bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential for the use of mHealth in the management of cardiovascular disease in Kerala: a qualitative study
Authors: Smith Rebecca , Menon Jaideep , Rajeev Jaya G , Feinberg Leo , Kumar Raman Krishan , Banerjee Amitava 
Published: November 2015

ObjectivesTo assess the potential for using mHealth in cardiovascular disease (CVD) management in Kerala by exploring: (1) experiences and challenges of current CVD management; (2) current mobile phone use; (3) expectations of and barriers to mobile phone use in CVD management.DesignQualitative, semistructured, individual interviews.Setting5 primary health centres in Ernakulam district, Kerala, India.Participants15 participants in total from 3 stakeholder groups: 5 patients with CVD and/or its risk factors, 5 physicians treating CVD and 5 Accredited Social Health Activists (ASHAs). Patients were sampled for maximum variation on the basis of age, sex, CVD diagnoses and risk factors. All participants had access to a mobile phone.ResultsThe main themes identified relating to the current challenges of CVD were poor patient disease knowledge, difficulties in implementing primary prevention and poor patient lifestyles. Participants noted phone calls as the main function of current mobile phone use. The expectations of mHealth use are to: improve accessibility to healthcare knowledge; provide reminders of appointments, medication and lifestyle changes; save time, money and travel; and improve ASHA job efficacy. All perceived barriers to mHealth were noted within physician interviews. These included fears of mobile phones negatively affecting physicians’ roles, the usability of mobile phones, radiation and the need for physical consultations.ConclusionsThere are three main potential uses of mHealth in this population: (1) as an educational tool, to improve health education and lifestyle behaviours; (2) to optimise the use of limited resources, by overcoming geographical barriers and financial constraints; (3) to improve use of healthcare, by providing appointment and treatment reminders in order to improve disease prevention and management. Successful mHealth design, which takes barriers into account, may complement current practice and optimise use of limited resources.
Reasons and remedies for under-representation of women in medical leadership roles: a qualitative study from Australia
Authors: Bismark Marie , Morris Jennifer , Thomas Laura , Loh Erwin , Phelps Grant , Dickinson Helen 
Published: November 2015

ObjectiveTo elicit medical leaders’ views on reasons and remedies for the under-representation of women in medical leadership roles.DesignQualitative study using semistructured interviews with medical practitioners who work in medical leadership roles. Interviews were transcribed verbatim and transcripts were analysed using thematic analysis.SettingPublic hospitals, private healthcare providers, professional colleges and associations and government organisations in Australia.Participants30 medical practitioners who hold formal medical leadership roles.ResultsDespite dramatic increases in the entry of women into medicine in Australia, there remains a gross under-representation of women in formal, high-level medical leadership positions. The male-dominated nature of medical leadership in Australia was widely recognised by interviewees. A small number of interviewees viewed gender disparities in leadership roles as a ‘natural’ result of women's childrearing responsibilities. However, most interviewees believed that preventable gender-related barriers were impeding women's ability to achieve and thrive in medical leadership roles. Interviewees identified a range of potential barriers across three broad domains—perceptions of capability, capacity and credibility. As a counter to these, interviewees pointed to a range of benefits of women adopting these roles, and proposed a range of interventions that would support more women entering formal medical leadership roles.ConclusionsWhile women make up more than half of medical graduates in Australia today, significant barriers restrict their entry into formal medical leadership roles. These constraints have internalised, interpersonal and structural elements that can be addressed through a range of strategies for advancing the role of women in medical leadership. These findings have implications for individual medical practitioners and health services, as well as professional colleges and associations.
Do patients with ankylosing spondylitis adapt to their disease? Evidence from a ‘then-test’ in patients treated with TNF inhibitors
Authors: Essers Ivette , van Tubergen Astrid , Heldmann Frank , Baraliakos Xenofon , Braun Jürgen , Kiltz Uta , Boonen Annelies 
Published: November 2015

ObjectiveTo investigate whether patients with ankylosing spondylitis (AS) adapt to their disease, using the ‘then-test’.MethodsData from patients participating in the AS Study for Evaluation of Recombinant Infliximab Therapy (ASSERT) and continuing in the European AS Infliximab Cohort (EASIC) were used. At 5 assessments in EASIC, patients were asked to rerate their global well-being before the start of infliximab in ASSERT. The patients evaluated their past situation by using a ‘then-test’ (‘retrospective patient global’). Initial and retrospective patient global were compared using a paired t test, and mixed linear models investigated whether the retrospective score of well-being was stable at all follow-up assessments in EASIC. Linear regression analysis explored whether treatment response was associated with the difference between the initial and retrospective score (‘gap’) while adjusting for possible confounders.Results86 patients (mean age 39.8 years (SD=10.4), mean disease duration 10.8 years (SD=8.5)) contributed to the current analyses. At the time of starting infliximab, patients judged their global at 7.0 (SD=1.6), and with the ‘then-test’ at 7.2 (SD=2.3) (p=0.45). Time elapsed did not influence the ‘then-test’ (p=0.13). Multivariably, the gap was irrespective of treatment response, but associated with initial patient global (p<0.01) and initial Bath AS Disease Activity Index (p=0.02).ConclusionsPatients with AS accurately judged their global well-being before starting treatment with tumour necrosis factor inhibition, even though substantial time had elapsed. The difference between initial and retrospective judgment was irrespective of treatment response. In this setting, the ‘then-test’ could not prove adaptation in AS.Trial registration numberNCT01286545.
Fibulin-5 Blocks Microenvironmental ROS in Pancreatic Cancer
Authors: Wang Miao , Topalovski Mary , Toombs Jason E. , Wright Christopher M. , Moore Zachary R. , Boothman David A. , Yanagisawa Hiromi , Wang Huamin , Witkiewicz Agnieszka , Castrillon Diego H. , Brekken Rolf A. 
Published: November 2015

Abstract
Elevated oxidative stress is an aberration seen in many solid tumors, and exploiting this biochemical difference has the potential to enhance the efficacy of anticancer agents. Homeostasis of reactive oxygen species (ROS) is important for normal cell function, but excessive production of ROS can result in cellular toxicity, and therefore ROS levels must be balanced finely. Here, we highlight the relationship between the extracellular matrix and ROS production by reporting a novel function of the matricellular protein Fibulin-5 (Fbln5). We used genetically engineered mouse models of pancreatic ductal adenocarcinoma (PDAC) and found that mutation of the integrin-binding domain of Fbln5 led to decreased tumor growth, increased survival, and enhanced chemoresponse to standard PDAC therapies. Through mechanistic investigations, we found that improved survival was due to increased levels of oxidative stress in Fbln5-mutant tumors. Furthermore, loss of the Fbln5–integrin interaction augmented fibronectin signaling, driving integrin-induced ROS production in a 5-lipooxygenase–dependent manner. These data indicate that Fbln5 promotes PDAC progression by functioning as a molecular rheostat that modulates cell–ECM interactions to reduce ROS production, and thus tip the balance in favor of tumor cell survival and treatment-refractory disease. Cancer Res; 75(23); 5058–69. ©2015 AACR.
KDR Amplification Is Associated with VEGF-Induced Activation of the mTOR and Invasion Pathways but does not Predict Clinical Benefit to the VEGFR TKI Vandetanib
Authors: Nilsson Monique B. , Giri Uma , Gudikote Jayanthi , Tang Ximing , Lu Wei , Tran Hai , Fan Youhong , Koo Andrew , Diao Lixia , Tong Pan , Wang Jing , Herbst Roy , Johnson Bruce E. , Ryan Andy , Webster Alan , Rowe Philip , Wistuba Ignacio I. , Heymach John V. 
Published: November 2015

Abstract
Purpose: VEGF pathway inhibitors have been investigated as therapeutic agents in the treatment of non–small cell lung cancer (NSCLC) because of its central role in angiogenesis. These agents have improved survival in patients with advanced NSCLC, but the effects have been modest. Although VEGFR2/KDR is typically localized to the vasculature, amplification of KDR has reported to occur in 9% to 30% of the DNA from different lung cancers. We investigated the signaling pathways activated downstream of KDR and whether KDR amplification is associated with benefit in patients with NSCLC treated with the VEGFR inhibitor vandetanib.
Methods: NSCLC cell lines with or without KDR amplification were studied for the effects of VEGFR tyrosine kinase inhibitors (TKI) on cell viability and migration. Archival tumor samples collected from patients with platinum-refractory NSCLC in the phase III ZODIAC study of vandetanib plus docetaxel or placebo plus docetaxel (N = 294) were screened for KDR amplification by FISH.
Results: KDR amplification was associated with VEGF-induced activation of mTOR, p38, and invasiveness in NSCLC cell lines. However, VEGFR TKIs did not inhibit proliferation of NSCLC cell lines with KDR amplification. VEGFR inhibition decreased cell motility as well as expression of HIF1α in KDR-amplified NSCLC cells. In the ZODIAC study, KDR amplification was observed in 15% of patients and was not associated with improved progression-free survival, overall survival, or objective response rate for the vandetanib arm.
Conclusions: Preclinical studies suggest KDR activates invasion but not survival pathways in KDR-amplified NSCLC models. Patients with NSCLC whose tumor had KDR amplification were not associated with clinical benefit for vandetanib in combination with docetaxel. Clin Cancer Res; 22(8); 1940–50. ©2015 AACR.
Targeting mTOR and p53 Signaling Inhibits Muscle Invasive Bladder Cancer In Vivo
Authors: Madka Venkateshwar , Mohammed Altaf , Li Qian , Zhang Yuting , Biddick Laura , Patlolla Jagan M.R. , Lightfoot Stan , Towner Rheal A. , Wu Xue-Ru , Steele Vernon E. , Kopelovich Levy , Rao Chinthalapally V. 
Published: November 2015

Abstract
Urothelial tumors, accompanied by mutations of the tumor suppressor protein TP53 and dysregulation of mTOR signaling, are frequently associated with aggressive growth and invasiveness. We investigated whether targeting these two pathways would inhibit urothelial tumor growth and progression. Six-week-old transgenic UPII-SV40T male mice (n = 15/group) were fed control diet (AIN-76A) or experimental diets containing mTOR inhibitor (rapamycin, 8 or 16 ppm), p53 stabilizing agent [CP31398 (CP), 150 ppm], or a combination. Mice were euthanized at 40 weeks of age. Urinary bladders were collected and evaluated to determine tumor weight and histopathology. Each agent alone, and in combination, significantly inhibited tumor growth. Treatment with rapamycin alone decreased tumor weight up to 67% (P &lt; 0.0001). Similarly, CP showed approximately 77% (P &lt; 0.0001) suppression of tumor weight. The combination of low-dose rapamycin and CP led to approximately 83% (P &lt; 0.0001) inhibition of tumor weight. There was no significant difference in tumor weights between rapamycin and CP treatments (P &gt; 0.05). However, there was a significant difference between 8 ppm rapamycin and the combination treatment. Tumor invasion was also significantly inhibited in 53% (P &lt; 0.005) and 66% (P &lt; 0.0005) mice after 8 ppm and 16 ppm rapamycin, respectively. However, tumor invasion was suppressed in 73% (P &lt; 0.0001) mice when CP was combined with 8 ppm rapamycin. These results suggest that targeting two or more pathways achieve better treatment efficacy than a single-agent high-dose strategy that could increase the risk of side effects. A combination of CP and rapamycin may be a promising method of inhibiting muscle-invasive urothelial transitional cell carcinoma. Cancer Prev Res; 9(1); 53–62. ©2015 AACR.
Lifestyle Intervention for Weight Loss and Cardiometabolic Changes in the Setting of Glucokinase Regulatory Protein Inhibition
Authors: Belalcazar L. Maria , Papandonatos George D. , Erar Bahar , Peter Inga , Alkofide Hadeel , Balasubramanyam Ashok , Brautbar Ariel , Kahn Steven E. , Knowler William C. , Ballantyne Christie M. , McCaffery Jeanne M. , Huggins Gordon S. 
Published: November 2015

Background—
Glucokinase regulatory protein (GCKR) inhibitors offer a novel treatment approach for glucose control in diabetes mellitus; however, their cardiometabolic effects, particularly in relation to increased triglycerides and C-reactive protein (CRP) levels, are of concern. GCKR Leu446Pro is a common variant associated with reduced GCKR function, increased triglycerides, and CRP.

Methods and Results—

We investigated whether a 1-year intensive lifestyle intervention (ILI) for weight loss would avert the unfavorable cardiometabolic effects associated with GCKR Leu446Pro when compared with a diabetes mellitus support and education arm in overweight/obese individuals with type 2 diabetes mellitus with triglyceride (n=3214) and CRP (n=1411) data participating in a randomized lifestyle intervention study for weight loss, Action for Health in Diabetes Mellitus (Look AHEAD). Once demographics, medication use and baseline adiposity, and fitness were accounted for, ILI did not modify the baseline association of GCKR-Leu446Pro with elevated triglycerides (β±SE=0.067±0.013,
P
=1.5×10
−7
and β±SE=0.052±0.015,
P
=5×10
−4
) or with elevated CRP (β±SE=0.136±0.034,
P
=5.1×10
−5
and β±SE=0.903±0.038,
P
=0.015) in the overall sample and Non-Hispanic Whites, respectively. The lack of a protective effect from ILI at 1 year when compared with diabetes mellitus support and education (ILI versus diabetes mellitus support and education interaction for triglyceride and CRP change, respectively:
P
=0.64 and 0.37 in the overall sample;
P
=0.27 and 0.05 in Non-Hispanic Whites) persisted after additional adjustment for changes in adiposity and fitness.

Conclusions—
Moderate improvements in adiposity and fitness with ILI did not mitigate the adverse cardiometabolic effects of GCKR inhibition in overweight/obese individuals with diabetes mellitus.
Derivation and Validation of a Novel Prognostic Scale (Modified–Stroke Subtype, Oxfordshire Community Stroke Project Classification, Age, and Prestroke Modified Rankin) to Predict Early Mortality in Acute Stroke
Authors: Abdul-Rahim Azmil H. , Quinn Terence J. , Alder Sarah , Clark Allan B. , Musgrave Stanley D. , Langhorne Peter , Potter John F. , Myint Phyo Kyaw 
Published: November 2015

Background and Purpose—
The stroke subtype, Oxfordshire Community Stroke Project classification, age, and prestroke modified Rankin (SOAR) score is a prognostic scale proposed for early mortality prediction after acute stroke. We aimed to evaluate whether including a measure of initial stroke severity (National Institutes of Health Stroke Scale and modified-SOAR [mSOAR] scores) would improve the prognostic accuracy.

Methods—
Using Anglia Stroke and Heart Clinical Network data, 2008 to 2011, we assessed the performance of SOAR and mSOAR against in-hospital mortality using area under the receiver operating curve statistics. We externally validated the prognostic utility of SOAR and mSOAR using an independent cohort data set from Glasgow. We described calibration using Hosmer–Lemeshow goodness-of-fit test.

Results—

A total of 1002 patients were included in the derivation cohort, and 105 (10.5%) died as inpatients. The area under the receiver operating curves for outcome of early mortality derived from the SOAR and mSOAR scores were 0.79 (95% confidence interval, 0.75–0.84) and 0.83 (95% confidence interval, 0.79–0.86), respectively (
P
=0.001). The external validation data set contained 1012 patients with stroke; of which, 121 (12.0%) patients died within 90 days. The mSOAR scores identified the risk of early mortality ranging from 3% to 42%. External validation of mSOAR score yielded an area under the receiver operating curve of 0.84 (95% confidence interval, 0.82–0.88) for outcome of early mortality. Calibration was good (
P
=0.70 for the Hosmer–Lemeshow test).

Conclusions—
Adding National Institutes of Health Stroke Scale data to create a modified-SOAR score improved prognostic utility in both derivation and validation data sets. The mSOAR may have clinical utility by using easily available data to predict mortality.
Multilingual Validation of the Questionnaire for Verifying Stroke-Free Status in West Africa
Authors: Sarfo Fred , Gebregziabher Mulugeta , Ovbiagele Bruce , Akinyemi Rufus , Owolabi Lukman , Obiako Reginald , Akpa Onoja , Armstrong Kevin , Akpalu Albert , Adamu Sheila , Obese Vida , Boa-Antwi Nana , Appiah Lambert , Arulogun Oyedunni , Mensah Yaw , Adeoye Abiodun , Tosin Aridegbe , Adeleye Osimhiarherhuo , Tabi-Ajayi Eric , Phillip Ibinaiye , Sani Abubakar , Isah Suleiman , Tabari Nasir , Mande Aliyu , Agunloye Atinuke , Ogbole Godwin , Akinyemi Joshua , Laryea Ruth , Melikam Sylvia , Uvere Ezinne , Adekunle Gregory , Kehinde Salaam , Azuh Paschal , Dambatta Abdul , Ishaq Naser , Saulson Raelle , Arnett Donna , Tiwari Hemnant , Jenkins Carolyn , Lackland Dan , Owolabi Mayowa 
Published: November 2015

Background and Purpose—
The Questionnaire for Verifying Stroke-Free Status (QVSFS), a method for verifying stroke-free status in participants of clinical, epidemiological, and genetic studies, has not been validated in low-income settings where populations have limited knowledge of stroke symptoms. We aimed to validate QVSFS in 3 languages, Yoruba, Hausa and Akan, for ascertainment of stroke-free status of control subjects enrolled in an on-going stroke epidemiological study in West Africa.

Methods—
Data were collected using a cross-sectional study design where 384 participants were consecutively recruited from neurology and general medicine clinics of 5 tertiary referral hospitals in Nigeria and Ghana. Ascertainment of stroke status was by neurologists using structured neurological examination, review of case records, and neuroimaging (gold standard). Relative performance of QVSFS without and with pictures of stroke symptoms (pictograms) was assessed using sensitivity, specificity, positive predictive value, and negative predictive value.

Results—
The overall median age of the study participants was 54 years and 48.4% were males. Of 165 stroke cases identified by gold standard, 98% were determined to have had stroke, whereas of 219 without stroke 87% were determined to be stroke-free by QVSFS. Negative predictive value of the QVSFS across the 3 languages was 0.97 (range, 0.93–1.00), sensitivity, specificity, and positive predictive value were 0.98, 0.82, and 0.80, respectively. Agreement between the questionnaire with and without the pictogram was excellent/strong with Cohen k=0.92.

Conclusions—
QVSFS is a valid tool for verifying stroke-free status across culturally diverse populations in West Africa.
Trajectories of Vasomotor Symptoms and Carotid Intima Media Thickness in the Study of Women’s Health Across the Nation
Authors: Thurston Rebecca C. , El Khoudary Samar R. , Tepper Ping Guo , Jackson Elizabeth A. , Joffe Hadine , Chen Hsiang-Yu , Matthews Karen A. ,   Appendix, Harlow Siobán , Sowers MaryFran , Finkelstein Joel , Neer Robert , Kravitz Howard , Powell Lynda , Gold Ellen , Greendale Gail , Derby Carol , Wildman Rachel , Santoro Nanette , Weiss Gerson , Rossi Winifred , Sherman Sherry , Ory Marcia , McConnell Daniel , Brooks Maria Mori , Sutton-Tyrrell Kim , McKinlay Sonja , Johnson Susan , Gallagher Chris 
Published: November 2015

Background and Purpose—
Emerging work has linked menopausal vasomotor symptoms (VMS) to subclinical cardiovascular disease (CVD) among women. However, VMS are dynamic over time. No studies have considered how temporal patterns of VMS may relate to subclinical CVD. We tested how temporal patterns of VMS assessed over 13 years were related to carotid intima media thickness (IMT) among midlife women.

Methods—
The Study of Women’s Health Across the Nation is a longitudinal cohort study of midlife women. Eight hundred and eleven white, black, Hispanic, and Chinese participants with a well-characterized final menstrual period completed measures of VMS, a blood draw, and physical measures approximately annually for 13 years. Women underwent a carotid artery ultrasound at study visit 12.

Results—

Four trajectories of VMS were identified by trajectory analysis (consistently high, early-onset, late-onset, persistently low VMS) and tested in relation to carotid indices in linear regression models. Results indicated that women with early-onset VMS had both greater mean IMT (beta, b [standard error, SE]=0.03 [0.01],
P
=0.03) and greater maximal IMT (b [SE]=0.04 [0.01],
P
=0.008) than women with consistently low VMS, adjusting for demographics and CVD risk factors.

Conclusions—
This is the first study to test trajectories of VMS in relation to subclinical CVD. Women with VMS early in the menopause transition had higher mean IMT and maximal IMT than those with consistently low VMS across the transition. Associations were not accounted for by demographic factors nor by CVD risk factors. Results can signal to women in need of early CVD risk reduction.
Occurrence of a new species of Letana (Orthoptera: Tettigoniidae: Phaneropterinae) in India
Authors: NAGAR RAJENDRA , SWAMINATHAN R. 
Published: November 2015

A new species of the Oriental genus Letana, Walker (Orthoptera: Tettigoniidae: Phaneropterinae), proposed as Letana dentata sp. nov., collected from the North-eastern province, Meghalaya, India (Ri bhoi 90°55’15 to 91°16’ latitude and 25°40’ to 25°21’ longitude, 993 MSL), is described together with the morphological characterization of eight reported species. Of these, Letana rubescens (Stål, 1861) collected from Shalimar, Srinagar, Jammu and Kashmir (India) is being reported for the first time from India. The other species of Letana include: L. atomifera, L. bulbosa, L. inflata, L. infurcata, L. pyrifera and L. rufonatata. Taxonomic and diagnostic characters with illustrations of the head, pronotum, ventral view of left tegmina to show stridulatory file teeth and the genitalia (supra-anal plate and subgenital plate) including the phallus sclerite has been given.