bluuebunny/crossref_metadata_2025_split huggingface dataset:
Home visits in primary care: contents and organisation in daily practice. Study protocol of a cross-sectional study
Authors: Voigt Karen , Bojanowski Stefan , Taché Stephanie , Voigt Roger , Bergmann Antje 
Published: February 2016

IntroductionMedical care of homebound patients by home visits is an integral part of primary care in Germany and other industrialised countries. Owing to the sociodemography and changes in the health system, the need for home visits is projected to increase rather than decrease. Our study will provide information on content and organisation of home visits. This evidence is needed to assure sufficient medical care for homebound patients. Germany is one of the European nations with highest proportions of elderly age groups, so that our results will be indicative for other European countries with comparable organisation of primary care.Methods and analysisThis cross-sectional study is conducted over a period of 12 months. All home visits of each participating family practice are documented within a 1-week time period. The anonymous documentation of home visits is carried out by the family practitioner or medical assistant conducting the home visit. All Saxon Family practitioners received study information and were personally invited to participate in our study. Almost 303 (of 2677) family practitioners expressed their interest to participate to generate data on the content and organisational characteristics of home visits. Data analysis of more than 4000 home visits will take into account several patient-related and system-related parameters. Descriptive and multivariate analysis will be carried out by using non-parametric methods. Regarding expected cluster structure of the data, a multilevel analysis will be necessary.Ethics and disseminationThe study received ethical approval by the Ethical Commission of the TU Dresden and adheres to the Declaration of Helsinki. Considering that the results of our project will be indicative for ageing societies with comparable organisation of primary care, we will publish them in international open access journals concerned with healthcare and primary care research and disseminate them by a final symposium and at national/international scientific events.
Print and online newspaper coverage of the link between HPV and oral cancer in the UK: a mixed-methods study
Authors: Dodd Rachael H , Marlow Laura A V , Forster Alice S , Waller Jo 
Published: February 2016

ObjectivesThe role of human papillomavirus (HPV) in some oral cancers has been reported in the news press, though little is known about the content of these articles. This study aimed to examine how frequently the link between HPV and oral cancer has been reported in the news press and to examine the content of these articles.DesignUK media articles were searched for articles relating to oral cancer and HPV in the database NexisUK. Of 854 articles identified by the initial search, 112 were eligible for inclusion (2002–2014) and content analysis was used to determine the main themes discussed.ResultsThemes included actor Michael Douglas’ claim that his throat cancer was caused by HPV, the riskiness of oral sex, health information (including HPV as a cause of oral cancer) and the need to vaccinate boys against HPV. Many articles also referred to the link between HPV and cervical cancer and the increasing incidence of HPV-related oral cancer. The largest peak in articles occurred when Michael Douglas discussed his cancer (June 2013). Facts about HPV and references to research were provided in some articles.ConclusionsThe link between HPV and oral cancer and the transmission of HPV via oral sex was regularly discussed, yet coverage often lacked detailed health information. This could increase awareness of the link between oral sex and HPV risk, but may also lead to public concern about oral sex as a sexual behaviour.
Acute effects of breaking up prolonged sitting on fatigue and cognition: a pilot study
Authors: Wennberg Patrik , Boraxbekk Carl-Johan , Wheeler Michael , Howard Bethany , Dempsey Paddy C , Lambert Gavin , Eikelis Nina , Larsen Robyn , Sethi Parneet , Occleston Jessica , Hernestål-Boman Jenny , Ellis Kathryn A , Owen Neville , Dunstan David W 
Published: February 2016

ObjectivesTo compare the acute effects of uninterrupted sitting with sitting interrupted by brief bouts of light-intensity walking on self-reported fatigue, cognition, neuroendocrine biomarkers and cardiometabolic risk markers in overweight/obese adults.DesignRandomised two-condition crossover trial.SettingLaboratory study conducted in Melbourne, Australia.Participants19 overweight/obese adults (45–75 years).InterventionsAfter an initial 2 h period seated, participants consumed a meal-replacement beverage and completed (on 2 days separated by a 6-day washout period) each condition over the next 5 h: uninterrupted sitting (sedentary condition) or sitting with 3 min bouts of light-intensity walking every 30 min (active condition).Primary outcome measuresSelf-reported fatigue, executive function and episodic memory at 0 h, 4 h and 7 h.Secondary outcome measuresNeuroendocrine biomarkers and cardiometabolic risk markers (blood collections at 0 h, 4 h and 7 h, blood pressure and heart rate measured hourly and interstitial glucose measured using a continuous glucose monitoring system).ResultsDuring the active condition, fatigue levels were lower at 4 h (−13.32 (95% CI −23.48 to −3.16)) and at 7 h (−10.73 (95% CI −20.89 to −0.58)) compared to the sedentary condition. Heart rate was higher at 4 h (4.47 (95% CI 8.37 to 0.58)) and at 7 h (4.32 (95% CI 8.21 to 0.42)) during the active condition compared to the sedentary condition. There were no significant differences between conditions by time for other variables. In the sedentary condition, changes in fatigue scores over time correlated with a decrease in heart rate and plasma dihydroxyphenylalanine (DOPA) and an increase in plasma dihydroxyphenylglycol (DHPG).ConclusionsInterrupting prolonged sitting with light-intensity walking breaks may be an effective fatigue countermeasure acutely. Fatigue levels corresponded with the heart rate and neuroendocrine biomarker changes in uninterrupted sitting in this pilot study. Further research is needed to identify potential implications, particularly for the occupational health context.Trial registration numberACTRN12613000137796; Results.
Intra-individual variation in urinary iodine concentration: effect of statistical correction on population distribution using seasonal three-consecutive-day spot urine in children
Authors: Ji Xiaohong , Liu Peng , Sun Zhenqi , Su Xiaohui , Wang Wei , Gao Yanhui , Sun Dianjun 
Published: February 2016

ObjectiveTo determine the effect of statistical correction for intra-individual variation on estimated urinary iodine concentration (UIC) by sampling on 3 consecutive days in four seasons in children.SettingSchool-aged children from urban and rural primary schools in Harbin, Heilongjiang, China.Participants748 and 640 children aged 8–11 years were recruited from urban and rural schools, respectively, in Harbin.Primary and secondary outcome measuresThe spot urine samples were collected once a day for 3 consecutive days in each season over 1 year. The UIC of the first day was corrected by two statistical correction methods: the average correction method (average of days 1, 2; average of days 1, 2 and 3) and the variance correction method (UIC of day 1 corrected by two replicates and by three replicates). The variance correction method determined the SD between subjects (Sb) and within subjects (Sw), and calculated the correction coefficient (Fi), Fi=Sb/(Sb+Sw/di), where diwas the number of observations. The UIC of day 1 was then corrected using the following equation:ResultsThe variance correction methods showed the overall Fiwas 0.742 for 2 days’ correction and 0.829 for 3 days’ correction; the values for the seasons spring, summer, autumn and winter were 0.730, 0.684, 0.706 and 0.703 for 2 days’ correction and 0.809, 0.742, 0.796 and 0.804 for 3 days’ correction, respectively. After removal of the individual effect, the correlation coefficient between consecutive days was 0.224, and between non-consecutive days 0.050.ConclusionsThe variance correction method is effective for correcting intra-individual variation in estimated UIC following sampling on 3 consecutive days in four seasons in children. The method varies little between ages, sexes and urban or rural setting, but does vary between seasons.
An in vitro evaluation of distal emboli following Lazarus Cover-assisted stent retriever thrombectomy
Authors: Chueh Ju-Yu , Puri Ajit S , Gounis Matthew J 
Published: February 2016

BackgroundFormation of clot fragments during mechanical thrombectomy for acute ischemic stroke can occlude the distal vasculature, which may reduce the rate of good clinical outcome.ObjectiveTo examine the hypothesis that distal embolization can be reduced using stent retriever thrombectomy in combination with Lazarus Cover technology.MethodsHard, fragment-prone clots were used to create middle cerebral artery occlusions in a vascular phantom. Three different treatment strategies using Solitaire FR included: group 1—proximal flow control with an 8F balloon guide catheter (BGC), group 2—thrombectomy through a 6F conventional guide catheter (CGC), and group 3—a similar thrombectomy procedure to group 2 but including the Lazarus Cover device. The primary endpoint was distal emboli quantified by the number and size of the clot debris.ResultsThe Cover-assisted stent retriever thrombectomy significantly reduced the generation of clot fragments >200 μm as compared with thrombectomy with a CGC, and was similar to the BGC group. Particle size distribution <200 μm was similar across the groups. All groups were associated with high rates of recanalization, with only one failed recanalization with partial clot retention after three passes in one experiment of stent retriever thrombectomy through a CGC. Use of the adjunctive Cover device did not prolong the procedure as compared with control groups.ConclusionsFor a fragment-prone clot, Solitaire thrombectomy in conjunction with the Cover device may lower the risk of distal embolization and is comparable to BGC-protected embolectomy.
Phosphatase PTP4A3 Promotes Triple-Negative Breast Cancer Growth and Predicts Poor Patient Survival
Authors: den Hollander Petra , Rawls Kathryn , Tsimelzon Anna , Shepherd Jonathan , Mazumdar Abhijit , Hill Jamal , Fuqua Suzanne A.W. , Chang Jenny C. , Osborne C. Kent , Hilsenbeck Susan G. , Mills Gordon B. , Brown Powel H. 
Published: February 2016

Abstract
Triple-negative breast cancer (TNBC) has the worst prognosis of all breast cancers, and women diagnosed with TNBC currently lack targeted treatment options. To identify novel targets for TNBC, we evaluated phosphatase expression in breast tumors and characterized their contributions to in vitro and in vivo growth of TNBC. Using Affymetrix microarray analysis of 102 breast cancers, we identified 146 phosphatases that were significantly differentially expressed in TNBC compared with estrogen receptor (ER)-positive tumors. Of these, 19 phosphatases were upregulated (0.66-fold; FDR = 0.05) in TNBC compared with ER-positive breast cancers. We knocked down 17 overexpressed phosphatases in four triple-negative and four ER-positive breast cancer lines using specific siRNAs and found that depletion of six of these phosphatases significantly reduced growth and anchorage-independent growth of TNBC cells to a greater extent than ER-positive cell lines. Further analysis of the phosphatase PTP4A3 (also known as PRL-3) demonstrated its requirement for G1–S cell-cycle progression in all breast cancer cells, but PTP4A3 regulated apoptosis selectively in TNBC cells. In addition, PTP4A3 inhibition reduced the growth of TNBC tumors in vivo. Moreover, in silico analysis revealed the PTP4A3 gene to be amplified in 29% of basal-like breast cancers, and high expression of PTP4A3 could serve as an independent prognostic indicator for worse overall survival. Collectively, these studies define the importance of phosphatase overexpression in TNBC and lay the foundation for the development of new targeted therapies directed against phosphatases or their respective signaling pathways for TNBC patients. Cancer Res; 76(7); 1942–53. ©2016 AACR.
Mutational Landscape and Antiproliferative Functions of ELF Transcription Factors in Human Cancer
Authors: Ando Mizuo , Kawazu Masahito , Ueno Toshihide , Koinuma Daizo , Ando Koji , Koya Junji , Kataoka Keisuke , Yasuda Takahiko , Yamaguchi Hiroyuki , Fukumura Kazutaka , Yamato Azusa , Soda Manabu , Sai Eirin , Yamashita Yoshihiro , Asakage Takahiro , Miyazaki Yasushi , Kurokawa Mineo , Miyazono Kohei , Nimer Stephen D. , Yamasoba Tatsuya , Mano Hiroyuki 
Published: February 2016

Abstract
ELF4 (also known as MEF) is a member of the ETS family of transcription factors. An oncogenic role for ELF4 has been demonstrated in hematopoietic malignancies, but its function in epithelial tumors remains unclear. Here, we show that ELF4 can function as a tumor suppressor and is somatically inactivated in a wide range of human tumors. We identified a missense mutation affecting the transactivation potential of ELF4 in oral squamous cell carcinoma cells. Restoration of the transactivation activity through introduction of wild-type ELF4 significantly inhibited cell proliferation in vitro and tumor xenograft growth. Furthermore, we found that ELF1 and ELF2, closely related transcription factors to ELF4, also exerted antiproliferative effects in multiple cancer cell lines. Mutations in ELF1 and ELF2, as in ELF4, were widespread across human cancers, but were almost all mutually exclusive. Moreover, chromatin immunoprecipitation coupled with high-throughput sequencing revealed ELF4-binding sites in genomic regions adjacent to genes related to cell-cycle regulation and apoptosis. Finally, we provide mechanistic evidence that the antiproliferative effects of ELF4 were mediated through the induction of HRK, an activator of apoptosis, and DLX3, an inhibitor of cell growth. Collectively, our findings reveal a novel subtype of human cancer characterized by inactivating mutations in the ELF subfamily of proteins, and warrant further investigation of the specific settings where ELF restoration may be therapeutically beneficial. Cancer Res; 76(7); 1814–24. ©2016 AACR.
MCAM and LAMA4 Are Highly Enriched in Tumor Blood Vessels of Renal Cell Carcinoma and Predict Patient Outcome
Authors: Wragg Joseph W. , Finnity Jonathan P. , Anderson Jane A. , Ferguson Henry J.M. , Porfiri Emilio , Bhatt Rupesh I. , Murray Paul G. , Heath Victoria L. , Bicknell Roy 
Published: February 2016

Abstract
The structure and molecular signature of tumor-associated vasculature are distinct from those of the host tissue, offering an opportunity to selectively target the tumor blood vessels. To identify tumor-specific endothelial markers, we performed a microarray on tumor-associated and nonmalignant endothelium collected from patients with renal cell carcinoma (RCC), colorectal carcinoma, or colorectal liver metastasis. We identified a panel of genes consistently upregulated by tumor blood vessels, of which melanoma cell adhesion molecule (MCAM) and its extracellular matrix interaction partner laminin alpha 4 (LAMA4) emerged as the most consistently expressed genes. This result was subsequently confirmed by immunohistochemical analysis of MCAM and LAMA4 expression in RCC and colorectal carcinoma blood vessels. Strong MCAM and LAMA4 expression was also shown to predict poor survival in RCC, but not in colorectal carcinoma. Notably, MCAM and LAMA4 were enhanced in locally advanced tumors as well as both the primary tumor and secondary metastases. Expression analysis in 18 different cancers and matched healthy tissues revealed vascular MCAM as highly specific in RCC, where it was induced strongly by VEGF, which is highly abundant in this disease. Lastly, MCAM monoclonal antibodies specifically localized to vessels in a murine model of RCC, offering an opportunity for endothelial-specific targeting of anticancer agents. Overall, our findings highlight MCAM and LAMA4 as prime candidates for RCC prognosis and therapeutic targeting. Cancer Res; 76(8); 2314–26. ©2016 AACR.
Resistance to Anti-VEGF Therapy Mediated by Autocrine IL6/STAT3 Signaling and Overcome by IL6 Blockade
Authors: Eichten Alexandra , Su Jia , Adler Alexander P. , Zhang Li , Ioffe Ella , Parveen Asma A. , Yancopoulos George D. , Rudge John , Lowy Israel , Lin Hsin Chieh , MacDonald Douglas , Daly Christopher , Duan Xunbao , Thurston Gavin 
Published: February 2016

Abstract
Anti-VEGF therapies benefit several cancer types, but drug resistance that limits therapeutic response can emerge. We generated cell lines from anti-VEGF–resistant tumor xenografts to investigate the mechanisms by which resistance develops. Of all tumor cells tested, only A431 (A431-V) epidermoid carcinoma cells developed partial resistance to the VEGF inhibitor aflibercept. Compared with the parental tumors, A431-V tumors secreted greater amounts of IL6 and exhibited higher levels of phospho-STAT3. Notably, combined blockade of IL6 receptor (IL6R) and VEGF resulted in enhanced activity against A431-V tumors. Similarly, inhibition of IL6R enhanced the antitumor effects of aflibercept in DU145 prostate tumor cells that displays high endogenous IL6R activity. In addition, post hoc stratification of data obtained from a clinical trial investigating aflibercept efficacy in ovarian cancer showed poorer survival in patients with high levels of circulating IL6. These results suggest that the activation of the IL6/STAT3 pathway in tumor cells may provide a survival advantage during anti-VEGF treatment, suggesting its utility as a source of response biomarkers and as a therapeutic target to heighten efficacious results. Cancer Res; 76(8); 2327–39. ©2016 AACR.
A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk
Authors: Travis Ruth C. , Appleby Paul N. , Martin Richard M. , Holly Jeff M.P. , Albanes Demetrius , Black Amanda , Bueno-de-Mesquita H. Bas , Chan June M. , Chen Chu , Chirlaque Maria-Dolores , Cook Michael B. , Deschasaux Mélanie , Donovan Jenny L. , Ferrucci Luigi , Galan Pilar , Giles Graham G. , Giovannucci Edward L. , Gunter Marc J. , Habel Laurel A. , Hamdy Freddie C. , Helzlsouer Kathy J. , Hercberg Serge , Hoover Robert N. , Janssen Joseph A.M.J.L. , Kaaks Rudolf , Kubo Tatsuhiko , Le Marchand Loic , Metter E. Jeffrey , Mikami Kazuya , Morris Joan K. , Neal David E. , Neuhouser Marian L. , Ozasa Kotaro , Palli Domenico , Platz Elizabeth A. , Pollak Michael N. , Price Alison J. , Roobol Monique J. , Schaefer Catherine , Schenk Jeannette M. , Severi Gianluca , Stampfer Meir J. , Stattin Pär , Tamakoshi Akiko , Tangen Catherine M. , Touvier Mathilde , Wald Nicholas J. , Weiss Noel S. , Ziegler Regina G. , Key Timothy J. , Allen Naomi E. 
Published: February 2016

Abstract
The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16–1.43) for IGF-I, 0.81 (0.68–0.96) for IGFBP-1, and 1.25 (1.12–1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. Cancer Res; 76(8); 2288–300. ©2016 AACR.
Intracellular Released Payload Influences Potency and Bystander-Killing Effects of Antibody-Drug Conjugates in Preclinical Models
Authors: Li Fu , Emmerton Kim K. , Jonas Mechthild , Zhang Xinqun , Miyamoto Jamie B. , Setter Jocelyn R. , Nicholas Nicole D. , Okeley Nicole M. , Lyon Robert P. , Benjamin Dennis R. , Law Che-Leung 
Published: February 2016

Abstract
Antibody-drug conjugates (ADC) comprise targeting antibodies armed with potent small-molecule payloads. ADCs demonstrate specific cell killing in clinic, but the basis of their antitumor activity is not fully understood. In this study, we investigated the degree to which payload release predicts ADC activity in vitro and in vivo. ADCs were generated to target different receptors on the anaplastic large cell lymphoma line L-82, but delivered the same cytotoxic payload (monomethyl auristatin E, MMAE), and we found that the intracellular concentration of released MMAE correlated with in vitro ADC-mediated cytotoxicity independent of target expression or drug:antibody ratios. Intratumoral MMAE concentrations consistently correlated with the extent of tumor growth inhibition in tumor xenograft models. In addition, we developed a robust admixed tumor model consisting of CD30+ and CD30− cancer cells to study how heterogeneity of target antigen expression, a phenomenon often observed in cancer specimens, affects the treatment response. CD30-targeting ADC delivering membrane permeable MMAE or pyrrolobenzodiazepine dimers demonstrated potent bystander killing of neighboring CD30− cells. In contrast, a less membrane permeable payload, MMAF, failed to mediate bystander killing in vivo, suggesting local diffusion and distribution of released payloads represents a potential mechanism of ADC-mediated bystander killing. Collectively, our findings establish that the biophysical properties and amount of released payloads are chief factors determining the overall ADC potency and bystander killing. Cancer Res; 76(9); 2710–9. ©2016 AACR.