bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of ACE gene D polymorphism with left ventricular hypertrophy in patients with diastolic heart failure: a case–control study
Authors: Bahramali Ehsan , Rajabi Mona , Jamshidi Javad , Mousavi Seyyed Mohammad , Zarghami Mehrdad , Manafi Alireza , Firouzabadi Negar 
Published: February 2016

ObjectivesTo explore the association between ACE gene insertion/deletion (I/D) polymorphism with left ventricular hypertrophy (LVH) in patients with hypertension who have developed heart failure with preserved ejection fraction (HFpEF). Being a major contributor to the development of diastolic heart dysfunction, the renin angiotensin aldosterone system and its genetic variations are thought to induce LVH in hypertensive hearts apart from haemodynamic factors.DesignCase control study.SettingAn Iranian referral university hospital.Participants176 patients with hypertension and a diagnosis of HFpEF on presence of symptoms of heart failure plus Doppler echocardiographic documentation of left ventricular (LV) diastolic dysfunction and/or elevated NT-proBNP levels. Those with significant coronary, valvular, pericardial and structural heart diseases were excluded as well as patients with atrial fibrillation, renal failure and pulmonary causes of dyspnoea. They were divided into two cohorts of 88 cases with and 88 controls without LVH, after determination of LV mass index, using two-dimensional and M-mode echocardiography. The I/D polymorphism of theACEgene was determined using the PCR method.ResultsThe D allele was significantly more prevalent among cases with compared with controls without LVH (p=0.0007). Genotype distributions also differed significantly under additive (p=0.005, OR=0.53, 95% CI 0.34 to 0.84) and recessive (p=0.001, OR=0.29, 95% CI 0.13 to 0.66) models.ConclusionsIn patients with hypertension who develop HFpEF, the D allele of theACEgene is probably associated with the development of LVH. With the detrimental effects of LVH on the heart's diastolic properties, this can signify the role of genetic contributors to the development of HFpEF in patients with hypertension and may serve as a future risk predictor for the disease.
Utilisation of helicopter emergency medical services in the early medical response to major incidents: a systematic literature review
Authors: Johnsen Anne Siri , Fattah Sabina , Sollid Stephen J M , Rehn Marius 
Published: February 2016

ObjectiveThis systematic review identifies, describes and appraises the literature describing the utilisation of helicopter emergency medical services (HEMS) in the early medical response to major incidents.SettingEarly prehospital phase of a major incident.DesignSystematic literature review performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Web of Science, PsycINFO, Scopus, Cinahl, Bibsys Ask, Norart, Svemed and UpToDate were searched using phrases that combined HEMS and ‘major incidents’ to identify when and how HEMS was utilised. The identified studies were subjected to data extraction and appraisal.ResultsThe database search identified 4948 articles. Based on the title and abstract, the full text of 96 articles was obtained; of these, 37 articles were included in the review, and an additional five were identified by searching the reference lists of the 37 articles. HEMS was used to transport medical and rescue personnel to the incident and to transport patients to the hospital, especially when the infrastructure was damaged. Insufficient air traffic control, weather conditions, inadequate landing sites and failing communication were described as challenging in some incidents.ConclusionsHEMS was used mainly for patient treatment and to transport patients, personnel and equipment in the early medical management of major incidents, but the optimal utilisation of this specialised resource remains unclear. This review identified operational areas with improvement potential. A lack of systematic indexing, heterogeneous data reporting and weak methodological design, complicated the identification and comparison of incidents, and more systematic reporting is needed.Trial registration numberCRD42013004473.
Drinking patterns of adolescents who develop alcohol use disorders: results from the Victorian Adolescent Health Cohort Study
Authors: Olsson Craig A , Romaniuk Helena , Salinger Jodi , Staiger Petra K , Bonomo Yvonne , Hulbert Carol , Patton George C 
Published: February 2016

ObjectiveWe identify drinking styles that place teens at greatest risk of later alcohol use disorders (AUD).DesignPopulation-based cohort study.SettingVictoria, Australia.ParticipantsA representative sample of 1943 adolescents living in Victoria in 1992.Outcome measuresTeen drinking was assessed at 6 monthly intervals (5 waves) between mean ages 14.9 and 17.4 years and summarised across waves as none, one, or two or more waves of: (1)frequent drinking(3+ days in the past week), (2)loss of control over drinking(difficulty stopping, amnesia), (3)binge drinking(5+ standard drinks in a day) and (4)heavy binge drinking(20+ and 11+ standard drinks in a day for males and females, respectively). Young Adult Alcohol Use Disorder (AUD) was assessed at 3 yearly intervals (3 waves) across the 20s (mean ages 20.7 through 29.1 years).ResultsWe show that patterns of teen drinking characterised by loss of control increase risk for AUD across young adulthood:loss of control over drinking(one wave OR 1.4, 95% CI 1.1 to 1.8; two or more waves OR 1.9, CI 1.4 to 2.7);binge drinking(one wave OR 1.7, CI 1.3 to 2.3; two or more waves OR 2.0, CI 1.5 to 2.6), andheavy binge drinking(one wave OR 2.0, CI 1.4 to 2.8; two or more waves OR 2.3, CI 1.6 to 3.4). This is not so for frequent drinking, which was unrelated to later AUD. Although drinking was more common in males, there was no evidence of sex differences in risk relationships.ConclusionsOur results extend previous work by showing that patterns of drinking that represent loss of control over alcohol consumption (however expressed) are important targets for intervention. In addition to current policies that may reduce overall consumption, emphasising prevention of more extreme teenage bouts of alcohol consumption appears warranted.
Cutaneous Human Papillomaviruses and Squamous Cell Carcinoma of the Skin: Nested Case–Control Study
Authors: Faust Helena , Andersson Kristin , Luostarinen Tapio , Gislefoss Randi E. , Dillner Joakim 
Published: February 2016

Abstract
Background: Cutaneous human papillomavirus (HPV) types have been associated with non-melanoma skin cancer (NMSC), including a previous nested case–control study using HPV serology with bacterially derived fusion proteins with the major HPV capsid protein L1 (GST-L1). However, HPV serology using conformationally intact pseudovirions has been shown to correlate better with natural infection. Prospective studies using a more valid marker of infection are therefore warranted.
Methods: Cancer registry follow-up of large Nordic biobanks identified prediagnostic serum samples from 633 subjects who later developed SCC, 1,990 subjects who developed basal cell carcinoma (BCC). The samples from cases and matched controls were tested for IgG to pseudovirions to 16 different HPV types (3, 5, 6, 11, 15, 16, 18, 31, 32, 33, 38, 45, 52, 58, 68, and 76) and two polyomaviruses (MCPyV and JCPyV).
Results: Baseline seropositivity was not associated with SCC risk, and there were only weak associations with BCC risk [HPV-5 (OR, 1.1; 95% confidence interval [CI], 1.0–1.3), HPV-15 (OR, 1.2; 95% CI, 1.0–1.4), HPV-38 (OR, 1.2; 95% CI, 1.0–1.3), and MCPyV (OR, 1.1; 95% CI, 1.0–1.3)]. Acquisition of HPV-5 seropositivity during follow-up was associated with SCC risk (OR, 3.2; 95% CI, 1.3–7.6). Persistent seropositivity for HPV-15 was weakly associated with BCC (OR, 1.4; 95% CI, 1.0–1.9) and HPV-6 antibody persistence was weakly associated with SCC (OR, 2.2; 95% CI, 1.0–4.8).
Conclusion: Considering the large number of viruses tested, the weak associations found do not support any strong links between studied HPV and NMSC, with the possible exception of HPV-5 seroconversion and SCC.
Impact: Known alpha and beta papillomaviruses do not appear to be risk factors for NMSC. Cancer Epidemiol Biomarkers Prev; 25(4); 721–4. ©2016 AACR.
Reduced Expression of SMAD4 Is Associated with Poor Survival in Colon Cancer
Authors: Yan Pu , Klingbiel Dirk , Saridaki Zenia , Ceppa Paola , Curto Monica , McKee Thomas Alexander , Roth Arnaud , Tejpar Sabine , Delorenzi Mauro , Bosman Fredrik T. , Fiocca Roberto 
Published: February 2016

Abstract
Purpose: SMAD4 loss is associated with the development of metastases and poor prognosis. We evaluated expression of SMAD4 protein and its association with tumor characteristics, including biomarkers and outcome in terms of relapse-free survival and overall survival.
Experimental design: We used 1,564 stage II/III colon cancer samples from PETACC-3 to evaluate SMAD4 expression by immunohistochemistry. SMAD4 protein expression was validated by assessing mRNA expression using available expression array data. SMAD4 expression was also studied on 34 adenomas and 10 colon cancer liver metastases with their primaries. Loss of SMAD4 immunoreactivity was defined as focal or diffuse. Cases without SMAD4 loss were subdivided into those with strong and weak expression.
Results: SMAD4 protein expression was informative in 1,381/1,564 cases. SMAD4 loss was found in 293/1,381 (21%) cases. Of 1,088 cases without SMAD4 loss (79%), 530 showed weak and 558 strong expression. SMAD4 loss occurred also in adenomas, but less extensively than in carcinomas. Liver metastases followed mostly the expression pattern of the primary tumor. SMAD4 loss, including weak expression, identified patients with poor survival in stage II as well as III and in both treatment arms. SMAD4 loss was less frequent in tumors with microsatellite instability and more frequent in those with loss of heterozygosity of 18q.
Conclusions: We conclude that clonal loss of SMAD4 expression in adenomas, carcinomas, and liver metastases increases with disease progression. SMAD4 loss, and to a lesser extent weak expression, is strongly associated with poor survival regardless of stage. Clin Cancer Res; 22(12); 3037–47. ©2016 AACR.
Bortezomib Inhibits Giant Cell Tumor of Bone through Induction of Cell Apoptosis and Inhibition of Osteoclast Recruitment, Giant Cell Formation, and Bone Resorption
Authors: Xu Leqin , Luo Jian , Jin Rongrong , Yue Zhiying , Sun Peng , Yang Zhengfeng , Yang Xinghai , Wan Wei , Zhang Jishen , Li Shichang , Liu Mingyao , Xiao Jianru 
Published: February 2016

Abstract
Giant cell tumor of bone (GCTB) is a rare and highly osteolytic bone tumor that usually leads to an extensive bone lesion. The purpose of this study was to discover novel therapeutic targets and identify potential agents for treating GCTB. After screening the serum cytokine profiles in 52 GCTB patients and 10 normal individuals using the ELISA assay, we found that NF-κB signaling–related cytokines, including TNFα, MCP-1, IL1α, and IL17A, were significantly increased in GCTB patients. The results were confirmed by IHC that the expression and activity of p65 were significantly increased in GCTB patients. Moreover, all of the NF-κB inhibitors tested suppressed GCTB cell growth, and bortezomib (Velcade), a well-known proteasome inhibitor, was the most potent inhibitor in blocking GCTB cells growth. Our results showed that bortezomib not only induced GCTB neoplastic stromal cell (NSC) apoptosis, but also suppressed GCTB NSC–induced giant cell differentiation, formation, and resorption. Moreover, bortezomib specifically suppressed GCTB NSC–induced preosteoclast recruitment. Furthermore, bortezomib ameliorated GCTB cell–induced bone destruction in vivo. As a result, bortezomib suppressed NF-κB–regulated gene expression in GCTB NSC apoptosis, monocyte migration, angiogenesis, and osteoclastogenesis. Particularly, the inhibitory effects of bortezomib were much better than zoledronic acid, a drug currently used in treating GCTB, in our in vitro experimental paradigms. Together, our results demonstrated that NF-κB signaling pathway is highly activated in GCTB, and bortezomib could suppress GCTB and osteolysis in vivo and in vitro, indicating that bortezomib is a potential agent in the treatment of GCTB. Mol Cancer Ther; 15(5); 854–65. ©2016 AACR.
Mammary Adipose Tissue-Derived Lysophospholipids Promote Estrogen Receptor–Negative Mammary Epithelial Cell Proliferation
Authors: Volden Paul A. , Skor Maxwell N. , Johnson Marianna B. , Singh Puneet , Patel Feenalie N. , McClintock Martha K. , Brady Matthew J. , Conzen Suzanne D. 
Published: February 2016

Abstract
Lysophosphatidic acid (LPA), acting in an autocrine or paracrine fashion through G protein–coupled receptors, has been implicated in many physiologic and pathologic processes, including cancer. LPA is converted from lysophosphatidylcholine (LPC) by the secreted phospholipase autotaxin (ATX). Although various cell types can produce ATX, adipocyte-derived ATX is believed to be the major source of circulating ATX and also to be the major regulator of plasma LPA levels. In addition to ATX, adipocytes secrete numerous other factors (adipokines); although several adipokines have been implicated in breast cancer biology, the contribution of mammary adipose tissue–derived LPC/ATX/LPA (LPA axis) signaling to breast cancer is poorly understood. Using murine mammary fat-conditioned medium, we investigated the contribution of LPA signaling to mammary epithelial cancer cell biology and identified LPA signaling as a significant contributor to the oncogenic effects of the mammary adipose tissue secretome. To interrogate the role of mammary fat in the LPA axis during breast cancer progression, we exposed mammary adipose tissue to secreted factors from estrogen receptor–negative mammary epithelial cell lines and monitored changes in the mammary fat pad LPA axis. Our data indicate that bidirectional interactions between mammary cancer cells and mammary adipocytes alter the local LPA axis and increase ATX expression in the mammary fat pad during breast cancer progression. Thus, the LPC/ATX/LPA axis may be a useful target for prevention in patients at risk of ER-negative breast cancer. Cancer Prev Res; 9(5); 367–78. ©2016 AACR.
Whole-Genome Sequencing of Salivary Gland Adenoid Cystic Carcinoma
Authors: Rettig Eleni M. , Talbot C. Conover , Sausen Mark , Jones Sian , Bishop Justin A. , Wood Laura D. , Tokheim Collin , Niknafs Noushin , Karchin Rachel , Fertig Elana J. , Wheelan Sarah J. , Marchionni Luigi , Considine Michael , Ling Shizhang , Fakhry Carole , Papadopoulos Nickolas , Kinzler Kenneth W. , Vogelstein Bert , Ha Patrick K. , Agrawal Nishant 
Published: February 2016

Abstract
Adenoid cystic carcinomas (ACC) of the salivary glands are challenging to understand, treat, and cure. To better understand the genetic alterations underlying the pathogenesis of these tumors, we performed comprehensive genome analyses of 25 fresh-frozen tumors, including whole-genome sequencing and expression and pathway analyses. In addition to the well-described MYB–NFIB fusion that was found in 11 tumors (44%), we observed five different rearrangements involving the NFIB transcription factor gene in seven tumors (28%). Taken together, NFIB translocations occurred in 15 of 25 samples (60%, 95% CI, 41%–77%). In addition, mRNA expression analysis of 17 tumors revealed overexpression of NFIB in ACC tumors compared with normal tissues (P = 0.002). There was no difference in NFIB mRNA expression in tumors with NFIB fusions compared with those without. We also report somatic mutations of genes involved in the axonal guidance and Rho family signaling pathways. Finally, we confirm previously described alterations in genes related to chromatin regulation and Notch signaling. Our findings suggest a separate role for NFIB in ACC oncogenesis and highlight important signaling pathways for future functional characterization and potential therapeutic targeting. Cancer Prev Res; 9(4); 265–74. ©2016 AACR.
Asthma Associates With Human Abdominal Aortic Aneurysm and Rupture
Authors: Liu Cong-Lin , Wemmelund Holger , Wang Yi , Liao Mengyang , Lindholt Jes S. , Johnsen Søren P. , Vestergaard Henrik , Fernandes Cleverson , Sukhova Galina K. , Cheng Xiang , Zhang Jin-Ying , Yang Chongzhe , Huang Xiaozhu , Daugherty Alan , Levy Bruce D. , Libby Peter , Shi Guo-Ping 
Published: February 2016

Objective—
Both asthma and abdominal aortic aneurysms (AAA) involve inflammation. It remains unknown whether these diseases interact.

Approach and Results—
Databases analyzed included Danish National Registry of Patients, a population-based nationwide case–control study included all patients with ruptured AAA and age- and sex-matched AAA controls without rupture in Denmark from 1996 to 2012; Viborg vascular trial, subgroup study of participants from the population-based randomized Viborg vascular screening trial. Patients with asthma were categorized by hospital diagnosis, bronchodilator use, and the recorded use of other anti-asthma prescription medications. Logistic regression models were fitted to determine whether asthma associated with the risk of ruptured AAA in Danish National Registry of Patients and an independent risk of having an AAA at screening in the Viborg vascular trial. From the Danish National Registry of Patients study, asthma diagnosed <1 year or 6 months before the index date increased the risk of AAA rupture before (odds ratio [OR]=1.60–2.12) and after (OR=1.51–2.06) adjusting for AAA comorbidities. Use of bronchodilators elevated the risk of AAA rupture from ever use to within 90 days from the index date, before (OR=1.10–1.37) and after (OR=1.10–1.31) adjustment. Patients prescribed anti-asthma drugs also showed an increased risk of rupture before (OR=1.12–1.79) and after (OR=1.09–1.48) the same adjustment. In Viborg vascular trial, anti-asthmatic medication use associated with increased risk of AAA before (OR=1.45) or after adjustment for smoking (OR=1.45) or other risk factors (OR=1.46).

Conclusions—
Recent active asthma increased risk of AAA and ruptured AAA. These findings document and furnish novel links between airway disease and AAA, 2 common diseases that share inflammatory aspects.
Transthoracic Echocardiography Provides Important Long-Term Prognostic Information in Selected Patients Undergoing Endovascular Abdominal Aortic Repair
Authors: O’Driscoll Jamie M. , Bahia Sandeep S. , Gravina Angela , Di Fino Sara , Thompson Matthew M. , Karthikesalingam Alan , Holt Peter J.E. , Sharma Rajan 
Published: February 2016

Background—
The value of performing transthoracic echocardiography (TTE) as part of the clinical assessment of patients awaiting endovascular repair of the abdominal aorta is little evaluated. We aimed to estimate the prognostic importance of information derived from TTE on long-term all-cause mortality in a selected group of patients undergoing endovascular aneurysm repair.

Methods and Results—
This was a retrospective cohort study of 273 consecutive patients selected for endovascular aneurysm repair. All patients included in the analysis underwent TTE before their procedure. Multivariable Cox regression analysis was used to estimate the effect of TTE measures on all-cause mortality. Over a mean follow-up of 3.2±1.5 years, there were 78 deaths with a mean time to death of 1.28±1.16 years. A greater tubular ascending aorta (hazard ratio [HR] 5.6, 95% confidence interval [CI] 2.77–11.33), presence of mitral regurgitation (HR 8.13, 95% CI 4.09–12.16), lower left ventricular ejection fraction (HR 0.96, 95% CI 0.93–0.98), younger age (HR 0.97, 95% CI 0.95–0.99), and presence of diabetes mellitus (HR 1.46, 95% CI 1.24–1.89) were predictors of all-cause mortality.

Conclusions—
Echocardiography provides important long-term prognostic information in patients undergoing endovascular aneurysm repair. These TTE indices were more important at predicting outcome than standard conventional risk factors in this patient group. A greater tubular ascending aorta, presence of mitral regurgitation, reduced left ventricular ejection fraction, younger age, and diabetes mellitus were independently associated with long-term mortality.
Paris, Rome, Venice, and Vienna in Peter Lambeck’s Network
Authors: Feola Vittoria 
Published: February 2016

This article considers, first, the roles of Paris, Rome, Venice, and Vienna in the network of Peter Lambeck, the librarian of the Hapsburg emperor Leopold I, and, secondly, Lambeck’s and Vienna’s own places in the Republic of Letters during the period 1662–1680. It begins with a biographical account, in which I situate Lambeck both geographically and intellectually. The importance of Paris is contrasted with his not so positive experience in Rome. Secondly, I focus on Lambeck’s declaration of intent to link Vienna to the Republic of Letters. Thirdly, I survey the eminently Venetian networks through which Lambeck tried to fulfil his intellectual goals. The tensions between France and the Habsburg Empire crashed against Lambeck’s idealistic aims. This raises the issue of the impact of geo-politics on the production and circulation of knowledge in early modern Europe, and prompts questions about openness and secrecy in the Republic of Letters.
Intelligent Agent Transparency in Human–Agent Teaming for Multi-UxV Management
Authors: Mercado Joseph E. , Rupp Michael A. , Chen Jessie Y. C. , Barnes Michael J. , Barber Daniel , Procci Katelyn 
Published: February 2016

Objective: We investigated the effects of level of agent transparency on operator performance, trust, and workload in a context of human–agent teaming for multirobot management. Background: Participants played the role of a heterogeneous unmanned vehicle (UxV) operator and were instructed to complete various missions by giving orders to UxVs through a computer interface. An intelligent agent (IA) assisted the participant by recommending two plans—a top recommendation and a secondary recommendation—for every mission. Method: A within-subjects design with three levels of agent transparency was employed in the present experiment. There were eight missions in each of three experimental blocks, grouped by level of transparency. During each experimental block, the IA was incorrect three out of eight times due to external information (e.g., commander’s intent and intelligence). Operator performance, trust, workload, and usability data were collected. Results: Results indicate that operator performance, trust, and perceived usability increased as a function of transparency level. Subjective and objective workload data indicate that participants’ workload did not increase as a function of transparency. Furthermore, response time did not increase as a function of transparency. Conclusion: Unlike previous research, which showed that increased transparency resulted in increased performance and trust calibration at the cost of greater workload and longer response time, our results support the benefits of transparency for performance effectiveness without additional costs. Application: The current results will facilitate the implementation of IAs in military settings and will provide useful data to the design of heterogeneous UxV teams.