bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and risk factors of clinically significant chemotherapy-induced thrombocytopenia in patients with solid tumors
Authors: Hitron Anna , Steinke Doug , Sutphin Stephanie , Lawson Amber , Talbert Jeff , Adams Val 
Published: September 2010

Purpose and relevance. Chemotherapy-induced thrombocytopenia (CIT) can be a significant problem in patients with cancer, leading to numerous clinical complications. Understanding the types of patients at risk for these complications is essential to improve monitoring, counseling, and provide future targeted prophylaxis measures. Previous studies have limited prospective utility since they do not examine risk factors associated with complications from multi-agent regimens. This evaluation aims to identify the incidence and risk factors associated with clinical complications of CIT in patients receiving common chemotherapy regimens.Methods. Retrospective evaluation of adult patients receiving first or second line regimens for the most common solid tumors associated with high rates (≥5%) of laboratory diagnosed thrombocytopenia. Patients were examined for clinically significant CIT (defined as platelet count <75,000 cells/µL as well as the presence of one of the following: bleeding, dose reduction/delay, platelet transfusion, or therapy cessation) and associated risk factors.Results. About 254 patients receiving a total of 278 regimens were evaluated. The incidence of clinically significant CIT = 10.1%; complications were most common in patients receiving cisplatin/gemcitabine for bladder cancer (57%), or carboplatin/gemcitabine (29%) or cisplatin/etoposide (18%) for lung cancer. Bladder cancer (OR = 13.7 (2.89–64.7); p = 0.001) and concurrent or recent infection (OR = 3.8 (1.45–10.1); p = 0.007) was found to increase the risk of clinical complications while smoking was found to have a protective effect (OR = 0.17 (0.04–0.71)).Conclusions. The incidence of clinically significant CIT is most commonly seen in patients using cisplatin/gemcitabine for bladder cancer, or carboplatin/gemcitabine or cisplatin/etoposide for lung cancer. Further evaluation of these patients is warranted.
Neuromyelitis optica: a demyelinating disease characterized by acute destruction and regeneration of perivascular astrocytes
Authors: Parratt John DE , Prineas John W 
Published: September 2010

Background: A serum antibody directed against astrocytes is present in a high proportion of patients with neuromyelitis optica (NMO). The pathogenicity of the antibody is uncertain because no consistent astrocyte lesion is known to occur in NMO. Objective: To determine whether there is an astrocyte lesion in NMO and if this differs from astrocyte changes in multiple sclerosis (MS). Methods: Astrocyte pathology in early (still-myelinated) lesions and subacute NMO and MS lesions was examined immunohistochemically and in sections stained for astrocytes using routine histological techniques. Results: Demyelination in early NMO lesions is accompanied by oligodendrocyte apoptosis in a pattern identical to that seen in MS and this is preceded by an abrupt destruction of perivascular astrocytes. Reparative astrogliosis is effected by a population of unipolar, new astrocytes. Evidence of a different type of astrocyte lesion was found in MS. Discussion: The findings add to experimental evidence that the antibody is pathogenic. They also raise the possibility that demyelination in MS may be a bystander effect of an astrocyte lesion, i.e. that MS is not a disease primarily of myelin and oligodendrocytes.
Increased thrombosis susceptibility and altered fibrin formation in STAT5-deficient mice
Authors: Nordstrom Sarah M. , Holliday Brian A. , Sos Brandon C. , Smyth James W. , Levy Robert E. , Dukes Jonathan W. , Lord Susan T. , Weiss Ethan J. 
Published: September 2010

Abstract
To explore the effect(s) of growth hormone signaling on thrombosis, we studied signal transduction and transcription factor 5 (STAT5)–deficient mice and found markedly reduced survival in an in vivo thrombosis model. These findings were not explained by a compensatory increase in growth hormone secretion. There was a modest increase in the activity of several procoagulant factors, but there was no difference in the rate or magnitude of thrombin generation in STAT5-deficient mice relative to control. However, thrombin-triggered clot times were markedly shorter, and fibrin polymerization occurred more rapidly in plasma from STAT5-deficient mice. Fibrinogen depletion and mixing studies indicated that the effect on fibrin polymerization was not due to intrinsic changes in fibrinogen, but resulted from changes in the concentration of a circulating plasma inhibitor. While thrombin-triggered clot times were significantly shorter in STAT5-deficient animals, reptilase-triggered clot times were unchanged. Accordingly, while the rate of thrombin-catalyzed release of fibrinopeptide A was similar, the release of fibrinopeptide B was accelerated in STAT5-deficient plasma versus control. Taken together, these studies demonstrated that the loss of STAT5 resulted in a decrease in the concentration of a plasma inhibitor affecting thrombin-triggered cleavage of fibrinopeptide B. This ultimately resulted in accelerated fibrin polymerization and greater thrombosis susceptibility in STAT5-deficient animals.
Racial disparities in incidence and outcome in multiple myeloma: a population-based study
Authors: Waxman Adam J. , Mink Pamela J. , Devesa Susan S. , Anderson William F. , Weiss Brendan M. , Kristinsson Sigurdur Y. , McGlynn Katherine A. , Landgren Ola 
Published: September 2010

Abstract
Multiple myeloma (MM) is the most common hematologic malignancy in blacks. Some prior studies suggest inferior survival in blacks; others suggest similar survival. Using the original 9 Surveillance, Epidemiology, and End Results registries, we conducted a large-scale population-based study including 5798 black and 28 939 white MM patients diagnosed 1973-2005, followed through 2006. Age-adjusted incidence rates, disease-specific survival, and relative survival rates were calculated by race, age, and time period of diagnosis. Mean age at diagnosis was 65.8 and 69.8 years for blacks and whites, respectively (P < .001). Incidence among blacks was m twice that among whites; this disparity was greater among patients < 50 years (P = .002). Over the entire study period, disease-specific and relative survival rates were higher in blacks than whites (P < .001). For whites, 5-year relative survival rates increased significantly 1973-1993 to 1994-1998 (26.3% to 30.8%; P < .001) and 1994-1998 to 1999-2005 (30.8% to 35.0%; P = .004). Survival improvements among blacks were smaller and nonsignificant (1973-1993 to 1999-2005: 31.0% to 34.1%; P = .07). We found (1) a younger age of onset among blacks; (2) better survival in blacks 1973-2005; and (3) significant survival improvement among whites over time, with smaller, nonsignificant change seen among blacks, possibly due to unequal access to and/or disparate responsiveness to novel therapies.
Markedly different genome arrangements between serotype a strains and serotypes b or c strains of Aggregatibacter actinomycetemcomitans
Authors: Kittichotirat Weerayuth , Bumgarner Roger , Chen Casey 
Published: September 2010

Abstract

Background
Bacterial phenotype may be profoundly affected by the physical arrangement of their genes in the genome. The Gram-negative species Aggregatibacter actinomycetemcomitans is a major etiologic agent of human periodontitis. Individual clonal types of A. actinomycetemcomitans may exhibit variable virulence and different patterns of disease association. This study examined the genome arrangement of A. actinomycetemcomitans using the genome sequences of serotypes a-c strains. The genome alignment and rearrangement were analyzed by the MAUVE and the GRIMM algorithms. The distribution patterns of genes along the leading/lagging strands were investigated. The occurrence and the location of repeat sequences relative to the genome rearrangement breakpoints were also determined.

Results
The genome arrangement of the serotype a strain D7S-1 is markedly different from the serotype b strain HK1651 or the serotype c strain D11S-1. Specific genome arrangements appear to be conserved among strains of the same serotypes. The reversal distance between D7S-1 and HK1651 by GRIMM analysis is also higher than the within-species comparisons of 7 randomly selected bacterial species. The locations of the orthologous genes are largely preserved between HK1651 and D11S-1 but not between D7S-1 and HK1651 (or D11S-1), irrespective of whether the genes are categorized as essential/nonessential or highly/nonhighly expressed. However, genome rearrangement did not disrupt the operons of the A. actinomycetemcomitans strains. A higher proportion of the genome in strain D7S-1 is occupied by repeat sequences than in strains HK1651 or D11S-1.

Conclusion
The results suggest a significant evolutionary divergence between serotype a strains and serotypes b/c strains of A. actinomycetemcomitans. The distinct patterns of genome arrangement may suggest phenotypic differences between serotype a and serotypes b/c strains.
Lack of association between peroxisome proliferator-activated receptors alpha and gamma2 polymorphisms and progressive liver damage in patients with non-alcoholic fatty liver disease: a case control study
Authors: Dongiovanni Paola , Rametta Raffaela , Fracanzani Anna Ludovica , Benedan Luca , Borroni Vittorio , Maggioni Paolo , Maggioni Marco , Fargion Silvia , Valenti Luca 
Published: September 2010

Abstract

Background
Peroxisome proliferator-activated receptors (PPARs) play key roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).

Aim
to assess the effect of functional single nucleotide polymorphisms (SNPs) of PPARα and PPARγ2, previously associated with insulin resistance and dyslipidemia, on liver damage in NAFLD, whose progression is influenced by metabolic abnormalities and inherited factors.

Methods
The Leu162Val PPARα and Pro12Ala PPARγ2 SNPs were evaluated by restriction analysis. We considered 202 Italian patients with biopsy-proven NAFLD.

Results
The frequency of the evaluated SNPs did not differ between patients and 346 healthy controls. The presence of the PPARα 162Val allele (prevalence 57%), but not of the PPARγ2 12Ala allele (prevalence 18%), was associated with higher insulin resistance (HOMA-IR index 4.71 ± 3.8 vs. 3.58 ± 2.7, p = 0.026), but not with hyperglycemia. The PPARα 162Val and PPARγ2 12Ala alleles were not associated with the severity of steatosis, necroinflammation, or fibrosis.

Conclusions
The presence of the PPARα 162Val allele was associated with insulin resistance, but not with liver damage in NAFLD. Because of the limited power of the present sample, larger studies are needed to exclude a minor effect of the PPARγ2 12Ala allele on necroinflammation/fibrosis in NAFLD.
Prevalence of Chlamydia infection among women visiting a gynaecology outpatient department: evaluation of an in-house PCR assay for detection of Chlamydia trachomatis
Authors: Patel Achchhe L , Sachdev Divya , Nagpal Poonam , Chaudhry Uma , Sonkar Subash C , Mendiratta Suman L , Saluja Daman 
Published: September 2010

Abstract

Background
Screening women for Chlamydia trachomatis infection in developing countries is highly desirable because of asymptomatic infection. The existing diagnostic methods in developing countries are not effective and their sensitivity fall below 45.0% which leads to further spread of infection. There is an urgent need for improved and cost effective diagnostic tests that will reduce the burden of sexually transmitted infections in the developing world.

Methods
Prevalence of C. trachomatis infection among women visiting gynaecology department of Hindu Rao hospital in Delhi, India was determined using Roche Amplicor Multi Well Plate kit (MWP) as well as using in-house PCR assay. We used 593 endocervical swabs for clinical evaluation of the in-house developed assay against Direct Fluorescence Assay (DFA; Group I n = 274) and Roche Amplicor MWP kit (Group II, n = 319 samples) and determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of the in-house developed assay.

Results
We detected 23.0% positive cases and there was a higher representation of women aged 18-33 in this group. An in-house PCR assay was developed and evaluated by targeting unique sequence within the gyrA gene of C. trachomatis. Specificity of the reaction was confirmed by using genomic DNA of human and other STI related microorganisms as template. Assay is highly sensitive and can detect as low as 10 fg of C. trachomatis DNA. The resolved sensitivity of in-house PCR was 94.5% compared with 88.0% of DFA assay. The high specificity (98.4%) and sensitivity (97.1%) of the in-house assay against Roche kit and availability of test results within 3 hours allowed for immediate treatment and reduced the risk of potential onward transmission.

Conclusions
The in-house PCR method is cost effective (~ 20.0% of Roche assay) and hence could be a better alternative for routine diagnosis of genital infection by C. trachomatis to facilitate improved screening and treatment management.
Identification of an effective siRNA target site and functional regulatory elements, within the hepatitis B virus posttranscriptional regulatory element
Authors: Panjaworayan Nattanan , Payungporn Sunchai , Poovorawan Yong , Brown Chris M 
Published: September 2010

Abstract

Background
Infection with hepatitis B virus (HBV) is major public health concern. The limitations of available antiviral drugs require development of novel approaches to inhibit HBV replication. This study was conducted to identify functional elements and new siRNA target sites within the highly conserved regions of the 533 base post-transcriptional regulatory element (PRE) of HBV RNAs.

Results
Computational analysis of the PRE sequence revealed several conserved regulatory elements that are predicted to form local secondary structures some of these within known regulatory regions. A deletion analysis showed that sub-elements of the PRE have different effects on the reporter activity suggesting that the PRE contains multiple regulatory elements. Conserved siRNA targets at nucleotide position 1317-1337 and 1329-1349 were predicted. Although the siRNA at the position 1329-1349 had no effect on the expression of reporter gene, the siRNA target site at the position 1317-1337 was observed to significantly decrease expression of the reporter protein. This siRNA also specifically reduced the level of cccDNA in transiently HBV infected cells.

Conclusion
The HBV PRE is likely to contain multiple regulatory elements. A conserved target within this region at 1317-1337 is an effective siRNA target.
The WW-HECT protein Smurf2 interacts with the Docking Protein NEDD9/HEF1 for Aurora A activation
Authors: Moore Finola E , Osmundson Evan C , Koblinski Jennifer , Pugacheva Elena , Golemis Erica A , Ray Dipankar , Kiyokawa Hiroaki 
Published: September 2010

Abstract
The multi-functional adaptor protein NEDD9/HEF1/Cas-L regulates cell motility, invasion and cell cycle progression, and plays key roles in cancer progression and metastasis. NEDD9 is localized to the centrosome and is required for activation of Aurora A kinase in mitosis. Here we demonstrate that the HECT-WW protein Smurf2 physically associates with NEDD9 and is required for the stability of NEDD9 protein. Smurf2 depletion results in a marked decrease in NEDD9 protein levels, by facilitating polyubiquitination and proteasomal degradation of NEDD9. Conversely, forced overexpression of Smurf2 results in upregulation of endogenous NEDD9 protein, confirming the role for Smurf2 in NEDD9 stability. Cells with Smurf2 depletion fail to activate Aurora A at the G2/M boundary, leading to a marked delay in mitotic entry. These observations suggest that the stable complex of Smurf2 and NEDD9 is required for timely entry into mitosis via Aurora A activation.
Chondroprotective effects and mechanisms of resveratrol in advanced glycation end products-stimulated chondrocytes
Authors: Liu Feng-Cheng , Hung Li-Feng , Wu Wan-Lin , Chang Deh-Ming , Huang Chuan-Yueh , Lai Jenn-Haung , Ho Ling-Jun 
Published: September 2010

Abstract
Introduction
Accumulation of advanced glycation end products (AGEs) in joints contributes to the pathogenesis of cartilage damage in osteoarthritis (OA). We aim to explore the potential chondroprotective effects of resveratrol on AGEs-stimulated porcine chondrocytes and cartilage explants.

Methods
Chondrocytes were isolated from pig joints. Activation of the IκB kinase (IKK)-IκBα-nuclear factor-kappaB (NF-κB) and c-Jun N-terminal kinase (JNK)/extracellular signal-regulated kinase (ERK)-activator protein-1 (AP-1) pathways was assessed by electrophoretic mobility shift assay (EMSA), Western blot and transfection assay. The levels of inducible nitric oxide synthase (iNOS)-NO and cyclooxygenase-2 (COX-2)-prostaglandin E2 (PGE2) were measured by Western blot, Griess reaction or ELISA. The expression and enzyme activity of matrix metalloproteinase-13 (MMP-13) were determined by real time RT/PCR and gelatin zymography, respectively.

Results
We show that AGEs-induced expression of iNOS and COX-2 and production of NO and PGE2 were suppressed by resveratrol. Such effects of resveratrol were likely mediated through inhibiting IKK-IκBα-NF-κB and JNK/ERK-AP-1 signaling pathways induced by AGEs. By targeting these critical signaling pathways, resveratrol decreased AGEs-stimulated expression and activity of MMP-13 and prevented AGEs-mediated destruction of collagen II. Histochemistry analysis further confirms that resveratrol could prevent AGEs-induced degradation of proteoglycan and aggrecan in cartilage explants.

Conclusions
The present study reveals not only the effects and mechanisms regarding how resveratrol may protect cartilage from AGEs-mediated damage but also the potential therapeutic benefit of resveratrol in the treatment of OA.
Interleukin-10 gene down-expression in circulating mononuclear cells during infusion of drotrecogin-α activated: a pilot study
Authors: Lavaux Thomas , Bilbault Pascal , Launoy Anne , Gaub Marie-Pierre , Oudet Pierre , Schneider Francis 
Published: September 2010

Abstract
Introduction
The purpose of this study was to investigate the gene expression of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) in circulating mononuclear cells harvested from septic shock patients on drotrecogin-α activated (DAA) in order to determine whether this treatment has any effect on the inflammation phase.

Methods
We conducted a prospective cohort study in two intensive care departments. Blood samples were collected at inclusion (T1) and 36 hours later (T2) to measure plasma cytokines and the changes in intracellular TNF-α, IL-10 and IFN-γ mRNA expressions using the real-time quantitative polymerase chain reaction (RT-qPCR). Thirty-two septic shock patients were included: 16 with DAA at 24 μg/kg/h for 96 hours (DAA+) and 16 control (DAA-) eligible but contraindicated for DAA because of low platelet count.

Results
The basal characteristics were similar in both groups: mortality (50%), plasma cytokine concentrations, and baseline IFN-γ, TNF-α and IL-10 mRNA expressions (DAA+ vs. DAA-). At T2, there was a significant IFN-γ gene down-regulation in DAA+ but not in DAA- patients (-0.34 (-0.62; +1.54) vs. +1.41 (+0.35; +5.87), P = 0.008). In survivors, DAA administration was associated with a down-expression of both IFN-γ (-0.65 (-0.93; 0.48) vs. +0.7 (-0.04; +1.26), P = 0.01) and IL-10 (-0.78 (-0.92; -0.6) vs. -0.18 (-0.68; +0.46), P = 0.038). In the non-survivors, DAA infusion was associated with IL-10 over-expression when compared with survivors (+0.54 (-0.35; +11.52) vs. -0.78 (-0.92; -0.6), P < 0.001).

Conclusions
In this study, lack of IL-10 gene down-expression despite a 36-hour infusion of DAA is an ominous sign in septic shock patients suggesting that DAA is not able to reverse the outcome. Our results suggest that DAA can decrease the expression of anti-inflammatory cytokines in septic shock patients. IL-10 or IFN-γ gene down-expression could represent markers of DAA response.
Medulloblastoma Comprises Four Distinct Molecular Variants
Authors: Northcott Paul A. , Korshunov Andrey , Witt Hendrik , Hielscher Thomas , Eberhart Charles G. , Mack Stephen , Bouffet Eric , Clifford Steven C. , Hawkins Cynthia E. , French Pim , Rutka James T. , Pfister Stefan , Taylor Michael D. 
Published: September 2010

PurposeRecent genomic approaches have suggested the existence of multiple distinct subtypes of medulloblastoma. We studied a large cohort of medulloblastomas to determine how many subgroups of the disease exist, how they differ, and the extent of overlap between subgroups.MethodsWe determined gene expression profiles and DNA copy number aberrations for 103 primary medulloblastomas. Bioinformatic tools were used for class discovery of medulloblastoma subgroups based on the most informative genes in the data set. Immunohistochemistry for subgroup-specific signature genes was used to determine subgroup affiliation for 294 nonoverlapping medulloblastomas on two independent tissue microarrays.ResultsMultiple unsupervised analyses of transcriptional profiles identified the following four distinct, nonoverlapping molecular variants: WNT, SHH, group C, and group D. Supervised analysis of these four subgroups revealed significant subgroup-specific demographics, histology, metastatic status, and DNA copy number aberrations. Immunohistochemistry for DKK1 (WNT), SFRP1 (SHH), NPR3 (group C), and KCNA1 (group D) could reliably and uniquely classify formalin-fixed medulloblastomas in approximately 98% of patients. Group C patients (NPR3-positive tumors) exhibited a significantly diminished progression-free and overall survival irrespective of their metastatic status.ConclusionOur integrative genomics approach to a large cohort of medulloblastomas has identified four disparate subgroups with distinct demographics, clinical presentation, transcriptional profiles, genetic abnormalities, and clinical outcome. Medulloblastomas can be reliably assigned to subgroups through immunohistochemistry, thereby making medulloblastoma subclassification widely available. Future research on medulloblastoma and the development of clinical trials should take into consideration these four distinct types of medulloblastoma.