bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic modulation of the drug resistance genes MGMT, ABCB1 and ABCG2 in glioblastoma multiforme
Authors: Oberstadt Moritz C , Bien-Möller Sandra , Weitmann Kerstin , Herzog Susann , Hentschel Katharina , Rimmbach Christian , Vogelgesang Silke , Balz Ellen , Fink Matthias , Michael Heike , Zeden Jan-Philip , Bruckmüller Henrike , Werk Anneke N , Cascorbi Ingolf , Hoffmann Wolfgang , Rosskopf Dieter , Schroeder Henry WS , Kroemer Heyo K 
Published: December 2013

Abstract

Background
Resistance of the highly aggressive glioblastoma multiforme (GBM) to drug therapy is a major clinical problem resulting in a poor patient’s prognosis. Beside promoter methylation of the O

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-methylguanine-DNA-methyltransferase (MGMT) gene the efflux transporters ABCB1 and ABCG2 have been suggested as pivotal factors contributing to drug resistance, but the methylation of ABCB1 and ABCG2 has not been assessed before in GBM.

Methods
Therefore, we evaluated the proportion and prognostic significance of promoter methylation of MGMT, ABCB1 and ABCG2 in 64 GBM patient samples using pyrosequencing technology. Further, the single nucleotide polymorphisms MGMT C-56 T (rs16906252), ABCB1 C3435T (rs1045642) and ABCG2 C421A (rs2231142) were determined using the restriction fragment length polymorphism method (RFLP). To study a correlation between promoter methylation and gene expression, we analyzed MGMT, ABCB1 and ABCG2 expression in 20 glioblastoma and 7 non-neoplastic brain samples.

Results
Despite a significantly increased MGMT and ABCB1 promoter methylation in GBM tissue, multivariate regression analysis revealed no significant association between overall survival of glioblastoma patients and MGMT or ABCB1 promoter methylation. However, a significant negative correlation between promoter methylation and expression could be identified for MGMT but not for ABCB1 and ABCG2. Furthermore, MGMT promoter methylation was significantly associated with the genotypes of the MGMT C-56 T polymorphism showing a higher methylation level in the T allele bearing GBM.

Conclusions
In summary, the data of this study confirm the previous published relation of MGMT promoter methylation and gene expression, but argue for no pivotal role of MGMT, ABCB1 and ABCG2 promoter methylation in GBM patients’ survival.
Systemic effect of catumaxomab in a patient with metastasized colorectal cancer: a case report
Authors: Bezan Angelika , Hohla Florian , Meissnitzer Thomas , Greil Richard 
Published: December 2013

Abstract

Background
Catumaxomab, the first anti-EpCAM antibody, was approved in 2009 for the treatment of malignant ascites in cancer patients with EpCAM positive tumors. We consider this case of interest as treatment with catumaxomab not only prolonged the puncture-free interval but also showed a systemic effect in a patient with metastasized colorectal cancer by regression of a pulmonary metastasis.

Case presentation
We describe the case of a 78 year old patient initially diagnosed with locally advanced colon cancer and one synchronous liver metastasis in September 2010 who was treated by hemicolectomy and simultaneous atypical liver resection. During adjuvant chemotherapy the patient developed a peritoneal carcinomatosis with ascites in March 2011. Palliative chemotherapy was not well tolerated and therefore refused by the patient. Because of disease progression in June 2011 with one pulmonary metastasis and clinically predominant ascites an immunotherapy with intraperitoneal catumaxomab was started in December 2011. After treatment with catumaxomab a puncture free survival of 12 months as well as a regression of the pulmonary lesion was achieved until January 2013.

Conclusion
This case suggests that treatment with catumaxomab does not only improve quality of life by local suppression of malignant ascites but also might have a systemic antitumor effect.
Berberine suppresses tumorigenicity and growth of nasopharyngeal carcinoma cells by inhibiting STAT3 activation induced by tumor associated fibroblasts
Authors: Tsang Chi Man , Cheung Yuk Chun , Lui Vivian Wai-Yan , Yip Yim Ling , Zhang Guitao , Lin Victor Weitao , Cheung Kenneth Chat-Pan , Feng Yibin , Tsao Sai Wah 
Published: December 2013

AbstractBackgroundCortidis rhizoma(Huanglian) and its major therapeutic component, berberine, have drawn extensive attention in recent years for their anti-cancer properties. Growth inhibitory effects of berberine on multiple types of human cancer cells have been reported. Berberine inhibits invasion, induces cell cycle arrest and apoptosis in human cancer cells. The anti-inflammatory property of berberine, involving inhibition ofSignalTransducer andActivator ofTranscription 3 (STAT3) activation, has also been documented.MethodsIn this study, we have examined the effects of berberine on tumorigenicity and growth of nasopharyngeal carcinoma (NPC) cells and their relationship to STAT3 signaling using bothin vivoandin vitromodels.ResultsBerberine effectively inhibited the tumorigenicity and growth of an EBV-positive NPC cell line (C666-1) in athymic nude mice. Inhibition of tumorigenic growth of NPC cellsin vivowas correlated with effective inhibition of STAT3 activation in NPC cells inside the tumor xenografts grown in nude mice.In vitro, berberine inhibited both constitutive and IL-6-induced STAT3 activation in NPC cells. Inhibition of STAT3 activation by berberine induced growth inhibition and apoptotic response in NPC cells. Tumor-associated fibroblasts were found to secret IL-6 and the conditioned medium harvested from the fibroblasts also induced STAT3 activation in NPC cells. Furthermore, STAT3 activation by conditioned medium of tumor-associated fibroblasts could be blocked by berberine or antibodies against IL-6 and IL-6R.ConclusionsOur observation that berberine effectively inhibited activation of STAT3 induced by tumor-associated fibroblasts suggests a role of berberine in modulating the effects of tumor stroma on the growth of NPC cells. The effective inhibition of STAT3 activation in NPC cells by berberine supports its potential use in the treatment of NPC.
Veterans Affairs databases are accurate for gout-related health care utilization: a validation study
Authors: Singh Jasvinder A 
Published: December 2013

Abstract
Introduction
The aim of this study was to assess the accuracy of Veterans Affairs (VA) databases for gout-related health care utilization.

Methods
This retrospective study utilized VA administrative and clinical databases. A random sample of gout patients with visits (outpatient, inpatient or emergent/urgent care) with or without the diagnosis of gout (International Classification of Diseases, ninth revision, common modification ICD-9-CM code of 274.x or 274.xx) at the Birmingham VA hospital was selected. A blinded abstractor performed a review of VA electronic health records for the documentation of gout or gout-related terms (gouty arthritis, tophaceous gout, tophus/tophi, acute gout, chronic gout, podagra, urate stones, urate or uric acid crystals and so on) in the chief complaint, history of present illness or assessment and plan for the visit; this constituted the gold standard for gout-related utilization. The accuracy of database-derived gout-related claims was assessed by calculating sensitivity, specificity, and positive and negative predictive values (PPV and NPV).

Results
Of 108 potential visits, 85 outpatient, inpatient or urgent care/emergency room visits to a health care provider (85 patients: 84 men and 1 woman with a mean age of 63 years) and retrievable data from medical records constituted the analyzed dataset. Administrative claims for gout-related utilization with ICD-9 code for gout were accurate with a PPV of 86%, specificity of 95%, sensitivity of 86% and NPV of 95%.

Conclusions
VA databases are accurate for gout-related visits. These findings support their use for studies of health services and outcome studies. It remains to be seen if these findings are generalizable to other settings and databases.
Co-binding by YY1 identifies the transcriptionally active, highly conserved set of CTCF-bound regions in primate genomes
Authors: Schwalie Petra C , Ward Michelle C , Cain Carolyn E , Faure Andre J , Gilad Yoav , Odom Duncan T , Flicek Paul 
Published: December 2013

Abstract
Background
The genomic binding of CTCF is highly conserved across mammals, but the mechanisms that underlie its stability are poorly understood. One transcription factor known to functionally interact with CTCF in the context of X-chromosome inactivation is the ubiquitously expressed YY1. Because combinatorial transcription factor binding can contribute to the evolutionary stabilization of regulatory regions, we tested whether YY1 and CTCF co-binding could in part account for conservation of CTCF binding.

Results
Combined analysis of CTCF and YY1 binding in lymphoblastoid cell lines from seven primates, as well as in mouse and human livers, reveals extensive genome-wide co-localization specifically at evolutionarily stable CTCF-bound regions. CTCF-YY1 co-bound regions resemble regions bound by YY1 alone, as they enrich for active histone marks, RNA polymerase II and transcription factor binding. Although these highly conserved, transcriptionally active CTCF-YY1 co-bound regions are often promoter-proximal, gene-distal regions show similar molecular features.

Conclusions
Our results reveal that these two ubiquitously expressed, multi-functional zinc-finger proteins collaborate in functionally active regions to stabilize one another's genome-wide binding across primate evolution.
Staged miRNA re-regulation patterns during reprogramming
Authors: Henzler Christine M , Li Zhonghan , Dang Jason , Arcila Mary Luz , Zhou Hongjun , Liu Jingya , Chang Kung-Yen , Bassett Danielle S , Rana Tariq M , Kosik Kenneth S 
Published: December 2013

Abstract
Background
MiRNAs often operate in feedback loops with transcription factors and represent a key mechanism for fine-tuning gene expression. In transcription factor-induced reprogramming, miRNAs play a critical role; however, detailed analyses of miRNA expression changes during reprogramming at the level of deep sequencing have not been previously reported.

Results
We use four factor reprogramming to induce pluripotent stem cells from mouse fibroblasts and isolate FACS-sorted Thy1- and SSEA1+ intermediates and Oct4-GFP+ induced pluripotent stem cells (iPSCs). Small RNAs from these cells, and two partial-iPSC lines, another iPSC line, and mouse embryonic stem cells (mES cells) were deep sequenced. A comprehensive resetting of the miRNA profile occurs during reprogramming; however, analysis of miRNA co-expression patterns yields only a few patterns of change. Dlk1-Dio3 region miRNAs dominate the large pool of miRNAs experiencing small but significant fold changes early in reprogramming. Overexpression of Dlk1-Dio3 miRNAs early in reprogramming reduces reprogramming efficiency, suggesting the observed downregulation of these miRNAs may contribute to reprogramming. As reprogramming progresses, fewer miRNAs show changes in expression, but those changes are generally of greater magnitude.

Conclusions
The broad resetting of the miRNA profile during reprogramming that we observe is due to small changes in gene expression in many miRNAs early in the process, and large changes in only a few miRNAs late in reprogramming. This corresponds with a previously observed transition from a stochastic to a more deterministic signal.
Activated macrophages release microvesicles containing polarized M1 or M2 mRNAs
Authors: Garzetti Livia , Menon Ramesh , Finardi Annamaria , Bergami Alessandra , Sica Antonio , Martino Gianvito , Comi Giancarlo , Verderio Claudia , Farina Cinthia , Furlan Roberto 
Published: December 2013

ABSTRACTMVs are known vehicles of horizontal communication among cells, currently under scrutiny as powerful biomarkers in several pathological processes. The potential advantage of MVs relies on the assumption that their content reflects processes ongoing in pathologically relevant cell types. We have described that MVs of myeloid origin in the CSF are a marker of microglia/macrophage activation. Myeloid cells have different activation types, resulting in diverse functional phenotypes. Knowledge on the activation type of myeloid cells during disease would be of paramount importance for the understanding of ongoing pathogenic processes. We show here that macrophages activated in vitro in different ways all release increased amounts of MVs compared with NS cells. Moreover, we show that macrophage-derived MVs contain a repertoire of mRNAs that is not the result of casual sampling from the parental cells, as it is characterized by distinct mRNA enrichments and species. Nevertheless, mRNA content of MVs clearly allows identification in vivo of the activated phenotype of the cell of origin, indicating carryover of functional macrophage traits. We propose that detection of mRNAs in myeloid MVs permits identification of myeloid cell activation type during disease, allowing for further stratification of pathological processes.
Introduction to this special section: Middle East
Authors: El-Emam Adel 
Published: December 2013

The article “Tuning is not necessarily bad—Channel sand delineation from seismic data of the Upper Gharif in Oman” is written by Fuping Zhu et al., with all authors from Petroleum Development of Oman (PDO). Until recently, the channels of the Upper Gharif were considered too thin (only a tenth of a wavelength) for seismic detection, and instead were explored using costly grid drilling. In this article, the authors report on the successful use of seismic data for reservoir characterization and well placement, following careful interpretation of seismic amplitudes in terms of tuning and prior constraints on the sand thicknesses (absence of thick sands, small NTG ratio). The proposed methodology has been developed on Field Z and has successfully predicted the sand thickness encountered in a new well. It is expected that this methodology will be applicable to several Upper Gharif reservoirs which hold a significant portion of PDO's reserve and resource volumes. Following Zhu's article is a workshop report. In the article “The big rush to the Middle East unconventional reservoirs,” Mohammed Badri of Schlumberger and Saleh Al-Saleh of Saudi Aramco share news of the successful SEG workshop highlighting seismic applications in exploiting unconventional reservoirs.
Phase II Trial of Imatinib in AIDS-Associated Kaposi's Sarcoma: AIDS Malignancy Consortium Protocol 042
Authors: Koon Henry B. , Krown Susan E. , Lee Jeannette Y. , Honda Kord , Rapisuwon Suthee , Wang Zhenghe , Aboulafia David , Reid Erin G. , Rudek Michelle A. , Dezube Bruce J. , Noy Ariela 
Published: December 2013

Purpose Kaposi's sarcoma (KS) is a disease of multifocal vascular proliferation that requires infection with KS herpes virus (KSHV/HHV-8). Activation of the c-kit and platelet-derived growth factor (PDGF) receptors by autocrine/paracrine mechanisms follows endothelial cell KSHV infection. In a pilot study, imatinib, a c-kit/PDGF-receptor inhibitor, induced partial regression of AIDS-associated KS (AIDS-KS) in five of 10 patients. Patients and Methods This multicenter phase II study was designed to estimate the response rate to imatinib in AIDS-KS. Secondary objectives included investigation of predictors of response and imatinib pharmacokinetics in patients on antiretrovirals. Patients received imatinib 400 mg/day by mouth for up to 12 months with dose escalation up to 600 mg/day at 3 months if their disease was stable. Results Thirty patients were treated at 12 AIDS Malignancy Consortium sites. Ten patients (33.3%) achieved partial response, six (20%) had stable disease, and seven (23.3%) exhibited KS progression. Nine patients completed 52 weeks of imatinib therapy. The median treatment duration was 22.5 weeks. Only five patients (16.7%) discontinued therapy owing to adverse events. Antiretroviral regimens did not significantly alter imatinib metabolism. Activating mutations in PDGF-R and c-kit were not found at baseline or at disease progression. We found no correlation with response with changes in any of the candidate cytokines. Conclusion Imatinib has activity in AIDS-KS. Pharmacokinetic interactions with antiretroviral drugs did not correlate with toxicity. Thirty percent of patients showed long-term clinical benefit and remained on imatinib for the entire year. These results suggest imatinib is well tolerated and may be an alternative therapy for some patients with AIDS-KS.
Prospective Stage-Stratified Approach to AIDS-Related Kaposi's Sarcoma
Authors: Bower Mark , Dalla Pria Alessia , Coyle Chris , Andrews Eileen , Tittle Victoria , Dhoot Sharanjit , Nelson Mark 
Published: December 2013

Purpose Combination antiretroviral therapy (cART) is standard of care for patients with HIV diagnosed with Kaposi's sarcoma (KS), but the current role of systemic chemotherapy is undefined. Patients and Methods Since 1998, a prospective stage-stratified approach has been adopted for 469 patients with HIV with KS. Patients with early-stage (T0) KS are treated with cART alone; patients with advanced-stage (T1) KS receive cART plus liposomal anthracycline chemotherapy. Clinical characteristics, overall survival, and KS progression–free survival were analyzed according to stage at presentation and treatment received. Results A total of 303 patients presented with T0 stage KS, including 237 who were not receiving cART, and 166 patients had T1 stage KS. Patients with T0 KS had higher CD4 cell counts (P < .001); 90% of patients with T0 KS who were not receiving cART and 84% of those with T1 KS were treated in accordance with the stage-stratified approach. Median follow-up was 4.6 years, and 5-year overall survival was 89%; 54 patients have died, 15 as a result of KS. Overall 5-year survival was 92% for T0 KS and 83% to T1 KS (P = .0024). On-treatment analysis of 213 cART-naive patients with T0 KS treated with cART alone revealed 5-year overall survival of 95% and progression-free survival of 77%. For 140 patients with T1 disease treated with cART and liposomal anthracycline chemotherapy, 5-year overall survival was 85%. Conclusion This stage-stratified approach to the management of KS achieves high survival in patients with advanced KS and reduces exposure to chemotherapy in patients with early-stage KS.
Outcomes in Hospitalized Pediatric Patients With Systemic Lupus Erythematosus
Authors: Son Mary Beth F. , Johnson Victor M. , Hersh Aimee O. , Lo Mindy S. , Costenbader Karen H. 
Published: December 2013

OBJECTIVE:
Disparities in outcomes among adults with systemic lupus erythematosus (SLE) have been documented. We investigated associations between sociodemographic factors and volume of annual inpatient hospital admissions with hospitalization characteristics and poor outcomes among patients with childhood-onset SLE.

METHODS:
By using the Pediatric Health Information System, we analyzed admissions for patients aged 3 to &lt;18 years at index admission with ≥1 International Classification of Diseases, Ninth Revision code for SLE from January 2006 to September 2011. Summary statistics and univariable analyses were used to examine demographic characteristics of hospital admissions, readmissions, and lengths of stay. We used multivariable logistic regression analyses, controlling for patient gender, age, race, ethnicity, insurance type, hospital volume, US census region, and severity of illness, to examine risk factors for poor outcomes.

RESULTS:
A total of 10 724 admissions occurred among 2775 patients over the study period. Hispanic patients had longer lengths of stay, more readmissions, and higher in-hospital mortality. In multivariable analysis, African American race was significantly associated with ICU admission. African American race and Hispanic ethnicity were associated with end-stage renal disease and death. Volume of patients with SLE per hospital and hospital location were not significantly associated with outcomes.

CONCLUSIONS:
In this cohort of hospitalized children with SLE, race and ethnicity were associated with outcomes. Further studies are needed to elucidate the relationship between sociodemographic factors and poor outcomes in patients with childhood-onset SLE.
Isotonic Versus Hypotonic Maintenance IV Fluids in Hospitalized Children: A Meta-Analysis
Authors: Wang Jingjing , Xu Erdi , Xiao Yanfeng 
Published: December 2013

OBJECTIVE:To assess evidence from randomized controlled trials (RCTs) on the safety of isotonic versus hypotonic intravenous (IV) maintenance fluids in hospitalized children.METHODS:We searched PubMed, Embase, Cochrane Library, and clinicaltrials.gov (up to April 11, 2013) for RCTs that compared isotonic to hypotonic maintenance IV fluid therapy in hospitalized children. Relative risk (RR), weighted mean differences, and 95% confidence intervals (CIs) were calculated based on the effects on plasma sodium (pNa). The risk of developing hyponatremia (pNa &lt;136 mmol/L), severe hyponatremia (pNa &lt;130 mmol/L), and hypernatremia (pNa &gt;145 mmol/L) was evaluated. We adopted a random-effects model in all meta-analyses. Sensitivity analyses by missing data were also performed.RESULTS:Ten RCTs were included in this review. The meta-analysis showed significantly higher risk of hypotonic IV fluids for developing hyponatremia (RR 2.24, 95% CI 1.52 to 3.31) and severe hyponatremia (RR 5.29, 95% CI 1.74 to 16.06). There was a significantly greater fall in pNa in children who received hypotonic IV fluids (–3.49 mmol/L versus isotonic IV fluids, 95% CI –5.63 to –1.35). No significant difference was found between the 2 interventions in the risk of hypernatremia (RR 0.73, 95% CI 0.22 to 2.48). None of the findings was sensitive to imputation of missing data.CONCLUSIONS:Isotonic fluids are safer than hypotonic fluids in hospitalized children requiring maintenance IV fluid therapy in terms of pNa.
Prospective Evaluation of a Clinical Pathway for Suspected Appendicitis
Authors: Saucier Ashley , Huang Eunice Y. , Emeremni Chetachi A. , Pershad Jay 
Published: December 2013

OBJECTIVE:
To evaluate the diagnostic accuracy of a clinical pathway for suspected appendicitis combining the Samuel’s pediatric appendicitis score (PAS) and selective use of ultrasonography (US) as the primary imaging modality.

METHODS:
Prospective, observational cohort study conducted at an urban, academic pediatric emergency department. After initial evaluation, patients were determined to be at low (PAS 1–3), intermediate (PAS 4–7), or high (PAS 8–10) risk for appendicitis. Low-risk patients were discharged with telephone follow-up. High-risk patients received immediate surgical consultation. Patients at intermediate risk for appendicitis underwent US.

RESULTS:
Of the 196 patients enrolled, 65 (33.2%) had appendicitis. An initial PAS of 1–3 was noted in 44 (22.4%), 4–7 in 119 (60.7%), and 8–10 in 33 (16.9%) patients. Ultrasonography was performed in 128 (65.3%) patients, and 48 (37.5%) were positive. An abdominal computed tomography scan was requested by the surgical consultants in 13 (6.6%) patients. The negative appendectomy rate was 3 of 68 (4.4%). Follow-up was established on 190 of 196 (96.9%) patients. Overall diagnostic accuracy of the pathway was 94% (95% confidence interval [CI] 91%–97%) with a sensitivity of 92.3% (95% CI 83.0%–97.5%), specificity of 94.7% (95% CI 89.3%–97.8%), likelihood ratio (+) 17.3 (95% CI 8.4–35.6) and likelihood ratio (−) 0.08 (95% CI 0.04–0.19).

CONCLUSIONS:
Our protocol demonstrates high sensitivity and specificity for diagnosis of appendicitis in children. Institutions should consider investing in resources that increase the availability of expertise in pediatric US. Standardization of care may decrease radiation exposure associated with use of computed tomography scans.