bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Application for Expanded Porphyrins: Sapphyrin and Heterosapphyrins as Inhibitors of Leishmania Parasites
Authors: Hooker Jaqueline D. , Nguyen Victoria H. , Taylor Viviana M. , Cedeño David L. , Lash Timothy D. , Jones Marjorie A. , Robledo Sara M. , Vélez Iván D. 
Published: November 2011

AbstractSapphyrins and a series of related porphyrinoid macrocycles have been investigated as potential agents for the treatment of leishmaniasis. The effectiveness of the compounds was evaluated in vitro upon incubation with Leishmania tarentolae or L. panamensis amastigotes and promastigotes. Their effectiveness was also assessed against intracellular L. panamensis. The cytotoxicity of the compounds was evaluated in vitro using the U937 human promonocyte cell line. Effectiveness and cytotoxicity were assessed in the presence and absence of visible light to assess the photodynamic activity of the compounds. Sapphyrin and two related heterosapphyrins were shown to be particularly effective as inhibitors of Leishmania. A photodynamic effect was observed, which may be attributed to the formation of reactive oxygen species. Yields of singlet oxygen (1O2) produced were determined in ethanol solutions by direct measurement of 1O2 phosphorescence. Confocal microscopy demonstrated that sapphyrin and related macrocycles were taken up by the Leishmania cells and that their presence induces the formation of mitochondrial superoxide. Sapphyrins have been widely investigated as anticancer agents and we here show activity against the Leishmania parasites.
Antitumor Efficacy of Photodynamic Therapy Using Novel Nanoformulations of Hypocrellin Photosensitizer SL052
Authors: Korbelik Mladen , Madiyalakan Ragupathy , Woo Thomas , Haddadi Azita 
Published: November 2011

AbstractRecent preclinical and clinical testing of hypocrellin‐based photosensitizer SL052 for use in photodynamic therapy (PDT) of cancer has shown encouraging results. Further optimization of its formulation for delivery could considerably extend the therapeutic efficiency of this drug. A nanoformulation encapsulating SL052 into biodegradable polymer poly(lactic‐co‐glycolic acid) (PLGA) was developed using a single‐emulsion solvent evaporation technique and characterized in terms of particle size and loading of the photosensitizing agent. This nanoformulation, SL052‐PLGA‐nanoparticles (NPs), was compared with recently created nanoformulation based on polyvinylpyrrolidone (SL052‐PVP‐NPs) and standard liposomal SL052 preparation in terms of efficacy when used for PDT treatment of squamous cell carcinomas SCCVII growing subcutaneously in syngeneic mice. The therapeutic effect of PDT using these three different SL052 formulations was tested for both 1 and 4 h intervals between drug injection and tumor light exposure. The longer time interval produced higher tumor cure rates with all SL052 preparations. With both drug‐light intervals, PDT based on SL052‐PLGA‐NPs produced superior therapeutic benefit compared with the other two SL052 formulations.
Events leading to anterior cruciate ligament injury in World Cup Alpine Skiing: a systematic video analysis of 20 cases
Authors: Bere Tone , Flørenes Tonje Wåle , Krosshaug Tron , Nordsletten Lars , Bahr Roald 
Published: November 2011

BackgroundThe authors have recently identified three main mechanisms for anterior cruciate ligament (ACL) injuries among World Cup (WC) alpine skiers, termed as “the slip-catch”, “the landing back-weighted” and “the dynamic snowplow”. However, for a more complete understanding of how these injuries occur, a description of the events leading to the injury situations is also needed.ObjectiveTo describe the skiing situation leading to ACL injuries in WC alpine skiing.MethodsTwenty cases of ACL injuries reported through the International Ski Federation Injury Surveillance System (FIS ISS)for three consecutive WC seasons (2006–2009) were obtained on video. Ten experts (9 WC coaches, 1 former WC athlete) performed visual analyses of each case to describe in their own words, factors they thought may have contributed to the injury situation related to different predefined categories: (1) skier technique, (2) skier strategy, (3) equipment, (4) speed and course setting, (5) visibility, snow and piste conditions and (6) any other factors.ResultsFactors related to the three categories, namely skier technique, skier strategy, and visibility, snow and piste conditions, were assumed to be the main contributors to the injury situations. Skier errors, technical mistakes and inappropriate tactical choices, were the dominant factors. In addition, bumpy conditions, aggressive snow, reduced visibility and course difficulties were assumed to contribute.ConclusionBased on this systematic video analysis of 20 injury situations, factors related to skier technique, skier strategy and specific race conditions were identified as the main contributors leading to injury situations.
The association of depression, risky sexual behaviours and herpes simplex virus type 2 in adults in NHANES, 2005–2008
Authors: Pratt L A , Xu F , McQuillan G M , Robitz R 
Published: November 2011

ObjectivesDepression has been linked to risky sexual behaviours in adolescents, but there is little research among adults. The goal of this analysis was to examine the associations between current depression and self-reported risky sexual behaviours in a nationally representative sample of US adults aged 20–59 years. The authors also examined the association between depression and infection with herpes simplex virus type 2 (HSV-2), a biological marker of risky sexual behaviours.MethodsThe authors used data from the 2005–2008 National Health and Nutrition Examination Surveys. Current depression was measured by the Patient Health Questionnaire-9. Antibodies to HSV-2 were tested using the enzymatic immunodot assay. The authors used logistic regression to examine the associations controlling for socio-demographic variables.ResultsAmong 5273 adults aged 20–59 years, 7% had depression, 36% reported 10 or more lifetime sex partners, 15% had two or more past-year sex partners and 13% had first sex before 15 years of age. Persons with each of the risky sexual behaviours were more likely to have depression than those without. In stratified analyses, risky sexual behaviours were associated with depression in women but not in men. Among 3940 adults aged 20–49 years, 19% had HSV-2 infection. Persons with HSV-2 infection were more likely to have depression (OR 2.1, 95% CI 1.5 to 2.9).ConclusionsRisky sexual behaviour is related to current depression in adult women. Healthcare providers should be aware of this association and its potential implications in order to deliver better care for patients with depression or sexually transmitted infections.
Defective NF-κB Signaling in Metastatic Head and Neck Cancer Cells Leads to Enhanced Apoptosis by Double-Stranded RNA
Authors: Umemura Naoki , Zhu Jianzhong , Mburu Yvonne K. , Forero Adriana , Hsieh Paishiun N. , Muthuswamy Ravikumar , Kalinski Pawel , Ferris Robert L. , Sarkar Saumendra N. 
Published: November 2011

Abstract
Ligands to several Toll-like receptors (TLR), which mediate innate immune responses and chronic inflammation have been used as adjuvants to immunotherapy to enhance their antitumor activity. In particular, double-stranded RNAs that are cognate ligands of TLR3 have been used to trigger proapoptotic activity in cancer cells. However, a mechanistic understanding of TLR3-mediated apoptosis and its potential involvement in controlling tumor metastasis has been lacking. In this study, we used paired cell lines and fresh tumor specimens, derived from autologous primary and metastatic head and neck squamous cell carcinoma, to investigate the role of TLR3 signaling in metastatic progression. Compared with primary tumor cells, metastatic tumor cells were highly sensitive to TLR3-mediated apoptosis after double-stranded RNA treatment. Enhanced apoptosis in metastatic cells was dependent on double-stranded RNA and TLR3 and also the TLR3 effector signaling protein TRIF. Downstream responses requiring NF-κB were critical for apoptosis in metastatic cells, the defects in which could be resuscitated by alternative pathways of NF-κB activation. By elucidating how TLR3 ligands trigger apoptosis in metastatic cells, our findings suggest insights into how to improve their clinical use. Cancer Res; 72(1); 45–55. ©2011 AACR.
A Combined Array-Based Comparative Genomic Hybridization and Functional Library Screening Approach Identifies mir-30d As an Oncomir in Cancer
Authors: Li Ning , Kaur Sippy , Greshock Joel , Lassus Heini , Zhong Xiaomin , Wang Yanling , Leminen Arto , Shao Zhongjun , Hu Xiaowen , Liang Shun , Katsaros Dionyssios , Huang Qihong , Bützow Ralf , Weber Barbara L. , Coukos George , Zhang Lin 
Published: November 2011

Abstract
Oncomirs are microRNAs (miRNA) that acts as oncogenes or tumor suppressor genes. Efficient identification of oncomirs remains a challenge. Here we report a novel, clinically guided genetic screening approach for the identification of oncomirs, identifying mir-30d through this strategy. mir-30d regulates tumor cell proliferation, apoptosis, senescence, and migration. The chromosomal locus harboring mir-30d was amplified in more than 30% of multiple types of human solid tumors (n = 1,283). Importantly, higher levels of mir-30d expression were associated significantly with poor clinical outcomes in ovarian cancer patients (n = 330, P = 0.0016). Mechanistic investigations suggested that mir-30d regulates a large number of cancer-associated genes, including the apoptotic caspase CASP3. The guided genetic screening approach validated by this study offers a powerful tool to identify oncomirs that may have utility as biomarkers or targets for drug development. Cancer Res; 72(1); 154–64. ©2011 AACR.
Tumor-Derived Autophagosome Vaccine: Mechanism of Cross-Presentation and Therapeutic Efficacy
Authors: Li Yuhuan , Wang Li-Xin , Pang Puiyi , Cui Zhihua , Aung Sandra , Haley Daniel , Fox Bernard A. , Urba Walter J. , Hu Hong-Ming 
Published: November 2011

AbstractPurpose: We previously reported that autophagy in tumor cells plays a critical role in cross-presentation of tumor antigens and that autophagosomes are efficient antigen carriers for cross-priming of tumor-reactive CD8+ T cells. Here, we sought to characterize further the autophagosome-enriched vaccine named DRibble (DRiPs-containing blebs), which is derived from tumor cells after inhibition of protein degradation, and to provide insights into the mechanisms responsible for their efficacy as a novel cancer immunotherapy.Experimental Design: DRibbles were characterized by Western blot and light or transmission electron microscopy. The efficiency of cross-presentation mediated by DRibbles was first compared with that of whole-tumor cells and pure proteins. The mechanisms of antigen cross-presentation by DRibbles were analyzed, and the antitumor efficacy of the DRibble vaccine was tested in 3LL Lewis lung tumors and B16F10 melanoma.Results: The DRibbles sequester both long-lived and short-lived proteins, including defective ribosomal products (DRiP), and damage-associated molecular pattern molecules exemplified by HSP90, HSP94, calreticulin, and HMGB1. DRibbles express ligands for CLEC9A, a newly described C-type lectin receptor expressed by a subset of conventional and plasmacytoid dendritic cells (DC), and cross-presentation was partially CLEC9A dependent. Furthermore, this autophagy-assisted antigen cross-presentation pathway involved both caveolae- and clathrin-mediated endocytosis and endoplasmic reticulum–associated degradation machinery. It depends on proteasome and TAP1, but not lysosome functions of antigen-presenting cells. Importantly, DCs loaded with autophagosome-enriched DRibbles can eradicate 3LL Lewis lung tumors and significantly delay the growth of B16F10 melanoma.Conclusions: These data documented the unique characteristics and potent antitumor efficacy of the autophagosome-based DRibble vaccine. The efficacy of DRibble cancer vaccine will be further tested in clinical trials. Clin Cancer Res; 17(22); 7047–57. ©2011 AACR.
Indoleamine 2,3-Dioxygenase Expression in Human Cancers: Clinical and Immunologic Perspectives
Authors: Godin-Ethier Jessica , Hanafi Laïla-Aïcha , Piccirillo Ciriaco A. , Lapointe Réjean 
Published: November 2011

Abstract
Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme with immune-regulating activities in many contexts, such as fetal protection, allograft protection, and cancer progression. Clinical trials are currently evaluating IDO inhibition with 1-methyltryptophan in cancer immunotherapy. However, the exact role of tryptophan catabolism by IDO in human cancers remains poorly understood. Here, we review several studies that correlate IDO expression in human cancer samples and tumor-draining lymph nodes, with relevant clinical or immunologic parameters. IDO expression in various histologic cancer types seems to decrease tumor infiltration of immune cells and to increase the proportion of regulatory T lymphocytes in the infiltrate. The impact of IDO on different immune cell infiltration leads to the conclusion that IDO negatively regulates the recruitment of antitumor immune cells. In addition, increased IDO expression correlates with diverse tumor progression parameters and shorter patient survival. In summary, in the vast majority of the reported studies, IDO expression is correlated with a less favorable prognosis. As we may see results from the first clinical trials with 1-methyltryptophan in years to come, this review brings together IDO studies from human studies and aims to help appreciate outcomes from current and future trials. Consequently, IDO inhibition seems a promising approach for cancer immunotherapy. Clin Cancer Res; 17(22); 6985–91. ©2011 AACR.
Clinical Outcome of Autologous Chondrocyte Implantation for Failed Microfracture Treatment of Full-Thickness Cartilage Defects of the Knee Joint
Authors: Pestka Jan M. , Bode Gerrit , Salzmann Gian , Südkamp Norbert P. , Niemeyer Philipp 
Published: November 2011

Background: Although various factors have been identified that influence outcome after autologous chondrocyte implantation (ACI), the relevance of prior treatment of the cartilage defect and its effect concerning the outcome of second-line ACI have not been evaluated to a full extent. Hypothesis: Autologous chondrocyte implantation used as a second-line treatment after failed arthroscopic microfracturing is associated with a higher failure rate and inferior clinical results compared with ACI as a first-line treatment. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 28 patients with isolated cartilage defects at the knee joint were treated with ACI after microfracture as a first-line treatment had failed (failure defined as the necessity of reintervention). These patients were assigned to group A and compared with a matched-pair cohort of patients of identical age, defect size, and defect location (group B) in which ACI was used as a first-line treatment. Failure rates in both groups were assessed. Postoperative knee status was evaluated with the International Knee Documentation Committee (IKDC) score and Knee injury and Osteoarthritis Outcome Score (KOOS), and sporting activity was assessed by use of the Activity Rating Scale. Mean follow-up times were 48.0 months (range, 15.1-75.1 months) in group A and 41.4 months (range, 15.4-83.6 months) in group B. Differences between groups A and B were analyzed by Student t test. Results: Group A had significantly greater failure rates (7 of 28 patients) in comparison with group B (1 of 28 patients; P = .0241). Mean (SD) postoperative IKDC scores revealed 58.4 (22.4) points in group A with a trend toward higher score results (69.0 [19.1] points) for patients in group B ( P = .0583). Significantly different results were obtained for KOOS pain and activity of daily living subscales, whereas the remaining KOOS subscales did not show significant differences. Despite the significantly higher failure rate observed in group A, those patients did not participate in fewer activities or perform physical activity less frequently or at a lower intensity. Conclusion: Autologous chondrocyte implantation after failed microfracturing appears to be associated with a significantly higher failure rate and inferior clinical outcome when compared with ACI as a first-line treatment.
The Chi-Square Test
Authors: Franke Todd Michael , Ho Timothy , Christie Christina A. 
Published: November 2011

The examination of cross-classified category data is common in evaluation and research, with Karl Pearson's family of chi-square tests representing one of the most utilized statistical analyses for answering questions about the association or difference between categorical variables. Unfortunately, these tests are also among the more commonly misinterpreted statistical tests in the field. The problem is not that researchers and evaluators misapply the results of chi-square tests, but rather they tend to over interpret or incorrectly interpret the results, leading to statements that may have limited or no statistical support based on the analyses preformed. This paper attempts to clarify any confusion about the uses and interpretations of the family of chi-square tests developed by Pearson, focusing primarily on the chi-square tests of independence and homogeneity of variance (identity of distributions). A brief survey of the recent evaluation literature is presented to illustrate the prevalence of the chi-square test and to offer examples of how these tests are misinterpreted. While the omnibus form of all three tests in the Karl Pearson family of chi-square tests—independence, homogeneity, and goodness-of-fit,—use essentially the same formula, each of these three tests is, in fact, distinct with specific hypotheses, sampling approaches, interpretations, and options following rejection of the null hypothesis. Finally, a little known option, the use and interpretation of post hoc comparisons based on Goodman's procedure ( Goodman, 1963 ) following the rejection of the chi-square test of homogeneity, is described in detail.
Validation of a multi-marker model for the prediction of incident type 2 diabetes mellitus: Combined results of the Inter99 and Botnia studies
Authors: Lyssenko Valeria , Jørgensen Torben , Gerwien Robert W , Hansen Torben , Rowe Michael W , McKenna Michael P , Kolberg Janice , Pedersen Oluf , Borch-Johnsen Knut , Groop Leif 
Published: November 2011

Purpose: To assess performance of a biomarker-based score that predicts the five-year risk of diabetes (Diabetes Risk Score, DRS) in an independent cohort that included 15-year follow-up. Method: DRS was developed on the Inter99 cohort, and validated on the Botnia cohort. Performance was benchmarked against other risk-assessment tools comparing calibration, time to event analysis, and net reclassification. Results: The area under the receiver-operating characteristic curve (AUC) was 0.84 for the Inter99 cohort and 0.78 for the Botnia cohort. In the Botnia cohort, DRS provided better discrimination than fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance, oral glucose tolerance test or risk scores derived from Framingham or San Antonio Study cohorts. Overall reclassification with DRS was significantly better than using FPG and glucose tolerance status ( p < 0.0001). In time to event analysis, rates of conversion to diabetes in low, moderate, and high DRS groups were significantly different ( p < 0.001). Conclusion: This study validates DRS performance in an independent population, and provides a more accurate assessment of T2DM risk than other methods.
Association of diabetes with increased all-cause mortality following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction in the contemporary era
Authors: Kahn Matthew B , Cubbon Richard M , Mercer Ben , Wheatcroft Alison CG , Gherardi Guy , Aziz Amir , Baliga Vivek , Blaxill Jonathan M , McLenachan Jim M , Blackman Daniel J , Greenwood John P , Wheatcroft Stephen B 
Published: November 2011

Background: We investigated the association between diabetes mellitus (DM) and all-cause mortality in a large cohort of consecutive patients treated with primary percutaneous coronary intervention (PPCI) in the contemporary era. Methods: We conducted a retrospective analysis of a single-centre registry of patients undergoing PPCI for ST-segment elevation myocardial infarction (STEMI) at a large regional PCI centre between 2005 and 2009. All-cause mortality in relation to patient and procedural characteristics was compared between patients with and without DM. Results: Of 2586 patients undergoing PPCI, 310 (12%) had DM. Patients with DM had a higher prevalence of multi-vessel coronary disease ( p<0.001) and prior myocardial infarction ( p<0.001). Patients with DM were less commonly admitted directly to the interventional centre ( p=0.002). Symptom-to-balloon ( p<0.001) and door-to-balloon time ( p=0.002) were longer in patients with DM. Final infarct-related-artery TIMI-flow grade was lower in patients with DM ( p=0.031). All-cause mortality at 30 days ( p=0.0025) and 1 year ( p<0.0001) was higher in patients with DM. DM was independently associated with increased mortality after multivariate adjustment for potential confounders. Conclusions: Mortality remains substantially higher in patients with DM following reperfusion for STEMI in comparison with those without diabetes, despite contemporary management with PPCI. Greater co-morbidity, delayed presentation, longer times-to-reperfusion, and less optimal reperfusion may contribute to adverse outcomes.