bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a pressure pulse in a fractured‐rock aquifer to reduce uncertainty of hydraulic conductivity measurements,RioGrandeRift,NewMexico,UnitedStates
Authors: Langman Jeff B. , Engdahl Nicholas B. 
Published: March 2013

AbstractFractured‐rock aquifers are inherently difficult for determining flow dynamics because of variability in fracture orientation and extension. A confined, fractured‐rock aquifer in a semi‐arid mountainous area of theRioGrandeRiftZone was analysed for its response to recharge events that produced a pressure pulse within its potentiometric surface. The pulse was evaluated at the well scale and subaquifer level to evaluate flowpaths, travel times and dispersion and compare the bulk‐scale aquifer response to possible velocities from slug test hydraulic conductivity measurements. Travel time and dispersion from the pulse proved comparable to probable travel times based on hydraulic conductivity measurements. Evaluation of the pressure pulse and the hydraulic conductivity measurements allowed for a holistic interpretation of the fractured‐rock aquifer through analysis of two distinct data sets that provided corroborative evidence of flow dynamics and fracture connectivity. This holistic approach reduced uncertainty regarding the individual hydraulic conductivity values.
Composite hydrogeological investigation and characterisation methods applied at a nuclear power plant site in Taiwan
Authors: Lo Hung‐Chieh , Chou Po‐Yi , Huang Chun‐Chieh , Chen Po‐Jui , Hsu Shih‐Meng 
Published: March 2013

AbstractDrawing from the lessons learnt from the Fukushima nuclear disaster in Japan, the assessment of subsurface environmental hazard around nuclear power plants has emerged as a critical task. Consequently, aiming to better understand the possible environmental impact of radiation leaks into the groundwater, a prescreening programme was initiated in 2011 by the Taiwanese government. As part of this programme, this study conducted various borehole prospecting techniques to identify in situ hydrogeological characteristics at Chin‐Shan Nuclear Power Plant. Borehole electrical log, sonic log and temperature/conductivity log were conducted to explain the regional lithologic conditions and permeability of the formation. In conjunction with this, the interwell tracer and pumping test was carried out to simultaneously determine the hydraulic parameters. In our opinion, the implementation of such in situ end‐to‐end investigations is essential in interpreting in situ fluid and solute transport dynamics prior to programming any numerical scheme for early warning, vulnerability assessment and regular monitoring of a nuclear power plant site.
Sarcomatoid carcinoma represents a complete phenotype with various pathways of epithelial mesenchymal transition
Authors: Sung Chang Ohk , Choi Hannah , Lee Keun-Woo , Kim Seok-Hyung 
Published: March 2013

AimsSarcomatoid carcinoma (SC) is considered to be a result of the sarcomatoid change of epithelial carcinoma. However, epithelial–mesenchymal transition (EMT) in SC has been insufficiently studied.MethodsWe evaluated the expression patterns of EMT-related phenotypic markers with transcription factors in 27 SCs originating from various organs, and we investigated the phenotypic characteristics of SCs classified as complete, incomplete or wild-type. We further analysed correlations between EMT-related phenotype markers and transcription factors.ResultsEpithelial markers (E-cadherin, claudin-3 and claudin-4) were consistently down-regulated, whereas mesenchymal markers (S100A4, α-smooth muscle actin (SMA), vimentin, PDGFRα and β-catenin) were variously expressed except for vimentin. EMT-related transcription factors (SIP1, Snail1, Slug, Twist1, ZEP1 and Oct-4) also showed various expression patterns. The expression patterns of phenotypic markers showed that most SCs (22/27, 81.5%, 95% CI 65.8 to 97.1%) had complete EMT phenotypes, whereas the remaining 5 (18.5%, 95% CI 2.8 to 24.1%) were of incomplete type. Unsupervised hierarchical clustering analysis revealed that SCs were clustered into several subgroups by EMT-related protein expression pattern. Twist1 positivity was significantly concordant with α-SMA positivity (κ value: 0.908; 95% CI 0.73 to 1.00, p<0.001, adjusted p<0.001). The EMT phenotypes of SC were simple, with complete phenotype being the predominant form, and the morphological changes of the SCs were also relevant in terms of EMT.ConclusionsSC seems to be an irreversible, permanent change in the EMT phenomenon, with complete EMT phenotypes and various EMT-related pathways being involved in SC.
Histochemical detection of platelet esterase activity in the bone marrow postmortem: can megakaryocytes serve as indicators for time since death?
Authors: Boehm Joachim , Schmidt Ulrike , Veeck Juergen , Porsche Michéle , Schaefer Hans-Eckart 
Published: March 2013

Aimsα-Naphthyl acetate esterase (ANAE) is one of the few enzymes that are histochemically detectable on formalin-fixed paraffin-embedded tissue. In bone marrow (BM) biopsies, ANAE staining highlights megakaryocytes. We investigated autopsy BM to determine whether ANAE staining intensity (SI) was associated with postmortem intervals (PMI, period between death and autopsy), and thus could allow the time of death of a patient to be deduced.MethodsANAE-stained BM slides of 74 forensic and pathology autopsies as well as 22 biopsies were histologically evaluated and their SIs semiquantitatively graded.ResultsANAE-SIs did not differ between men and women and slightly decreased with age. Biopsies had significantly higher ANAE-SIs than pathology cases. In autopsies, ANAE-SIs were not associated with PMI, except for cases with PMI ≥7 days which were consistently ANAE-negative.ConclusionsANAE-SIs in postmortem BM samples were independent of PMI. Thus, ANAE staining of BM megakaryocytes cannot serve as an indicator for time-since-death of a patient.
Crustal-scale architecture and segmentation of the South Atlantic volcanic margin
Authors: Blaich O. A. , Faleide J. I. , Tsikalas F. , Gordon A. C. , Mohriak W. 
Published: March 2013

Abstract
Seismic reflection and refraction profiles, and potential field data, complemented by crustal-scale gravity modelling, plate reconstructions and well cross-sections are used to study the evolution of the South Segment of the South Atlantic conjugate margins. Distinct along-margin structural and magmatic changes that are spatially related to a number of conjugate transfer systems are revealed. The northern province, between the Rio Grande Fracture Zone and the Salado Transfer Zone, is characterized by symmetrical seawards-dipping reflections (SDRs) and symmetrical continent–ocean transitional domain. The central province, between the Salado Transfer Zone and the conjugate Colorado–Hope transfer system, is characterized by along-strike tectonomagmatic asymmetry. The Tristan da Cunha plume, located on the central province of the South Segment, may have influenced the volume of magmatism but did not necessarily alter the process of rifted margin formation. Thus implying that, apart from voluminous magmatism, the extensional evolution of the central province of the South Segment may have much in common with ‘magma-poor’ margins.
Salt tectonics along the Atlantic margin of Morocco
Authors: Tari Gabor , Jabour Haddou 
Published: March 2013

Abstract
The Moroccan salt basin appears to be very unique in the sense that it is not sedimentary loading but tectonic inversion which appears to drive the latest stages of salt-related deformation in the central part of the basin. The gravity potential to maintain salt tectonics is provided by the differential uplift of the Atlas Mountains, located adjacent and striking almost perpendicular to the margin.
Along the offshore part of the Moroccan salt basin there are many play types, most of them related to the Triassic syn-rift salt. Toe-thrust anticlines at the basinwards edge of the salt basin form very large structures. Traps associated with salt tongues and diapirs define a more ‘classical’ salt-flank play. Numerous salt tongues, sheets and canopy complexes provide for a ‘Gulf of Mexico-style’ subsalt play. Despite the numerous untested play types, there have been only four deep-water exploration wells drilled in the entire Moroccan salt basin, none of them having subsalt penetrations.
Improved Survival with HPV among African Americans with Oropharyngeal Cancer
Authors: Worsham Maria J. , Stephen Josena K. , Chen Kang Mei , Mahan Meredith , Schweitzer Vanessa , Havard Shaleta , Divine George 
Published: March 2013

AbstractPurpose: A major limitation of studies reporting a lower prevalence rate of human papilloma virus (HPV) in African American patients with oropharyngeal squamous cell cancer (OPSCC) than Caucasian Americans, with corresponding worse outcomes, was adequate representation of HPV-positive African American patients. This study examined survival outcomes in HPV-positive and HPV-negative African Americans with OPSCC.Experimental Design: The study cohort of 121 patients with primary OPSCC had 42% African Americans. Variables of interest included age, race, gender, HPV status, stage, marital status, smoking, treatment, and date of diagnosis.Results: Caucasian Americans are more likely to be HPV positive (OR = 3.28; P = 0.035), as are younger age (age &lt; 50 OR = 7.14; P = 0.023 compared with age &gt; 65) or being married (OR = 3.44; P = 0.016). HPV positivity and being unmarried were associated with being late stage (OR = 3.10; P = 0.047 and OR = 3.23; P = 0.038, respectively). HPV-negative patients had 2.7 times the risk of death as HPV-positive patients (P = 0.004). Overall, the HPV-race groups differed (log-rank P &lt; 0.001), with significantly worse survival for HPV-negative African Americans versus (i) HPV-positive African Americans (HR = 3.44; P = 0.0012); (ii) HPV-positive Caucasian Americans (HR = 3.11; P = &lt; 0.049); and (iii) HPV-negative Caucasian Americans (HR = 2.21; P = 0.049).Conclusions: HPV has a substantial impact on overall survival in African American patients with OPSCC. Among African American patients with OPSCC, HPV-positive patients had better survival than HPV negative. HPV-negative African Americans also did worse than both HPV-positive Caucasian Americans and HPV-negative Caucasian Americans. This study adds to the mounting evidence of HPV as a racially linked sexual behavior life style risk factor impacting survival outcomes for both African American and Caucasian American patients with OPSCC. Clin Cancer Res; 19(9); 2486–92. ©2013 AACR.
Tivantinib (ARQ197) Displays Cytotoxic Activity That Is Independent of Its Ability to Bind MET
Authors: Basilico Cristina , Pennacchietti Selma , Vigna Elisa , Chiriaco Cristina , Arena Sabrina , Bardelli Alberto , Valdembri Donatella , Serini Guido , Michieli Paolo 
Published: March 2013

Abstract
Purpose: MET, the high-affinity receptor for hepatocyte growth factor, is frequently deregulated in human cancer. Tivantinib (ARQ197; Arqule), a staurosporine derivative that binds to the dephosphorylated MET kinase in vitro, is being tested clinically as a highly selective MET inhibitor. However, the mechanism of action of tivantinib is still unclear.
Experimental Design: The activity of tivantinib was analyzed in multiple cellular models, including: cells displaying c-MET gene amplification, strictly ‘addicted’ to MET signaling; cells with normal c-MET gene copy number, not dependent on MET for growth; cells not expressing MET; somatic knockout cells in which the ATP-binding cleft of MET, where tivantinib binds, was deleted by homologous recombination; and a cell system ‘poisoned’ by MET kinase hyperactivation, where cells die unless cultured in the presence of a specific MET inhibitor.
Results: Tivantinib displayed cytotoxic activity independently of c-MET gene copy number and regardless of the presence or absence of MET. In both wild-type and isogenic knockout cells, tivantinib perturbed microtubule dynamics, induced G2/M arrest, and promoted apoptosis. Tivantinib did not rescue survival of cells ‘poisoned’ by MET kinase hyperactivation, but further incremented cell death. In all cell models analyzed, tivantinib did not inhibit HGF-dependent or -independent MET tyrosine autophosphorylation.
Conclusions: We conclude that tivantinib displays cytotoxic activity via molecular mechanisms that are independent from its ability to bind MET. This notion has a relevant impact on the interpretation of clinical results, on the design of future clinical trials, and on the selection of patients receiving tivantinib treatment. Clin Cancer Res; 19(9); 2381–92. ©2013 AACR.
Sorafenib in Combination with Oxaliplatin, Leucovorin, and Fluorouracil (Modified FOLFOX6) as First-line Treatment of Metastatic Colorectal Cancer: The RESPECT Trial
Authors: Tabernero Josep , Garcia-Carbonero Rocio , Cassidy James , Sobrero Alberto , Van Cutsem Eric , Köhne Claus-Henning , Tejpar Sabine , Gladkov Oleg , Davidenko Irina , Salazar Ramon , Vladimirova Liubov , Cheporov Sergey , Burdaeva Olga , Rivera Fernando , Samuel Leslie , Bulavina Irina , Potter Vanessa , Chang Yu-Lin , Lokker Nathalie A. , O'Dwyer Peter J. 
Published: March 2013

Abstract
Purpose: This randomized, double-blind, placebo-controlled, phase IIb study evaluated adding sorafenib to first-line modified FOLFOX6 (mFOLFOX6) for metastatic colorectal cancer (mCRC).
Experimental Design: Patients were randomized to sorafenib (400 mg b.i.d.) or placebo, combined with mFOLFOX6 (oxaliplatin 85 mg/m2; levo-leucovorin 200 mg/m2; fluorouracil 400 mg/m2 bolus and 2400 mg/m2 continuous infusion) every 14 days. Primary endpoint was progression-free survival (PFS). Target sample was 120 events in 180 patients for &gt;85% power (two-sided α = 0.20) to detect an HR = 0.65.
Results: Of 198 patients randomized, median PFS for sorafenib plus mFOLFOX6 was 9.1 months versus 8.7 months for placebo plus mFOLFOX6 (HR = 0.88; 95% CI, 0.64–1.23; P = 0.46). There was no difference between treatment arms for overall survival. Subgroup analyses of PFS and overall survival showed no difference between treatment arms by KRAS or BRAF status (mutant and wild type). The most common grade 3/4 adverse events in the sorafenib and placebo arms were neutropenia (48% vs. 22%), peripheral neuropathy (16% vs. 21%), and grade 3 hand–foot skin reaction (20% vs. 0%). Treatment discontinuation because of adverse events was 9% and 6%, respectively. Generally, dose intensity (duration and cumulative doses) was lower in the sorafenib arm than in the placebo arm.
Conclusion: This study did not detect a PFS benefit with the addition of sorafenib to first-line mFOLFOX6 for mCRC. KRAS and BRAF status did not seem to impact treatment outcomes but the subgroups were small. These results do not support further development of sorafenib in combination with mFOLFOX6 in molecularly unselected patients with mCRC. Clin Cancer Res; 19(9); 2541–50. ©2013 AACR.
Classifying MMR Variants: Time for Revised Nomenclature in Lynch Syndrome
Authors: You Y. Nancy , Vilar Eduardo 
Published: March 2013

Abstract
Inactivating germline mutations in DNA mismatch repair (MMR) genes are diagnostic for Lynch syndrome. However, the clinical significance of missense variants is uncertain. A threshold level of compromised MLH1 expression, correlating with greater protein instability and MMR functional defect, has been identified to help classify the pathogenicity of missense variants. Clin Cancer Res; 19(9); 2280–2. ©2013 AACR.
Molecular Imaging of Cyclooxygenase-2 in Canine Transitional Cell Carcinomas In Vitro and In Vivo
Authors: Cekanova Maria , Uddin Md. Jashim , Bartges Joseph W. , Callens Amanda , Legendre Alfred M. , Rathore Kusum , Wright Laura , Carter Amanda , Marnett Lawrence J. 
Published: March 2013

Abstract
The enzyme COX-2 is induced at high levels in tumors but not in surrounding normal tissues, which makes it an attractive target for molecular imaging of cancer. We evaluated the ability of novel optical imaging agent, fluorocoxib A to detect urinary bladder canine transitional cell carcinomas (K9TCC). Here, we show that fluorocoxib A uptake overlapped with COX-2 expression in primary K9TCC cells in vitro. Using subcutaneously implanted primary K9TCC in athymic mice, we show specific uptake of fluorocoxib A by COX-2–expressing K9TCC xenograft tumors in vivo. Fluorocoxib A uptake by COX-2–expressing xenograft tumors was blocked by 70% (P &lt; 0.005) when pretreated with the COX-2 selective inhibitor, celecoxib (10 mg/kg), 4 hours before intravenous administration of fluorocoxib A (1 mg/kg). Fluorocoxib A was taken up by COX-2–expressing tumors but not by COX-2–negative human UMUC-3 xenograft tumors. UMUC-3 xenograft tumors with no expression of COX-2 showed no uptake of fluorocoxib A. In addition, fluorocoxib A uptake was evaluated in five dogs diagnosed with TCC. Fluorocoxib A specifically detected COX-2–expressing K9TCC during cystoscopy in vivo but was not detected in normal urothelium. Taken together, our findings show that fluorocoxib A selectively bound to COX-2–expressing primary K9TCC cells in vitro, COX-2–expressing K9TCC xenografts tumors in nude mice, and heterogeneous canine TCC during cystoscopy in vivo. Spontaneous cancers in companion animals offer a unique translational model for evaluation of novel imaging and therapeutic agents using primary cancer cells in vitro and in heterogeneous cancers in vivo. Cancer Prev Res; 6(5); 466–76. ©2013 AACR.
Increased Levels of Urinary PGE-M, a Biomarker of Inflammation, Occur in Association with Obesity, Aging, and Lung Metastases in Patients with Breast Cancer
Authors: Morris Patrick G. , Zhou Xi Kathy , Milne Ginger L. , Goldstein Daniel , Hawks Laura C. , Dang Chau T. , Modi Shanu , Fornier Monica N. , Hudis Clifford A. , Dannenberg Andrew J. 
Published: March 2013

AbstractElevated levels of COX-derived prostaglandin E2 (PGE2) occur in inflamed tissues. To evaluate the potential links between inflammation and breast cancer, levels of urinary prostaglandin E metabolite (PGE-M), a stable end metabolite of PGE2, were quantified. We enrolled 400 patients with breast cancer: controls with early breast cancer (n = 200), lung metastases (n = 100), and metastases to other sites (n = 100). Patients completed a questionnaire, provided urine, and had measurements of height and weight. Urinary PGE-M was quantified by mass spectrometry. Ever smokers with lung metastasis who had not been exposed to nonsteroidal anti-inflammatory drugs (NSAIDs) had the highest PGE-M levels. PGE-M levels were increased in association with elevated body mass index (BMI; P &lt; 0.001), aging (P &lt; 0.001), pack-year smoking history (P = 0.02), lung metastases (P = 0.02), and recent cytotoxic chemotherapy (P = 0.03). Conversely, use of NSAIDs, prototypic inhibitors of COX activity, was associated with reduced PGE-M levels (P &lt; 0.001). On the basis of the current findings, PGE-M is likely to be a useful biomarker for the selection of high-risk subgroups to determine the use of interventions that aim to reduce inflammation and possibly the development and progression of breast cancer, especially in overweight and obese women. Cancer Prev Res; 6(5); 428–36. ©2013 AACR.
MicroRNA and Cancer Chemoprevention
Authors: Yi Bin , Piazza Gary A. , Su Xiulan , Xi Yaguang 
Published: March 2013

Abstract
MicroRNAs (miRNA) are a group of naturally occurring, small, noncoding, and single-strand RNA molecules that regulate gene expression at the posttranscriptional and translational levels. By controlling the expression of oncogenic and tumor suppressor proteins, miRNAs are believed to play an important role in pathologic processes associated with malignant progression including tumor cell proliferation, apoptosis, differentiation, angiogenesis, invasion, and metastasis. However, relatively few studies have investigated the influence of chemopreventive agents on miRNA expression and their regulation of target genes. Given the significance of miRNAs in modulating gene expression, such research can provide insight into the pleiotropic biologic effects that chemopreventive agents often display and a deeper understanding of their mechanism of action to inhibit carcinogenesis. In addition, miRNAs can provide useful biomarkers for assessing antineoplastic activity of these agents in preclinical and clinical observations. In this review, we summarize recent publications that highlight a potentially important role of miRNAs in cancer chemoprevention research. Cancer Prev Res; 6(5); 401–9. ©2013 AACR.
Association of Body Mass Index With Major Cardiovascular Events and With Mortality After Percutaneous Coronary Intervention
Authors: Park Duk-Woo , Kim Young-Hak , Yun Sung-Cheol , Ahn Jung-Min , Lee Jong-Young , Kim Won-Jang , Kang Soo-Jin , Lee Seung-Whan , Lee Cheol Whan , Park Seong-Wook , Park Seung-Jung 
Published: March 2013

Background—
Conflicting data exist regarding the relation between body mass index (BMI) and cardiovascular events and mortality after percutaneous coronary intervention.

Methods and Results—
We performed pooled analyses to evaluate the association between BMI (weight in kilograms divided by the square of the height in meters) and the risks of major cardiovascular events (defined as death from cardiovascular causes, nonfatal myocardial infarction, stent thrombosis, or stroke) and death among 23 181 patients from 11 prospective percutaneous coronary intervention studies. Overall, mean (±SD) BMI was 24.9±3.0. During follow-up (median, 2.1 years), 2381 patients had a major cardiovascular event, and 1004 patients died. After adjusting covariates, there was an inverse relationship between BMI and adverse outcomes. With a BMI of 22.5 to 24.9 as the reference category, the risk of major cardiovascular events was elevated among patients with a lower BMI (by a factor of 1.52 for a BMI <18.5; 1.05 for a BMI of 18.5–19.9; 1.03 for a BMI of 20.0–22.4); by contrast, the risk declined among patients with a higher BMI (by a factor of 0.97 for a BMI of 25.0–27.4; 0.97 for a BMI of 27.5–29.9; and 0.78 for a BMI of ≥30.0). In general, the hazard ratios for deaths were similar.

Conclusions—
Among patients undergoing percutaneous coronary intervention, a low BMI was associated with increased risks of major cardiovascular events and death. However, there were no excess risks of these events associated with a high BMI.