bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of three commercial ELISA kits for anticardiolipin and anti‐beta2‐glycoprotein I antibodies in the laboratory diagnosis of the antiphospholipid syndrome
Authors: DECAVELE A. S. , SCHOUWERS S. , DEVREESE K. M. J. 
Published: September 2010

SummaryIntroduction:  The laboratory criteria of the antiphospholipid syndrome (APS) include lupus anticoagulant (LAC), anticardiolipin antibodies (aCL) and anti‐β2glycoprotein I antibodies (aβ2GPI) IgG or IgM.Methods:  We evaluated three commercial ELISAs for aCL and aβ2GPI IgG and IgM: Asserachrom® (‘Stago’), Bio‐Rad (‘BR’) and the Bindazyme™ (the Binding Site, ‘BS’).Results:  Results of all assays and of LAC were correlated with the clinical background (n = 228). Sensitivity for Stago/BS/BR aCL IgG was 14%/15%/18%, for aCL IgM 1%/5%/4%, for aβ2GPI IgG 9%/10%/17% and for aβ2GPI IgM 4%/4%/3%. The specificity for Stago/BS/BR for all assays ranged from 86% to 98%. The positive predictive value (PPV) for Stago/BS/BR aCL IgG was 46%/52%/40%, for aCL IgM 8%/36%/19%, for aβ2GPI IgG 70%/67%/45% and for aβ2GPI IgM 23%/23%/20%. Combining LAC with aCL and aβ2GPI antibodies increased the sensitivity (Stago/BS/BR IgG: 26%/27%/31%, IgM: 22%/21%/26%) and PPV (Stago/BS/BR IgG: 41%/46%/36%, IgM: 34%/40%/36%). Comparing the diagnostic power of the tests, only Stago/BS aβ2GPI IgG had a Chi‐square P‐value lower than 0.05. The combination of LAC and IgG ELISAs of BS resulted in the lowest P‐value (0.098) compared to the other combinations.Conclusion:  All evaluated ELISAs are a practical tool in the laboratory diagnosis of APS. The diagnostic performance shows slight differences between the ELISAs from the different manufacturers.
Genetic Variations in Shiga Toxin‐Producing Abilities of Bovine and Human Escherichia coli O157:H7
Authors: Taylor E. V. , Shi X. , Alam M. J. , Peterson G. , Narayanan S. K. , Renter D. G. , Nagaraja T. G. 
Published: September 2010

SummaryCattle are a primary reservoir of Escherichia coli O157:H7, a major foodborne pathogen. The organism causes haemorrhagic colitis which can lead to serious complications, including haemolytic–uraemic syndrome. Although E. coli O157:H7 is widely prevalent in cattle and cattle environments, the number of human cases remain relatively low, suggesting possible strain diversity and differences in virulence between human and bovine strains. Shiga toxins, Stx1 and Stx2, are the major virulence factors. Differences in Stx2 production between human and bovine strains have been demonstrated previously, and isolates possessing the stx2 gene, but not producing Stx2 [toxin non‐producing (TNP) strains] have been identified. In this study, 150 isolates (56 human, 94 bovine) were tested by PCR for stx2 upstream regions associated with TNP and the Q933 gene, which has been previously associated with toxin production. A reverse passive latex agglutination test was used to evaluate 107 isolates (50 human, 57 bovine) for Stx1 and Stx2 production. The percentages of human and bovine isolates positive for presence of the TNP regions were similar (57.1% and 53.1% respectively), while a higher percentage of human isolates was positive for Q933 gene (89.3% versus 54.3%). Stx2 production of ≥1 : 8 was found in 86.0% of human isolates compared with 26.3% of bovine isolates. Bovine isolates with the presence of the TNP regions were associated with significantly lower Stx2 production (P < 0.05), while the Q933 gene was associated with higher Stx2 production (P < 0.05). However, the presence of the TNP region was not associated (P > 0.05) with low Stx2 production in human isolates. Therefore, Q933 was a better indicator of high Stx2 production by human and bovine isolates and may be a useful screening method to assess their potential to cause human disease.
A Specific Need for CRKL in p210BCR-ABL–Induced Transformation of Mouse Hematopoietic Progenitors
Authors: Seo Ji-Heui , Wood Lisa J. , Agarwal Anupriya , O'Hare Thomas , Elsea Collin R. , Griswold Ian J. , Deininger Michael W.N. , Imamoto Akira , Druker Brian J. 
Published: September 2010

Abstract
CRKL (CRK-like) is an adapter protein predominantly phosphorylated in cells that express the tyrosine kinase p210BCR-ABL, the fusion product of a (9;22) chromosomal translocation causative for chronic myeloid leukemia. It has been unclear, however, whether CRKL plays a functional role in p210BCR-ABL transformation. Here, we show that CRKL is required for p210BCR-ABL to support interleukin-3–independent growth of myeloid progenitor cells and long-term outgrowth of B-lymphoid cells from fetal liver–derived hematopoietic progenitor cells. Furthermore, a synthetic phosphotyrosyl peptide that binds to the CRKL SH2 domain with high affinity blocks association of endogenous CRKL with the p210BCR-ABL complex and reduces c-MYC levels in K562 human leukemic cells as well as in mouse hematopoietic cells transformed by p210BCR-ABL or the imatinib-resistant mutant T315I. These results indicate that the function of CRKL as an adapter protein is essential for p210BCR-ABL–induced transformation. Cancer Res; 70(18); 7325–35. ©2010 AACR.
Neurotensin Receptor 1 Determines the Outcome of Non–Small Cell Lung Cancer
Authors: Alifano Marco , Souazé Frédérique , Dupouy Sandra , Camilleri-Broët Sophie , Younes Mohamad , Ahmed-Zaïd Sadi-Menad , Takahashi Takashi , Cancellieri Alessandra , Damiani Stefania , Boaron Maurizio , Broët Philippe , Miller Lance D. , Gespach Christian , Regnard Jean François , Forgez Patricia 
Published: September 2010

Abstract
Purpose: This study aimed to investigate the role of the neurotensin/neurotensin receptor I (NTSR1) complex in non–small cell lung cancer (NSCLC) progression.
Experimental Design: The expression of neurotensin and NTSR1 was studied by transcriptome analysis and immunohistochemistry in two series of 74 and 139 consecutive patients with pathologic stage I NSCLC adenocarcinoma. The findings were correlated with clinic-pathologic features. Experimental tumors were generated from the malignant human lung carcinoma cell line A459, and a subclone of LNM35, LNM-R. The role of the neurotensin signaling system on tumor growth and metastasis was investigated by small hairpin RNA–mediated silencing of NTSR1 and neurotensin.
Results: Transcriptome analysis carried out in a series of 74 patients showed that the positive regulation of NTSR1 put it within the top 50 genes related with relapse-free survival. Immunohistochemistry revealed neurotensin- and NTSR1-positive staining in 60.4% and 59.7% of lung adenocarcinomas, respectively. At univariate analysis, NTSR1 expression was strongly associated with worse 5-year overall survival rate (P = 0.0081) and relapse-free survival (P = 0.0024). Multivariate analysis showed that patients over 65 years of age (P = 0.0018) and NTSR1 expression (P = 0.0034) were independent negative prognostic factors. Experimental tumor xenografts generated by neurotensin- and NTSR1-silenced human lung cancer cells revealed that neurotensin enhanced primary tumor growth and production of massive nodal metastasis via autocrine and paracrine regulation loops.
Conclusion: NTSR1 expression was identified as a potential new prognostic biomarker for surgically resected stage I lung adenocarcinomas, as NTSR1 activation was shown to participate in lung cancer progression. Clin Cancer Res; 16(17); 4401–10. ©2010 AACR.
Hypoxia Inducible Factor 1α and Hypoxia Inducible Factor 2α Play Distinct and Functionally Overlapping Roles in Oral Squamous Cell Carcinoma
Authors: Zhu Gui-quan , Tang Ya-ling , Li Ling , Zheng Min , Jiang Jian , Li Xiao-yu , Chen Si-xiu , Liang Xin-hua 
Published: September 2010

AbstractPurpose: This study aimed to investigate the functional difference between hypoxia inducible factor (HIF)-1α and HIF-2α in oral squamous cell carcinomas (OSCC).Experimental Design: We evaluated the correlations between HIF-1α and HIF-2α expression and the clinical-pathologic characteristics of 97 patients with OSCC by immunohistochemical staining. OSCC cell lines transfected with lentivirus encoding short hairpin RNA against HIF-1α/2α were used to investigate the HIF-1α/2α–dependent target genes. Xenograft tumors in nude mice were established using cells affected by lentivirus, and tumor growth, angiogenesis, proliferation, and apoptosis were measured.Results: HIF-1α expression was significantly associated with T stage (P = 0.004), lymph node involvement (P = 0.006), histologic differentiation (P = 0.013), and microvessel density (P = 0.014), whereas that of HIF-2α was associated with T stage (P = 0.011) and microvessel density (P = 0.005). Patients with positive HIF-1α nuclear staining had a significantly worse overall survival (P &lt; 0.001) and disease-free survival (P &lt; 0.001) than those with negative HIF-1α staining. When OSCC cells were cultured at 5% O2, only HIF-2α contributed to the expression of vascular endothelial growth factor. At 1% O2, vascular endothelial growth factor was regulated by both HIF-1α and HIF-2α, but glucose transporter 1, carbonic anhydrase 9, and urokinase-type plasminogen activator receptor were regulated by HIF-1α rather than by HIF-2α. Knocking down HIF-1α or HIF-2α individually inhibited the xenograft tumor angiogenesis and growth, and knocking them down simultaneously revealed a better inhibitory effect than knocking down either unit alone.Conclusions: HIF-1α and HIF-2α correlated with different clinical-pathologic parameters, stabilized at different oxygen levels, and regulated different genes in OSCC. However, both HIF-1α and HIF-2α showed promoting roles in tumor angiogenesis and growth, and therapeutic outcome may benefit from combined targeting of HIF-1α and HIF-2α. Clin Cancer Res; 16(19); 4732–41. ©2010 AACR.
Impact of a Statewide ST-Segment–Elevation Myocardial Infarction Regionalization Program on Treatment Times for Women, Minorities, and the Elderly
Authors: Glickman Seth W. , Granger Christopher B. , Ou Fang-Shu , O'Brien Sean , Lytle Barbara L. , Cairns Charles B. , Mears Greg , Hoekstra James W. , Garvey J. Lee , Peterson Eric D. , Jollis James G. 
Published: September 2010

Background—
Prior studies have demonstrated differences in time to reperfusion for ST-segment–elevation myocardial infarction (STEMI) in women, minorities, and the elderly, relative to their counterparts. Regionalization has been shown to improve overall STEMI treatment times, but its impact on care differences among these important patient subgroups is unknown. The objective of this analysis was to assess the impact of a statewide system of STEMI care (The Reperfusion of Acute Myocardial Infarction in North Carolina Emergency Departments) on treatment times according to patient sex, race, and age.

Methods and Results—

STEMI treatment times were determined before (July 2005 to September 2005) and after (January 2007 to March 2007) a year-long implementation of coordinated regional treatment protocols. Times in the pre- and postintervention periods were compared by mixed-effects models. A total of 2063 STEMI patients were analyzed: 1140 at percutaneous coronary intervention hospitals and 923 at non–percutaneous coronary intervention hospitals. The Reperfusion of Acute Myocardial Infarction in North Carolina Emergency Departments was associated with significant improvements in treatment times in women and the elderly, including door-to-ECG, door-to-device, door-in–door-out, and door-to-needle times (all
P
<0.05). Temporal improvements in treatment times at percutaneous coronary intervention hospitals were not significantly different in blacks than in whites. There was a reduction in baseline treatment disparities in door-to-ECG times in women versus men (4.4-minute reduction in difference; 95% CI, −8.1 to −0.4;
P
=0.03). After Reperfusion of Acute Myocardial Infarction in North Carolina Emergency Departments, an age–treatment time gap persisted in the elderly, relative to younger patients.

Conclusions—
A statewide STEMI regionalization program was associated with comparable improvement in treatment times for female, black, and elderly patients compared with middle-aged, white male patients. Nevertheless, there remain opportunities to further narrow treatment differences, particularly among the elderly.
Frontostriatal Maturation Predicts Cognitive Control Failure to Appetitive Cues in Adolescents
Authors: Somerville Leah H. , Hare Todd , Casey B. J. 
Published: September 2010

Abstract
Adolescent risk-taking is a public health issue that increases the odds of poor lifetime outcomes. One factor thought to influence adolescents' propensity for risk-taking is an enhanced sensitivity to appetitive cues, relative to an immature capacity to exert sufficient cognitive control. We tested this hypothesis by characterizing interactions among ventral striatal, dorsal striatal, and prefrontal cortical regions with varying appetitive load using fMRI scanning. Child, teen, and adult participants performed a go/no-go task with appetitive (happy faces) and neutral cues (calm faces). Impulse control to neutral cues showed linear improvement with age, whereas teens showed a nonlinear reduction in impulse control to appetitive cues. This performance decrement in teens was paralleled by enhanced activity in the ventral striatum. Prefrontal cortical recruitment correlated with overall accuracy and showed a linear response with age for no-go versus go trials. Connectivity analyses identified a ventral frontostriatal circuit including the inferior frontal gyrus and dorsal striatum during no-go versus go trials. Examining recruitment developmentally showed that teens had greater between-subject ventral-dorsal striatal coactivation relative to children and adults for happy no-go versus go trials. These findings implicate exaggerated ventral striatal representation of appetitive cues in adolescents relative to an intermediary cognitive control response. Connectivity and coactivity data suggest these systems communicate at the level of the dorsal striatum differentially across development. Biased responding in this system is one possible mechanism underlying heightened risk-taking during adolescence.
Electromyographic Study of the Popliteus Muscle in the Dynamic Stabilization of the Posterolateral Corner Structures of the Knee
Authors: Schinhan Martina , Bijak Manfred , Unger Ewald , Nau Thomas 
Published: September 2010

Background: The posterolateral corner of the knee consists of static and dynamic stabilizing structures. Knee injuries often include the posterolateral structures. The popliteus muscle-tendon unit is known as the major dynamic stabilizer of the posterolateral corner. Hypothesis: The dynamic stabilization of the posterolateral structures of the knee via the popliteus muscle-tendon unit during a squatting exercise follows a constant activation pattern. Study Design: Controlled laboratory study. Methods: Within the pilot study, 6 volunteers performed 2 exercises to verify the electrode position scheme and to analyze cross-talk. In the main study 2 static exercises (standing and standing with knees flexed 90°) and 2 dynamic exercises (isolated popliteus muscle activation and squats) were recorded in 17 volunteers. Electromyograms were obtained of the popliteus, medial and lateral gastrocnemius, and quadriceps muscles. Knee angle-related muscle activity was recorded. Results: In the pilot study it was assumed that the chosen electrode position allowed selective measurement of popliteus muscle activity. In the main study the mean popliteus onset angle was 43° ± 14° of flexion; activity lasted through the reversal point of the squat to 58° ± 21° of flexion during extension movement. Popliteus activity during all testing cycles revealed that the activity in the standing position is the smallest. The highest activity was recorded during the squat and the popliteus muscle-tendon unit exercise. Conclusion: This study demonstrates an activation pattern of the popliteus muscle-tendon unit with high interindividual differences in the onset angles. A constant activation during the reversal phase of the squatting exercise could be observed. Clinical Relevance: Reconstructive procedures of the posterolateral structures often include reconstruction of the popliteus muscle-tendon unit. Reconstructive procedures are usually done in a static manner, thus not addressing the dynamic stabilizing structure in a true functional way. The findings of the current study may be a useful contribution to the ongoing discussion of this topic.
BCOR as a novel fusion partner of retinoic acid receptor alpha in a t(X;17)(p11;q12) variant of acute promyelocytic leukemia
Authors: Yamamoto Yukiya , Tsuzuki Sachiko , Tsuzuki Motohiro , Handa Kousuke , Inaguma Yoko , Emi Nobuhiko 
Published: September 2010

AbstractThe majority of acute promyelocytic leukemia (APL) cases are characterized by the presence of a promyelocytic leukemia–retinoic acid receptor alpha(RARA) fusion gene. In a small subset, RARA is fused to a different partner, usually involved in regulating cell growth and differentiation. Here, we identified a novel RARA fusion transcript, BCOR-RARA, in a t(X;17)(p11;q12) variant of APL with unique morphologic features, including rectangular and round cytoplasmic inclusion bodies. Although the patient was clinically responsive to all-trans retinoic acid, several relapses occurred with standard chemotherapy and all-trans retinoic acid. BCOR is a transcriptional corepressor through the proto-oncoprotein, BCL6, recruiting histone deacetylases and polycomb repressive complex 1 components. BCOR-RARA was found to possess common features with other RARA fusion proteins. These included: (1) the same break point in RARA cDNA; (2) self-association; (3) retinoid X receptor alpha is necessary for BCOR-RARA to associate with the RARA responsive element; (4) action in a dominant-negative manner on RARA transcriptional activation; and (5) aberrant subcellular relocalization. It should be noted that there was no intact BCOR found in the 45,-Y,t(X;17)(p11;q12) APL cells because they featured only a rearranged X chromosome. These results highlight essential features of pathogenesis in APL in more detail. BCOR appears to be involved not only in human congenital diseases, but also in a human cancer.
Lineage-instructive function of C/EBPα in multipotent hematopoietic cells and early thymic progenitors
Authors: Wölfler Albert , Danen-van Oorschot Astrid A. , Haanstra Jurgen R. , Valkhof Marijke , Bodner Claudia , Vroegindeweij Eric , van Strien Paulette , Novak Alexandra , Cupedo Tom , Touw Ivo P. 
Published: September 2010

AbstractHematopoiesis is tightly controlled by transcription regulatory networks, but how and when specific transcription factors control lineage commitment are still largely unknown. Within the hematopoietic stem cell (Lin−Sca-1+c-Kit+) compartment these lineage-specific transcription factors are expressed at low levels but are up-regulated with the process of lineage specification. CCAAT/enhancer binding protein α (C/EBPα) represents one of these factors and is involved in myeloid development and indispensable for formation of granulocytes. To track the cellular fate of stem and progenitor cells, which express C/EBPα, we developed a mouse model expressing Cre recombinase from the Cebpa promoter and a conditional EYFP allele. We show that Cebpa/EYFP+ cells represent a significant subset of multipotent hematopoietic progenitors, which predominantly give rise to myeloid cells in steady-state hematopoiesis. C/EBPα induced a strong myeloid gene expression signature and down-regulated E2A-induced regulators of early lymphoid development. In addition, Cebpa/EYFP+ cells compose a fraction of early thymic progenitors with robust myeloid potential. However, Cebpa/EYFP+ multipotent hematopoietic progenitors and early thymic progenitors retained the ability to develop into erythroid and T-lymphoid lineages, respectively. These findings support an instructive but argue against a lineage-restrictive role of C/EBPα in multipotent hematopoietic and thymic progenitors.
Efficacy and safety of once-weekly bortezomib in multiple myeloma patients
Authors: Bringhen Sara , Larocca Alessandra , Rossi Davide , Cavalli Maide , Genuardi Mariella , Ria Roberto , Gentili Silvia , Patriarca Francesca , Nozzoli Chiara , Levi Anna , Guglielmelli Tommasina , Benevolo Giulia , Callea Vincenzo , Rizzo Vincenzo , Cangialosi Clotilde , Musto Pellegrino , De Rosa Luca , Liberati Anna Marina , Grasso Mariella , Falcone Antonietta P. , Evangelista Andrea , Cavo Michele , Gaidano Gianluca , Boccadoro Mario , Palumbo Antonio 
Published: September 2010

AbstractIn a recent phase 3 trial, bortezomib-melphalan-prednisone-thalidomide followed by maintenance treatment with bortezomib-thalidomide demonstrated superior efficacy compared with bortezomib-melphalan-prednisone. To decrease neurologic toxicities, the protocol was amended and patients in both arms received once-weekly instead of the initial twice-weekly bortezomib infusions: 372 patients received once-weekly and 139 twice-weekly bortezomib. In this post-hoc analysis we assessed the impact of the schedule change on clinical outcomes and safety. Long-term outcomes appeared similar: 3-year progression-free survival rate was 50% in the once-weekly and 47% in the twice-weekly group (P > .999), and 3-year overall survival rate was 88% and 89%, respectively (P = .54). The complete response rate was 30% in the once-weekly and 35% in the twice-weekly group (P = .27). Nonhematologic grade 3/4 adverse events were reported in 35% of once-weekly patients and 51% of twice-weekly patients (P = .003). The incidence of grade 3/4 peripheral neuropathy was 8% in the once-weekly and 28% in the twice-weekly group (P < .001); 5% of patients in the once-weekly and 15% in the twice-weekly group discontinued therapy because of peripheral neuropathy (P < .001). This improvement in safety did not appear to affect efficacy. This study is registered at http://www.clinicaltrials.gov as NCT01063179.
Isolated splenic metastasis from lung cancer: ringleader of continuous fever
Authors: Tang H. , Huang H. , Xiu Q. , Shi Z. 
Published: September 2010

The spleen is an infrequent metastatic organ of solid tumours, the prevalence of which ranges between 2.3% and 7.1% in populations with cancer as determined through autopsy. The most common sources of metastasis are breast, lung, colorectal and ovarian carcinoma and melanoma. Isolated metastasis of the spleen is rarely reported with only 93 cases from all sources having been reported up to 2007. Therefore, isolated splenic metastasis from primary lung cancer is exceedingly rare with only 11 cases reported to date.Herein, we report a rare case of isolated splenic metastasis in a 49-yr-old female 3 months after lobectomy for an undifferentiated large cell carcinoma in the right lung (pT2aN0M0). The only symptom the patient presented with was continuous high fever, which had never been previously reported. This patient presented diagnostic challenges due to the presentation of high fever, leukoapenia after chemotherapy and the cystic splenic mass, all of which led to the initial consideration of splenic abscess. The patient's high fever resolved rapidly after splenectomy and splenic metastasis was confirmed by pathological findings.We also reviewed all 11 reported previously cases and summarised the characteristics and appropriate management of isolated splenic metastasis from lung cancer.