin , Gong Xiaojing , Song Liang 
Published: October 2018

In this study, a photoacoustic/ultrasonic dual‐modality endoscopic system with a miniaturized, encapsulated imaging catheter, which provides a full 360° field‐of‐view was developed. We conducted invivo rat studies to demonstrate the performance of this dual‐modality system. The results showed the typical morphology and vasculature, which is valuable for evaluating the gastrointestinal tract.Further details can be found in the article by Yan Li, Riqiang Lin, Chengbo Liu, et al. (e201800034).
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LINC00152 promotes the proliferation of gastric cancer cells by regulating B‐cell lymphoma‐2
Authors: Mao Ye , Tie Yan , Du Jing , He Jianping 
Published: October 2018

AbstractLINC00152 has been considered to be associated with the tumorigenesis and the occurrence of gastric cancer; however, the mechanism of LINC00152 has yet to be fully elucidated. In the present study, the expression levels of LINC00152 in tissues, serum, and peripheral blood mononuclear cells (PBMCs) of patients with gastric cancer were determined using real‐time polymerase chain reaction. The functions of LINC00152 with respect to the proliferation, apoptosis, migration, and invasive abilities of the gastric cancer cells were evaluated by cell proliferation analysis, flow cytometry, cell scratch wound assay, and transwell migration experiments. A mouse xenotransplant model of gastric tumors was established to detect the role of LINC00152 in vivo, and the expression levels of B‐cell lymphoma‐2 (Bcl‐2) family proteins were investigated by Western blot analysis. The results revealed that LINC00152 was overexpressed in tissues, serum, and PBMCs of patients with gastric cancer. Moreover, LINC00152 could promote the migration and invasive abilities and suppress the apoptosis, of gastric cancer cells through regulating the Bcl‐2 protein family. LINC00152 could bind with Bcl‐2 directly to induce the activation of cell cycle signaling, and this may be a potential target for the therapy of gastric cancer in the future.
Long noncoding RNA PVT1 promotes laryngeal squamous cell carcinoma development by acting as a molecular sponge to regulate miR‐519d‐3p
Authors: Zheng Xiling , Zhao Kang , Liu Tao , Liu Lei , Zhou Changming , Xu Min 
Published: October 2018

AbstractObjectiveThis study was designed to investigate the effects and mechanism of long noncoding RNA (lncRNA) PVT1 on cell migration, proliferation, and apoptosis of laryngeal squamous cell carcinoma (LSCC).MethodsWe screened lncRNAs expression profiles in four pair LSCC and matched noncancerous tissues by microarray assay. The messenger RNA levels of PVT1 in tissues and cells were evaluated by quantitative real‐time polymerase chain reaction analysis. StarBase website was used to predict the target miRNAs for PVT1. And the interaction between PVT1 and target miRNA‐519d‐3p in LSCC cells was analyzed using dual‐luciferase reporter assay. MTT assay was used to investigate the cell viability. Cell counting assay was used to explore the cell proliferation. Annexin‐V propidium iodide flow cytometry was used to examine the cell apoptosis, and transwell assay was used to investigate the effects of lncRNA PVT1 on cell migration.ResultsPVT1 was significantly overexpressed in human LSCC tissues and several LSCC cell lines. Upregulation of lncRNA PVT1 markedly facilitated proliferation suppressed apoptosis and promoted cell migration in LSCC cells. We further demonstrated that silencing PVT1 strikingly suppressed proliferation, promoted apoptosis, and reduced migration in LSCC cells. Further bioinformatic analysis and dual‐luciferase reporter assay revealed that PVT1 could function as an oncogenic transcript partly through sponging miR‐519d‐3p. Besides, mechanistic investigations indicated that PVT1 could promote cell and migration through interacting with miR‐519d‐3p.ConclusionLncRNA PVT1 is consistently overexpressed in human LSCC, and overexpression of lncRNA PVT1 contributes to the proliferation and migration of LSCC through inhibiting miR‐519d‐3p expression.