bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis C virus core protein upregulates the expression of vascular endothelial growth factor via the nuclear factor‐κB/hypoxia‐inducible factor‐1α axis under hypoxic conditions
Authors: Abe Mitsuhiko , Koga Hironori , Yoshida Takafumi , Masuda Hiroshi , Iwamoto Hideki , Sakata Masahiro , Hanada Shinichiro , Nakamura Toru , Taniguchi Eitaro , Kawaguchi Takumi , Yano Hirohisa , Torimura Takuji , Ueno Takato , Sata Michio 
Published: January 2012

Aim:  Hepatitis C virus (HCV) core protein critically contributes to hepatocarcinogenesis, which is often observed in liver cirrhosis. Since the liver cirrhosis microenvironment is affected by hypoxia, we focused on the possible driving force of HCV core protein on signal relay from hypoxia‐inducible factor (HIF)‐1α to vascular endothelial growth factor (VEGF).Methods:  Human hepatocellular carcinoma cells stably overexpressing HCV core (Core cells) and NS5A (NS5A cells) were established; empty vector‐transfected (EV) cells were used as controls. Hypoxia was induced by oxygen deprivation or by using cobalt chloride (CoCl2). YC‐1 was used to inhibit HIF‐1α expression. Protein analyses for cultured cells and liver tissues obtained from CoCl2‐treated HCV core‐transgenic (Core‐Tg) mice were performed by western blot and/or immunocytochemistry. Cellular mRNA levels were evaluated by quantitative real‐time reverse transcription‐polymerase chain reaction.Results:  Under hypoxia, the sustained expression of HIF‐1α, but not HIF‐2α, was profoundly observed in Core cells but, was faint in EV and NS5A cells. Immunocytochemistry revealed increased HIF‐1α in the nucleus. HIF‐1α mRNA levels were significantly higher in Core cells than in EV cells under both normoxia and hypoxia. The HIF‐1α‐targeted VEGF and Bcl‐xL expressions were increased in Core cells under hypoxia and abolished by YC‐1 treatment. Hypoxic liver samples of Core‐Tg mice indicated significant increases in both HIF‐1α and VEGF expression compared with the wild type.Conclusions:  Hepatitis C virus core protein has the distinct potential to transcriptionally upregulate and sustain HIF‐1α expression under hypoxia, thereby contributing to increased VEGF expression, a key regulator in the hypoxic milieu of liver cirrhosis.
Distinctive expression of CD133 between intraductal papillary neoplasms of the bile duct and bile duct adenocarcinomas
Authors: Ohtsubo Izuru , Ajiki Tetsuo , Hori Yuichi , Murakami Sae , Shimizu Kazuya , Itoh Tomoo , Shimizu Michio , Fukumoto Takumi , Ku Yonson 
Published: January 2012

Aim:  Intraductal papillary neoplasm of the bile duct (IPNB), a novel entity of biliary disease, is recently advocated as the counterpart of pancreatic intraductal papillary mucinous neoplasm (IPMN) because both are in common with a large amount of mucin production and papillary growth. Based on our recent finding that expression of CD133, a cancer stem cell marker, is lacking in pancreatic IPMN, we herein focused on CD133 expression of IPNB in comparison with intrahepatic cholangiocellular carcinoma (IHCCC) or hilar bile duct cancer (HBDC).Methods:  Expression of CD133 protein was immunohistochemically determined in patients with IPNB (n = 7), IHCCC (n = 16) or HBDC (n = 8). In addition, morphological and immunohistochemical mucin expression patterns were characterized in IPNB, and clinicopathological features including prognosis were compared between IPNB and other biliary tumors.Results:  The IPNB group included significantly more females than the other two groups, and had a longer survival time. While no CD133 expression was observed in IPNB tumor, 16.4% of cancer cells in IHCCC and 17.2% of cells in HBDC expressed CD133. Among seven patients with IPNB, six (86%) were morphologically the pancreatobiliary type and four of six showed mucin expression pattern of the typical pancreatobiliary type (MUC1+/MUC2‐/MUC5AC+).Conclusion:  Loss of CD133 expression supports the hypothesis that IPNB is a counterpart of pancreatic IPMN with a differing carcinogenesis from conventional bile duct adenocarcinomas.
Reopke Lecture in Economic Geography: Notes from the Underground: Why the History of Economic Geography Matters: The Case of Central Place Theory
Authors: Barnes Trevor J. 
Published: January 2012

abstractThe discipline of Anglo‐American economic geography seems to care little about its history. Its practitioners tend toward the “just do it” school of scholarship, in which a concern with the present moment in economic geography subordinates all else. In contrast, I argue that it is vital to know economic geography's history. Historical knowledge of our discipline enables us to realize that we are frequently “slaves of some defunct” economic geographer; that we cannot escape our geography and history, which seep into the very pores of the ideas that we profess; and that the full connotations of economic geographic ideas are sometimes purposively hidden, secret even, revealed only later by investigative historical scholarship. My antidote: “notes from the underground,” which means a history of economic geography that delves below the reported surface. This history is often subversive, contradicting conventional depictions; it is antirationalist, querying universal (timeless) foundations; it seeks out deliberately hidden and buried economic geographic practices, relying on sources literally found underground—personal papers and correspondence stored in one subterranean archive or another. To exemplify the importance of notes from the underground, I present an extended case study—the 20th‐century development of central place theory, associated with two economic geographers: the German, Walter Christaller (1893–1969), and the American, Edward L. Ullman (1912–76).
Serial Kinetics of the Antibody Response against the Complete Brucella melitensis ORFeome in Focal Vertebral Brucellosis
Authors: Cannella Anthony P. , Lin Jennifer C. , Liang Li , Atluri Vidya , Gotuzzo Eduardo , Felgner Philip L. , Tsolis Renee M. , Vinetz Joseph M. 
Published: January 2012

ABSTRACT

Human brucellosis is a common zoonosis worldwide. Here we present a case of focal vertebral brucellosis in a 71-year-old Mexican-American woman who contracted infection from unpasteurized goat milk. Standard agglutination serology was negative; the diagnosis was established by the isolation of
Brucella melitensis
from abscess fluid. A
B. melitensis
protein microarray comprised of nearly all proteins encoded by the bacterial genome was used to determine the kinetics of this patient's antibody responses to the complete collection of open reading frames existing in the genome (ORFeome). Three patterns of antibody responses against
B. melitensis
antigens were seen for serum samples obtained on days 0 (pretreatment), 14, 49, 100, and 180: (i) stable titers over time, (ii) a steady fall in titers, and (iii) an initial rise in titers followed by declining titers. Sera from this patient with chronic brucellosis recognized some of the same
B. melitensis
proteins as those recognized by sera from acute/subacute, blood culture-positive brucellosis patients but also recognized a distinct set of proteins. This study is the first to determine the kinetics of the human antibody responses to the complete repertoire of proteins encoded by a bacterial genome and demonstrates fundamentally different immunopathogenetic mechanisms between acute human brucellosis and chronic human brucellosis. While an extension of these findings to a larger patient population is necessary, these findings have important clinical and diagnostic implications and lead toward new insights into the fundamental immunopathogenesis of brucellosis.
Emergency department crowding
Authors: Higginson Ian 
Published: January 2012

BackgroundEmergency department (ED) crowding is a significant international problem. There is increasing overseas research into this field. In the UK, the focus has been on waiting times in EDs, and on the government's 4 h standard, rather than on crowding itself.AimsTo examine the causes and effects of ED crowding, along with solutions. To consider whether the 4 h standard has had an effect on ED crowding in the UK.MethodsA structured literature review on ED crowding.ResultsThe evidence base largely consists of retrospective or descriptive studies (65% combined) from North America and Australasia (89% combined). Measurement of crowding is not well developed, and the lack of a gold standard additionally limits the quality of research. The main cause of crowding is access block, because of high levels of hospital occupancy. Crowding carries a number of adverse consequences for patients and staff. Many solutions are described, but with weak evidence behind them. Most of these focus on interventions in the ED, despite the fact that the main causes lie outside. Solutions aimed at achieving the 4 h standard may mitigate crowding.ConclusionThe extent of ED crowding in the UK is unknown. The problem is probably mitigated by process standards such as the 4 h standard. The causes and effects of crowding are likely to be the same as overseas, but there is little research to validate this. The best solutions are not known.
A comparative analysis of fine-scale genetic structure in three closely related syntopic species of the grasshopper genusCalliptamus
Authors: Blanchet E. , Lecoq M. , Sword G.A. , Berthier K. , Pages C. , Billot C. , Rivallan R. , Foucart A. , Vassal J.-M. , Risterucci A.M. , Chapuis M.-P. 
Published: January 2012

Landscape analysis and genetics can allow a better understanding of grasshoppers for which ecology is not very well known. We analysed landscape changes between 1990 and 2006 at two areas from southern France where three grasshopper species ( Calliptamus italicus (L., 1758), Calliptamus wattenwylianus Pantel, 1896, and Calliptamus barbarus (Costa, 1836)) occur. We then applied microsatellite markers to the study of 1200 georeferenced samples collected over both areas. We used a recent Bayesian clustering method with correlated allele frequencies to detect weak population genetic structure. We found evidence of breaks in gene flow only in C. wattenwylianus, thought to be sedentary relative to its congenerics. By using different allele frequency models and prior information to different levels of genetic differentiation for our six real data sets, our study also informs on the ability of the newly available Bayesian clustering methods model to detect weak genetic structure in natural field populations.
Trophic cascades linking wolves (Canis lupus), coyotes (Canis latrans), and small mammals
Authors: Miller Brian J. , Harlow Henry J. , Harlow Tyler S. , Biggins Dean , Ripple William J. 
Published: January 2012

When large carnivores are extirpated from ecosystems that evolved with apex predators, these systems can change at the herbivore and plant trophic levels. Such changes across trophic levels are called cascading effects and they are very important to conservation. Studies on the effects of reintroduced wolves in Yellowstone National Park have examined the interaction pathway of wolves ( Canis lupus L., 1758) to ungulates to plants. This study examines the interaction effects of wolves to coyotes to rodents (reversing mesopredator release in the absence of wolves). Coyotes ( Canis latrans Say, 1823) generally avoided areas near a wolf den. However, when in the proximity of a den, they used woody habitats (pine or sage) compared with herbaceous habitats (grass or forb or sedge)– when they were away from the wolf den. Our data suggested a significant increase in rodent numbers, particularly voles (genus Microtus Schrank, 1798), during the 3-year study on plots that were within 3 km of the wolf den, but we did not detect a significant change in rodent numbers over time for more distant plots. Predation by coyotes may have depressed numbers of small mammals in areas away from the wolf den. These factors indicate a top–down effect by wolves on coyotes and subsequently on the rodents of the area. Restoration of wolves could be a powerful tool for regulating predation at lower trophic levels.
Genetic structure of a Virginia opossum (Didelphis virginiana) population inhabiting a fragmented agricultural ecosystem
Authors: Beatty William S. , Beasley James C. , Dharmarajan Guha , Rhodes Olin E. 
Published: January 2012

Fragmentation has drastically altered the quality of habitats throughout numerous ecosystems, often leading to dramatic changes in the composition of wildlife communities. The ecology and associated movement behavior of a species may also be modified as a result of forest fragmentation, resulting in changes in genetic composition of the affected species. In this research, we evaluated the genetic structure of the Virginia opossum ( Didelphis virginiana Kerr, 1792) at the landscape and local scales in a fragmented, agricultural ecosystem in northern Indiana using 13 microsatellite loci. We examined 290 samples from opossums inhabiting 28 discrete habitat patches, and evaluated partitioning of genetic variation of opossums among and within habitat patches. We observed low but significant levels of genetic structure (FST = 0.005) overall, and pairwise comparisons of FSTvalues among habitat patches also were relatively low. Relatedness within patches was highly variable (–0.077 ≤ rxy ≤ 0.060), with a few patches exhibiting significantly higher levels of relatedness than random expectations, and we detected no evidence of sex-biased natal dispersal. These results contrast with previous field studies that documented male-biased dispersal in the Virginia opossum, indicating dispersal in this species is plastic and dependent upon local environmental conditions.
Age-Group Differences in Human Papillomavirus Types and Cofactors for Cervical Intraepithelial Neoplasia 3 among Women Referred to Colposcopy
Authors: Gargano Julia W. , Nisenbaum Rosane , Lee Daisy R. , Ruffin IV Mack T. , Steinau Martin , Horowitz Ira R. , Flowers Lisa C. , Tadros Talaat S. , Birdsong George , Unger Elizabeth R. 
Published: January 2012

Abstract
Background: Recommendations for high-risk human papillomavirus (HR-HPV) testing as an adjunct to cytology for cervical cancer screening differ by age group, because HR-HPV tests lack adequate specificity in women aged &lt;30. Here, we assess age-group differences in HPV types and other risk factors for cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) versus CIN0–2 in women from four colposcopy clinics.
Methods: Women ages 18 to 69 (n = 1,658) were enrolled and completed structured interviews to elicit data on behavioral risk factors prior to their examinations. HPV genotyping was done on exfoliated cervical cell samples. We estimated relative risks (RR) for HPV types and cofactors for CIN3+, overall and stratified by age group.
Results: After 2 years of follow-up, we identified 178 CIN3+, 1,305 CIN0–2, and 175 indeterminate outcomes. Nonvaccine HR-HPV types were only associated with CIN3+ among women ≥30 (RR = 2.3, 95% CI: 1.5–3.4; &lt;30: RR = 0.9). Among all HR-HPV–positive women, adjusting for age, significant cofactors for CIN3+ included current smoking (RR = 1.5), former smoking (RR = 1.8), regular Pap screening (RR = 0.7), current regular condom use (RR = 0.5), and parity ≥5 (RR = 1.6, Ptrend for increasing parity = 0.07). However, the parity association differed by age group (≥30: RR = 1.8, Ptrend = 0.008; &lt;30: RR = 0.9; Ptrend =.55).
Conclusion: Subgroup variation by age in the risk of CIN3+ points to the importance of the timing of exposures in relation to CIN3+ detection.
Impact: Future screening strategies need to consider natural history and secular trends in cofactor prevalence in the pursuit of appropriately sensitive and specific screening tools applied to appropriate age groups. Cancer Epidemiol Biomarkers Prev; 21(1); 111–21. ©2011 AACR.
Risk Factors for Oral HPV Infection among a High Prevalence Population of HIV-Positive and At-Risk HIV-Negative Adults
Authors: Beachler Daniel C. , Weber Kathleen M. , Margolick Joseph B. , Strickler Howard D. , Cranston Ross D. , Burk Robert D. , Wiley Dorothy J. , Minkoff Howard , Reddy Susheel , Stammer Emily E. , Gillison Maura L. , D'Souza Gypsyamber 
Published: January 2012

AbstractIntroduction: Human papillomavirus (HPV) is an important risk factor for oropharyngeal cancer. Individuals with human immunodeficiency virus (HIV) have higher oral HPV prevalence but the risk factors for oral HPV infection are not well understood for either HIV-positive or HIV-negative individuals.Methods: This study was nested within the Multicenter AIDS Cohort Study (MACS; men) and Women Interagency HIV Study (WIHS; women) cohorts. Exfoliated oral epithelial cells were collected from 379 HIV-positive and 266 at-risk HIV-negative individuals using a rinse and gargle with Scope mouthwash. Samples were tested for 36 types of HPV DNA using PGMY09/11 consensus primers and reverse line blot hybridization. Risk factors for oral HPV infection were explored using logistic regression with generalized estimating equations in this cross-sectional analysis.Results: Prevalent oral HPV infection was common (34%), including HPV16 infection in 5.7% of participants. HIV-positive individuals had increased odds of prevalent oral HPV infection compared with HIV-negative individuals [adjusted OR = 2.1; 95% confidence interval (CI), 1.6–2.8]. Risk factors for prevalent oral HPV differed in HIV-positive and HIV-negative participants. Among HIV-negative individuals, higher number of recent oral sex or rimming partners were strong risk factors for prevalent oral HPV infection (each Ptrend &lt; 0.01). In contrast, among HIV-positive individuals, lower CD4 T-cell count (Ptrend &lt; 0.001) and higher number of lifetime sexual partners (Ptrend = 0.03) were strong risk factors.Conclusions: Oral HPV prevalence was elevated in HIV-positive individuals after controlling for differences in cigarette smoking and sexual behavior, supporting the possibility that HIV may affect the natural history of oral HPV.Impact: Immunosuppression may contribute to increased persistence or progression of oral HPV infection. Cancer Epidemiol Biomarkers Prev; 21(1); 122–33. ©2011 AACR.
Results of a Phase 1 Study of AME-133v (LY2469298), an Fc-Engineered Humanized Monoclonal Anti-CD20 Antibody, in FcγRIIIa-Genotyped Patients with Previously Treated Follicular Lymphoma
Authors: Forero-Torres Andres , de Vos Sven , Pohlman Brad L. , Pashkevich Maksim , Cronier Damien M. , Dang Nam H. , Carpenter Susan P. , Allan Barrett W. , Nelson James G. , Slapak Christopher A. , Smith Mitchell R. , Link Brian K. , Wooldridge James E. , Ganjoo Kristen N. 
Published: January 2012

Abstract
Purpose: AME-133v is a humanized monoclonal antibody engineered to have increased affinity to CD20 and mediate antibody-dependent cell-mediated cytotoxicity (ADCC) better than rituximab. Safety, pharmacokinetics, and efficacy were assessed in a phase 1/2 trial in patients with previously treated follicular lymphoma (FL).
Patients and Methods: AME-133v was characterized in vitro by ADCC and cell binding assays. A phase 1 study was conducted in which 23 previously treated patients with FL were assigned sequentially to one of five dose-escalation cohorts of AME-133v at 2, 7.5, 30, 100, or 375 mg/m2 weekly × 4 doses.
Results: AME-133v showed a 13- to 20-fold greater binding affinity for CD20 and was 5- to 7-fold more potent than rituximab in ADCC assays. Cell binding assays showed AME-133v and rituximab competed for an overlapping epitope on the CD20 antigen, and AME-133v inhibited binding of biotinylated rituximab to CD20 in a concentration-dependent manner. AME-133v was well tolerated by patients and common related adverse events included chills and fatigue. One patient experienced a dose-limiting toxicity of neutropenia. AME-133v showed nonlinear pharmocokinetics with properties similar to rituximab. Selective reduction of B cells during and after AME-133v treatment was shown by flow cytometry of peripheral blood. A partial or complete response was observed in 5 of 23 (22%) patients and the median progression-free survival was 25.4 weeks.
Conclusions: AME-133v was safe and well tolerated at the doses tested. AME-133v showed encouraging results as an anti-CD20 therapy in heavily pretreated FL patients with the less favorable FcγRIIIa F-carrier genotype. Clin Cancer Res; 18(5); 1395–403. ©2012 AACR.
Inhibition of Collagen Receptor Discoidin Domain Receptor-1 (DDR1) Reduces Cell Survival, Homing, and Colonization in Lung Cancer Bone Metastasis
Authors: Valencia Karmele , Ormazábal Cristina , Zandueta Carolina , Luis-Ravelo Diego , Antón Iker , Pajares María J. , Agorreta Jackeline , Montuenga Luis M. , Martínez-Canarias Susana , Leitinger Birgit , Lecanda Fernando 
Published: January 2012

Abstract
Purpose: We investigated the role of the collagen-binding receptor discoidin domain receptor-1 (DDR1) in the initiation and development of bone metastasis.
Experimental Design: We conducted immunohistochemical analyses in a cohort of 83 lung cancer specimens and examined phosphorylation status in a panel of human lung cancer cell lines. Adhesion, chemotaxis, invasiveness, metalloproteolytic, osteoclastogenic, and apoptotic assays were conducted in DDR1-silenced cells. In vivo, metastatic osseous homing and colonization were assessed in a murine model of metastasis.
Results: DDR1 was expressed in a panel of human lung cancer cell lines, and high DDR1 levels in human lung tumors were associated with poor survival. Knockdown (shDDR1) cells displayed unaltered growth kinetics in vitro and in vivo. In contrast, shDDR1 cells showed reduced invasiveness in collagen matrices and increased apoptosis in basal conditions and induced apoptosis in vitro. More importantly, conditioned media of DDR1-knockdown cells decreased osteoclastogenic activity in vitro. Consequently, in a model of tumor metastasis to bone, lack of DDR1 showed decreased metastatic activity associated with reduced tumor burden and osteolytic lesions. These effects were consistent with a substantial reduction in the number of cells reaching the bone compartment. Moreover, intratibial injection of shDDR1 cells significantly decreased bone tumor burden, suggesting impaired colonization ability that was highly dependent on the bone microenvironment.
Conclusions: Disruption of DDR1 hampers tumor cell survival, leading to impaired early tumor–bone engagement during skeletal homing. Furthermore, inhibition of DDR1 crucially alters bone colonization. We suggest that DDR1 represents a novel therapeutic target involved in bone metastasis. Clin Cancer Res; 18(4); 969–80. ©2012 AACR.