bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resilience does matter: evidence from a 10-year cohort record linkage study
Authors: Elliott Alison M , Burton Christopher D , Hannaford Philip C 
Published: January 2014

ObjectivesTo examine 10-year mortality and hospital use among individuals categorised as resilient and vulnerable to the impact of chronic pain.DesignA cohort record linkage study.SettingGrampian, Scotland.Participants5858 individuals from the Grampian Pain Cohort, established in 1996, were linked, by probability matching, with national routinely collected datasets.Main outcome measuresHRs for subsequent 10-year mortality and ORs/incidence rate ratios for subsequent 10-year hospital use, each with adjustment for potential confounding variables.Results36.5% of those with high pain intensity reported a low pain-related disability (categorised resilient) and 7.1% of those reporting low pain intensity reported a high pain-related disability (categorised vulnerable). Sex, age, housing, employment and long-term limiting illness were independently associated with being vulnerable or resilient. After adjustment for these variables, individuals in the resilient group were 25% less likely to die within 10 years of the survey compared with non-resilient individuals: HR 0.75, 95% CI 0.62 to 0.91 and vulnerable individuals were 45% more likely to die than non-vulnerable individuals: HR 1.45, 95% CI 1.01 to 2.11. Resilient individuals were less likely to have had an outpatient or day-case visit for anaesthetics: OR 0.46, 95% CI 0.27 to 0.79, but no other clinical specialities. Vulnerable individuals were significantly less likely to have had any outpatient or day-case visit (OR 0.43, 0.25 to 0.75); but more likely to have had a psychiatric visit (OR 1.96, 1.06 to 3.61). No significant differences in likelihood of any inpatient visits were found.ConclusionsResilient individuals have a better 10-year survival than non-resilient individuals indicating that resilience is a phenomenon worth researching. Further research is needed to explore who is likely to become resilient, why and how, as well as to tease out the internal and external factors that influence resilience.
Does legislation to prevent alcohol sales to drunk individuals work? Measuring the propensity for night-time sales to drunks in a UK city
Authors: Hughes Karen , Bellis Mark A , Leckenby Nicola , Quigg Zara , Hardcastle Katherine , Sharples Olivia , Llewellyn David J 
Published: January 2014

BackgroundBy measuring alcohol retailers’ propensity to illegally sell alcohol to young people who appear highly intoxicated, we examine whether UK legislation is effective at preventing health harms resulting from drunk individuals continuing to access alcohol.Methods73 randomly selected pubs, bars and nightclubs in a city in North West England were subjected to an alcohol purchase test by pseudo-drunk actors. Observers recorded venue characteristics to identify poorly managed and problematic (PMP) bars.Results83.6% of purchase attempts resulted in a sale of alcohol to a pseudo-intoxicated actor. Alcohol sales increased with the number of PMP markers bars had, yet even in those with no markers, 66.7% of purchase attempts resulted in a sale. Bar servers often recognised signs of drunkenness in actors, but still served them. In 18% of alcohol sales, servers attempted to up-sell by suggesting actors purchase double rather than single vodkas.ConclusionsUK law preventing sales of alcohol to drunks is routinely broken in nightlife environments, yet prosecutions are rare. Nightlife drunkenness places enormous burdens on health and health services. Preventing alcohol sales to drunks should be a public health priority, while policy failures on issues, such as alcohol pricing, are revisited.
Application of lipoarabinomannan antigen in tuberculosis diagnostics: current evidence
Authors: Sarkar Pronoti , Biswas Debasis , Sindhwani Girish , Rawat Jagdish , Kotwal Aarti , Kakati Barnali 
Published: January 2014

Abstract
Tests based on the detection of mycobacterial lipoarabinomannan (LAM) antigen in urine have emerged as potential point-of-care tests for tuberculosis (TB). We aimed to assimilate the current evidence regarding the diagnostic performance of LAM assays and to ascertain their clinical indication in settings with high and low prevalence of HIV-TB co-infection. Owing to suboptimal sensitivity, the urinary LAM assays are unsuitable as general screening tests for TB. However, unlike traditional diagnostic methods, they demonstrate improved sensitivity in HIV-TB co-infection which further increases with low CD4 counts. Accordingly, these assays are indicated as rule-in tests for TB in patients with advanced HIV-induced immunosuppression, and facilitate the early initiation of antituberculous treatment in them. They also offer incremental sensitivity and specificity when used as adjunct tests to smear microscopy and chest radiography in HIV-TB co-infection. They obviate the biohazards associated with sputum samples and provide an alternative diagnostic tool in sputum-scarce patients. Notwithstanding these advantages, the specificity of these assays is variable, which is mostly attributable to misclassification bias and cross-reactivity with non-tuberculous mycobacteria or other commensal flora. Furthermore, the inability to detect low titres of antigen in HIV-uninfected patients makes these assays unsuitable for use in settings with a low HIV prevalence. Future research targeted towards inclusion of specific monoclonal antibodies and more sensitive immunoassay platforms might help to improve the diagnostic performance of these assays and extend their applicability to the general population of patients with TB.
The Activity of [60]Fullerene Derivatives Bearing Amine and Carboxylic Solubilizing Groups against Escherichia coli: A Comparative Study
Authors: Deryabin Dmitry G. , Davydova Olga K. , Yankina Zulfiya ZH. , Vasilchenko Alexey S. , Miroshnikov Sergei A. , Kornev Alexey B. , Ivanchikhina Anastasiya V. , Troshin Pavel A. 
Published: January 2014

We report a comparative investigation of the antibacterial activity of two water‐soluble fullerene derivatives bearing protonated amine (AF) and deprotonated carboxylic (CF) groups appended to the fullerene cage via organic linkers. The negatively charged fullerene derivative CF showed no tendency to bind to the bacterial cells and, consequently, no significant antibacterial activity. In contrast, the compound AF loaded with cationic groups showed strong and partially irreversible binding to the negatively charged Escherichia coli K12 TG1 cells and to human erythrocytes, also possessing negative zeta potential. Adsorption of AF on the bacterial surface was visualized by atomic force microscopy revealing the formation of specific clusters (AF aggregates) surrounding the bacterial cell. Incubation of E. coli K12 TG1 with AF led to a dose‐dependent bactericidal effect with LD50 = 79.1 µM. The presence of human erythrocytes in the test medium decreased the AF antibacterial activity. Thus we reveal that the water‐soluble cationic fullerene derivative AF possesses promising antibacterial activity, which might be utilized in the development of novel types of chemical disinfectants.
Risk of Prostate Cancer in Lynch Syndrome: A Systematic Review and Meta-analysis
Authors: Ryan Shae , Jenkins Mark A. , Win Aung Ko 
Published: January 2014

Abstract
It has been controversial that men carrying a DNA mismatch repair (MMR) gene mutation (Lynch syndrome) are at heightened risk of prostate cancer given that an increased risk is likely to be modest and the prevalence of prostate cancer is high. We used PubMed to search for “molecular studies” that reported MMR-deficiency status of prostate cancer tumors in men with an MMR gene mutation, and “risk studies” that reported prostate cancer risk for men known or suspected to have an MMR gene mutation relative to that for noncarriers or the general population. Of the six molecular studies, 32 of 44 [73%, 95% confidence intervals (CI), 57%–85%] prostate cancer tumors in carriers were MMR deficient, which equates to carriers having a 3.67-fold increased risk of prostate cancer (95% CI, 2.32–6.67). Of the 12 risk studies, we estimated a 2.13-fold increased risk of prostate cancer (95% CI, 1.45–2.80) for male carriers in clinic-based retrospective cohorts, 2.11 (95% CI, 1.27–2.95) for male carriers with a prior diagnosis of colorectal cancer, and 2.28 (95% CI, 1.37–3.19) for all men from mutation-carrying families. The combination of evidence from molecular and risk studies in the current literature supports consideration of prostate cancer as part of Lynch syndrome. Cancer Epidemiol Biomarkers Prev; 23(3); 437–49. ©2014 AACR.
Decitabine Induces Delayed Reactive Oxygen Species (ROS) Accumulation in Leukemia Cells and Induces the Expression of ROS Generating Enzymes
Authors: Fandy Tamer E. , Jiemjit Anchalee , Thakar Manjusha , Rhoden Paulette , Suarez Lauren , Gore Steven D. 
Published: January 2014

Abstract
Purpose: Azanucleoside DNA methyltransferase (DNMT) inhibitors are currently approved by the U.S. Food and Drug Administration for treatment of myelodysplastic syndrome. The relative contributions of DNMT inhibition and other off-target effects to their clinical efficacy remain unclear. Data correlating DNA methylation reversal and clinical response have been conflicting. Consequently, it is necessary to investigate so-called off-target effects and their impact on cell survival and differentiation.
Experimental Design: Flow cytometry was used for cell cycle, apoptosis, and reactive oxygen species (ROS) accumulation analysis. Gene expression analysis was performed using real-time PCR. DNA methylation was detected by methylation-specific PCR. Mitochondrial membrane potential was analyzed using JC-1 dye staining. Western blotting was used for quantitative protein expression analysis.
Results: 5-Aza-2′-deoxycytidine (DAC) induced cell-cycle arrest and apoptosis in leukemia cells. p53 expression was dispensable for DAC-induced apoptosis. DAC induced delayed ROS accumulation in leukemia cells but not in solid tumor cells and p53 expression was dispensable for ROS increase. ROS increase was deoxycytidine kinase dependent, indicating that incorporation of DAC into nuclear DNA is required for ROS generation. ROS accumulation by DAC was caspase-independent and mediated the dissipation of the mitochondrial membrane potential. Concordantly, ROS scavengers diminished DAC-induced apoptosis. DAC induced the expression of different NADPH oxidase isoforms and upregulated Nox4 protein expression in an ATM-dependent manner, indicating the involvement of DNA damage signaling in Nox4 upregulation.
Conclusion: These data highlight the importance of mechanisms other than DNA cytosine demethylation in modulating gene expression and suggest investigating the relevance of ROS accumulation to the clinical activity of DAC. Clin Cancer Res; 20(5); 1249–58. ©2014 AACR.
Inflammatory Markers and Development of Symptom Burden in Patients with Multiple Myeloma during Autologous Stem Cell Transplantation
Authors: Wang Xin Shelley , Shi Qiuling , Shah Nina D. , Heijnen Cobi J. , Cohen Evan N. , Reuben James M. , Orlowski Robert Z. , Qazilbash Muzaffar H. , Johnson Valen E. , Williams Loretta A. , Mendoza Tito R. , Cleeland Charles S. 
Published: January 2014

Abstract
Purpose: Increasing research suggests that inflammation mediates symptom development. In this longitudinal study, we examined inflammatory factors related to the development of high symptom burden during autologous hematopoietic stem cell transplant (AuSCT) for multiple myeloma.
Experimental Design: Patients (n = 63) repeatedly reported symptom severity on the MD Anderson Symptom Inventory multiple myeloma module (MDASI-MM) and contributed blood samples periodically for up to 100 days after AuSCT for inflammatory marker assays. The temporal associations between serum inflammatory marker concentrations and symptom severity outcomes were examined by nonlinear mixed-effect modeling.
Results: Fatigue, pain, disturbed sleep, lack of appetite, and drowsiness were consistently the most severe MDASI-MM symptoms during the study. Peak symptom severity occurred on day 8 after AuSCT, during white blood cell count nadir. Patterns of serum interleukin (IL)-6 (peak on day 9) and soluble IL-6 receptor (sIL-6R; nadir on day 8) expression paralleled symptom development over time (both P &lt; 0.0001). By univariate analysis, serum IL-6, sIL-6R, IL-10, C-reactive protein, macrophage inflammatory protein (MIP)-1α, sIL-1R2, sIL-1RA, and soluble tumor necrosis factor receptor 1 were significantly related to the most severe symptoms during the first 30 days after AuSCT (all P &lt; 0.05). By multivariate analysis, IL-6 (estimate = 0.170; P = 0.004) and MIP-1α (estimate = −0.172; P = 0.006) were temporally associated with the severity of the component symptom score.
Conclusions: Systemic inflammatory response was associated with high symptom burden during the acute phase of AuSCT. Additional research is needed to understand how the inflammatory response is mechanistically associated with symptom expression and whether suppression of this response can reduce symptoms without compromising tumor control. Clin Cancer Res; 20(5); 1366–74. ©2014 AACR.
XPO1 (CRM1) Inhibition Represses STAT3 Activation to Drive a Survivin-Dependent Oncogenic Switch in Triple-Negative Breast Cancer
Authors: Cheng Yan , Holloway Michael P. , Nguyen Kevin , McCauley Dilara , Landesman Yosef , Kauffman Michael G. , Shacham Sharon , Altura Rachel A. 
Published: January 2014

Abstract
Inhibition of XPO1 (CRM1)-mediated nuclear export of multiple tumor suppressor proteins has been proposed as a novel cancer therapeutic strategy to turn off oncogenic signals and enhance tumor suppression. Survivin is a multifunctional protein with oncogenic properties when expressed in the cytoplasm that requires the XPO1–RanGTP complex for its nuclear export. We investigated the antitumor mechanisms of the drug-like selective inhibitors of nuclear export (SINE) XPO1 antagonists KPT-185, KPT-251 KPT-276, and KPT-330 in estrogen receptor–positive and triple-negative breast cancer (TNBC) cell lines and xenograft models of human breast tumors. KPT compounds significantly inhibited breast cancer cell growth and induced tumor cell death, both in vitro and in vivo. These drugs initially promoted survivin accumulation within tumor cell nuclei. However, their major in vitro effect was to decrease survivin cytoplasmic protein levels, correlating with the onset of apoptosis. XPO1 inhibition repressed Survivin transcription by inhibiting CREB-binding protein-mediated STAT3 acetylation, and blocking STAT3 binding to the Survivin promoter. In addition, caspase-3 was activated to cleave survivin, rendering it unavailable to bind X-linked inhibitor of apoptosis protein and block the caspase cascade. Collectively, these data demonstrate that XPO1 inhibition by SINE compounds represses STAT3 transactivation to block the selective oncogenic properties of survivin and supports their clinical use in TNBC. Mol Cancer Ther; 13(3); 675–86. ©2014 AACR.
HSPC111 Governs Breast Cancer Growth by Regulating Ribosomal Biogenesis
Authors: Zhang Changwen , Yin Chunyang , Wang Lei , Zhang Shuping , Qian Yi , Ma Juan , Zhang Zhihong , Xu Yong , Liu Sijin 
Published: January 2014

Abstract
Activation of c-Myc plays a decisive role in the development of many human cancers. As a transcription factor, c-Myc facilitates cell growth and proliferation by directly transcribing a multitude of targets, including rRNAs and ribosome proteins. However, how to elucidate the deregulation of rRNAs and ribosome proteins driven by c-Myc in cancer remains a significant challenge and thus warrants close investigation. In this report, a crucial role for the HSPC111 (NOP16) multiprotein complex in governing ribosomal biogenesis and tumor growth was determined. It was discovered that enhanced HSPC111 expression paralleled the upregulation of c-Myc and was directly regulated by c-Myc in breast cancer cells. Knockdown of HSPC111 dramatically reduced the occurrence of tumorigenesis in vivo, and largely restrained tumor cell growth in vitro and in vivo. In stark contrast, HSPC111 overexpression significantly promoted tumor cell growth. Biochemically, it was demonstrated that RNA 3′-phosphate cyclase (RTCD1/RTCA) interacted with HSPC111, and RTCD1 was involved in the HSPC111 multiprotein complex in regulating rRNA production and ribosomal biogenesis. Moreover, HSPC111 and RTCD1 synergistically modulated cell growth and cellular size through commanding rRNA synthesis and ribosome assembly coupled to protein production. Finally, overall survival analysis revealed that concomitant upregulation of HSPC111 and RTCD1 correlated with the worst prognosis in a breast cancer cohort.
Implications: Inhibition of HSPC111-dependent ribosomal biosynthesis and protein synthesis is a promising therapeutic strategy to diminish breast cancer tumor progression. Mol Cancer Res; 12(4); 583–94. ©2014 AACR.
Raloxifene and Antiestrogenic Gonadorelin Inhibits Intestinal Tumorigenesis by Modulating Immune Cells and Decreasing Stem-like Cells
Authors: Janakiram Naveena B. , Mohammed Altaf , Brewer Misty , Bryant Taylor , Biddick Laura , Lightfoot Stan , Pathuri Gopal , Gali Hariprasad , Rao Chinthalapally V. 
Published: January 2014

Abstract
Studies suggest that estrogen plays a contributing role in colorectal cancer. This project examined the preventive effects of raloxifene, a selective estrogen receptor modulator (SERM), and gonadorelin, an antiestrogenic drug, in female ApcMin/+ mouse intestinal tumorigenesis. Six-week-old ApcMin/+mice were fed diet containing 1 ppm raloxifene or control diet. Gonadorelin (150 ng/mouse) was injected subcutaneously into one treatment group. Intestinal tumors were evaluated for tumor multiplicity and size. Mice treated with raloxifene and gonadorelin showed colon tumor inhibition of 80% and 75%, respectively. Both drugs significantly inhibited small intestinal tumor multiplicity and size (75%–65%, P &lt; 0.0001). Raloxifene and gonadorelin showed significant tumor inhibition with 98% and 94% inhibition of polyps &gt;2 mm in size. In mice fed with raloxifene or injected with gonadorelin, tumors showed significantly reduced proliferating cell nuclear antigen expression (58%–65%, P &lt; 0.0001). Raloxifene treatment decreased β-catenin, cyclin D1, laminin 1β, Ccl6, and stem-like cells (Lgr 5, EpCAM, CD44/CD24), as well as suppressed inflammatory genes (COX-2, mPGES-1, 5-LOX,). Gonadorelin showed significant decrease in COX-2, mPGES-1, iNOS, and stem-like cells or increased NK cells and chemokines required for NK cells. Both drugs were effective in suppressing tumor growth albeit with different mechanisms. These observations show that either suppression of estrogen levels or modulation of estrogen receptor dramatically suppresses small intestinal and colonic tumor formation in female ApcMin/+ mice. These results support the concept of chemoprevention by these agents in reducing endogenous levels of estrogen or modulating ER signaling. Cancer Prev Res; 7(3); 300–9. ©2014 AACR.
Risk of bleeding and antibiotic use in patients receiving continuous phenprocoumon therapy
Authors: Ihle Peter , Harder Sebastian , Schubert Ingrid , Abbas Sascha 
Published: January 2014

SummaryThere is major concern about coumarins interacting with various drug classes and increasing the risk of overanticoagulation. The aim of the study was to assess bleeding risk in patients with concurrent use of antibiotics and phenprocoumon, the most widely prescribed coumarin in many European countries. We conducted a nested-case-control study within a cohort of 513,338 incident and continuous phenpro-coumon users ≥18 years of age using claims data of the statutory health insurance company AOK, covering 30% of the German population. Bleeding risk associated with current use of antibiotics for systemic use (antibacterials/antimycotics) was calculated using conditional logistic regression in 13,785 cases with a bleeding event and 55,140 risk-set sampling-matched controls. Bleeding risk associated with any antibacterial use in phenprocoumon users was significantly increased [odds ratio (OR) 2.37, 95% confidence interval (CI) 2.20–2.56]. The association was stronger for gastrointestinal than for cerebral bleeding (OR 2.09, 95% CI 1.84–2.38 and OR 1.34, 95% CI 1.03–1.74, respectively) and highest for other/unspecified bleeding (OR 2.92, 95% CI 2.62–3.26). Specific antibiotic classes were strongly associated with bleeding risk, e.g. cotrimoxazole (OR 3.86, 95% CI 3.08–4.84) and fluorquinolones (OR 3.13, 95% CI 2.74–3.59), among those highest for ofloxacin (OR 5.00, 95% CI 3.01–8.32). Combined use of phenprocoumon and antimycotics was not significantly associated with bleeding risk. Risk was not significantly modified by age (pint=0.25) or sex (pint=0.96). The association was stronger the closer the antibiotic exposure was to the bleeding event. Among continuous phenprocoumon users, antibiotics – particularly quinolones and co-trimoxazole – should be prescribed after careful consideration due to an increased bleeding risk. Close monitoring of international normalised ratio levels after prescription is recommended.
Cyclophilin A is an important mediator of platelet function by regulating integrin αIIbβ3 bidirectional signalling
Authors: Wang Lian , Soe Nwe Nwe , Sowden Mark , Xu Yingqian , Modjeski Kristina , Baskaran Padmamalini , Kim Yeonghwan , Smolock Elaine M. , Morrell Craig N. , Berk Bradford C. 
Published: January 2014

SummaryCyclophilin A (CyPA) is an important mediator in cardiovascular diseases. It possesses peptidyl-prolyl cis-trans isomerase activity (PPIase) and chaperone functions, which regulate protein folding, intracellular trafficking and reactive oxygen species (ROS) production. Platelet glycoprotein receptor αIIbβ3 integrin activation is the common pathway for platelet activation. It was our objective to understand the mechanism by which CyPA-regulates αIIbβ3 activation in platelets. Mice deficient for CyPA (CyPA−/−) had prolonged tail bleeding time compared to wild-type (WT) controls despite equivalent platelet numbers. In vitro studies revealed that CyPA−/− platelets exhibited dramatically decreased thrombin-induced platelet aggregation. In vivo, formation of occlusive thrombi following FeCl3 injury was also significantly impaired in CyPA−/− mice compared with WT-controls. Furthermore, CyPA deficiency inhibited flow-induced thrombus formation in vitro. Flow cytometry demonstrated that thrombin-induced ROS production and αIIbβ3 activation were reduced in CyPA−/− platelets. Coimmunoprecipitation studies showed ROS-dependent increased association of CyPA and αIIbβ3. This association was dependent upon the PPIase activity of CyPA. Significantly, fibrinogen-platelet binding, platelet spreading and cytoskeleton reorganisation were also altered in CyPA−/− platelets. Moreover, CyPA deficiency prevented thrombin-induced αIIbβ3 and cytoskeleton association. In conclusion, CyPA is an important mediator in platelet function by regulation of αIIbβ3 bidirectional signalling through increased ROS production and facilitating interaction between αIIbβ3 and the cell cytoskeleton.