bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediagnosis biomarkers of insulin-like growth factor-1, insulin, and interleukin-6 dysregulation and multiple myeloma risk in the Multiple Myeloma Cohort Consortium
Authors: Birmann Brenda M. , Neuhouser Marian L. , Rosner Bernard , Albanes Demetrius , Buring Julie E. , Giles Graham G. , Lan Qing , Lee I-Min , Purdue Mark P. , Rothman Nathaniel , Severi Gianluca , Yuan Jian-Min , Anderson Kenneth C. , Pollak Michael , Rifai Nader , Hartge Patricia , Landgren Ola , Lessin Lawrence , Virtamo Jarmo , Wallace Robert B. , Manson JoAnn E. , Colditz Graham A. 
Published: October 2012

Abstract
Insulin-like growth factor-1 (IGF-1), insulin, and IL-6 are dysregulated in multiple myeloma pathogenesis and may also contribute to multiple myeloma etiology. To examine their etiologic role, we prospectively analyzed concentrations of serologic markers in 493 multiple myeloma cases and 978 controls from 8 cohorts in the Multiple Myeloma Cohort Consortium. We computed odds ratios (ORs) and 95% confidence intervals (CIs) for multiple myeloma per 1-SD increase in biomarker concentration using conditional logistic regression. We examined heterogeneity by time since blood collection (≤ 3, 4- ≤ 6, and > 6 years) in stratified models. Fasting IGF binding protein-1 concentration was associated with multiple myeloma risk within 3 years (OR, 95% CI per 1-SD increase: 2.3, 1.4-3.8, P = .001) and soluble IL-6 receptor level was associated within 6 years after blood draw (OR ≤ 3 years, 95% CI, 1.4, 1.1-1.9, P = .01; OR4- ≤ 6 years, 95% CI, 1.4, 1.1-1.7, P = .002). No biomarker was associated with longer-term multiple myeloma risk (ie, > 6 years). Interactions with time were statistically significant (IGF binding protein-1, P-heterogeneity = .0016; sIL6R, P-heterogeneity = .016). The time-restricted associations probably reflect the bioactivity of tumor and microenvironment cells in transformation from monoclonal gammopathy of undetermined significance or smoldering multiple myeloma to clinically manifest multiple myeloma.
Antagonism of VEGF-A–induced increase in vascular permeability by an integrin α3β1-Shp-1-cAMP/PKA pathway
Authors: Kim Soo Hyeon , Cho Young-Rak , Kim Hyeon-Ju , Oh Joa Sub , Ahn Eun-Kyung , Ko Hye-Jin , Hwang Byung Joon , Lee Seo-Jin , Cho Yongwan , Kim Yong Kee , Stetler-Stevenson William G. , Seo Dong-Wan 
Published: October 2012

AbstractIn cancer, VEGF-induced increase in vascular permeability results in increased interstitial pressure, reducing perfusion and increasing hypoxia, which reduce delivery of chemotherapeutic agents and increase resistance to ionizing radiation. Here, we show that both TIMP-2 and Ala + TIMP-2, a TIMP-2 mutant without matrix metalloproteinase inhibitory activity, antagonize the VEGF-A–induced increase in vascular permeability, both in vitro and in vivo. Like other agents known to preserve endothelial barrier function, TIMP-2 elevates cytosolic levels of cAMP and increases cytoskeletal-associated vascular endothelial cadherin in human microvascular endothelial cells. All of these effects are completely ablated by selective knockdown of integrin α3β1 expression, expression of a dominant negative protein tyrosine phosphatase Shp-1 mutant, administration of the protein tyrosine phosphatase inhibitor orthovanadate, or the adenylate cyclase inhibitor SQ22536. This TIMP-2–mediated inhibition of vascular permeability involves an integrin α3β1-Shp-1-cAMP/protein kinase A-dependent vascular endothelial cadherin cytoskeletal association, as evidenced by using siRNAs to integrin α3β1 and Shp-1, or treatment with Shp-1 inhibitor NSC87877 and protein kinase A inhibitor H89. Our results demonstrate the potential utility for TIMP-2 in cancer therapy through “normalization” of vascular permeability in addition to previously described antiangiogenic effects.
Endothelial endoglin is involved in inflammation: role in leukocyte adhesion and transmigration
Authors: Rossi Elisa , Sanz-Rodriguez Francisco , Eleno Nelida , Düwell Annette , Blanco Francisco J. , Langa Carmen , Botella Luisa M. , Cabañas Carlos , Lopez-Novoa José M. , Bernabeu Carmelo 
Published: October 2012

AbstractHuman endoglin is an RGD-containing transmembrane glycoprotein identified in vascular endothelial cells. Although endoglin is essential for angiogenesis and its expression is up-regulated in inflammation and at sites of leukocyte extravasation, its role in leukocyte trafficking is unknown. This function was tested in endoglin heterozygous mice (Eng+/−) and their wild-type siblings Eng+/+ treated with carrageenan or LPS as inflammatory agents. Both stimuli showed that inflammation-induced leukocyte transendothelial migration to peritoneum or lungs was significantly lower in Eng+/− than in Eng+/+ mice. Leukocyte transmigration through cell monolayers of endoglin transfectants was clearly enhanced in the presence of endoglin. Coating transwells with the RGD-containing extracellular domain of endoglin, enhanced leukocyte transmigration, and this increased motility was inhibited by soluble endoglin. Leukocytes stimulated with CXCL12, a chemokine involved in inflammation, strongly adhered to endoglin-coated plates and to endoglin-expressing endothelial cells. This endoglin-dependent adhesion was abolished by soluble endoglin, RGD peptides, the anti-integrin α5β1 inhibitory antibody LIA1/2 and the chemokine receptor inhibitor AMD3100. These results demonstrate for the first time that endothelial endoglin interacts with leukocyte integrin α5β1 via its RGD motif, and this adhesion process is stimulated by the inflammatory chemokine CXCL12, suggesting a regulatory role for endoglin in transendothelial leukocyte trafficking.
Deep-sequencing approach for minimal residual disease detection in acute lymphoblastic leukemia
Authors: Faham Malek , Zheng Jianbiao , Moorhead Martin , Carlton Victoria E. H. , Stow Patricia , Coustan-Smith Elaine , Pui Ching-Hon , Campana Dario 
Published: October 2012

Abstract
The persistence of minimal residual disease (MRD) during therapy is the strongest adverse prognostic factor in acute lymphoblastic leukemia (ALL). We developed a high-throughput sequencing method that universally amplifies antigen-receptor gene segments and identifies all clonal gene rearrangements (ie, leukemia-specific sequences) at diagnosis, allowing monitoring of disease progression and clonal evolution during therapy. In the present study, the assay specifically detected 1 leukemic cell among greater than 1 million leukocytes in spike-in experiments. We compared this method with the gold-standard MRD assays multiparameter flow cytometry and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) using diagnostic and follow-up samples from 106 patients with ALL. Sequencing detected MRD in all 28 samples shown to be positive by flow cytometry and in 35 of the 36 shown to be positive by ASO-PCR and revealed MRD in 10 and 3 additional samples that were negative by flow cytometry and ASO-PCR, respectively. We conclude that this new method allows monitoring of treatment response in ALL and other lymphoid malignancies with great sensitivity and precision. The www.clinicaltrials.gov identifier number for the Total XV study is NCT00137111.
Dysregulation of MicroRNAs in cancer
Authors: Chen Pai-Sheng , Su Jen-Liang , Hung Mien-Chie 
Published: October 2012

Abstract
MicroRNAs (miRNAs) are involved in multiple biological activities as well as disease progression including cancer. Interestingly, miRNAs could act as either tumor suppressors or oncogenes depending on the functions of their targets. Using high-throughput profiling, dysregulation of miRNAs has been widely observed in different stages of cancer, and there is mounting evidence demonstrating several misguided mechanisms that cause miRNA dysregulation. In this review, we summarize the key functions of miRNAs in cancer, especially those affecting tumor metastasis and drug resistance. Moreover, the mechanisms leading to dysregulation of miRNAs, including genomic abnormalities, DNA/histone modifications, transcriptional regulation, abnormal biogenesis, and interaction between miRNAs, are also discussed.
Effects of coffee, smoking, and alcohol on liver function tests: a comprehensive cross-sectional study
Authors: Jang Eun Sun , Jeong Sook-Hyang , Hwang Sung Ho , Kim Hyun Young , Ahn So Yeon , Lee Jaebong , Lee Sang Hyub , Park Young Soo , Hwang Jin Hyeok , Kim Jin-Wook , Kim Nayoung , Lee Dong Ho 
Published: October 2012

Abstract

Background
Liver function tests (LFTs) can be affected by many factors and the proposed effects of coffee on LFT require a comprehensive evaluation. The aim of this study was to elucidate whether drinking coffee, smoking, or drinking alcohol have independent effects on LFTs in Korean health-check examinees.

Methods
We used the responses of 500 health-check examinees, who had participated in a self-administered questionnaire survey about coffee, alcohol drinking, and smoking habits.

Results
Coffee consumption was closely related to male gender, high body mass index (BMI), alcohol drinking, and smoking. On univariable and multivariable analyses, drinking coffee lowered serum levels of total protein, albumin, and aspartate aminotransferases (AST). On multivariable analyses, smoking raised serum γ-glutamyl transferase (GGT) level and decreased serum protein and albumin levels, while alcohol drinking raised GGT level after adjustment for age, gender, regular medication, BMI, coffee and alcohol drinking amounts, and smoking.

Conclusions
Coffee consumption, smoking, and alcohol drinking affect the individual components of LFT in different ways, and the above 3 habits each have an impact on LFTs. Therefore, their effects on LFTs should be carefully interpreted, and further study on the mechanism of the effects is warranted.
P276-00, a cyclin-dependent kinase inhibitor, modulates cell cycle and induces apoptosis in vitro and in vivo in mantle cell lymphoma cell lines
Authors: Shirsath Nitesh P , Manohar Sonal M , Joshi Kalpana S 
Published: October 2012

Abstract

Background
Mantle cell lymphoma (MCL) is a well-defined aggressive lymphoid neoplasm characterized by proliferation of mature B-lymphocytes that have a remarkable tendency to disseminate. This tumor is considered as one of the most aggressive lymphoid neoplasms with poor responses to conventional chemotherapy and relatively short survival. Since cyclin D1 and cell cycle control appears as a natural target, small-molecule inhibitors of cyclin-dependent kinases (Cdks) and cyclins may play important role in the therapy of this disorder. We explored P276-00, a novel selective potent Cdk4-D1, Cdk1-B and Cdk9-T1 inhibitor discovered by us against MCL and elucidated its potential mechanism of action.

Methods
The cytotoxic effect of P276-00 in three human MCL cell lines was evaluated in vitro. The effect of P276-00 on the regulation of cell cycle, apoptosis and transcription was assessed, which are implied in the pathogenesis of MCL. Flow cytometry, western blot, immunoflourescence and siRNA studies were performed. The in vivo efficacy and effect on survival of P276-00 was evaluated in a Jeko-1 xenograft model developed in SCID mice. PK/PD analysis of tumors were performed using LC-MS and western blot analysis.

Results
P276-00 showed a potent cytotoxic effect against MCL cell lines. Mechanistic studies confirmed down regulation of cell cycle regulatory proteins with apoptosis. P276-00 causes time and dose dependent increase in the sub G1 population as early as from 24 h. Reverse transcription PCR studies provide evidence that P276-00 treatment down regulated transcription of antiapoptotic protein Mcl-1 which is a potential pathogenic protein for MCL. Most importantly, in vivo studies have revealed significant efficacy as a single agent with increased survival period compared to vehicle treated. Further, preliminary combination studies of P276-00 with doxorubicin and bortezomib showed in vitro synergism.

Conclusion
Our studies thus provide evidence and rational that P276-00 alone or in combination is a potential therapeutic molecule to improve patients’ outcome in mantle cell lymphoma.
The multi-step process of building TB/HIV collaboration in Cambodia
Authors: Eang Mao Tan , Vun Mean Chhi , Eam Khun Kim , Sovannarith Samreth , Sopheap Seng , Bora Ngauv , Yadav Rajendra , Fujita Masami , Tomas Bernard , Ghidinelli Massimo , van Maaren Pieter , Wells William A 
Published: October 2012

Abstract
Tuberculosis and HIV/AIDS have synergistic health impacts in terms of disease development and progression. Therefore, collaborative TB and HIV/AIDS activities are a logical health systems response. However, the establishment of these activities presents a challenge for countries that have strong vertical disease programs that differ in their implementation philosophies. Here, we review the process by which TB/HIV collaboration was established in Cambodia. A cycle of overlapping and mutually reinforcing initiatives – local research; piloted implementation with multiple options; and several rounds of policy formulation guided by a cross-functional Technical Working Group – was used to drive nationwide introduction of a full set of TB/HIV collaborative activities. Senior Ministry of Health officials and partner organizations brought early attention to TB/HIV. Both national programs implemented initial screening and testing interventions, even in the absence of a detailed, overarching framework. The use of multiple options for HIV testing identified which programmatic options worked best, and early implementation and pilots determined what unanswered questions required further research. Local conduct of this research – on co-treatment timing and TB symptom screening – speeded adoption of the results into policy guidance, and clarified the relative roles of the two programs. Roll-out is continuing, and results for a variety of key indicators, including screening PLHIV for TB, and testing TB patients for HIV, are at 70-80% and climbing. This experience in Cambodia illustrates the influence of health research on policy, and demonstrates that clear policy guidance, the pursuit of incremental advances, and the use of different approaches to generate evidence can overcome structural barriers to change and bring direct benefits to patients.
Successful resolution of refractory chronic cough induced by gastroesophageal reflux with treatment of baclofen
Authors: Xu Xianghuai , Chen Qiang , Liang Siwei , LÜ Hanjing , Qiu Zhongmin 
Published: October 2012

Abstract
Gastroesophageal reflux induced cough is a common cause of chronic cough, and proton pump inhibitors are a standard therapy. However, the patients unresponsive to the standard therapy are difficult to treat and remain a challenge to doctors. Here, we summarized the experience of successful resolution of refractory chronic cough due to gastroesophageal reflux with baclofen in three patients. It is concluded that baclofen may be a viable option for gastroesophageal reflux induced cough unresponsive to proton pump inhibitor therapy.
CellNOptR: a flexible toolkit to train protein signaling networks to data using multiple logic formalisms
Authors: Terfve Camille , Cokelaer Thomas , Henriques David , MacNamara Aidan , Goncalves Emanuel , Morris Melody K , Iersel Martijn van , Lauffenburger Douglas A , Saez-Rodriguez Julio 
Published: October 2012

Abstract

Background
Cells process signals using complex and dynamic networks. Studying how this is performed in a context and cell type specific way is essential to understand signaling both in physiological and diseased situations. Context-specific medium/high throughput proteomic data measured upon perturbation is now relatively easy to obtain but formalisms that can take advantage of these features to build models of signaling are still comparatively scarce.

Results
Here we present CellNOptR, an open-source R software package for building predictive logic models of signaling networks by training networks derived from prior knowledge to signaling (typically phosphoproteomic) data. CellNOptR features different logic formalisms, from Boolean models to differential equations, in a common framework. These different logic model representations accommodate state and time values with increasing levels of detail. We provide in addition an interface via Cytoscape (CytoCopteR) to facilitate use and integration with Cytoscape network-based capabilities.

Conclusions
Models generated with this pipeline have two key features. First, they are constrained by prior knowledge about the network but trained to data. They are therefore context and cell line specific, which results in enhanced predictive and mechanistic insights. Second, they can be built using different logic formalisms depending on the richness of the available data. Models built with CellNOptR are useful tools to understand how signals are processed by cells and how this is altered in disease. They can be used to predict the effect of perturbations (individual or in combinations), and potentially to engineer therapies that have differential effects/side effects depending on the cell type or context.
Seroprevalence of Toxoplasma gondii infection in slaughtered chickens, ducks, and geese in Shenyang, northeastern China
Authors: Yang Na , Mu Ming-Yang , Li Hong-Kui , Long Miao , He Jian-Bin 
Published: October 2012

Abstract

Background
In recent years, investigations of Toxoplasma gondii infection in poultry (chickens, ducks, and geese) have been reported worldwide, including China. However, little is known about the prevalence of T. gondii infection in poultry in northeastern China. Therefore, the present study was performed to determine the prevalence of T. gondii infection in slaughtered chickens, ducks, and geese in Shenyang, northeastern China.

Methods
In the present study, the seroprevalence of T. gondii in 502 adult chickens, 268 adult ducks, and 128 adult geese was surveyed using the modified agglutination test (MAT).

Results
The seroprevalences of T. gondii were 5.8%, 7.8%, and 4.7% in chickens, ducks, and geese, respectively. Prevalence was higher in free-range groups (11.2%, 12.3%, and 8.9%) than caged groups (4.7%, 7.5%, and 6.0%), and there was a statistically significant difference only between free-range chickens and caged chickens, but no significant difference was found between free-range ducks, geese and caged ducks, geese.

Conclusions
The present study shows the prescence of T. gondii infection in slaughtered chickens, ducks, and geese in Shenyang, northeastern China, which suggests that consumption of poultry meat in Shenyang may pose a potential threat to human health and should be given attention.
Nitric oxide and histone deacetylases modulate cocaine-induced mu-opioid receptor levels in PC12 cells
Authors: Winick-Ng Warren , Leri Francesco , Kalisch Bettina E 
Published: October 2012

AbstractBackgroundCocaine exposure has been reported to alter central μ-opioid receptor (MOR) expressionin vivo. The present study employed anin vitrocellular model to explore possible mechanisms that may be involved in this action of cocaine.MethodsTo assess the effects of cocaine on MOR levels, two treatment regimens were tested in PC12 cells: single continuous or multiple intermittent. MOR protein levels were assessed by western blot analysis and quantitative PCR was used to determine relative MOR mRNA expression levels. To evaluate the role of nitric oxide (NO) and histone acetylation in cocaine-induced MOR expression, cells were pre-treated with the NO synthase inhibitor Nω-nitro-L-arginine methylester (L-NAME) or the non-selective histone acetyltransferase inhibitor curcumin.ResultsBoth cocaine treatment regimens significantly increased MOR protein levels and protein stability, but only multiple intermittent treatments increased MOR mRNA levels as well asc-fosmRNA levels and activator protein 1 binding activity. Both regimens increased NO production, and pre-treatment with L-NAME prevented cocaine-induced increases in MOR protein and mRNA levels. Single and multiple cocaine treatment regimens inhibited histone deacetylase activity, and pre-treatment with curcumin prevented cocaine-induced up-regulation of MOR protein expression.ConclusionsIn the PC12 cell model, both NO and histone deacetylase activity regulate cocaine-induced MOR expression at both the transcriptional and post-transcriptional levels. Based on these novel findings, it is hypothesized that epigenetic mechanisms are implicated in cocaine’s action on MOR expression in neurons.
Endothelin-receptor antagonists for aneurysmal subarachnoid hemorrhage: an updated meta-analysis of randomized controlled trials
Authors: Ma Junpeng , Huang Siqing , Ma Lu , Liu Yi , Li Hao , You Chao 
Published: October 2012

Abstract
Introduction
The previous meta-analysis on the use of endothelin-receptor antagonists (ETRAs) to treat aneurysmal subarachnoid hemorrhage (SAH) has become outdated due to recently published phase 3 clinical trials. An up-to-date meta-analysis is needed to provide the best available evidence for the efficacy of ETRAs for aneurysmal SAH.

Methods
We performed a systematic review and meta-analysis of published randomized controlled trials that investigate efficacy of ETRAs in patients with aneurysmal SAH. Mortality, unfavorable outcome, delayed ischemic neurological deficit (DIND), delayed cerebral infarction (DCI), angiographic vasospasm and adverse events were analyzed. Meta-analysis was performed in terms of the risk ratio (RR) and 95% confidence interval (CI).

Results
Five eligible studies were reviewed and analyzed, involving 2,595 patients. The pooled RRs of mortality and unfavorable outcome after SAH were 1.03 (95% CI = 0.77 to 1.36) and 1.07 (95% CI = 0.93 to 1.22), respectively. The pooled RRs were 0.87 (95% CI = 0.74 to 1.03) for DCI, 0.77 (95% CI = 0.66 to 0.90) for DIND, and 0.66 (95% CI = 0.57 to 0.77) for angiographic vasospasm. There were significant increases in lung complications (RR = 1.80, 95% CI = 1.55 to 2.09), hypotension (RR = 2.42, 95% CI = 1.78 to 3.29) and anemia (RR = 1.47, 95% CI = 1.19 to 1.83) in patients administered ETRAs.

Conclusion
There is no evidence that ETRAs could benefit clinical outcome in patients with SAH. Owing to the increased adverse events, further clinical trials of ETRAs in SAH patients should be more carefully formulated and designed. The present results also suggest that DCI may be a better outcome measure than vasospasm and DIND in SAH clinical trials and observational studies.
Anti-Gr-1 antibody depletion fails to eliminate hepatic myeloid-derived suppressor cells in tumor-bearing mice
Authors: Ma Chi , Kapanadze Tamar , Gamrekelashvili Jaba , Manns Michael P , Korangy Firouzeh , Greten Tim F 
Published: October 2012

Abstract
Systemic anti-Gr-1 antibody treatment fails to deplete hepatic MDSC.
Recent studies show that the liver is a preferred organ for the accumulation of MDSC. In this study, we examined the effect of systemic RB6-8C5 treatment on hepatic MDSC in tumor-bearing mice. EL4 tumor-bearing mice were injected i.p. with RB6-8C5, and hepatic, splenic, and blood MDSCs were analyzed by flow cytometry. Unexpectedly, hepatic MDSC remained in the liver, although RB6-8C5 completely eliminated them from the spleen and peripheral blood 24 h after treatment. Secondary antibody staining confirmed the presence of RB6-8C5-bound MDSC in the liver of mice with s.c. tumors. Similar observations were made in two other (colon and melanoma) tumor models. Whereas RB6-8C5 injection induced cell death of hepatic MDSC, as shown by Annexin V/7-AAD staining, these cells were replaced immediately, leading to a constant, increased frequency of hepatic MDSC. Adoptively transferred MDSC migrated preferentially to the liver after RB6-8C5 treatment, suggesting that hepatic MDSCs are reconstituted rapidly after depletion. Finally, hepatic MDSC remained immunosuppressive despite RB6-8C5 injection. Our study demonstrates that RB6-8C5 is not suitable for depletion of hepatic MDSCs and analysis of their function.