bluuebunny/crossref_metadata_2025 huggingface dataset:
Negative-Pressure Wound Therapy in aPseudomonas aeruginosaInfection Model
Authors: Wang Guoqi , Li Zhirui , Li Tongtong , Wang Song , Zhang Lihai , Zhang Licheng , Tang Peifu
Published: May 2018

Background. Negative-pressure wound therapy (NPWT) is an effective strategy for the management of contaminated wounds, including those infected byPseudomonas aeruginosa. We hypothesized that NPWT would reduce virulence factors as well as biofilm components and inhibit virulence-regulated gene expression in a model ofP. aeruginosawound infection.Methods. Wounds were created in anesthetized rabbits andP. aeruginosawas inoculated to the wound surface for 24 h. Wounds were treated with either NPWT or a sterile gauze dressing. Virulence factors including exotoxin A, rhamnolipid, and elastase were quantified by the enzyme-linked immunosorbent assay, orcinol, and elastin-Congo red methods, respectively. A biofilm component, eDNA, was quantified using a commercial kit. Virulence-regulated genes were determined by quantitative real-time polymerase chain reaction (RT-PCR). Biofilms were observedin vivoby staining with concanavalin A conjugated to Alexa Fluor® 647.Results. NPWT was more effective than the control treatment in reducing virulence factors and bacteria countsin vivo. A biofilm component, eDNA, was less abundant in the NPWT group. The results of the RT-PCR indicated that the expression levels ofP. aeruginosavirulence-regulated genes and quorum-sensing population density-dependent systems were significantly inhibited by NPWT treatment.Conclusion. NPWT reduced bacteria counts, virulence factors, and eDNA in aP. aeruginosawound infection modelin vivo. These beneficial effects are likely to be related to the reduced expression of virulence-regulated genes and the drainage induced by NPWT treatment. These findings may help clinicians to obtain a better understanding of the mechanism of NPWT for the treatment of infected wounds.
Helicopter Rotor Flow Analysis Using Mapped Chebyshev Pseudospectral Method and Overset Mesh Topology
Authors: Im Dong Kyun , Choi Seongim
Published: May 2018

Unsteady helicopter rotor flows are solved by a Chebyshev pseudospectral method with overset mesh topology which employs Chebyshev polynomials for solution approximation and a Chebyshev collocation operator to represent the time derivative term of the unsteady flow governing equations. Spatial derivative terms of the flux Jacobians are discretized implicitly while the Chebyshev spectral derivative term is treated in explicit form. Unlike the Fourier spectral method, collocation points of standard Chebyshev polynomials are not evenly distributed and heavily clustered near the extremities of the time interval, which makes the spectral derivative matrix ill-conditioned and deteriorates the stability and convergence of the flow solution. A conformal mapping of an arcsin function is applied to redistribute those points more evenly and thus to improve the numerical stability of the linear system. A parameter study on the condition number of the spectral derivative matrix with respect to the control parameters of the mapping function is also carried out. For the validation of the proposed method, both periodic and nonperiodic unsteady flow problems were solved with two-dimensional problems: an oscillating airfoil with a fixed frequency and a plunging airfoil with constant plunging speed without considering gravitational force. Computation results of the Chebyshev pseudospectral method showed excellent agreements with those of the time-marching computation. Subsequently, helicopter rotor flows in hovering and nonlifting forward flight are solved. Moving boundaries of the rotating rotor blades are efficiently managed by the overset mesh topology. As a set of subgrids are constructed only one time at the beginning of the solution procedure corresponding to the mapped Chebyshev collocation points, computation time for mesh interpolation of hole-cutting between background and near-body grids becomes drastically reduced when compared to the time-marching computation method where subgrid movement and the hole-cutting need to be carried out at each physical time step. The number of the collocation points was varied to investigate the sensitivity of the solution accuracy, computation time, and memory. Computation results are compared with those from the time-marching computation, the Fourier spectral method, and wind-tunnel experimental data. Solution accuracy and computational efficiency are concluded to be great with the Chebyshev pseudospectral method. Further applications to unsteady nonperiodic problems will be left for future work.
Fibrin Stiffness Mediates Dormancy of Tumor-Repopulating Cells via a Cdc42-Driven Tet2 Epigenetic Program
Authors: Liu Yuying , Lv Jiadi , Liang Xiaoyu , Yin Xiaonan , Zhang Le , Chen Degao , Jin Xun , Fiskesund Roland , Tang Ke , Ma Jingwei , Zhang Huafeng , Dong Wenqian , Mo Siqi , Zhang Tianzhen , Cheng Feiran , Zhou Yabo , Xie Jing , Wang Ning , Huang Bo
Published: May 2018

Dormancy is recognized as a critical biological event for tumorigenic cells surviving in an extremely harsh environment. Understanding the molecular process of dormancy can unlock novel approaches to tackle cancers. We recently reported that stem-like tumor-repopulating cells (TRC) sense mechanical signals and rapidly proliferate in a 90 Pa soft fibrin matrix. Here, we show that a stiff mechanical environment induces TRC dormancy via an epigenetic program initiated by translocation of Cdc42, a cytosolic regulator of mechanotransduction, into the nucleus, where it promotes transcription of hydroxymethylating enzyme Tet2. Tet2 epigenetically activated cell-cycle–inhibiting genes p21 and p27 to induce dormancy, but also caused downregulation of integrin β3 to maintain dormancy. This stiffness-mediated dormancy was recapitulated in mouse models for both murine and primary human melanoma TRCs. These data identify an epigenetic program directed by mechanics, which drives highly tumorigenic TRCs to enter dormancy in a stiff mechanical environment.

Significance: A mechanics-directed epigenetic program enables tumor-repopulating cells to enter dormancy in a stiff mechanical environment. Cancer Res; 78(14); 3926–37. ©2018 AACR.
LRRC15 Is a Novel Mesenchymal Protein and Stromal Target for Antibody–Drug Conjugates
Authors: Purcell James W. , Tanlimco Sonia G. , Hickson Jonathan , Fox Melvin , Sho Mien , Durkin Lisa , Uziel Tamar , Powers Rick , Foster Kelly , McGonigal Thomas , Kumar Subashri , Samayoa Josue , Zhang Dong , Palma Joann P. , Mishra Sasmita , Hollenbaugh Diane , Gish Kurt , Morgan-Lappe Susan E. , Hsi Eric D. , Chao Debra T.
Published: May 2018

Progress in understanding tumor stromal biology has been constrained in part because cancer-associated fibroblasts (CAF) are a heterogeneous population with limited cell-type–specific protein markers. Using RNA expression profiling, we identified the membrane protein leucine-rich repeat containing 15 (LRRC15) as highly expressed in multiple solid tumor indications with limited normal tissue expression. LRRC15 was expressed on stromal fibroblasts in many solid tumors (e.g., breast, head and neck, lung, pancreatic) as well as directly on a subset of cancer cells of mesenchymal origin (e.g., sarcoma, melanoma, glioblastoma). LRRC15 expression was induced by TGFβ on activated fibroblasts (αSMA+) and on mesenchymal stem cells. These collective findings suggested LRRC15 as a novel CAF and mesenchymal marker with utility as a therapeutic target for the treatment of cancers with LRRC15-positive stromal desmoplasia or cancers of mesenchymal origin. ABBV-085 is a monomethyl auristatin E (MMAE)-containing antibody–drug conjugate (ADC) directed against LRRC15, and it demonstrated robust preclinical efficacy against LRRC15 stromal-positive/cancer-negative, and LRRC15 cancer-positive models as a monotherapy, or in combination with standard-of-care therapies. ABBV-085′s unique mechanism of action relied upon the cell-permeable properties of MMAE to preferentially kill cancer cells over LRRC15-positive CAF while also increasing immune infiltrate (e.g., F4/80+ macrophages) in the tumor microenvironment. In summary, these findings validate LRRC15 as a novel therapeutic target in multiple solid tumor indications and support the ongoing clinical development of the LRRC15-targeted ADC ABBV-085.

Significance: These findings identify LRRC15 as a new marker of cancer-associated fibroblasts and cancers of mesenchymal origin and provide preclinical evidence for the efficacy of an antibody-drug conjugate targeting the tumor stroma. Cancer Res; 78(14); 4059–72. ©2018 AACR.
TP53, STK11, and EGFR Mutations Predict Tumor Immune Profile and the Response to Anti–PD-1 in Lung Adenocarcinoma
Authors: Biton Jérôme , Mansuet-Lupo Audrey , Pécuchet Nicolas , Alifano Marco , Ouakrim Hanane , Arrondeau Jennifer , Boudou-Rouquette Pascaline , Goldwasser François , Leroy Karen , Goc Jeremy , Wislez Marie , Germain Claire , Laurent-Puig Pierre , Dieu-Nosjean Marie-Caroline , Cremer Isabelle , Herbst Ronald , Blons Hélène , Damotte Diane
Published: May 2018

Purpose: By unlocking antitumor immunity, antibodies targeting programmed cell death 1 (PD-1) exhibit impressive clinical results in non–small cell lung cancer, underlining the strong interactions between tumor and immune cells. However, factors that can robustly predict long-lasting responses are still needed.

Experimental Design: We performed in-depth immune profiling of lung adenocarcinoma using an integrative analysis based on immunohistochemistry, flow-cytometry, and transcriptomic data. Tumor mutational status was investigated using next-generation sequencing. The response to PD-1 blockers was analyzed from a prospective cohort according to tumor mutational profiles and PD-L1 expression, and a public clinical database was used to validate the results obtained.

Results: We showed that distinct combinations of STK11, EGFR, and TP53 mutations were major determinants of the tumor immune profile (TIP) and of the expression of PD-L1 by malignant cells. Indeed, the presence of TP53 mutations without co-occurring STK11 or EGFR alterations (TP53-mut/STK11-EGFR-WT), independently of KRAS mutations, identified the group of tumors with the highest CD8 T-cell density and PD-L1 expression. In this tumor subtype, pathways related to T-cell chemotaxis, immune cell cytotoxicity, and antigen processing were upregulated. Finally, a prolonged progression-free survival (PFS: HR = 0.32; 95% CI, 0.16–0.63, P < 0.001) was observed in anti–PD-1-treated patients harboring TP53-mut/STK11-EGFR-WT tumors. This clinical benefit was even more remarkable in patients with associated strong PD-L1 expression.

Conclusions: Our study reveals that different combinations of TP53, EGFR, and STK11 mutations, together with PD-L1 expression by tumor cells, represent robust parameters to identify best responders to PD-1 blockade. Clin Cancer Res; 24(22); 5710–23. ©2018 AACR.
Combined HDAC and Bromodomain Protein Inhibition Reprograms Tumor Cell Metabolism and Elicits Synthetic Lethality in Glioblastoma
Authors: Zhang Yiru , Ishida Chiaki Tsuge , Ishida Wataru , Lo Sheng-Fu L. , Zhao Junfei , Shu Chang , Bianchetti Elena , Kleiner Giulio , Sanchez-Quintero Maria J. , Quinzii Catarina M. , Westhoff Mike-Andrew , Karpel-Massler Georg , Canoll Peter , Siegelin Markus D.
Published: May 2018

Purpose: Glioblastoma remains a challenge in oncology, in part due to tumor heterogeneity.

Experimental Design: Patient-derived xenograft and stem-like glioblastoma cells were used as the primary model systems.

Results: Based on a transcriptome and subsequent gene set enrichment analysis (GSEA), we show by using clinically validated compounds that the combination of histone deacetylase (HDAC) inhibition and bromodomain protein (BRD) inhibition results in pronounced synergistic reduction in cellular viability in patient-derived xenograft and stem-like glioblastoma cells. Transcriptome-based GSEA analysis suggests that metabolic reprogramming is involved with synergistic reduction of oxidative and glycolytic pathways in the combination treatment. Extracellular flux analysis confirms that combined HDAC inhibition and BRD inhibition blunts oxidative and glycolytic metabolism of cancer cells, leading to a depletion of intracellular ATP production and total ATP levels. In turn, energy deprivation drives an integrated stress response, originating from the endoplasmic reticulum. This results in an increase in proapoptotic Noxa. Aside from Noxa, we encounter a compensatory increase of antiapoptotic Mcl-1 protein. Pharmacologic, utilizing the FDA-approved drug sorafenib, and genetic inhibition of Mcl-1 enhanced the effects of the combination therapy. Finally, we show in orthotopic patient-derived xenografts of GBM, that the combination treatment reduces tumor growth, and that triple therapy involving the clinically validated compounds panobinostat, OTX015, and sorafenib further enhances these effects, culminating in a significant regression of tumors in vivo.

Conclusions: Overall, these results warrant clinical testing of this novel, efficacious combination therapy. Clin Cancer Res; 24(16); 3941–54. ©2018 AACR.
Temporal Efficacy of a Sulforaphane-Based Broccoli Sprout Diet in Prevention of Breast Cancer through Modulation of Epigenetic Mechanisms
Authors: Li Yuanyuan , Buckhaults Phillip , Li Shizhao , Tollefsbol Trygve
Published: May 2018

Breast cancer is the most common cancer and the second leading cause of cancer-related death among women. An important risk factor for breast cancer is individual genetic background, which is initially generated early in human life, for example, during the processes of embryogenesis and fetal development in utero. Bioactive dietary components such as sulforaphane (SFN), an isothiocyanate from cruciferous vegetables including broccoli sprouts (BSp), cabbage, and kale, has been shown to reduce the risk of developing many common cancers through regulation of epigenetic mechanisms. Our study indicates a prenatal/maternal BSp dietary treatment exhibited maximal preventive effects in inhibiting breast cancer development compared with postnatal early-life and adult BSp treatments in two transgenic mouse models that can develop breast cancer. Postnatal early-life BSp treatment starting prior to puberty onset showed protective effects in prevention of breast cancer but was not as effective as the prenatal/maternal BSp treatment. However, adulthood-administered BSp diet did not reduce mammary tumorigenesis. Our results suggest that the prenatal/maternal BSp bioactive natural plant product may impact early embryonic development by regulating global differential gene expression through affecting epigenetic profiles resulting in differential susceptibility to breast cancer later in life. These results suggest that a temporal exposure to epigenetic-modulating dietary components such as cruciferous vegetables could be a key factor for maximizing chemopreventive effects on human breast cancer. This study may lead to translational breast cancer chemopreventive potential by appropriate administration of key dietary components leading to early breast cancer prevention in humans. Cancer Prev Res; 11(8); 451–64. ©2018 AACR.
Relevance of Dementia in Atrial Fibrillation Patients within a Specific European Health Care Area
Authors: Rodríguez-Mañero Moisés , López-Pardo Estrella , Cordero Alberto , Kreidieh Omar , Novo Platas José , Valdés Luis , Cid-Menendez Adrian , García-Seara Javier , Pereira-Vázquez María , Martínez-Sande Jose-Luis , Ruano Alberto , Peña-Gil Carlos , Mazón Pilar , García-Acuña Jose María , González-Juanatey José Ramón
Published: May 2018

Introduction: Atrial fibrillation might increase the risk of dementia. We aim to test the hypothesis that dementia could reclassify the actual risk of stroke and death predicted by the CHA2DS2-VASc in patients with atrial fibrillation (AF). Methods: A prospective study performed in a specific health care area. Results: From our health care area (n = 348,985), throughout 2013, AF was codified in 7,990 (2.08%). Mean age was 76.83 ± 10.5, mean CHA2DS2-VASc = 3.5, 4,056 (50.8%) were females and 287 (3.6%) were diagnosed to have dementia. Patients with dementia were older and presented a higher rate of all the components of the CHA2DS2-VASc-expect vasculopathy. Differences in overall mortality were observed but not in stroke and haemorrhagic events. After propensity score matched analysis, dementia was independently associated with all-cause mortality. Addition of dementia to CHA2DS2-VASc reclassified 7.7 and 16.6% of the cohort with regard to thromboembolic events and death risk respectively. Conclusions: Patients with dementia presented a more adverse risk profile, with significant differences in all-cause mortality.
Epidemiology of Traumatic Spinal Cord Injury in Ireland, 2010–2015
Authors: Smith Eimear , Fitzpatrick Patricia , Murtagh John , Lyons Frank , Morris Seamus , Synnott Keith
Published: May 2018

Background: The International Spinal Cord Society and World Health Organisation recommend the collection of epidemiological data on traumatic spinal cord injury (TSCI). A 1-year prospective study is ongoing in Ireland. While the results of this study are awaited, it was concluded from a feasibility exercise that a complete retrospective dataset, 2010–2015, could be obtained and would be useful for service planning. Methods: All patients with TSCI discharged from the national SCI acute and rehabilitation centres were included. Data was collected on gender, age, aetiology, level of injury, American Spinal Injuries Association impairment scale, length of rehabilitation admission and discharge destination. Population denominators were national census figures 2006 and 2011, rolled forward. Results: The incidence of TSCI remained constant throughout the study period, 11.5–13.3 per million per year. The mean age of injury onset was 48.9 (SD 19.8) years. Males accounted for 71.5%. The most common injury level/AIS was incomplete tetraplegia, accounting for 43.2% of all TSCI. Leading aetiology was falls, accounting for 53.3% of injuries. Patients with incomplete tetraplegia were older than those with all other injuries (p < 0.001). Conclusions: The epidemiological trends identified are similar to those prevalent elsewhere in the developed world. More incomplete tetraplegia among an older patient population necessitates a review of how acute care and rehabilitation services are delivered.
Evaluation of the HER2 and Hormone Receptor Status in Metastatic Breast Cancer Using Cell Blocks: A Multi-Institutional Study
Authors: Nishimura Rieko , Murata Yuya , Mori Kiyoshi , Yamashiro Katsushige , Kuraoka Kazuya , Ichihara Shu , Taguchi Kenichi , Suzuki Hiroyoshi , Ito Masahiro , Yamashita Natsumi
Published: May 2018

Objective: We explore the problems associated with the cell block (CB) method for receptor analysis in breast cancer metastases and propose a method for reporting the results. Study Design: Nine institutions used the CB method for the analysis of hormone receptors (HRs) and HER2 (human epidermal growth factor receptor 2) protein in cytological specimens of breast cancer metastases in routine practice. The stained slides were independently evaluated by 8 pathologists. Dual in situ hybridization assay was performed in cases of discordant results for HER2 protein. Based on the results, we propose a method for receptor scoring in the CB method. Results: Of 61 specimens, 57 contained tumor cells. Two or more pathologists disagreed on the results for the estrogen receptor, progesterone receptor, and HER2 protein in 3 (5.3%), 13 (22.8%), and 19 (33.3%) cases, respectively. The discrepant results for the HRs were attributed to the presence of a few positive cells or faintly stained cells. The high interobserver discordance rate for HER2 protein was explained by interobserver differences in the scoring criteria. Conclusion: The use of categorical scoring into positive and negative is recommended for evaluating the HR expressions. Use of strict criteria for HER2 protein 2+ and 3+ cases is recommended, as HER2-positive cases should not be missed.
Reactive Lymphoid Hyperplasia or Tubercular Lymphadenitis: Can Real-Time PCR on Fine-Needle Aspirates Help Physicians in Concluding the Diagnosis?
Authors: Gupta Vivek , Bhake Arvind
Published: May 2018

Background: Enlarged lymph nodes in adult patients often present a diagnostic challenge. In the absence of granuloma or necrosis, the cytology/tissue findings are misleading and relate the enlarged lymph nodes to reactive lymphoid hyperplasia (RLH), because granuloma formation is an immunological response that usually takes 14–100 days to develop. This study assesses the role of real-time (RT)-PCR in the diagnosis of the Mycobacterium complex (MTBC) in lymph node aspirates compared with culture in cases of RLH. Methods: A cross-sectional study was conducted on 112 patients, aged 15–74 years, with a diagnosis of RLH on cytology. RT-PCR for MTBC detection and culture on Löwenstein-Jensen medium for tubercular bacilli was done on lymph node aspirates. Comparative values with reference to culture were calculated. The χ2 value, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LR) were calculated. Results: Out of 112 RLH cases, 35 (31%) were positive on both RT-PCR and culture. RT-PCR was positive in 43 cases and culture was positive in 44 cases. The χ2 test was found to be highly significant. PPV, NPV, positive LR, and negative LR were 81.4%, 87%, 6.76, and 0.23, respectively. Conclusion: RT-PCR for MTBC proves to be useful in arriving at a conclusive diagnosis in patients with a cytological diagnosis of RLH.
SCCA, TSGF, and the Long Non-Coding RNA AC007271.3 are Effective Biomarkers for Diagnosing Oral Squamous Cell Carcinoma
Authors: Shao Tingru , Huang Jiaxin , Zheng Zenan , Wu Qingqing , Liu Tiancai , Lv Xiaozhi
Published: May 2018

Background/Aims: Oral squamous cell carcinoma (OSCC) is one of the most lethal malignancies worldwide and the most common type of oral cancer, characterized by invasive growth, frequent regional metastases, high recurrence, and poor prognosis. In the current study, we investigated the use of long non-coding RNAs (lncRNAs), tumor-specific growth factor (TSGF), and squamous cell carcinoma antigen (SCCA) as potential biomarkers for OSCC screening. Methods: LncRNA expression was measured by microarray analysis in three sets of OSCC and paired normal mucosal tissues. The potential lncRNAs involved in OSCC development were investigated by bioinformatics and verification experiments. We also determined the expression of these potential biomarkers in tissue and serum samples in a case–control study of 80 OSCC cases and 70 controls. Receiver operating characteristics, decision curve analysis, and the combined detection of lncRNA AC007271.3, TSGF, and SCCA were carried out to screen for OSCC biomarkers. Results: A total of 691 lncRNAs (433 upregulated and 258 downregulated) were differentially expressed in OSCC tissues compared with normal controls (p< 0.05). Based on Gene Ontology and pathway analysis, we selected four differentially expressed lncRNAs (AC007271.3, AC007182.6, LOC283481, and RP11-893F2.9), and showed that aberrant AC007271.3 levels in OSCC patients were significantly associated with clinical stage, especially in early-stage disease, in an expanded case–control study. The combination of AC007271.3 and SCCA (AUC=0.902, p< 0.001) showed significantly better ability to discriminate between OSCC and controls compared with SCCA or AC007271.3 alone. Serum AC007271.3, SCCA, and TSGF levels could also discriminate between OSCC and normal controls with sensitivities of 77.6%, 55.0%, and 63.3%, and specificities of 84.5%, 93.3%, and 66.7%, respectively. Conclusions: These results suggest that AC007271.3, SCCA, and TSGF could be novel circulating biomarkers for the determination of OSCC. However, further validation in large-scale prospective studies is necessary.
Peptidomic Analysis of Endometrial Tissue from Patients with Ovarian Endometriosis
Authors: Xue Yunping , Xu Pengfei , Xu Sujuan , Xue Kai , Xu Lingling , Chen Jie , Xu Juan , Shi Xiaoyan , Li Qian , Gu Lin
Published: May 2018

Background/Aims: Ovarian endometriosis (OvE) is ovarian cyst that is lined with endometrial tissue. They are found in 17–44% of women with endometriosis. Their clinical manifestations include pelvic pain, dysmenorrhea, dyspareunia, and infertility. Although the incidence of OvE has increased yearly, the exact pathogenesis of OvE is still unclear. We used peptidomics, an emerging branch of proteomics, to identify differentially expressed peptides in order to determine the possible roles of these peptides in the pathogenesis of OvE. Methods: The ectopic and eutopic endometria of OvE were used to extract peptides with 10-kDa molecular weight cutoff filters, and the peptide precursor proteins were then identified with PEAKS software, followed by quantification with the TMT labeling method and subsequent analysis by liquid chromatography-tandem mass spectrometry. Gene ontology (GO) analysis, pathway analysis, SMART, and SABLE were used to study the possible functions of these peptide according to their precursor proteins’ function. The effects of peptides derived from VCAM-1 (PDFV) on endometrial stromal cell (ESC) migration and invasion were examined with wound healing assays and Transwell assays and the expression of E-cadherin was detected by western blotting. Results: A total of 491 peptides were identified with abundant differences between the two groups of samples (p < 0.05, and absolute fold change ≥ 2). SMART and SABLE database showed that 42 of the 491 peptides were located in the conserved structural domains of their protein precursors and contained secondary structure and, among them, 2 peptides’ precursor proteins were associated with the cell proliferation. Additionally, 5 peptides’ precursor proteins were associated with endometriosis. Our study confirmed that PDFV promoted ESC migration and invasion and reduced E-cadherin expression (p < 0.05). Conclusion: PDFV and its precursor protein VCAM-1 may be involved in the process of OvE formation by reducing the expression of E-cadherin. The peptidomics analysis provides new insight for future studies of the mechanisms of OvE development.
FGFR4 Links Glucose Metabolism and Chemotherapy Resistance in Breast Cancer
Authors: Xu Min , Chen Shuzheng , Yang Weibin , Cheng Xue , Ye Yani , Mao Jianting , Wu Xulu , Huang Li , Ji Jiansong
Published: May 2018

Background/Aims: Poor response to chemotherapy leads to the relapse and metastatic progression of tumors. Reprogrammed glucose metabolism is one of the important hallmarks of cancer that facilitates cancer cell survival, proliferation and chemoresistance. However, the precise fate of glucose metabolism and its role in therapy responsiveness in cancers remains largely unexplored. Methods: The glycolytic phenotype of doxorubicin (ADR)-resistant breast cancer cells and their parental cells was assessed by measuring glucose uptake, lactate release, and extracellular acidification rate (ECAR). Protein expression was detected by Western blotting analysis and mRNA expression was detected using q-PCR. Cell survival ratio was determined by the cell counting kit 8 assay. The role of fibroblast growth factor receptor 4 (FGFR4) in glycolysis, chemoresistance, and the underlying mechanisms were studied by using gene expression microarray and short hairpin RNA-mediated gene knockdown. Results: We found that glycolytic flux are increased in two doxorubicin (ADR)-resistant breast cancer cell lines compared with their parental wild type cells, as demonstrated by increased glucose uptake, lactate release, and extracellular acidification rate (ECAR). By gene expression microarray, we identified FGFR4 as a critical modulator of ADR resistance and enhanced glucose metabolism. Genetic silencing of FGFR4 increased the chemosensitivity and suppressed the enhanced glycolytic flux in ADR-resistant cells. Mechanistically, activation of FGFR4 signaling in ADR-resistant cells led to the phosphorylation of FGF receptor substrate 2 (FRS2) and further activated the downstream MAPK/ERK signaling. Pharmacological inhibition of FGFR4-FRS2-ERK signaling pathway significantly blocked the chemoresistant and glycolytic phenotypes of ADR-resistant cells. Conclusion: Our findings suggest that high levels of FGFR4 can increase glucose metabolism and lead to chemoresistance in breast cancer and reveal the mechanistic basis for targeting FGFR4 as a therapeutic opportunity for chemoresistant tumors.
Interleukin-33 Predicts Poor Prognosis and Promotes Renal Cell Carcinoma Cell Growth Through its Receptor ST2 and the JNK Signaling Pathway
Authors: Wu Chang-wen , Wu Yi-guo , Cheng Cheng , Hong Zheng-dong , Shi Zi-min , Lin Shuang-quan , Li Jie , He Xiao-yi , Zhu An-yi
Published: May 2018

Background/Aims: Renal cell carcinoma (RCC) is currently the ninth most common cancer in men. Interleukin (IL)-33 expression has previously been associated with a number of cancers; however, its biological role in RCC is poorly understood. In this study, we sought to elucidate the role of IL-33 in RCC. Methods: Serum IL-33 levels were measured by ELISA. IL-33 expression in clinical RCC samples was examined by immunocytochemistry. The proliferation and apoptosis rate of RCC were determined by CCK8 and flow cytometry. Mcl1 and Bcl-2 expression were measured by quantitative real-time PCR and western blotting. JNK expression were measured by western blotting and flow cytometry. The in vivo role of IL-33 in RCC tumorigenesis was examined by animal models. Results: We found that increased expression of IL-33 in RCC was associated with tumor-lymph node-metastasis (TNM) stage and inversely correlated with prognosis. IL-33 enhances RCC cell growth in vivo and stimulates RCC cell proliferation and prevents chemotherapy-induced tumor apoptosis in vitro. Furthermore, we demonstrated that IL-33 promotes RCC cell proliferation and chemotherapy resistance via its receptor ST2 and the JNK signaling activation in tumor cells. Conclusion: Our findings suggest that targeting IL-33/ST2 and JNK signaling may have potential value in the treatment of RCC.
Treatment of Cutaneous Ulcers with Multilayered Mixed Sheets of Autologous Fibroblasts and Peripheral Blood Mononuclear Cells
Authors: Mizoguchi Takahiro , Ueno Koji , Takeuchi Yuriko , Samura Makoto , Suzuki Ryo , Murata Tomoaki , Hosoyama Tohru , Morikage Noriyasu , Hamano Kimikazu
Published: May 2018

Background/Aims: We have developed a mixed-cell sheet consisting of autologous fibroblasts and peripheral blood mononuclear cells with a high potency for angiogenesis and wound healing against refractory cutaneous ulcers in mouse and rabbit models. To increase the effectiveness of the mixed sheet, we developed a multilayered mixed sheet. Methods: We assessed the therapeutic effects of multilayered sheets on cutaneous ulcers in mice. Growth factors and chemokines were assessed by enzyme-linked immunosorbent assay. Angiogenesis and fibroblast migration were measured by using tube formation and migration assays. Wound healing rate of cutaneous ulcers was evaluated in mice with diabetes mellitus. Results: The concentration of secreted vascular endothelial growth factor, hepatocyte growth factor, transforming growth factor, C-X-C motif chemokine ligand (CXCL)-1, and CXCL-2 in multilayered sheets was much higher than that in single-layered mixed-cell sheets (single-layered sheets) and multilayered sheets of fibroblasts alone (fibroblast sheets). The supernatant in multilayered sheets enhanced angiogenic potency and fibroblast migration compared with single-layered and fibroblast sheets in an in vitro experiment. The wound healing rate in the multilayered sheet-treated group was higher compared with the no-treatment group (control) at the early stage of healing. Moreover, both vessel lumen area and microvessel density in tissues treated with multilayered sheets were significantly increased compared with tissues in the control group. Conclusion: Multilayered sheets promoted wound healing and microvascular angiogenesis in the skin by supplying growth factors and cytokines. Accordingly, our data suggest that multilayered sheets may be a promising therapeutic material for refractory cutaneous ulcers.
Observação participante do processo de ensaio: considerações práticas e dilemas éticos
Authors: McAuley Gay
Published: May 2018

Observação e análise do processo de ensaio praticado na Universidade de Sydney. Comparação com a genética do teatro. Relato histórico do desenvolvimento do modelo de Sydney, baseado na colaboração com artistas de teatro profissionais. Objetivos da pesquisa: reforçar a apreciação da mise-en-scène, insights sobre os processos de criatividade do grupo. Conceitos e abordagens metodológicas emprestadas da etnografia e aplicadas ao estudo do ensaio: campo e trabalho de campo, observação participante/não participante, sociabilidade do grupo, insiders e outsiders, prestar atenção às palavras usadas, descrição densa. O artigo conclui com observações relativas à agência criativa na prática de ensaio e a natureza da criatividade do grupo.
Autoetnografia: um caminho metodológico para a pesquisa em artes performativas
Authors: Santos Camila Matzenauer dos , Biancalana Gisela Reis
Published: May 2018

Este artigo discorre acerca do método de pesquisa autoetnográfico aplicado a um fazer artístico performativo em desenvolvimento no mestrado em Artes Visuais. Neste contexto, o trabalho é acompanhado e, consequentemente, atravessado colaborativamente pela artista docente-pesquisadora que orienta a investigação. O percurso reflexivo desenvolvido ancora-se em diferentes autores, como Laplantine, Fortin e Cattani, para abordagem deste procedimento metodológico e sua aplicação em duas performances: Diane e Yasmin.
Parâmetros fenomenológicos para pesquisa qualitativa em artes cênicas
Authors: Silva Carlos Alberto
Published: May 2018

Este artigo é a primeira parte de um ensaio cujo objetivo é expor o emprego de alguns parâmetros do método fenomenológico de pesquisa qualitativa, estruturado para um estudo sobre a operacionalidade do gesto cênico e que constituiu minha tese de doutorado no âmbito do programa de pós-graduação da ECA-USP, a qual foi editada pela Nova Editora Acadêmica com o título Operacionalidade do gesto poético: do cotidiano à cena. Nesta etapa são abordados, em particular, aspectos epistemológicos que fundamentam o método, bem como alguns procedimentos que pontuam o trânsito entre noções teóricas e articulações práticas na estruturação metodológica para orientar a percepção, o registro, a organização e a análise de dados, que derivaram do acompanhamento de performances cênicas envolvendo três atrizes em processos criativos de diferentes montagens.
Ânima trama: memória, afeto e artesania como tecido de um processo de criação
Authors: Lavand Ana Rosangela Colares
Published: May 2018

Este artigo deve ser compreendido como produção têxtil, tessitura e texto de uma dança tramada, um tecido doutoral bordado em linhas de processos de criação, sendo estes cerzidos a partir de três fios condutores: memória, afeto e artesania. Arte(sanato) que se alinha a têxteis outros – tessituras de Saramago, Spinoza, Sennett, Ostrower e Salles – a compor uma trama inicial de um processo que se pretende criação de uma dança bordada, configurada a partir de linhas, fios e tecidos.
Combined Electrophysiological and Behavioral Evidence for the Suppression of Salient Distractors
Authors: Gaspelin Nicholas , Luck Steven J.
Published: May 2018

Researchers have long debated how salient-but-irrelevant features guide visual attention. Pure stimulus-driven theories claim that salient stimuli automatically capture attention irrespective of goals, whereas pure goal-driven theories propose that an individual's attentional control settings determine whether salient stimuli capture attention. However, recent studies have suggested a hybrid model in which salient stimuli attract visual attention but can be actively suppressed by top–down attentional mechanisms. Support for this hybrid model has primarily come from ERP studies demonstrating that salient stimuli, which fail to capture attention, also elicit a distractor positivity (PD) component, a putative neural index of suppression. Other support comes from a handful of behavioral studies showing that processing at the salient locations is inhibited compared with other locations. The current study was designed to link the behavioral and neural evidence by combining ERP recordings with an experimental paradigm that provides a behavioral measure of suppression. We found that, when a salient distractor item elicited the PD component, processing at the location of this distractor was suppressed below baseline levels. Furthermore, the magnitude of behavioral suppression and the magnitude of the PD component covaried across participants. These findings provide a crucial connection between the behavioral and neural measures of suppression, which opens the door to using the PD component to assess the timing and neural substrates of the behaviorally observed suppression.
A common heritage of behaviour systems
Authors: Bowers Robert Ian
Published: May 2018

Behaviour systems theory had its beginnings with Nikolaas Tinbergen’s “hierarchical systems”, an aspect of his thinking and writing that he conspicuously left out of his very memorable 1963 manifesto. This starting point has since been developed within psychology, where it has provided numerous advances. Tinbergen’s aspiration for behaviour systems had been principled integration of ethology with physiology, but the bridge among sciences it ultimately provided led to psychology. To an ethology audience, this paper attempts to reintroduce behaviour systems as a part of Tinbergen’s legacy to make accessible the theoretical developments of behaviour systems theory that have occurred outside of ethology over the last several decades. To a psychology audience, the paper serves as a reminder of the ethological origins of behaviour systems. Both sciences and their integration stand to benefit from recognising this point of common heritage.
The Status of the Bihari Community in Bangladesh under Domestic and International Law
Authors: Arif Md. Kamrul Hasan
Published: May 2018

The problems concerning the Bihari community is one of the oldest long-standing issues between Bangladesh and Pakistan. In 1971, after the independence of Bangladesh, the Bihari lost their citizenship. Presently, they are stateless and living in various camps in different parts of Bangladesh. This community wanted to be repatriated to their own country, Pakistan, but it denied them citizenship status, although a large number have been repatriated to Pakistan as their country of origin. Recently, in March 2015 the Supreme Court of Pakistan rejected the issue of stranded Pakistanis in Bangladesh regarding repatriation or taking these people back. This article has tried to determine the status of the Bihari community, what a lasting solution might be, and what the role is of international organisations in helping this community under domestic and international law.
Implications and Prospects of Jewish Jesus Research
Authors: Chilton Bruce
Published: May 2018

Consideration of a recent monograph by Walter Homolka invites evaluation of Jesus’ Judaic identity, as well as the hermeneutical issues implicit in approaches to Jesus from the perspective of Judaism and especially by Jewish practitioners. Issues of historiography and Christology naturally emerge from those reflections. Homolka’s application of postcolonial theory is assessed, as well as his linkage between Jewish reclamation and “the Third Quest of the historical Jesus.” The work of David Flusser and “the Jerusalem School” takes up attention in relation to Homolka’s argument. Progress occasioned by interaction with R. G. Collingwood’s view of history is considered, using the term “rabbi” as a lens of analysis. Homolka’s book closes with an argument for factoring Trinitarian perspectives within historical work. The essay concludes with a cautionary observation that claims of Jesus’ divine nature, as well as assertions of his Resurrection, are eschatological and transcendent evaluations, and so not strictly historical.
Memory as Method: Some Observations on Two Recent Accounts
Authors: Gregory Andrew
Published: May 2018

This review essay considers the use of social memory theory in two monographs on the gospels, and the extent to which that theory aids their arguments and conclusions. In the case of Jesus’ Literacy: Scribal Culture and the Teacher from Galilee, by Chris Keith, I argue that the author uses social memory theory to provide a helpful account of what historians do, but that his conclusion could stand without explicit appeal to his theoretical understanding. In the case of Q in Matthew: Ancient Media, Memory, and Early Scribal Transmission of the Jesus Tradition, by Alan Kirk, I argue that his use of social memory theory, alongside his account of individual neurobiological memory and cognitive processes, is a vital part of the argument that he presents.
What is History? Reading John 1 as Historical Representation
Authors: Rodríguez Rafael
Published: May 2018

As Pontius Pilate nearly asked, What is history? This article draws upon memory and media studies to question the notion that we find history within the text of the Fourth Gospel. Rather than trying to identify and isolate history within John’s Gospel, our discussion aims to recover how the Gospel works as a set of historical claims, joining with or competing against other historical claims within the social sphere of its author, redactor, and/or audience. After a précis of memory’s and media’s significance for our question (What is history?), we will localize these abstract issues by turning to the Johannine portrayal of John the Baptist and his testimony for Jesus. This approach respects the Fourth Gospel as a written text that developed and was compiled/redacted in the late first century without imposing a rigidly atemporal conception of Johannine theology onto John’s claims about events six or seven decades earlier.
A Chaotic Jesus: A Response to Simon Joseph
Authors: Crossley James
Published: May 2018

This article is a response to the points raised by Simon Joseph’s review of Jesus and the Chaos of History: Redirecting the Life of the Historical Jesus (Oxford: Oxford University Press, 2015).
Taxonomic status and typification of a neglected name Symphytum leonhardtianum from the Symphytum tuberosum complex (Boraginaceae)
Authors: KOBRLOVÁ LUCIE , MANDÁKOVÁ TEREZIE , HRONEŠ MICHAL
Published: May 2018

Symphytum leonhardtianum, a member of the S. tuberosum complex, is investigated. This taxon was described by Pugsley in 1931, from the vicinity of Vienna, Austria. Nevertheless, it is generally not accepted in European floras. In this study, we conducted an evaluation of this taxon using flow cytometry, karyology and morphological analysis. Flow cytometric and karyological investigations of plants from the type locality of S. leonhardtianum revealed only dodecaploids (2n = 12x = 96), a ploidy level corresponding to the S. tuberosum subsp. tuberosum. The chromosome number of the S. tuberosum from Austria is here recorded for the first time. Morphological comparison of Central European populations of S. tuberosum complex showed that S. leonhardtianum did not differ significantly from S. tuberosum subsp. tuberosum. Based on our findings, we propose treating the name S. leonhardtianum as a heterotypic synonym of S. tuberosum subsp. tuberosum. The lectotype of S. leonhardtianum is designated.
Bulbophyllum yongtaiense (Orchidaceae, Epidendroideae, Dendrobiinae), a new species from Fujian, China: Evidence from morphological and molecular analyses
Authors: LIU JIANGFENG , LI MINGHE , LAN SIREN , LIANG YICHI
Published: May 2018

Bulbophyllum yongtaiense, a new orchid species from Fujian, China, is described and illustrated based on morphological and molecular analyses. Detailed morphological comparisons indicate that B. yongtaiense is similar to B. kuanwuense, but it can be distinguished from longer scape, fimbriate-ciliate on margins of dorsal sepals and petals, petals with obtuse apex and a lip with finely papillose near base. Molecular analyses based on nuclear ITS and plastid matK, atpI-atpH, and trnL-F DNA sequence data support B. yongtaiense is genetically similar to B. hirundinis and B. pecten-veneris, but it can be distinguished from them by having shorter lateral sepals, petals with obtuse apex and a lip with finely papillose near base.
Chalcogenia brandli sp. nov. from Ethiopia (Coleoptera: Buprestidae: Anthaxiini)
Authors: BÍLÝ SVATOPLUK
Published: May 2018

Chalcogenia brandli sp. nov. from Ethiopia is described, illustrated and compared with the most similar species, and attributed to the Chalcogenia sulcipennis species-group within the genus Chalcogenia.
Three new species of Entomobryoidea (Collembola: Entomobryomorpha) from Brazilian Caatinga-Cerrado transition, with identification keys to Brazilian Cyphoderus, Pseudosinella and Trogolaphysa species
Authors: NUNES RUDY CAMILO , BELLINI BRUNO CAVALCANTE
Published: May 2018

Three new species of Entomobryoidea from Brazilian Caatinga-Cerrado transitional zone are described and illustrated, all from Sete Cidades National Park. Cyphoderus equidenticulati sp. nov. resembles C. javanus Börner and C. songkhlaensis Jantarit, Satasook & Deharveng in number of mucro teeth, one inner distal tooth on unguis and four ciliated chaetae between the two rows of feathered scales of dens, but differs in claw with a pair of equally developed inner basal teeth, collophore, labial and dorsal chaetotaxy. Pseudosinella triocellata sp. nov. is mostly similar to P. stewartpecki Katz, Soto-Adames & Taylor in number of eyes, presence of apical bulb on antennomere IV and one macrochaeta on mesothorax, but differs in head with S2 macrochaeta, anterior and posterior collophore chaetotaxy and empodial complex morphology. Trogolaphysa piracurucaensis sp. nov. is quite similar to the recently described T. ernersti Cipola & Bellini in overall dorsal chaetotaxy but differs in ventral head, collophore and manubrial plate chaetotaxy. Identification keys for Brazilian species of Cyphoderus, Pseudosinella and Trogolaphysa are also provided.
A Global Climatology of Tropical Cyclone Eyes
Authors: Knapp Kenneth R. , Velden Christopher S. , Wimmers Anthony J.
Published: May 2018

Intense tropical cyclones (TCs) generally produce a cloud-free center with calm winds, called the eye. The Automated Rotational Center Hurricane Eye Retrieval (ARCHER) algorithm is used to analyze Hurricane Satellite (HURSAT) B1 infrared satellite imagery data for storms occurring globally from 1982 to 2015. HURSAT B1 data provide 3-hourly observations of TCs. The result is a 34-yr climatology of eye location and size. During that time period, eyes are identified in about 13% of all infrared images and slightly more than half of all storms produced an eye. Those that produce an eye have (on average) 30 h of eye scenes. Hurricane Ioke (1992) had the most eye images (98, which is 12 complete days with an eye). The median wind speed of a system with an eye is 97 kt (50 m s−1) [cf. 35 kt (18 m s−1) for those without an eye]. Eyes are much more frequent in the Northern Hemisphere (particularly in the western Pacific) but eyes are larger in the Southern Hemisphere. The regions where eyes occur are expanding poleward, thus expanding the area at risk of TC-related damage. Also, eye scene occurrence can provide an objective measure of TC activity in place of those based on maximum wind speeds, which can be affected by available observations and forecast agency practices.