bluuebunny/crossref_metadata_2025 huggingface dataset:
Early information processing contributions to object individuation revealed by perception of illusory figures
Authors: Naughtin Claire K. , Mattingley Jason B. , Dux Paul E.
Published: September 2016

To isolate multiple coherent objects from their surrounds, each object must be represented as a stable perceptual entity across both time and space. Recent theoretical and empirical work has proposed that this process of object individuation is a mid-level operation that emerges around 200–300 ms after stimulus onset. However, this hypothesis is based on paradigms that have potentially obscured earlier effects. Furthermore, no study to date has directly assessed whether object individuation occurs for task-irrelevant objects. In the present study we used electroencephalography (EEG) to measure the time course of individuation, for stimuli both within and outside the focus of attention, to assess the information processing stage at which object individuation arises for both types of objects. We developed a novel paradigm involving items defined by illusory contours, which allowed us to vary the number of to-be-individuated objects while holding the physical elements of the display constant (a design characteristic not present in earlier work). As early as 100 ms after stimulus onset, event-related potentials tracked the number of objects in the attended hemifield, but not those in the unattended hemifield. By contrast, both attended and unattended objects could be individuated at a later stage. Our findings challenge recent conceptualizations of the time course of object individuation and suggest that this process arises earlier for attended than unattended items, implying that voluntary spatial attention influences the time course of this operation.
Self‐Administered Mind‐Body Practices for Reducing Health Disparities: An Interprofessional Opinion and Call to Action
Authors: Kinser Patricia A. , Robins Jo Lynne W. , Masho Saba W.
Published: September 2016

Health disparities (HD) continue to persist in the United States which underscores the importance of using low‐cost, accessible, evidence‐based strategies that can improve health outcomes, especially for chronic conditions that are prevalent among underserved minority populations. Complementary/integrative health modalities, particularly self‐administered mind‐body practices (MBP), can be extremely useful in reducing HD because they are intrinsically patient‐centered and they empower patients to actively engage in self‐care of health and self‐management of symptoms. Interprofessional healthcare providers and patients can engage in powerful partnerships that encompass self‐administered MBP to improve health. This is a call to action for interprofessional researchers to engage in high‐quality research regarding efficacy and cost‐effectiveness of self‐administered MBP, for practitioners to engage patients in self‐administered MBP for health promotion, disease prevention, and symptom management, and for healthcare institutions to integrate self‐administered MBP into conventional health practices to reduce HD in their communities.
Structural Modifications for Torsional Vibration Control of Shafting Systems Based on Torsional Receptances
Authors: Liu Zihao , Li Wanyou , Ouyang Huajiang
Published: September 2016

Torsional vibration of shafts is a very important problem in engineering, in particular in ship engines and aeroengines. Due to their high levels of integration and complexity, it is hard to get their accurate structural data or accurate modal data. This lack of data is unhelpful to vibration control in the form of structural modifications. Besides, many parts in shaft systems are not allowed to be modified such as rotary inertia of a pump or an engine, which is designed for achieving certain functions. This paper presents a strategy for torsional vibration control of shaft systems in the form of structural modifications based on receptances, which does not need analytical or modal models of the systems under investigation. It only needs the torsional receptances of the system, which can be obtained by testing simple auxiliary structure attached to relevant locations of the shaft system and using the finite element model (FEM) of the simple structure. An optimization problem is constructed to determine the required structural modifications, based on the actual requirements of modal frequencies and mode shapes. A numerical experiment is set up and the influence of several system parameters is analysed. Several scenarios of constraints in practice are considered. The numerical simulation results demonstrate the effectiveness of this method and its feasibility in solving torsional vibration problems in practice.
Polythiophene-Chitosan Magnetic Nanocomposite as a Highly Efficient Medium for Isolation of Fluoxetine from Aqueous and Biological Samples
Authors: Feizbakhsh Alireza , Sarrafi Amir Hossein Mohsen , Ehteshami Shokooh
Published: September 2016

Polythiophene/chitosan magnetic nanocomposite as an adsorbent of magnetic solid phase extraction was proposed for the isolation of fluoxetine in aqueous and biological samples prior to fluorescence detection at 246 nm. The synthesized nanoparticles, chitosan and polythiophene magnetic nanocomposite, were characterized by scanning electron microscopy, FT-IR, TGA, and EDAX. The separation of the target analyte from the aqueous solution containing the fluoxetine and polythiophene/chitosan magnetic nanocomposite was simply achieved by applying external magnetic field. The main factors affecting the extraction efficiency including desorption conditions, extraction time, ionic strength, and sample solution pH were optimized. The optimum extraction conditions were obtained as 10 min for extraction time, 25 mg for sorbent amount, 50 mL for initial sample volume, methanol as desorption solvent, 1.5 mL for desorption solvent volume, 3 min for desorption time, and being without salt addition. Under the optimum conditions, good linearity was obtained within the range of 15–1000 μg L−1for fluoxetine, with correlation coefficients 0.9994. Furthermore, the method was successfully applied to the determination of fluoxetine in urine and human blood plasma samples. Compared with other methods, the current method is characterized with highly easy, fast separation and low detection limits.
Novel Tubular Biomarkers Predict Renal Progression in Type 2 Diabetes Mellitus: A Prospective Cohort Study
Authors: Satirapoj Bancha , Aramsaowapak Kasemsan , Tangwonglert Theerasak , Supasyndh Ouppatham
Published: September 2016

Background.Tubulointerstitial injury is both a key feature of diabetic nephropathy and an important predictor of renal dysfunction. Novel tubular biomarkers related to renal injury in diabetic nephropathy could improve risk stratification and prediction.Methods.A total of 303 type 2 diabetic patients were followed up. The baseline urine values of cystatin-C to creatinine ratio (UCCR), angiotensinogen to creatinine ratio (UANG), NGAL to creatinine ratio (UNGAL), and KIM-1 to creatinine ratio (UKIM-1) were measured. The primary outcome was a decline in estimated GFR of ≥25% yearly from baseline.Results.Urine tubular biomarkers of UCCR, UANG, UNGAL, and UKIM-1 were significantly higher according to the degree of albuminuria and all were significantly higher among patients with rapid decline in estimated GFR of ≥25% yearly from baseline. All biomarkers predicted primary outcomes with ROC for UCCR of 0.72; 95% CI 0.64–0.79, for UANG of 0.71; 95% CI 0.63–0.79, for UNGAL of 0.64; 95% CI 0.56–0.72, and for UKIM-1 of 0.71; 95% CI 0.63–0.79. Using multivariate Cox regression analysis, the number of patients with rapid renal progression was higher among those in the upper quartiles of all biomarkers than in those in the lower quartiles.Conclusions. Type 2 diabetic patients with high levels of urine tubular biomarkers had a more rapid decline in renal function.
Solitary Fibrous Tumor of the Sigmoid Colon Masquerading as an Adnexal Neoplasm
Authors: Bratton Laura , Salloum Rabih , Cao Wenqing , Huber Aaron R.
Published: September 2016

Solitary fibrous tumor is a rare, benign spindle cell neoplasm that was first described in the thoracic pleura. This tumor is now known to occur at many extrapleural sites. There are established criteria for the diagnosis of malignant solitary fibrous tumor including ≥4 mitotic figures per 10 high-power fields, increased cellularity, cytologic atypia, infiltrative margins, and/or necrosis. Although all solitary fibrous tumors have the potential to recur or metastasize, those with malignant histologic features tend to behave more aggressively. We report a case of solitary fibrous tumor, with malignant histologic features, in a 21-year-old woman which arose from the serosal surface of the sigmoid colon.
Improving the Treatment and Assessment of Moderate and Severe Pain in a Pediatric Emergency Department
Authors: Chafe Roger , Harnum Debbie , Porter Robert
Published: September 2016

Background.The Janeway Children’s Hospital previously enacted a number of measures to improve pain management for patients in its emergency department (ED). While improvements were demonstrated, rates for the timely assessment and treatment of pain remain below standards of care.Objectives.The study objectives are to investigate the impact of the previous attempts to improve the treatment of pain and to explore ways to further improve pain management in the ED.Methods.Key informant interviews and a focus group were conducted with nurses, physicians, and parents whose children were identified as having severe pain.Results.Interviews were conducted with 31 parents or children, 9 physicians, and 8 nurses. The focus group was attended by 15 nurses. Previous initiatives were viewed as improvements. Continued barriers include difficulties in accurately capturing the level of pain, issues in treating pain for specific types of patients, and inadequacy in addressing patients in severe pain.Conclusion.Changes in pain treatment protocols can result in positive impacts but are likely insufficient on their own to achieve desired standards of care. Consistent measurement and engagement with staff can identify additional opportunities for improving pain management within an ED setting.
Acute and Subacute Toxicological Evaluation of the Aerial Extract of Monsonia angustifolia E. Mey. ex. A. Rich in Wistar Rats
Authors: Afolayan Anthony Jide , Wintola Olubunmi Abosede , Fouche Gerda
Published: September 2016

The acute and subacute toxicity profile of the aerial extract of Monsonia angustifolia in Wistar rats was evaluated. The Organization for Economic Cooperation and Development (OECD) 420 guideline was adopted in the acute toxicity testing with a single oral dose of 5000 mg/kg (b.w.). For the 28‐day daily oral dosing, the extract was administered at 75, 150, and 300 mg/kg b.w.; 1% ethanol in sterile distilled water was used as control. Clinical toxicity signs were subsequently evaluated. At a single dose of 5000 mg/kg b.w. the extract elicited no treatment‐related signs of toxicity in the animals during the 14 days of experimental period. In the subacute toxicity, there was no significant difference in hematological, renal, and liver function indices. However, dose‐dependent significant increases were observed on the plasma concentrations of white blood cell and platelet counts of the treated animals compared to the control group. While cage observations revealed no treatment‐facilitated signs of toxicity, histopathological examinations of the kidneys and liver also showed no obvious lesions and morphological changes. These results suggest that the extract may be labelled and classified as safe and practically nontoxic within the doses and period of investigation in this study.
Forward VNS, Reverse VNS, and Multi-VNS Algorithms for Job-Shop Scheduling Problem
Authors: Pongchairerks Pisut
Published: September 2016

This paper proposes a number of forward VNS and reverse VNS algorithms for job-shop scheduling problem. The forward VNS algorithms are the variable neighborhood search algorithms applied to the original problem (i.e., the problem instance with the original precedence constraints). The reverse VNS algorithms are the variable neighborhood search algorithms applied to the reversed problem (i.e., the problem instance with the reversed precedence constraints). This paper also proposes a multi-VNS algorithm which assigns an identical initial solution-representing permutation to the selected VNS algorithms, runs these VNS algorithms, and then uses the best solution among the final solutions of all selected VNS algorithms as its final result. The aim of the multi-VNS algorithm is to utilize each single initial solution-representing permutation most efficiently and thus receive its best result in return.
Lobular Carcinoma of the Breast Metastatic to the Spleen and Accessory Spleen: Report of a Case
Authors: Groisman Gabriel M.
Published: September 2016

Despite the fact that accessory spleen (also known as supernumerary spleen, splenunculus, or splenule) can be found in 10–30% of patients undergoing autopsies, metastatic disease occurring in this organ has been barely reported. A case of lobular breast carcinoma metastatic to the spleen and accessory spleen found incidentally at therapeutic splenectomy for severe anemia and thrombocytopenia is described. On microscopic examination both organs revealed severe fibrocongestive changes and extramedullary hematopoiesis with no obvious carcinomatous involvement. Cytokeratin 7, estrogen receptors, and GATA3 immunohistochemistry disclosed the presence of numerous metastatic breast carcinoma cells infiltrating the splenic parenchyma. This case demonstrates that metastatic carcinoma can be encountered, although rarely, in accessory spleens and that cytokeratin stain should be performed in sections of spleens and/or accessory spleens excised from cancer patients in which the presence of malignant epithelial cells is not recognized on routine sections.
Analysis of the Influence of Complexity and Entropy of Odorant on Fractal Dynamics and Entropy of EEG Signal
Authors: Namazi Hamidreza , Akrami Amin , Nazeri Sina , Kulish Vladimir V.
Published: September 2016

An important challenge in brain research is to make out the relation between the features of olfactory stimuli and the electroencephalogram (EEG) signal. Yet, no one has discovered any relation between the structures of olfactory stimuli and the EEG signal. This study investigates the relation between the structures of EEG signal and the olfactory stimulus (odorant). We show that the complexity of the EEG signal is coupled with the molecular complexity of the odorant, where more structurally complex odorant causes less fractal EEG signal. Also, odorant having higher entropy causes the EEG signal to have lower approximate entropy. The method discussed here can be applied and investigated in case of patients with brain diseases as the rehabilitation purpose.
Circulating Calreticulin Is Increased in Myelofibrosis: Correlation with Interleukin-6 Plasma Levels, Bone Marrow Fibrosis, and Splenomegaly
Authors: Sollazzo Daria , Forte Dorian , Polverelli Nicola , Perricone Margherita , Romano Marco , Luatti Simona , Vianelli Nicola , Cavo Michele , Palandri Francesca , Catani Lucia
Published: September 2016

Myelofibrosis (MF) is a clonal neoplasia of the hemopoietic stem/progenitor cells associated with genetic mutations in the Janus kinase 2 (JAK2), myeloproliferative leukemia virus oncogene (MPL), and calreticulin (CALR) genes. MF is also characterized by a state of chronic inflammation. Calreticulin (CRT), as a multifunctional protein, is involved in a spectrum of cellular processes including inflammation, autoimmunity, and cancer initiation/progression. Based on this background, we hypothesised that in MF circulating CRT might reflect the inflammatory process. In the present study we show that circulating CRT is increased in MF patients compared to healthy controls. Also, in MF, CRT levels highly correlate with bone marrow fibrosis, splenomegaly, and Interleukin-6 (IL-6) plasma levels. In turn, higher IL-6 levels also correlated with disease severity in terms of increased spleen size, bone marrow fibrosis, number of circulating CD34+cells, and lower hemoglobin values. These results demonstrate that the circulating CRT takes part in the inflammatory network of MF and correlates with aggressiveness of the disease.
The Significance of Long Noncoding RNA H19 in Predicting Progression and Metastasis of Cancers: A Meta-Analysis
Authors: Jing Wei , Zhu Man , Zhang Xian-wei , Pan Zhong-ya , Gao Shan-shan , Zhou Hu , Qiu Shi-li , Liang Chun-zi , Tu Jian-cheng
Published: September 2016

Recently, numerous studies indicate that H19 plays a key role in tumorigenesis, but the results have been disputed, especially in the aspects of tumor progression and metastasis. Therefore, we performed this meta-analysis to systematically summarize the relationship between H19 and cancers. We searched PubMed, the Cochrane Library, CNKI, and Chinese Wan Fang to identify eligible studies. Odds ratios and 95% confidence intervals were calculated to assess the effect size. A total of 13 studies were enrolled in this meta-analysis, which was performed by Revman5.3 and Stata11.0 software. Our meta-analysis showed that the expression of H19 was associated with distant metastasis in nongastrointestinal tumors (OR = 3.85, 95% CI = 1.31–11.36,P=0.01) and, in gastrointestinal tumors (OR = 0.34, 95% CI = 0.15–0.78,P=0.01), lymph node metastasis (OR = 2.04, 95% CI = 1.19–3.48,P=0.009). Moreover, in gastric cancer, H19 expression was significantly related to histological grade (OR = 0.50, 95% CI = 0.29–0.86,P=0.01), TNM stage (OR = 0.19, 95% CI = 0.11–0.33,P<0.01), and tumor invasion depth (OR = 0.11, 95% CI = 0.04–0.27,P<0.01). Therefore, H19 could serve as a potential marker for progression and metastasis evaluation of cancers.
Assessment of Physicochemical Properties of Tequila Brands: Authentication and Quality
Authors: Carreon-Alvarez Alejandra , Suárez-Gómez Amaury , Zurita Florentina , Gómez-Salazar Sergio , Soltero J. Felix Armando , Barcena-Soto Maximiliano , Casillas Norberto , Porfirio-Gutierrez  , Moreno-Medrano Edgar David
Published: September 2016

Several physicochemical properties were measured in commercial tequila brands: conductivity, density, pH, sound velocity, viscosity, and refractive index. Physicochemical data were analyzed by Principal Component Analysis (PCA), cluster analysis, and the one-way analysis of variance to identify the quality and authenticity of tequila brands. According to the Principal Component Analysis, the existence of 3 main components was identified, explaining the 87.76% of the total variability of physicochemical measurements. In general, all tequila brands appeared together in the plane of the first two principal components. In the cluster analysis, four groups showing similar characteristics were identified. In particular, one of the clusters contains some tequila brands that are not identified by the Regulatory Council of Tequila and do not meet the quality requirements established in the Mexican Official Standard 006. These tequila brands are characterized by having higher conductivity and density and lower viscosity and refractive index, determined by one-way analysis of variance. Therefore, these economical measurements, PCA, and cluster analysis can be used to determinate the authenticity of a tequila brand.
Functions ofthga1Gene inTrichoderma harzianumBased on Transcriptome Analysis
Authors: Sun Qing , Jiang Xiliang , Pang Li , Wang Lirong , Li Mei
Published: September 2016

Trichodermaspp. are important biocontrol filamentous fungi, which are widely used for their adaptability, broad antimicrobial spectrum, and various antagonistic mechanisms. In our previous studies, we clonedthga1gene encoding GαI protein fromTrichoderma harzianumTh-33. Its knockout mutant showed that the growth rate, conidial yield, cAMP level, antagonistic action, and hydrophobicity decreased. Therefore, Illumina RNA-seq technology (RNA-seq) was used to determine transcriptomic differences between the wild-type strain andthga1mutant. A total of 888 genes were identified as differentially expressed genes (DEGs), including 427 upregulated and 461 downregulated genes. All DEGs were assigned to KEGG pathway databases, and 318 genes were annotated in 184 individual pathways. KEGG analysis revealed that these unigenes were significantly enriched in metabolism and degradation pathways. GO analysis suggested that the majority of DEGs were associated with catalytic activities and metabolism processes that encode carbohydrate-active enzymes, secondary metabolites, secreted proteins, or transcription factors. According to the functional annotation of these DEGs by KOG, the most abundant group was “secondary metabolite biosynthesis, transport, and catabolism.” Further studies for functional characterization of candidate genes and pathways reported in this paper are necessary to further define the G protein signaling system inT. harzianum.
Vibration Induces BAFF Overexpression and Aberrant O-Glycosylation of IgA1 in Cultured Human Tonsillar Mononuclear Cells in IgA Nephropathy
Authors: Ye Muyao , Peng Youming , Liu Chan , Yan Wenzhe , Peng Xiaofei , He Liyu , Liu Hong , Liu Fuyou
Published: September 2016

Objective. To investigate the influence ofin vitrovibratory stimulation of human tonsillar mononuclear cells (TMCs).Methods. Fourteen IgA nephropathy (IgAN) patients with chronic tonsillitis (CT) and 12 CT patients with no renal pathology were enrolled. Group A TMCs were collected after 24 hours of culture and used to determine baseline levels. TMCs in groups B, C, D, E, and F were exposed to vibratory stimulation (60 Hz) for 0 (as the control group), 1, 3, 5, and 10 minutes, respectively.Results. Baseline concentrations of B-cell-activation factor (BAFF) and IgA1, BAFF mRNA expression, and aberrant O-glycosylation IgA1 level were higher in the IgAN group as compared to that in the CT group, and all increased after vibratory stimulation. Baseline mRNA expressions of coreβ1,3-galactosyltransferase (C1GALT1) and coreβ1,3GalT-specific molecular chaperone (Cosmc) were lower in the IgAN group; the levels decreased further after vibratory stimulation.Conclusion. In patients with IgAN, vibratory stimulation of TMCs appears to induce IgA1 secretion through activation of BAFF release and to aberrant O-glycosylation IgA1 by suppressing C1GALT1 and Cosmc expression.In vitrovibratory stimulation of human TMCs mimics the vibratory simulation of palatine tonsils produced by vocal cords during phonation.
How Effective and Safe Is Bronchial Thermoplasty in “Real Life” Asthmatics Compared to Those Enrolled in Randomized Clinical Trials?
Authors: Arrigo Rita , Failla Giuseppe , Scichilone Nicola , La Sala Alba , Galeone Carla , Battaglia Salvatore , Benfante Alida , Facciolongo Nicola
Published: September 2016

There is limited information on the efficacy and safety of bronchial thermoplasty (BT) inreal life. We evaluated the outcomes of the randomized clinical trials for BT in severe asthmatics, in whom the exclusion criteria were not strictly controlled. A case series of seven asthmatics (M/F: 4/3; age:54.6±2.9years) is reported. Subjects had a statistically significant improvement in AQLQ (from a mean of3.96±1.1to4.5±1.2and5.5±0.6after 6 and 12 months of treatment;p=0.0007) and in the ACQ score (from2.77±0.8to1.83±1.2and1.5±0.8after 6 and 12 months;p<0.001). In the year after BT, severe exacerbations, salbutamol use, and OCS use were significantly lower compared with the 1-yr pretreatment period (p<0.001). No ED visits and hospitalization occurred in the year after BT. No changes in functional parameters were recorded. Our investigation confirms the safety and efficacy of BT in severe asthmatics inreal lifesettings.
A Case of Acute Budd-Chiari Syndrome Complicating Primary Antiphospholipid Syndrome Presenting as Acute Abdomen and Responding to Tight Anticoagulant Therapy
Authors: Chinen Naofumi , Koyama Yasushi , Sato Shinji , Suzuki Yasuo
Published: September 2016

A 34-year-old woman with primary antiphospholipid syndrome was admitted to the Gastroenterology Department of our hospital with fever, acute abdomen, watery diarrhea, and extremely high levels of inflammatory parameters. She had a history of left lower limb deep vein thrombosis and pulmonary embolism and was taking warfarin potassium. Acute gastroenteritis was suspected and an antibiotic was administered, but symptoms progressed. Abdominal ultrasonography showed occlusion of the left hepatic vein and the middle hepatic vein and her D-dimer level was high. Accordingly, Budd-Chiari syndrome was diagnosed and high-dose intravenous infusion of heparin was initiated. Her abdominal symptoms improved and the levels of inflammatory parameters and D-dimer decreased rapidly. It is known that antiphospholipid syndrome can be complicated by Budd-Chiari syndrome that usually occurs as subacute or chronic onset, but acute onset is rare. It is difficult to diagnose acute Budd-Chiari syndrome complicating antiphospholipid syndrome and this complication generally has a poor outcome. However, the present case can get early diagnosis and successful treatment with tight anticoagulant therapy.
Cell Adhesion Molecule CD166 Drives Malignant Progression and Osteolytic Disease in Multiple Myeloma
Authors: Xu Linlin , Mohammad Khalid S. , Wu Hao , Crean Colin , Poteat Bradley , Cheng Yinghua , Cardoso Angelo A. , Machal Christophe , Hanenberg Helmut , Abonour Rafat , Kacena Melissa A. , Chirgwin John , Suvannasankha Attaya , Srour Edward F.
Published: September 2016

Multiple myeloma is incurable once osteolytic lesions have seeded at skeletal sites, but factors mediating this deadly pathogenic advance remain poorly understood. Here, we report evidence of a major role for the cell adhesion molecule CD166, which we discovered to be highly expressed in multiple myeloma cell lines and primary bone marrow cells from patients. CD166+ multiple myeloma cells homed more efficiently than CD166− cells to the bone marrow of engrafted immunodeficient NSG mice. CD166 silencing in multiple myeloma cells enabled longer survival, a smaller tumor burden, and less osteolytic lesions, as compared with mice bearing control cells. CD166 deficiency in multiple myeloma cell lines or CD138+ bone marrow cells from multiple myeloma patients compromised their ability to induce bone resorption in an ex vivo organ culture system. Furthermore, CD166 deficiency in multiple myeloma cells also reduced the formation of osteolytic disease in vivo after intratibial engraftment. Mechanistic investigation revealed that CD166 expression in multiple myeloma cells inhibited osteoblastogenesis of bone marrow–derived osteoblast progenitors by suppressing Runx2 gene expression. Conversely, CD166 expression in multiple myeloma cells promoted osteoclastogenesis by activating TRAF6-dependent signaling pathways in osteoclast progenitors. Overall, our results define CD166 as a pivotal director in multiple myeloma cell homing to the bone marrow and multiple myeloma progression, rationalizing its further study as a candidate therapeutic target for multiple myeloma treatment. Cancer Res; 76(23); 6901–10. ©2016 AACR.
Olaparib, Monotherapy or with Ionizing Radiation, Exacerbates DNA Damage in Normal Tissues: Insights from a New p21 Reporter Mouse
Authors: McMahon Michael , Frangova Tania G. , Henderson Colin J. , Wolf C. Roland
Published: September 2016

Many drugs targeting the DNA damage response are being developed as anticancer therapies, either as single agents or in combination with ionizing radiation (IR) or other cytotoxic agents. Numerous clinical trials in this area are either in progress or planned. However, concerns remain about the potential of such treatments to increase toxicity to normal tissues. In order to address this issue, a novel reporter mouse line was created through the simultaneous incorporation of multiple reporters, β-galactosidase, and firefly luciferase, into the DNA damage–inducible p21 (CDKN1A) locus. The data demonstrate that in situ β-galactosidase staining facilitates high fidelity mapping of p21 expression across multiple organs and tissues at single-cell resolution, whereas the luciferase reporter permits noninvasive bioluminescent imaging of p21 expression. This model was used to determine the capacity of a number of DNA-damaging agents, including IR, cisplatin, and etoposide to induce p21 expression in normal tissues. In addition, the PARP inhibitor olaparib was examined alone or in combination with IR as well as cisplatin. A single exposure to olaparib alone caused DNA damage to cells in the mucosal layer lining mouse large intestine. It also exacerbated DNA damage induced in this organ and the kidney by coadministered IR. These studies suggest that olaparib has carcinogenic potential and illustrate the power of this new model to evaluate the safety of new therapeutic regimens involving combination therapies.

Implications: Olaparib causes DNA damage to normal tissues and might be a carcinogen. Mol Cancer Res; 14(12); 1195–203. ©2016 AACR.
Sleep and Breathing … and Cancer?
Authors: Owens Robert L. , Gold Kathryn A. , Gozal David , Peppard Paul E. , Jun Jonathan C. , Dannenberg Andrew J. , Lippman Scott M. , Malhotra Atul
Published: September 2016

Sleep, like eating and breathing, is an essential part of the daily life cycle. Although the science is still emerging, sleep plays an important role in immune, cardiovascular, and neurocognitive function. Despite its great importance, nearly 40% of U.S. adults experience problems with sleep ranging from insufficient total sleep time, trouble initiating or maintaining sleep (Insomnia), circadian rhythm disorders, sleep-related movement disorders, and sleep-related breathing disorders such as obstructive sleep apnea (OSA). Herein, we discuss new evidence that suggests that sleep may also affect carcinogenesis. Specifically, we review recent epidemiologic data suggesting links between cancer and OSA. As OSA is a common, underdiagnosed, and undertreated condition, this has public health implications. Intriguing animal model data support a link between cancer and sleep/OSA, although mechanisms are not yet clear. Leaders in the fields of sleep medicine, pulmonology, and oncology recently met to review and discuss these data, as well as to outline future directions of study. We propose a multidisciplinary, three-pronged approach to studying the associations between cancer and sleep, utilizing mutually interactive epidemiologic studies, preclinical models, and early-phase clinical trials. Cancer Prev Res; 9(11); 821–7. ©2016 AACR.
Systematic Functional Characterization of Resistance to PI3K Inhibition in Breast Cancer
Authors: Le Xiuning , Antony Rajee , Razavi Pedram , Treacy Daniel J. , Luo Flora , Ghandi Mahmoud , Castel Pau , Scaltriti Maurizio , Baselga José , Garraway Levi A.
Published: September 2016

PIK3CA (which encodes the PI3K alpha isoform) is the most frequently mutated oncogene in breast cancer. Small-molecule PI3K inhibitors have shown promise in clinical trials; however, intrinsic and acquired resistance limits their utility. We used a systematic gain-of-function approach to identify genes whose upregulation confers resistance to the PI3K inhibitor BYL719 in breast cancer cells. Among the validated resistance genes, Proviral Insertion site in Murine leukemia virus (PIM) kinases conferred resistance by maintaining downstream PI3K effector activation in an AKT-independent manner. Concurrent pharmacologic inhibition of PIM and PI3K overcame this resistance mechanism. We also observed increased PIM expression and activity in a subset of breast cancer biopsies with clinical resistance to PI3K inhibitors. PIM1 overexpression was mutually exclusive with PIK3CA mutation in treatment-naïve breast cancers, suggesting downstream functional redundancy. Together, these results offer new insights into resistance to PI3K inhibitors and support clinical studies of combined PIM/PI3K inhibition in a subset of PIK3CA-mutant cancers.

Significance: PIM kinase overexpression confers resistance to small-molecule PI3K inhibitors. Combined inhibition of PIM and PI3K may therefore be warranted in a subset of breast cancers. Cancer Discov; 6(10); 1134–47. ©2016 AACR.

This article is highlighted in the In This Issue feature, p. 1069
Potential Significance of Circular RNA in Human Placental Tissue for Patients with Preeclampsia
Authors: Qian Yating , Lu Yuanqing , Rui Can , Qian Yujia , Cai Manhong , Jia Ruizhe
Published: September 2016

Aims: This study aimed to identify the different expression of circular RNAs (circRNAs) in the placental tissues of pregnant women with preeclampsia (PE) and to provide a new avenue of research regarding the pathological mechanisms of PE. Methods: In this study, we collected 40 placental tissues from PE patients and 35 placental tissues from gestational age-matched patients who gave premature birth. Arraystar circRNA Microarray Technology (KANGCHEN, Shanghai, China) was used to analyze the differential expression of circRNAs. According to the basic content of circRNAs in the two groups and their fold changes and due to the practicability of the designed divergent primers of each candidate circRNA, we selected three up-regulated circRNAs, hsa_circRNA_100782, hsa_circRNA_102682 and hsa_circRNA_104820, to validate the data. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was utilized to estimate the Ct values in both groups. We further evaluated the differences with a paired t-test and a receiver operating characteristic (ROC) curve. Results: Many circRNAs were found to be differentially expressed in PE placental tissues versus their controls; of these, 143 circRNAs were up-regulated and 158 were down-regulated. The expression levels of hsa_circRNA_100782 (p < 0.05), hsa_circRNA_102682 (p < 0.05), and hsa_circRNA_104820 (p < 0.0001) were validated as significantly up-regulated in the experimental group compared with the controls. Finally, we performed a literature comparison to forecast the possible mechanisms of circRNA function during PE. Conclusion: circRNA expression significantly differed in placental PE tissues compared with controls. According to the circRNA microarray results and the existing papers, circRNAs may contribute to the pathogenesis of PE by acting as miRNA sponges; this possibility requires additional investigation in future studies.
Dimethyloxalylglycine Promotes Bone Marrow Mesenchymal Stem Cell Osteogenesis via Rho/ROCK Signaling
Authors: Zhang Lei , Jiang Guoliang , Zhao Xueling , Gong Yuekun
Published: September 2016

Background/Aims: We investigated the role of dimethyloxalylglycine (DMOG) in bone marrow mesenchymal stem cell (BMSC) osteogenesis mediated by RhoA/ROCK. Methods: BMSCs were cultured with and without DMOG and/or Y-27632 (ROCK1 inhibitor). Cell proliferation, alkaline phosphatase (ALP) levels, and calcium deposits were determined. The expression of Runx2, OSX, p-cofilin, RhoA, and GTP-bound RhoA was determined by real-time RT-PCR and Western blot. Rho-associated coiled-coil-containing protein kinase (ROCK) activity was determined by measuring the phosphorylation of myosin-binding subunit of myosin phosphatase using an ELISA kit. Actin morphology was observed by immunofluorescence. Results: After 24 h, DMOG (0.5 mM) increased the expression of GTP-bound RhoA (+141%, P < 0.001) and enhanced ROCK activity (315%, P < 0.001). DMOG (0.5 mM) enhanced ALP levels after 3, 7, and 21 days of osteogenic induction (all P < 0.001) and strengthened calcium deposition (P < 0.001). In addition, compared with controls, DMOG (0.5 mM) increased the mRNA levels of osteogenesis genes RUNX2 and OSX (all P < 0.001). Furthermore, compared with controls, DMOG increased the expression of p-cofilin (+57%, P < 0.001), which resulted in rearrangement of actin filaments. All these effects were abolished, at least in part, by Y-27632. Conclusion: DMOG promotes BMSC osteogenic differentiation via activation of RhoA/ROCK, suggesting clues for future therapies using BMSCs.
Effects of Different Substrates on Lignocellulosic Enzyme Expression, Enzyme Activity, Substrate Utilization and Biological Efficiency of Pleurotus Eryngii
Authors: Xie Chunliang , Yan Li , Gong Wenbing , Zhu Zuohua , Tan Senwei , Chen Du , Hu Zhenxiu , Peng Yuande
Published: September 2016

Background/Aims: Pleurotus eryngii is one of the most valued and delicious mushrooms which are commercially cultivated on various agro-wastes. How different substrates affect lignocellulosic biomass degradation, lignocellulosic enzyme production and biological efficiency in Pleurotus eryngii was unclear. Methods and Results: In this report, Pleurotus eryngii was cultivated in substrates including ramie stalks, kenaf stalks, cottonseed hulls and bulrush stalks. The results showed that ramie stalks and kenaf stalks were found to best suitable to cultivate Pleurotus eryngii with the biological efficiency achieved at 55% and 57%, respectively. In order to establish correlations between different substrates and lignocellulosic enzymes expression, the extracellular proteins from four substrates were profiled with high throughput TMT-based quantitative proteomic approach. 241 non-redundant proteins were identified and 74 high confidence lignocellulosic enzymes were quantified. Most of the cellulases, hemicellulases and lignin depolymerization enzymes were highly up-regulated when ramie stalks and kenaf stalks were used as carbon sources. The enzyme activities results suggested cellulases, hemicellulases and lignin depolymerization enzymes were significantly induced by ramie stalks and kenaf stalks. Conclusion: The lignocelluloses degradation, most of the lignocellulosic enzymes expressions and activities of Pleurotus eryngii had positive correlation with the biological efficiency, which depend on the nature of lignocellulosic substrates. In addition, the lignocellulosic enzymes expression profiles during Pleurotus eryngii growth in different substrates were obtained. The present study suggested that most of the lignocellulosic enzymes expressions and activities can be used as tools for selecting better performing substrates for commercial mushroom cultivation.
Findings of Optical Coherence Tomographic Angiography at the Choriocapillaris Level in Central Serous Chorioretinopathy
Authors: Shinojima Ari , Kawamura Akiyuki , Mori Ryusaburo , Fujita Kyoko , Yuzawa Mitsuko
Published: September 2016

Purpose: To reveal vascular signals at the choriocapillaris level in central serous chorioretinopathy (CSC) using optical coherence tomographic angiography (OCTA). Procedures: We analyzed vascular signals at the choriocapillaris level in 58 CSC and 51 contralateral eyes by OCTA (RTVue XR Avanti with AngioVue; Optovue Inc., Fremont, Calif., USA). Data analysis included age, best corrected visual acuity (BCVA), disease duration and serous retinal detachment (SRD) height. Results: Morphologically, abnormal signals at the choriocapillaris level were detected in all CSC eyes (100%), and then classified into three patterns. Age, BCVA, disease duration and SRD height showed no significant correlation with signal patterns. Thirty-one contralateral eyes (61%) showed abnormal signals at the choriocapillaris level on OCTA, while 20 (39%) had a normal pattern. Conclusions: OCTA revealed three types of abnormal signals not only in CSC eyes but also in fellow eyes without SRD. OCTA may provide information for elucidating the underlying pathogenesis of CSC.
Missense mutations in the gene encoding prothrombin corresponding to Arg596 cause antithrombin resistance and thrombomodulin resistance
Authors: Takagi Yuki , Murata Moe , Kozuka Toshihiro , Nakata Yukiko , Hasebe Ryo , Tamura Shogo , Takagi Akira , Matsushita Tadashi , Saito Hidehiko , Kojima Tetsuhito
Published: September 2016

Antithrombin (AT) and thrombomodulin (TM) play important roles in the process of natural anticoagulation in vivo. Recently, we reported that the prothrombin Yukuhashi mutation (p.Arg596Leu) was associated with AT and TM resistance-related thrombophilia. To assess the AT and TM resistances associated with other missense mutations by single base substitution in the Arg596 codon, we generated recombinant variants (596Gln, 596Trp, 596Gly, and 596Pro) and investigated the effects on AT and TM anticoagulant functions. All variants except 596Pro were secreted in amounts comparable to that of the wild-type but exhibited variable procoagulant activities. After a 30-minute inactivation by AT, the relative residual activity of wild-type thrombin decreased to 15 ± 4.0%, in contrast to values of all variants were maintained at above 80%. The thrombin–AT complex formation, as determined by enzyme-linked immunosorbent assay, was reduced with all tested variants in the presence and absence of heparin. In the presence of soluble TM (sTM), the relative fibrinogen clotting activity of wild-type thrombin decreased to 16 ± 0.12%, whereas that of tested variants was 37%–56%. In a surface plasmon resonance assay, missense Arg596 mutations reduced thrombin–TM affinity to an extent similar to the reduction of fibrinogen clotting inhibition. In the presence of sTM or cultured endothelial-like cells, APC generation was enhanced differently by variant thrombins in a thrombin–TM affinity- dependent manner. These data indicate that prothrombin Arg596 missense mutations lead to AT and TM resistance in the variant thrombins and suggest that prothrombin Arg596 is important for AT- and TM- mediated anticoagulation.
Monocyte subset distribution is associated with mortality in critically ill patients
Authors: Krychtiuk Konstantin A. , Lenz Max , Koller Lorenz , Honeder Maria C. , Wutzlhofer Lisa , Zhang Chao , Chi Lijian , Maurer Gerald , Niessner Alexander , Huber Kurt , Heinz Gottfried , Speidl Walter S. , Wojta Johann
Published: September 2016

Although patients admitted to an intensive care unit (ICU) suffer from various pathologies, many develop a systemic inflammatory response syndrome (SIRS). As key regulators of innate immunity, monocytes may be crucially involved in SIRS development. Monocytes can be distinguished into three subsets: Classical monocytes (CD14++CD16−; CM), non-classical monocytes (CD14+CD16++CCR2−; NCM) and intermediate monocytes (CD14++CD16+CCR2+; IM). The aim of this prospective, observational study was to analyse whether monocyte subset distribution is associated with 30-day survival in critically ill patients. A total of 195 consecutive patients admitted to a cardiac ICU at a tertiary-care centre were enrolled, blood was taken at admission and after 72 hours and monocyte subset distribution was analysed. Mean APACHE II score was 19.5 ± 8.1 and 30-day mortality was 25.4 %. At admission, NCM were significantly lower in non-survivors as compared to survivors [2.7 (0.4–5.5) vs 4.2 (1.6–7.5)%; p=0.012] whereas CM and IM did not differ according to 30-day survival. In contrast, 72 hours after admission, monocyte subset distribution shifted towards an increased proportion of IM [8.2 (3.9–13.2) vs 4.2 (2.3–7.9)%; p=0.003] with a concomitant decrease of CM [86.9 (78.6–89.2) vs 89.6 (84.9–93.1)%; p=0.02] in non-survivors vs survivors, respectively. NCM at day 3 were not associated with death at 30 days. These results were independent from age, gender, CRP, APACHE II score and primary diagnosis. In conclusion, circulating monocyte subsets are associated with 30-day mortality in critically ill patients. The innate immune system as reflected by monocyte subset distribution may play a major role in ICU outcome despite varying admittance pathologies.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Lower aerobic fitness levels among adolescents of a city in southern Brazil
Authors: Gonçalves Eliane C. A. , Silva Diego A. S.
Published: September 2016

Study design: Cross sectional study. Objective: To analyze the association between lower levels of aerobic fitness and sociodemographic factors, lifestyle and excess body fatness in students. Methods: Study with 84 adolescents aged 14 to 19 years from southern Santa Catarina. Aerobic fitness was assessed by the modified Canadian Aerobic Fitness test-mCAFT. Sociodemographic variables, sexual maturation and lifestyle were assessed self-administered questionnaire. Excess body fatness assessed the sum of skin folds triceps and subscapular. Results: The prevalence of lower level of aerobic fitness was 83.3%. The female gender (OR: 5,99; IC95%: 1,40-25,52) and adolescents little physically active (OR: 5,62; IC95%: 1,21-26,38) had low levels aerobic fitness. Conclusion: The factors had associated with low levels of aerobic fitness were females and physical inactivity
Hospitalization, deaths, expenses respiratory diseases and its relationship with climate change in the municipality of San Carlos - SP, Brazil
Authors: Cruz Deise M. da , Ohara Daniela G. , Castro Shamyr S. de , Jamami Mauricio
Published: September 2016

Study design: Ecological time-series study Objectives: To describe respiratory disease (RD) hospitalizations, deaths, costs and verify their relations with climate change. Methods: Annual and monthly data were collected from hospital admission record (HAR) and deaths of the Department of the Unified Health System provided by the system of the SUS Hospital Information, in the period 2008 to 2012, which included the number of HAR, deaths and costs with RD, according to International Classification of Diseases, in São Carlos/SP, Brazil. In addition, we collected meteorological data (average maximum temperature, average minimum temperature and humidity relative air) through the National Institute of Meteorology (INMET) in the same period. Results: A total of 7.144 RD hospitalizations were authorized, and pneumonia was the most prevalent (59.93%). There was a decrease of HAR and public costs and increased total mortality rate RD (10.8%) from 2008 to 2012. The HAR had moderate (0.50- 0.69) and negative correlation with the average temperature compensated and maximum; and weak negative correlation with average temperature minimum. Mortality rate had a positive weak correlation (0.26-0.49) with average temperature compensated and maximum temperature. Costs had a negative weak correlation with average temperature compensated, maximum and minimum. Conclusion: RD responsible for the largest HAR values and deaths were pneumonia, COPD, acute bronchitis, acute bronchiolitis, asthma and chronic diseases of tonsils and adenoids. It was also observed that climate change were associated with HAR, mortality rate and health costs
Efficacy of indigenous Steinernema abbasi and Heterorhabditis indica isolates as potential biocontrol agent against Holotrichia consanguinea Blanch. (Coleoptera: Scarabaeidae)
Authors: Patil Jagadeesh , Rangasamy Vijayakumar , Verghese Abraham
Published: September 2016

Holotrichia consanguinea is a serious pest of peanut and sugarcane that attacks other commercial crops in India. The efficacy of two species of entomopathogenic nematodes (EPN), Steinernema abbasi and Heterorhabditis indica, against H. consanguinea was tested under laboratory and field conditions. In a laboratory assay, H. indica caused significantly greater mortality (25-100%) than S. abbasi (20-80%) against second instars and H. indica caused 17.5-82.5% mortality in third-instar grub larvae, while S. abbasi caused (10-60%) mortality. These results revealed that second-instar grubs were more susceptible than third-instar grubs and efficacy of EPN against H. consanguinea varies with nematode species. The penetration and multiplication rate for H. indica was significantly higher than those of S. abbasi. Infective juveniles (IJ) of both nematode species and a commonly used insecticide (phorate) were tested against this insect in a field experiment. Field trail data showed that the percentage reduction in H. consanguinea grub population was significantly higher using H. indica at a dose of 2.5 × 109 IJ ha−1 than S. abbasi and phorate application. Phorate application was more efficient in reducing the grub population than both nematode species at the lower application rate (1.25 × 109 IJ ha−1). Overall, these experiments suggest that H. indica may be a promising biocontrol agent against H. consanguinea.