bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stoic beliefs and health: development and preliminary validation of the Pathak-Wieten Stoicism Ideology Scale
Authors: Pathak Elizabeth B , Wieten Sarah E , Wheldon Christopher W 
Published: November 2017

IntroductionWe developed and validated a new parsimonious scale to measure stoic beliefs. Key domains of stoicism are imperviousness to strong emotions, indifference to death, taciturnity and self-sufficiency. In the context of illness and disease, a personal ideology of stoicism may create an internal resistance to objective needs, which can lead to negative consequences. Stoicism has been linked to help-seeking delays, inadequate pain treatment, caregiver strain and suicide after economic stress.MethodsDuring 2013–2014, 390 adults aged 18+ years completed a brief anonymous paper questionnaire containing the preliminary 24-item Pathak-Wieten Stoicism Ideology Scale (PW-SIS). Confirmatory factor analysis (CFA) was used to test an a priori multidomain theoretical model. Content validity and response distributions were examined. Sociodemographic predictors of strong endorsement of stoicism were explored with logistic regression.ResultsThe final PW-SIS contains four conceptual domains and 12 items. CFA showed very good model fit: root mean square error of approximation (RMSEA)=0.05 (95% CI 0.04 to 0.07), goodness-of-fit index=0.96 and Tucker-Lewis Index=0.93. Cronbach’s alpha was 0.78 and ranged from 0.64 to 0.71 for the subscales. Content validity analysis showed a statistically significant trend, with respondents who reported trying to be a stoic ‘all of the time’ having the highest PW-SIS scores. Men were over two times as likely as women to fall into the top quartile of responses (OR=2.30, 95% CI 1.44 to 3.68, P<0.001). ORs showing stronger endorsement of stoicism by Hispanics, Blacks and biracial persons were not statistically significant.DiscussionThe PW-SIS is a valid and theoretically coherent scale which is brief and practical for integration into a wide range of health behaviour and outcomes research studies.
Incidence of shoulder dislocations in the UK, 1995–2015: a population-based cohort study
Authors: Shah Anjali , Judge Andrew , Delmestri Antonella , Edwards Katherine , Arden Nigel K , Prieto-Alhambra Daniel , Holt Tim A , Pinedo-Villanueva Rafael A , Hopewell Sally , Lamb Sarah E , Rangan Amar , Carr Andrew J , Collins Gary S , Rees Jonathan L 
Published: November 2017

ObjectiveThis cohort study evaluates the unknown age-specific and gender-specific incidence of primary shoulder dislocations in the UK.SettingUK primary care data from the Clinical Practice Research Datalink (CPRD) were used to identify patients aged 16–70 years with a shoulder dislocation during 1995–2015. Coding of primary shoulder dislocations was validated using the CPRD general practitioner questionnaire service.ParticipantsA cohort of 16 763 patients with shoulder dislocation aged 16–70 years during 1995–2015 were identified.Primary outcome measureIncidence rates per 100 000 person-years and 95% CIs were calculated.ResultsCorrect coding of shoulder dislocation within CPRD was 89% (95% CI 83% to 95%), and confirmation that the dislocation was a ‘primary’ was 76% (95% CI 67% to 85%). Seventy-two percent of shoulder dislocations occurred in men. The overall incidence rate in men was 40.4 per 100 000 person-years (95% CI 40.4 to 40.4), and in women was 15.5 per 100 000 person-years (95% CI 15.5 to 15.5). The highest incidence was observed in men aged 16–20 years (80.5 per 100 000 person-years; 95% CI 80.5 to 80.6). Incidence in women increased with age to a peak of 28.6 per 100 000 person-years among those aged 61–70 years.ConclusionsThis is the first time the incidence of shoulder dislocations has been studied using primary care data from a national database, and the first time the results for the UK have been produced. While most primary dislocations occurred in young men, an unexpected finding was that the incidence increased in women aged over 50 years, but not in men. The reasons for this are unknown. Further work is commissioned by the National Institute for Health Research to examine treatments and predictors for recurrent shoulder dislocation.Study registrationThe design of this study was approved by the Independent Scientific Advisory Committee (15_260) for the Medicines & Healthcare products Regulatory Agency.
Norwegian trends in numbers of lower extremity revascularisations and amputations including regional trends in endovascular treatments for peripheral arterial disease: a retrospective cross-sectional registry study from 2001 to 2014
Authors: Wendt Kjersti , Kristiansen Ronny , Krohg-Sørensen Kirsten , Gregersen Fredrik Alexander , Fosse Erik 
Published: November 2017

ObjectiveThe numbers of lower extremity revascularisations and amputations are insufficiently reported in Norway. To support future policy decisions regarding the provision of vascular treatment, knowledge of such trends is important.MethodsThis retrospective cross-sectional study from 2001 to 2014 used data from the Norwegian Patient Registry. The revascularisation treatments were categorised in multilevel, aortoiliac, femoral to popliteal and popliteal to foot levels and sorted as open, endovascular and hybrid. The sessions in amputations were divided in major (thigh and below knee) and minor (ankle, foot or digit). Incidence rates were assessed per 100 000 for patients in the age group>60 years. The diabetic prevalence was calculated and the endovascular numbers at the South-Eastern, Western, Central and Northern Norway Regional Health Authority were compared.ResultsThe overall revascularisation rates increased from 308.7 to 366.8 (p=0.02). Open revascularisations decreased from 158.9 to 98.7 (p<0.01) while endovascular revascularisations increased from 142.2 to 243.4 (p<0.01). Hybrid revascularisations increased from 7.4 to 24.8 (p<0.01). Major amputation rates decreased from 87.8 to 48.7 (p<0.01) while minor amputations increased from 12.3 to 19.6 (p=0.01). The diabetic percentages increased from 12.2 to 22.3 (p<0.01) in revascularisations, from 26.5 to 30.8 (p=0.02) in major amputations and from 43.0 to 49.3 (p=0.13) in minor. (p values refer to average annual changes.) The regional trends in endovascular treatments varied within and between the vascular groups.ConclusionFrom 2001 to 2014, the revascularisation rates increased due to the rise in endovascular procedures. Open revascularisations and major amputation rates decreased, minor increased. The regional variances in endovascular treatments indicate that the availability of this technology differed between the health regions of Norway. The increase in patients with diabetes requires continued awareness of diabetes and its complications.
Development of a discussion tool to enable well-being by providing choices for people with dementia: a qualitative study incorporating codesign and participatory action research
Authors: Goeman Dianne Patricia , Dickins Marissa , Iliffe Steve , Pond Dimity , O’Keefe Fleur 
Published: November 2017

ObjectiveTo codesign a discussion tool to facilitate negotiation of risk between health professionals, people with dementia and carers.MethodsA qualitative approach using codesign. Thematic analysis was used to analyse interviews and focus groups with people with dementia, carers, healthcare staff and healthy older people exploring the issue of risk in dementia, the acceptability and development of a discussion tool.ResultsSixty-one participants identified the breadth, depth and complexity of risk in dementia care and the need for individualised solutions. They also deemed a discussion tool to facilitate negotiation of risk was acceptable and responses informed the tool development. Twenty-two participants provided feedback that was used to refine the final version.ConclusionOur discussion tool enables choices for people with dementia by focusing on abilities rather than deficits and assists health professionals to deliver person-centred care. Flash cards prompt concerns and the tool provides a range of strategies to address these issues.
A Transactional Correctness Tool for Abstract Data Types
Authors: Peterson Christina , Dechev Damian 
Published: November 2017

Transactional memory simplifies multiprocessor programming by providing the guarantee that a sequential block of code in the form of a transaction will exhibit atomicity and isolation. Transactional data structures offer the same guarantee to concurrent data structures by enabling the atomic execution of a composition of operations. The concurrency control of transactional memory systems preserves atomicity and isolation by detecting read/write conflicts among multiple concurrent transactions. State-of-the-art transactional data structures improve on this concurrency control protocol by providing explicit transaction-level synchronization for only non-commutative operations. Since read/write conflicts are handled by thread-level concurrency control, the correctness of transactional data structures cannot be evaluated according to the read/write histories. This presents a challenge for existing correctness verification techniques for transactional memory, because correctness is determined according to the transitions taken by the transactions in the presence of read/write conflicts.
In this article, we present Transactional Correctness tool for Abstract Data Types (TxC-ADT), the first tool that can check the correctness of transactional data structures. TxC-ADT elevates the standard definitions of transactional correctness to be in terms of an abstract data type, an essential aspect for checking correctness of transactions that synchronize only for high-level semantic conflicts. To accommodate a diverse assortment of transactional correctness conditions, we present a technique for defining correctness as a happens-before relation. Defining a correctness condition in this manner enables an automated approach in which correctness is evaluated by generating and analyzing a transactional happens-before graph during model checking. A transactional happens-before graph is maintained on a per-thread basis, making our approach applicable to transactional correctness conditions that do not enforce a total order on a transactional execution. We demonstrate the practical applications of TxC-ADT by checking Lock Free Transactional Transformation and Transactional Data Structure Libraries for serializability, strict serializability, opacity, and causal consistency.
Targeting the MYCN–PARP–DNA Damage Response Pathway in Neuroendocrine Prostate Cancer
Authors: Zhang Wei , Liu Bo , Wu Wenhui , Li Likun , Broom Bradley M. , Basourakos Spyridon P. , Korentzelos Dimitrios , Luan Yang , Wang Jianxiang , Yang Guang , Park Sanghee , Azad Abul Kalam , Cao Xuhong , Kim Jeri , Corn Paul G. , Logothetis Christopher J. , Aparicio Ana M. , Chinnaiyan Arul M. , Navone Nora , Troncoso Patricia , Thompson Timothy C. 
Published: November 2017

Abstract
Purpose: We investigated MYCN-regulated molecular pathways in castration-resistant prostate cancer (CRPC) classified by morphologic criteria as adenocarcinoma or neuroendocrine to extend the molecular phenotype, establish driver pathways, and identify novel approaches to combination therapy for neuroendocrine prostate cancer (NEPC).
Experimental Design and Results: Using comparative bioinformatics analyses of CRPC-Adeno and CRPC-Neuro RNA sequence data from public data sets and a panel of 28 PDX models, we identified a MYCN–PARP–DNA damage response (DDR) pathway that is enriched in CRPC with neuroendocrine differentiation (NED) and CRPC-Neuro. ChIP-PCR assay revealed that N-MYC transcriptionally activates PARP1, PARP2, BRCA1, RMI2, and TOPBP1 through binding to the promoters of these genes. MYCN or PARP1 gene knockdown significantly reduced the expression of MYCN–PARP–DDR pathway genes and NED markers, and inhibition with MYCNsi and/or PARPsi, BRCA1si, or RMI2si significantly suppressed malignant activities, including cell viability, colony formation, and cell migration, in C4-2b4 and NCI-H660 cells. Targeting this pathway with AURKA inhibitor PHA739358 and PARP inhibitor olaparib generated therapeutic effects similar to those of gene knockdown in vitro and significantly suppressed tumor growth in both C4-2b4 and MDACC PDX144-13C subcutaneous models in vivo.
Conclusions: Our results identify a novel MYCN–PARP–DDR pathway that is driven by N-MYC in a subset of CRPC-Adeno and in NEPC. Targeting this pathway using in vitro and in vivo CRPC-Adeno and CRPC-Neuro models demonstrated a novel therapeutic strategy for NEPC. Further investigation of N-MYC–regulated DDR gene targets and the biological and clinical significance of MYCN–PARP–DDR signaling will more fully elucidate the importance of the MYCN–PARP–DDR signaling pathway in the development and maintenance of NEPC. Clin Cancer Res; 24(3); 696–707. ©2017 AACR.
Ceritinib Enhances the Efficacy of Trametinib inBRAF/NRAS-Wild-Type Melanoma Cell Lines
Authors: Verduzco Daniel , Kuenzi Brent M. , Kinose Fumi , Sondak Vernon K. , Eroglu Zeynep , Rix Uwe , Smalley Keiran S.M. 
Published: November 2017

AbstractTargeted therapy options are currently lacking for the heterogeneous population of patients whose melanomas lack BRAF or NRAS mutations (∼35% of cases). We undertook a chemical biology screen to identify potential novel drug targets for this understudied group of tumors. Screening a panel of 8 BRAF/NRAS-WT melanoma cell lines against 240 targeted drugs identified ceritinib and trametinib as potential hits with single-agent activity. Ceritinib enhanced the efficacy of trametinib across the majority of the BRAF/NRAS-WT cell lines, and the combination showed increased cytotoxicity in both three-dimensional spheroid culture and long-term colony formation experiments. Coadministration of ceritinib and trametinib led to robust inhibition of tumor growth in an in vivo xenograft BRAF/NRAS-WT melanoma model; this was not due to ALK inhibition by ceritinib. Mechanistic studies showed the ceritinib–trametinib combination to increase suppression of MAPK and TORC1 signaling. Similar results were seen when BRAF/NRAS-WT melanoma cells were treated with a combination of trametinib and the TORC1/2 inhibitor INK128. We next used mass spectrometry–based chemical proteomics and identified known and new ceritinib targets, such as IGF1R and ACK1, respectively. Validation studies suggested that ceritinib could suppress mTORC1 signaling in the presence of trametinib through inhibition of IGF1R and/or ACK1 in a cell line–dependent manner. Together, our studies demonstrated that combining a specific inhibitor (trametinib) with a more broadly targeted agent (ceritinib) has efficacy against tumors with heterogeneous mutational profiles. Mol Cancer Ther; 17(1); 73–83. ©2017 AACR.
Response and Resistance to Paradox-Breaking BRAF Inhibitor in Melanomas In Vivo and Ex Vivo
Authors: Hartsough Edward J. , Kugel Curtis H. , Vido Michael J. , Berger Adam C. , Purwin Timothy J. , Goldberg Allison , Davies Michael A. , Schiewer Matthew J. , Knudsen Karen E. , Bollag Gideon , Aplin Andrew E. 
Published: November 2017

Abstract
FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K–mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox-breaking RAF inhibitor (PLX8394) has been designed. Here, we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts. Ex vivo treatment of xenografts and use of a patient-derived explant system (PDeX) revealed that PLX8394 suppressed ERK1/2 signaling and elicited apoptosis more effectively than the FDA-approved BRAF inhibitor, vemurafenib. Furthermore, PLX8394 was efficacious against vemurafenib-resistant BRAF splice variant–expressing tumors and reduced splice variant homodimerization. Importantly, PLX8394 did not induce paradoxical activation of ERK1/2 in wild-type BRAF cell lines or PDeX. Continued in vivo dosing of xenografts with PLX8394 led to the development of acquired resistance via ERK1/2 reactivation through heterogeneous mechanisms; however, resistant cells were found to have differential sensitivity to ERK1/2 inhibitor. These findings highlight the efficacy of a paradox-breaking selective BRAF inhibitor and the use of PDeX system to test the efficacy of therapeutic agents. Mol Cancer Ther; 17(1); 84–95. ©2017 AACR.
Chemokine Signaling Facilitates Early-Stage Breast Cancer Survival and Invasion through Fibroblast-Dependent Mechanisms
Authors: Brummer Gage , Acevedo Diana S. , Hu Qingting , Portsche Mike , Fang Wei Bin , Yao Min , Zinda Brandon , Myers Megan , Alvarez Nehemiah , Fields Patrick , Hong Yan , Behbod Fariba , Cheng Nikki 
Published: November 2017

Abstract
Ductal carcinoma in situ (DCIS) is the most common form of breast cancer, with 50,000 cases diagnosed every year in the United States. Overtreatment and undertreatment remain significant clinical challenges in patient care. Identifying key mechanisms associated with DCIS progression could uncover new biomarkers to better predict patient prognosis and improve guided treatment. Chemokines are small soluble molecules that regulate cellular homing through molecular gradients. CCL2-mediated recruitment of CCR2+ macrophages are a well-established mechanism for metastatic progression. Although the CCL2/CCR2 pathway is a therapeutic target of interest, little is known about the role of CCR2 expression in breast cancer. Here, using a mammary intraductal injection (MIND) model to mimic DCIS formation, the role of CCR2 was explored in minimally invasive SUM225 and highly invasive DCIS.com breast cancer cells. CCR2 overexpression increased SUM225 breast cancer survival and invasion associated with accumulation of CCL2 expressing fibroblasts. CCR2-deficient DCIS.com breast cancer cells formed fewer invasive lesions with fewer CCL2+ fibroblasts. Cografting CCL2-deficient fibroblasts with DCIS.com breast cancer cells in the subrenal capsule model inhibited tumor invasion and survival associated with decreased expression of aldehyde dehydrogenase (ALDH1), a proinvasive factor, and decreased expression of HTRA2, a proapoptotic serine protease. Through data mining analysis, high expression of CCR2 and ALDH1 and low HTRA2 expression were correlated with poor prognosis of breast cancer patients.
Implications: This study demonstrates that CCR2 overexpression in breast cancer drives early-stage breast cancer progression through stromal-dependent expression of CCL2 with important insight into prognosis and treatment of DCIS. Mol Cancer Res; 16(2); 296–308. ©2017 AACR.
Genotoxic Damage Activates the AMPK-α1 Isoform in the Nucleus via Ca2+/CaMKK2 Signaling to Enhance Tumor Cell Survival
Authors: Vara-Ciruelos Diana , Dandapani Madhumita , Gray Alexander , Egbani Ejaife O. , Evans A. Mark , Hardie D. Grahame 
Published: November 2017

AbstractMany genotoxic cancer treatments activate AMP-activated protein kinase (AMPK), but the mechanisms of AMPK activation in response to DNA damage, and its downstream consequences, have been unclear. In this study, etoposide activates the α1 but not the α2 isoform of AMPK, primarily within the nucleus. AMPK activation is independent of ataxia-telangiectasia mutated (ATM), a DNA damage-activated kinase, and the principal upstream kinase for AMPK, LKB1, but correlates with increased nuclear Ca2+ and requires the Ca2+/calmodulin-dependent kinase, CaMKK2. Intriguingly, Ca2+-dependent activation of AMPK in two different LKB1-null cancer cell lines caused G1-phase cell-cycle arrest, and enhanced cell viability/survival after etoposide treatment, with both effects being abolished by knockout of AMPK-α1 and α2. The CDK4/6 inhibitor palbociclib also caused G1 arrest in G361 but not HeLa cells and, consistent with this, enhanced cell survival after etoposide treatment only in G361 cells. These results suggest that AMPK activation protects cells against etoposide by limiting entry into S-phase, where cells would be more vulnerable to genotoxic stress.Implications: These results reveal that the α1 isoform of AMPK promotes tumorigenesis by protecting cells against genotoxic stress, which may explain findings that the gene encoding AMPK-α1 (but not -α2) is amplified in some human cancers. Furthermore, α1-selective inhibitors might enhance the anticancer effects of genotoxic-based therapies. Mol Cancer Res; 16(2); 345–57. ©2017 AACR.
Precision Oncology beyond Targeted Therapy: Combining Omics Data with Machine Learning Matches the Majority of Cancer Cells to Effective Therapeutics
Authors: Ding Michael Q. , Chen Lujia , Cooper Gregory F. , Young Jonathan D. , Lu Xinghua 
Published: November 2017

Abstract
Precision oncology involves identifying drugs that will effectively treat a tumor and then prescribing an optimal clinical treatment regimen. However, most first-line chemotherapy drugs do not have biomarkers to guide their application. For molecularly targeted drugs, using the genomic status of a drug target as a therapeutic indicator has limitations. In this study, machine learning methods (e.g., deep learning) were used to identify informative features from genome-scale omics data and to train classifiers for predicting the effectiveness of drugs in cancer cell lines. The methodology introduced here can accurately predict the efficacy of drugs, regardless of whether they are molecularly targeted or nonspecific chemotherapy drugs. This approach, on a per-drug basis, can identify sensitive cancer cells with an average sensitivity of 0.82 and specificity of 0.82; on a per-cell line basis, it can identify effective drugs with an average sensitivity of 0.80 and specificity of 0.82. This report describes a data-driven precision medicine approach that is not only generalizable but also optimizes therapeutic efficacy. The framework detailed herein, when successfully translated to clinical environments, could significantly broaden the scope of precision oncology beyond targeted therapies, benefiting an expanded proportion of cancer patients. Mol Cancer Res; 16(2); 269–78. ©2017 AACR.
One-to-One Correspondence Locations of Resected Polyps after Endoscopic Resection Using Catcher Tagged Method: A Randomized Prospective Study
Authors: Mori Hirohito , Kobara Hideki , Kobayashi Nobuya  , Nishiyama Noriko , Kobayashi Seiki , Yagi Takaharu , Masaki Tsutomu 
Published: November 2017

<b><i>Background/Aims:</i></b> Multiple colorectal polyps with a diameter in the range of 10–19 mm are unable to be retrieved through a 3-mm endoscopic channel by the aspiration method. This study aims to assess the usefulness of Catcher Tag retrieval, which not only allows the accurate identification of the resected location but also enables the easiest retrieval in a short time without any special device. <b><i>Methods:</i></b> One hundred thirty five patients (483 polyps) were diagnosed with colorectal neoplasm, and 64 patients (225 polyps) were enrolled and randomly allocated into the Net forceps group (NET) and the Catcher Tagged group (TAG). In TAG, 3 types of colored ring-threads were used to retrieve resected polyps. After local injection of natural saline, ring-threads were placed close to polyps. The primary outcome was the number of one-to-one correspondence locations (UMIN000020826). <b><i>Results:</i></b> There was significant difference in one-to-one correspondence (<i>p =</i> 0.004). The average retrieval procedure time was 13.56 ± 3.47 (min) in NET and 3.55 ± 1.68 in TAG (<i>p</i> = 0.006). In NET, 1 polyp in each of 4 cases was lost during endoscopic mucosal resection and 2 polyps were lost in 1 case. In TAG, no polyp was lost (<i>p</i> = 0.016). <b><i>Conclusion:</i></b> The Catcher Tagged method is very useful for accurate one-to-one correspondence locations and pathological evaluation, and easy-to-retrieve multiple resected specimens.