bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecotoxicity of bisphenol S to Caenorhabditis elegans by prolonged exposure in comparison with bisphenol A
Authors: Zhou Dong
Published: June 2018

Because of increasing concerns about its toxic effects, bisphenol A (BPA) has been gradually replaced in industrial applications by analogs such as bisphenol S (BPS). Few comparative toxicity evaluations of bisphenol analogs have been done. In the present study, 72-h exposure in L1 larvae of the model animal Caenorhabditis elegans was used to evaluate low-concentration BPS toxicity. Multiple indicators at the physiological, biochemical, and molecular levels were tested. At the physiological level, BPS exposure resulted in significantly negative effects at treatments >1 µM, with head thrash being the most sensitive endpoint. At the biochemical level, BPS exposure induced no significant oxidative stress, but significantly increased apoptosis at 1 µM. At the molecular level, BPS exposure induced small but significant variations in most stress-related gene expressions at all doses. In addition, the transgenic nematode TJ375 cell line with the green fluorescent protein–based reporter hsp-16.2 was used to determine stress responses; it was found that TJ375 was not sensitive to BPS exposure. Compared with the effects of BPA shown in our previous 2016 study, the overall results showed that BPS was less noxious to C. elegans than BPA. These toxicity data for BPS could provide a foundation to evaluate the comparative toxicity of BPA alternatives. Environ Toxicol Chem 2018;37:2560–2565. © 2018 SETAC
Dissociations of cognitive inhibition, response inhibition, and emotional interference: Voxelwise ALE meta‐analyses of fMRI studies
Authors: Hung Yuwen , Gaillard Schuyler L. , Yarmak Pavel , Arsalidou Marie
Published: June 2018

Inhibitory control is the stopping of a mental process with or without intention, conceptualized as mental suppression of competing information because of limited cognitive capacity. Inhibitory control dysfunction is a core characteristic of many major psychiatric disorders. Inhibition is generally thought to involve the prefrontal cortex; however, a single inhibitory mechanism is insufficient for interpreting the heterogeneous nature of human cognition. It remains unclear whether different dimensions of inhibitory processes—specifically cognitive inhibition, response inhibition, and emotional interference—rely on dissociated neural systems. We conducted systematic meta‐analyses of fMRI studies in the BrainMap database supplemented by PubMed using whole‐brain activation likelihood estimation. A total of 66 study experiments including 1,447 participants and 987 foci revealed that while the left anterior insula was concordant in all inhibitory dimensions, cognitive inhibition reliably activated specific dorsal frontal inhibitory system, engaging dorsal anterior cingulate, dorsolateral prefrontal cortex, and parietal areas, whereas emotional interference reliably implicated a ventral inhibitory system, involving the ventral surface of the inferior frontal gyrus and the amygdala. Response inhibition showed concordant clusters in the fronto‐striatal system, including the dorsal anterior cingulate region and extended supplementary motor areas, the dorsal and ventral lateral prefrontal cortex, basal ganglia, midbrain regions, and parietal regions. We provide an empirically derived dimensional model of inhibition characterizing neural systems underlying different aspects of inhibitory mechanisms. This study offers a fundamental framework to advance current understanding of inhibition and provides new insights for future clinical research into disorders with different types of inhibition‐related dysfunctions.
Regional structural hypo‐ and hyperconnectivity of frontal–striatal and frontal–thalamic pathways in behavioral variant frontotemporal dementia
Authors: Jakabek David , Power Brian D. , Macfarlane Matthew D. , Walterfang Mark , Velakoulis Dennis , van Westen Danielle , Lätt Jimmy , Nilsson Markus , Looi Jeffrey C. L. , Santillo Alexander F.
Published: June 2018

Behavioral variant frontotemporal dementia (bvFTD) has been predominantly considered as a frontotemporal cortical disease, with limited direct investigation of frontal–subcortical connections. We aim to characterize the grey and white matter components of frontal–thalamic and frontal–striatal circuits in bvFTD. Twenty‐four patients with bvFTD and 24 healthy controls underwent morphological and diffusion imaging. Subcortical structures were manually segmented according to published protocols. Probabilistic pathways were reconstructed separately from the dorsolateral, orbitofrontal and medial prefrontal cortex to the striatum and thalamus. Patients with bvFTD had smaller cortical and subcortical volumes, lower fractional anisotropy, and higher mean diffusivity metrics, which is consistent with disruptions in frontal–striatal–thalamic pathways. Unexpectedly, regional volumes of the striatum and thalamus connected to the medial prefrontal cortex were significantly larger in bvFTD (by 135% in the striatum, p = .032, and 217% in the thalamus, p = .004), despite smaller dorsolateral prefrontal cortex connected regional volumes (by 67% in the striatum, p = .002, and 65% in the thalamus, p = .020), and inconsistent changes in orbitofrontal cortex connected regions. These unanticipated findings may represent compensatory or maladaptive remodeling in bvFTD networks. Comparisons are made to other neuropsychiatric disorders suggesting a common mechanism of changes in frontal–subcortical networks; however, longitudinal studies are necessary to test this hypothesis.
Heat transfer in the flow of blood‐gold Carreau nanofluid induced by partial slip and buoyancy
Authors: Koriko Olubode K , Animasaun IL , Mahanthesh B , Saleem S , Sarojamma G , Sivaraj R
Published: June 2018

Dynamics of blood containing gold nanoparticles on a syringe and other objects with a nonuniform thickness is of importance to experts in the industry. This study presents the significance of partial slip (i.e. combination of linear stretching and velocity gradient) and buoyancy on the boundary layer flow of blood‐gold Carreau nanofluid over an upper horizontal surface of a paraboloid of revolution (uhspr). In this report, the viscosity of the Carreau fluid corresponding to an infinite shear‐rate is assumed as zero, meanwhile, the viscosity corresponding to zero shear‐rate, density, thermal conductivity, and heat capacity were assumed to vary with the volume fraction of nanoparticles. The governing equation that models the transport phenomenon were non‐dimensionalized and parameterized using suitable similarity variables and solved numerically using classical Runge–Kutta method with shooting techniques and MATLAB bvp4c package for validation. The results show that temperature distribution across the flow decreases more significantly with buoyancy‐related parameter when the influence of partial slip was maximized. Maximum velocity of the flow is ascertained at larger values of partial slip and buoyancy parameters. At smaller values of Deborah number and large values of volume fraction, maximum local skin friction coefficient, and local heat transfer rate are ascertained.
Circulating tumor DNA analysis enables molecular characterization of pediatric renal tumors at diagnosis
Authors: Jiménez Irene , Chicard Mathieu , Colmet‐Daage Léo , Clément Nathalie , Danzon Adrien , Lapouble Eve , Pierron Gaelle , Bohec Mylène , Baulande Sylvain , Berrebi Dominique , Fréneaux Paul , Coulomb Aurore , Galmiche‐Rolland Louise , Sarnacki Sabine , Audry Georges , Philippe‐Chomette Pascale , Brisse Hervé J. , Doz François , Michon Jean , Delattre Olivier , Schleiermacher Gudrun
Published: June 2018

Circulating tumor DNA (ctDNA) is a powerful tool for the molecular characterization of cancer. The most frequent pediatric kidney tumors (KT) are Wilms’ tumors (WT), but other diagnoses may occur. According to the SIOP strategy, in most countries pediatric KT have a presumptive diagnosis of WT if they are clinically and radiologically compatible. The histologic confirmation is established after post‐chemotherapy nephrectomy. Thus, there is a risk for a small fraction of patients to receive neoadjuvant chemotherapy that is not adapted to the disease. The aim of this work is to perform molecular diagnosis of pediatric KT by tumor genetic characterization based on the analysis of ctDNA. We analyzed ctDNA extracted from plasma samples of 18 pediatric patients with KT by whole‐exome sequencing and compared the results to their matched tumor and germline DNA. Copy number alterations (CNAs) and single nucleotide variations (SNVs) were analyzed. We were able to detect tumor cell specific genetic alterations—CNAs, SNVs or both—in ctDNA in all patients except in one (for whom the plasma sample was obtained long after nephrectomy). These results open the door to new applications for the study of ctDNA with regards to the molecular diagnosis of KT, with a possibility of its usefulness for adapting the treatment early after diagnosis, but also for disease monitoring and follow up.
Profiles of brain metastases: Prioritization of therapeutic targets
Authors: Ferguson Sherise D. , Zheng Siyuan , Xiu Joanne , Zhou Shouhao , Khasraw Mustafa , Brastianos Priscilla K. , Kesari Santosh , Hu Jethro , Rudnick Jeremy , Salacz Michael E. , Piccioni David , Huang Suyun , Davies Michael A. , Glitza Isabella C. , Heymach John V. , Zhang Jianjun , Ibrahim Nuhad K. , DeGroot John F. , McCarty Joseph , O'Brien Barbara J. , Sawaya Raymond , Verhaak Roeland G.W. , Reddy Sandeep K. , Priebe Waldemar , Gatalica Zoran , Spetzler David , Heimberger Amy B.
Published: June 2018

We sought to compare the tumor profiles of brain metastases from common cancers with those of primary tumors and extracranial metastases in order to identify potential targets and prioritize rational treatment strategies. Tumor samples were collected from both the primary and metastatic sites of nonsmall cell lung cancer, breast cancer and melanoma from patients in locations worldwide, and these were submitted to Caris Life Sciences for tumor multiplatform analysis, including gene sequencing (Sanger and next‐generation sequencing with a targeted 47‐gene panel), protein expression (assayed by immunohistochemistry) and gene amplification (assayed by in situ hybridization). The data analysis considered differential protein expression, gene amplification and mutations among brain metastases, extracranial metastases and primary tumors. The analyzed population included: 16,999 unmatched primary tumor and/or metastasis samples: 8,178 nonsmall cell lung cancers (5,098 primaries; 2,787 systemic metastases; 293 brain metastases), 7,064 breast cancers (3,496 primaries; 3,469 systemic metastases; 99 brain metastases) and 1,757 melanomas (660 primaries; 996 systemic metastases; 101 brain metastases). TOP2A expression was increased in brain metastases from all 3 cancers, and brain metastases overexpressed multiple proteins clustering around functions critical to DNA synthesis and repair and implicated in chemotherapy resistance, including RRM1, TS, ERCC1 and TOPO1. cMET was overexpressed in melanoma brain metastases relative to primary skin specimens. Brain metastasis patients may particularly benefit from therapeutic targeting of enzymes associated with DNA synthesis, replication and/or repair.
Glucocorticoid Exposure and Fracture Risk in a Cohort of US Patients With Selected Conditions
Authors: Balasubramanian Akhila , Wade Sally W , Adler Robert A , Saag Kenneth , Pannacciulli Nicola , Curtis Jeffrey R
Published: June 2018

The purpose of this work was to evaluate systemic glucocorticoid exposure and fracture among patients with newly-diagnosed inflammatory and immune-modulated conditions. Using administrative data, inception cohorts of rheumatoid arthritis (RA), asthma/chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), multiple sclerosis (MS), lupus, and sarcoidosis patients age 18 to 64 years with benefits coverage ≥12 months before diagnosis (January 1, 2005 to December 31, 2012) were followed to clinical fracture, cancer diagnosis, or December 31, 2012. Glucocorticoid users were new to therapy. Fracture incidence rates (IRs) per 1000 person-years were stratified by prednisone equivalent doses. Cox's proportional hazards models assessed risk by daily and cumulative dose, and by time since discontinuation, adjusted for baseline characteristics. Most patients (72% of 403,337) had glucocorticoid exposure; 52% were under age 50. IR (95% confidence interval [CI]) of any osteoporotic fracture was elevated at doses <5 mg/day (IR 9.33; 95% CI, 7.29 to 11.77) versus 0 mg/day (IR 4.87 (95% CI, 4.72 to 5.02). Fracture rates were elevated at doses <5 mg/day in patients <50 years and those ≥50 years. In both age groups, fracture risk increased with increasing cumulative exposure, being approximately 2.5-fold higher at cumulative dose ≥5400 mg compared to <675 mg. At ≥5400 mg, IR values were 5.69 (95% CI, 4.32 to 7.35) in patients <50 years and 17.10 (95% CI, 14.97 to 19.46) in older patients. Fracture risk decreased significantly within months following glucocorticoid discontinuation. In patients with a variety of inflammatory conditions, fracture risk increased at doses as low as <5 mg/day. Risk increased with increasing cumulative exposure and decreased soon following glucocorticoid discontinuation. Trends were similar between patients older and younger than 50 years. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
Number, Location, and Time Since Prior Fracture as Predictors of Future Fracture in the Elderly From the General Population
Authors: Beaudoin Claudia , Jean Sonia , Moore Lynne , Gamache Philippe , Bessette Louis , Ste-Marie Louis-Georges , Brown Jacques P
Published: June 2018

Prognostic tools are available to identify individuals at high risk of osteoporotic fracture and to assist physicians in management decisions. Some authors have suggested improving the predictive ability of these tools by integrating characteristics of prior fractures (number, location, and time since prior fracture). The objectives of this study were: (1) to evaluate the sex- and age-specific associations between characteristics of prior fractures and the occurrence of a future osteoporotic fracture; and (2) to assess whether the characteristics of prior fractures could increase the discriminative ability of fracture risk prediction tools. A retrospective cohort study was conducted using administrative data. Men and women aged ≥66 years were selected and grouped into two cohorts. In cohort #1 (N = 759,500), history of fractures was measured between fiscal years 1997–1998 and 2003–2004, and future fractures were identified between 2004–2005 and 2013–2014. In cohort #2 (N = 807,245), history of fractures was measured between 1997–1998 and 2008–2009, and future fractures were identified between 2009–2010 and 2013–2014. Time until a first hip/femur and major osteoporotic fracture were the outcomes of interest. Adjusted HRs and c-indices were calculated. The association between history of prior fractures and future fracture was stronger in men and younger individuals. The locations of prior fractures associated with the lowest and highest risks were foot/ankle/tibia/fibula (maximal HR = 1.64) and hip/femur (maximal HR = 9.02), respectively. The association was stronger for recent fractures (maximal HR = 4.93), but was still significant for fractures occurring 10 to 12 years prior to the beginning of follow-up (maximal HR = 1.99). Characteristics of prior fractures did not increase model discrimination. Our study confirms that the risk of future fracture increases with the number of prior fractures, varies according to prior fracture location, and decreases with time since prior fracture. However, the integration of these characteristics in current fracture risk prediction tools is not required because it does not improve predictive ability. © 2018 American Society for Bone and Mineral Research.
Identification of an Epigenetic Signature of Osteoporosis in Blood DNA of Postmenopausal Women
Authors: Cheishvili David , Parashar Surabhi , Mahmood Niaz , Arakelian Ani , Kremer Richard , Goltzman David , Szyf Moshe , Rabbani Shafaat A
Published: June 2018

Osteoporosis is one of the most common age-related progressive bone diseases in elderly people. Approximately one in three women and one in five men are predisposed to developing osteoporosis. In postmenopausal women, a reduction in BMD leads to an increased risk of fractures. In the current study, we delineated the DNA methylation signatures in whole blood samples of postmenopausal osteoporotic women. We obtained whole blood DNA from 22 normal women and 22 postmenopausal osteoporotic women (51 to 89 years old) from the Canadian Multicenter Osteoporosis Study (CaMos) cohort. These DNA samples were subjected to Illumina Infinium human methylation 450 K analysis. Illumina 450K raw data were analyzed by Genome Studio software. Analysis of the female participants with early and advanced osteoporosis resulted in the generation of a list of 1233 differentially methylated CpG sites when compared with age-matched normal women. T test, ANOVA, and post hoc statistical analyses were performed, and 77 significantly differentially methylated CpG sites were identified. From the 13 most significant genes, ZNF267, ABLIM2, RHOJ, CDKL5, and PDCD1 were selected for their potential role in bone biology. A weighted polygenic DNA methylation score of these genes predicted osteoporosis at an early stage with high sensitivity and specificity and correlated with measures of bone density. Pyrosequencing analysis of these genes was performed to validate the results obtained from Illumina 450 K methylation analysis. The current study provides proof of principal for the role of DNA methylation in osteoporosis. Using whole blood DNA methylation analysis, women at risk of developing osteoporosis can be identified before a diagnosis of osteoporosis is made using BMD as a screening method. Early diagnosis will help to select patients who might benefit from early therapeutic intervention. © 2018 American Society for Bone and Mineral Research.
A New Fracture Risk Assessment Tool (FREM) Based on Public Health Registries
Authors: Rubin Katrine Hass , Möller Sören , Holmberg Teresa , Bliddal Mette , Søndergaard Jens , Abrahamsen Bo
Published: June 2018

Some conditions are already known to be associated with an increased risk of osteoporotic fractures. Other conditions may also be significant indicators of increased risk. The aim of the current study was to identify conditions for inclusion in a fracture prediction model (fracture risk evaluation model [FREM]) for automated case finding of high-risk individuals of hip or major osteoporotic fractures (MOFs). We included the total population of Denmark aged 45+ years (N = 2,495,339). All hospital diagnoses from 1998 to 2012 were used as possible conditions; the primary outcome was MOFs during 2013. Our cohort was split randomly 50/50 into a development and a validation dataset for deriving and validating the predictive model. We applied backward selection on ICD-10 codes (International Classification of Diseases and Related Health Problems, 10th Revision) by logistic regression to develop an age-adjusted and sex-stratified model. The FREM for MOFs included 38 and 43 risk factors for women and men, respectively. Testing FREM for MOFs in the validation cohort showed good accuracy; it produced receiver-operating characteristic (ROC) curves with an area under the ROC curve (AUC) of 0.750 (95% CI, 0.741 to 0.795) and 0.752 (95% CI, 0.743 to 0.761) for women and men, respectively. The FREM for hip fractures included 32 risk factors for both genders and showed an even higher accuracy in the validation cohort as AUCs of 0.874 (95% CI, 0.869 to 0.879) and 0.851 (95% CI, 0.841 to 0.861) for women and men were found, respectively. We have developed and tested a prediction model (FREM) for identifying men and women at high risk of MOFs or hip fractures by using solely existing administrative data. The FREM could be employed either at the point of care integrated into electronic patient record systems to alert physicians or deployed centrally in a national case-finding strategy where patients at high fracture risk could be invited to a focused DXA program. © 2018 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).
Chiari I Malformation and Basilar Invagination in Fibrous Dysplasia: Prevalence, Mechanisms, and Clinical Implications
Authors: Pan Kristen S , Heiss John D , Brown Sydney M , Collins Michael T , Boyce Alison M
Published: June 2018

Fibrous dysplasia (FD) is a mosaic disorder of benign fibro-osseous lesions, which may be associated with extraskeletal features as part of McCune-Albright syndrome (MAS). Cranial base abnormalities, including Chiari I malformation (CM1), in which the cerebellum extends below the foramen magnum, and secondary basilar invagination (BI), in which the odontoid prolapses into the posterior cranial fossa, are potentially serious complications of metabolic bone disorders. The purpose of this study was to determine the prevalence, natural history, and risk factors for CM1 and BI in patients with FD/MAS, and to determine mechanisms of cranial base deformities. Clinical and radiographic data from subjects in an FD/MAS natural history study were evaluated and compared to normal controls. In 158 patients with craniofacial FD, 10 (6.3%) cases of CM1 and 12 (7.6%) cases of BI were diagnosed. No cranial base abnormalities were identified in 10 control subjects. Craniomorphometric and volumetric analyses identified cranial constriction and cranial settling as the primary mechanisms of cranial base abnormalities, whereas intracranial hypertension was a contributing factor in a minority of subjects. Longitudinal analyses found progression of odontoid position with age, but no progression of tonsillar position. No endocrinopathies were associated with CM1. MAS endocrinopathies associated with BI included hyperthyroidism (odds ratio [OR] 12.0; 95% confidence interval [CI], 2.9 to 55.6; p < 0.01), precocious puberty (OR 5.6; 95% CI, 1.2 to 26.0; p < 0.05), and hypophosphatemia (OR 7.7; 95% CI, 1.9 to 27.0; p < 0.01). Scoliosis was associated with both CM1 (OR 4.8; 95% CI, 1.1 to 22.8; p < 0.05) and BI (OR = infinity; 95% CI, 4.7 to infinity; p < 0.01). This study successfully characterized cranial base abnormalities in FD/MAS and the pathophysiological connection between them. These findings support routine screening for cranial base abnormalities in patients with craniofacial FD, as well as aggressive management of contributory risk factors. © 2018 American Society for Bone and Mineral Research.
Betulinic acid induces apoptosis and inhibits metastasis of human renal carcinoma cells in vitro and in vivo
Authors: Yang Chunming , Li Yan , Fu Liye , Jiang Tao , Meng Fandong
Published: June 2018

Betulinic acid (BA), a natural product with a broad range of biological properties, is a lupane‐type pentacyclic triterpene isolated from various plants. Evidence is accumulating that BA is cytotoxic against multiple types of human cancer cells; however, its effects on renal carcinoma cells remain obscure. This study aimed to evaluate the anticancer activity of BA in human renal cancer cells in vitro and in vivo. In the current study, we found that BA inhibited renal cancer cell proliferation in a time‐dependent and dose‐dependent manner in vitro. Moreover, flow cytometry analysis revealed that BA affected the survival of renal cancer cells via the induction of apoptosis. Western blot analysis showed that the occurrence of apoptosis was associated with upregulation of Bcl2‐associated X protein and cleaved caspase‐3 and downregulation of B‐cell lymphoma 2 in renal cancer cells. Additionally, BA treatment augmented the production of reactive oxygen species and induced a significant loss of mitochondrial membrane potential in renal cancer cells, suggesting that BA may trigger apoptosis via the mitochondria‐mediated apoptotic pathway. Furthermore, the migrative and invasive capabilities of renal cancer cells were markedly repressed by BA treatment, which was related to upregulation of matrix metalloproteinase (MMP)2, MMP9, and vimentin, and downregulation of tissue inhibitor of metalloproteinase 2 and E‐cadherin. Notably, administration of BA retarded tumor growth in 786‐O–bearing mice in vivo. Taken together, our results demonstrated the anticancer potential of BA in human renal cancer cells by triggering apoptosis and suppressing migration and invasion.
Inhibition of maternally expressed gene 3 attenuated lipopolysaccharide‐induced apoptosis through sponging miR‐21 in renal tubular epithelial cells
Authors: Yang Ru , Liu Suxuan , Wen Jian , Xue Leixi , Zhang Yi , Yan Dong , Wang Guokun , Liu Zhichun
Published: June 2018

Acute kidney injury (AKI) results in retention of waste products and dysregulation of extracellular volume and electrolytes, thus leading to a variety of complications. Recent advances in long noncoding RNAs suggested their close relationship with disease progression. In the current study, we investigated the role and mechanism of maternally expressed gene 3 (MEG3) on AKI pathogenesis. Real‐time polymerase chain reaction found that the expression of MEG3 was significantly increased in both kidney tissues and TKPTS cells induced by lipopolysaccharide (LPS). Western blot assay showed that the expression of apoptosis regulator Bcl‐2 was increased in MEG3‐inhibited TKPTS cells. Flow cytometry assay confirmed that LPS‐induced apoptosis was significantly attenuated after transfection of si‐MEG3. The RNAhybrid informatics algorithm predicted that there was a strong binding capacity between miR‐21 and MEG3. Luciferase reporter assay confirmed that MEG3 could function as a competing endogenous RNA of miR‐21. The antiapoptotic effect of si‐MEG3 could be neutralized by a miR‐21 inhibitor, demonstrated by the decreased expression of Bcl‐2 and flow cytometry results. Further investigation showed that programmed cell death protein 4 (PDCD4), a validated target of miR‐21, was highly expressed in both injured kidney tissues and LPS‐stimulated TKPTS cells. Meanwhile, the protein expression of PDCD4 was significantly reduced by inhibition of MEG3, but retrieved by coinhibition of MEG3 and miR‐21. In conclusion, our results demonstrated that inhibition of MEG3 could attenuate LPS‐induced apoptosis in TKPTS cells by regulating the miR‐21/PDCD4 pathway, suggesting that the MEG3/miR‐21/PDCD4 axis could be developed as a potential therapeutic target of AKI.
A multi‐method evaluation of the effects of Inflammatory cytokines (IL‐1β, IFN‐γ, TNF‐α) on pancreatic β‐cells
Authors: Xie Kaipeng , Xu Bo , Zhang Yuqing , Chen Minjian , Ji Yinwen , Wang Jie , Huang Zhenyao , Zhou Kun , Xia Yankai , Tang Wei
Published: June 2018

We aimed to explore the effects of Inflammatory cytokines (IL‐1β, IFN‐γ, TNF‐α) on pancreatic β‐cells. CCK‐8 assay showed that the cell viability decreased after 24 hr treatment of TNF‐α, 48 hr of IFN‐γ, and 84 hr of IL‐1β. EdU assay illustrated that after 24 hr treatment, there were significantly reduced EdU‐labeled red fluorescence cells in TNF‐α group while not in IFN‐γ and IL‐1β groups. Flow Cytometry results displayed that TNF‐α and IFN‐γ groups increased apoptosis while IL‐1β group did not. Cell apoptosis results found that there was an increase in the S‐phase population of IL‐1β and TNF‐α groups, however, there was no significant difference in cell cycle between IFN‐γ group and the control. TEM images showed that there were reduction in the number of granules and mitochondria in IL‐1β and IFN‐γ groups, in particular paucity of insulin granules and mitochondria in TNF‐α group. Radioimmunoassay results presented that TNF‐α inhibited glucose‐induced insulin secretion, while there were no significant changes in IL‐1β and IFN‐γ groups when compared with the control. Metabolomic analysis found amino acid metabolism and Krebs cycle were the most robust altered metabolism pathways after inflammatory cytokines treatments. Overall, the altered amino acid metabolism and Krebs cycle metabolism might be important mechanisms of TNF‐α induced mouse pancreatic β‐cells dysfuction.
p120‐catenin is required for regulating epidermal proliferation, differentiation, and barrier function
Authors: Xie Zhongjian , Tang Yuanyuan , Man Mao‐Qiang , Shrestha Chandrama , Bikle Daniel D.
Published: June 2018

p120‐catenin (p120) is an important regulator in the function and stability of E‐cadherin. However, the role of p120 in the epidermis is unclear. Previous studies have shown that globally knockout of p120 caused increased epidermal proliferation but little changes in epidermal differentiation and permeability. In the present study, we generated a conditional knockout mouse model and examined epidermal proliferation, differentiation and permeability. The results showed that conditional knockout of p120 in the epidermis caused not only increased epidermal proliferation but also decreased epidermal differentiation and increased permeability. These data suggest that p120 is required for suppressing epidermal proliferation, promoting epidermal differentiation and maintaining permeability barrier function of the epidermis.
Circular RNA hsa_circ_0016788 regulates hepatocellular carcinoma tumorigenesis through miR‐486/CDK4 pathway
Authors: Guan Zheng , Tan Jing , Gao Wei , Li Xin , Yang Yuandong , Li Xiaogang , Li Yingchao , Wang Qiang
Published: June 2018

Recent studies have revealed that circular RNAs (circRNAs) play important roles in the tumorigenesis of human cancer, including hepatocellular carcinoma (HCC). In present study, we screen the circular RNA expression profiles in HCC tissue and investigate the molecular roles on HCC tumorigenesis. Human circRNA microarray analysis showed there were total 1,245 differently expressed circular RNAs, including 756 up‐regulated circRNAs and 489 down‐regulated circRNAs, in three pairs of HCC tissue and adjacent normal tissue. Hsa_circ_0016788 was identified to be up‐regulated in both HCC tissue and cell lines. Loss‐of‐functional experiments in vivo and vitro revealed that hsa_circ_0016788 silencing inhibited the proliferation, invasion and promoted the apoptosis in vitro, and inhibited the tumor growth in vivo. Bioinformatics tools and luciferase reporter assay validated that miR‐486 targeted hsa_circ_0016788 and CDK4 accompanying with negatively correlated expression, suggesting the hsa_circ_0016788/miR‐486/CDK4 pathway. Receiver operating characteristic (ROC) curve showed that hsa_circ_0016788 had high diagnostic value (AUC = 0.851). In summary, results reveal the role of hsa_circ_0016788/miR‐486/CDK4 in HCC tumorigenesis, providing a novel therapeutic target for HCC.
Transdifferentiation of human gingival mesenchymal stem cells into functional keratinocytes by Acalypha indica in three‐dimensional microenvironment
Authors: Murugan Girija Dinesh , Kalachaveedu Mangathayaru , Ranga Rao Suresh , Subbarayan Rajasekaran
Published: June 2018

Gingival tissue is reportedly a promising, easily accessible, abundant resource of mesenchymal stem cells (MSC) for use in various tissue engineering strategies. Human gingival MSC (HGMSCs) were successfully isolated from gingival tissue and characterized. To analyze in a two‐dimensional form, HGMSCs were cultured with basal medium and induced with 25 µg/ml of Acalypha indica. Quantitative real‐time polymerase chain reaction (qPCR) and western blot analysis showed the presence of keratinocyte‐specific markers, including cytokeratin‐5 and involucrin. To further assess its capability for stratification akin to human keratinocytes, HGMSCs were encapsulated in a HyStem®‐HP Cell Culture Scaffold Kit and cultured in the presence of A. indica. Calcein AM staining indicated that the HyStem®‐HP Scaffold Kit has excellent biocompatibility. Immunofluorescence and qPCR analysis revealed the presence of keratinocyte‐specific markers. The study concluded that the three‐dimensional microenvironment is a novel method for inducing epidermal differentiation of HGMSCs to engineer epidermal substitutes with the help of A. indica, which provides an alternative strategy for skin tissue engineering.
Induction of endoplasmic reticulum stress under endotoxin tolerance increases inflammatory responses and decreases Pseudomonas aeruginosa pneumonia
Authors: Kim Sena , Joe Yeonsoo , Park Se-Ung , Jeong Sun Oh , Kim Jin-Kyung , Park Seong Hoon , Pae Hyun-Ock , Surh Young-Joon , Shin Jaekyoon , Chung Hun Taeg
Published: June 2018

Endotoxin tolerance develops in the late phase of sepsis to protect cells from an early hyperinflammatory response. Nonetheless, because it induces an immunosuppressive environment, patients with sepsis in its late phase are affected by secondary infections, particularly bacterial pneumonia. Here, we showed that induction of endoplasmic reticulum (ER) stress leads to activation of glycogen synthase kinase 3β (GSK-3β) and X-box–binding protein 1 (XBP-1) in an inositol-requiring enzyme 1α (IRE1α)-mediated manner, which in turn restores the inflammatory response in endotoxin-tolerant macrophages. Animal and in vitro models of endotoxin tolerance were studied along with a model of LPS-induced endotoxin tolerance and a model of cecal ligation and puncture (CLP)-induced endotoxin tolerance. To detect the suppressed inflammatory response during endotoxin tolerance, inflammatory-cytokine expression levels were measured by quantitative real-time PCR and an ELISA. Our research revealed that induction of ER stress alleviated lung injury in a septic host infected with Pseudomonas aeruginosa via the activation of GSK-3β and XBP-1 in an IRE1α-mediated manner. Consequently, in the lungs of the septic host infected with P. aeruginosa, symptoms of pneumonia improved and the infecting bacteria were cleared. Thus, for septic patients, determination of immune status may guide the selection of appropriate immunomodulation, and ER stress can be a novel therapeutic strategy restoring the immune response in patients with endotoxin tolerance.

Induction of ER stress alleviates the lung injury of septic host infected P. aeruginosa via the activation of GSK-3β and XBP-1 in an IRE1α-mediated manner.
177Lu‐DOTMP induces G2/M cell cycle arrest and apoptosis in MG63 cell line
Authors: Kumar Chandan , Sharma Rohit , Das Tapas , Korde Aruna , Sarma Haladhar , Banerjee Sharmila , Dash Ashutosh
Published: June 2018

Bone pain is the major manifestation of skeletal metastases. Although various treatment modalities are available for bone pain palliation, use of radiolabeled phosphonates is documented to be more effective. Among radionuclides available for this purpose, lutetium‐177 is gaining popularity due to its moderate beta energy, theranostic capability, favorable half‐life and convenient production logistics. 177Lu‐DOTMP has shown considerable promise as a metastatic bone pain palliating agent in preliminary evaluations and recent clinical studies. Therefore, an attempt was made to elucidate the possible mechanism of in vitro cell death induced by 177Lu‐DOTMP in MG63 cells. 177Lu‐DOTMP binding studies were carried out in mineralized bone of MG63 cells and around 50% binding was observed. Skeletons of Wistar rats showed 1.78 ± 0.5% IA/g at a 3 h time period which was almost constant up to 7 days. MG63 cells were incubated with 3.7 and 37 MBq of 177Lu‐DOTMP for 48 h prior to perform assays. An increase in the magnitude of cell toxicity and apoptotic DNA fragmentation was observed. Enhancement of G2/M phase cell cycle arrest and apoptosis were documented which were dose‐dependent. Thus, 177Lu‐DOTMP induced apoptotic cell death in MG63 cells, which might be one of the primary causes of pain relief in osseous metastases.
Improving the well‐being of staff through mindfulness at the Tees, Esk, and Wear Valleys NHS Foundation Trust
Authors: Hodgson Russell , Graham Elinor Morgan , McGough Amanda
Published: June 2018

Work‐related stress can affect employees’ health, as well as the quality of the work that they perform. Mindfulness is a way to diminish stress and improve well‐being, which in turn can reduce absenteeism and improve on‐the‐job performance. Recognizing the potential value of mindfulness training, the Tees, Esk, and Wear Valleys NHS Foundation Trust, a part of the United Kingdom's National Health Service responsible for mental health and learning disability services in northeast England, introduced a mindfulness program for its employees and service users. Subsequent evaluations have found that the initiative has had an overwhelmingly positive impact on measures such as general health, perceived stress, and well‐being. These results indicate the value of implementing a similar program in any organization where staff members have demanding workloads and are required to deal with people who may be distressed or disturbed.
How the service industry can corral big data into a business‐building tool
Authors: Heymann Mark
Published: June 2018

For many in the service industry, the availability of big data is overwhelming. With volumes of information available at the push of a button, managers are awash in statistics, but not always sure of how useful they are. A shift from viewing data in terms of absolute numbers to understanding it in terms of cause and effect can help organizational leaders move the needle from merely measuring performance to creating the conditions to guarantee optimal outcomes. Applicable to all industries, such an approach filters out extraneous information while taking into account and correlating essential variables, such as competition, market conditions, and customer touch points, that have a significant impact on the bottom line.
Managing strategic performance in a dynamic business environment: A study of two Indian oil companies
Authors: Akhtar Mohammad , Sushil  
Published: June 2018

In a volatile, uncertain, complex, and ambiguous work environment, organizations must adopt an effective strategic performance measurement (SPM) system that ensures their ability to be as flexible as circumstances require. A case study of two Indian oil companies—Oil and Natural Gas Corporation Ltd. and Oil India Ltd.—uses the situation actor process‐learning action performance framework to investigate the interaction among seven factors—strategic planning, strategic flexibility, strategy implementation, SPM system design, information system flexibility, SPM management issues, and performance feedback and learning—on the companies’ performance. The results lead to the formation of a dynamic model that managers can use to ensure that their organization's strategy is being translated into attainable goals and to drive enterprise‐wide performance improvement.
What Happens to Nutrition Intake in the Post–Intensive Care Unit Hospitalization Period? An Observational Cohort Study in Critically Ill Adults
Authors: Ridley Emma J. , Parke Rachael L. , Davies Andrew R. , Bailey Michael , Hodgson Carol , Deane Adam M. , McGuinness Shay , Cooper D. James
Published: June 2018

Background

Little is currently known about nutrition intake and energy requirements in the post–intensive care unit (ICU) hospitalization period in critically ill patients. We aimed to describe energy and protein intake, and determine the feasibility of measuring energy expenditure during the post‐ICU hospitalization period in critically ill adults.

Methods

This is a nested cohort study within a randomized controlled trial in critically ill patients. After discharge from ICU, energy and protein intake was quantified periodically and indirect calorimetry attempted. Data are presented as n (%), mean (SD), and median (interquartile range [IQR]).

Results

Thirty‐two patients were studied in the post‐ICU hospitalization period, and 12 had indirect calorimetry. Mean age and BMI was 56 (18) years and 30 (8) kg/m2, respectively, 75% were male, and the median estimated energy and protein requirement were 2000 [1650–2550] kcal and 112 [84–129] g, respectively. Oral nutrition either alone (n = 124 days, 55%) or in combination with enteral nutrition (n = 96 days, 42%) was the predominant mode. Over 227 total days in the post‐ICU hospitalization period, a median [IQR] of 1238 [869–1813] kcal and 60 [35–89.5] g of protein was received from nutrition therapy. In the 12 patients who had indirect calorimetry, the median measured daily energy requirement was 1982 [1843–2345] kcal and daily energy deficit was −95 [−1050 to 347] kcal compared with the measured energy requirement.

Conclusions

Energy and protein intake in the post‐ICU hospitalization period was less than estimated and measured energy requirements. Oral nutrition provided alone was the most common mode of nutrition therapy.
Simultaneous screening and quantification of aminoglycoside antibiotics in honey using mixed‐mode liquid chromatography with quadrupole time‐of‐flight mass spectroscopy with heated electrospray ionization
Authors: Perkons Ingus , Pugajeva Iveta , Bartkevics Vadims
Published: June 2018

An analytical method based on liquid chromatography with quadrupole time‐of‐flight mass spectrometry has been developed for the simultaneous determination of six aminoglycoside antibiotics in honey. The sample pretreatment included extraction with aqueous trichloroacetic acid followed by solid‐phase extraction on Strata‐X polymeric reversed phase cartridges. Liquid chromatography separation was performed on an Obelisc R zwitterionic type mixed‐mode column. An ionBooster™ heated electrospray source was used and showed enhanced ionization efficiency in comparison to a conventional electrospray source. The observed signal enhancement ranged from 3‐ (neomycin) to 16‐fold (gentamicin C1). A data‐dependent mass spectrometry acquisition approach was employed, in which the full mass spectrometry dataset provided quantification and a scheduled precursor list was used to trigger an alternating data‐dependent acquisition of MS2 spectra for confirmation purposes. The described method was validated in accordance to CD 2002/657/EC. Decision limit values were in the range 11.2–33.6 ng/g, and satisfactory performance characteristics were obtained for recovery (65–76%), repeatability (3.8–7.3%), and linearity (≥0.995). The method was applied to the analysis of 49 real honey samples from the country of Georgia. Streptomycin was detected in two samples at 117 and 35 ng/g, and gentamicin C1 was detected in one sample at 32 ng/g.
Preparation, Post‐Modification, and Antibacterial Application of Gelatin Electrospun Membranes
Authors: Yu Xi , Wang Liang , Yang Pengfei , Xu Jinku , Moloney Mark G. , Liu Lian , Pan Yunlin , Wang Yongqing
Published: June 2018

Two bis(diaryldiazomethane)s substituted with amino groups are synthesized and used for the surface modification of membranes electrospun from gelatin. These membranes are then reacted with tolylene‐2,4‐diisocyanate to give urea‐functionalized materials, so that hydrogen peroxide can be reversibly bound onto their surface. These membranes are characterized by scanning electron microscopy, XPS, differential scanning calorimeter, and tensile test to show their surface properties and bulk properties. The surface modification with amino‐substituted diazomethanes and the subsequent cross‐linking reaction with diisocyanates contribute to high loadings of hydrogen peroxide, and greatly increase the antibacterial activity of gelatin‐derived membranes, which open a new horizon in the preparation of high loading antiseptic/antibacterial biomacromolecular surfaces and interfaces.
Beyond Simple AB Diblock Copolymers: Application of Bifunctional and Trifunctional RAFT Agents to PISA in Water
Authors: Mellot Gaëlle , Beaunier Patricia , Guigner Jean‐Michel , Bouteiller Laurent , Rieger Jutta , Stoffelbach François
Published: June 2018

The influence of the macromolecular reversible addition‐fragmentation chain transfer (macro‐RAFT) agent architecture on the morphology of the self‐assemblies obtained by aqueous RAFT dispersion polymerization in polymerization‐induced self‐assembly (PISA) is studied by comparing amphiphilic AB diblock, (AB)2 triblock, and triarm star‐shaped (AB)3 copolymers, constituted of N,N‐dimethylacrylamide (DMAc = A) and diacetone acrylamide (DAAm = B). Symmetrical triarm (AB)3 copolymers could be synthesized for the first time in a PISA process. Spheres and higher order morphologies, such as worms or vesicles, could be obtained for all types of architectures and the parameters that determine their formation have been studied. In particular, we found that the total DPn of the PDMAc and the PDAAm segments, i.e., the same overall molar mass, at the same Mn(PDMAc)/Mn(PDAAm) ratio, rather than the individual length of the arms determined the morphologies for the linear (AB)2 and star shaped (AB)3 copolymers obtained by using the bi‐ and trifunctional macro‐RAFT agents.
A relative ranking with multidimensional indicators. Application to the Spanish banking sector
Authors: Rubiales Victoriana , Monroy Luisa , Mármol Amparo M.
Published: June 2018

In this paper, we propose a procedure to determine an overall ranking of a group of entities when the information available on the entities consists of the values of a set of indicators, which have a multidimensional nature. The multiplicity of the data available for each indicator may represent the valuation of the indicator in different scenarios, in different periods of time, or the assessment of various agents on the value of the indicator. A multicriteria treatment allows us to maintain the multidimensional nature of each indicator in order to avoid the possibility that some relevant information may be lost, and it permits the inclusion of partial information about the importance of the indicators. The proposal consists of a recursive procedure such that, at each stage, the resolution of a multiciteria linear problem yields a set of valuation vectors for each entity and subsequently, by using a distance‐based method, an overall ranking that synthesises the information given by these valuation vectors is obtained. The applicability of the proposed procedure is shown with the construction of the ranking of the main banks of the Spanish banking sector from a set of financial indicators.
Dynamics of DS‐I‐A epidemic model with multiple stochastic perturbations
Authors: Liu Songnan , Jiang Daqing , Xu Xiaojie , Alsaedi Ahmed , Hayat Tasawar
Published: June 2018

In this paper, we investigate the dynamics behavior of DS‐I‐A epidemic model with multiple stochastic perturbations. Sufficient conditions for extinction of disease are established. Especially, we conclude that there is a stationary distribution for the stochastic system and it has ergodicity under appropriate conditions. At last, some examples and simulations are provided to illustrate our results.
Mathematical modelling of methanol poisoning with impulsive dosing of antidote therapeutics to prevent toxicity
Authors: Ghosh Priyanka , Roy Priti Kumar
Published: June 2018

The harmful use of methanol is a worldwide problem resulting in millions of deaths, including thousands of young lives lost. Although methanol itself may be harmless, it is oxidized to formaldehyde and, further, it breaks down to formic acid, which is lethal for humans with high concentration. The primary treatment of methanol poisoning is the administration of ethanol to slow down the formation of toxic metabolites by competitive substitution of the methanol due to its intrinsic binding affinity. Moreover, supportive role of administering sodium bicarbonate in the patient assists the neutralization of the metabolic acidosis in human for the accumulation of formic acid. In this research article, we formulate a mathematical model to study the effect of co‐administration of ethanol and sodium bicarbonate to treat methanol toxicity. This treatment procedure may help the health workers to provide at least a basic emergency care to minimize the death toll in the remote and distant places. The experimental data were used to acquire the model generated time and dosing prediction through which patient is to be benefited in obtaining the normalcy within minimum therapy time.