bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cocarcinogenic Effect of Capsaicin Involves Activation of EGFR Signaling but Not TRPV1
Authors: Hwang Mun Kyung , Bode Ann M. , Byun Sanguine , Song Nu Ry , Lee Hyong Joo , Lee Ki Won , Dong Zigang 
Published: July 2010

AbstractEpidemiologic and animal studies revealed that capsaicin can act as a carcinogen or cocarcinogen. However, the molecular mechanisms of the cancer-promoting effects of capsaicin are not clear. Here, we report that capsaicin has a cocarcinogenic effect on 12-O-tetradecanoylphorbol-13-acetate (TPA)–promoted skin carcinogenesis in vivo and is mediated through the epidermal growth factor receptor (EGFR), but not the transient receptor potential vanilloid subfamily member 1 (TRPV1). Topical application of capsaicin on the dorsal skin of 7,12-dimetylbenz(a)anthracene–initiated and TPA-promoted TRPV1 wild-type (WT) and TRPV1 knockout (KO) mice induced more and larger skin tumors in TRPV1/KO mice, suggesting a TRPV1-independent mechanism. Cyclooxygenase-2 (COX-2) was highly elevated by capsaicin treatment in tumors and murine embryonic fibroblasts from TRPV1/KO mice. Inhibitors of EGFR/MEK signaling suppressed TPA/capsaicin-induced COX-2 expression in TRPV1/KO cells, indicating that activation of EGFR and its downstream signaling is involved in COX-2 elevation. Capsaicin induced a further induction of TPA-increased COX-2 expression in EGFR/WT cells, but not in EGFR/KO cells. TPA/capsaicin cotreatment caused EGFR tyrosine phosphorylation and activated EGFR downstream signaling, including ERKs and Akt in EGFR/WT, but not EGFR/KO cells. Specific inhibition of EGFR and TRPV1 indicated that capsaicin-induced ERK activation in A431 cells was dependent on EGFR, but not TRPV1. Together, these findings suggest that capsaicin might act as a cocarcinogen in TPA-induced skin carcinogenesis through EGFR-dependent mechanisms. Cancer Res; 70(17); 6859–69. ©2010 AACR.
Effect of Hyperconcavity of the Lumbar Vertebral Endplates on the Playing Careers of Professional American Football Linemen
Authors: Paxton E. Scott , Moorman Claude T. , Chehab Eric L. , Barnes Ronnie P. , Warren Russell F. , Brophy Robert H. 
Published: July 2010

Background Hyperconcavity of the lumbar spine has been found in a disproportionate percentage of college football lineman evaluated at the National Football League (NFL) Combine compared with age-matched controls. Hypothesis College football linemen with hyperconcavity of the lumbar spine are more likely to play in the NFL and to have a longer career in professional football. Study Design Cohort study; Level of evidence, 3. Methods Ninety three linemen from the 1992 and 1993 NFL Combines with hyperconcavity of the lumbar spine were compared with 191 linemen from the same combines without these changes in the lumbar spine. The percentage of athletes who played at least 1 game for an NFL team and the average length of career was calculated for both groups. In addition, the length of career for players with these changes was compared with those of matched controls based on other injuries and surgeries, year drafted, and round drafted. Results There was no difference in the likelihood of playing professional football between linemen with lumbar spine changes (54 of 93 [58%]) and those without (101 of 191 [53%]) (P = .41). There was no significant difference between the 2 groups in length of career in terms of years played, games played, or games started. Conclusion Hyperconcavity of the lumbar spine does not appear to have any effect on the potential professional American football careers of college football linemen entering the NFL. Endplate changes on radiographs are not a significant screening tool for elite American football linemen. Further study of larger populations is needed to definitively answer whether these adaptive changes in the lumbar spine have any clinical relevance to these athletes.
The David Gordon Memorial Lecture: Finance without Financiers: Prospects for Radical Change In Financial Governance
Authors: Epstein Gerald 
Published: July 2010

In response to the financial crisis of 2007—2010, governments in the United States, Europe, and elsewhere have invested billions of dollars in financial institutions to prevent them from going bankrupt and from further disrupting the global economy. Despite these massive public bail-outs, a government and “elite” consensus has emerged that these nationalized or quasi-nationalized financial institutions should be privatized as soon as possible, and that, apart from modest changes in financial regulation, our economies should return to the status quo ante financial structure. I disagree. As the crisis reveals, “financier” dominated finance has a number of devastating flaws: it creates major externalities that contribute to financial and real economic instability; it promotes short-term investment strategies; it contributes to inequality; and it undermines economic efficiency and the achievement of social goals in the real economy. I argue that a better strategy for achieving economic recovery, restructuring, and widely shared, sustainable prosperity is to use public investments in the financial sector to build on the successful post-World War II experiences of publicly oriented financial institutions to create a stronger presence of “finance without financiers.” JEL classification: E02, E44, G28
Some Critical Notes on Citation Metrics and Heterodox Economics
Authors: Kapeller Jakob 
Published: July 2010

This article investigates citations metrics as an institutional phenomenon from two perspectives: first it tries to articulate the role of citation metrics within a Gramscian framework; second it compares citation patterns from orthodox and heterodox economic journals to gain insights on the current economic discourse. Complementary to this general question the role of the Review of Radical Political Economics within citation metrics will be discussed. JEL classification: A14, B50, B51
Seeds of Change: Hybrid Corn, Monopoly, and the Hunt for Superprofits
Authors: Ramey Elizabeth A. 
Published: July 2010

Hybrid corn is widely acknowledged to be the cornerstone of twentieth century breakthroughs in agricultural technology, an essential step toward achieving the “pushbutton cornucopia” to which modern agriculture aspires. This paper challenges this view by examining the social causes and consequences of technical change in corn production, and shows how the development and adoption of hybrid technologies has contributed to the perpetual crisis of corn farming, while sustaining the expansion of the seed corn industry. JEL classification: B51, Q16, O33
Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies
Authors: Orjuela-Sánchez Pamela , Karunaweera Nadira D , da Silva-Nunes Mônica , da Silva Natal S , Scopel Kézia KG , Gonçalves Raquel M , Amaratunga Chanaki , Sá Juliana M , Socheat Duong , Fairhust Rick M , Gunawardena Sharmini , Thavakodirasah Thuraisamy , Galapaththy Gawrie LN , Abeysinghe Rabindra , Kawamoto Fumihiko , Wirth Dyann F , Ferreira Marcelo U 
Published: July 2010

Abstract

Background
The ideal malaria parasite populations for initial mapping of genomic regions contributing to phenotypes such as drug resistance and virulence, through genome-wide association studies, are those with high genetic diversity, allowing for numerous informative markers, and rare meiotic recombination, allowing for strong linkage disequilibrium (LD) between markers and phenotype-determining loci. However, levels of genetic diversity and LD in field populations of the major human malaria parasite P. vivax remain little characterized.

Results
We examined single-nucleotide polymorphisms (SNPs) and LD patterns across a 100-kb chromosome segment of P. vivax in 238 field isolates from areas of low to moderate malaria endemicity in South America and Asia, where LD tends to be more extensive than in holoendemic populations, and in two monkey-adapted strains (Salvador-I, from El Salvador, and Belem, from Brazil). We found varying levels of SNP diversity and LD across populations, with the highest diversity and strongest LD in the area of lowest malaria transmission. We found several clusters of contiguous markers with rare meiotic recombination and characterized a relatively conserved haplotype structure among populations, suggesting the existence of recombination hotspots in the genome region analyzed. Both silent and nonsynonymous SNPs revealed substantial between-population differentiation, which accounted for ~40% of the overall genetic diversity observed. Although parasites clustered according to their continental origin, we found evidence for substructure within the Brazilian population of P. vivax. We also explored between-population differentiation patterns revealed by loci putatively affected by natural selection and found marked geographic variation in frequencies of nucleotide substitutions at the pvmdr-1 locus, putatively associated with drug resistance.

Conclusion
These findings support the feasibility of genome-wide association studies in carefully selected populations of P. vivax, using relatively low densities of markers, but underscore the risk of false positives caused by population structure at both local and regional levels.
See commentary: http://www.biomedcentral.com/1741-7007/8/90
Association of childhood trauma with cognitive function in healthy adults: a pilot study
Authors: Majer Matthias , Nater Urs M , Lin Jin-Mann S , Capuron Lucile , Reeves William C 
Published: July 2010

Abstract

Background
Animal and human studies suggest that stress experienced early in life has detrimental consequences on brain development, including brain regions involved in cognitive function. Cognitive changes are cardinal features of depression and posttraumatic stress disorder. Early-life trauma is a major risk factor for these disorders. Only few studies have measured the long-term consequences of childhood trauma on cognitive function in healthy adults.

Methods
In this pilot study, we investigated the relationship between childhood trauma exposure and cognitive function in 47 healthy adults, who were identified as part of a larger study from the general population in Wichita, KS. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the Wide-Range-Achievement-Test (WRAT-3) to examine cognitive function and individual achievement. Type and severity of childhood trauma was assessed by the Childhood Trauma Questionnaire (CTQ). Data were analyzed using multiple linear regression on CANTAB measures with primary predictors (CTQ scales) and potential confounders (age, sex, education, income).

Results
Specific CTQ scales were significantly associated with measures of cognitive function. Emotional abuse was associated with impaired spatial working memory performance. Physical neglect correlated with impaired spatial working memory and pattern recognition memory. Sexual abuse and physical neglect were negatively associated with WRAT-3 scores. However, the association did not reach the significance level of p < 0.01.

Conclusions
Our results suggest that physical neglect and emotional abuse might be associated with memory deficits in adulthood, which in turn might pose a risk factor for the development of psychopathology.
Dissemination of multidrug resistant Acinetobacter baumannii in various hospitals of Antananarivo Madagascar
Authors: Andriamanantena Tahiry S , Ratsima Elisoa , Rakotonirina Hanitra C , Randrianirina Frédérique , Ramparany Lovasoa , Carod Jean-François , Richard Vincent , Talarmin Antoine 
Published: July 2010

AbstractThis study reports the dissemination of multidrug-resistant (MDR) OXA-23-producingAcinetobacter baumanniiclones in hospitals in Antananarivo, Madagascar. A total of 53 carbapenem-resistantA. baumanniiisolates were obtained from September 2006 to March 2009 in five hospitals. These resistant strains represent 44% of allA. baumanniiisolates. The double disk synergy test was performed to screen for production of metallo-beta-lactamases. Polymerase chain reaction (PCR) and DNA sequencing were performed for the detection ofbla(AmpC), bla(OXA-51),bla(OXA-23), bla(OXA-24), bla(IMP),bla(VIM). The presence of the insertion sequence ISAba1relative toblaOXA-23 andblaOXA-51 was assessed by PCR. Isolates were typed by Rep-PCR. All the isolates were MDR and produced the OXA-23 carbapenemase, which was confirmed by sequencing. PCR analysis for AmpC and OXA-51 gave positive results for all strains studied. No isolates produced metallo-beta-lactamases. In all isolates ISAba1laid upstream ofblaOXA-23. TheA. baumanniiisolates were separated into two genotypes; genotype A had a higher prevalence (41 strains) than genotype B (12 strains). Genotype A was present in four hospitals, whilst genotype B had spread in two hospitals. The high frequency of MDR OXA-23-producingA. baumanniiin various hospitals in Antananarivo is curious since carbapenems are not available in Madagascar, but it emphasises the need for infection control procedures and strict adherence to them to prevent the spread of these resistant organisms in Antananarivo and also the need to control the use of carbapenems in the future.
Ezetimibe/simvastatin vs simvastatin in coronary heart disease patients with or without diabetes
Authors: Rotella Carlo M , Zaninelli Augusto , Le Grazie Cristina , Hanson Mary E , Gensini Gian Franco 
Published: July 2010

Abstract

Background
Treatment guidelines recommend LDL-C as the primary target of therapy in patients with hypercholesterolemia. Moreover, combination therapies with lipid-lowering drugs that have different mechanisms of action are recommended when it is not possible to attain LDL-C targets with statin monotherapy. Understanding which treatment or patient-related factors are associated with attaining a target may be clinically relevant.

Methods
Data were pooled from two multicenter, randomized, double-blind studies. After stabilization on simvastatin 20 mg, patients with coronary heart disease (CHD) alone and/or type 2 diabetes mellitus (T2DM) were randomized to ezetimibe 10 mg/simvastatin 20 mg (EZ/Simva) or simvastatin 40 mg. The change from baseline in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C ratio, triglycerides, and the proportion of patients achieving LDL-C < 2.6 mmol/L (100 mg/dL) after 6 weeks of treatment were assessed, and factors significantly correlated with the probability of achieving LDL-C < 2.6 mmol/L in a population of high cardiovascular risk Italian patients were identified. A stepwise logistic regression model was conducted with LDL-C < 2.6 mmol/L at endpoint as the dependent variable and study, treatment, gender, age (≥65 years or < 65 years), as independent variables and baseline LDL-C (both as continuous and discrete variable).

Results
EZ/Simva treatment (N = 93) resulted in significantly greater reductions in LDL-C, TC, and TC/HDL-C ratio and higher attainment of LDL-C < 2.6 mmol/L vs doubling the simvastatin dose to 40 mg (N = 106). Study [including diabetic patients (OR = 2.9, p = 0.003)], EZ/Simva treatment (OR = 6.1, p < 0.001), and lower baseline LDL-C (OR = 0.9, p = 0.001) were significant positive predictors of LDL-C target achievement. When baseline LDL-C was expressed as a discrete variable, the odds of achieving LDL-C < 2.6 mmol/L was 4.8 in favor of EZ/Simva compared with Simva 40 mg (p < 0.001), regardless of baseline LDL-C level.

Conclusion
EZ/Simva is an effective therapeutic option for patients who have not achieved recommended LDL-C treatment targets with simvastatin 20 mg monotherapy.

Trial Registration
Clinical trial registration numbers: NCT00423488 and NCT00423579
Chemoimmunotherapy With a Modified Hyper-CVAD and Rituximab Regimen Improves Outcome in De Novo Philadelphia Chromosome–Negative Precursor B-Lineage Acute Lymphoblastic Leukemia
Authors: Thomas Deborah A. , O'Brien Susan , Faderl Stefan , Garcia-Manero Guillermo , Ferrajoli Alessandra , Wierda William , Ravandi Farhad , Verstovsek Srdan , Jorgensen Jeffrey L. , Bueso-Ramos Carlos , Andreeff Michael , Pierce Sherry , Garris Rebecca , Keating Michael J. , Cortes Jorge , Kantarjian Hagop M. 
Published: July 2010

PurposeThe adverse prognosis of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia (ALL) prompted incorporation of monoclonal antibody therapy with rituximab into the intensive chemotherapy regimen hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone). Other modifications (irrespective of CD20 expression) included early anthracycline intensification, alterations in number of risk-adapted intrathecal chemotherapy treatments for CNS prophylaxis, additional early and late intensifications, and extension of maintenance phase chemotherapy by 6 months.Patients and MethodsTwo hundred eighty-two adolescents and adults with de novo Philadelphia chromosome (Ph)–negative precursor B-lineage ALL were treated with standard or modified hyper-CVAD regimens. The latter incorporated standard-dose rituximab if CD20 expression ≥ 20%.ResultsThe complete remission (CR) rate was 95% with 3-year rates of CR duration (CRD) and survival (OS) of 60% and 50%, respectively. In the younger (age < 60 years) CD20-positive subset, rates of CRD and OS were superior with the modified hyper-CVAD and rituximab regimens compared with standard hyper-CVAD (70% v 38%; P < .001% and 75% v 47%, P = .003). In contrast, rates of CRD and OS for CD20-negative counterparts treated with modified versus standard hyper-CVAD regimens were similar (72% v 68%, P = not significant [NS] and 64% v 65%, P = NS, respectively). Older patients with CD20-positive ALL did not benefit from rituximab-based chemoimmunotherapy (rates of CRD 45% v 50%, P = NS and OS 28% v 32%, P = NS, respectively), related in part to deaths in CR.ConclusionThe incorporation of rituximab into the hyper-CVAD regimen appears to improve outcome for younger patients with CD20-positive Ph-negative precursor B-lineage ALL.
Identification and evaluation of a new nucleic acid amplification test target for specific detection of Mycobacterium tuberculosis
Authors: Qin Lianhua , Zheng Ruijuan , Fan Chao , Cai Jiangli , Liu Zhonghua , Wang Jie , Lu Junmei , Jin Ruiliang , Yang Hua , Cui Zhenling , Feng Yonghong , Hu Zhongyi 
Published: July 2010

Abstract

Background: Accurate and early diagnosis of tuberculosis (TB) is of major importance in the management and control of TB. Because the conventional bacteriological diagnosis of TB has several limitations, nucleic acid amplification (NAA) tests have emerged as promising alternatives. A potential problem with NAA tests is that some strains lack a target, which may be the one of main reasons for the much lower and highly variable accuracy in diagnosis. A possible solution may be to use more valid and applicable targets to increase detection accuracy.

Methods: In this paper, we designed a two-step program to obtain NAA test targets. Inter-simple sequence repeats (ISSR) based on oligonucleotide (GTG)5 were first constructed to genotype Mycobacterium strains to obtain Mycobacterium tuberculosis (MTB)-specific fragment. Second, sequence characterized amplified region (SCAR) markers were developed from these species-specific sequences to identify MTB. Some 312 Mycobacterium strains were used to evaluate the efficacy of the SCAR markers, IS6110 element [specific identification of Mycobacterium tuberculosis complex (MTC)] and 16SrRNA gene (specific identification of Mycobacterium) amplification, together with traditional bacteriology testing was used as a control.

Results: MTB-specific sequences located in a gene coding for Rv1508c, as a new NAA test target, were obtained using ISSR-PCR genotyping. Based on these sequences, the SCAR primer pairs MISP1 and MISP2 were designed. All 312 strains from Mycobacterium accurately produced the genus-specific 16SrRNA amplicon. 271 MTB strains and M. africanum were positive. However, all nontuberculous mycobacteria (NTM) strains and 1 MTB strain named 1143 were negative in both SCAR and IS6110 PCR amplification. M. bovis, bacille Calmette-Guérin (BCG) were IS6110-PCR positive, while SCAR-PCR was negative. Strain 1143 was defined as M. arupense with 99% identity by 16SrRNA gene sequencing identification, despite being diagnosed as MTB using traditional testing.

Conclusions: SCAR markers developed with this two-step program can be used as a new NAA test target to correctly detect MTB.
Clin Chem Lab Med 2010;48:1501–5.
Targeting DNA Double-Strand Breaks with TAL Effector Nucleases
Authors: Christian Michelle , Cermak Tomas , Doyle Erin L , Schmidt Clarice , Zhang Feng , Hummel Aaron , Bogdanove Adam J , Voytas Daniel F 
Published: July 2010

Abstract
Engineered nucleases that cleave specific DNA sequences in vivo are valuable reagents for targeted mutagenesis. Here we report a new class of sequence-specific nucleases created by fusing transcription activator-like effectors (TALEs) to the catalytic domain of the FokI endonuclease. Both native and custom TALE-nuclease fusions direct DNA double-strand breaks to specific, targeted sites.
Noninvasive Continuous Positive Airway Pressure in Acute Respiratory Failure: Helmet Versus Facial Mask
Authors: Chidini Giovanna , Calderini Edoardo , Cesana Bruno Mario , Gandini Cristiano , Prandi Edi , Pelosi Paolo 
Published: July 2010

OBJECTIVE:Noninvasive continuous positive airway pressure (nCPAP) is applied through different interfaces to treat mild acute respiratory failure (ARF) in infants. Recently a new pediatric helmet was introduced in clinical practice to deliver nCPAP. The objective of this study was to compare the feasibility of the delivery of nCPAP by the pediatric helmet with delivery by a conventional facial mask in infants with ARF.PATIENTS AND METHODS:We conducted a single-center physiologic, randomized, controlled study with a crossover design on 20 consecutive infants with ARF. All patients received nCPAP by helmet and facial mask in random order for 90 minutes. In infants in both trials, nCPAP treatment was preceded by periods of unassisted spontaneous breathing through a Venturi mask. The primary end point was the feasibility of nCPAP administered with the 2 interfaces (helmet and facial mask). Feasibility was evaluated by the number of trial failures defined as the occurrence of 1 of the following: intolerance to the interface; persistent air leak; gas-exchange derangement; or major adverse events. nCPAP application time, number of patients who required sedation, and the type of complications with each interface were also recorded. The secondary end point was gas-exchange improvement.RESULTS:Feasibility of nCPAP delivery was enhanced by the helmet compared with the mask, as indicated by a lower number of trial failures (P &lt; .001), less patient intolerance (P &lt; .001), longer application time (P &lt; .001), and reduced need for patient sedation (P &lt; .001). For both delivery methods, no major patient complications occurred.CONCLUSIONS:The results of this current study revealed that the helmet is a feasible alternative to the facial mask for delivery of nCPAP to infants with mild ARF.