bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the Behavior of Domestic Emus: A Means to Improve Their Management and Welfare—Major Behaviors and Activity Time Budgets of Adult Emus
Authors: Menon Deepa G. , Bennett Darin C. , Cheng Kimberly M.
Published: November 2014

Information on domestic emu behavior is sparse and hence a study was undertaken to identify and describe the behavior of domestic emus in a farm setting. The behavioral repertoires, activity time budgets, effect of time of the day, sex, weather, and relative humidity on activities of adult emus were investigated. Eight randomly selected emus were observed using one-zero sampling method for 12 days, each period of observation lasting 30 minutes. The major behavioral categories identified were ingestive drinking, standing, locomotion, grooming, socialization, vocalization, and resting. The emus spent most of their time walking, standing, and eating. Immediately after moving to a new pen, emus were found to huddle together to keep away from emus already resident in the pen. The time spent on each activity was not significantly different between the sexes. The findings from this study provided important information on the behavior and activities of emus. The observed behaviors need to be further examined to assess their relations to the birds’ welfare.
A Noninvasive Procedure for Early-Stage Discrimination of Malignant and Precancerous Vocal Fold Lesions Based on Laryngeal Dynamics Analysis
Authors: Unger Jakob , Lohscheller Jörg , Reiter Maximilian , Eder Katharina , Betz Christian S. , Schuster Maria
Published: November 2014

About two thirds of laryngeal cancers originate at the vocal cords. Early-stage detection of malignant vocal fold alterations, including a discrimination of premalignant lesions, represents a major challenge in laryngology as precancerous vocal fold lesions and small carcinomas are difficult to distinguish by means of regular endoscopy only. We report a procedure to discriminate between malignant and precancerous lesions by measuring the characteristics of vocal fold dynamics by means of a computerized analysis of laryngeal high-speed videos. Ten patients with squamous cell T1a carcinoma, ten with precancerous lesions with hyperkeratosis, and ten subjects without laryngeal disease underwent high-speed laryngoscopy yielding 4,000 images per second. By means of wavelet-based phonovibrographic analysis, a set of three clinically meaningful vibratory measures was extracted from the videos comprising a total number of 15,000 video frames. Statistical analysis (ANOVA with post hoc two-sided t tests, P < 0.05) revealed that vocal fold dynamics is significantly affected in the presence of precancerous lesions and T1a carcinoma. On the basis of the three measures, a discriminating pattern was extracted using a support vector machine-learning algorithm performing an individual classification in respect to the different clinical groups. By applying a leave-one-out cross-validation strategy, we could show that the proposed measures discriminate with a very high performance between precancerous lesions and T1a carcinoma (sensitivity, 100%; specificity, 100%). Although a large-scale study will be necessary to confirm clinical significance, the set of vibratory measures derived in this study may be applicable to improve the accuracy and reliability of noninvasive diagnostics of vocal fold lesions. Cancer Res; 75(1); 31–39. ©2014 AACR.
Cytotoxicity of Human Endogenous Retrovirus K–Specific T Cells toward Autologous Ovarian Cancer Cells
Authors: Rycaj Kiera , Plummer Joshua B. , Yin Bingnan , Li Ming , Garza Jeremy , Radvanyi Laszlo , Ramondetta Lois M. , Lin Kevin , Johanning Gary L. , Tang Dean G. , Wang-Johanning Feng
Published: November 2014

Purpose: To determine whether HERV-K envelope (ENV) protein could function as a tumor-associated antigen and elicit specific T-cell responses against autologous ovarian cancer cells.

Experimental Design: The expression of HERV-K transcripts and ENV protein, the presence of serum antibodies against HERV-K, reverse transcriptase (RT) activities, and cellular immune responses in primary ovarian cancer tissues and patient blood samples were analyzed and compared with samples from patients with benign ovarian diseases and normal female donors.

Results: Ovarian cancer cells in primary tumors and ascites expressed markers of cancer stem cells and markers of both mesenchymal and epithelial cells. Expression of HERV transcripts and HERV-K ENV protein and reverse transcriptase activities were higher in ovarian cancer compared with adjacent normal and benign tissues. The ovarian cancer patient plasma also had high reverse transcriptase activities and the ovarian cancer patient sera contained HERV-K immunoreactive antibodies. HERV-K–specific T cells generated from autologous dendritic cells pulsed with HERV-K ENV antigens exhibited phenotypes and functions consistent with a cellular immune response including T-cell proliferation, IFNγ production, and HERV-K–specific cytotoxic T lymphocyte (CTL) activity. Significantly higher CTL lysis of autologous tumor cells than of uninvolved normal cells was demonstrated in patients with ovarian cancer than patients with benign diseases and further enhanced lysis was observed if T regulatory cells were depleted.

Conclusion: Endogenous retroviral gene products in ovarian cancer may represent a potentially valuable new pool of tumor-associated antigens for targeting of therapeutic vaccines to ovarian cancer. Clin Cancer Res; 21(2); 471–83. ©2014 AACR.
Livin Contributes to Tumor Hypoxia–Induced Resistance to Cytotoxic Therapies in Glioblastoma Multiforme
Authors: Hsieh Chia-Hung , Lin Yu-Jung , Wu Chung-Pu , Lee Hsu-Tung , Shyu Woei-Cherng , Wang Chi-Chung
Published: November 2014

Purpose: Tumor hypoxia is one of the crucial microenvironments to promote therapy resistance (TR) in glioblastoma multiforme (GBM). Livin, a member of the family of inhibitor of apoptosis proteins, contributes antiapoptosis. However, the role of tumor hypoxia in Livin regulation and its impact on TR are unclear.

Experimental Design: Livin expression and apoptosis for tumor hypoxic cells derived from human glioblastoma xenografts or in vitro hypoxic stress-treated glioblastoma cells were determined by Western blotting, immunofluorescence imaging, and annexin V staining assay. The mechanism of hypoxia-induced Livin induction was investigated by chromatin immunoprecipitation assay and reporter assay. Genetic and pharmacologic manipulation of Livin was utilized to investigate the role of Livin on tumor hypoxia–induced TR in vitro or in vivo.

Results: The upregulation of Livin expression and downregulation of caspase activity were observed under cycling and chronic hypoxia in glioblastoma cells and xenografts, concomitant with increased TR to ionizing radiation and temozolomide. However, knockdown of Livin inhibited these effects. Moreover, hypoxia activated Livin transcription through the binding of hypoxia-inducible factor-1α to the Livin promoter. The targeted inhibition of Livin by the cell-permeable peptide (TAT-Lp15) in intracerebral glioblastoma-bearing mice demonstrated a synergistic suppression of tumor growth and increased the survival rate in standard-of-care treatment with radiation plus temozolomide.

Conclusions: These findings indicate a novel pathway that links upregulation of Livin to tumor hypoxia–induced TR in GBM and suggest that targeting Livin using cell-permeable peptide may be an effective therapeutic strategy for tumor microenvironment–induced TR. Clin Cancer Res; 21(2); 460–70. ©2014 AACR.
First-in-Human Phase I Study of Pictilisib (GDC-0941), a Potent Pan–Class I Phosphatidylinositol-3-Kinase (PI3K) Inhibitor, in Patients with Advanced Solid Tumors
Authors: Sarker Debashis , Ang Joo Ern , Baird Richard , Kristeleit Rebecca , Shah Krunal , Moreno Victor , Clarke Paul A. , Raynaud Florence I. , Levy Gallia , Ware Joseph A. , Mazina Kathryn , Lin Ray , Wu Jenny , Fredrickson Jill , Spoerke Jill M. , Lackner Mark R. , Yan Yibing , Friedman Lori S. , Kaye Stan B. , Derynck Mika K. , Workman Paul , de Bono Johann S.
Published: November 2014

Purpose: This first-in-human dose-escalation trial evaluated the safety, tolerability, maximal-tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, pharmacodynamics, and preliminary clinical activity of pictilisib (GDC-0941), an oral, potent, and selective inhibitor of the class I phosphatidylinositol-3-kinases (PI3K).

Patients and Methods: Sixty patients with solid tumors received pictilisib at 14 dose levels from 15 to 450 mg once-daily, initially on days 1 to 21 every 28 days and later, using continuous dosing for selected dose levels. Pharmacodynamic studies incorporated 18F-FDG-PET, and assessment of phosphorylated AKT and S6 ribosomal protein in platelet-rich plasma (PRP) and tumor tissue.

Results: Pictilisib was well tolerated. The most common toxicities were grade 1–2 nausea, rash, and fatigue, whereas the DLT was grade 3 maculopapular rash (450 mg, 2 of 3 patients; 330 mg, 1 of 7 patients). The pharmacokinetic profile was dose-proportional and supported once-daily dosing. Levels of phosphorylated serine-473 AKT were suppressed >90% in PRP at 3 hours after dose at the MTD and in tumor at pictilisib doses associated with AUC >20 h·μmol/L. Significant increase in plasma insulin and glucose levels, and >25% decrease in 18F-FDG uptake by PET in 7 of 32 evaluable patients confirmed target modulation. A patient with V600E BRAF–mutant melanoma and another with platinum-refractory epithelial ovarian cancer exhibiting PTEN loss and PIK3CA amplification demonstrated partial response by RECIST and GCIG-CA125 criteria, respectively.

Conclusion: Pictilisib was safely administered with a dose-proportional pharmacokinetic profile, on-target pharmacodynamic activity at dose levels ≥100 mg and signs of antitumor activity. The recommended phase II dose was continuous dosing at 330 mg once-daily. Clin Cancer Res; 21(1); 77–86. ©2014 AACR.
Habitual Myofibrillar Protein Synthesis Is Normal in Patients with Upper GI Cancer Cachexia
Authors: MacDonald Alisdair J. , Johns Neil , Stephens Nathan , Greig Carolyn , Ross James A. , Small Alexandra C. , Husi Holger , Fearon Kenneth C. H. , Preston Tom
Published: November 2014

Purpose: Skeletal muscle wasting and weight loss are characteristic features of cancer cachexia and contribute to impaired function, increased morbidity, and poor tolerance of chemotherapy. This study used a novel technique to measure habitual myofibrillar protein synthesis in patients with cancer compared with healthy controls.

Experimental design: An oral heavy water (87.5 g deuterium oxide) tracer was administered as a single dose. Serum samples were taken over the subsequent week followed by a quadriceps muscle biopsy. Deuterium enrichment was measured in body water, serum alanine, and alanine in the myofibrillar component of muscle using gas chromatography–pyrolysis–isotope ratio mass spectrometry and the protein synthesis rate calculated from the rate of tracer incorporation. Net change in muscle mass over the preceding 3 months was calculated from serial CT scans and allowed estimation of protein breakdown.

Results: Seven healthy volunteers, 6 weight-stable, and 7 weight-losing (≥5% weight loss) patients undergoing surgery for upper gastrointestinal cancer were recruited. Serial CT scans were available in 10 patients, who lost skeletal muscle mass preoperatively at a rate of 5.6%/100 days. Myofibrillar protein fractional synthetic rate was 0.058%, 0.061%, and 0.073%/hour in controls, weight-stable, and weight-losing patients, respectively. Weight-losing patients had higher synthetic rates than controls (P = 0.03).

Conclusion: Contrary to previous studies, there was no evidence of suppression of myofibrillar protein synthesis in patients with cancer cachexia. Our finding implies a small increase in muscle breakdown may account for muscle wasting. Clin Cancer Res; 21(7); 1734–40. ©2014 AACR.
Potential Mechanisms for Thrombocytopenia Development with Trastuzumab Emtansine (T-DM1)
Authors: Uppal Hirdesh , Doudement Estelle , Mahapatra Kaushiki , Darbonne Walter C. , Bumbaca Daniela , Shen Ben-Quan , Du Xiaoyan , Saad Ola , Bowles Kristin , Olsen Steve , Lewis Phillips Gail D. , Hartley Dylan , Sliwkowski Mark X. , Girish Sandhya , Dambach Donna , Ramakrishnan Vanitha
Published: November 2014

Purpose: Trastuzumab-emtansine (T-DM1) is an antibody–drug conjugate (ADC) comprising the cytotoxic agent DM1 conjugated to trastuzumab with a stable linker. Thrombocytopenia was the dose-limiting toxicity in the phase I study, and grade ≥3 thrombocytopenia occurred in up to 13% of patients receiving T-DM1 in phase III studies. We investigated the mechanism of T-DM1–induced thrombocytopenia.

Experimental Design: The effect of T-DM1 on platelet function was measured by aggregometry, and by flow cytometry to detect the markers of activation. The effect of T-DM1 on differentiation and maturation of megakaryocytes (MK) from human hematopoietic stem cells was assessed by flow cytometry and microscopy. Binding, uptake, and catabolism of T-DM1 in MKs, were assessed by various techniques including fluorescence microscopy, scintigraphy to detect T-[H3]-DM1 and 125I-T-DM1, and mass spectrometry. The role of FcγRIIa was assessed using blocking antibodies and mutant constructs of trastuzumab that do not bind FcγR.

Results: T-DM1 had no direct effect on platelet activation and aggregation, but it did markedly inhibit MK differentiation via a cytotoxic effect. Inhibition occurred with DM1-containing ADCs but not with trastuzumab demonstrating a role for DM1. MKs internalized these ADCs in a HER2-independent, FcγRIIa-dependent manner, resulting in intracellular release of DM1. Binding and internalization of T-DM1 diminished as MKs matured; however, prolonged exposure of mature MKs to T-DM1 resulted in a disrupted cytoskeletal structure.

Conclusions: These data support the hypothesis that T-DM1–induced thrombocytopenia is mediated in large part by DM1-induced impairment of MK differentiation, with a less pronounced effect on mature MKs. Clin Cancer Res; 21(1); 123–33. ©2014 AACR.
Tasquinimod Modulates Suppressive Myeloid Cells and Enhances Cancer Immunotherapies in Murine Models
Authors: Shen Li , Sundstedt Anette , Ciesielski Michael , Miles Kiersten Marie , Celander Mona , Adelaiye Remi , Orillion Ashley , Ciamporcero Eric , Ramakrishnan Swathi , Ellis Leigh , Fenstermaker Robert , Abrams Scott I. , Eriksson Helena , Leanderson Tomas , Olsson Anders , Pili Roberto
Published: November 2014

A major barrier for cancer immunotherapy is the presence of suppressive cell populations in patients with cancer, such as myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM), which contribute to the immunosuppressive microenvironment that promotes tumor growth and metastasis. Tasquinimod is a novel antitumor agent that is currently at an advanced stage of clinical development for treatment of castration-resistant prostate cancer. A target of tasquinimod is the inflammatory protein S100A9, which has been demonstrated to affect the accumulation and function of tumor-suppressive myeloid cells. Here, we report that tasquinimod provided a significant enhancement to the antitumor effects of two different immunotherapeutics in mouse models of cancer: a tumor vaccine (SurVaxM) for prostate cancer and a tumor-targeted superantigen (TTS) for melanoma. In the combination strategies, tasquinimod inhibited distinct MDSC populations and TAMs of the M2-polarized phenotype (CD206+). CD11b+ myeloid cells isolated from tumors of treated mice expressed lower levels of arginase-1 and higher levels of inducible nitric oxide synthase (iNOS), and were less immunosuppressive ex vivo, which translated into a significantly reduced tumor-promoting capacity in vivo when these cells were coinjected with tumor cells. Tumor-specific CD8+ T cells were increased markedly in the circulation and in tumors. Furthermore, T-cell effector functions, including cell-mediated cytotoxicity and IFNγ production, were potentiated. Taken together, these data suggest that pharmacologic targeting of suppressive myeloid cells by tasquinimod induces therapeutic benefit and provide the rationale for clinical testing of tasquinimod in combination with cancer immunotherapies. Cancer Immunol Res; 3(2); 136–48. ©2014 AACR.
Social Dysfunctioning and Brain in Borderline Personality Disorder
Authors: Herpertz Sabine C. , Jeung Haang , Mancke Falk , Bertsch Katja
Published: November 2014

Interpersonal dysfunction is the most prominent and best discriminating characteristic in individuals with borderline personality disorder (BPD). Data from experimental psychopathology point to emotional lability, (auto-)aggression, threat hypersensitivity, poor chance of interpersonal repair, frequent misunderstandings and self/other diffusion as the most significant factors which contribute to the interpersonal derailments typical of BPD. Neuroscientific methods are suitable to elucidate the mechanisms which mediate deficient social functioning in BPD, i.e. affective dysregulation, impulsivity/disinhibition and poor social cognition as well as their neurobiological correlates. Low prefrontoamygdalar coupling together with low activity in inhibiting prefrontal areas, high activity in the mirror neuron system, low activity in the mentalizing circuit, and low anterior insular activity in case of social norm violations are the most significant functional neuroimaging findings that have been reported from individuals with BPD, up to now. In addition, peculiarities of facial emotion processing have been detected by means of psychophysiological methodology in BPD patients. Data have led to preliminary models of social dysfunctioning in BPD that have to be experimentally tested in the future, evolving neuroscience into an important tool to better understand what distresses patients with BPD when communicating with others.
The Shanghai Aging Study: Study Design, Baseline Characteristics, and Prevalence of Dementia
Authors: Ding Ding , Zhao Qianhua , Guo Qihao , Meng Haijiao , Wang Bei , Yu Peimin , Luo Jianfeng , Zhou Yan , Yu Lirong , Zheng Li , Chu Shuguang , Mortimer James A. , Borenstein Amy R. , Hong Zhen
Published: November 2014

Background: To establish a prospective cohort to enumerate the prevalence, incidence and risk factors for dementia and mild cognitive impairment (MCI) among residents aged ≥60 in an urban community of Shanghai, China. Methods: Participants received clinical evaluations including physical measurements, demographic and lifestyle questionnaires, physical and neurologic examinations, and neuropsychological testing. Urine and blood samples were collected, aliquoted, and stored. DNA was extracted for Apolipoprotein (APOE) genotyping. Diagnoses of dementia and MCI were made using standard criteria via consensus diagnosis. Results: Among 3,141 participants aged ≥60, 1,438 (45.8%) were men. The average age of participants was 72.3 years (SD 8.1), and they had an average of 11.6 years (SD 4.4) of education. The most common chronic disease of participants was hypertension (56.4%). The frequencies of APOE-​ε2, ε3 and ε4 were 7.9, 82.7 and 9.4%, respectively. We diagnosed 156 (5.0%, 95% CI 4.3-5.8%) participants with dementia. The prevalence rates of Alzheimer's disease and vascular dementia were 3.6% (95% CI 3.0-4.3%) and 0.8% (95% CI 0.5-1.1%). Conclusions: The Shanghai Aging Study is the first prospective community-based cohort study of cognitive impairment in China, with a comparable study design, procedures, and diagnostic criteria for dementia and MCI to most previous cohort studies in developed countries.
Non-Steroidal Anti-Inflammatory Drug Use and Essential Tremor
Authors: Pan Jie , Michalec Monika , Louis Elan D.
Published: November 2014

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be inversely related to Parkinson's disease and Alzheimer's disease, both of which may share common mechanisms with essential tremor (ET). Use of these medications has not been studied in ET cases vs. controls. Objective: To investigate the relationships between NSAID (esp. ibuprofen) and aspirin use and ET. Methods: Subjects were enrolled in a case-control study of the environmental epidemiology of ET at the Columbia University Medical Center (CUMC; 2009-2014). We compared 92 ET cases to 107 controls (∼1:1 matching) in terms of self-reported NSAID (esp. ibuprofen) and aspirin use. Results: The proportion of NSAID or aspirin users (current or past) was similar in ET cases and controls (for current user, p = 0.66; for past user, p = 0.90). Among users, however, the total dosage of ibuprofen (frequency in past year × number of tablets taken at a time × typical average strength of tablets) was higher in controls than ET cases (p = 0.04). ET cases and controls did not differ with respect to aspirin use in the past year. Conclusion: The proportion of NSAID or aspirin users did not differ in ET cases or controls; yet interestingly, ibuprofen use was less in ET cases than in controls. The latter raises the possibility that ibuprofen use could have a potential protective role in ET.
Internal Quality Control for Cervical Cytopathology: Comparison of Potential False-Negatives Detected at Rapid Prescreening and at 100% Rapid Review
Authors: Tavares Suelene Brito do Nascimento , de Souza Nádja L. Alves , Manrique Edna J.C. , Ázara Cinara Zago Silveira , da Silveira Erika Aparecida , Amaral Rita Goreti
Published: November 2014

Objective: To evaluate the performance of rapid prescreening (RPS) and 100% rapid review (RR-100%) as internal quality control (IQC) methods assessed by outcome at colposcopy, histopathology and repeat cytopathology for cases with false-negative results on cervical cytopathology at routine screening (RS). Study Design: Out of 12,208 cytology smears analyzed, 900 were abnormal. Of these, 656 were identified at RS, and 244 were false-negative, with 90.2% identified at RPS and 57.4% at RR-100%. Of the 900 abnormal cases, 436 were submitted for additional testing. Results: Of the 244 women with cytopathological abnormalities identified only by the IQC methods, 114 had supplementary examinations: 35 were submitted for colposcopy, 22 for biopsy and 99 for repeat cytopathology. The sensitivity of RPS for the detection of abnormalities identified on colposcopy, histopathology and repeat cytopathology was 87.5% (95% CI 67.6-97.3), 82.4% (95% CI 56.6-96.2) and 95.7% (95% CI 85.2-99.5), respectively. The sensitivity of RR-100% was 54.2% (95% CI 32.8-74.4), 52.9% (95% CI 27.8-77.0) and 47.8% (95% CI 32.9-63.1), respectively. RPS was more sensitive than RR-100% when compared to the findings on colposcopy (p = 0.011) and repeat cytopathology (p = 0.000). When compared to colposcopy, histopathology and repeat cytopathology, the sensitivity of RS was 83.2% (95% CI 76.1-88.9), 85.7% (95% CI 78.1-91.5) and 73.3% (95% CI 66.0-79.7), respectively. Conclusion: RPS performed better than RR-100% when compared to the results of colposcopy and repeat cytopathology.
Lung Ultrasonography May Provide an Indirect Estimation of Lung Porosity and Airspace Geometry
Authors: Soldati Gino , Smargiassi Andrea , Inchingolo Riccardo , Sher Sara , Nenna Rosanna , Valente Salvatore , Inchingolo Cosimo Damiano , Corbo Giuseppe Maria
Published: November 2014

Background: Echographic vertical artifacts (B-lines) in chest ultrasonography have often been associated with pathological patterns. A scientifically sound explanation of these artifacts has not yet been proposed. Objectives: The ‘spongy' nature of the lung in its liquid and solid components and the changes that take place in peripheral airspace (PAS) geometry might be the key point to understanding these phenomena. Methods: Six excised right rabbit lungs were obtained. Each lung underwent direct ultrasound evaluation in two different conditions: at complete tissue elastic recoil volume and at pulmonary expansion volume achieved by applying a constant positive pressure of 12 cm H2O. Lung volumes and densities were reported in both conditions. Histological examination was performed on three naturally collapsed lungs and on three lungs under positive pressure inflation after having been fixed in formalin solution. Results: Mean volumes of naturally collapsed lungs and fixed expanded lungs were 11.2 ± 0.36 and 44.83 ± 3.03 ml, respectively. Mean densities were 0.622 ± 0.016 and 0.155 ± 0.007 g/ml, respectively. Ultrasound evaluation of collapsed lungs showed dense vertical artifacts and a ‘white lung' pattern, while the evaluation of expanded lungs showed hyperechoic line and horizontal artifacts of reflection. Histological evaluation showed a different PAS geometry in collapsed lungs caused by alveolar size reduction and shape changes with unfolded and closed units modifying the peripheral porosity of the frothy nature of the lung. Conclusions: Airspace geometry, frothy nature and porosity are the determinants of the different behavior of ultrasound interacting with the subpleural lung parenchyma. Chest ultrasound may thus be interpreted as an indirect ‘estimator' of lung porosity.
Vasopressin Aggravates Cardiopulmonary Bypass-Induced Gastric Mucosal Ischemia
Authors: Bomberg Hagen , Bierbach Benjamin , Flache Stephan , Novák Matous , Bandner-Risch Doris , Menger Michael D. , Schäfers Hans-Joachim
Published: November 2014

Background/Aim: Upper gastrointestinal bleeding (UGIB) is one of the most frequent gastrointestinal complications after cardiac surgery with cardiopulmonary bypass (CPB). Endothelin expression and microcirculatory dysfunction have been shown to be involved in UGIB. The aim of this study was to analyze the effect of vasopressin during CPB on the gastric mucosal microcirculation and the involvement of the endothelin system. Methods: Eighteen pigs were randomized into three groups (n = 6 each): group I = sham, group II = CPB (1-hour CPB) and group III = CPB + vasopressin (1-hour CPB and vasopressin administration during CPB to maintain baseline arterial pressure). All animals were observed for a further 90 min after termination of CPB. Systemic hemodynamics as well as blood flow and oxygen saturation of the gastric mucosa were measured continuously. At the end of the experiment, the gastric mucosal expressions of endothelin-1 (ET-1) and its receptor subtypes A (ETA) and B (ETB) were determined by polymerase chain reaction. Gastric mucosal injury, apoptotic cell death and leukocytic infiltration were determined by histology and immunohistochemical analyses of cleaved caspase-3 and myeloperoxidase. Results: CPB decreased gastric microvascular perfusion, which was associated with an increased expression of ET-1 and ETA. Vasopressin aggravated the CPB-associated malperfusion, whereas it completely abrogated the upregulation of ET-1 and ETA. Interestingly, vasopressin did not induce gastric mucosal morphologic injury, leukocytic infiltration or apoptotic cell death. Conclusion: Vasopressin aggravates CPB-associated microvascular malperfusion of the gastric mucosa but does not induce gastric mucosal injury.
Efficacy and Safety of Prolonged-Release Trazodone in Major Depressive Disorder: A Multicenter, Randomized, Double-Blind, Flexible-Dose Trial
Authors: Zhang Lin , Xie Wei-Wei , Li Le-Hua , Zhang Hong-Geng , Wang Gang , Chen Da-Chun , Cao Yi , Cui Li-Jun , Zhang Ke-Rang , Shi Jian-Guo , Tan Qing-Rong , Zheng Hong-Bo , Xu Xiu-Feng , Cheng Zao-Huo , Zhao Jing-Ping
Published: November 2014

Objective: To investigate the efficacy, safety, and clinical benefit of prolonged-release trazodone (Trittico) in the treatment of major depressive disorder (MDD). Methods: In this study, 363 Chinese patients with MDD were randomized 1:1 to receive either prolonged-release trazodone (150-450 mg) or placebo treatment for 6 weeks. The primary efficacy measurement was the change of the 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the end of the study. The secondary efficacy measurements were the response and remission rates, the Clinical Global Impression - Improvement of Illness (CGI-I) score at the end of the study, and the change of the HAMD-14 total score and quality of sleep [evaluated by the Pittsburgh Sleep Quality Index (PSQI) scale] during the study period. Results: The mean maximum daily dose was 273.11 mg for the trazodone group and 290.92 mg for the placebo group. At the end of the study, there was a significant difference between the two groups in the HAMD-17 change score (trazodone vs. placebo: -11.07 vs. -8.29, p < 0.001). Trazodone showed advantages at 1 week of treatment, and the effect lasted until the end of the study (week 6). The response and remission rates of the trazodone group were significantly higher than those in the placebo group (response rate: 59.6 vs. 37.2%, p < 0.001; remission rate: 35.5 vs. 22.2%, p = 0.005). The majority of the adverse reactions of trazodone were mild to moderate, and the most frequent adverse reactions (≥5%) were dizziness, dry mouth, somnolence, and nausea. Conclusions: Prolonged-release trazodone was more effective than placebo in MDD and was well tolerated. i 2014 S. Karger AG, Basel
Guideline for the Acquisition and Preparation of Conventional and Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Specimens for the Diagnosis and Molecular Testing of Patients with Known or Suspected Lung Cancer
Authors: van der Heijden Erik H.F.M. , Casal Roberto F. , Trisolini Rocco , Steinfort Daniel P. , Hwangbo Bin , Nakajima Takahiro , Guldhammer-Skov Birgit , Rossi Giulio , Ferretti Maurizio , Herth Felix F.J. , Yung Rex , Krasnik Mark ,   on behalf of the International World Association for Bronchology and Interventional Pulmonology Task Force on Specimen Guidelines
Published: November 2014

Rationale: Conventional transbronchial needle aspiration (TBNA) and endobronchial ultrasound (EBUS)-TBNA are widely accepted tools for the diagnosis and staging of lung cancer and the initial procedure of choice for staging. Obtaining adequate specimens is key to provide a specific histologic and molecular diagnosis of lung cancer. Objectives: To develop practice guidelines on the acquisition and preparation of conventional TBNA and EBUS-TBNA specimens for the diagnosis and molecular testing of (suspected) lung cancer. We hope to improve the global unification of procedure standards, maximize the yield and identify areas for research. Methods: Systematic electronic database searches were conducted to identify relevant studies for inclusion in the guideline [PubMed and the Cochrane Library (including the Cochrane Database of Systematic Reviews)]. Main Results: The number of needle aspirations with both conventional TBNA and EBUS-TBNA was found to impact the diagnostic yield, with at least 3 passes needed for optimal performance. Neither needle gauge nor the use of miniforceps, the use of suction or the type of sedation/anesthesia has been found to improve the diagnostic yield for lung cancer. The use of rapid on-site cytology examination does not increase the diagnostic yield. Molecular analysis (i.e. EGFR, KRAS and ALK) can be routinely performed on the majority of cytological samples obtained by EBUS-TBNA and conventional TBNA. There does not appear to be a superior method for specimen preparation (i.e. slide staining, cell blocks or core tissue). It is likely that optimal specimen preparation may vary between institutions depending on the expertise of pathology colleagues.
Remarkable Response to Neoadjuvant Therapy with Methotrexate, Vinblastine, Adriamycin, and Cisplatin for Undifferentiated Bladder Carcinoma: A Case Report and Literature Review
Authors: Numahata Kenji , Hoshi Senji , Hoshi Kiyotsugu , Yasuno Nobuhiro , Kubo Maiko , Sasagawa Isoji , Ohta Shoichiro
Published: November 2014

We report a case of primary undifferentiated bladder carcinoma, which revealed a remarkable response to methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) therapy. A 46-year-old Japanese woman presented at the hospital with the chief complaints of gross hematuria and pain during urination. Cystoscopy revealed a large smooth-surfaced tumor in the urinary bladder. The histopathological diagnosis was undifferentiated carcinoma. The patient then received 3 courses of MVAC over a 3-month period. Hydronephrosis disappeared after the first course, and the tumor shrank rapidly. After completion of the third MVAC course, radical cystectomy and ileal conduit surgery were performed. After 7 years, the patient has still had no recurrences or metastases. We retrospectively review the relative efficacy of the two popular chemotherapeutic regimens in the management of muscle-invasive bladder cancer in patients who had had radical cystectomy.
Shared Molecular Pathways and Gene Networks for Cardiovascular Disease and Type 2 Diabetes Mellitus in Women Across Diverse Ethnicities
Authors: Chan Kei Hang K. , Huang Yen-Tsung , Meng Qingying , Wu Chunyuan , Reiner Alexander , Sobel Eric M. , Tinker Lesley , Lusis Aldons J. , Yang Xia , Liu Simin
Published: November 2014

Background—

Although cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D) share many common risk factors, potential molecular mechanisms that may also be shared for these 2 disorders remain unknown.

Methods and Results—

Using an integrative pathway and network analysis, we performed genome-wide association studies in 8155 blacks, 3494 Hispanic American, and 3697 Caucasian American women who participated in the national Women’s Health Initiative single-nucleotide polymorphism (SNP) Health Association Resource and the Genomics and Randomized Trials Network. Eight top pathways and gene networks related to cardiomyopathy, calcium signaling, axon guidance, cell adhesion, and extracellular matrix seemed to be commonly shared between CVD and T2D across all 3 ethnic groups. We also identified ethnicity-specific pathways, such as cell cycle (specific for Hispanic American and Caucasian American) and tight junction (CVD and combined CVD and T2D in Hispanic American). In network analysis of gene–gene or protein–protein interactions, we identified key drivers that included
COL1A1, COL3A1
, and
ELN
in the shared pathways for both CVD and T2D. These key driver genes were cross-validated in multiple mouse models of diabetes mellitus and atherosclerosis.

Conclusions—

Our integrative analysis of American women of 3 ethnicities identified multiple shared biological pathways and key regulatory genes for the development of CVD and T2D. These prospective findings also support the notion that ethnicity-specific susceptibility genes and process are involved in the pathogenesis of CVD and T2D.
Stent Coverage and Neointimal Proliferation in Bare Metal Stents Postdilated With a Paclitaxel-Eluting Balloon Versus Everolimus-Eluting Stents
Authors: Poerner Tudor C. , Otto Sylvia , Gassdorf Johannes , Nitsche Kristina , Janiak Florian , Scheller Bruno , Goebel Björn , Jung Christian , Figulla Hans R.
Published: November 2014

Background—

In this randomized trial, strut coverage and neointimal proliferation of a therapy of bare metal stents (BMSs) postdilated with the paclitaxel drug-eluting balloon (DEB) was compared with everolimus drug-eluting stents (DESs) at 6-month follow-up using optical coherence tomography. We hypothesized sufficient stent coverage at follow-up.

Methods and Results—

A total of 105 lesions in 90 patients were treated with either XIENCE V DES (n=51) or BMS postdilated with the SeQuent Please DEB (n=54). At follow-up, comparable results on the primary optical coherence tomography end point (percentage uncovered struts 5.64±9.65% in BMS+DEB versus 4.93±9.29% in DES;
P
=0.366) were found. Thus, BMS+DEB achieved the prespecified noninferiority margin of 5% uncovered struts versus DES (difference between treatment means, 0.71%; one-sided upper 95% confidence interval, 4.14%; noninferiority
P
=0.04). Optical coherence tomography analysis showed significantly more global neointimal proliferation in the BMS+DEB group (15.7±7.8 versus 11.0±5.2 mm
3
proliferation volume/cm stent length;
P
=0.002). No significant focal in-stent stenosis analyzed with angiography (percentage diameter stenosis at follow-up, 22.8±11.9 versus 16.9±10.4;
P
=0.014) and optical coherence tomography (peak local area stenosis, 39.5±13.8% versus 36.8±15.6%;
P
=0.409) was found.

Conclusions—

Good stent strut coverage of >94% was found in both therapy groups. Despite greater suppression of global neointimal growth in DES, both DES and BMS+DEB effectively prevented clinically relevant focal restenosis at 6-month follow-up.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01056744.
Worsening of Renal Function During 1 Year After Hospital Discharge Is a Strong and Independent Predictor of All‐Cause Mortality in Acute Decompensated Heart Failure
Authors: Ueda Tomoya , Kawakami Rika , Sugawara Yu , Okada Sadanori , Nishida Taku , Onoue Kenji , Soeda Tsunenari , Okayama Satoshi , Takeda Yukiji , Watanabe Makoto , Kawata Hiroyuki , Uemura Shiro , Saito Yoshihiko
Published: November 2014

Background

Renal impairment is a common comorbidity and the strongest risk factor for poor prognosis in acute decompensated heart failure (
ADHF
). In clinical practice, renal function is labile during episodes of
ADHF
, and often worsens after discharge. The significance of worsening of renal function (
WRF
) after discharge has not been investigated as extensively as baseline renal function at admission or
WRF
during hospitalization.

Methods and Results

Among 611 consecutive patients with ADHF emergently admitted to our hospital, 233 patients with 3 measurements of serum creatinine (SCr) level measurements (on admission, at discharge, and 1 year after discharge) were included in the present study. Patients were divided into 2 groups according to the presence or absence of WRF at 1 year after discharge (1y‐WRF), defined as an absolute increase in SCr >0.3 mg/
dL
(>26.5 μmol/L) plus a ≥25% increase in SCr at 1 year after discharge compared to the SCr value at discharge. All‐cause and cardiovascular mortality were assessed as adverse outcomes. During a mean follow‐up of 35.4 months, 1y‐
WRF
occurred in 48 of 233 patients. There were 66 deaths from all causes. All‐cause and cardiovascular mortality were significantly higher in patients with 1y‐
WRF
(log‐rank
P
<0.0001 and
P
<0.0001, respectively) according to Kaplan–Meier analysis. In a multivariate Cox proportional hazards model, 1y‐
WRF
was a strong and independent predictor of all‐cause and cardiovascular mortality. Hemoglobin and B‐type natriuretic peptide at discharge, as well as left ventricular ejection fraction <50%, were independent predictors of 1y‐
WRF
.

Conclusions

In patients with
ADHF
, 1y‐
WRF
is a strong predictor of all‐cause and cardiovascular mortality.
Rule-Based Automatic Generation of Logo Designs
Authors: Li Yi-Na , Zhang Kang , Li Dong-Jin
Published: November 2014

This article proposes the application of shape grammar to the automatic generation of logo designs based on artists’ logo creation knowledge and visual structures of logos. The authors propose a set of rules to encode the design knowledge and enable automatic generation. They then present an experiment that was conducted to validate the feasibility of the proposed approach.
Biopaintings Produced by Filamentous Fungi
Authors: Noronha Patrícia
Published: November 2014

The author explores the use of tridimensional filamentous fungi patterns to produce biopaintings. The painting process involves incorporation of food dyes into a fungi growth medium. Then, after some biochemical processes, the fungal forms are dehydrated and immobilized in polyester resin. Changes in colors and texture occur, resulting in lively images.
A Strong Couple: New Media and Socially Engaged Art
Authors: van der Meulen Sjoukje
Published: November 2014

Despite the relevance of new media art for the critical understanding of the information and network societies today, it is largely ignored as a socially engaged practice—certainly compared to other forms of socially engaged artistic practices in the international field of contemporary art. This article outlines the reasons for this relative neglect and specifies different kinds of new media art that qualify for the category of socially engaged art beyond leftist politics and ideologies transposed to the realm of art. Proposing and mobilizing a “media-reflexive” art theory, which emerged from the author’s doctoral dissertation, this claim is substantiated by the analysis of three exemplary digital art projects by Joseph Nechvatal, George Legrady and Blast Theory, respectively.
Reproductive potential and stock recruitment of the Caribbean and Brazilian metapopulations of the spiny lobster, Panulirus argus (Latreille, 1804)
Authors: Cruz Raúl , Silva Katia C. A. , Santana João V. M. , Gaeta Juliana C. , Cintra Israel H. A.
Published: November 2014

The spiny lobsterPanulirus argus(Latreille, 1804) is the most important commercial fishing resource in the western central Atlantic and Brazil. Field studies covering the waters off southwestern Cuba and northern Brazil have improved our understanding of the variations in the reproductive potential (number of eggs), stock recruitment and reproductive efficiency of spiny lobsters according to location, depth and size class. Using the spawner-recruitment model, the reproductive potential index was correlated with the index of subsequent recruitment based on field sampling. Spiny lobster habitats in deeper waters need special attention in order to protect the species from overfishing of the recruitment. Considering the longevity and absence of reproductive senility in spiny lobsters, management strategies should ideally include the creation of spawner sanctuaries (marine protected areas) capable of restoring and maintaining the biomass of the spawning stock and the establishment of a maximum catch size of 135 mm (CL) for both sexes along the entire Brazilian coast. Based on our findings, we propose to establish spiny lobster sanctuaries (50-100 m) on the continental shelf off northern Brazil, from Amapá (5°25′N 51°0′W) to the western reaches of the coast of Pará (1°11′N 46°27′W, 0°42′N 46°45′W), covering a total surface area of 64 230 km2.
Soft-body preservation in the leaiid clam shrimp (Branchiopoda, Diplostraca) and its palaeoecological implications
Authors: Shen Yan-Bin , Schram Frederick R.
Published: November 2014

Leaiais a special genus of extinct “conchostracan” branchiopods; its soft parts have not been known until now. The leaiid specimens with soft bodies reported in the present paper came from two localities: the Upper Carboniferous Canso Group of New Brunswick, Canada, and the Permian Mount Glossopteris Formation of the Ohio Range, Holick Mountains, Antarctica. They include head, biramous antennae, mandible, shell gland, male claspers, and digestive tube. These parts together fully demonstrate that the leaiid clam shrimp indeed should be attributed to the crustaceans, instead of Mollusca. Based on the ribbed valves and structure of soft parts it should be placed in the branchiopodan Diplostraca. We believe that this group, which went extinct at the end of the Permian, is quite different from those of Laevicaudata, Spinicaudata, and Cyclestheriida. Hence, it should have its own higher taxon, Leaiina. The well-developed and sharply pointed head, delicate and short biramous antennae, in concert with the radial ribs on the valves probably indicate a burrowing in-faunal habit.
A null model to study community structure of microcrustacean assemblages in north Patagonian urban wetlands (39-41°S, Chile)
Authors: De los Ríos-Escalante Patricio , Muñoz-Pedreros Andrés , Möller Patricia
Published: November 2014

The inland water bodies of northern Chilean Patagonia (38-41°S) have many lakes, wetlands and ponds with different littoral and zooplanktonic crustacean assemblages. This study presents field observations of species associations sampled from shallow wetlands located in the urban zones of Valdivia (39°S) and Puerto Montt (41°S). A species presence-absence matrix was created for calculating the Jaccard Index of community similarity and for testing null models of species associations, with the aim of determining whether species associations are random or not. The results of the Jaccard Index calculations indicated the existence of non-defined groups. The results of the null model analysis denoted the presence of regulating factors for Valdivia wetlands, whereas for Puerto Montt wetlands no such factors could be demonstrated. The outcomes of both the Jaccard Index and the significant null model analysis agree with previous ecological descriptions of changes in trophic status as a consequence of changes in the surrounding basin as a determinant of species associations. The ecology of these communities is also discussed.
Niche segregation between two closely similar gammarids (Peracarida, Amphipoda) — native vs. naturalized non-native species
Authors: Mauchart Péter , Bereczki Csaba , Ortmann-Ajkai Adrienne , Csabai Zoltán , Szivák Ildikó
Published: November 2014

Closely similar species may occupy similar niches, but usually divergence can be found in one or more traits when they inhabit the same habitat. In this study, we examined how two co-occurring gammarids — the nativeGammarus fossarumand the naturalizedG. roeselii — are distributed among microhabitats, depending on their sympatric or allopatric distribution. We hypothesized that the larger body-sized species (G. roeselii), exploiting their advantages in competition, restrict smaller species to microhabitats with smaller particle sizes. Four headwaters were sampled in the Mecsek Mountains (SW Hungary) in May, July and October 2009, and 37 local scale environmental variables at each site were measured. AlthoughG. fossarumis smaller in size, significantly more individuals were collected from the more favourable lithal and biotic microhabitats, whereas a strong negative association was observed between the two species.Gammarus roeseliioccurred at sites characterized by degraded riparian vegetation, which indicates stronger anthropogenic impacts, but still has a disadvantage in competition in mountainous streams under anthropogenic influence.
Reproduction and growth of the spiny lebbeid shrimp, Lebbeus groenlandicus (Fabricius, 1775) (Caridea, Hippolytidae) in the East Sea of Korea
Authors: Bae Ho Jin , Oh Chul-Woong
Published: November 2014

Reproduction and growth of the spiny lebbeid shrimp, Lebbeus groenlandicus (Fabricius, 1775), were investigated based on samples in the East Sea of Korea [= Sea of Japan], from January 2012 to April 2013. We collected 2964 shrimp samples during the study period, which included significantly more females than males (male : female ratio, 1.0 : 1.17). The females were generally larger than the males, and significant differences in the linear-regression slopes of carapace length (CL) versus body weight between the sexes indicate sex-specific differences in allometric growth. The gonadosomatic index (GSI) varied monthly, reaching a maximum in November 2012 (10.28) and a minimum in March 2013 (2.15). The proportion of ovigerous females varied from month to month. The highest values of the GSI coincided with the breeding period, and there was a significant difference between the mean GSI of females with non-eyed and those with eyed eggs, indicating that L. groenlandicus is a consecutive breeder. There was a significant correlation between CL and the number of eggs (EN) in the early egg stages. There was also a significant difference in the slopes of the regressions of CL versus EN between females carrying non-eyed and eyed egg stages. Based on the dry weights in the early egg stages, reproductive output was determined to be 0.18 ± 0.006. The Von Bertalanffy growth function parameters were CL∞ = 38.80 mm, year−1, , and WP = 0.4 for males, and CL∞ = 43.64 mm, year−1, , and WP = 0.6 for females. The growth performance index () was 2.86 for males and 2.89 for females.