bluuebunny/crossref_metadata_2025 huggingface dataset:
T790M-Selective EGFR-TKI Combined with Dasatinib as an Optimal Strategy for Overcoming EGFR-TKI Resistance in T790M-Positive Non–Small Cell Lung Cancer
Authors: Watanabe Satomi , Yoshida Takeshi , Kawakami Hisato , Takegawa Naoki , Tanizaki Junko , Hayashi Hidetoshi , Takeda Masayuki , Yonesaka Kimio , Tsurutani Junji , Nakagawa Kazuhiko
Published: August 2017

T790M mutation–selective EGFR tyrosine kinase inhibitors (EGFR-TKI) have demonstrated clinical benefits in non–small cell lung cancer (NSCLC) patients harboring T790M mutation, which is the major cause of resistance to EGFR-TKI. However, their efficacy is limited, possibly due to the emergence of apoptosis resistance in T790M-positive NSCLC. We previously identified Src family kinases as cooncogenic drivers along with T790M and found that the Src inhibitor dasatinib combined with an irreversible or a preclinical T790M-selective EGFR-TKI enhanced antitumor activity in T790M-positive cells. In the current study, we evaluated the efficacy of dasatinib combined with the clinically relevant T790M-selective EGFR-TKI ASP8273 or osimertinib in EGFR mutation–positive NSCLC with or without T790M mutation. A cell viability assay revealed that dasatinib had synergistic effects with these TKIs in T790M-positive cells and simultaneously inhibited Src, Akt, and Erk, which remained activated upon single-agent treatment. Dasatinib also increased the rate of apoptosis in T790M-positive cells induced by T790M-selective EGFR-TKIs, as determined by the Annexin-V binding assay; this was associated with downregulation of the antiapoptotic Bcl-2 family member Bcl-xL, a finding that was confirmed in mice bearing T790M-positive xenografts. Our results suggest that Bcl-xL plays a key role in the apoptosis resistance of T790M-positive NSCLC, and that dasatinib combined with clinically relevant T790M-selective EGFR-TKIs is potentially effective in overcoming resistance to first-generation EGFR-TKIs in NSCLC patients with acquired T790M. Mol Cancer Ther; 16(11); 2563–71. ©2017 AACR.
How Can We Enhance the Sense of Self-Efficacy in Epilepsy Individual Responses from 2 Qualitative Case Reports
Authors: Michaelis Rosa , Niedermann Christina , Berger Bettina
Published: August 2017

Background: Epilepsy is a serious, common and chronic neurological condition characterized by an increased disposition to suffer occasional seizures. Psychological interventions may enhance the well-being of individuals with epilepsy. So far, no qualitative study has investigated the complex effects of psychotherapeutic interventions in epilepsy. Methods: This study examined the questions as to if and how the participation in a patient-centered 6-month resource-oriented mindfulness-based intervention would enhance an individual's well-being and sense of self-efficacy. Pre- and post-intervention semi-structured interviews were conducted with a total of 9 participants. Qualitative data analysis (Mayring) in an inter-professional group was combined with the evaluation of the Quality of Life in Epilepsy Inventory-31. The case reports follow the CAse REport Guidelines for Anthroposophic Art Therapies (CARE-AAT). To show the diverse nature of individual intervention objectives, we chose the single case study format, contrasting 2 participants with diagnosed focal epilepsy. Results: Pre-intervention deductive and inductive outcome categories revealed high levels of stress regarding personal seizure experience and loss of autonomy, for both participants. Post-intervention interviews consist of increased seizure-related self-efficacy and self-awareness: while minimizing the debilitating impact of the seizures on her life was relevant to Iris, Carl developed a personalized aura interruption technique. Conclusions: These qualitative case analyses suggest that enhanced psychological well-being and even positive medical results may be achieved when epilepsy care focuses on the wishes that are most meaningful to the individual. The possibility of improving the quantitative evaluation of the effects of psychotherapeutic interventions needs to be explored.
Evaluation of Infliximab Therapy in Children with Crohn's Disease Using Trough Levels Predictors
Authors: Ohem Jan , Hradsky Ondrej , Zarubova Kristyna , Copova Ivana , Bukovska Petra , Prusa Richard , Malickova Karin , Bronsky Jiri
Published: August 2017

Background: In adults, infliximab (IFX) levels correlate with disease activity, and antibodies to IFX (ATIs) predict treatment failure. We aimed to determine the association of IFX levels and ATIs with disease activity in a paediatric population. We prospectively collected blood, stool, and clinical data from 65 patients (age 10.5-15.1 years) with Crohn's disease (CD) before IFX administration, and measured IFX trough levels, ATIs, and faecal calprotectin levels (CPT). Samples were collected during maintenance therapy. We used multivariate analysis to identify the predictors of IFX levels. Summary: Lower levels of IFX were associated with ATIs positivity (OR 0.027, 95% CI 0.009-0.077). Higher C-reactive protein (CRP) level, erythrocyte sedimentation rate, and CPT levels were found in patients with lower IFX levels. The optimal combination of sensitivity (0.5) and specificity (0.74) for disease activity was calculated for IFX levels ≥1.1 µg/mL using CRP level <5 mg/L as a marker of laboratory remission. In a model that used CPT ≤100 µg/g as the definition of remission, the optimal IFX trough level was 3.5 µg/mL. No independent association between remission and ATIs was found in our study population. However, we found an independentz association between IFX levels and serum albumin levels (OR 1.364, 95% CI 1.169-1.593), p < 0.001. Key Messages: The paediatric population was similar to adult populations in terms of the association between IFX and ATIs as well as between IFX and disease activity.
Role of Next-Generation Sequencing as a Diagnostic Tool for the Evaluation of Bone and Soft-Tissue Tumors
Authors: Szurian Kinga , Kashofer Karl , Liegl-Atzwanger Bernadette
Published: August 2017

Bone and soft-tissue tumors are in general rare. Diagnosing these tumors is challenging based on the significant number of different tumor entities, the rareness of these tumors, and the considerable morphological heterogeneity which can be found within a single tumor entity. Considering that more than half of the described soft-tissue tumors and approximately 25% of the bone tumors harbor recurrent genetic alterations, the use of auxiliary molecular examinations should be strongly considered. Molecular analyses are important to confirm the diagnosis, to guide treatment, to provide information about prognosis, and to allow patient recruitment for basket trials based on the molecular signature of a tumor. In addition, novel molecular alterations detected by next-generation sequencing (NGS) obtain further insights into the pathogenesis of these rare tumors and allow a more detailed genetic classification. Based on our single-center results of NGS using the Ion AmpliSeq Cancer Hotspot Panel v2 and the Ion AmpliSeq Comprehensive Cancer Panel (Thermo Fisher Scientific) for mutational analyses as well as the Archer FusionPlex Sarcoma Kit (ArcherDX, Inc) to detect gene fusions in 26 genes since early 2016, we have experienced NGS as a very sensitive method to detect genetic alterations. In our experience, the use of the Archer FusionPlex Sarcoma Kit is superior to fluorescent in situ hybridization as an auxiliary tool in the routine workup of soft-tissue and bone tumors.
Muscle Strength and Muscle Mass in Older Patients during Hospitalization: The EMPOWER Study
Authors: Van Ancum Jeanine M. , Scheerman Kira , Pierik Vincent D. , Numans Siger T. , Verlaan Sjors , Smeenk Hanne E. , Slee-Valentijn Monique , Kruizinga Roeliene C. , Meskers Carel G.M. , Maier Andrea B.
Published: August 2017

Background: Low muscle strength and muscle mass are associated with an increased length of hospital stay and higher mortality rate in inpatients. To what extent hospitalization affects muscle strength and muscle mass is unclear. Objective: We aimed to assess muscle strength and muscle mass at admission and during hospitalization in older patients and its relation with being at risk of geriatric conditions. Methods: The EMPOWER study included patients aged 70 years and older, admitted to 4 wards of the VU University Medical Center in the Netherlands between April and December 2015. At admission, patients were screened for being at risk of 4 geriatric conditions: delirium, falls, malnutrition, and functional disability. At admission and at discharge, muscle strength and muscle mass were assessed. Results: A total of 373 patients (mean age, standard deviation [SD]: 79.6, 6.38 years) were included at admission, and 224 patients (mean age, SD: 80.1, 6.32 years) at discharge. At admission, lower muscle strength in both female and male patients and low muscle mass in male patients were associated with being at risk of a higher cumulative number of geriatric conditions. Muscle strength increased during hospitalization, but no change in muscle mass was observed. Changes in muscle measures were not associated with being at risk of geriatric conditions. Discussion: Older patients with lower muscle strength and muscle mass at admission were at risk of a higher cumulative number of geriatric conditions. However, being at risk of geriatric conditions did not forecast further decrease in muscle strength and muscle mass during hospitalization
Trends in Minimally Invasive Hysterectomy Techniques for Nonmalignant Conditions in a Defined Population
Authors: Hansdottir Kristin , Gudmundsson Jens A.
Published: August 2017

Background: Minimally invasive surgical techniques are increasingly being used for performing hysterectomy. We assessed changes in surgical techniques for hysterectomy that happened during the last decade among the complete Icelandic population. Methods: Databases in all hospitals in the country were searched to identify all women undergoing hysterectomy during the years 2001-2010 inclusive. Information on age at surgery, indication for surgery, surgical techniques, additional intraoperative procedures, and length of hospital stay was gathered. Two 5-year periods, 2001-2005 and 2006-2010, were compared. The proportion of minimally invasive surgery (MIS) was calculated. Results: There were 5,288 hysterectomies that were performed, giving a mean annual incidence of 352/100,000 women. The proportion of MIS increased from 30 to 74% at the main university hospital (p < 0.0001), where the mean hospital stay decreased from 5.4 to 1.7 days. Fewer oophorectomies were performed during the second 5-year period. The most common diagnoses were fibromyomas and abnormal uterine bleeding. The rate of recorded complications was low. A decreasing yearly incidence was observed from 389/100,000 in 2001 to 266/100,000 by 2010. Conclusion: For benign indications, the surgical approach has changed markedly with a high proportion of the operations being performed with minimally invasive techniques, mainly at a secondary/tertiary level.
MicroRNA-200a Inhibits Transforming Growth Factor β1-Induced Proximal Tubular Epithelial-Mesenchymal Transition by Targeting β-Catenin
Authors: Gong Yi , Qin Zhexue , Zhou Baoshang , Chen Hua , Shi Zhengmin , Zhang Jing
Published: August 2017

Background: The epithelial-mesenchymal transition (EMT) is a crucial event in the development of renal interstitial fibrosis (RIF). A growing body of evidence indicates that β-catenin plays an important role in various types of fibrosis. Although members of the microRNA (miRNA)-200 family have been suggested to suppress EMT in cancer and fibrosis, the function of miRNA-200a in regulating the progression of RIF is unknown. We speculate that miRNA-200a may hinder this progression through the suppression of β-catenin. Methods: Transforming growth factor β1 (TGF β1) was used to induce EMT of proximal tubule epithelial (HK-2) cells in vitro, quantitative real time polymerase chain reaction (qPCR) and Western Blot analysis measured the miRNA-200a and β-catenin expression. qPCR, Western Blot analysis, Migration Assay and cell immunofluorescence were applied to detect the influence of up- and downregulated miRNA-200a expression and β-catenin siRNA on β-catenin and EMT. Dual luciferase report plasmid (CTNNB1 UTR WT/MT) verifies the target relationship between miRNA-200a and CTNNB1 (β-catenin gene). Results: miRNA-200a is downregulated and β-catenin is upregulated during TGF β1-induced EMT. Upregulation of miRNA-200a inhibits β-catenin and attenuates TGF β1-induced EMT and cell migration, while its downregulation increases β-catenin and induces EMT and HK-2 cell migration. Further, knocking down β-catenin suppressed the EMT induced by miRNA-200a downregulation. miRNA-200a directly targets for CTNNB1. Conclusions: miRNA-200a inhibits TGF β1-induced EMT by directly targeting β-catenin in proximal tubule epithelial cells.
Testicular XX (SRY-Negative) Disorder of Sex Development in Cat
Authors: De Lorenzi Lisa , Banco Barbara , Previderè Carlo , Bonacina Stefania , Romagnoli Stefano , Grieco Valeria , Parma Pietro
Published: August 2017

In most mammals, the sex of an individual is genetically determined by the Y chromosome-specific SRY gene. The presence of at least one functional copy of this gene determines the development of the primordial gonads into testes. However, testicular tissue does develop in the absence of SRY, albeit rarely, which is the case in testicular XX (SRY-negative) disorder of sex development (DSD). This condition is very important for studying the process of sexual determination because it allows the identification of genetic factors that are able to promote the male developmental pathway in the absence of SRY and thereby enables a better understanding of this process. Until now, this condition has been identified in various animal species but has never been reported in cat. In this study, we describe the first case of an XX (SRY-negative) DSD cat. The cat possesses a tortoiseshell coat associated with male-like external genitalia, including normal scrotum with 2 palpably normal testicles. Histological analysis confirmed the presence of the testes, and cytogenetic and genetic analyses showed a female karyotype associated with the absence of the SRY gene. Finally, sequencing of the RSPO1 gene revealed no mutation, and FISH analysis of the SOX9 locus did not reveal any large abnormalities.
Unintentional Head Injury in Children Less than 3 Years of Age: An Insight into Safety Practices in a Developing Country
Authors: Waqas Muhammad , Jooma Rashid
Published: August 2017

Being dependent on caretakers for their safety, children under the age of 3 years are particularly vulnerable to unintentional injury. To identify the circumstances and consequences of head injury in this age group and to assess preventability in a setting of low parental educational levels, we conducted a retrospective cohort study of children less than 3 years of age admitted to hospital with a head injury and in addition categorized the degree of preventability of injury. This study included 109 children, representing a third of head-injured children under the age of 16 years, and 23.4% of these were infants. A significant proportion of head injuries, i.e., 20.18%, were designated “serious” and there was an in-hospital mortality rate of 7.3%. Most of the injuries (80%) occurred in the home and 76% could have been prevented through improved parental supervision and safety measures. We conclude that, in a setting of low maternal education, head injuries in preschoolers largely result from a lack of diligence of the caretakers, presenting opportunities for prevention strategies via a multidimensional approach that integrates safety information into the preexisting national health programs.
Assessment of Direct-to-Consumer Genetic Testing Policy in Korea Based on Consumer Preference
Authors: Jeong Gicheol
Published: August 2017

Aims: In June 2016, Korea permitted direct-to-consumer genetic testing (DTC-GT) on 42 genes. However, both the market and industry have not yet been fully activated. Considering the aforementioned context, this study provides important insights. Methods: The Korean DTC-GT policy assessment is based on consumer preference analysis using a discrete choice experiment. In August 2016, a web-based survey was conducted to collect data from 1,200 respondents. Results: The estimation results show that consumers prefer a DTC-GT product that is cheap, tests various items or genes, offers accurate test results, and guarantees the confidentiality of all information. However, consumers are not entirely satisfied by current DTC-GT products due to the existence of insufficient and/or inadequate policies. First, the permitted testing of 42 genes is insufficient to satisfy consumers' curiosity regarding their genes. Second, the accuracy of the DTC-GT products has not been fully verified, assessed, and communicated to consumers. Finally, regulatory loopholes that allow information leaks in the DTC-GT process can occur. Conclusions: These findings imply that DTC-GT requires an improvement in government policy-making criteria and the implementation of practical measures to guarantee test accuracy and genetic information.
Traumatic Posterior Fossa Subdural Hygroma and Secondary Occlusive Hydrocephalus
Authors: Luo Anqi , Eibach Sebastian , Zovickian John , Pang Dachling
Published: August 2017

Background: Infratentorial subdural hygromas causing secondary occlusive hydrocephalus are extremely rare in children. Only a handful of cases have been reported in the literature. Methods: We present a case of a 6-month-old infant with an occipital fracture and slow enlargement of a posterior fossa subdural hygroma that culminated in obstructive hydrocephalus. We give a review of the literature on post-traumatic posterior fossa hygroma with secondary occlusive hydrocephalus and discuss its pathogenesis and the mechanism of its later resolution, as well as the available treatment options. Results: A temporary external ventricular drain led to acute relief of the hydrocephalus and subsequent complete resolution of the subdural hygroma. Conclusion: Temporary external ventricular drain placement led to complete resolution of the subdural hygroma and hydrocephalus. We recommend close clinical follow-up, and imaging if indicated, for as long as 4 weeks after trauma with occipital skull fractures.
Ophthalmic Start-Up Chief Executive Officers' Perceptions of Development Hurdles
Authors: Stewart William C. , Nelson Lindsay A. , Kruft Bonnie , Stewart Jeanette A.
Published: August 2017

Purpose: To identify current challenges facing ophthalmic pharmaceutical start-ups in developing new products. Methods: Surveys were distributed to the chief executive officer (CEO) or president of ophthalmic start-ups. Results: The survey attracted 24 responses from 78 surveys distributed (31%). The CEOs stated that a lack of financial capital (n = 18, 75%), FDA regulations (n = 6, 25%), and failure to meet clinical endpoints (n = 6, 25%) were their greatest development hurdles. Risk aversion to medicines in early development (n = 18, 75%), mergers and acquisitions reducing corporate choice for licensing agreements (n = 7, 29%), the emergence of large pharmaceutical-based venture capital funding groups (n = 12, 50%), and the failure of many large pharmaceutical companies to develop their own medicines (n = 10, 42%) were noted as recent prominent trends affecting fundraising. Conclusion: The study suggests that development funding, regulatory burden, and meeting clinical endpoints are the greatest development challenges faced by ophthalmic start-up CEOs.
Practical Value of Anti-Xa Activity in the Evaluation of Extracorporeal Circuit Anticoagulation during Haemodialysis: Results of a Cross-Sectional Single-Centre Study
Authors: Coene Karlien L.M. , Dekker Marijke J.E. , Kerskes Marieke C.H.M. , Hengst Maaike , Schonck Marc J.M. , Konings Constantijn J.A.M. , Scharnhorst Volkher
Published: August 2017

Background/Aims: Anticoagulation of the extracorporeal circuit is essential for adequate haemodialysis (HD). Low molecular weight heparins (LMWHs) are safe and sufficient towards achieving this goal. In the Netherlands, dosage is based on bodyweight and adjusted based on clinical events. LMWH levels during dialysis can be quantified through measurement of the anti-Xa activity and a target range of 0.5-1.0 IU/mL has been proposed. We aimed to evaluate the practical value of the anti-Xa activity to guide LMWH dosage in HD patients. Additionally, the value of the activated partial thromboplastin time (APTT) was investigated. Methods: All prevalent adult HD patients of our dialysis clinic were included. APTT and anti-Xa activity were measured before, during and after 2 dialysis sessions. Clinical and dialysis characteristics, including LMWH dosage, were derived from digital patient charts. Results: Our final study cohort consisted of 83 patients. LMWH dosage during dialysis was appropriate for bodyweight in 61% of cases, of which 50% reached an anti-Xa activity within the putative target range of 0.5-1.0 IU/mL. Forty-six percent of patients had an anti-Xa activity >1.0 IU/mL. Anti-Xa levels during and after dialysis were significantly correlated (r = 0.803, p < 0.01). No thrombotic or haemorrhagic complications were observed in this study. Correlation of APTT with anti-Xa activity was poor. Conclusion: Anti-Xa activity measurements during dialysis can identify patients in whom LMWH dosage should be lowered in a subsequent dialysis session. Whether such an intervention leads to a decrease in haemorrhagic complications needs to be evaluated in prospective studies.
Combination Therapy with Capecitabine and Cisplatin as Second-Line Chemotherapy for Advanced Biliary Tract Cancer
Authors: Jung Jang Han , Lee Hee Seung , Jo Jung Hyun , Cho In Rae , Chung Moon Jae , Bang Seungmin , Park Seung Woo , Song Si Young , Park Jeong Youp
Published: August 2017

Background/Aims: Palliative chemotherapy is the main treatment for advanced biliary tract cancer (BTC). However, there is a lack of established second-line chemotherapy to treat disease progression after first-line chemotherapy. We examined combination therapy with capecitabine and cisplatin for advanced BTC as a second-line regimen. Methods: We analyzed the medical records of 40 patients diagnosed with BTC who received palliative second-line chemotherapy with capecitabine and cisplatin. Results: The median overall survival from the start of second-line chemotherapy was 6.3 months. The median overall survival from diagnosis was 17.9 months. The median progression-free survival during second-line chemotherapy was 2.3 months. Nine (30%) patients experienced adverse events of grade ≥3. Eastern Cooperative Oncology Group performance score was an independent predictor of adverse events. Conclusions: Combination therapy with capecitabine and cisplatin may be an option for second-line chemotherapy in some of patients with advanced BTC.
The XY Body of the Cat (Felis catus): Structural Differentiations and Protein Immunolocalization
Authors: Sciurano Roberta B. , De Luca Geraldine , Rahn I. Mónica , Solari Alberto J.
Published: August 2017

The heteromorphic X and Y chromosomes behave in a special way in mammalian spermatocytes; they form the XY body and synapse only partially. The aim of this article was to study the origin and the role of the special differentiations in the XY pair of the domestic cat during pachytene by analyzing its fine structural characteristics and the immunolocalization of the main meiotic proteins SYCP3, SYCP1, SYCE3, SMC3, γ-H2AX, BRCA1, H3K27me3, and MLH1. The cat XY body shows particularly striking structures: an extreme degree of axial fibrillation in late pachynema and a special location of SYCP3-containing fibrils, bridging different regions of the main X axis, as well as one bridge at the inner end of the pairing region that colocalizes with the single mandatory MLH1 focus. There are sequential changes, first bullous expansions, then subdivision into fibrils, all involving axial thickening. The chromatin of the XY body presents the usual features of meiotic sex chromosome inactivation. An analysis of the XY body of many eutherians and metatherians suggests that axial thickenings are primitive features. The sequential changes in the mass and location of SYCP3-containing fibers vary among the clades because of specific processes of axial assembly/disassembly occurring in different species.
Need for Digital Biomarkers in Musculoskeletal Trials
Authors: Goldhahn Jörg
Published: August 2017

Pain and loss of function – both problems cause patients to visit a musculoskeletal specialist. Therefore, both lead symptoms should serve as a benchmark for new therapeutic approaches. New technologies generating digital biomarkers have the potential to significantly change musculoskeletal trials. However, more work is needed to agree upon data and variable standards, to improve user friendliness, and to ensure data integrity along the whole processing way. Therefore, rigorous and systematic testing of new technological approaches is required to establish new outcome variables suitable for musculoskeletal trials. Consortia of researchers working on similar technologies and outcome variables should collaborate from the beginning to enable comparing and pooling data. Early interaction with health authorities and regulatory bodies are necessary to pave the way for a widespread use of a new technology.
Diagnosis of Cytomegalovirus Infection during Exacerbation of Ulcerative Colitis
Authors: Levin Avi , Yaari Shaul , Stoff Ronen , Caplan Orit , Wolf Dana G. , Israeli Eran
Published: August 2017

Background/Aims: The role of cytomegalovirus (CMV) reactivation during exacerbations of ulcerative colitis (UC) is yet a matter of debate, and assessment of CMV infection in UC patients remains an ongoing challenge. We aimed to identify associated parameters and compare detection methods for CMV infection during UC exacerbation. Methods: Clinical, pathological and virological parameters were retrospectively analyzed in all patients hospitalized in our institution for UC exacerbation between January 2009 and April 2015, who underwent full evaluation for CMV infection in colonic tissue by histopathology, immunohistochemistry (IHC) and CMV-PCR. Results: Of 28 patients who underwent full examination for tissue CMV-infection, 13 (46.4%) were found to be positive for CMV. Tissue CMV-PCR was more sensitive for the detection of CMV infection than histopathology and IHC. CMV-positive patients had a statistically higher frequency of recent steroid treatment and fever, with higher mean partial Mayo scores and lower mean albumin levels. There were no significant differences between CMV-positive and CMV-negative patients in terms of age, severity of colitis and disease duration. In a multivariable model, only recent steroid treatment and fever were independently associated with colonic CMV infection. Conclusions: This study provides a clinical model to detect the presence of CMV infection in patients hospitalized with UC exacerbation, which could direct proper investigation and facilitate timely empirical therapy
Comparison of Fetomaternal Outcome between 47 Deliveries Following Successful External Cephalic Version for Breech Presentation and 7456 Deliveries Following Spontaneous Cephalic Presentation
Authors: de Gregorio Nikolaus , Friedl Thomas , Schramm Amelie , Reister Frank , Janni Wolfgang , Ebner Florian
Published: August 2017

Background: Achieving a cephalic position after a successful external cephalic version (ECV) is desired to result in delivery and fetal outcomes that are similar to those of deliveries following spontaneous cephalic presentation. Methods: We performed a retrospective cohort study including patients with successful ECV following fetal breech position (ECV cohort, n = 47) or with a singleton spontaneous cephalic pregnancy at ≥37 weeks of gestational age (control group, n = 7,456) attempting a vaginal delivery between 2010 and 2013 at the University Hospital Ulm. The mode of delivery and fetal outcome parameters were compared between these 2 groups using nonparametric statistics. Results: ECV cohort and control group did not differ with respect to maternal age, parity, gestational age at birth, and fetal gender. There were no significant differences between the 2 groups with regard to all parameters indicating fetal outcome. However, the rate of cesarean sections was higher after successful ECV compared to spontaneous cephalic presentation (27.7 vs. 12.8%, OR 2.615). Conclusion: While vaginal delivery is less likely to happen after a successful ECV compared to spontaneous cephalic singleton pregnancies, fetal outcome parameters showed no difference between the 2 groups. Physicians should be counseling and encouraging women to attempt ECV, as it is a safe and effective procedure.
TGF-β1 Induces EMT in Bovine Mammary Epithelial Cells Through the TGFβ1/Smad Signaling Pathway
Authors: Chen Qing , Yang Wei , Wang Xixi , Li Xueru , Qi Shaopei , Zhang Yong , Gao Ming-Qing
Published: August 2017

Background/Aims: Transforming growth factor-β1 (TGF-β1) plays a crucial role in chronic inflammation in various tissues, and is related to inflammation-caused organ fibrogenesis associated with the epithelial-mesenchymal transition (EMT) and the deposition of the extracellular matrix (ECM). However, the effect of TGF-β1 on bovine mammary epithelial cells (BMECs) with mastitis, and its mechanism, remain unknown. Methods: We analyzed the level of TGF-β1 in inflamed mammary tissues and cells using western blotting. BMECs were treated with TGF-β1, and EMT-related gene and protein expression changes were evaluated using quantitative real-time polymerase chain reaction (qPCR), western blotting, and immunofluorescence. We also inhibited the TGF/Smad signaling pathway using a receptor inhibitor, and analyzed EMT-related protein expression by western blotting. In addition, we injected TGF-β1 into mice mammary glands to investigate whether it can cause mammary fibrosis in vivo. Results: The TGF-β1 level was up-regulated in mammary tissues with mastitis and in inducible inflammatory BMECs. TGF-β1 treatment activated the TGF/ Smad signaling pathway in BMECs during their transition to the EMT phenotype, as indicated by morphological changes from a cobblestone-like shape to a spindle-like one. TGF-β1 treatment also up-regulated the expression of α-smooth muscle actin, vimentin, and collagen I, albumin, and down-regulated the expression of E-cadherin both in mRNA level and protein level. Furthermore, TGF-β1 enhanced the gene expressions of MMP2, MMP7, and fibronectin in BMECs. TGF-β1 injection induced mice mammary infection and fibrosis. Conclusion: These findings suggested that aberrant up-regulation of TGF-β1 in bovine mastitic mammary glands might play an important role in bovine mammary fibrosis caused by unresolved inflammation.
CyclinG1 Amplification Enhances Aurora Kinase Inhibitor-Induced Polyploid Resistance and Inhibition of Bcl-2 Pathway Reverses the Resistance
Authors: Zhang Wenfeng , Xu Jie , Ji Dexiang , Li Zhangyun , He Wenxing , Yang Fei , Lan Huiyin , Wang Yu , Wu Zhengping , Liu Xiaoshan , Huang Shanhua , Li Longkun , Zhou Weihua
Published: August 2017

Background/Aims: CyclinG1 (CycG1) is frequently overexpressed in solid tumors and overexpression of CycG1 promotes cell survival upon paclitaxel exposure by inducing polyploidy. Whether and how CycG1 regulates polyploidization caused by small molecular targeted inhibitors remains unclear. Methods: Immunohistochemistry and immunoblotting were utilized to examine protein expression. Cell proliferation was measured by ATPlite assay, and cell cycle distribution and apoptosis were measured by flow cytometry and/or DNA fragmentation assays. Results: Overexpression of CycG1 in breast cancer cells caused apoptosis-resistant polyploidy upon treatment with Aurora kinase inhibitor, ZM447439 (ZM). Addition of ABT-263, a small-molecule BH3 mimetic, to ZM, produced a synergistic loss of cell viability with greater sustained tumor growth inhibition in breast cancer cell lines. Decrease of Mcl-1 and increase of NOXA caused by ZM treatment, were responsible for the synergy. Furthermore, CycG1 was highly expressed in Triple-Negative-Breast-Cancer patients treated with paclitaxel and was paralleled by decreased cell survival. Conclusion: CycG1 is a crucial factor in ZM-induced polyploidy resistance, and ABT-263/ZM combination hold therapeutic utility in the CycG1-amplified subset of breast cancer and CycG1, thus, is a promising target in breast cancer.
Colonic PDGFRα Overexpression Accompanied Forkhead Transcription Factor FOXO3 Up-Regulation in STZ-Induced Diabetic Mice
Authors: Lu Hongli , Zhang Chunmei , Song Nina , Lu Chen , Tong Ling , Huang Xu , Kim Young-chul , Chen Jie , Xu Wenxie
Published: August 2017

Background: Colonic transit disorder-induced constipation is a major complication in diabetic patients. PDGFRα+ (platelet-derived growth factor receptor α-positive) cells play critical roles in the inhibitory regulation of colonic motility, and FOXO3 (forkhead transcription factor 3) has a broad range of biological functions. The present study was designed to investigate the relationship between FOXO3 and PDGFRα+ cell proliferation in streptozotocin (STZ)-induced diabetic mice. Methods: The major experimental techniques used in this paper are immunohistochemistry, quantitative RT-RCR and Western blotting for the evaluation of specific protein expression; ChIP assay for identifying the interaction between FOXO3 protein and the PDGFRα promotor; and lentiviral transfection for the overexpression of short hairpin RNAs (shRNAs) to down-regulate FOXO3. Results: In proximal colonic smooth muscle tissue of STZ-induced diabetic mice, there was a significant increase in PDGFRα and Ki67 immunoreactivity. PDGFRα mRNA and protein expression levels were both significantly increased in colonic smooth muscle tissue, but PDGFRβ expression was unchanged. Meanwhile, the expression of PDGF ligands, including both PDGFα and PDGFβ, was significantly increased in diabetic colonic smooth muscle tissue. In whole cell and nuclear extracts, the expression of FOXO3 protein was also significantly increased; however, the expression of P-FOXO3 (phosphorylated FOXO3) protein was significantly decreased. When NIH cells were incubated with 50 mmol/L glucose for 12 h, 24 h and 48 h, the expression of PDGFRα significantly increased, and in whole cell and nuclear extracts, the expression of FOXO3 protein was significantly increased. However, the expression of P-FOXO3 protein was significantly decreased. FOXO3 could bind to a site on the PDGFRα promoter, and the basal expression of PDGFRα was significantly reduced when endogenous FOXO3 expression was knocked down with FOXO3 short hairpin RNA (shRNA) in NIH cells. The expression of phosphorylated Akt was significantly down-regulated in diabetic colonic muscle tissue. Conclusions: These results suggest that diabetes-induced colonic PDGFRα+ cell proliferation is mediated by FOXO3 up-regulation. FOXO3 up-regulation may be induced by inhibiting the PI3K/Akt signaling pathway in STZ-induced diabetic mice. PDGFRα+ cell proliferation could be a new target for clinical therapy of diabetes-induced colonic transit disorder.
Lipoprotein(a) and Risk of Myocardial Infarction and Death in Chronic Kidney Disease
Authors: Bajaj Archna , Damrauer Scott M. , Anderson Amanda H. , Xie Dawei , Budoff Matthew J. , Go Alan S. , He Jiang , Lash James P. , Ojo Akinlolu , Post Wendy S. , Rahman Mahboob , Reilly Muredach P. , Saleheen Danish , Townsend Raymond R. , Chen Jinbo , Rader Daniel J.
Published: August 2017

Objective—

To investigate the effect of
LPA
gene variants and renal function on lipoprotein(a) [Lp(a)] levels in people with chronic kidney disease and determine the association between elevated Lp(a) and myocardial infarction and death in this setting.

Approach and Results—

The CRIC Study (Chronic Renal Insufficiency Cohort) is an ongoing prospective study of 3939 participants with chronic kidney disease. In 3635 CRIC participants with genotype data, carriers of the rs10455872 or rs6930542 variants had a higher median Lp(a) level (mg/dL) compared with noncarriers (73 versus 23;
P
<0.001 and 56 versus 22;
P
<0.001, respectively). The 3744 participants (55% male and 41% non-Hispanic White) with available baseline Lp(a) levels were stratified into quartiles of baseline Lp(a) (mg/dL): <9.8, 9.8 to 26.0, 26.1 to 61.3, and >61.3. There were 315 myocardial infarctions and 822 deaths during a median follow-up of 7.5 years. The second quartile had the lowest event rate. After adjusting for potential confounders and using a Cox proportional hazards model, the highest quartile of Lp(a) was associated with increased risk of myocardial infarction (hazard ratio, 1.49; 95% confidence interval, 1.05–2.11), death (hazard ratio, 1.28; 95% confidence interval, 1.05–1.57), and the composite outcome (hazard ratio, 1.29; 95% confidence interval, 1.07–1.56) compared with the second quartile of Lp(a).

Conclusions—

Among adults with chronic kidney disease, elevated Lp(a) is independently associated with myocardial infarction and death. Future studies exploring pharmacological Lp(a) reduction in this population are warranted.
Cybernetic-Existentialism and Being-towards-death in Contemporary Art and Performance
Authors: Dixon Steve
Published: August 2017

Ideas and themes central to both cybernetics and existentialist philosophy converge in the work of some of the world’s most celebrated contemporary artists. Utilizing little or no technology, these artists nonetheless employ “systems” approaches and protocybernetic models, while simultaneously exploring themes directly related to existentialism.
Asian Theatre as Method: The Toki Experimental Project and Sino-Japanese Transnationalism in Performance
Authors: Ferrari Rossella
Published: August 2017

In 2012, Zuni Icosahedron (Hong Kong), Za-Koenji Public Theatre (Tokyo), and the Jiangsu Kun Opera Theatre (Nanjing) initiated the Toki Project, an intercultural platform devoted to the transmission of kunqu and noh through contemporary performance. Originating from a Shanghai Expo 2010 commission, Toki provides a theatrical application of Chen Kuan-hsing’s influential notion of “Asia as method.” As epitomized by the yearly One Table, Two Chairs performances at Nanjing’s Toki Arts Festival, Toki partakes in Asia as method’s effort toward “decolonization, deimperialization, and de-cold war” through aesthetic and epistemological deconstruction, endorsing a dialogic model of intercultural performance as inter-Asian relation.
Updated catalogue of Iranian Anthocoridae (Hemiptera: Heteroptera: Cimicomorpha)
Authors: OSTOVAN HADI , GHAHARI HASSAN , MOULET PIERRE
Published: August 2017

The published data on Iranian Anthocoridae (Hemiptera) are summarized in this paper. In total 51 species of three subfamilies Anthocorinae, Lyctocorinae and Scolopinae within 10 genera (Amphiareus Distant, Anthocoris Fallén, Buchananiella Reuter, Cardiastethus Fieber, Dufouriellus Kirkaldy, Elatophilus Reuter, Lyctocoris Hahn, Orius Wolff, Temnostethus Fieber, and Xylocoris Dufour) are listed as the fauna of Iran. Xylocoris (Xylocoris) ciliatus (Jakovlev, 1877) is new record for the fauna of Iran.
The discovery of the orb-weaving spider genus Pinkfloydia (Araneae, Tetragnathidae) in eastern Australia with description of a new species from New South Wales and comments on the phylogeny of Nanometinae
Authors: HORMIGA GUSTAVO
Published: August 2017

A new species of the Australian genus Pinkfloydia, P. rixi new species, is described and illustrated. This new tetragnathid species is known only from the type locality in the eastern part of New South Wales, more than 3,200 km away from the distribution range of it sister species from Western Australia, P. harveii Dimitrov & Hormiga, 2011. The nature of such a disjunct distribution is discussed based on morphological data and on the nucleotide sequence of the mitochondrial protein-encoding gene cytochrome c oxidase subunit I. The placement of Pinkfloydia in the subfamily Nanometinae and recent advances in the phylogeny of Tetragnathidae are also discussed.
Do resettlement variables predict psychiatric treatment outcomes in a sample of asylum-seeking survivors of torture?
Authors: Whitsett David , Sherman Martin F
Published: August 2017

Purpose:

Mental health clinicians who work with asylum seekers provide services to patients who face stressful everyday living conditions. However, little is known about how these problems potentially impact psychiatric treatment within these populations. The purpose of this study was thus to examine whether resettlement factors predict outcomes of a mental health intervention for a sample of asylum-seeking survivors of torture.

Methods:

The study included data from a US outpatient clinic that specialized in treating asylum-seeking survivors of torture. Patients (primarily from Iraq, Afghanistan and African Countries) were evaluated on demographic factors at intake and psychiatric symptoms throughout the course of treatment.

Results:

Patients experienced significant reductions in depression, anxiety and trauma symptoms, although symptoms still remained near or above clinical thresholds. Stable, uncrowded housing conditions significantly predicted lower depression, anxiety and trauma symptoms at follow-up.

Conclusion:

These findings support the hypotheses that individuals seeking asylum within the United States who have survived torture can benefit from psychiatric treatment and emphasize the importance of stable living conditions in improving treatment effectiveness. This suggests the need for further research on social predictors of treatment outcomes, as well as the need for clinicians and policymakers to target improved housing as a potentially important tool to reduce psychiatric problems related to torture and forced migration.
Electroencephalography Pattern Variations During Motor Skill Acquisition
Authors: Ghasemian Mohammadreza , Taheri Hamidreza , Saberi Kakhki Alireza , Ghoshuni Majid
Published: August 2017

The present study examined how motor skill acquisition affects electroencephalography patterns and compared short- and long-term electroencephalography variations. For this purpose, 17 volunteers with no history of disease, aged 18 to 22 years, attended seven training sessions every other day to practice a pursuit tracking motor skill. Electroencephalography brainwaves were recorded and analyzed on the first and last days within pre- and post-training intervals. The results showed a significant decrease in performance error and variability with practice over time. This progress slowed at the end of training, and there was no significant improvement in individual performance at the last session. In accordance with performance variations, some changes occurred in brainwaves. Specifically, θ power at Fz and α power at Cz increased on the last test day, compared with the first, while the coherence of α at Fz-T3 and Fz-Cz decreased. β Coherence between Fz-Cz was significantly reduced from pre- to posttest. Based on these results, power changes seem to be more affected by long-term training, whereas coherence changes are sensitive to both short- and long-term training. Specifically, β coherence at Fz-Cz was more influenced by short-term effects of training, whereas θ power at Fz, α power at Cz, and α coherence at Fz-T3 and Fz-Cz were affected by longer training.
Conflict imagery in a connective environment: audiovisual content on Twitter following the 2015/2016 terror attacks in Paris and Brussels
Authors: Bruns Axel , Hanusch Folker
Published: August 2017

Acute crisis events ranging from natural disasters to terrorist incidents now tend to generate an almost immediate response from social media users. This is especially pronounced on Twitter, due to that platform’s specific affordances as a particularly open and real-time medium. While analyses of such events have increased over recent years, we still understand relatively little about the way in which audiovisual materials relating to such crises are circulated and what they contribute to processes of witnessing. This is important, however, in an increasingly visual age when audiovisual material tends to be more widely viewed and shared than plain-text updates, and thus has a greater potential to influence viewers’ interpretations of an event. To address this gap in our understanding, this article investigates the distribution dynamics of audiovisual content on Twitter in the immediate aftermath of terror attacks in Paris and Brussels. Results point to the importance of broadening conceptualisations of conflict-related visuals and the ongoing relevance of affective content in such material. Furthermore, this article argues that contexts of time and space are crucial to consider, as is the role that individual actors – both human and non-human – play in disseminating such content.
Neuroendocrine regulation of energy balance: Implications on the development and surgical treatment of obesity
Authors: Farias Gisele , Netto Bárbara Dal Molin , Bettini Solange Cravo , Dâmaso Ana Raimunda , de Freitas Alexandre Coutinho Teixeira
Published: August 2017

Introduction:

Obesity, a serious public health problem, occurs mainly when food consumption exceeds energy expenditure. Therefore, energy balance depends on the regulation of the hunger–satiety mechanism, which involves interconnection of the central nervous system and peripheral signals from the adipose tissue, pancreas and gastrointestinal tract, generating responses in short-term food intake and long-term energy balance. Increased body fat alters the gut- and adipose-tissue-derived hormone signaling, which promotes modifications in appetite-regulating hormones, decreasing satiety and increasing hunger senses. With the failure of conventional weight loss interventions (dietary treatment, exercise, drugs and lifestyle modifications), bariatric surgeries are well-accepted tools for the treatment of severe obesity, with long-term and sustained weight loss. Bariatric surgeries may cause weight loss due to restriction/malabsorption of nutrients from the anatomical alteration of the gastrointestinal tract that decreases energy intake, but also by other physiological factors associated with better results of the surgical procedure.

Objective:

This review discusses the neuroendocrine regulation of energy balance, with description of the predominant hormones and peptides involved in the control of energy balance in obesity and all currently available bariatric surgeries.

Conclusions:

According to the findings of our review, bariatric surgeries promote effective and sustained weight loss not only by reducing calorie intake, but also by precipitating changes in appetite control, satiation and satiety, and physiological changes in gut-, neuro- and adipose-tissue-derived hormone signaling.