bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of alcohol drinking pattern and self-inflicted intentional injury in Korea: a cross-sectional WHO collaborative emergency room study
Authors: Chun Sungsoo , Reid Easton A , Yun Mieun 
Published: May 2013

ObjectivesSelf-inflicted intentional injuries are increasing at an alarming rate in the Republic of Korea, yet few reports describe their relationship with alcohol consumption. The aim of this study was to characterise the association of alcohol drinking patterns and self-inflicted intentional injury in Korean emergency departments (EDs) using WHO collaborative study protocol.DesignCross-sectional study.SettingData were collected from four general hospital EDs in four geographically diverse regions of Korea: Seoul, Suwon, Chuncheon and Gwangju.ParticipantsInformation was collected on 1989 patients aged 18 and above. A representative probability sample was drawn from patients admitted to each ED for the first time within 6 h of injury.Primary and secondary outcome measuresAlcohol-related non-fatal injuries.ResultsAmong 467 persons with alcohol-related injuries, 33 (7.1%), were self-inflicted intentional injuries and 137 (29.3%) were intentional injuries caused by someone else. The adjusted odds of self-inflicted intentional injury verses unintentional injury were calculated for heavy (OR 1.764; 95% CI 0.783 to 3.976), binge (OR 2.125; 95% CI 0.930 to 4.858) and moderate drinking (OR 3.039; 95% CI 1.129 to 8.178) after controlling for demographic variables. Similar odds were reported for pooled intentional injury data (self-inflicted and caused by someone else) and drinking patterns.ConclusionsThese data show a strong association between all patterns of acute alcohol consumption and self-inflicted intentional injury in the Republic of Korea.
The eye response test alone is sufficient to predict stroke outcome—reintroduction of Japan Coma Scale: a cohort study
Authors: Shigematsu Kazuo , Nakano Hiromi , Watanabe Yoshiyuki 
Published: May 2013

ObjectivesPrompt assessment of consciousness levels is vitally important during the emergency care of stroke patients. The Japan Coma Scale (JCS) is a one-axis coma scale published in 1974 with outstanding simplicity. The hypothesis is that JCS is sufficient to predict stroke outcome. The aim of the study was to verify the predictability of JCS, which should help JCS attain international recognition.DesignA cohort study.SettingA prefectural stroke registry.ParticipantsWe analysed 13 788 stroke patients identified from January 1999 to December 2009 inclusive in the entire Kyoto prefecture and registered in the Kyoto Stroke Registry (KSR).Main outcome measuresWe investigated the relationship between consciousness levels, based on JCS at stroke onset and activities of daily living (ADL) at 30 days or deaths within 30 days in a large population-based stroke registry. We calculated Spearman's coefficient for the correlation between JCS and the ADL scale, generated estimated survival curves by the Kaplan-Meier method and finally compared HRs for death within 30 days after onset, comparing patients with different conscious levels based on JCS.ResultsA total of 13 406 (97.2%) patients were graded based on JCS. JCS correlated to the ADL scale with Spearman's correlation coefficient of 0.61. HRs for death within 30 days were 1 (reference) (95% CIs), 5.55 (4.19 to 7.37), 9.54 (7.16 to 12.71) and 35.21 (26.10 to 44.83) in those scored as JCS0, JCS1, JCS2 and JCS3, respectively.ConclusionsUsing a single test of eye response, JCS has outstanding merits as a coma scale, that is, simplicity and applicability. The present study adds predictability for early outcome in stroke patients. JCS is valuable, especially in an emergency setting, when a prompt assessment of consciousness levels is needed.
The benefits of thermal clothing during winter in patients with heart failure: a pilot randomised controlled trial
Authors: Barnett Adrian G , Lucas Margaret , Platts David , Whiting Elizabeth , Fraser John F 
Published: May 2013

ObjectivesTo examine whether providing thermal clothing to heart failure patients improves their health during winter.DesignA randomised controlled trial with an intervention group and a usual care group.SettingHeart failure clinic in a large tertiary referral hospital in Brisbane, Australia.ParticipantsEligible participants were those with known systolic heart failure who were over 50  years of age and lived in Southeast Queensland. Participants were excluded if they lived in a residential aged care facility, had incontinence or were unable to give informed consent. Fifty-five participants were randomised and 50 completed.InterventionsParticipants randomised to the intervention received two thermal hats and tops and a digital thermometer.Primary and secondary outcome measuresThe primary outcome was the mean number of days in hospital. Secondary outcomes were the number of general practitioner (GP) visits and self-rated health.ResultsThe mean number of days in hospital per 100 winter days was 2.5 in the intervention group and 1.8 in the usual care group, with a mean difference of 0.7 (95% CI −1.5 to 5.4). The intervention group had 0.2 fewer GP visits on average (95% CI −0.8 to 0.3), and a higher self-rated health, mean improvement –0.3 (95% CI −0.9 to 0.3). The thermal tops were generally well used, but even in cold temperatures the hats were only worn by 30% of the participants.ConclusionsThermal clothes are a cheap and simple intervention, but further work needs to be done on increasing compliance and confirming the health and economic benefits of providing thermals to at-risk groups.Trial registrationThe study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612000378820)
Determining immunisation status of children from history: a diagnostic accuracy study
Authors: Nohavicka Laura , Ashdown Helen F , Kelly Dominic F 
Published: May 2013

ObjectivesChildren presenting unplanned to healthcare services are routinely asked about previous immunisations as part of their assessment. We aimed to assess the accuracy of screening children for immunisation status by history.DesignDiagnostic accuracy study. We compared information from patient history by a retrospective review of notes and used a central database of child immunisation records as the reference standard.SettingPaediatric emergency department in a tertiary hospital in Oxford, UK.ParticipantsConsecutive children aged 6 months to 6 years presenting over a 2-month period.Outcome measuresProportion of children with documented immunisation history; sensitivity and specificity of detecting overdue immunisations by history compared to central records.Results1166 notes were surveyed. 76.3% children were asked about immunisations. The proportion of children who were fully immunised on central records was 93.1%. History had a sensitivity of 41.3% (95% CI 27% to 56.8%) and a specificity of 98.7% (95% CI 97.5% to 99.4%) for detecting those who were overdue. Negative predictive value was 95.8% (95% CI 93.9% to 97.2%). Only around a third of children with overdue immunisations are detected by the current screening methods, and approximately 1 in 20 children stated as being up to date are in fact overdue.ConclusionsHistory had poor sensitivity for identifying overdue immunisation. Strategies to improve detection of children overdue with immunisation should focus on alternative strategies for alerting clinicians, such as linkage of community and hospital electronic records.
Association ofTrichomonas vaginaliswith its symbiontMycoplasma hominissynergistically upregulates the in vitro proinflammatory response of human monocytes
Authors: Fiori Pier Luigi , Diaz Nicia , Cocco Anna Rita , Rappelli Paola , Dessì Daniele 
Published: May 2013

ObjectivesTrichomonas vaginalisis the causative agent of trichomoniasis, one of the most common sexually transmitted diseases worldwide. In recent years we have described the symbiotic relationship betweenT vaginalisandMycoplasma hominis. How this biological association might affect the pathogenicity of one or both the microorganisms is still unknown. Since local inflammation is thought to play a central role inT vaginalisinfection, we investigated the in vitro response of human macrophages to naturally mycoplasma-freeT vaginalis, as compared to a mycoplasma-infected trichomonad isolate.MethodsTHP-1 cells were stimulated with two isogenicT vaginalisisolates, one naturally mycoplasma-free and one stably associated withM hominis, and secreted cytokines measured by ELISA. Nuclear factor κB (NFκB) involvement in THP-1 response toT vaginalisandM hominiswas evaluated by means of a reporter system based on detection of alkaline phosphatase activity.ResultsWe found that the presence ofM hominisupregulates the expression of a panel of proinflammatory cytokines in a synergistic fashion. We also found that the upregulation of the proinflammatory response by THP-1 cells involves the transcription factor NFκB.ConclusionsThese findings suggest that the presence ofM hominisinT vaginalisisolates might play a key role in inflammation during trichomoniasis, thus affecting the severity of the disease. The synergistic upregulation of the macrophage proinflammatory response might also affect some important clinical conditions associated withT vaginalisinfection, such as the increased risk of acquiring cervical cancer or HIV, which are thought to be affected by the inflammatory milieu during trichomoniasis.
Practical Integrated Analysis of Pointers, Dataflow and Control Flow
Authors: Staiger-Stöhr Stefan 
Published: May 2013

This article presents a family of static analyses to determine pointer targets, control flow, and dataflow in combination. The integrated solution to these mutually dependent problems approaches the result from the optimistic side. It is a general strategy for static program analysis and does not need any upfront approximation for one of the problems to overcome the mutual dependencies. A degenerated case yields Andersen’s famous pointer analysis; otherwise, the analyses are flow-sensitive and can support direct and indirect strong updates, within the same cubic asymptotic complexity as known for Andersen, albeit with larger constants.
Surprisingly, the ideas behind the integrated analysis are intuitive. The strategy we describe naturally evolves from considering the mutual dependencies between the three problems, or from generalizing Andersen’s analysis to flow sensitivity. Such a flow-sensitive Andersen analysis not only computes pointer targets with higher precision than the original analysis, but it also creates an interprocedural SSA form at the same time.
Our extensive experimental evaluation shows that the integrated solution is practical as it can be applied to reasonably large real-world programs within a few seconds or minutes. This uses some optimizations which together achieve a speedup of more than 100 for several programs. We compare several members of the family of analyses, from flow- and field-insensitive to flow- and field-sensitive with strong updates, both with and without optimizations. This gives some insights into the effects of these dimensions of precision on the results. It also sheds new light on the benefits of flow sensitivity versus the costs associated with it.
Hypoxia Triggers Hedgehog-Mediated Tumor–Stromal Interactions in Pancreatic Cancer
Authors: Spivak-Kroizman Taly R. , Hostetter Galen , Posner Richard , Aziz Meraj , Hu Chengcheng , Demeure Michael J. , Von Hoff Daniel , Hingorani Sunil R. , Palculict Timothy B. , Izzo Julie , Kiriakova Galina M. , Abdelmelek Mena , Bartholomeusz Geoffrey , James Brian P. , Powis Garth 
Published: May 2013

Abstract
Pancreatic cancer is characterized by a desmoplastic reaction that creates a dense fibroinflammatory microenvironment, promoting hypoxia and limiting cancer drug delivery due to decreased blood perfusion. Here, we describe a novel tumor–stroma interaction that may help explain the prevalence of desmoplasia in this cancer. Specifically, we found that activation of hypoxia-inducible factor-1α (HIF-1α) by tumor hypoxia strongly activates secretion of the sonic hedgehog (SHH) ligand by cancer cells, which in turn causes stromal fibroblasts to increase fibrous tissue deposition. In support of this finding, elevated levels of HIF-1α and SHH in pancreatic tumors were determined to be markers of decreased patient survival. Repeated cycles of hypoxia and desmoplasia amplified each other in a feed forward loop that made tumors more aggressive and resistant to therapy. This loop could be blocked by HIF-1α inhibition, which was sufficient to block SHH production and hedgehog signaling. Taken together, our findings suggest that increased HIF-1α produced by hypoxic tumors triggers the desmoplasic reaction in pancreatic cancer, which is then amplified by a feed forward loop involving cycles of decreased blood flow and increased hypoxia. Our findings strengthen the rationale for testing HIF inhibitors and may therefore represent a novel therapeutic option for pancreatic cancer. Cancer Res; 73(11); 3235–47. ©2013 AACR.
Melanoma-Educated CD14+ Cells Acquire a Myeloid-Derived Suppressor Cell Phenotype through COX-2–Dependent Mechanisms
Authors: Mao Yumeng , Poschke Isabel , Wennerberg Erik , Pico de Coaña Yago , Egyhazi Brage Suzanne , Schultz Inkeri , Hansson Johan , Masucci Giuseppe , Lundqvist Andreas , Kiessling Rolf 
Published: May 2013

Abstract
Tumors can suppress the host immune system by employing a variety of cellular immune modulators, such as regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells (MDSC). In the peripheral blood of patients with advanced stage melanoma, there is an accumulation of CD14+HLA-DRlo/− MDSC that suppress autologous T cells ex vivo in a STAT-3–dependent manner. However, a precise mechanistic basis underlying this effect is unclear, particularly with regard to whether the MDSC induction mechanism relies on cell–cell contact of melanoma cells with CD14+ cells. Here, we show that early-passage human melanoma cells induce phenotypic changes in CD14+ monocytes, leading them to resemble MDSCs characterized in patients with advanced stage melanoma. These MDSC-like cells potently suppress autologous T-cell proliferation and IFN-γ production. Notably, induction of myeloid-suppressive functions requires contact or close proximity between monocytes and tumor cells. Further, this induction is largely dependent on production of cyclooxygenase-2 (COX-2) because its inhibition in these MDSC-like cells limits their ability to suppress T-cell function. We confirmed our findings with CD14+ cells isolated from patients with advanced stage melanoma, which inhibited autologous T cells in a manner relying up prostaglandin E2 (PGE2), STAT-3, and superoxide. Indeed, PGE2 was sufficient to confer to monocytes the ability to suppress proliferation and IFN-γ production by autologous T cells ex vivo. In summary, our results reveal how immune suppression by MDSC can be initiated in the tumor microenvironment of human melanoma. Cancer Res; 73(13); 3877–87. ©2013 AACR.
Coevolution of Solid Stress and Interstitial Fluid Pressure in Tumors During Progression: Implications for Vascular Collapse
Authors: Stylianopoulos Triantafyllos , Martin John D. , Snuderl Matija , Mpekris Fotios , Jain Saloni R. , Jain Rakesh K. 
Published: May 2013

Abstract
The stress harbored by the solid phase of tumors is known as solid stress. Solid stress can be either applied externally by the surrounding normal tissue or induced by the tumor itself due to its growth. Fluid pressure is the isotropic stress exerted by the fluid phase. We recently showed that growth-induced solid stress is on the order of 1.3 to 13.0 kPa (10–100 mmHg) – high enough to cause compression of fragile blood vessels, resulting in poor perfusion and hypoxia. However, the evolution of growth-induced stress with tumor progression and its effect on cancer cell proliferation in vivo is not understood. To this end, we developed a mathematical model for tumor growth that takes into account all three types of stresses: growth-induced stress, externally applied stress, and fluid pressure. First, we conducted in vivo experiments and found that growth-induced stress is related to tumor volume through a biexponential relationship. Then, we incorporated this information into our mathematical model and showed that due to the evolution of growth-induced stress, total solid stress levels are higher in the tumor interior and lower in the periphery. Elevated compressive solid stress in the interior of the tumor is sufficient to cause the collapse of blood vessels and results in a lower growth rate of cancer cells compared with the periphery, independently from that caused by the lack of nutrients due to vessel collapse. Furthermore, solid stress in the periphery of the tumor causes blood vessels in the surrounding normal tissue to deform to elliptical shapes. We present histologic sections of human cancers that show such vessel deformations. Finally, we found that fluid pressure increases with tumor growth due to increased vascular permeability and lymphatic impairment, and is governed by the microvascular pressure. Crucially, fluid pressure does not cause vessel compression of tumor vessels. Cancer Res; 73(13); 3833–41. ©2013 AACR.
Growth of Triple-Negative Breast Cancer Cells Relies upon Coordinate Autocrine Expression of the Proinflammatory Cytokines IL-6 and IL-8
Authors: Hartman Zachary C. , Poage Graham M. , den Hollander Petra , Tsimelzon Anna , Hill Jamal , Panupinthu Nattapon , Zhang Yun , Mazumdar Abhijit , Hilsenbeck Susan G. , Mills Gordon B. , Brown Powel H. 
Published: May 2013

Abstract
Triple-negative breast cancers (TNBC) are aggressive with no effective targeted therapies. A combined database analysis identified 32 inflammation-related genes differentially expressed in TNBCs and 10 proved critical for anchorage-independent growth. In TNBC cells, an LPA-LPAR2-EZH2 NF-κB signaling cascade was essential for expression of interleukin (IL)-6, IL-8, and CXCL1. Concurrent inhibition of IL-6 and IL-8 expression dramatically inhibited colony formation and cell survival in vitro and stanched tumor engraftment and growth in vivo. A Cox multivariable analysis of patient specimens revealed that IL-6 and IL-8 expression predicted patient survival times. Together these findings offer a rationale for dual inhibition of IL-6/IL-8 signaling as a therapeutic strategy to improve outcomes for patients with TNBCs. Cancer Res; 73(11); 3470–80. ©2013 AACR.
BMP-6 in Renal Cell Carcinoma Promotes Tumor Proliferation through IL-10–Dependent M2 Polarization of Tumor-Associated Macrophages
Authors: Lee Jae-Ho , Lee Geun Taek , Woo Seung Hyo , Ha Yun-Sok , Kwon Seok Joo , Kim Wun-Jae , Kim Isaac Yi 
Published: May 2013

Abstract
Dysregulated bone morphogenetic proteins (BMP) may contribute to the development and progression of renal cell carcinoma (RCC). Herein, we report that BMP-6 promotes the growth of RCC by interleukin (IL)-10–mediated M2 polarization of tumor-associated macrophages (TAM). BMP-6–mediated IL-10 expression in macrophages required Smad5 and STAT3. In human RCC specimens, the three-marker signature BMP-6/IL-10/CD68 was associated with a poor prognosis. Furthermore, patients with elevated IL-10 serum levels had worse outcome after surgery. Together, our results suggest that BMP-6/macrophage/IL-10 regulates M2 polarization of TAMs in RCC. Cancer Res; 73(12); 3604–14. ©2013 AACR.
Conditional Loss of ErbB3 Delays Mammary Gland Hyperplasia Induced by Mutant PIK3CA without Affecting Mammary Tumor Latency, Gene Expression, or Signaling
Authors: Young Christian D. , Pfefferle Adam D. , Owens Philip , Kuba María G. , Rexer Brent N. , Balko Justin M. , Sánchez Violeta , Cheng Hailing , Perou Charles M. , Zhao Jean J. , Cook Rebecca S. , Arteaga Carlos L. 
Published: May 2013

Abstract
Mutations in PIK3CA, the gene encoding the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K), have been shown to transform mammary epithelial cells (MEC). Studies suggest this transforming activity requires binding of mutant p110α via p85 to phosphorylated YXXM motifs in activated receptor tyrosine kinases (RTK) or adaptors. Using transgenic mice, we examined if ErbB3, a potent activator of PI3K, is required for mutant PIK3CA-mediated transformation of MECs. Conditional loss of ErbB3 in mammary epithelium resulted in a delay of PIK3CAH1047R-dependent mammary gland hyperplasia, but tumor latency, gene expression, and PI3K signaling were unaffected. In ErbB3-deficient tumors, mutant PI3K remained associated with several tyrosyl phosphoproteins, potentially explaining the dispensability of ErbB3 for tumorigenicity and PI3K activity. Similarly, inhibition of ErbB RTKs with lapatinib did not affect PI3K signaling in PIK3CAH1047R-expressing tumors. However, the p110α-specific inhibitor BYL719 in combination with lapatinib impaired mammary tumor growth and PI3K signaling more potently than BYL719 alone. Furthermore, coinhibition of p110α and ErbB3 potently suppressed proliferation and PI3K signaling in human breast cancer cells harboring PIK3CAH1047R. These data suggest that PIK3CAH1047R-driven tumor growth and PI3K signaling can occur independently of ErbB RTKs. However, simultaneous blockade of p110α and ErbB RTKs results in superior inhibition of PI3K and mammary tumor growth, suggesting a rational therapeutic combination against breast cancers harboring PIK3CA activating mutations. Cancer Res; 73(13); 4075–85. ©2013 AACR.
The Increased Risk of Colon Cancer Due to Cigarette Smoking May Be Greater in Women than Men
Authors: Parajuli Ranjan , Bjerkaas Eivind , Tverdal Aage , Selmer Randi , Le Marchand Loïc , Weiderpass Elisabete , Gram Inger T. 
Published: May 2013

Abstract
Background: Smoking is a recently established risk factor for colon cancer. We wanted to explore the hypothesis that women may be more susceptible to smoking-attributed colon cancer than men as one of the possible explanations for the high colon cancer risk of Norwegian women.
Methods: We followed 602,242 participants aged 19 to 67 years at enrollment in 1972–2003, by linkage to national registries through December 2007. We used Cox proportional hazard models to estimate HRs and 95% confidence intervals (CI).
Results: During a mean follow-up of 14 years, altogether 3,998 (46% women) subjects developed colon cancer. Female ever-smokers had a 19% (HR = 1.19, 95% CI = 1.09–1.32) and male ever-smokers an 8% (HR = 1.08, CI = 0.97–1.19) increased risk of colon cancer compared with never smokers. For all the four dose–response variables examined, female ever-smokers in the most exposed category of smoking initiation, (HR = 1.48, 95% CI = 1.21–1.81), of daily cigarette consumption (HR = 1.28, 95% CI = 1.06–1.55), of smoking duration (HR = 1.47, 95% CI = 1.11–1.95), and of pack-years of smoking (HR = 1.33, 95% CI = 1.11–1.57) had a significantly increased risk of more than 20% for colon cancer overall and of more than 40% for proximal colon cancer, compared with never smokers. A test for heterogeneity by gender was statistically significant only for ever smoking and risk of proximal colon cancer (Wald χ2, P = 0.02).
Conclusions: Female smokers may be more susceptible to colon cancer and especially to proximal colon cancer than male smokers.
Impact: Women who smoke are more vulnerable to colon cancer than men. Cancer Epidemiol Biomarkers Prev; 22(5); 862–71. ©2013 AACR.