bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin D Deficiency Is Associated with Endoscopic Severity in Patients with Crohn’s Disease
Authors: Ye Lingna , Lin Ziwen , Liu Jing , Cao Qian
Published: November 2017

Background and Aims. Vitamin D deficiency is common in patients with Crohn’s disease and is associated with disease activity. Relationship between vitamin D and endoscopic disease activity is unknown. The aim of the study is to determine the association between vitamin D status and endoscopic disease activity in CD patients.Methods. Consecutive hospitalized CD patients from 2014 to 2016 who received vitamin D assessment and colonoscopy were retrospectively evaluated. Clinical disease activity was assessed by Crohn’s disease activity index and C-reactive protein. Endoscopic activity was calculated using simple endoscopic score for Crohn’s disease.Results. Median serum 25OHD level of 131 patients was lower than healthy controls [21.1 nmol/L (11.8–32.3) versus 49.9 nmol/L (44.9–57.4),P=0.007]. 125 (95%) patients had vitamin D deficiency and the rest (5%) had vitamin D insufficiency. Serum 25OHD was inversely correlated with CRP (r=−0.308,P<0.001), CDAI (r=−0.582,P<0.001), SES-CD (r=−0.294,P=0.001), and endoscopic severity stratified by SES-CD (P=0.001).Conclusion. Vitamin D deficiency was prevalent among hospitalized CD patients. Vitamin D levels were inversely correlated with endoscopic disease activity. Vitamin D status could be a biomarker in assessing disease activity among hospitalized CD patients in addition to CDAI and CRP.
A Longitudinal fMRI Research on Neural Plasticity and Sensory Outcome of Carpal Tunnel Syndrome
Authors: Ma Hao , Lu Yechen , Hua Xuyun , Shen Yundong , Zheng Mouxiong , Xu Wendong
Published: November 2017

Peripheral nerve compression is reported to induce cortical plasticity, which was well pictured by former researches. However, the longitudinal changes brought by surgical treatment are not clear. In this research, 18 subjects who suffered from bilateral carpal tunnel syndrome were evaluated using task-dependent fMRI and electromyography assessment before and after surgery. The third digit was tactually simulated by von Frey filaments. The results demonstrated that the pattern of activation was similar but a decreased extent of activation in the postcentral gyrus, inferior frontal lobe, superior frontal lobe, and parahippocampal gyrus after surgery was found. The correlation analysis showed a significant correlation between the decreased number of activated voxels and the improvement of EMG performance. This result implied a potential connection between fMRI measurement and clinical improvement.
Prenatal Diagnosis of Thoracoschisis and Review of Literature
Authors: Hanafi Hasaruddin R. , Zakaria Zahar A.
Published: November 2017

Thoracoschisis is a rare congenital malformation characterized by herniation of the abdominal content through a defect in the thorax. There are previously 12 reported cases, most discussing the postnatal findings and management. Here we describe a case of left thoracoschisis with associated upper limb abnormality which was diagnosed antenatally with the aid of 3D ultrasound.
The NOTCH4–HEY1 Pathway Induces Epithelial–Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma
Authors: Fukusumi Takahito , Guo Theresa W. , Sakai Akihiro , Ando Mizuo , Ren Shuling , Haft Sunny , Liu Chao , Amornphimoltham Panomwat , Gutkind J. Silvio , Califano Joseph A.
Published: November 2017

Purpose: Recently, several comprehensive genomic analyses demonstrated NOTCH1 and NOTCH3 mutations in head and neck squamous cell carcinoma (HNSCC) in approximately 20% of cases. Similar to other types of cancers, these studies also indicate that the NOTCH pathway is closely related to HNSCC progression. However, the role of NOTCH4 in HNSCC is less well understood.

Experimental Design: We analyzed NOTCH4 pathway and downstream gene expression in the TCGA data set. To explore the functional role of NOTCH4, we performed in vitro proliferation, cisplatin viability, apoptosis, and cell-cycle assays. We also compared the relationships among NOTCH4, HEY1, and epithelial–mesenchymal transition (EMT)-related genes using the TCGA data set and in vitro assays.

Results: HEY1 is specifically upregulated in HNSCC compared with normal tissues in the TCGA data set. NOTCH4 is more significantly related to HEY1 activation in HNSCC in comparison with other NOTCH receptors. NOTCH4 promotes cell proliferation, cisplatin resistance, inhibition of apoptosis, and cell-cycle dysregulation. Furthermore, NOTCH4 and HEY1 upregulation resulted in decreased E-cadherin expression and increased Vimentin, Fibronectin, TWIST1, and SOX2 expression. NOTCH4 and HEY1 expression was associated with an EMT phenotype as well as increased invasion and cell migration.

Conclusions: In HNSCC, the NOTCH4–HEY1 pathway is specifically upregulated, induces proliferation and cisplatin resistance, and promotes EMT. Clin Cancer Res; 24(3); 619–33. ©2017 AACR.
Development of a Function-Blocking Antibody Against Fibulin-3 as a Targeted Reagent for Glioblastoma
Authors: Nandhu Mohan S. , Behera Prajna , Bhaskaran Vivek , Longo Sharon L. , Barrera-Arenas Lina M. , Sengupta Sadhak , Rodriguez-Gil Diego J. , Chiocca E. Antonio , Viapiano Mariano S.
Published: November 2017

Purpose: We sought a novel approach against glioblastomas (GBM) focused on targeting signaling molecules localized in the tumor extracellular matrix (ECM). We investigated fibulin-3, a glycoprotein that forms the ECM scaffold of GBMs and promotes tumor progression by driving Notch and NFκB signaling.

Experimental Design: We used deletion constructs to identify a key signaling motif of fibulin-3. An mAb (mAb428.2) was generated against this epitope and extensively validated for specific detection of human fibulin-3. mAb428.2 was tested in cultures to measure its inhibitory effect on fibulin-3 signaling. Nude mice carrying subcutaneous and intracranial GBM xenografts were treated with the maximum achievable dose of mAb428.2 to measure target engagement and antitumor efficacy.

Results: We identified a critical 23-amino acid sequence of fibulin-3 that activates its signaling mechanisms. mAb428.2 binds to that epitope with nanomolar affinity and blocks the ability of fibulin-3 to activate ADAM17, Notch, and NFκB signaling in GBM cells. mAb428.2 treatment of subcutaneous GBM xenografts inhibited fibulin-3, increased tumor cell apoptosis, and enhanced the infiltration of inflammatory macrophages. The antibody reduced tumor growth and extended survival of mice carrying GBMs as well as other fibulin-3–expressing tumors. Locally infused mAb428.2 showed efficacy against intracranial GBMs, increasing tumor apoptosis and reducing tumor invasion and vascularization, which are enhanced by fibulin-3.

Conclusions: To our knowledge, this is the first rationally developed, function-blocking antibody against an ECM target in GBM. Our results offer a proof of principle for using “anti-ECM” strategies toward more efficient targeted therapies for malignant glioma. Clin Cancer Res; 24(4); 821–33. ©2017 AACR.
JQ1 Induces DNA Damage and Apoptosis, and Inhibits Tumor Growth in a Patient-Derived Xenograft Model of Cholangiocarcinoma
Authors: Garcia Patrick L. , Miller Aubrey L. , Gamblin Tracy L. , Council Leona N. , Christein John D. , Arnoletti J. Pablo , Heslin Marty J. , Reddy Sushanth , Richardson Joseph H. , Cui Xiangqin , van Waardenburg Robert C.A.M. , Bradner James E. , Yang Eddy S. , Yoon Karina J.
Published: November 2017

Cholangiocarcinoma (CCA) is a fatal disease with a 5-year survival of <30%. For a majority of patients, chemotherapy is the only therapeutic option, and virtually all patients relapse. Gemcitabine is the first-line agent for treatment of CCA. Patients treated with gemcitabine monotherapy survive ∼8 months. Combining this agent with cisplatin increases survival by ∼3 months, but neither regimen produces durable remissions. The molecular etiology of this disease is poorly understood. To facilitate molecular characterization and development of effective therapies for CCA, we established a panel of patient-derived xenograft (PDX) models of CCA. We used two of these models to investigate the antitumor efficacy and mechanism of action of the bromodomain inhibitor JQ1, an agent that has not been evaluated for the treatment of CCA. The data show that JQ1 suppressed the growth of the CCA PDX model CCA2 and demonstrate that growth suppression was concomitant with inhibition of c-Myc protein expression. A second model (CCA1) was JQ1-insensitive, with tumor progression and c-Myc expression unaffected by exposure to this agent. Also selective to CCA2 tumors, JQ1 induced DNA damage and apoptosis and downregulated multiple c-Myc transcriptional targets that regulate cell-cycle progression and DNA repair. These findings suggest that c-Myc inhibition and several of its transcriptional targets may contribute to the mechanism of action of JQ1 in this tumor type. We conclude that BET inhibitors such as JQ1 warrant further investigation for the treatment of CCA. Mol Cancer Ther; 17(1); 107–18. ©2017 AACR.
Pharmacologic Inhibition of the Menin–MLL Interaction Leads to Transcriptional Repression of PEG10 and Blocks Hepatocellular Carcinoma
Authors: Kempinska Katarzyna , Malik Bhavna , Borkin Dmitry , Klossowski Szymon , Shukla Shirish , Miao Hongzhi , Wang Jingya , Cierpicki Tomasz , Grembecka Jolanta
Published: November 2017

Hepatocellular carcinoma (HCC) accounts for approximately 85% of malignant liver tumors and results in 600,000 deaths each year, emphasizing the need for new therapies. Upregulation of menin was reported in HCC patients and high levels of menin correlate with poor patient prognosis. The protein–protein interaction between menin and histone methyltransferase mixed lineage leukemia 1 (MLL1) plays an important role in the development of HCC, implying that pharmacologic inhibition of this interaction could lead to new therapeutic strategy for the HCC patients. Here, we demonstrate that the menin–MLL inhibitor MI-503 shows antitumor activity in in vitro and in vivo models of HCC and reveals the potential mechanism of menin contribution to HCC. Treatment with MI-503 selectively kills various HCC cell lines and this effect is significantly enhanced by a combination of MI-503 with sorafenib, the standard-of-care therapy for HCC. Furthermore, MI-503 reduces sphere formation and cell migration in in vitro HCC models. When applied in vivo, MI-503 gives a strong antitumor effect both as a single agent and in combination with sorafenib in mice xenograft models of HCC. Mechanistically, treatment with MI-503 downregulates expression of several genes known to play a critical role in proliferation and migration of HCC cells, including PEG10, and displaces the menin–MLL1 complex from the PEG10 promoter, resulting in reduced H3K4 methylation and transcriptional repression. Overall, our studies reveal a mechanistic link between menin and genes involved in HCC and demonstrate that pharmacologic inhibition of the menin–MLL interaction might represent a promising therapeutic approach for HCC. Mol Cancer Ther; 17(1); 26–38. ©2017 AACR.
CAT-02-106, a Site-Specifically Conjugated Anti-CD22 Antibody Bearing an MDR1-Resistant Maytansine Payload Yields Excellent Efficacy and Safety in Preclinical Models
Authors: Drake Penelope M. , Carlson Adam , McFarland Jesse M. , Bañas Stefanie , Barfield Robyn M. , Zmolek Wesley , Kim Yun Cheol , Huang Betty C.B. , Kudirka Romas , Rabuka David
Published: November 2017

Hematologically derived tumors make up ∼10% of all newly diagnosed cancer cases in the United States. Of these, the non-Hodgkin lymphoma (NHL) designation describes a diverse group of cancers that collectively rank among the top 10 most commonly diagnosed cancers worldwide. Although long-term survival trends are improving, there remains a significant unmet clinical need for treatments to help patients with relapsed or refractory disease, one cause of which is drug efflux through upregulation of xenobiotic pumps, such as MDR1. CD22 is a clinically validated target for the treatment of NHL, but no anti-CD22 agents have yet been approved for this indication. Recent approval of an anti-CD22 antibody–drug conjugate (ADC) for the treatment of relapsed/refractory ALL supports the rationale for targeting this protein. An opportunity exists for a next-generation anti-CD22 antibody–drug conjugate (ADC) to address unmet medical needs in the relapsed/refractory NHL population. We describe a site-specifically conjugated antibody–drug conjugate, made using aldehyde tag technology, targeted against CD22 and bearing a noncleavable maytansine payload that is resistant to MDR1-mediated efflux. The construct was efficacious against CD22+ NHL xenografts and could be repeatedly dosed in cynomolgus monkeys at 60 mg/kg with no observed significantly adverse effects. Exposure to total ADC at these doses (as assessed by AUC0-inf) indicated that the exposure needed to achieve efficacy was below tolerable limits. Together, the data suggest that this drug has the potential to be used effectively in patients with CD22+ tumors that have developed MDR1-related resistance to prior therapies. Mol Cancer Ther; 17(1); 161–8. ©2017 AACR.
Intercavernous Sinus Dural Arteriovenous Fistula Treated with Transvenous Coil Embolization: A Case Report
Authors: Melake Mostafa Saleh , Oishi Hidenori , Suga Yasuo , Yamamoto Munetaka , Arai Hajime
Published: November 2017

The blood supply to the region of the cavernous sinus is provided by interconnecting branches of the internal and external carotid arteries, and it is from these vessels that dural arteriovenous fistulas (DAVFs) arise. It is very rare that DAVFs are located at the intercavernous sinuses region; in this case, a proper localization of the fistulous site is of extreme importance in order to successfully eliminate the disease. Here, we describe a case of a 65-year-old female with intercavernous sinus DAVF. A complete obliteration of the fistulous points was performed by coil embolization through a transvenous approach. i 2014 S. Karger AG, Basel
Decline in Search Speed and Verbal Memory Over 26 Years of Midlife in a British Birth Cohort
Authors: Davis Daniel , Bendayan Rebecca , Muniz Terrera Graciela , Hardy Rebecca , Richards Marcus , Kuh Diana
Published: November 2017

Background: Cognitive capabilities change in later life, although their onset and rate of decline, and how they are shaped by lifetime socioeconomic position, childhood cognition and adult health status are all unclear. Methods: From the Medical Research Council National Survey of Health and Development, we analysed 3,192 participants undergoing one or more cognitive assessments at ages 43, 53, 60–64 and 69. Linear mixed models described cognitive trajectories, adjusting for factors across the life course. Results: For both search speed and verbal memory, better performance at age 43 (the intercept) was associated with higher paternal and own education, childhood cognition, and adult occupational class. For search speed, the trajectory was best described as a quadratic function (decline of 45.6 letters/5-years + 4.6 letters). Verbal memory showed a linear decline of 0.20 words/5-years between ages 43 and 60 and a steeper linear decline of 0.95 words/5-years between ages 60 and 69. Decline in verbal memory in the latter period was steeper in those with higher educational achievements at age 26 (additional 0.28 words/5-years for highest attainment). Conclusions: Decline in verbal memory and search speed across midlife is evident, though with different non-linear trajectories. By implication, pathways to cognitive impairment and dementia in older age may have their origins in this period.
Did the DSM-5 Improve the Traumatic Stressor Criterion?: Association of DSM-IV and DSM-5 Criterion A with Posttraumatic Stress Disorder Symptoms
Authors: Larsen Sadie E. , Berenbaum Howard
Published: November 2017

Objective: A recent meta-analysis found that DSM-III- and DSM-IV-defined traumas were associated with only slightly higher posttraumatic stress disorder (PTSD) symptoms than nontraumatic stressors. The current study is the first to examine whether DSM-5-defined traumas were associated with higher levels of PTSD than DSM-IV-defined traumas. Further, we examined theoretically relevant event characteristics to determine whether characteristics other than those outlined in the DSM could predict PTSD symptoms. Method: One hundred six women who had experienced a trauma or significant stressor completed questionnaires assessing PTSD, depression, impairment, and event characteristics. Events were rated for whether they qualified as DSM-IV and DSM-5 trauma. Results: There were no significant differences between DSM-IV-defined traumas and stressors. For DSM-5, effect sizes were slightly larger but still nonsignificant (except for significantly higher hyperarousal following traumas vs. stressors). Self-reported fear for one's life significantly predicted PTSD symptoms. Conclusions: Our results indicate that the current DSM-5 definition of trauma, although a slight improvement from DSM-IV, is not highly predictive of who develops PTSD symptoms. Our study also indicates the importance of individual perception of life threat in the prediction of PTSD.
Patient-Reported Outcome Results from the Open-Label Randomized Phase III SELECT BC Trial Evaluating First-Line S-1 Therapy for Metastatic Breast Cancer
Authors: Kawahara Takuya , Shimozuma Kojiro , Shiroiwa Takeru , Hagiwara Yasuhiro , Uemura Yukari , Watanabe Takanori , Taira Naruto , Fukuda Takashi , Ohashi Yasuo , Mukai Hirofumi
Published: November 2017

Objective: To evaluate the effects of S-1, an orally administered 5-FU agent, versus taxane on patient-reported outcomes (PROs) in the SELECT BC trial. Methods: Patients with HER2-negative and endocrine treatment-resistant breast cancer with metastasis or recurrence after surgery were randomly assigned to receive first-line taxane or S-1. PROs (secondary endpoint) were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and Patient Neurotoxicity Questionnaire (PNQ) at baseline and at 3, 6, and 12 months. We conducted a responder analysis for the QLQ-C30 and PNQ and created cumulative distribution function (CDF) plots as a sensitivity analysis. Results: The questionnaire response rates were over 80% from 386 patients, who completed at least one baseline questionnaire. S-1 was significantly superior to taxane with respect to 6 scales (physical functioning [p = 0.03], role functioning [p = 0.04], social functioning [p < 0.01], financial difficulties [p = 0.01], global health status [p = 0.02], and constipation [p < 0.01]) and sensory neuropathy (p = 0.01). The CDF plots partially supported the conclusions and their robustness. Conclusion: First-line S-1 therapy has clinical benefits with respect to many aspects of health-related quality of life for metastatic breast cancer patients.
Current Indications and Outcome of Pulmonary Resections for Tuberculosis Complications in Ibadan, Nigeria
Authors: Salami Mudasiru A. , Sanusi Arinola A. , Adegboye Victor O.
Published: November 2017

Objectives: To review the current indications and outcome of pulmonary resections for tuberculosis (TB) at the Cardiothoracic Surgery Unit of the University College Hospital, Ibadan, Nigeria. Subjects and Methods: A retrospective case series review of patients who had lung resections from January 2014 to January 2017 was performed. Data obtained from medical records included demographics, presenting symptoms, indication for surgery, preoperative evaluation and preparation, operative procedure, postoperative complications, and follow-up. The presence of TB in the patients was confirmed by detecting pathological changes suggestive of TB and/or past history of pulmonary TB associated with its anatomical complications such as cavitation and bronchiectasis. Data were analysed using descriptive statistics. Results: Ten patients had pulmonary resections during this study period. The median age was 33.5 years (range: 3-50). The indication for lung resection was massive or persistent haemoptysis, and 2 patients also had aspergilloma. Six patients (60%) had lobectomy, 1 had a bilobectomy, and the remaining 3 had pneumonectomy. Complications included partial wound dehiscence in 2 patients, 1 of whom also had postoperative empyema thoracis. One patient died immediately due to haemorrhage. Follow-up ranged from 6 to 37 months. Conclusion: This study showed that the factors for a good outcome in patients presenting with massive or recurrent haemoptysis from TB complications were initial stabilization and multidisciplinary care. Hence, improved awareness of high-standard care to encourage inclusion of patients with TB complications in the surgical care protocol as part of national control programmes is recommended.
Trabalho, atividades de lazer e apoio familiar: fatores para proteção da qualidade de vida de idosos residentes no município de Sacramento-MG
Authors: Silva Maysa De Oliveira , Santos Álvaro Da Silva , Angelotti Lucila Costa Zini , Andrade Valéria Sousa de , Tavares Grasielle Silveira
Published: November 2017

Este estudo objetivou verificar a influência do trabalho, apoio familiar e das atividades de lazer na qualidade de vida (QV) de idosos. A amostra foi composta por 169 idosos residentes no município de Sacramento-MG com idade ≥ a 60 anos. Foram utilizados os instrumentos WHOQOL-Bref e WHOQOL-Old para avaliação da QV. Informações acerca do trabalho, apoio familiar e lazer foram coletadas por meio de questionários semiestruturados. Os dados foram analisados pelos testes t de Student e Mann Whitney, considerando-se p<0,05. As atividades de lazer correlacionaram-se com domínios “físico”, “psicológico” e “global” do WHOQOL-Bref e, com “funcionamento dos sentidos”, “autonomia”, “participação social” e com escore global do WHOQOL-Old. Os aposentados que ainda trabalham tiveram escore do domínio “físico” e na faceta “morte e morrer” significativamente mais altos em relação aos idosos que não trabalham mais. O apoio social configurou como importante estratégia para o enfrentamento das adversidades cotidianas, sendo que o convívio familiar mostrou ser um fator com efeito significativo sobre os escores médios de QV em quase todos os domínios dos instrumentos. O bom convívio familiar, o trabalho remunerado e a participação em atividades de lazer podem ser considerados fatores de proteção para QV dos idosos entrevistados.
Statins Promote Cardiac Infarct Healing by Modulating Endothelial Barrier Function Revealed by Contrast-Enhanced Magnetic Resonance Imaging
Authors: Leenders Geert J. , Smeets Mirjam B. , van den Boomen Maaike , Berben Monique , Nabben Miranda , van Strijp Dianne , Strijkers Gustav J. , Prompers Jeanine J. , Arslan Fatih , Nicolay Klaas , Vandoorne Katrien
Published: November 2017

Objective—

The endothelium has a crucial role in wound healing, acting as a barrier to control transit of leukocytes. Endothelial barrier function is impaired in atherosclerosis preceding myocardial infarction (MI). Besides lowering lipids, statins modulate endothelial function. Here, we noninvasively tested whether statins affect permeability at the inflammatory (day 3) and the reparative (day 7) phase of infarct healing post-MI using contrast-enhanced cardiac magnetic resonance imaging (MRI).

Approach and Results—

Noninvasive permeability mapping by MRI after MI in C57BL/6, atherosclerotic ApoE
−/−
, and statin-treated ApoE
−/−
mice was correlated to subsequent left ventricular outcome by structural and functional cardiac MRI. Ex vivo histology, flow cytometry, and quantitative polymerase chain reaction were performed on infarct regions. Increased vascular permeability at ApoE
−/−
infarcts was observed compared with C57BL/6 infarcts, predicting enhanced left ventricular dilation at day 21 post-MI by MRI volumetry. Statin treatment improved vascular barrier function at ApoE
−/−
infarcts, indicated by reduced permeability. The infarcted tissue of ApoE
−/−
mice 3 days post-MI displayed an unbalanced
Vegfa
(vascular endothelial growth factor A)/
Angpt1
(angiopoetin-1) expression ratio (explaining leakage-prone vessels), associated with higher amounts of CD45
+
leukocytes and inflammatory LY6C
hi
monocytes. Statins reversed the unbalanced
Vegfa/Angpt1
expression, normalizing endothelial barrier function at the infarct and blocking the augmented recruitment of inflammatory leukocytes in statin-treated ApoE
−/−
mice.

Conclusions—

Statins lowered permeability and reduced the transit of unfavorable inflammatory leukocytes into the infarcted tissue, consequently improving left ventricular outcome.
Interleukin-1 Blockade in Recently Decompensated Systolic Heart Failure
Authors: Van Tassell Benjamin W. , Canada Justin , Carbone Salvatore , Trankle Cory , Buckley Leo , Oddi Erdle Claudia , Abouzaki Nayef A. , Dixon Dave , Kadariya Dinesh , Christopher Sanah , Schatz Aaron , Regan Jessica , Viscusi Michele , Del Buono Marco , Melchior Ryan , Mankad Pranav , Lu Juan , Sculthorpe Robin , Biondi-Zoccai Giuseppe , Lesnefsky Edward , Arena Ross , Abbate Antonio
Published: November 2017

Background

An enhanced inflammatory response predicts worse outcomes in heart failure (HF). We hypothesized that administration of IL-1 (interleukin-1) receptor antagonist (anakinra) could inhibit the inflammatory response and improve peak aerobic exercise capacity in patients with recently decompensated systolic HF.

Methods and Results

We randomly assigned 60 patients with reduced left ventricular ejection fraction (<50%) and elevated C-reactive protein levels (>2 mg/L), within 14 days of hospital discharge, to daily subcutaneous injections with anakinra 100 mg for 2 weeks, 12 weeks, or placebo. Patients underwent measurement of peak oxygen consumption (V
o
2
[mL/kg per minute]) and ventilatory efficiency (the VE/V
co
2
slope). Treatment with anakinra did not affect peak V
o
2
or VE/V
co
2
slope at 2 weeks. At 12 weeks, patients continued on anakinra showed an improvement in peak V
o
2
from 14.5 (10.5–16.6) mL/kg per minute to 16.1 (13.2–18.6) mL/kg per minute (
P
=0.009 for within-group changes), whereas no significant changes occurred within the anakinra 2-week or placebo groups. The between-groups differences, however, were not statistically significant. The incidence of death or rehospitalization for HF at 24 weeks was 6%, 31%, and 30%, in the anakinra 12-week, anakinra 2-week, and placebo groups, respectively (log-rank test
P
=0.10).

Conclusions

No change in peak V
o
2
occurred at 2 weeks in patients with recently decompensated systolic HF treated with anakinra, whereas an improvement was seen in those patients in whom anakinra was continued for 12 weeks. Additional larger studies are needed to validate the effects of prolonged anakinra on peak V
o
2
and rehospitalization for HF.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01936909.
Mobile Interventional Stroke Teams Lead to Faster Treatment Times for Thrombectomy in Large Vessel Occlusion
Authors: Wei Daniel , Oxley Thomas J. , Nistal Dominic A. , Mascitelli Justin R. , Wilson Natalie , Stein Laura , Liang John , Turkheimer Lena M. , Morey Jacob R. , Schwegel Claire , Awad Ahmed J. , Shoirah Hazem , Kellner Christopher P. , De Leacy Reade A. , Mayer Stephan A. , Tuhrim Stanley , Paramasivam Srinivasan , Mocco J , Fifi Johanna T.
Published: November 2017

Background and Purpose—

Endovascular recanalization treatment for acute ischemic stroke is a complex, time-sensitive intervention. Trip-and-treat is an interhospital service delivery model that has not previously been evaluated in the literature and consists of a shared mobile interventional stroke team that travels to primary stroke centers to provide on-site interventional capability. We compared treatment times between the trip-and-treat model and the traditional drip-and-ship model.

Methods—

We performed a retrospective analysis on 86 consecutive eligible patients with acute ischemic stroke secondary to large vessel occlusion who received endovascular treatment at 4 hospitals in Manhattan. Patients were divided into 2 cohorts: trip-and-treat (n=39) and drip-and-ship (n=47). The primary outcome was initial door-to-puncture time, defined as the time between arrival at any hospital and arterial puncture. We also recorded and analyzed the times of last known well, IV-tPA (intravenous tissue-type plasminogen activator) administration, transfer, and reperfusion.

Results—

Mean initial door-to-puncture time was 143 minutes for trip-and-treat and 222 minutes for drip-and-ship (
P
<0.0001). Although there was a trend in longer puncture-to-recanalization times for trip-and-treat (
P
=0.0887), initial door-to-recanalization was nonetheless 79 minutes faster for trip-and-treat (
P
<0.0001). There was a trend in improved admission-to-discharge change in National Institutes of Health Stroke Scale for trip-and-treat compared with drip-and-ship (
P
=0.0704).

Conclusions—

Compared with drip-and-ship, the trip-and-treat model demonstrated shorter treatment times for endovascular therapy in our series. The trip-and-treat model offers a valid alternative to current interhospital stroke transfers in urban environments.
Fundamentals of the Real Estate Legislative System and Its Impact on Sustainable Development: Dubai Case Study
Authors: Jadalhaq Iyad Mohammed
Published: November 2017

The real estate legislative system is one of the bases of the sustainable development process. This research focuses on the role of the legal system in sustainable development, according to the most prominent relevant international reports. The uae ranked forty-first globally in the Human Development Index (hdi). In the World Bank’s ‘Doing Business Report’, the uae ranked second globally and first in the Middle East and North Africa (mena) for the ‘Dealing with Construction Permits’ indicator. Thus, the Emirate of Dubai is deemed the second-best city in the world in terms of ease of dealing with construction permits. For the ‘Registering Property’ indicator, the uae ranked tenth globally and first in the Middle East and North Africa (mena). Despite the uae’s great achievements in terms of developmental ranking at the global level, there is still more to achieve in the field of development.
Recent Constitutional Reforms in Kazakhstan: A Move towards Democratic Transition?
Authors: Kembayev Zhenis
Published: November 2017

This article aims at examining the major principles and provisions of the constitutional structure of Kazakhstan in the context of the amendments introduced to the Constitution of Kazakhstan on 10 March 2017. In doing so, it provides an analysis of the fundamentals of Kazakhstan’s constitutional system as well as major constitutional provisions underlying the status of the capital, the status of individuals, the Kazakh-style strong presidency and weak parliament. The article provides background to Kazakhstan’s constitutional development and elections. It pays particular attention to the relationship between the President, the Parliament and the Government, but also expounds the influence of the President on the Constitutional Council and judicial bodies. Finally, it summarizes and demonstrates major features and problems of Kazakhstan’s constitutional system in order to provide an answer as to whether the recent constitutional reforms constitute a move towards the country’s democratic transition.
A new troglobiotic Protaphorura (Collembola, Hexapoda) from the Siberia, Russia
Authors: PARIMUCHOVÁ ANDREA , KOVÁČ ĽUBOMÍR , ŽUROVCOVÁ MARTINA , KADEBSKAYA OĽGA IVANOVNA
Published: November 2017

A new species of Protaphorura Absolon, 1901 (Collembola, Onychiuridae), P. cykini sp.nov., is described from a cold karst cave in the Irkutsk region, Siberia, Russia. It is an obligate cave species with the largest body size (4.3–5.6 mm) of all congeners. The species is further characteristic by the pseudocellar formula as 3(2)2/022/33343, high number of vesicles in postantennal organ (65–71) and subapical organite protected with two papillae. A partial sequence of cytochrome oxidase I (COI DNA barcoding marker) gene is used to verify the taxonomic status of the new species and the barcode sequence is compared with other congeners available in GenBank database. Distribution and diversity of cave Collembola of Siberia is discussed.
A new species of Phrynobatrachus (Anura: Phrynobatrachidae) from the Eastern Arc Mountians of Tanzania
Authors: PICKERSGILL MARTIN , ZIMKUS BREDA M. , RAW LYNN R. G.
Published: November 2017

Phrynobatrachus discogularis sp. nov. (Anura, Phrynobatrachidae) is described from the Eastern Arc Mountains in Tanzania. It occupies upland grasslands and while it morphologically most resembles West and Central African P. gutturosus (Chabanaud, 1921), P. rungwensis (Loveridge, 1932), and P. anotis Schmidt and Inger, 1959, preliminary analysis of mitochondrial 16S rRNA indicates that the new species differs from all other species with published sequence data by a minimum distance of 4.1% and has affinities with P. rungwensis, P. uzungwensis Grandison and Howell, 1983 and P. keniensis Barbour and Loveridge, 1928—all diminutive upland eastern African taxa. The shape and colour of the male’s external gular apparatus distinguish this species from all other described Phrynobatrachus species. Although geographically either sympatric or closely allopatric with P. uzungwensis, the lack of overlapping morphological characters indicates the two forms are distinct species. The new taxon is compared with other species from the region.
Estimation and optimisation of effective thermal conductivity for polymer matrix composites with hybrid inclusions
Authors: Siddiqui MU , Arif Abul Fazal M
Published: November 2017

Composites with hybrid inclusions have shown remarkable thermal conductivity enhancement over composites with a single type of inclusion. However, to achieve maximum thermal conductivity enhancement, the optimum ratio of inclusions in the hybrid mix needs to be determined. In this communication, an effective medium theory based model for the estimation of effective thermal conductivity of composites with hybrid inclusions is presented. The proposed model accurately captures the synergic effect of hybrid inclusions within the composite and can be used to optimise the filler ratio in the hybrid mix. The model has been validated against several published experimental results and is found to be in good agreement with them. Parametric studies have also been carried out to study the effect of material and model parameters on the optimum ratio of hybrid inclusions.
A Grounded Theory of Adolescent High School Women’s Choir Singers’ Process of Social Identity Development
Authors: Parker Elizabeth Cassidy
Published: November 2017

The purpose of this grounded theory study was to discover the process of social identity development for adolescent high school women’s choir participants. Purposive maximum variation sampling was used to identify three public high school women’s choirs where 54 interviews were conducted with 40 different public school singers. Three waves of data collection and analysis revealed a seven-step process beginning with coming in singing and ending with envisioning myself. The central phenomenon was identified as opening up my voice and me and emphasized singers’ increased self-confidence. Intervening conditions included competition, the absence of choral opportunities, and lack of understanding from those outside of the choral program. Amount of time in the choral program, number of groups, and community recognition were identified as contextual conditions. Dimensionalized properties, a temporal matrix, and propositional statements are presented.
Effect of swirl on the performance and stability of transonic axial compressor
Authors: Tu Baofeng , Zhang Luyao , Hu Jun
Published: November 2017

To investigate the effect of twin swirl and bulk swirl on the performance and stability of a transonic axial compressor, a blade swirl generator was designed and simulated with a transonic single rotor using steady and unsteady numerical calculation methods. The bulk swirl intensity was adjusted by replacing the blades with different camber angles. The twin swirl intensity was decreased by reducing the blade number. The counter-rotating bulk swirl generated a significant drop in both the efficiency and stall margin, and resulted in an increase in the choked mass flow, and total pressure ratio. The co-rotating bulk swirl generated a decrease in the mass flow, total pressure ratio and stable operating range. The counter-rotating bulk swirl resulted in suction surface boundary layer separation beyond 50% of the span-wise height as well as more serious tip leakage blockage. The twin swirl resulted in a decrease in the total pressure ratio, maximum efficiency and stable operating range. The steady and unsteady numerical calculation results were consistent, though some differences were observed in the values. For the steady calculation, the maximum efficiency and choked mass flow decreased by 0.88% and 1.74%, respectively, and the mass flow at the stable boundary increased by 3.92% as compared to the uniform inlet flow at twin swirl intensity of 24°. During the unsteady calculation, the mass flow exhibited an increase of only 2.2% at the stable boundary. Under twin swirl and co-rotating bulk swirl and uniform inlet flow, the leading edge spillage of the tip leakage flow resulted in compressor instability. The counter-rotating bulk swirl changed the mechanism of instability. The characterisation of the swirl distortion presented a difference between the steady and unsteady calculations near the stable boundary. The unsteady calculation exhibited a lower mass flow at the stable boundary point and a higher total pressure ratio.
Introduction
Authors: Diduck Alison , Sheldon Sally
Published: November 2017

This short article introduces the five review articles, which make up this special issue to mark the 25th anniversary of Social & Legal Studies.
A transaction-based approach to social innovation
Authors: Slimane Karim Ben , Lamine Wadid
Published: November 2017

This article aims to provide a transaction-based approach to social innovation based on the three modes of transaction coordination and governance as identified by Powell. We produce a grid that explains how social innovation can be implemented in the market, in hierarchies or in networks. This work makes a number of theoretical contributions. First, it provides an integrative framework of social innovation that is firmly rooted in organization theory. Second, we introduce two new concepts: social entrepreneurship orientation and the social innovation ecosystem, believing that these concepts can contribute to a better understanding of the field of social innovation in the context of sustainable development.
A numerical study on drag reduction of underwater vehicles using hydrophobic surfaces
Authors: Anbarsooz Morteza
Published: November 2017

During last decades, many investigations have been done to find suitable solutions to reduce the drag force of underwater vehicles. These attempts can be divided into two main categories: supercavitating vehicles and unseparated flow patterns. In this study, a novel approach is introduced which uses hydrophobic surfaces for an underwater vehicle with an unseparated flow body profile. Fluid slippage on hydrophobic walls can lead to a considerable reduction of skin friction drag. The effectiveness of this approach for underwater hulls has been examined numerically. In this regard, first, the numerical procedure is validated by comparing the numerical results for the slip flow over a micron-sized spherical particle with the analytical results available in the literature. Next, numerical simulations are performed for an unseparated flow profile at various values of the sliding coefficients. Results show that the principal drag of such profiles is the skin friction drag which can be drastically reduced using hydrophobic surfaces. For the sliding coefficients smaller than 10, the drag coefficient of the underwater vehicle with an unseparated flow profile can be even lower than that of a supercavitating hull.
Methionine adenosyltransferases in cancers: Mechanisms of dysregulation and implications for therapy
Authors: Maldonado Lauren Y , Arsene Diana , Mato José M , Lu Shelly C
Published: November 2017

Methionine adenosyltransferase genes encode enzymes responsible for the biosynthesis of S-adenosylmethionine, the principal biological methyl donor and precursor of polyamines and glutathione. Mammalian cells express three genes – MAT1A, MAT2A, and MAT2B – with distinct expression and functions. MAT1A is mainly expressed in the liver and maintains the differentiated states of both hepatocytes and bile duct epithelial cells. Conversely, MAT2A and MAT2B are widely distributed in non-parenchymal cells of the liver and extrahepatic tissues. Increasing evidence suggests that methionine adenosyltransferases play significant roles in the development of cancers. Liver cancers, namely hepatocellular carcinoma and cholangiocarcinoma, involve dysregulation of all three methionine adenosyltransferase genes. MAT1A reduction is associated with increased oxidative stress, progenitor cell expansion, genomic instability, and other mechanisms implicated in tumorigenesis. MAT2A/MAT2B induction confers growth and survival advantage to cancerous cells, enhancing tumor migration. Highlighted examples from colon, gastric, breast, pancreas and prostate cancer studies further underscore methionine adenosyltransferase genes’ role beyond the liver in cancer development. In this subset of extra-hepatic cancers, MAT2A and MAT2B are induced via different regulatory mechanisms. Understanding the role of methionine adenosyltransferase genes in tumorigenesis helps identify attributes of these genes that may serve as valuable targets for therapy. While S-adenosylmethionine, and its metabolite, methylthioadenosine, have been largely explored as therapeutic interventions, targets aimed at regulation of MAT gene expression and methionine adenosyltransferase protein–protein interactions are now surfacing as potential effective strategies for treatment and chemoprevention of cancers.

Impact statement

This review examines the role of methionine adenosyltransferases (MATs) in human cancer development, with a particular focus on liver cancers in which all three MAT genes are implicated in tumorigenesis. An overview of MAT genes, isoenzymes and their regulation provide context for understanding consequences of dysregulation. Highlighting examples from liver, colon, gastric, breast, pancreas and prostate cancers underscore the importance of understanding MAT’s tumorigenic role in identifying future targets for cancer therapy.
Attention Deficit Hyperactivity Disorder: Unique Considerations in Athletes
Authors: Stewman Chaney G. , Liebman Catherine , Fink Laura , Sandella Brad
Published: November 2017

Context:

Attention deficit hyperactivity disorder (ADHD) is a common psychiatric condition in the general population, with evidence suggesting that it may be more common among athletes.

Evidence Acquisition:

Literature searches were performed on PubMed, MEDLINE, and Cochrane databases for the years 2000 to 2016 utilizing the following key search terms: ADHD, ADD, guidelines, diagnosis, athlete, sports, treatment, pharmacotherapy, stimulants, risk, cardiovascular effects, concussion, and traumatic brain injury (TBI).

Study Design:

Clinical review.

Level of Evidence:

Level 4.

Results:

ADHD exists among athletes at all levels of play, and symptomatology overlaps significantly with that of concussion. Treatment with stimulants has cardiovascular effects and may not be permitted by the athlete’s governing body. An athlete’s level of competition and individual cardiovascular risk factors may therefore affect medication choices.

Conclusion:

ADHD diagnosis and treatment are paramount to optimal quality of life and functioning in affected individuals. Pharmacologic treatment options should not specifically be avoided in athletes; however, stimulant use is an independent risk factor for heat illness. Concussion, a common athletic injury, may have an altered course in those affected by ADHD, specifically with regard to neurocognitive testing and recovery.
From macro-state to meso-organizing: A sociological review of the transition of Chinese local governments in the past 30 years
Authors: Ye Liangfei
Published: November 2017

Studying the transition of Chinese local governments has continuously been the main theme for sociologists since the fiscal, administrative, and market reforms launched in the 1980s. In reference to other countries’ experience, sociological studies about this transition are generally from three macro-theoretical perspectives: Weberian modernity, local transitional state, and local developmental state. However, they have two common problems: first, perceiving the transition as a paradigm shift, not a process; and, second, perceiving local governments as static entities, without internal dynamics. As an alternative, the paper argues that a meso-theoretical perspective should be adopted to inductively study the organization of Chinese local governments in the transitional process. Through exploring the two schools of the meso-organizing perspective—‘structuralism’ and ‘agency with plural institutions’—the paper proposes that sociologists should explore the transition as a dynamic process, an open system, an interaction of ‘structuralism’ and ‘agency with plural institutions’, and with an internal perspective.
Emotion Regulation Predicts Everyday Emotion Experience and Social Function in Schizophrenia
Authors: Moran Erin K. , Culbreth Adam J. , Barch Deanna M.
Published: November 2017

While recent evidence has pointed to disturbances in emotion regulation strategy use in schizophrenia, few studies have examined how these regulation strategies relate to emotionality and social behavior in daily life. Using ecological momentary assessment (EMA), we investigated the relationship between emotion regulation, emotional experience, and social interaction in the daily lives of individuals with schizophrenia. Participants ( N = 30) used mobile phones to complete online questionnaires reporting their daily emotional experience and social interaction. Participants also completed self-report measures of habitual emotion regulation. Hierarchical linear modeling revealed that self-reported use of cognitive reappraisal and savoring of emotional experiences were related to greater positive emotion in daily life. In contrast, self-reported suppression was related to greater negative emotion, reduced positive emotion, and reduced social interaction in daily life. These findings suggest that individual differences in habitual emotion regulation strategy usage have important relationships to everyday emotional and social experiences in schizophrenia.
A landscape of germ line mutations in a cohort of inherited bone marrow failure patients
Authors: Bluteau Olivier , Sebert Marie , Leblanc Thierry , Peffault de Latour Régis , Quentin Samuel , Lainey Elodie , Hernandez Lucie , Dalle Jean-Hugues , Sicre de Fontbrune Flore , Lengline Etienne , Itzykson Raphael , Clappier Emmanuelle , Boissel Nicolas , Vasquez Nadia , Da Costa Mélanie , Masliah-Planchon Julien , Cuccuini Wendy , Raimbault Anna , De Jaegere Louis , Adès Lionel , Fenaux Pierre , Maury Sébastien , Schmitt Claudine , Muller Marc , Domenech Carine , Blin Nicolas , Bruno Bénédicte , Pellier Isabelle , Hunault Mathilde , Blanche Stéphane , Petit Arnaud , Leverger Guy , Michel Gérard , Bertrand Yves , Baruchel André , Socié Gérard , Soulier Jean
Published: November 2017

Key Points

Next-generation sequencing broadens the spectrum of germ line mutations in a cohort of patients with likely-inherited BMF. Salient clinical features and distinct natural histories are consistently found in SAMD9L and SAMD9, MECOM/EVI1, and ERCC6L2 disorders.
Role of slough and biofilm in delaying healing in chronic wounds
Authors: Newton Heather , Edwards Jacky , Mitchell Louise , Percival Steven L
Published: November 2017

The management of biofilms with maintenance desloughing and antimicrobial therapy is fast becoming the accepted treatment strategy for chronic wounds