bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comorbidities predict inferior outcomes in chronic lymphocytic leukemia treated with ibrutinib
Authors: Gordon Max J. , Churnetski Michael , Alqahtani Hamood , Rivera Xavier , Kittai Adam , Amrock Stephen M. , James Spencer , Hoff Sheila , Manda Sudhir , Spurgeon Stephen E. , Choi Michael , Cohen Jonathon B. , Persky Daniel , Danilov Alexey V. 
Published: May 2018

BACKGROUNDMost patients with chronic lymphocytic leukemia (CLL) present with multiple comorbidities. Although comorbidities negatively affect outcomes for patients treated with chemoimmunotherapy, their impact on patients who receive targeted therapies is unknown.METHODSThis multicenter, retrospective analysis evaluated the significance of comorbidities, as assessed by the Cumulative Illness Rating Scale (CIRS), among patients with CLL treated with ibrutinib.RESULTSOne hundred forty‐five patients received ibrutinib (80% in a relapsed/refractory setting). A high burden of comorbidities (CIRS score ≥ 7) was associated with inferior median event‐free survival (EFS; 24 vs 37 months; P = .003) and 2‐year overall survival (OS; 79% vs 100%; P = .005). In an adjusted Cox model, both EFS and OS worsened with an incremental increase in the CIRS score. Furthermore, comorbidities were associated with an increased risk of ibrutinib dose reduction and therapy discontinuation. CIRS was predictive in both frontline and relapsed CLL, regardless of patient age.CONCLUSIONSComorbidities portend a poor prognosis among patients with CLL treated with ibrutinib. Prospective studies are needed to optimize the treatment of patients with CLL who have comorbidities. Cancer 2018. © 2018 American Cancer Society.
Cytopathologic features of SMARCB1 (INI‐1)‐deficient sinonasal carcinoma
Authors: Allard Felicia D. , Bell Diana , Stelow Edward B. 
Published: May 2018

BACKGROUNDSMARCB1 (INI‐1)‐deficient sinonasal carcinoma (IDSNC) is a newly described, poorly differentiated carcinoma. Herein, the authors describe the cytopathologic features of IDSNC in fine‐needle aspiration (FNA) samples.METHODSThe pathology archives of 2 academic institutions were searched for cases of IDSNC with available cytologic materials. All available slides were reviewed and a detailed morphological analysis was performed.RESULTSSix cases were identified from 6 patients. FNA specimens were obtained from metastatic sites (4 cases), a local disease recurrence (1 case), and a primary lesion extending into the orbit (1 case). The majority of cases had cellular specimens with features of nonkeratinizing squamous cell carcinoma composed of cohesive clusters and sheets of oval to polygonal cells with indistinct cell borders present within a background of necrotic debris. Two cases had single rhabdoid cells with more abundant cytoplasm. The nuclei generally were small and uniform with fine chromatin, small nucleoli, and mild nuclear membrane irregularities; moderate anisonucleosis and multinucleation were noted in one case. Apoptotic bodies were common in 5 of 6 cases, and readily identifiable mitoses in 3 of 6 cases. Immunohistochemistry demonstrated that all cases expressed cytokeratins, 4 of 5 cases expressed p63, and all cases demonstrated loss of INI‐1 nuclear expression. All cases were negative for neuroendocrine markers and aberrant p16 staining.CONCLUSIONSA diagnosis of IDSNC can be suspected on FNA specimens from patients with high‐grade sinonasal carcinomas that have either a nonkeratinizing squamous cell carcinoma or rhabdoid morphology. Clinical history and the availability of material for immunohistochemistry are key in confirming the diagnosis. Cancer Cytopathol 2018. © 2018 American Cancer Society.
Cloud parallel spatial‐temporal data model with intelligent parameter adaptation for spatial‐temporal big data
Authors: Zhu Dingju 
Published: May 2018

SummaryWith the fast development of earth observation technology and internet of things technology, the spatial‐temporal data can be obtained with higher speed and lower cost, and spatial‐temporal big data management with existing spatial‐temporal data model has become one of the bottlenecks of spatial‐temporal applications such as e‐government construction, digital city, and smart city. Cloud parallel spatial‐temporal data model with intelligent parameter adaptation for spatial‐temporal big data provided in this paper is able to divide a spatial‐temporal problem into a lot of subdivided spatial‐temporal problems and to map the subdivided problems onto different cloud parallel computing nodes to process. This paper includes the concept, division methods, and mathematical formulas of cloud parallel spatial‐temporal data model and provides the method to intelligently find the best parameter of cloud parallel spatial‐temporal data model for solving the problem with highest parallel speedup or highest parallel efficiency in cloud parallel computing environment.
Efficient Fabrication of Stable Graphene‐Molecule‐Graphene Single‐Molecule Junctions at Room Temperature
Authors: Sun Hantao , Jiang Zhuoling , Xin Na , Guo Xuefeng , Hou Shimin , Liao Jianhui 
Published: May 2018

AbstractWe present a robust approach to fabricate stable single‐molecule junctions at room temperature using single‐layer graphene as nanoelectrodes. Molecular scale nano‐gaps in graphene were generated using an optimized fast‐speed feedback‐controlled electroburning process. This process shortened the time for creating a single nano‐gap to be less than one minute while keeping a yield higher than 97 %. To precisely control the gap position and minimize the effects of edge defects and the quantum confinement, extra‐narrow grooves were pre‐patterned in the graphene structures with oxygen plasma etching. Molecular junctions were formed by bridging the nano‐gaps with amino‐functionalized hexaphenyl molecules by taking advantage of chemical reactions between the amino groups at the two ends of the molecules and the carboxyl groups at the edges of graphene electrodes. Electronic transport measurements and transition voltage spectroscopy analysis verified the formation of single‐molecule devices. First‐principles quantum transport calculations show that the highest occupied molecular orbital of hexaphenyl is closer to the Fermi level of the graphene electrodes and thus the devices exhibit a hole‐type transport characteristics. Some of these molecular devices remained stable up to four weeks, highlighting the potential of graphene nano‐electrodes in the fabrication of stable single‐molecule devices at room temperature.
Chromatographic behavior of new deazapurine ribonucleosides in hydrophilic interaction liquid chromatography
Authors: Kalíková Květa , Voborná Markéta , Tesařová Eva 
Published: May 2018

AbstractThe chromatographic behavior of new biogenic purine nucleosides in hydrophilic interaction liquid chromatography was examined on three different stationary phases, namely bare silica, and amide‐ and cyclofructan‐based stationary phases. The effects of buffer concentration, pH and acetonitrile‐to‐aqueous‐part ratio in the mobile phase on retention and peak shape were assessed. The retention coefficients and peak symmetry values substantially differed with respect to analytes´ structures, stationary phase properties and mobile phase composition. The bare silica column was unsuitable for these compounds under the chromatographic conditions tested due to very broad and asymmetrical peaks. Furthermore, the cyclofructan‐based stationary phase provided almost Gaussian peak shapes of all deazapurine nucleosides under most conditions tested. Therefore, the cyclofructan‐based stationary phase is the most suitable choice for the chromatographic analysis of nucleosides.
Non‐Gaussian autoregressive processes with Tukey ‐and‐htransformations
Authors: Yan Yuan , Genton Marc G. 
Published: May 2018

AbstractWhen performing a time series analysis of continuous data, for example, from climate or environmental problems, the assumption that the process is Gaussian is often violated. Therefore, we introduce two non‐Gaussian autoregressive time series models that are able to fit skewed and heavy‐tailed time series data. Our two models are based on the Tukey‐and‐htransformation. We discuss parameter estimation, order selection, and forecasting procedures for our models and examine their performances in a simulation study. We demonstrate the usefulness of our models by applying them to two sets of wind speed data.
Resilience and social support as protective factors against abuse of patients with dementia: A study on family caregivers
Authors: Serra Lídia , Contador Israel , Fernández‐Calvo Bernardino , Ruisoto Pablo , Jenaro Cristina , Flores Noelia , Ramos Francisco , Rivera‐Navarro Jesús 
Published: May 2018

ObjectiveScientific literature has identified different vulnerability factors associated to abuse in people with dementia (PWD), but little is known about the psychosocial protective variables against abuse. The main objective of this study is to investigate a set of caregiver and patient factors linked to abuse‐related behavior of PWD.MethodsA total of 326 primary and family caregivers, residents of the Castilla and León community (Spain), were evaluated. All participants filled out a standardized protocol, which assessed the sociodemographic characteristics, patient and care‐related variables, as well as the perceived burden, resilience, and social support. Abuse‐related behavior was evaluated using the Caregiver Abuse Screen.ResultsResults show that the severity of cognitive impairment and behavior disorders of PWD, a greater number of caregiving hours, a worse previous relationship with the caregiver, and perceived burden are positively related with abuse. However, resilience and social support showed a negative relationship with Caregiver Abuse Screen scores, suggesting a protective effect on abuse, even after controlling the effect of a number of covariates. Indeed, resilience was the only variable that remained significant after including the effect of burden.ConclusionsThis paper states the role of burden in abuse of PWD, while resilience and social support are abuse protective factors. These variables should be considered in future guidelines for the prevention of abuse against PWD.
Hemin provides protection against lead neurotoxicity through heme oxygenase 1/carbon monoxide activation
Authors: Ye Fang , Li Xiaoyi , Liu Yawen , Chang Wei , Liu Wenqi , Yuan Jing , Chen Jun 
Published: May 2018

AbstractThe neurotoxicity of lead (Pb) is well established, and oxidative stress is strongly associated with Pb‐induced neurotoxicity. Heme oxygenase 1 (HO‐1) is an important antioxidative enzyme for protection against oxidative stress in many disease models. In this study, we applied hemin, the substrate and a well‐known inducer of HO‐1, to investigate the possible role of HO‐1 in protecting against Pb neurotoxicity. Hemin can significantly attenuate Pb acetate‐induced cell death and oxidative stress in the hippocampus and frontal cortex of developmental rats. Consistent with in vivo results, the protective effects of hemin were also observed in SH‐SY5Y cells after inducing cell survival and maintaining redox balance. However, knocking down HO‐1 could significantly abolish the cytoprotective action of hemin against Pb toxicity, confirming HO‐1 contributed to the protection. Finally, the HO‐1‐derived production of carbon monoxide, but not of bilirubin or Fe2+, mediated the protective effects of HO‐1 activation induced by hemin treatment against Pb‐induced cell death and oxidative stress in SHSY5Y cells. Overall, this study showed that hemin provided protection against Pb neurotoxicity by HO‐1/carbon monoxide activation.
Genome‐wide analysis reveals that altered methylation in specific CpG loci is associated with childhood obesity
Authors: Li Yun , Zhou Yahui , Zhu Lijun , Liu Guiyou , Wang Xing , Wang Xingyun , Wang Jian , You Lianghui , Ji Chenbo , Guo Xirong , Zhao Yingmin , Cui Xianwei 
Published: May 2018

AbstractOver the past decades, the epidemic of childhood obesity has greatly increased, and it has recently become a global public health concern. Methylation, serving as a crucial regulator of the gene‐environment interaction, has exhibited a strong association with obesity. In this study, we aimed to evaluate the relationship between DNA methylation and childhood obesity, and further uncover the potential association of aberrantly methylated genes with obesity. DNA samples of peripheral blood leukocytes from three obese subjects (mean BMI: 21.67) and 4 age/sex matched controls (mean BMI: 14.92) were subjected to Infinium Human Methylation 450 Bead Array analysis. A total of more than 4 85 000 methylation sites were identified across the genome, and 226 methylated CpGs (DMCpGs) were differentially methylated between these two groups. Subsequent Gene Ontology (GO) and KEGG Pathway analyses showed that these DMCpGs were mainly engaged in immunity and lipoprotein metabolism, indicating their physiological significance. Further verification of the candidate CpG sites within the HDAC4, RAX2, APOA5, CES1, and SLC25A20 gene loci, were performed using bisulfite sequencing PCR (BSP) in a cohort of 42 controls and 39 obese cases. The results revealed that methylation levels within HDAC4 and RAX2 loci were positively associated with obesity, while the methylation levels of loci within APOA5 and CES1 loci were negatively correlated with obesity. Thus, alterations in methylation of CpG sites of specific genes may contribute to childhood obesity, which provide novel insights into the aetiology of obesity.
High accuracy of proximity extension assay technology for the quantification of plasma brain natriuretic peptide
Authors: Arrigo Mattia , Vodovar Nicolas , Von Moos Seraina , Masson Elisabeth , Segerer Stephan , Cippà Pietro E. , Mebazaa Alexandre 
Published: May 2018

BackgroundNovel multiplex assays allow the simultaneous identification of a large number of plasma proteins. While these new technologies have been shown to be highly sensitive and accurate for the identification of plasma proteins, the use of this technology to quantify those proteins has not been properly investigated. In this pilot study, we tested the accuracy of the proximity extension assay (PEA) for the quantification of the cardiac biomarker brain natriuretic peptide (BNP) compared to a standard clinically approved method.MethodsConcentrations of BNP were assessed in 120 plasma samples from 30 patients with PEA and compared to chemiluminescent microparticle immunoassay (CMIA). Venous blood samples were collected from in tubes containing ethylenediaminetetraacetic acid, centrifuged within 6 hours at 3,500 rpm for 15 minutes at 4°C, frozen and stored at −80°C until analyzed. Correlation between the CMIA and PEA techniques was tested using the Spearman’s rank correlation coefficient (rho) and the agreement was described with a Bland‐Altman plot.ResultsBrain natriuretic peptide values obtained by CMIA and PEA were highly correlated (Spearman’s rho = 0.865, P < .0001). In two patients, PEA consistently overestimated resp. underestimated BNP values compared to CMIA. After removal of those two patients, a very high correlation between the two techniques was shown (rho = 0.966, P < .0001). A high agreement between the two techniques over the whole range of tested concentrations was shown.ConclusionThis pilot study showed for the first time an excellent correlation between a clinically approved method and the PEA‐based approach for quantification of circulating plasma BNP.
Sequence variations of Epstein‐Barr virus‐encoded BARF1 gene in nasopharyngeal carcinomas and healthy donors from southern and northern China
Authors: Liu Jincheng , Ji Xinqiang , Shen Zhichao , Wang PhD Yun , Luo PhD Bing 
Published: May 2018

The BamHI A rightward frame 1 (BARF1) gene of the Epstein‐Barr virus (EBV) is involved in carcinogenesis and immunomodulation of EBV‐associated malignancies. The geographical distributions and the disease associations of BARF1 variants remain unclear. In the current study, the BARF1 variants in nasopharyngeal carcinoma (NPC) cases and healthy donors from southern and northern China, the NPC endemic and non‐endemic areas, as well as in 153 sequenced EBV genomes from diseased and normal people from around the world, were determined and compared among areas and populations. Only 1 consistent coding change, V29A, and several consistent silent mutations were identified. Two BARF1 types (B95‐8 and V29A) and 2 B95‐8 subtypes (B95‐8t165545c and B95‐8P) were classified. For Chinese isolates, the B95‐8 type was dominant in both southern and northern China, but the isolates from southern China showed a higher frequency of the B95‐8t165545c subtype than the isolates from northern China (76.0%, 38/50 NPC cases and 50.7%, 37/73 healthy donors vs 26.4%, 24/91 NPC cases and 7.6%, 6/79 healthy donors, P < .0001). Furthermore, the B95‐8t165545c subtype was more frequent in NPC cases than healthy donors in both southern China (P = .005) and northern China (P = .001). For EBV genomes, the B95‐8P subtype was dominant in northern China, Europe, America, and Australia, while V29A was dominant in Africa. The B95‐8t165545c subtype was only identified in Asia and demonstrated high frequency (81.2%, 26/32) in genomes from NPC cases in southern China. These results further reveal conservation and possibly geographically spread variations of BARF1 and may also indicate the preference of EBV strains with the B95‐8t165545c subtype in NPC cases, without biological or pathogenic implications.
Determinants of the presence of human papillomaviruses in the anal canal of Russian men
Authors: Smelov Vitaly , Elfström K. Miriam , Eklund Carina , Sokolova Olga , Dillner Joakim 
Published: May 2018

Knowledge of determinants of anal human papillomavirus (HPV) infections among men is still limited as most of the studies are focused on high‐risk populations and geographically narrowed. Such knowledge obtained in different populations is essential for better understanding of HPV natural history, transmission dynamics, and its role in the development and prevention of anogenital malignancies in different regions. Here we tested anal canal swab samples from 359 Russian heterosexual (323 human immunodeficiency virus [HIV]‐negative and 27 HIV‐positive, aged 18‐67 years) men attending a sexually transmitted infection clinic 36 HPV types using a proficient Luminex assay. HPV‐positivity in anal samples was common for 332 HIV‐negative heterosexual men for overall HPV (15.7%, n = 52), oncogenic HPV (9.6%, n = 32), nononcogenic HPV (8.1%, n = 27), and multiple HPV infections (4.5%, n = 14). The most common anal HPV types were HPV16 (5.7%), HPV45, and HPV51 (1.8% each), HPV66, and HPV87 (1.8% each). No association was found with the number of lifetime sexual partners, age of participants at the time of the study, or their sexual debut. Although anal HPV positivity was more common among HIV‐positive men, the current study provides additional evidence that anal HPV can be frequently detected in heterosexual HIV‐negative men favoring further studies on transmission routes to discriminate between contamination and true HPV infection.
Anterior longitudinal ligament in diffuse idiopathic skeletal hyperostosis: Ossified or displaced?
Authors: Kuperus Jonneke S. , Smit Esther J. M. , Pouran Behdad , van Hamersvelt Robbert W. , van Stralen Marijn , Seevinck Peter R. , Buckens Constantinus F. , Bleys Ronald L. A. W. , Weinans Harrie H. , Oner F. Cumhur , de Jong Pim A. , Verlaan Jorrit‐Jan 
Published: May 2018

ABSTRACTDiffuse idiopathic skeletal hyperostosis (DISH) is often theorized to be an ossification of the anterior longitudinal ligament (ALL). Using computed tomography (CT) imaging and cryomacrotome sectioning, we investigated the spatial relationship between the ALL and newly formed bone in DISH to test this hypothesis. In the current study, four human cadaveric spines diagnosed with DISH using CT imaging were frozen and sectioned using a cryomacrotome. Photographs were obtained of the specimen at 125 µm intervals. Manual segmentations of the ALL on cryomacrotome photographs were projected onto the three‐dimensional reconstructed CT scans. The presence and location of newly formed bone were assessed in relationship to the location of the ALL. The ALL could be identified and segmented on the photographs at all levels. The ALL was located at the midline at levels where no new bone had formed. At the locations where new bone had abundantly formed, the ALL was displaced towards to the contralateral side and not replaced by bony tissue. The displacement of the—morphologically normal appearing—ALL away from the newly formed bone implies that newly formed bone in DISH may not originate from the ALL. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 36:2491–2496, 2018.
Evaluating the role of subacromial impingement in rotator cuff tendinopathy: Development and analysis of a novel murine model
Authors: Cong Guang‐Ting , Lebaschi Amir H. , Camp Christopher L. , Carballo Camila B. , Nakagawa Yusuke , Wada Susumu , Deng Xiang‐Hua , Rodeo Scott A. 
Published: May 2018

ABSTRACTSubacromial impingement of the rotator cuff is understood as a contributing factor in the development of rotator cuff tendinopathy. However, changes that occur in the impinged tendon are poorly understood and warrant further study. To enable further study of rotator cuff tendinopathy, we performed a controlled laboratory study to determine feasibility and baseline characteristics of a new murine model for subacromial impingement. This model involves surgically inserting a microvascular clip into the subacromial space in adult C57Bl/6 mice. Along with a sham surgery arm, 90 study animals were distributed among time point groups for sacrifice up to 6 weeks. All animals underwent bilateral surgery (total N = 180). Biomechanical, histologic, and molecular analyses were performed to identify and quantify the progression of changes in the supraspinatus tendon. Decreases in failure force and stiffness were found in impinged tendon specimens compared to sham and no‐surgery controls at all study time points. Semi‐quantitative scoring of histologic specimens demonstrated significant, persistent tendinopathic changes over 6 weeks. Quantitative real‐time polymerase chain reaction analysis of impinged tendon specimens demonstrated persistently increased expression of genes related to matrix remodeling, inflammation, and tendon development. Overall, this novel murine subacromial impingement model creates changes consistent with acute tendonitis, which may mimic the early stages of rotator cuff tendinopathy. A robust, simple, and reproducible animal model of rotator cuff tendinopathy is a valuable research tool to allow further studies of cellular and molecular mechanisms and evaluation of therapeutic interventions in rotator cuff tendinopathy. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2780–2788, 2018.