bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV and sexually transmitted infections at the borderlands: situational analysis of sexual health in the Brazilian Amazon
Authors: Benzaken Adele , Sabidó Meritxell , Galban Enrique , Rodrigues Dutra Daniel Lúcio , Leturiondo André Luiz , Mayaud Philippe 
Published: February 2012

ObjectivesThe borderlands are considered areas of increased vulnerability to HIV and sexually transmitted infections (STI). The study aimed to determine the STI/HIV prevalence and risk factors in the triple-border area of the Brazilian Amazon.MethodsA situational analysis of sexual health was conducted in three cities of the Alto Solimões region. This multicomponent research approach included key informant interviews, participant observations and mapping of places where people meet sexual partners. Volunteers recruited from the ‘hot spots’ in each city were invited for interview and STI/HIV testing.ResultsOver 6 months, 598 participants were recruited, 285 men of median age 28 years (IQR, 23–37) and 313 women of median age 29 years (IQR, 24–37). Overall, 49.3% reported a casual partner during the past 3 months, but only 38.5% reported consistent condom use. The respective prevalences in men and women wereNeisseria gonorrhoeae(1.1% and 0.3%),Chlamydia trachomatis(1.4% and 4.8%), high-risk human papillomavirus (14.4% and 24.0%), active syphilis (3.2% and 2.6%), herpes simplex virus type-2 (51.1% and 72.1%), hepatitis B virus (by hepatitis B virus surface antigen) (7.5% and 4.6%), hepatitis C virus (0.7% and 0.7%) and HIV (1.4% and 0.0%). Risk factors for viral STIs included female sex and age.ConclusionsWhile the main conditions that contribute to the spread of HIV are in place in the triple-border area, the prevalence of bacterial STIs and HIV are still relatively low, providing a window of opportunity for interventions.
Population dynamics and asynchrony at fine spatial scales: a case history of sockeye salmon (Oncorhynchus nerka) population structure in Alaska, USA
Authors: Quinn Thomas P. , Rich Harry B. , Gosse Dido , Schtickzelle Nicolas 
Published: February 2012

Pacific salmon (Oncorhynchus spp.) exemplify the ways in which populations are structured by homing and the abiotic factors affecting their dynamics in discrete breeding and rearing habitats. What is the finest spatial scale of their population structure, and where do clusters of spatially proximate breeding groups lie along the continuum from isolated populations – metapopulation – patchy panmictic population? To investigate these questions, we monitored sockeye salmon, Oncorhynchus nerka, spawning in a complex of habitats ~1 km apart, joining to form a single stream flowing into Iliamna Lake, Alaska, USA. Annual surveys revealed levels of asynchrony in productivity that were comparable with values reported for sockeye salmon spawning in separate streams flowing into lakes elsewhere in Bristol Bay. A mark–recapture study revealed very little movement of spawning adults among habitats. The ponds occupied at highest density varied among years, and salmon consistently arrived and spawned later in one pond than the others. These results are consistent with the hypothesis that the salmon structured as a small-scale metapopulation rather than a single panmictic population.
Integrative Genomics Identified RFC3 As an Amplified Candidate Oncogene in Esophageal Adenocarcinoma
Authors: Lockwood William W. , Thu Kelsie L. , Lin Lin , Pikor Larissa A. , Chari Raj , Lam Wan L. , Beer David G. 
Published: February 2012

Abstract
Purpose: Esophageal adenocarcinoma (EAC) is a lethal malignancy that can develop from the premalignant condition, Barrett's esophagus (BE). Currently, there are no validated simple methods to predict which patients will progress to EAC. A better understanding of the genetic mechanisms driving EAC tumorigenesis is needed to identify new therapeutic targets and develop biomarkers capable of identifying high-risk patients that would benefit from aggressive neoadjuvant therapy. We employed an integrative genomics approach to identify novel genes involved in EAC biology that may serve as useful clinical markers.
Experimental Design: Whole genome tiling-path array comparative genomic hybridization was used to identify significant regions of copy number alteration in 20 EACs and 10 matching BE tissues. Copy number and gene expression data were integrated to identify candidate oncogenes within regions of amplification and multiple additional sample cohorts were assessed to validate candidate genes.
Results: We identified RFC3 as a novel, candidate oncogene activated by amplification in approximately 25% of EAC samples. RFC3 was also amplified in BE from a patient whose EAC harbored amplification and was differentially expressed between nonmalignant and EAC tissues. Copy number gains were detected in other cancer types and RFC3 knockdown inhibited proliferation and anchorage-independent growth of cancer cells with increased copy number but had little effect on those without. Moreover, high RFC3 expression was associated with poor patient outcome in multiple cancer types.
Conclusions: RFC3 is a candidate oncogene amplified in EAC. RFC3 DNA amplification is also prevalent in other epithelial cancer types and RFC3 expression could serve as a prognostic marker. Clin Cancer Res; 18(7); 1936–46. ©2012 AACR.
Phase I/II Trial of Carboplatin and Paclitaxel Chemotherapy in Combination with Intravenous Oncolytic Reovirus in Patients with Advanced Malignancies
Authors: Karapanagiotou Eleni M. , Roulstone Victoria , Twigger Katie , Ball Mercel , Tanay MaryAnne , Nutting Chris , Newbold Kate , Gore Martin E. , Larkin James , Syrigos Konstantinos N. , Coffey Matt , Thompson Brad , Mettinger Karl , Vile Richard G. , Pandha Hardev S. , Hall Geoff D. , Melcher Alan A. , Chester John , Harrington Kevin J. 
Published: February 2012

Abstract
Purpose: Reovirus type 3 Dearing (RT3D) replicates preferentially in Ras-activated cancers. RT3D shows synergistic in vitro cytotoxicity in combination with platins and taxanes. The purpose of this phase I/II study was to assess RT3D combined with carboplatin/paclitaxel in patients with advanced cancers.
Experimental Design: Patients were initially treated in a dose-escalating, phase I trial with intravenous RT3D days 1 to 5, carboplatin [area under curve (AUC) 5, day 1] and paclitaxel (175 mg/m2, day 1) 3-weekly. RT3D was escalated through three dose levels: 3 × 109, 1 × 1010, and 3 × 1010 TCID50 in cohorts of three. Primary endpoints were to define the maximum tolerated dose and dose-limiting toxicity and to recommend a dose for phase II studies. Secondary endpoints included pharmacokinetics, immune response, and antitumor activity. A subsequent phase II study using the 3 × 1010 TCID50 dose characterized the response rate in patients with head and neck cancer.
Results: Thirty-one heavily pretreated patients received study therapy. There were no dose-limiting toxicities during dose-escalation and most toxicities were grade I/II. Overall effectiveness rates were as follows: one patient had a complete response (3.8%), six patients (23.1%) had partial response, two patients (7.6%) had major clinical responses clinically evaluated in radiation pretreated lesions which are not evaluable by Response Evaluation Criteria in Solid Tumors (RECIST), nine patients (34.6%) had stable disease, and eight patients (30.8%) had disease progression. Viral shedding was minimal and antiviral immune responses were attenuated compared with previous single-agent data for RT3D.
Conclusions: The combination of RT3D plus carboplatin/paclitaxel is well tolerated with evidence of activity in cancer of the head and neck. A randomized phase III study is currently open for recruitment. Clin Cancer Res; 18(7); 2080–9. ©2012 AACR.
A Three-Gene Expression Signature Model for Risk Stratification of Patients with Neuroblastoma
Authors: Garcia Idoia , Mayol Gemma , Ríos José , Domenech Gema , Cheung Nai-Kong V. , Oberthuer André , Fischer Matthias , Maris John M. , Brodeur Garrett M. , Hero Barbara , Rodríguez Eva , Suñol Mariona , Galvan Patricia , de Torres Carmen , Mora Jaume , Lavarino Cinzia 
Published: February 2012

Abstract
Purpose: Neuroblastoma is an embryonal tumor with contrasting clinical courses. Despite elaborate stratification strategies, precise clinical risk assessment still remains a challenge. The purpose of this study was to develop a PCR-based predictor model to improve clinical risk assessment of patients with neuroblastoma.
Experimental Design: The model was developed using real-time PCR gene expression data from 96 samples and tested on separate expression data sets obtained from real-time PCR and microarray studies comprising 362 patients.
Results: On the basis of our prior study of differentially expressed genes in favorable and unfavorable neuroblastoma subgroups, we identified three genes, CHD5, PAFAH1B1, and NME1, strongly associated with patient outcome. The expression pattern of these genes was used to develop a PCR-based single-score predictor model. The model discriminated patients into two groups with significantly different clinical outcome [set 1: 5-year overall survival (OS): 0.93 ± 0.03 vs. 0.53 ± 0.06, 5-year event-free survival (EFS): 0.85 ± 0.04 vs. 0.042 ± 0.06, both P &lt; 0.001; set 2 OS: 0.97 ± 0.02 vs. 0.61 ± 0.1, P = 0.005, EFS: 0.91 ± 0.8 vs. 0.56 ± 0.1, P = 0.005; and set 3 OS: 0.99 ± 0.01 vs. 0.56 ± 0.06, EFS: 0.96 ± 0.02 vs. 0.43 ± 0.05, both P &lt; 0.001]. Multivariate analysis showed that the model was an independent marker for survival (P &lt; 0.001, for all). In comparison with accepted risk stratification systems, the model robustly classified patients in the total cohort and in different clinically relevant risk subgroups.
Conclusion: We propose for the first time in neuroblastoma, a technically simple PCR-based predictor model that could help refine current risk stratification systems. Clin Cancer Res; 18(7); 2012–23. ©2012 AACR.
CEP-32496: A Novel Orally Active BRAFV600E Inhibitor with Selective Cellular and In Vivo Antitumor Activity
Authors: James Joyce , Ruggeri Bruce , Armstrong Robert C. , Rowbottom Martin W. , Jones-Bolin Susan , Gunawardane Ruwanthi N. , Dobrzanski Pawel , Gardner Michael F. , Zhao Hugh , Cramer Merryl D. , Hunter Kathryn , Nepomuceno Ronald R. , Cheng Mangeng , Gitnick Dana , Yazdanian Mehran , Insko Darren E. , Ator Mark A. , Apuy Julius L. , Faraoni Raffaella , Dorsey Bruce D. , Williams Michael , Bhagwat Shripad S. , Holladay Mark W. 
Published: February 2012

Abstract
Mutations in the BRAF gene have been identified in approximately 7% of cancers, including 60% to 70% of melanomas, 29% to 83% of papillary thyroid carcinomas, 4% to 16% colorectal cancers, and a lesser extent in serous ovarian and non–small cell lung cancers. The V600E mutation is found in the vast majority of cases and is an activating mutation, conferring transforming and immortalization potential to cells. CEP-32496 is a potent BRAF inhibitor in an in vitro binding assay for mutated BRAFV600E (Kd BRAFV600E = 14 nmol/L) and in a mitogen-activated protein (MAP)/extracellular signal–regulated (ER) kinase (MEK) phosphorylation (pMEK) inhibition assay in human melanoma (A375) and colorectal cancer (Colo-205) cell lines (IC50 = 78 and 60 nmol/L). In vitro, CEP-32496 has multikinase binding activity at other cancer targets of interest; however, it exhibits selective cellular cytotoxicity for BRAFV600E versus wild-type cells. CEP-32496 is orally bioavailable in multiple preclinical species (&gt;95% in rats, dogs, and monkeys) and has single oral dose pharmacodynamic inhibition (10–55 mg/kg) of both pMEK and pERK in BRAFV600E colon carcinoma xenografts in nude mice. Sustained tumor stasis and regressions are observed with oral administration (30–100 mg/kg twice daily) against BRAFV600E melanoma and colon carcinoma xenografts, with no adverse effects. Little or no epithelial hyperplasia was observed in rodents and primates with prolonged oral administration and sustained exposure. CEP-32496 benchmarks favorably with respect to other kinase inhibitors, including RAF-265 (phase I), sorafenib, (approved), and vemurafenib (PLX4032/RG7204, approved). CEP-32496 represents a novel and pharmacologically active BRAF inhibitor with a favorable side effect profile currently in clinical development. Mol Cancer Ther; 11(4); 930–41. ©2012 AACR.
Nanobodies Targeting the Hepatocyte Growth Factor: Potential New Drugs for Molecular Cancer Therapy
Authors: Vosjan Maria J.W.D. , Vercammen Jo , Kolkman Joost A. , Stigter-van Walsum Marijke , Revets Hilde , van Dongen Guus A.M.S. 
Published: February 2012

AbstractHepatocyte growth factor (HGF) and its receptor c-Met are associated with increased aggressiveness of tumors and poor prognostic outcome of patients with cancer. Here, we report the development and characterization of therapeutic anti-HGF (αHGF)-Nanobodies and their potential for positron emission tomographic (PET) imaging to assess HGF expression in vivo. Two αHGF-Nanobodies designated 1E2 and 6E10 were identified, characterized, and molecularly fused to an albumin-binding Nanobody unit (Alb8) to obtain serum half-life extension. The resulting Nanobody formats were radiolabeled with the positron emitter zirconium-89 (89Zr, t½ = 78 hours), administered to nude mice bearing U87 MG glioblastoma xenografts, and their biodistribution was assessed. In addition, their therapeutic effect was evaluated in the same animal model at doses of 10, 30, or 100 μg per mouse. The 89Zr-Nanobodies showed similar biodistribution with selective tumor targeting. For example, 1E2-Alb8 showed decreased blood levels of 12.6%ID/g ± 0.6%ID/g, 7.2%ID/g ± 1.0%ID/g, 3.4%ID/g ± 0.3%ID/g, and 0.3%ID/g ± 0.1%ID/g at 1, 2, 3, and 7 days after injection, whereas tumor uptake levels remained relatively stable at these time points: 7.8%ID/g ± 1.1%ID/g, 8.9%ID/g ± 1.0%ID/g, 8.7%ID/g ± 1.5%ID/g, and 7.2%ID/g ±1.6%ID/g. Uptake in normal tissues was lower than in tumor, except for kidneys. In a therapy study, all Nanobody-treated mice showed tumor growth delay compared with the control saline group. In the 100-μg group, four of six mice were cured after treatment with 1E2-Alb8 and 73 days follow-up, and three of six mice when treated with 6E10-Alb8. These results provide evidence that Nanobodies 1E2-Alb8 and 6E10-Alb8 have potential for therapy and PET imaging of HGF-expressing tumors. Mol Cancer Ther; 11(4); 1017–25. ©2012 AACR.
Oncogenic Function and Early Detection Potential of miRNA-10b in Oral Cancer as Identified by microRNA Profiling
Authors: Lu Ya-Ching , Chen Yin-Ju , Wang Hung-Ming , Tsai Chi-Ying , Chen Wen-Ho , Huang Yu-Chen , Fan Kang-Hsing , Tsai Chi-Neu , Huang Shiang-Fu , Kang Chung-Jan , Chang Joseph Tung-Chieh , Cheng Ann-Joy 
Published: February 2012

Abstract
The miRNA participates in a variety of biologic processes, and dysregulation of miRNA is associated with malignant transformation. In this study, we determined specific profile of miRNA associated with oral cancer by using miRNA array screening method. There were 23 miRNAs found with considerably differential expressions between six oral cancer cell lines and five lines of normal oral keratinocytes, in which, 10 miRNAs showed the highest significant difference after independent examination by reverse transcription quantitative PCR. Eight molecules were upregulated, miR-10b, miR-196a, miR-196b, miR-582-5p, miR-15b, miR-301, miR-148b, and miR-128a, and two molecules, miR-503 and miR-31, were downregulated. The most upregulated miR-10b was further examined, and its functions were characterized in two oral cancer cell lines. The miR-10b actively promotes cell migration (2.6- to 3.6-fold) and invasion (1.7- to 1.9-fold) but has minimal effect on cell growth or chemo-/radiosensitivity. Furthermore, miR-10b was considerably elevated in the plasma of xenografted tumor mice (20-fold). This upregulation of miR-10b in plasma was further shown in the patients with oral cancer [P &lt; 0.0001, area under curve (AUC) = 0.932] and precancer lesions (P &lt; 0.0001, AUC = 0.967), suggesting that miR-10b possesses a high potential to discriminate the normal subjects. In conclusion, we have identified at least 10 miRNAs significantly associated with oral cancer, including the most elevated miR-10b. The miR-10b actively participates in cancer formation by promoting cell migration and invasion. Our study using clinical samples suggests that plasma miR-10b has high potential as an early detection marker for oral cancer. Cancer Prev Res; 5(4); 665–74. ©2012 AACR.
Protection of Humans by Plant Glucosinolates: Efficiency of Conversion of Glucosinolates to Isothiocyanates by the Gastrointestinal Microflora
Authors: Fahey Jed W. , Wehage Scott L. , Holtzclaw W. David , Kensler Thomas W. , Egner Patricia A. , Shapiro Theresa A. , Talalay Paul 
Published: February 2012

Abstract
Plant-based diets rich in crucifers are effective in preventing cancer and other chronic diseases. Crucifers contain very high concentrations of glucosinolates (GS; β-thioglucoside-N-hydroxysulfates). Although not themselves protective, GS are converted by coexisting myrosinases to bitter isothiocyanates (ITC) which defend plants against predators. Coincidentally, ITC also induce mammalian genes that regulate defenses against oxidative stress, inflammation, and DNA-damaging electrophiles. Consequently, the efficiency of conversion of GS to ITC may be critical in controlling the health-promoting benefits of crucifers. If myrosinase is heat-inactivated by cooking, the gastrointestinal microflora converts GS to ITC, a process abolished by enteric antibiotics and bowel cleansing. When single oral doses of GS were administered as broccoli sprout extracts (BSE) to two dissimilar populations (rural Han Chinese and racially mixed Baltimoreans) patterns of excretions of urinary dithiocarbamates (DTC) were very similar. Individual conversions in both populations varied enormously, from about 1% to more than 40% of dose. In contrast, administration of ITC (largely sulforaphane)-containing BSE resulted in uniformly high (70%–90%) conversions to urinary DTC. Despite the remarkably large range of conversion efficiencies between individuals, repeated determinations within individuals were much more consistent. The rates of urinary excretion (slow or fast) were unrelated to the ultimate magnitudes (low or high) of these conversions. Although no demographic factors affecting conversion efficiency have been identified, there are clearly diurnal variations: conversion of GS to DTC was greater during the day, but conversion of ITC to DTC was more efficient at night. Cancer Prev Res; 5(4); 603–11. ©2012 AACR.
Essential Role of Caveolin-3 in Adiponectin Signalsome Formation and Adiponectin Cardioprotection
Authors: Wang Yajing , Wang Xiaoliang , Jasmin Jean-François , Lau Wayne Bond , Li Rong , Yuan Yuexin , Yi Wei , Chuprun Kurt , Lisanti Michael P. , Koch Walter J. , Gao Erhe , Ma Xin-Liang 
Published: February 2012

Objective—
Adiponectin (APN) system malfunction is causatively related to increased cardiovascular morbidity/mortality in diabetic patients. The aim of the current study was to investigate molecular mechanisms responsible for APN transmembrane signaling and cardioprotection.

Methods and Results—

Compared with wild-type mice, caveolin-3 knockout (Cav-3KO) mice exhibited modestly increased myocardial ischemia/reperfusion injury (increased infarct size, apoptosis, and poorer cardiac function recovery;
P
<0.05). Although the expression level of key APN signaling molecules was normal in Cav-3KO, the cardioprotective effects of APN observed in wild-type were either markedly reduced or completely lost in Cav-3KO. Molecular and cellular experiments revealed that APN receptor 1 (AdipoR1) colocalized with Cav-3, forming AdipoR1/Cav-3 complex via specific Cav-3 scaffolding domain binding motifs. AdipoR1/Cav-3 interaction was required for APN-initiated AMP-activated protein kinase (AMPK)–dependent and AMPK-independent intracellular cardioprotective signalings. More importantly, APPL1 and adenylate cyclase, 2 immediately downstream molecules required for AMPK-dependent and AMPK-independent signaling, respectively, formed a protein complex with AdipoR1 in a Cav-3 dependent fashion. Finally, pharmacological activation of both AMPK plus protein kinase A significantly reduced myocardial infarct size and improved cardiac function in Cav-3KO animals.

Conclusion—
Taken together, these results demonstrated for the first time that Cav-3 plays an essential role in APN transmembrane signaling and APN anti-ischemic/cardioprotective actions.
Percutaneous Femoral Arteriovenous Shunt Creation for Advanced Chronic Obstructive Pulmonary Disease
Authors: Bertog Stefan C. , Kolmer Christina , Kleschnew Swetlana , Franke Jennifer , Wunderlich Nina , Kardos Peter , Sievert Horst 
Published: February 2012

Background—
Advanced chronic obstructive pulmonary disease causes a significant reduction in functional capacity because of dyspnea and fatigue, partially related to hypoxemia and compromised oxygen delivery. Percutaneous creation of an arteriovenous shunt may increase oxygen delivery and, hence, improve patients' functional capacity.

Methods and Results—

This is a prospective, single-center, proof-of-concept pilot study. Patients with advanced chronic obstructive pulmonary disease underwent percutaneous arteriovenous shunt creation. End points were the change in 6-minute walking distance; quality of life, measured by St George's Respiratory Questionnaire; and physiological parameters at 12-week follow-up. Fifteen patients underwent percutaneous arteriovenous shunt creation. Cardiac output and oxygen delivery increased significantly from 4.1 L/min at baseline to 5.9 L/min at 12 weeks (
P
<0.01) and from 751 mL/min at baseline to 972 mL/min at 12 weeks (
P
<0.01), respectively; however, there was a trend toward a significant decrease in the 6-minute walking distance between baseline (338 m) and 12-week follow-up (294 m) (
P
=0.07). There was no significant difference in the St George's Respiratory Questionnaire score, oxygen saturation, or lung function tests. Lower extremity edema, venous stenosis, right heart failure, and deep venous thrombosis occurred in 10, 7, 4, and 4 patients, respectively.

Conclusions—
Though it causes a significant increase in cardiac output and oxygen delivery , the creation of an arteriovenous shunt in the setting of severe chronic obstructive pulmonary disease did not improve functional capacity or quality of life. A significant number of adverse events occurred. This concept cannot be recommended for routine clinical use in unselected patients with advanced chronic obstructive pulmonary disease.
The Thermally Driven Cross-Basin Circulation in Idealized Basins under Varying Wind Conditions
Authors: Lehner Manuela , Whiteman C. David 
Published: February 2012

AbstractThe Weather Research and Forecasting model is used to perform large-eddy simulations of thermally driven cross-basin winds in idealized, closed basins. A spatially and temporally varying heat flux is prescribed at the surface as a function of slope inclination and orientation to produce a horizontal temperature gradient across the basin. The thermal asymmetry leads to the formation of a closed circulation cell flowing toward the more strongly heated sidewall, with a return flow in the upper part of the basin. In the presence of background winds above the basin, a second circulation cell forms in the upper part of the basin, resulting in one basin-sized cell, two counterrotating cells, or two cells with perpendicular rotation axes, depending on the background-wind direction with respect to the temperature gradient. The thermal cell near the basin floor and the background-wind-induced cell interact with each other either to enhance or to reduce the thermal cross-basin flow and return flow. It is shown that in 5–10-km-wide basins cross-basin temperature differences that are representative of east- and west-facing slopes are insufficient to maintain perceptible cross-basin winds because of reduced horizontal temperature and pressure gradients, particularly in a neutrally stratified atmosphere.