bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Rotating Direction on the Tribological Behavior of Grey Cast Iron with Curve Distributed Pit Textured Surface
Authors: Sun Shaoni , Xie Liyang , Kelly Peter , Long Risheng , Li Manhong , Feng Jiling
Published: September 2017

To investigate the influence of surface features, in the form of pits, on the wear resistance of grey cast iron (GCI), a finite element model of the pin‐on‐disc friction system, with pits distributed in a curved radial direction, was developed using APDL programming and the tribological behavior of textured surfaces was studied. The influence of relative rotation direction between the disc and the pin on the thermal behavior of the friction system under dry wear conditions was researched. GCI and C30E steel samples with pit textured surfaces were manufactured using laser marking equipment and tested using a tribology wear testing rig. The mass losses were measured and the worn surfaces were characterized. The influence of different rotation directions on the tribological behavior of the pit textured surfaces was also investigated. The simulation and test results revealed that rotation direction was a crucial parameter in determining the tribological behavior of surfaces with these features, regardless of the material. Under the conditions tested, when the pin rotated anticlockwise, the samples showed better friction and wear behavior than when the pin rotated clockwise. These results can provide important guidance for the optimization of the design of heavy‐load brake systems and other similar applications.
Chemical Profile and Antioxidant Activity of the Oil from Peony Seeds (Paeonia suffruticosa Andr.)
Authors: Yang Xin , Zhang Di , Song Li-min , Xu Qian , Li Hong , Xu Hui
Published: September 2017

Peony seed oil (PSO) is a novel vegetable oil developed from the seeds of Paeonia suffruticosa Andr. The present study aimed to make an overall investigation on the chemical profile and antioxidant activities of PSO for reasonable development and utilization of this new resource food. Chemical analysis revealed that PSO was characterized by an uncommon high portion of α‐linolenic acid (>38%), fairly low ratio of n‐6 to n‐3 polyunsaturated fatty acids (0.69), and much higher content of γ‐tocopherol than various conventional seed oils. In vitro assay indicated that PSO is a more potent scavenger of free radicals than extra virgin olive oil. Moderate intake of PSO exhibited obvious protection against various oxidative damages such as tetrachloromethane‐induced acute liver injury in mice and diet‐induced hyperlipidemia in rats. The changes in the key indicators of oxidative injury and fatty acid composition in the liver caused by PSO administration were measured, and the results demonstrated that antioxidant properties of PSO are closely related to their characteristic chemical composition. Consequently, the present study provided new evidence for the health implications of PSO, which deserves further development for medical and nutritional use against oxidative damages that are associated with various diseases.
The Biomechanical Study of Extraforaminal Lumbar Interbody Fusion: A Three-Dimensional Finite-Element Analysis
Authors: Yang Mingjie , Sun Guixin , Guo Song , Zeng Cheng , Yan Meijun , Han Yingchao , Xia Dongdong , Zhang Jingjie , Li Xinhua , Xiang Yang , Pan Jie , Li Lijun , Tan Jun
Published: September 2017

Objective. Finite-element method was used to evaluate biomechanics stability of extraforaminal lumbar interbody fusion (ELIF) under different internal fixation. Methods. The L3–L5 level finite-element model was established to simulate decompression and internal fixation at L4-L5 segment. The intact finite model was treated in accordance with the different internal fixation. The treatment groups were exerted 400 N load and 6 N·m additional force from motion to calculate the angular displacement of L4-L5. Results. The ROMs were smaller in all internal fixation groups than those in the intact model. Furthermore, the ROMs were smaller in ELIF + UPS group than in TLIF + UPS group under all operating conditions, especially left lateral flexion and right rotation. The ROMs were higher in ELIF + UPS group than in TLIF + BPS group. The ROMs of ELIF + UPS + TLFS group were much smaller than those in ELIF + UPS group, and as compared with TLIF + BPS group, there was no significant difference in the range of experimental loading. Discussion. The biomechanical stability of ELIF with unilateral pedicle screw fixation is superior to that of TLIF with unilateral pedicle screw fixation but lower than that of TLIF with bilateral pedicle screws fixation. The stability of ELIF with unilateral fixation can be further improved by supplementing a translaminar facet screw.
A Comprehensive Study on Gamma Rays and Fast Neutron Sensing Properties of GAGOC and CMO Scintillators for Shielding Radiation Applications
Authors: Issa Shams A. M. , Sayyed M. I. , Zaid M. H. M. , Matori K. A.
Published: September 2017

The WinXCom program has been used to calculate the mass attenuation coefficients (μm), effective atomic numbers (Zeff), effective electron densities (Nel), half-value layer (HVL), and mean free path (MFP) in the energy range 1 keV–100 GeV for Gd3Al2Ga3O12Ce (GAGOC) and CaMoO4 (CMO) scintillator materials. The geometrical progression (G-P) method has been used to compute the exposure buildup factors (EBF) and gamma ray energy absorption (EABF) in the photon energy range 0.015–15 MeV and up to a 40 penetration depth (mfp). In addition, the values of the removal cross section for a fast neutron ∑R have been calculated. The computed data observes that GAGOC showed excellent γ-rays and neutrons sensing a response in the broad energy range. This work could be useful for nuclear radiation sensors, detectors, nuclear medicine applications (medical imaging and mammography), nuclear engineering, and space technology.
Integrated Analysis of Whole-Genome ChIP-Seq and RNA-Seq Data of Primary Head and Neck Tumor Samples Associates HPV Integration Sites with Open Chromatin Marks
Authors: Kelley Dylan Z. , Flam Emily L. , Izumchenko Evgeny , Danilova Ludmila V. , Wulf Hildegard A. , Guo Theresa , Singman Dzov A. , Afsari Bahman , Skaist Alyza M. , Considine Michael , Welch Jane A. , Stavrovskaya Elena , Bishop Justin A. , Westra William H. , Khan Zubair , Koch Wayne M. , Sidransky David , Wheelan Sarah J. , Califano Joseph A. , Favorov Alexander V. , Fertig Elana J. , Gaykalova Daria A.
Published: September 2017

Chromatin alterations mediate mutations and gene expression changes in cancer. Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) has been utilized to study genome-wide chromatin structure in human cancer cell lines, yet numerous technical challenges limit comparable analyses in primary tumors. Here we have developed a new whole-genome analytic pipeline to optimize ChIP-Seq protocols on patient-derived xenografts from human papillomavirus–related (HPV+) head and neck squamous cell carcinoma (HNSCC) samples. We further associated chromatin aberrations with gene expression changes from a larger cohort of the tumor and normal samples with RNA-Seq data. We detect differential histone enrichment associated with tumor-specific gene expression variation, sites of HPV integration in the human genome, and HPV-associated histone enrichment sites upstream of cancer driver genes, which play central roles in cancer-associated pathways. These comprehensive analyses enable unprecedented characterization of the complex network of molecular changes resulting from chromatin alterations that drive HPV-related tumorigenesis. Cancer Res; 77(23); 6538–50. ©2017 AACR.
4-1BB Agonist Focuses CD8+ Tumor-Infiltrating T-Cell Growth into a Distinct Repertoire Capable of Tumor Recognition in Pancreatic Cancer
Authors: Sakellariou-Thompson Donastas , Forget Marie-Andrée , Creasy Caitlin , Bernard Vincent , Zhao Li , Kim Young Uk , Hurd Mark W. , Uraoka Naohiro , Parra Edwin Roger , Kang Ya'an , Bristow Christopher A. , Rodriguez-Canales Jaime , Fleming Jason B. , Varadhachary Gauri , Javle Milind , Overman Michael J. , Alvarez Hector A. , Heffernan Timothy P. , Zhang Jianhua , Hwu Patrick , Maitra Anirban , Haymaker Cara , Bernatchez Chantale
Published: September 2017

Purpose: Survival for pancreatic ductal adenocarcinoma (PDAC) patients is extremely poor and improved therapies are urgently needed. Tumor-infiltrating lymphocyte (TIL) adoptive cell therapy (ACT) has shown great promise in other tumor types, such as metastatic melanoma where overall response rates of 50% have been seen. Given this success and the evidence showing that T-cell presence positively correlates with overall survival in PDAC, we sought to enrich for CD8+ TILs capable of autologous tumor recognition. In addition, we explored the phenotype and T-cell receptor repertoire of the CD8+ TILs in the tumor microenvironment.

Experimental Design: We used an agonistic 4-1BB mAb during the initial tumor fragment culture to provide 4-1BB costimulation and assessed changes in TIL growth, phenotype, repertoire, and antitumor function.

Results: Increased CD8+ TIL growth from PDAC tumors was achieved with the aid of an agonistic 4-1BB mAb. Expanded TILs were characterized by an activated but not terminally differentiated phenotype. Moreover, 4-1BB stimulation expanded a more clonal and distinct CD8+ TIL repertoire than IL2 alone. TILs from both culture conditions displayed MHC class I-restricted recognition of autologous tumor targets.

Conclusions: Costimulation with an anti-4-1BB mAb increases the feasibility of TIL therapy by producing greater numbers of these tumor-reactive T cells. These results suggest that TIL ACT for PDAC is a potential treatment avenue worth further investigation for a patient population in dire need of improved therapy. Clin Cancer Res; 23(23); 7263–75. ©2017 AACR.
Treg Depletion Licenses T Cell–Driven HEV Neogenesis and Promotes Tumor Destruction
Authors: Colbeck Emily J. , Jones Emma , Hindley James P. , Smart Kathryn , Schulz Ralph , Browne Molly , Cutting Scott , Williams Anwen , Parry Lee , Godkin Andrew , Ware Carl F. , Ager Ann , Gallimore Awen
Published: September 2017

T-cell infiltration into tumors represents a critical bottleneck for immune-mediated control of cancer. We previously showed that this bottleneck can be overcome by depleting immunosuppressive Foxp3+ regulatory T cells (Tregs), a process that can increase frequencies of tumor-infiltrating lymphocytes through promoting the development of specialized portals for lymphocyte entry, namely high endothelial venules (HEVs). In this paper, we used a carcinogen-induced tumor model that allows for coevolution of the tumor microenvironment and the immune response to demonstrate that Treg depletion not only results in widespread disruption to HEV networks in lymph nodes (LNs) but also activates CD8+ T cells, which then drive intratumoral HEV development. Formation of these vessels contrasts with ontogenic HEV development in LNs in that the process is dependent on the TNF receptor and independent of lymphotoxin β receptor–mediated signaling. These intratumoral HEVs do not express the chemokine CCL21, revealing a previously undescribed intratumoral blood vessel phenotype. We propose a model where Treg depletion enables a self-amplifying loop of T-cell activation, which promotes HEV development, T-cell infiltration, and ultimately, tumor destruction. The findings point to a need to test for HEV development as part of ongoing clinical studies in patients with cancer. Cancer Immunol Res; 5(11); 1005–15. ©2017 AACR.
Fortschritte in der Behandlung von Zwangsstörungen bei Kindern und Jugendlichen: Empirische Evidenz, Behandlungsprobleme und Verbesserungsmöglichkeiten
Authors: Simons Michael , Vloet Timo D.
Published: September 2017

Obwohl Zwangsstörungen im Kindes- und Jugendalter mittlerweile als gut behandelbar gelten, sind die Behandlungsergebnisse in der Praxis häufig unbefriedigend. Dies liegt daran, dass nachweislich wirksame Interventionen nicht oder unzureichend angewendet werden. Die vorliegende Arbeit gibt eine Übersicht über evidenzbasierte psychotherapeutische und medikamentöse Behandlungsmöglichkeiten. Die Behandlung der Wahl ist die Kognitive Verhaltenstherapie mit Exposition und Reaktionsverhinderung, die, falls erforderlich, um eine Pharmakotherapie mit einem selektiven Serotonin-Wiederaufnahme-Hemmer ergänzt wird. Befunde zu Prädiktoren, Moderatoren und Mediatoren der Behandlung sind uneinheitlich. Neue Entwicklungen in der Psychotherapie beinhalten Anwendungen der Expositionsbehandlung, die nicht einem Habituationsrational folgen, sondern auf Angsthemmung und Angsttoleranz sowie auf kognitive (Erwartungsverletzung) oder metakognitive Veränderungen abzielen. Bei Kindern mit geringer Behandlungsmotivation und starker Einbindung der Familie in die Zwänge des Kindes sind elternbezogene Interventionen indiziert. Behandlungsfehler in der Expositionsbehandlung sollten in der Ausbildung von Kinder- und Jugendlichenpsychotherapeuten besonders berücksichtigt werden.
Clinicopathological Significance of S100A14 Expression in Lung Adenocarcinoma
Authors: Katono Ken , Sato Yuichi , Kobayashi Makoto , Saito Keita , Nagashio Ryo , Ryuge Shinichiro , Igawa Satoshi , Nakashima Hiroyasu , Shiomi Kazu , Satoh Yukitoshi , Ichinoe Masaaki , Murakumo Yoshiki , Saegusa Makoto , Masuda Noriyuki
Published: September 2017

Background: Several studies have reported that S100A14 plays important roles during different steps of the tumorigenic process and tumor progression of several types of cancer. The aim of the present study was to investigate the clinicopathological and prognostic significance and functional roles of S100A14 in lung adenocarcinoma. Patients and Methods: S100A14 expression was immunohistochemically studied in 166 consecutive resected lung adenocarcinomas, and its correlation with clinicopathological parameters was evaluated. Functional roles of S100A14 in lung adenocarcinoma were investigated based on invasion and migration assays on a small interfering (si)RNA-treated lung adenocarcinoma cell line. Results: S100A14 expression was detected in 82 of the 166 (49.4%) lung adenocarcinomas. S100A14 expression was significantly correlated with sex, poorer tumor differentiation, higher disease stages, larger tumor size, lymph node metastasis, intratumoral vascular invasion, intratumoral lymphatic invasion, pleural invasion, and poorer prognosis. Invasion and wound healing assays showed that S100A14 siRNA knockdown cells had significantly decreased invasion and migration abilities compared with siRNA control cells. Conclusion: S100A14 is expressed in a subset of lung adenocarcinoma, and its expression is related to certain clinicopathological parameters. Furthermore, S100A14 expression was strongly correlated with migration and invasion in lung adenocarcinoma cells.
Automation of the Fetal Right Myocardial Performance Index to Optimise Repeatability
Authors: Leung Viviena , Avnet Hagai , Henry Amanda , Wang Jingjing , Redmond Stephen , Welsh Alec W.
Published: September 2017

Objectives: To compare the repeatability and degree of absolute agreement of an automated fetal right myocardial performance index (MPI) algorithm with manual measurements along with the impact of MPI observer experience on these two aspects. Methods: Prospective cross-sectional study of 65 uncomplicated singleton pregnancies from 22 to 39 weeks' gestation. Image analysis of double-waveform right MPI measurements was conducted first with a MATLAB automated MPI software and then independently by an experienced and an inexperienced observer. Intraclass correlation coefficients (ICCs) and 95% confidence intervals (95% CI) were used to evaluate manual and automated intra- and interobserver repeatability. In addition, Bland-Altman plots were used to determine the degree of absolute agreement. Results: Successful automation was performed on 63 cases (97%) showing repeatability ICCs of: 0.83 manual intraobserver; 0.77 manual interobserver; 1.00 automated. The degree of absolute agreement between manual and automated values was: inexperienced observer ICC 0.43 (95% CI 0.21-0.62); experienced observer ICC 0.76 (95% CI 0.63-0.85). Conclusion: Automation of right MPI demonstrates a superior reproducibility over manual measurements and reduces the experience required for successful analysis. This may lend a greater clinical applicability to MPI, and future studies to develop an automated universal reference range would be useful.
Carbohydrate Antigen 19-9-Positive Gastric Adenocarcinoma: Autopsy Findings and Review of the Literature
Authors: Wang Tan , Matsuda Yoko , Seki Atsuko , Nonaka Keisuke , Kakizaki Mototsune , Kaneda Daita , Takahashi-Fujigasaki Junko , Murayama Shigeo  , Arai Tomio
Published: September 2017

Carbohydrate antigen 19-9 (CA19-9) is a well-known tumor marker for pancreatobiliary cancer, and several studies have shown that an elevated serum CA19-9 level is associated with more aggressive biological behavior in gastric cancer (GC). However, the clinicopathological characteristics of CA19-9-positive GC remain unclear. We herein report an autopsy case of CA19-9-positive GC in an 84-year-old man who was admitted to our hospital because of paralysis and anemia. Autopsy revealed an ulcerative-invasive tumor measuring 72 × 60 mm in the anterior wall of the gastric body. The tumor had invaded beyond the muscularis propria, and metastasized to the lung, liver, and regional lymph nodes. Histologically, the tumor cell had oval nuclei with abundant clear cytoplasm, and tubular and/or papillary features with prominent lymphovascular permeation and perineural invasion, mimicking pancreatobiliary carcinoma. Immunohistochemically, the tumor cells showed diffuse immunopositivity for CA19-9 and carcinoembryonic antigen. According to a review of cases reported in the literature, CA19-9-positive GCs show clinicopathological characteristics such as antral location, ulcerative-infiltrating gross feature, differentiated histology, prominent lymphatic and venous invasion, higher proportion of metastasis, and higher clinical stage. These results suggest that CA19-9-positive GC is pathologically a distinctive type of tumor with aggressive biological behavior.
A Case of Basaloid Squamous Cell Carcinoma of Polypoid Type in the Esophagus
Authors: Lee Ki Hun , Lee Sang Jin , Kim Hak Soo , Kim Sung Eun , Choi Soo Yong , Lee Hyun Ju , Ha Suk Hun , Oh Kwang Hoon , Eom Dae-Woon
Published: September 2017

Basaloid squamous cell carcinoma of the esophagus is very rare. Further, polypoid type of esophageal cancer is also rare. We have recently treated a case of basaloid squamous cell carcinoma which presented as a 1.3-cm esophageal polyp. A 48-year-old woman was referred to our hospital because of a polypoid mass at 36 cm distance from the upper incisor on endoscopic examination, and the result of the biopsy was basaloid squamous cell carcinoma. The patient underwent Ivor Lewis operation with lymph node dissection. Two basaloid squamous cell carcinomas, of 1.3 and 0.4 cm, were diagnosed in the final pathologic examination. Regular periodic follow-up showed no evidence of recurrence or metastasis in the 5-month postoperative period.
Venom Immunotherapy in High-Risk Patients: The Advantage of the Rush Build-Up Protocol
Authors: Rosman Yossi , Confino-Cohen Ronit , Goldberg Arnon
Published: September 2017

Background: Venom immunotherapy (VIT) is considered to be the gold standard treatment for patients with hymenoptera venom allergy. This treatment induces systemic reactions (SR) in a significant number of patients. Objective: To evaluate the outcome of VIT in patients with known risk factors for VIT-induced SR and to compare rush VIT (RVIT) and conventional VIT (CVIT). Methods: All of the patients who received VIT and had at least one of the following risk factors were included: current cardiovascular disease, uncontrolled asthma, high basal serum tryptase, current treatment with β-blockers or angiotensin-converting enzyme inhibitors, and age >70 or <5 years. Results: Sixty-four patients were included, and most of them (52; 81.5%) were allergic exclusively to bee venom. Thirty-five (54.7%) patients underwent RVIT and 29 CVIT. The incidence of patients who developed SR during the build-up phase was similar for RVIT and CVIT (25.7 and 27.5%, respectively; p = 1). However, the incidence of SR per injection was significantly higher in CVIT than in RVIT (5.6 and 2.75%, respectively; p = 0.01). Most reactions (79.1%) were mild, limited to the skin. Most of the patients (92.1%) reached the full maintenance dose of 100 μg. This dose was reached by a significantly larger number of patients receiving RVIT compared to CVIT (100 and 82.7%, respectively; p = 0.01). None of the patients experienced exacerbation of their concurrent chronic disease during VIT. Conclusion: VIT can be performed safely and efficiently in patients with risk factors for immunotherapy. In these patients RVIT appears to be safer and more efficient than CVIT.
An ABC of the Warning Signs of Hereditary Angioedema
Authors: Grumach Anete Sevciovic , Ferraroni Natasha , Olivares Maria Margarita , López-Serrano Maria Concepción , Bygum Anette
Published: September 2017

Hereditary angioedema (HAE) with C1 inhibitor deficiency is a genetic disorder that clinically manifests with attacks of angioedema in the subcutaneous and submucosal tissues, mainly in the extremities, abdomen, and upper airway. During attacks, vascular permeability is increased due to increased bradykinin (BK). This means that special therapies are needed for attacks that do not respond to traditional antiallergic therapies involving antihistamines, corticosteroids, and epinephrine. The recurring attacks may disable patients and lead to frequent visits to emergency rooms where misdiagnoses are common. HAE attacks may be fatal when upper-airway edema occurs, if proper treatment with a C1 inhibitor concentrate or BK receptor antagonist is not administered or an emergency tracheostomy is not performed. We propose a mnemonic method for the warning signs of HAE for the use as a diagnostic tool, i.e., the so-called “ABC” of the warning signs of HAE. The letters represent the following: A = Angioedema, B = Bradykinin, C = C1 inhibitor, D = Distress factors, E = Epinephrine nonresponsive, F = Family history, and G = Glottis/Gastrointestinal edema. To avoid fatalities, medical staff and patients, including family members, must be aware of HAE. An alphabetical mnemonic method has been developed and we hope it may benefit patients.
Overexpression of Insulin-Like Growth Factor-2 in Expanded Endothelial Progenitor Cells Improves Left Ventricular Function in Experimental Myocardial Infarction
Authors: Demetz Gabi , Oostendorp Robert A.J. , Boxberg A. Melanie , Sitz Wibke , Farrell Eliane , Steppich Birgit , Steinsiek Anna-Lena , Rudelius Martina , Ott Ilka
Published: September 2017

Insulin-like growth factors (IGFs) are mediators of growth hormone-induced metabolic and anabolic actions, but also regulate cell growth, differentiation, and apoptosis and show beneficial effects in acute myocardial ischemia. Since endothelial progenitor cells (EPCs) improve myocardial function after acute myocardial infarction, we sought to investigate whether overexpression of IGF-2 in expanded EPCs (eEPCs) further contributes to improvement in left ventricular function after myocardial infarction. EPCs were isolated from human cord blood and transduced by a retroviral vector expression of IGF-2 (IGF-2 eEPCs) or vector only. Expression levels were confirmed by RT-PCR. Vector only-transduced eEPCs or IGF-2 eEPCs were transplanted after ligation of the left anterior descending coronary artery in athymic nude rats. Transplantation of eEPCs improved the left ventricular ejection fraction after 2 weeks. Overexpression of IGF-2 further improved the left ventricular ejection fraction and reduced the myocardial infarction size. Immunohistological analysis revealed an increase in proliferating cells and a decrease in monocytes and apoptotic myocytes within the infarction zone after transplantation of IGF-2-overexpressing eEPCs. Transplantation of IGF-2-overexpressing eEPCs in acute myocardial infarction may improve early myocardial function by enhancing proliferation and limiting the inflammatory response and apoptosis.
Chronological Changes in Brain Blood Flow and Central Benzodiazepine Receptor Binding Potential in a Patient with Symptomatic Epilepsy after Surgery for Aneurysmal Subarachnoid Hemorrhage: 123I-Iomazenil Single-Photon Emission Computed Tomography Studies
Authors: Murakami Toshiyuki , Kashimura Hiroshi , Endo Hidehiko , Kuroda Hiroki , Ogasawara Kuniaki
Published: September 2017

Early 123I-iomazenil single-photon emission computed tomography (SPECT) images are correlated with blood flow in the brain, and late images are correlated with cortical benzodiazepine receptor binding potential. Reduced metabolism in the contralateral cerebral hemisphere is indicated by crossed cerebellar hypoperfusion (CCH). We present the case of a 63-year-old man who developed symptomatic epilepsy 13 days after surgery for an aneurysmal subarachnoid hemorrhage. Early images on 123I-iomazenil SPECT 2 days after seizure onset revealed CCH and hyperperfusion in the affected cerebral hemisphere where benzodiazepine receptor binding potential was reduced in late images on 123I-iomazenil SPECT. These abnormal findings resolved on repeated 123I-iomazenil SPECT 1 month after seizure onset. The case we present here is consistent with the idea that the central benzodiazepine receptor system in the human brain undergoes changes that are related to seizures due to epilepsy.
Permanent Deployment of the Solitaire FR™ Device in the Basilar Artery in an Acute Stroke Scenario
Authors: Litao Miguel S. , Nossek Erez , DeSousa Keith , Favate Albert , Raz Eytan , Shapiro Maksim , Becske Tibor , Nelson Peter Kim
Published: September 2017

Background: Scarce reports exist of permanent deployment of Solitaire FR™ devices for arterial steno-occlusive disease as it is primarily indicated for temporary deployment for thrombectomy in large-vessel, anterior-circulation ischemic strokes. Even more scarce are reports describing permanent deployment of the Solitaire device for posterior circulation strokes. Summary: We present 2 cases where the Solitaire device was electrolytically detached to re-establish flow in an occluded or stenotic basilar artery in acutely symptomatic patients. In both cases, a 4 × 15 mm Solitaire device was positioned across the stenotic or occluded portion of the basilar artery and electrolytically detached to maintain vessel patency. Both cases had good clinical outcomes with a National Institutes of Health Stroke Scale (NIHSS) score of 1 (from 24) on 90-day follow-up and an NIHSS score of 2 (from 7) on 30-day follow-up. Key Messages: Permanent deployment of the Solitaire device may potentially be a safe and effective means of maintaining vessel patency in an occluded or stenotic basilar artery.
Early Changes of Retinal Morphology in Therapy of Neovascular Age-Related Macular Degeneration with Three Commonly Used Anti-VEGF Agents
Authors: Enders Philip , Sitnilska Vasilena , Altay Lebriz , Fauser Sascha
Published: September 2017

Purpose: To compare changes of retinal morphology in the first weeks following injection of anti-VEGF agents for neovascular age-related macular degeneration (nAMD). Procedures: In a prospective study 50 patients with active choroidal neovascularization secondary to nAMD were monitored weekly by spectral-domain optical coherence tomography for 3 weeks after treatment. Twenty-two patients received bevacizumab, 15 ranibizumab, and 13 aflibercept. Morphological parameters of retinal compartments were compared. Results: Mean central retinal thickness (391.22 ± 123.41 µm) was reduced by -26.15 µm (p < 0.001) after 1 week, by -12.54 µm (p < 0.001) after 2 weeks, and by -3.52 µm (p = 0.09) after 3 weeks. Mean intraretinal layer thickness changed only significantly between baseline and week 1 (p < 0.001). Mean subretinal thickness also decreased between weeks 1 and 2 (p = 0.01). Conclusions: Early morphological changes occur primarily in the first 14 days after treatment. This information could be clinically helpful to evaluate early non-response.
Prognostic Features and Long-Term Outcome in Patients with Isolated Fetal Ventriculomegaly
Authors: Winkler Alice , Tölle Sandra , Natalucci Giancarlo , Plecko Barbara , Wisser Josef
Published: September 2017

Objective: In order to provide aid for prenatal counseling in fetal isolated ventriculomegaly (IVM) on ultrasound, we recorded the latest long-term clinical and imaging outcomes of children with a mean age of 7.2 years (range 2.1-14.6). Methods: In 72 fetuses with IVM, diagnosed between 1999 and 2011, the measurement quality of atrial diameter was reviewed in the axial plane. We assessed the association of characteristics of IVM with outcome parameters in the cohort and in subgroups. Prognostic values of significant associations were reported by receiver operating characteristic curve analysis. Results: Cerebral anomalies were diagnosed postnatally in 42% and genetic disorders in 12% of 45 live births. Significant associations of outcome parameters were found between the degree of IVM and genetic disorders (p = 0.017) with an area under the curve (AUC) of 0.866, and between progression of IVM and motor impairment (p = 0.024) with an AUC of 0.789. No significant correlation was found with the other assessed outcome parameters. Furthermore, our subgroup analysis clearly showed that, if cerebral or genetic anomalies are not found postnatally, a favorable outcome may be expected. Discussion: Diameter and progression in IVM are not significantly associated with most outcome parameters. Cerebral anomalies and genetic disorders may contribute to an unfavorable outcome.
The Adenosine A1 Receptor Antagonist DPCPX Inhibits Tumor Progression via the ERK/JNK Pathway in Renal Cell Carcinoma
Authors: Zhou Yihong , Tong Liang , Chu Xi , Deng Fei , Tang Jin , Tang Yuxin , Dai Yingbo
Published: September 2017

Background/Aims: The adenosine A1 receptor (A1R) has been reported to be involved in the pathogenesis of various cancers, and the effects of A1R on different cancers are pleiotropic. However, the role of A1R in renal cell carcinoma (RCC) remains not well-known. Methods: The expression of A1R in RCC cells was detected by quantitative real-time PCR and Western blotting analysis. Cell proliferation was detected using an MTT assay and a colony formation assay. Tumor growth was also evaluated in nude mice. Cell invasion and migration were evaluated using a wound healing assay and a transwell assay. Cell cycle distribution and apoptosis rates were analyzed by flow cytometry. Results: A1R was the main subtype of ARs and was up-regulated in 786-O and ACHN cells. Functionally, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), an A1R antagonist, inhibited RCC cell proliferation in vitro and tumor growth in vivo. Furthermore, DPCPX inhibited RCC cell migration, while N6-Cyclopentyladenosine (CPA), a selective A1 agonist, was able to rescue RCC cell migration. In addition, DPCPX promoted 786-O and ACHN cell apoptosis and induced an S phase cell cycle arrest. Finally, we demonstrated that DPCPX inhibited tumor progression in part via the ERK/JNK pathway. Conclusion: These findings suggest the potentially important role of DPCPX in the control of RCC cell proliferation and migration by regulating the ERK/JNK signaling pathway.
MicroRNA-196b Inhibits Cell Growth and Metastasis of Lung Cancer Cells by Targeting Runx2
Authors: Bai Xiaoxue , Meng Lin , Sun Huijie , Li Zhuo , Zhang Xiufang , Hua Shucheng
Published: September 2017

Background/Aims: Lung cancer is one of the most common causes of cancer related deaths worldwide. The role of several microRNAs (miRNAs) including miR-196b in different cancers has already been established. The study was aimed to explore the role of miR-196b in lung cancer and its possible underlying mechanism. Methods: Human lung cancer cell line A549 was transfected with miR-196b mimic, miR-196b inhibitor and corresponding controls. Then cell viability, migration, invasion, and apoptosis of A549 lung cancer cells either with overexpression or with suppression of miR-196b were estimated sequentially. Next, dual luciferase activity assay was performed to clarify whether Runx2 was a direct target of miR-196b. Finally, the expressions of main factors associated with epithelial mesenchymal transition (EMT), PI3K/AKT/GSK3β, Smad, and JNK pathways were detected by western blot. Results: MiR-196b expression was significantly decreased in A549, H1650 and H1299 cell lines compared with in WI-38 and HEL-1 cell lines. Overexpression of miR-196b suppressed cell viability, migration, invasion, and induced apoptosis as well as inhibited TGF-β induced EMT process in A549 cells. In addition, Runx2 was a putative target of miR-196b, and Runx2 silence remarkably increased cell apoptosis and abolished the promotive effects of miR-196b suppression on cell viability, migration and invasion. Finally, miR-196b also mediated its action by inactivation of PI3K/AKT/GSK3β, Smad, and JNK pathways by down-regulation of Runx2. Conclusion: MiR-196b functions as a tumor suppressor that inhibited cell growth and metastasis of lung cancer cells by targeting Runx2. These findings provided further evidences for treatment of lung cancer.
Genotype Distribution and Molecular Epidemiology of Hepatitis C Virus in Guangzhou, China: Predominance of Genotype 1b and Increasing Incidence of Genotype 6a
Authors: Yuan Guosheng , Liu Junwei , Hu Chengguang , Huang Huaping , Qi Minghua , Wu Tao , Liang Weifang , Li Yi-Ping , Zhang Yong-Yuan , Zhou Yuanping
Published: September 2017

Background/Aims: Distribution of Hepatitis C virus (HCV) genotypes vary geographically and may associate with the mode of transmission. Little is known about the molecular epidemiology of HCV infection in Guangzhou, China. Methods: A cross-sectional survey included 561 subjects with chronic HCV infection registered at Nanfang Hospital, Southern Medical University, was performed. All residents were invited for a questionnaire interview to collect information about their personal status and commercial blood donation history. Results: A total of 463 chronic hepatitis C (CHC) patients were finally enrolled. Among the 463 samples, 426 were characterized by partial core-E1 sequences and classified into 7 subtypes: 1b (n=263, 61.7%), 6a (n=86, 20.2%), 2a (n=26, 6.1%), 3b (n=26, 6.1%), 3a (n=22, 5.2%), 6u (n=2, 0.5%), and 4a (n=1, 0.2%). Analysis of genotype-associated risk factors revealed that blood donation and transfusion were strongly associated with subtypes 1b and 2a, while genotype 3b and 6a were more frequent in intravenous drug users. Conclusions: Phylogeographic analyses demonstrated that the distribution of HCV genotypes in Guangzhou is complex. Interestingly, 6a has become a local endemic in Guangzhou and may be the second source region to disseminate 6a to other provinces.
Transthyretin Exerts Pro-Apoptotic Effects in Human Retinal Microvascular Endothelial Cells Through a GRP78-Dependent Pathway in Diabetic Retinopathy
Authors: Shao Jun , Yin Ying , Yin Xiaowen , Ji Li , Xin Yu , Zou Jian , Yao Yong
Published: September 2017

Background/Aims: Diabetic retinopathy (DR) is one of the main causes of blindness in the world. Our previous study showed that transthyretin (TTR) regulates key genes in the Tie2 pathway and inhibits the development of neovascularization in DR, but the mechanism is still unclear. Here, we investigated how TTR affects the progression of neovascularization in DR. Methods: Natural and simulated DR media (hyperglycemia and hypoxia) were used to culture human retinal microvascular endothelial cells (hRECs). Flow cytometry was employed to investigate the effect of TTR on apoptosis of hRECs. Fluorescent labeling and immunofluorescence staining were used to determine the TTR distribution in hRECs. The membrane proteins of hRECs were extracted and applied to a sepharose-TTR column, and the captured proteins were identified by Mass Spectrometric analysis. Gene knock-down and western blotting assays were used to study the key signal pathway of the most abundant identified protein. Results: TTR induced apoptosis of hRECs in an environment that simulated hypoxia. Immunofluorescent staining showed that TTR could enter the nuclei of hRECs. A total of 30 unique TTR-captured proteins were identified by Mass Spectrometry, and glucose-regulated protein 78 (GRP78) was one of the most abundant. Western blotting and gene knock-down indicated that TTR might upregulate GRP78 and facilitate apoptosis through the eIF2α/CHOP pathway. Conclusions: In the DR environment (hyperglycemia and hypoxia), TTR was shown to repress neovascularization by promoting apoptosis of hRECs through a GRP78-dependent pathway.
ОСОБЛИВОСТІ ЗМІНИ КЛІМАТУ У МІСТІ ТЕРНОПІЛЬ: ЧИ ВІДОБРАЖАЮТЬ РЕГІОНАЛЬНІ ЗМІНИ ГЛОБАЛЬНІ ПРОЦЕСИ?
Authors: Marushchak M. I. , Krynytska I. Y. , Rudenko O. V. , Gabor G. G.
Published: September 2017

Мета роботи – вивчити особливості зміни регіональної температури у місті Тернопіль за 10 років та порівняти отримані дані з такими в Україні та Європі.Матеріали і методи. Для визначення параметрів температури повітря та кількості опадів використали оригінальний статистичний аналіз інструментальних гідрометеоспостережень на метеостанції м. Тернопіль за останні 10 років та інших міст України у 2015 році. Для аналізу показників атмосферного повітря в окремих європейських країнах використали глобальні кліматичні дані.Результати. Аналіз показників атмосферного повітря в окремих європейських країнах показав значні її коливання. Найбільший приріст температури з 2011 р. до 2014 р. відмічено у Хорватії (на 50,0%), значно зріс показник за три роки у Великобританії (на 13,0%) та Іспанії (на 16,0%). В Україні середньорічна температура повітря підвищилася у 2014 р. на 16,3%, у 2015 р. – на 11,3% стосовно попереднього року. Температурні криві в Україні свідчать про загальну тенденцію до потепління з ймовірністю значного підвищення температури у літні місяці.Висновки. Протягом останніх 10 років реєструється зростання температури атмосферного повітря у м. Тернопіль у межах 0,8–2,30Сз найвищим показником у 2015 р., що відповідає загальним тенденціям як в Україні, так і в Європі. Це необхідно враховувати при розробці протоколів профілактики і лікування соматичних захворювань.
Effects of the invasive Tilapia on the Common Spiny Loach (Cypriniformes: Cobitidae: Lepidocephalichthys thermalis) - implications for conservation
Authors: Tapkir Sandip D. , Kharat Sanjay S. , Kumkar Pradeep , Gosavi Sachin M.
Published: September 2017

The introduction of invasive species leading to decline of freshwater fauna is a major concern for conservation biologists.  In this study we examined the effect of introduced Tilapia on the survival of the loach Lepidocephalichthys thermalis via predation experiments with Tilapia and a native predator, the Snakehead fish Channa gachua.  Examining the chemoecology of prey-predator interactions, we found that L. thermalis failed to detect water-borne cues from Tilapia but did recognize cues from C. gachua, indicating innate predator recognition.  We also observed that L. thermalis can learn to associate kairomones with Tilapia when conditioned with kairomones and injured conspecific cues.  Trained L. thermalis showed higher survival during Tilapia predation trials.  Thus under experimental conditions the vulnerability of L. thermalis to Tilapia predation due to failure to detect chemical cues can be reduced via associative training.  It remains to be determined how useful this behavioral plasticity can be in wild L. thermalis populations exposed to introduced Tilapia.
SIRT2 Acts as a Cardioprotective Deacetylase in Pathological Cardiac Hypertrophy
Authors: Tang Xiaoqiang , Chen Xiao-Feng , Wang Nan-Yu , Wang Xiao-Man , Liang Shu-Ting , Zheng Wei , Lu Yun-Biao , Zhao Xiang , Hao De-Long , Zhang Zhu-Qin , Zou Ming-Hui , Liu De-Pei , Chen Hou-Zao
Published: September 2017

Background:

Pathological cardiac hypertrophy induced by stresses such as aging and neurohumoral activation is an independent risk factor for heart failure and is considered a target for the treatment of heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. We aimed to investigate the roles of SIRT2 in aging-related and angiotensin II (Ang II)–induced pathological cardiac hypertrophy.

Methods:

Male C57BL/6J wild-type and
Sirt2
knockout mice were subjected to the investigation of aging-related cardiac hypertrophy. Cardiac hypertrophy was also induced by Ang II (1.3 mg/kg/d for 4 weeks) in male C57BL/6J
Sirt2
knockout mice, cardiac-specific
SIRT2
transgenic (
SIRT2
-Tg) mice, and their respective littermates (8 to ≈12 weeks old). Metformin (200 mg/kg/d) was used to treat wild-type and
Sirt2
knockout mice infused with Ang II. Cardiac hypertrophy, fibrosis, and cardiac function were examined in these mice.

Results:

SIRT2 protein expression levels were downregulated in hypertrophic hearts from mice.
Sirt2
knockout markedly exaggerated cardiac hypertrophy and fibrosis and decreased cardiac ejection fraction and fractional shortening in aged (24-month-old) mice and Ang II–infused mice. Conversely, cardiac-specific
SIRT2
overexpression protected the hearts against Ang II–induced cardiac hypertrophy and fibrosis and rescued cardiac function. Mechanistically, SIRT2 maintained the activity of AMP-activated protein kinase (AMPK) in aged and Ang II–induced hypertrophic hearts in vivo as well as in cardiomyocytes in vitro. We identified the liver kinase B1 (LKB1), the major upstream kinase of AMPK, as the direct target of SIRT2. SIRT2 bound to LKB1 and deacetylated it at lysine 48, which promoted the phosphorylation of LKB1 and the subsequent activation of LKB1-AMPK signaling. Remarkably, the loss of SIRT2 blunted the response of AMPK to metformin treatment in mice infused with Ang II and repressed the metformin-mediated reduction of cardiac hypertrophy and protection of cardiac function.

Conclusions:

SIRT2 promotes AMPK activation by deacetylating the kinase LKB1. Loss of SIRT2 reduces AMPK activation, promotes aging-related and Ang II–induced cardiac hypertrophy, and blunts metformin-mediated cardioprotective effects. These findings indicate that SIRT2 will be a potential target for therapeutic interventions in aging- and stress-induced cardiac hypertrophy.
Activating Transcription Factor 3 Is Reduced in Preeclamptic Placentas and Negatively Regulates sFlt-1 (Soluble fms-Like Tyrosine Kinase 1), Soluble Endoglin, and Proinflammatory Cytokines in Placenta
Authors: Kaitu’u-Lino Tu’uhevaha J. , Brownfoot Fiona C. , Hastie Roxanne , Chand Ashwini , Cannon Ping , Deo Minh , Tuohey Laura , Whitehead Clare , Hannan Natalie J. , Tong Stephen
Published: September 2017

Preeclampsia is a major pregnancy complication associated with poor placental perfusion and placental hypoxia. Systemic and placental inflammation and elevated placental secretion of the antiangiogenic factors sFlt-1 (soluble fms-like tyrosine kinase 1) and sEng (soluble endoglin) are hallmarks of preeclampsia, causing endothelial dysfunction and multiorgan injury. A molecule that links placental hypoxia, inflammation, and antiangiogenic factor release has not been described. ATF3 (activating transcription factor 3) is highly expressed in placenta. We assessed whether placental ATF3 is dysregulated in preterm preeclampsia, is altered by hypoxia, and regulates proinflammatory cytokine and antiangiogenic factor production. ATF3 mRNA and protein expression was significantly reduced in preterm preeclamptic placentas compared with gestation-matched controls. Hypoxia reduced ATF3 expression in primary cytotrophoblast and placental explants. Silencing ATF3 in primary cytotrophoblast increased proinflammatory cytokine (IL-6 [interleukin 6], TNF-α [tumor necrosis factor α]) and NF-κB (nuclear factor κB) expression. In silico analysis identified an ATF3–binding site in the promoter of Flt-1 (the transcript from which sFlt-1 is produced). Silencing ATF3 increased sFlt-1 and sEng secretion from primary cytotrophoblast possibly by increasing Rab11a and Arf1, cargo proteins that facilitate exosomal release of sFlt-1. ATF3 knockout mice did not have a preeclampsia phenotype, suggesting that these pathways may be specific to humans (preeclampsia is a uniquely human condition). To conclude, we have shown that ATF3 is decreased in preeclamptic placentas and that this decrease is likely to occur after prolonged hypoxia. We show that ATF3 is a regulator of placental proinflammatory cytokines and antiangiogenic factors sFlt-1 and sEng. Therefore, reduced ATF3 may be centrally involved in the pathology of preeclampsia.
Vascular ADAM17 (a Disintegrin and Metalloproteinase Domain 17) Is Required for Angiotensin II/β-Aminopropionitrile–Induced Abdominal Aortic Aneurysm
Authors: Kawai Tatsuo , Takayanagi Takehiko , Forrester Steven J. , Preston Kyle J. , Obama Takashi , Tsuji Toshiyuki , Kobayashi Tomonori , Boyer Michael J. , Cooper Hannah A. , Kwok Hang Fai , Hashimoto Tomoki , Scalia Rosario , Rizzo Victor , Eguchi Satoru
Published: September 2017

Angiotensin II (AngII)–activated epidermal growth factor receptor has been implicated in abdominal aortic aneurysm (AAA) development. In vascular smooth muscle cells (VSMCs), AngII activates epidermal growth factor receptor via a metalloproteinase, ADAM17 (a disintegrin and metalloproteinase domain 17). We hypothesized that AngII-dependent AAA development would be prevented in mice lacking ADAM17 in VSMCs. To test this concept, control and VSMC ADAM17-deficient mice were cotreated with AngII and a lysyl oxidase inhibitor, β-aminopropionitrile, to induce AAA. We found that 52.4% of control mice did not survive because of aortic rupture. All other surviving control mice developed AAA and demonstrated enhanced expression of ADAM17 in the AAA lesions. In contrast, all AngII and β-aminopropionitrile-treated VSMC ADAM17-deficient mice survived and showed reduction in external/internal diameters (51%/28%, respectively). VSMC ADAM17 deficiency was associated with lack of epidermal growth factor receptor activation, interleukin-6 induction, endoplasmic reticulum/oxidative stress, and matrix deposition in the abdominal aorta of treated mice. However, both VSMC ADAM17-deficient and control mice treated with AngII and β-aminopropionitrile developed comparable levels of hypertension. Treatment of C57Bl/6 mice with an ADAM17 inhibitory antibody but not with control IgG also prevented AAA development. In conclusion, VSMC ADAM17 silencing or systemic ADAM17 inhibition seems to protect mice from AAA formation. The mechanism seems to involve suppression of epidermal growth factor receptor activation.