bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gender comparisons in non-acute cardiac symptom recognition and subsequent help-seeking decisions: a mixed methods study protocol
Authors: Stain Nolan , Ridge Damien , Cheshire Anna 
Published: November 2014

IntroductionCoronary heart disease (CHD) is one of the leading causes of death in both men and women worldwide. Despite the common misconception that CHD is a ‘man's disease’, it is now well accepted that women endure worse clinical outcomes than men following CHD-related events. A number of studies have explored whether or not gender differences exist in patients presenting with CHD, and specifically whether women delay seeking help for cardiac conditions. UK and overseas studies on help-seeking for emergency cardiac events are contradictory, yet suggest that women often delay help-seeking. In addition, no studies have looked at presumed cardiac symptoms outside an emergency situation. Given the lack of understanding in this area, an explorative qualitative study on the gender differences in help-seeking for a non-emergency cardiac events is needed.Methods and analysisA purposive sample of 20–30 participants of different ethnic backgrounds and ages attending a rapid access chest pain clinic will be recruited to achieve saturation. Semistructured interviews focusing on help-seeking decision-making for apparent cardiac symptoms will be undertaken. Interview data will be analysed thematically using qualitative software (NVivo) to understand any similarities and differences between the way men and women construct help-seeking. Findings will also be used to inform the preliminary development of a cardiac help-seeking intentions questionnaire.Ethics and disseminationEthical approvals were sought and granted. Namely, the University of Westminster (sponsor) and St Georges NHS Trust REC, and the Trust Research and Development Office granted approval to host the study on the Queen Mary's Roehampton site. The study is low risk, with interviews being conducted on hospital premises during working hours. Investigators will disseminate findings via presentations and publications. Participants will receive a written summary of the key findings.
Is progression-free survival associated with a better health-related quality of life in patients with lung cancer? Evidence from two randomised trials with afatinib
Authors: Griebsch Ingolf , Palmer Michael , Fayers Peter M , Ellis Stuart 
Published: November 2014

ObjectiveProgression-free survival (PFS) is frequently used as an efficacy end point in oncology clinical trials. However, there is limited evidence to support a positive association between improvement in PFS and improvement in health-related quality of life (HRQoL). The association between PFS and HRQoL was evaluated in two randomised trials.Materials and methodsData from two randomised controlled trials in patients with non-small cell lung cancer (NSCLC; LUX-Lung 1 and LUX-Lung 3) were used to investigate HRQoL in patients to determine whether tumour progression is accompanied by worsening HRQoL. HRQoL was assessed using the cancer-specific European Organization for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30, the EuroQol EQ-5D overall utility and EuroQol EQ visual analogue scale. In both studies, progression was evaluated by independent review using RECIST criteria (primary end point) and also by investigator assessment. The relationship between tumour progression and HRQoL was evaluated using analysis of covariance and a longitudinal model.ResultsCompliance with HRQoL questionnaire completion was high. In both studies, patients with progression consistently experienced numerically poorer HRQoL at the time of progression than patients without progression. Differences in mean scores were statistically significant (p<0.05) between patients with and without progression at week 4 in all analyses in LUX-Lung 1 and at multiple time points in LUX-Lung 3. Results from the longitudinal analysis showed that progression (by independent review and investigator assessment) appears to have consistent negative impact on all three HRQoL measures (all p<0.0001).ConclusionsTumour progression in patients with NSCLC was associated with statistically significant worsening in HRQoL. These findings confirm the value of PFS as a patient-relevant end point.
Cables1 Complex Couples Survival Signaling to the Cell Death Machinery
Authors: Shi Zhi , Park Hae R. , Du Yuhong , Li Zijian , Cheng Kejun , Sun Shi-Yong , Li Zenggang , Fu Haian , Khuri Fadlo R. 
Published: November 2014

Abstract
Cables1 is a candidate tumor suppressor that negatively regulates cell growth by inhibiting cyclin-dependent kinases. Cables1 expression is lost frequently in human cancer but little is known about its regulation. Here, we report that Cables1 levels are controlled by a phosphorylation and 14-3-3–dependent mechanism. Mutagenic analyses identified two residues, T44 and T150, that are specifically critical for 14-3-3 binding and that serve as substrates for phosphorylation by the cell survival kinase Akt, which by binding directly to Cables1 recruits 14-3-3 to the complex. In cells, Cables1 overexpression induced apoptosis and inhibited cell growth in part by stabilizing p21 and decreasing Cdk2 kinase activity. Ectopic expression of activated Akt (AKT1) prevented Cables1-induced apoptosis. Clinically, levels of phosphorylated Cables1 and phosphorylated Akt correlated with each other in human lung cancer specimens, consistent with pathophysiologic significance. Together, our results illuminated a dynamic regulatory system through which activated Akt and 14-3-3 work directly together to neutralize a potent tumor suppressor function of Cables1. Cancer Res; 75(1); 147–58. ©2014 AACR.
IPH4102, a Humanized KIR3DL2 Antibody with Potent Activity against Cutaneous T-cell Lymphoma
Authors: Marie-Cardine Anne , Viaud Nicolas , Thonnart Nicolas , Joly Rachel , Chanteux Stéphanie , Gauthier Laurent , Bonnafous Cécile , Rossi Benjamin , Bléry Mathieu , Paturel Carine , Bensussan Armand , Bagot Martine , Sicard Hélène 
Published: October 2014

AbstractAdvanced cutaneous T-cell lymphoma (CTCL) remains an unmet medical need, which lacks effective targeted therapies. In this study, we report the development of IPH4102, a humanized monoclonal antibody that targets the immune receptor KIR3DL2, which is widely expressed on CTCL cells but few normal immune cells. Potent antitumor properties of IPH4102 were documented in allogeneic human CTCL cells and a mouse model of KIR3DL2+ disease. IPH4102 antitumor activity was mediated by antibody-dependent cell cytotoxicity and phagocytosis. IPH4102 improved survival and reduced tumor growth in mice inoculated with KIR3DL2+ tumors. Ex vivo efficacy was further evaluated in primary Sézary patient cells, sorted natural killer–based autologous assays, and direct spiking into Sézary patient peripheral blood mononuclear cells. In these settings, IPH4102 selectively and efficiently killed primary Sézary cells, including at unfavorable effector-to-target ratios characteristic of unsorted PBMC. Together, our results offer preclinical proof of concept for the clinical development of IPH4102 to treat patients with advanced CTCL. Cancer Res; 74(21); 6060–70. ©2014 AACR.
T Cells Bearing a Chimeric Antigen Receptor against Prostate-Specific Membrane Antigen Mediate Vascular Disruption and Result in Tumor Regression
Authors: Santoro Stephen P. , Kim Soorin , Motz Gregory T. , Alatzoglou Dimitrios , Li Chunsheng , Irving Melita , Powell Daniel J. , Coukos George 
Published: October 2014

Abstract
Aberrant blood vessels enable tumor growth, provide a barrier to immune infiltration, and serve as a source of protumorigenic signals. Targeting tumor blood vessels for destruction, or tumor vascular disruption therapy, can therefore provide significant therapeutic benefit. Here, we describe the ability of chimeric antigen receptor (CAR)–bearing T cells to recognize human prostate–specific membrane antigen (hPSMA) on endothelial targets in vitro as well as in vivo. CAR T cells were generated using the anti-PSMA scFv, J591, and the intracellular signaling domains: CD3ζ, CD28, and/or CD137/4-1BB. We found that all anti-hPSMA CAR T cells recognized and eliminated PSMA+ endothelial targets in vitro, regardless of the signaling domain. T cells bearing the third-generation anti-hPSMA CAR, P28BBζ, were able to recognize and kill primary human endothelial cells isolated from gynecologic cancers. In addition, the P28BBζ CAR T cells mediated regression of hPSMA-expressing vascular neoplasms in mice. Finally, in murine models of ovarian cancers populated by murine vessels expressing hPSMA, the P28BBζ CAR T cells were able to ablate PSMA+ vessels, cause secondary depletion of tumor cells, and reduce tumor burden. Taken together, these results provide a strong rationale for the use of CAR T cells as agents of tumor vascular disruption, specifically those targeting PSMA. Cancer Immunol Res; 3(1); 68–84. ©2014 AACR.
Homocysteine Accelerates Senescence of Endothelial Cells via DNA Hypomethylation of Human Telomerase Reverse Transcriptase
Authors: Zhang Donghong , Sun Xiaoli , Liu Jianlan , Xie Xina , Cui Wei , Zhu Yi 
Published: October 2014

Objective—
Homocysteine can accelerate the senescence of endothelial progenitor cells or endothelial cells (ECs) via telomerase inactivation and length shortening. However, the underlying mechanism is unclear. Here, we investigated whether homocysteine promotes endothelial senescence by reducing the expression and activity of human telomerase reverse transcriptase (hTERT) by DNA methylation to reduce ECs telomerase activity.

Approach and Results—
When compared with primary human umbilical vein endothelial cells grown under standard conditions, ECs with chronic homocysteine treatment showed accelerated upregulation of p16, p21, and p53, markers of cellular senescence, during 6 to 10 passages. Interestingly, homocysteine-stimulated but not angiotensin II–stimulated ECs senescence could be reversed by hypermethylation induced by folic acid or s-adenosylmethionine supplementation. Meanwhile, homocysteine promoted the shortening of telomere length specifically related to restoration of hTERT transcriptional expression and CCCTC-binding factor binding sites with hTERT promoter hypomethylation, as detected by quantitative real-time polymerase chain reaction, Western blot, methylation-specific polymerase chain reaction, and bisulfite sequencing assay. Electrophoretic mobility shift assay and chromatin immunoprecipitation results showed that homocysteine-reduced telomere activity and homocysteine-induced EC senescence might contribute to hTERT promoter demethylation by increasing CCCTC-binding factor repression and interfering in the SP1 binding to the demethylated hTERT promoter, which might relate with reduced of DNA methyltransferase 1. Furthermore, the CCCTC-binding factor–dependent mechanism of homocysteine-reduced hTERT expression via DNA demethylation was confirmed in aortic endothelia of mice with hyperhomocysteine levels.

Conclusions—
CCCTC-binding factor and SP1 cross talk may contribute to homocysteine-reduced hTERT DNA methylation and expression in endothelial senescence.
Introduction to İsmail Saray's Leonardo da
Vinci
Authors: Demir Duygu 
Published: October 2014

Abstract
Aiming to contextualize Turkish artist İsmail Saray's artist book Leonardo da Vinci (1976), this text centers around the artist's educational formation and the early years of his artistic practice between the years of 1973–1980, when he was based in Turkey. Tracing key moments in this period including his participation in the Paris Biennial of 1977, the Yeni Eğilimler [New Trends in Art] exhibition of 1979 in Istanbul as well as his guest appearance in the exhibition Sanat Olarak Betik [Book as Art] organized by the conceptualist artist collective Sanat Tanım Topluluğu. This essay also gives a glimpse of the conditions under which artists were operating at the time, heavily influenced by the political developments in Turkey. The dematerialization of Saray's practice is traced through the artist books and his production on paper, including correspondence that led to the production of his artworks by fellow artists elsewhere, a phenomenon that awaits further investigation.
Leonardo da Vinci
Authors: Saray İsmail 
Published: October 2014

Abstract
Aiming to contextualize Turkish artist İsmail Saray's artist book Leonardo da Vinci (1976), this text centers around the artist's educational formation and the early years of his artistic practice between the years of 1973–1980, when he was based in Turkey. Tracing key moments in this period including his participation in the Paris Biennial of 1977, the Yeni Eğilimler [New Trends in Art] exhibition of 1979 in Istanbul as well as his guest appearance in the exhibition Sanat Olarak Betik [Book as Art] organized by the conceptualist artist collective Sanat Tanım Topluluğu. This essay also gives a glimpse of the conditions under which artists were operating at the time, heavily influenced by the political developments in Turkey. The dematerialization of Saray's practice is traced through the artist books and his production on paper, including correspondence that led to the production of his artworks by fellow artists elsewhere, a phenomenon that awaits further investigation.
An Observational Study of the Effects of Dry Air Produced in Dissipating Convective Storms on the Predictability of Severe Weather
Authors: Bluestein Howard B. , Snyder Jeffrey C. 
Published: October 2014

Abstract
This paper documents features that led to major forecast errors on the 12–24-h time scale in the nature and location of severe weather in the southern plains on 30 May 2012. Evidence is presented that the forecast errors were the result of 1) dry air that originated in a region of dissipating, elevated convective storms, and which was advected in a narrow tongue into western Oklahoma, inhibiting convective initiation; 2) the development of a cyclone along the dryline in western Texas, to the east of which several supercells formed; 3) the upscale development of the supercells into a mesoscale convective system (MCS) at nightfall; and 4) the dissipation of an MCS that had formed along a cold front in southwestern Kansas and was propagating into northwestern Oklahoma, as it encountered dry, subsiding air underneath the stratiform precipitation region of the rear portion of the MCS farther south. There was a meridionally oriented swath of high winds in clear air, in between the two MCSs. This swath of high winds may have been associated with a bore triggered at night by the MCSs approaching from the north, as the MCS collapsed, producing a gust front that propagated through stable, low-level air. This case study illustrates how the predictability of severe weather in a region can be extremely sensitive to the details of where nearby convective storms form and how they evolve. It also highlights the likely importance of the accurate representation of cloud microphysics and dynamics in numerical forecast models on predictability.
Effect of Septoplasty With a Caudal Septal Batten Graft on Changes in Nasal Shape
Authors: Yi Jong Sook , Jang Yong Ju 
Published: October 2014

Objective: This study aimed to determine frequency of external nasal deformities in patients with deviated septa and the effect of endonasalseptoplasty with batten grafting on the external nasal appearance. Methods: The 52 patients who underwent endonasalseptoplasty with a batten graft for the correction of caudal septal deviations were included in the study. The preoperative and postoperative photographs of 52 patients were reviewed retrospectively. Gross changes (nasal deviation, dorsal middle vault height, tip height change, and nostril asymmetry) were assessed. Anthropometric measurements (dorsal height, nasal tip projection, nasolabial angle, nasofrontal angle, and deviation angle) were performed. Results: Preoperative assessment showed that 71% of the 52 patients had deformities, including nasal deviation (n = 28), hump nose (n = 19), saddle nose (n = 3), and nostril asymmetry (n = 15). On postoperative analysis, favorable changes in dorsal deviations were seen in 61% of patients. There were no aesthetic changes for hump or saddle nose deformities, whereas nostril asymmetry was corrected in 20% of patients. Anthropometric measurements also showed that dorsal deviation angles were corrected after surgery ( P < .05), whereas other parameters showed no significant changes. Conclusion: In selected cases, deviated noses can be corrected to some extent by septoplasty with caudal septal batten grafting.
Suicidal behavior during economic hard times
Authors: Elliott Marta , Naphan Dara E , Kohlenberg Barbara L 
Published: October 2014

Background: Most research on suicide is quantitative, and qualitative research is needed to reveal how individuals subjectively experience and account for suicidal behaviors. Aims: The aim of this study is to learn about the circumstances, motivations and consequences of suicidal behavior among individuals hospitalized for attempted suicide and suicidal ideation during the global economic recession. Methods: In-depth semi-structured interviews were conducted with in-patients hospitalized for suicidal behavior in a state-subsidized public mental hospital and analyzed with framework analysis. Results: Interpersonal conflict in the context of severe economic hardship and inadequate mental health care preceded suicidal behavior, rescue and a subsequent respite from desperate situations. Attempted suicide led to increased attention and concern from loved ones and immediate access to mental health care. Conclusions: Government-subsidized funding for outpatient mental health care should be sustained or increased during economic recessions to protect the most vulnerable from suicidal behavior when it is the only viable path toward immediate psychiatric treatment.
Late complication after repair of aortic coarctation
Authors: Lemaire Anaïs , Cuttone Fabio , Desgué Julien , Ivascau Calin , Caprio Sabino , Saplacan Vladimir , Belin Annette , Babatasi Gérard 
Published: October 2014

Background Coarctation of the aorta is a congenital malformation that has long been considered completely correctable with appropriate surgery in childhood. However, with the aging of these patients, many late complications have been reported, and this notion must be reevaluated. Methods We retrospectively reviewed all patients who underwent reoperation between 1992 and 2012 in our adult cardiac surgery department following surgical correction of coarctation in childhood; 18 patients over 15-years old were included in the study. Results The median time from coarctation repair to reoperation was 25 years. Patients were reoperated on for several late complications: aortic valve disease secondary to bicuspid aortic valve, ascending aortic aneurysm, recoarctation, aortic arch hypoplasia, pseudoaneurysm, associated recoarctation and pseudoaneurysm, subvalvular aortic obstruction, and descending thoracic aortic aneurysm. One patient died due to an intraoperative complication. In the other cases, the surgical results were satisfactory at the 6-month follow-up. According to literature data, age at coarctation repair and surgical technique appear to be essential factors in late complications: older age and surgical repair with prosthesis interposition are associated with a higher rate of reintervention. Conclusion Patients who have undergone repair of aortic coarctation frequently remain asymptomatic for a long time. Late complications can be appropriately treated when diagnosed early. Consequently, all coarctation patients need careful lifelong follow-up, especially those with congenital aortic valve disease or surgery in childhood with interposition of prosthetic material.
Coronary collateral circulation in patients with chronic coronary total occlusion; its relationship with cardiac risk markers and SYNTAX score
Authors: Börekçi A , Gür M , Şeker T , Baykan AO , Özaltun B , Karakoyun S , Karakurt A , Türkoğlu C , Makça İ , Çaylı M 
Published: October 2014

Background: Compared to patients without a collateral supply, long-term cardiac mortality is reduced in patients with well-developed coronary collateral circulation (CCC). Cardiovascular risk markers, such as N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive C-reactive protein (hs-CRP) and high-sensitive cardiac troponin T (hs-cTnT) are independent predictors for cardiovascular mortality. Objectives: The main goal of this study was to examine the relationship between CCC and cardiovascular risk markers. Methods: We prospectively enrolled 427 stable coronary artery disease patients with chronic total occlusion (mean age: 57.5±11.1 years). The patients were divided into two groups, according to their Rentrop scores: (a) poorly developed CCC group (Rentrop 0 and 1) and (b) well-developed CCC group (Rentrop 2 and 3). NT-proBNP, hs-CRP, hs-cTnT, uric acid and other biochemical markers were also measured. The SYNTAX score was calculated for all patients. Results: The patients in the poorly developed CCC group had higher frequencies of diabetes and hypertension (p<0.05 for both). Compared to the well-developed CCC group, the SYNTAX score, Hs-cTnT, hs-CRP, NT-proBNP, uric acid, neutrophil count and mean platelet volume (MPV) values were higher in patients with poorly developed CCC (p<0.05 for all). On multivariate logistic regression analysis, hs-cTnT (β=0.658, 95% CI=0.589-0.735, p<0.001) and NT-proBNP (β=0.991, 95% CI=0.987-0.995, p<0.001) as well as hs-CRP and diabetes were independent predictors of CCC. Conclusion: Cardiac risk markers, such as NT-proBNP, hs-cTnT and hs-CRP are independently associated with CCC in stable coronary artery disease with chronic total occlusion.
Arthroscopic suprascapular neurotomy for the painful irreparable rotator cuff tear
Authors: Kenyon Peter , Mclaughlin-Symon Iain , Heasley Richard , Morgan Barnes , Ravenscroft Matt 
Published: October 2014

Background Massive irreparable rotator cuff tears are becoming increasingly difficult to manage. Methods Patients were considered for treatment if they had a painful shoulder in the presence of a compensated cuff tear. All patients had radiological evidence of a massive irreparable cuff tear and underwent suprascapular neurotomy, arthroscopically. Results There were 15 males and 25 females with a mean age of 74 years (range 59 years to 88 years). The mean pre-operative Oxford Shoulder Score (OSS) in all patients was 17.7, with a mean pre-operative visual analogue score (VAS) of 8.0. The mean post-operative OSS was 30.8 [27.42–34.18 = confidence interval (CI) 95%] with a mean VAS of 3.6 (2.64–4.56 CI 95%) at the 3-month (short-term) period ( n = 32). The medium-term (1-year) OSS and VAS had improved to 33.6 (32.27–34.93 = CI 95%) and 3.7 (0–8.39 CI 95%) respectively ( n = 26). The difference pre- and postoperatively at 12 months was statistically significant ( p < 0.001). Patients who underwent biceps tenotomy at the time of surgery had a less significant improvement in their VAS and OSS. Conclusions Suprascapular neurotomy can afford medium-term benefit in over two-thirds of the patients who would otherwise have undergone reverse polarity shoulder replacements. We consider that this is a reproducible technique.