bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV Coreceptor Tropism in Paired Plasma, Peripheral Blood Mononuclear Cell, and Cerebrospinal Fluid Isolates from Antiretroviral-Naïve Subjects
Authors: Parisi S. G. , Andreoni C. , Sarmati L. , Boldrin C. , Buonomini A. R. , Andreis S. , Scaggiante R. , Cruciani M. , Bosco O. , Manfrin V. , d'Ettorre G. , Mengoli C. , Vullo V. , Palù G. , Andreoni M. 
Published: March 2011

ABSTRACTA survey of HIV coreceptor usage in cerebrospinal fluid (CSF) samples, peripheral blood mononuclear cells (PBMCs), and plasma samples from naïve seropositive patients was conducted. One hundred patients were enrolled in this study. Of the 100 patients, 36 had a primary or recent infection (P-RI), 31 had an early chronic infection (>350 CD4 cells) (ECI), and 33 had a late chronic infection (LCI). All 3 compartments were sampled in a subset of 33 participants, while the remaining 67 patients provided plasma samples and PBMCs only. Seventy-seven patients harbored the R5 virus in plasma samples and had a significantly higher median and percentage of CD4+T cells than patients with X4 virus (437 and 281 cells/μl, respectively;P= 0.0086; 20.6% and 18.6%, respectively). The X4 strain was detected more frequently in patients with LCI than in patients with P-RI or ECI (39.3%, 19.4%, and 9.6%, respectively;P= 0.0063). PBMC and plasma tropism was concordant in 90 patients, and 73 had the R5 strain. Among patients with discordant results, 4 had the R5 virus in their plasma and the X4 virus in PBMCs; 6 showed the opposite profile. Plasma, PBMC, and CSF tropism determinations were concordant in 26/33 patients (21 patients had R5, and 5 had X4). The tropism was discordant in 5/33 patients, with the X4 virus in plasma and R5 in CSF; the HIV tropism in PBMCs was X4 in 3 patients. The remaining 2/33 patients had the R5 virus in plasma and PBMCs and the X4 virus in CSF; one of these patients had a P-RI. The discordant tropism in CSF and blood may have implications for chemokine (C-C motif) receptor 5 (CCR5) antagonist use in patients with limited response to antiretroviral therapy (ART) or in responding patients evaluated for simplification of treatment.
A report of the medical team activity at the 2009 Special Olympics GB
Authors: Wheeler Patrick C , Williamson Tim , Stephens Catherine , Ferguson Mike 
Published: March 2011

ObjectiveTo quantify and categorise medical workload from the 2009 Special Olympics GB (SOL GB) which involved 2500 athletes with learning disabilities across 21 different sports supported by nearly 9000 family members, volunteers and staff over a 7-day period.Design and participantsProspective survey of all medical contacts that took place at the 2009 SOL GB with subsequent analysis of consultation rates, medical problems and medical activity.Results581 medical consultations occurred during the 2009 SOL GB, with 95% of these for athletes. The majority of the athlete consultations were for musculoskeletal disorders, followed by skin wound care. Most athletes were judged fit to participate following their consultation.ConclusionA large multisport event for athletes with learning disabilities carries a significant medical workload that has not been studied previously, with different sports having different individual risks and demands. The vast majority of consultations are for systemically well athletes that can be managed locally without necessity for hospital admission. This study identifies the quantity and nature of medical consultations undertaken during this event in an attempt to inform planning for future events.
Trends in hospitalisations associated with paediatric burns
Authors: Bowman Stephen M , Aitken Mary E , Maham Sabrina A , Sharar Sam R 
Published: March 2011

BackgroundIn the United States, burns are the third leading cause of unintentional injury death in children aged 1–14 years, accounting for more than 600 deaths per year in children aged 0–19 years.ObjectiveTo describe trends in paediatric burn hospitalisations in the United States and provide national benchmarks for state and regional comparisons.MethodsAnalysis of existing data (1993–2006) from the Nationwide Inpatient Sample—the largest, longitudinal, all-payer inpatient care database in the United States. Children aged 0–19 years were included. Main outcome measures: estimated national annual rates of burn-related hospitalisations, stratified by age, gender, and in-hospital mortality.ResultsFrom 1993 to 2006, the estimated annual incidence rate of paediatric hospitalisations associated with burns declined 40% from 27.3 (1993–94) to 16.1 per 100 000 (p<0.001). The rates declined for all age groups and for both boys and girls. Boys were consistently more likely to be hospitalised than girls (20.3 vs 11.7 hospitalisations per 100 000 during 2004–06, p<0.001). For children less than 5 years of age, burn hospitalisations decreased 46% from 65.2 per 100 000 in 1993–94 to 35.1 per 100 000 in 2004–06 (p<0.001). Fatal hospitalisation rates also declined from 0.3 deaths per 100 000 in 1993–94 to 0.1 in 2004–06 (p<0.001).ConclusionPaediatric hospitalisation rates for burns have decreased over the past 14 years. The study also provides national estimates of paediatric burn hospitalisations that can be used as benchmarks to further injury prevention effectiveness through targeting of effective strategies.
On the Quality of Examples in Introductory Java Textbooks
Authors: Börstler Jürgen , Nordström Marie , Paterson James H. 
Published: March 2011

Example programs play an important role in the teaching and learning of programming. Students as well as teachers rank examples as the most important resources for learning to program. Example programs work as role models and must therefore always be consistent with the principles and rules we are teaching.
However, it is difficult to find or develop examples that are fully faithful to all principles and guidelines of the object-oriented paradigm and also follow general pedagogical principles and practices. Unless students are able to engage with good examples, they will not be able to tell desirable from undesirable properties in their own and others’ programs.
In this article we report on a study in which experienced educators evaluated the quality of object-oriented example programs for novices from popular Java textbooks. The evaluation was accomplished using an online checklist that elicited responses on the technical, object-oriented, and didactic quality of examples.
In total 25 reviewers contributed 215 reviews to our dataset, based on 38 example programs from 13 common introductory programming textbooks. Results show that the evaluation instrument is reliable in terms of inter-rater agreement. Overall, example quality was not as good as one might expect from common textbooks, in particular regarding certain object-oriented properties.
We conclude that educators should be careful when taking examples straight out of a textbook.
The PowerNap Server Architecture
Authors: Meisner David , Gold Brian T. , Wenisch Thomas F. 
Published: March 2011

Data center power consumption is growing to unprecedented levels: the EPA estimates U.S. data centers will consume 100 billion kilowatt hours annually by 2011. Much of this energy is wasted in idle systems: in typical deployments, server utilization is below 30%, but idle servers still consume 60% of their peak power draw. Typical idle periods---though frequent---last seconds or less, confounding simple energy-conservation approaches.
In this article, we propose PowerNap, an energy-conservation approach where the entire system transitions rapidly between a high-performance active state and a near-zero-power idle state in response to instantaneous load. Rather than requiring fine-grained power-performance states and complex load-proportional operation from individual system components, PowerNap instead calls for minimizing idle power and transition time, which are simpler optimization goals. Based on the PowerNap concept, we develop requirements and outline mechanisms to eliminate idle power waste in enterprise blade servers. Because PowerNap operates in low-efficiency regions of current blade center power supplies, we introduce the Redundant Array for Inexpensive Load Sharing (RAILS), a power provisioning approach that provides high conversion efficiency across the entire range of PowerNap’s power demands. Using utilization traces collected from enterprise-scale commercial deployments, we demonstrate that, together, PowerNap and RAILS reduce average server power consumption by 74%.
Using Marketing Muscle to Sell Fat: The Rise of Obesity in the Modern Economy
Authors: Zimmerman Frederick J. 
Published: March 2011

The large increase in obesity in the past 30 years has often been explained in rational choice terms; for example, a decline in food prices has engendered greater food consumption. On closer examination, this kind of explanation does not fit the facts of the current obesity epidemic. Instead, an unprecedented expansion in the scope, power, and ubiquity of food marketing has coincided with an unprecedented expansion in food consumption in predictable ways. Ongoing protestations that the causes of the recent increase in obesity are unknown may overstate the case. Ample evidence indicates that the obesity epidemic is, at least to a large degree, the result of increased marketing power over the American diet. Only by reigning in or countering marketing power can rationality be restored to the dietary choices of Americans.
Rho Kinase Phosphorylation Promotes Ezrin-Mediated Metastasis in Hepatocellular Carcinoma
Authors: Chen Yong , Wang Dongmei , Guo Zhen , Zhao Jun , Wu Bing , Deng Hui , Zhou Ti , Xiang Hongjun , Gao Fei , Yu Xue , Liao Jian , Ward Tarsha , Xia Peng , Emenari Chibuzo , Ding Xia , Thompson Winston , Ma Kelong , Zhu Jingde , Aikhionbare Felix , Dou Kefen , Cheng Shi-Yuan , Yao Xuebiao 
Published: March 2011

Abstract
During progression of hepatocellular carcinoma, multiple genetic and epigenetic alterations act to posttranslationally modulate the function of proteins that promote cancer invasion and metastasis. To define such abnormalities that contribute to liver cancer metastasis, we carried out a proteomic comparison of primary hepatocellular carcinoma and samples of intravascular thrombi from the same patient. Mass spectrometric analyses of the liver cancer samples revealed a series of acidic phospho-isotypes associated with the intravascular thrombi samples. In particular, we found that Thr567 hyperphosphorylation of the cytoskeletal protein ezrin was tightly correlated to an invasive phenotype of clinical hepatocellular carcinomas and to poor outcomes in tumor xenograft assays. Using phospho-mimicking mutants, we showed that ezrin phosphorylation at Thr567 promoted in vitro invasion by hepatocarcinoma cells. Phospho-mimicking mutant ezrinT567D, but not the nonphosphorylatable mutant ezrinT567A, stimulated formation of membrane ruffles, suggesting that Thr567 phosphorylation promotes cytoskeletal-membrane remodeling. Importantly, inhibition of Rho kinase, either by Y27632 or RNA interference, resulted in inhibition of Thr567 phosphorylation and a blockade to cell invasion, implicating Rho kinase-ezrin signaling in hepatocellular carcinoma cell invasion. Our findings suggest a strategy to reduce liver tumor metastasis by blocking Rho kinase-mediated phosphorylation of ezrin. Cancer Res; 71(5); 1721–9. ©2011 AACR.
Comprehensive Pathway-Based Association Study of DNA Repair Gene Variants and the Risk of Nasopharyngeal Carcinoma
Authors: Qin Hai-De , Shugart Yin Yao , Bei Jin-Xin , Pan Qing-Hua , Chen Lina , Feng Qi-Sheng , Chen Li-Zhen , Huang Wei , Liu Jian Jun , Jorgensen Timothy J. , Zeng Yi-Xin , Jia Wei-Hua 
Published: March 2011

Abstract
DNA repair plays a central role in protecting against environmental carcinogenesis, and genetic variants of DNA repair genes have been reported to be associated with several human malignancies. To assess whether DNA gene variants were associated with nasopharyngeal carcinoma (NPC) risk, a candidate gene association study was conducted among the Cantonese population within the Guangdong Province, China, the ethnic group with the highest risk for NPC. A 2-stage study design was utilized. In the discovery stage, 676 tagging SNPs covering 88 DNA repair genes were genotyped in a matched case-control study (cases/controls = 755/755). Eleven SNPs with Ptrend &lt; 0.01 were identified. Seven of these SNPs were located within 3 genes, RAD51L1, BRCA2, and TP53BP1. In the validation stage, these 11 SNPs were genotyped in a separate Cantonese population (cases/controls = 1,568/1,297). Two of the SNPs (rs927220 and rs11158728), both in RAD51L1, remained strongly associated with NPC. The SNP rs927220 had a significant Pcombined of 5.55 × 10−5, with OR = 1.20 (95% CI = 1.10–1.30), Bonferroni corrected P = 0.0381. The other SNP (rs11158728), which is in strong linkage disequilibrium with rs927220 (r2 = 0.7), had a significant Pcombined of 2.0 × 10−4, Bonferroni corrected P = 0.1372. Gene–environment interaction analysis suggested that the exposures of salted fish consumption and cigarette smoking had potential interactions with DNA repair gene variations, but need to be further investigated. Our findings support the notion that DNA repair genes, in particular RAD51L1, play a role in NPC etiology and development. Cancer Res; 71(8); 3000–8. ©2011 AACR.
Ulcerative Colitis–Associated Colorectal Cancer Arises in a Field of Short Telomeres, Senescence, and Inflammation
Authors: Risques Rosa Ana , Lai Lisa A. , Himmetoglu Cigdem , Ebaee Anoosheh , Li Lin , Feng Ziding , Bronner Mary P. , Al-Lahham Bassel , Kowdley Kris V. , Lindor Keith D. , Rabinovitch Peter S. , Brentnall Teresa A. 
Published: March 2011

Abstract
Inflammation plays a role in the progression to cancer and it is linked to the presence of senescent cells. Ulcerative colitis (UC) is a chronic inflammatory disease that predisposes to colorectal cancer. Tumorigenesis in this setting is associated with telomere shortening that can be observed in the nondysplastic epithelium of UC patients with high-grade dysplasia (HGD) or cancer (UC progressors). We hypothesized that a preneoplastic field of inflammation, telomere shortening, and senescence underlies tumor progression in UC progressors. Multiple biopsies of varying histologic grade were collected along the colon of nine UC progressors and analyzed for telomere length, DNA damage, senescence, p53, p16, and chronic and acute inflammation. Twenty biopsies from four UC nonprogressors and twenty-one biopsies from control individuals without UC were also analyzed. Short telomeres and increased DNA damage, senescence, and infiltrating leukocytes were observed in biopsies located less than 10 cm from HGD or cancer. Low-grade dysplasia (LGD) had the shortest telomeres along with the highest levels of senescence and infiltrating leukocytes, whereas HGD biopsies showed the opposite pattern. The expression of p16 and p53 was low in nondysplastic biopsies but progressively increased in LGD and HGD. In addition, high levels of infiltrating leukocytes were associated with telomere shortening, senescence, and reduced p53 expression. These results suggest that dysplasia arises in a preneoplastic field of chronic inflammation, which leads to telomere shortening, DNA damage, and senescence. Our findings argue that senescence acts as a tumor suppressor mechanism that is abrogated during the transition from LGD to HGD in UC. Cancer Res; 71(5); 1669–79. ©2011 AACR.
Identification of N-Terminally Truncated Stable Nuclear Isoforms of CDC25B That Are Specifically Involved in G2/M Checkpoint Recovery
Authors: Jullien Denis , Bugler Beatrix , Dozier Christine , Cazales Martine , Ducommun Bernard 
Published: March 2011

Abstract
CDC25B phosphatases must activate cyclin B-CDK1 complexes to restart the cell cycle after an arrest in G2 phase caused by DNA damage. However, little is known about the precise mechanisms involved in this process, which may exert considerable impact on cancer susceptibility and therapeutic responses. Here we report the discovery of novel N-terminally truncated CDC25B isoforms, referred to as ΔN-CDC25B, with an exclusively nuclear and nonredundant function in cell cycle re-initiation after DNA damage. ΔN-CDC25B isoforms are expressed from a distinct promoter not involved in expression of canonical full-length isoforms. Remarkably, in contrast to the high lability and spatial dynamism of the full-length isoforms, ΔN-CDC25B isoforms are highly stable and exclusively nuclear, strongly suggesting the existence of two pools of CDC25B phosphatases in the cell that have functionally distinct properties. Using isoform-specific siRNA, we found that depleting full-length isoforms, but not ΔN-CDC25B isoforms, delays entry into mitosis. Thus, in an unperturbed cell cycle, the full-length isoforms are exclusively responsible for activating cyclin B-CDK1. Strikingly, in the late response to DNA damage, we found a CHK1-dependent shift in accumulation of CDC25B isoforms toward the ΔN-CDC25B species. Under this physiological stress condition, the ΔN-CDC25B isoform was found to play a crucial, nonredundant function in restarting the cell cycle after DNA damage-induced G2 phase arrest. Our findings reveal the existence of a previously unrecognized CDC25B isoform that operates specifically in the nucleus to reinitiate G2/M transition after DNA damage. Cancer Res; 71(5); 1968–77. ©2011 AACR.
The ΔNp63 Proteins Are Key Allies of BRCA1 in the Prevention of Basal-Like Breast Cancer
Authors: Buckley Niamh E. , Conlon Susan J. , Jirstrom Karin , Kay Elaine W. , Crawford Nyree T. , O'Grady Anthony , Sheehan Katherine , Mc Dade Simon S. , Wang Ching-Wei , McCance Dennis J. , Johnston Patrick G. , Kennedy Richard D. , Harkin D. Paul , Mullan Paul B. 
Published: March 2011

Abstract
Little is known about the origin of basal-like breast cancers, an aggressive disease that is highly similar to BRCA1-mutant breast cancers. p63 family proteins that are structurally related to the p53 suppressor protein are known to function in stem cell regulation and stratified epithelia development in multiple tissues, and p63 expression may be a marker of basal-like breast cancers. Here we report that ΔNp63 isoforms of p63 are transcriptional targets for positive regulation by BRCA1. Our analyses of breast cancer tissue microarrays and BRCA1-modulated breast cancer cell lines do not support earlier reports that p63 is a marker of basal-like or BRCA1 mutant cancers. Nevertheless, we found that BRCA1 interacts with the specific p63 isoform ΔNp63γ along with transcription factor isoforms AP-2α and AP-2γ. BRCA1 required ΔNp63γ and AP-2γ to localize to an intronic enhancer region within the p63 gene to upregulate transcription of the ΔNp63 isoforms. In mammary stem/progenitor cells, siRNA-mediated knockdown of ΔNp63 expression resulted in genomic instability, increased cell proliferation, loss of DNA damage checkpoint control, and impaired growth control. Together, our findings establish that transcriptional upregulation of ΔNp63 proteins is critical for BRCA1 suppressor function and that defects in BRCA1-ΔNp63 signaling are key events in the pathogenesis of basal-like breast cancer. Cancer Res; 71(5); 1933–44. ©2011 AACR.
LPS-Induced TLR4 Signaling in Human Colorectal Cancer Cells Increases β1 Integrin-Mediated Cell Adhesion and Liver Metastasis
Authors: Hsu Rich Y.C. , Chan Carlos H.F. , Spicer Jonathan D. , Rousseau Mathieu C. , Giannias Betty , Rousseau Simon , Ferri Lorenzo E. 
Published: March 2011

Abstract
Infectious complications resulting from resection of colorectal cancer (CRC) elevates the risk of cancer recurrence and metastasis, but the reason for this risk relationship is unknown. Defining the mechanisms responsible may offer opportunities to improve outcomes in a majority of patients whose tumors are resected as part of their therapy. The complex formed between Toll receptor TLR4 and myeloid differentiation factor MD2 defines a major cell surface receptor for lipopolysaccharide (LPS), a gram-negative bacterial antigen that has been implicated in infectious complications after CRC resection. As the TLR4/MD2 complex is expressed on CRC cells, we hypothesized that LPS may promote liver metastasis in CRC by stimulating TLR4 signaling. In support of this hypothesis, we report here that LPS enhances liver metastasis of human CRC cells that express TLR4/MD2 after intrasplenic graft of immunocompromised nude mice. Compared with TLR4 nonexpressing, nonmetastatic CRC cells, we observed increased in vitro adherence to different extracellular matrices and human umbilical vein endothelial cells (HUVEC). Furthermore, we observed an increased likelihood of in vivo capture within hepatic sinusoids after LPS treatment. No differences were apparent in phosphorylation of p38 and MAPK isoforms, but in metastatic CRC cells expressing surface TLR4 treatment with LPS increased Ser473 phosphorylation of AKT kinase. We showed that enhanced adherence elicited by LPS in these cells could be blocked at three different levels, using Eritoran (TLR4 small molecule antagonist), PI-103 (PI3K inhibitor), or anti-β1 integrin blocking antibodies. Taken together, the results indicate that stimulation of the TLR4/MD2 complex by LPS activates PI3K/AKT signaling and promotes downstream β1 integrin function, thereby increasing the adhesiveness and metastatic capacity of CRC cells. Our findings suggest that inhibiting LPS-induced TLR4 signaling could improve therapeutic outcomes by preventing cancer metastasis during the perioperative period of CRC resection. Cancer Res; 71(5); 1989–98. ©2011 AACR.
Stromal Deletion of the APC Tumor Suppressor in Mice Triggers Development of Endometrial Cancer
Authors: Tanwar Pradeep S. , Zhang LiHua , Roberts Drucilla J. , Teixeira Jose M. 
Published: March 2011

Abstract
The contribution of the stromal microenvironment to the progression of endometrial cancer has not been well explored. We have conditionally expressed a mutant allele of adenomatous polyposis coli (APCcKO) in murine uterine stroma cells to study its effect on uterine development and function. In addition to metrorrhagia, the mice develop complex atypical endometrial gland hyperplasia that progresses to endometrial carcinoma in situ and endometrial adenocarcinoma as evidenced by myometrial invasion. Stromal cells subjacent to the carcinoma cells express alpha-smooth muscle actin (αSMA) with fewer cells expressing platelet-derived growth factor α compared with normal stromal cells, suggesting that the mutant stromal cells have acquired a more myofibroblastic phenotype, which have been described as cancer-associated fibroblasts and have been shown to induce carcinogenesis in other organ systems. Analyses of human endometrial cancer specimens showed substantial αSMA expression in the stroma compared with normal endometrial stroma cells. We also show that APCcKO mutant uteri and human endometrial cancer have decreased stromal levels of transforming growth factor β and bone morphogenetic protein activities and that the mutant uteri failed to respond to exogenous estradiol stimulation. The mutant stroma cells also had higher levels of vascular endothelial growth factor and stromal derived factor signaling components and diminished expression of estrogen receptor α and progesterone receptor, which is common in advanced stages of human endometrial cancer and is an indicator of poor prognosis. Our results indicate that de novo mutation or loss of heterozygosity in stromal APC is sufficient to induce endometrial hyperplasia and endometrial carcinogenesis by mechanisms that are consistent with unopposed estrogen signaling in the endometrial epithelium. Cancer Res; 71(5); 1584–96. ©2011 AACR.