bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibrinogen and future cardiovascular disease in people with diabetes: Aetiological associations and risk prediction using individual participant data from nine community-based prospective cohort studies
Authors: Kengne Andre P , Czernichow Sebastien , Stamatakis Emmanuel , Hamer Mark , Batty G David 
Published: July 2012

Aims: We assessed the associations of fibrinogen levels with cardiovascular disease (CVD) risks in people with and without diabetes, and quantified the value of adding fibrinogen to the established predictive algorithms for CVD. Methods: We used Cox models to analyse data from prospective cohorts totalling 33,091 adults (1006 with diabetes) who took part in British and Scottish general population-based health surveys. Discrimination was assessed through c-statistic. Results: During a median follow-up of 116 months, 351 deaths (119 CVD) were recorded in participants with diabetes and 4157 deaths (1167 CVD) in those without. After adjustment for age and sex, fibrinogen (per standard deviation loge) was positively associated with a 34% (26–42%) higher risk of cardiovascular disease and 30% (26–35%) greater risk all-cause mortality. These associations were log-linear, similar in people with and without diabetes ( p-value for interaction ≥0.21), robust to the adjustment of additional major CVD risk factors. Adding fibrinogen to a model containing conventional CVD risk factors resulted in only modest improvement in risk prediction. Conclusions: The associations of fibrinogen with CVD and all-cause mortality are broadly similar in people with and without diabetes status. Improvement in predictive accuracy after adding fibrinogen to established risk factors is not clinically important.
Structural basis for catalytic activation of protein Z–dependent protease inhibitor (ZPI) by protein Z
Authors: Huang Xin , Yan Yahui , Tu Yizheng , Gatti Jeffrey , Broze George J. , Zhou Aiwu , Olson Steven T. 
Published: July 2012

AbstractThe anticoagulant serpin, protein Z-dependent protease inhibitor (ZPI), is catalytically activated by its cofactor, protein Z (PZ), to regulate the function of blood coagulation factor Xa on membrane surfaces. The X-ray structure of the ZPI-PZ complex has shown that PZ binds to a unique site on ZPI centered on helix G. In the present study, we show by Ala-scanning mutagenesis of the ZPI-binding interface, together with native PAGE and kinetic analyses of PZ binding to ZPI, that Tyr240 and Asp293 of ZPI are crucial hot spots for PZ binding. Complementary studies with protein Z–protein C chimeras show the importance of both pseudocatalytic and EGF2 domains of PZ for the critical ZPI interactions. To understand how PZ acts catalytically, we analyzed the interaction of reactive loop–cleaved ZPI (cZPI) with PZ and determined the cZPI X-ray structure. The cZPI structure revealed changes in helices A and G of the PZ-binding site relative to native ZPI that rationalized an observed 6-fold loss in PZ affinity and PZ catalytic action. These findings identify the key determinants of catalytic activation of ZPI by PZ and suggest novel strategies for ameliorating hemophilic states through drugs that disrupt the ZPI-PZ interaction.
The sixth sense: hematopoietic stem cells detect danger through purinergic signaling
Authors: Rossi Lara , Salvestrini Valentina , Ferrari Davide , Di Virgilio Francesco , Lemoli Roberto M. 
Published: July 2012

AbstractOver the past decade, extracellular nucleotides (such as ATP and UTP) have emerged as key immunomodulators. This family of molecules, already known for its key metabolic functions, has been the focus of intense investigation that has unambiguously shown its crucial role as mediators of cell-to-cell communication. More recently, in addition to its involvement in inflammation and immunity, purinergic signaling has also been shown to modulate BM-derived stem cells. Extracellular nucleotides promote proliferation, CXCL12-driven migration, and BM engraftment of hematopoietic progenitor and stem cells. In addition, purinergic signaling acts indirectly on hematopoietic progenitor and stem cells by regulating differentiation and release of proinflammatory cytokines in BM-derived human mesenchymal stromal cells, which are part of the hematopoietic stem cell (HSC) niche. HSC research has recently blended into the field of immunology, as new findings highlighted the role played by immunologic signals (such as IFN-α, IFN-γ, or TNF-α) in the regulation of the HSC compartment. In this review, we summarize recent reports unveiling a previously unsuspected ability of HSCs to integrate inflammatory signals released by immune and stromal cells, with particular emphasis on the dual role of extracellular nucleotides as mediators of both immunologic responses and BM stem cell functions.
Genome-wide methylation profiling in decitabine-treated patients with acute myeloid leukemia
Authors: Yan Pearlly , Frankhouser David , Murphy Mark , Tam Hok-Hei , Rodriguez Benjamin , Curfman John , Trimarchi Michael , Geyer Susan , Wu Yue-Zhong , Whitman Susan P. , Metzeler Klaus , Walker Alison , Klisovic Rebecca , Jacob Samson , Grever Michael R. , Byrd John C. , Bloomfield Clara D. , Garzon Ramiro , Blum William , Caligiuri Michael A. , Bundschuh Ralf , Marcucci Guido 
Published: July 2012

AbstractThe outcome of older (≥ 60 years) acute myeloid leukemia (AML) patients is poor, and novel treatments are needed. In a phase 2 trial for older AML patients, low-dose (20 mg/m2 per day for 10 days) decitabine, a DNA hypomethylating azanucleoside, produced 47% complete response rate with an excellent toxicity profile. To assess the genome-wide activity of decitabine, we profiled pretreatment and post treatment (day 25/course 1) methylomes of marrow samples from patients (n = 16) participating in the trial using deep-sequencing analysis of methylated DNA captured by methyl-binding protein (MBD2). Decitabine significantly reduced global methylation compared with pretreatment baseline (P = .001). Percent marrow blasts did not correlate with global methylation levels, suggesting that hypomethylation was related to the activity of decitabine rather than to a mere decrease in leukemia burden. Hypomethylation occurred predominantly in CpG islands and CpG island-associated regions (P ranged from .03 to .04) A significant concentration (P < .001) of the hypomehtylated CpG islands was found in chromosome subtelomeric regions, suggesting a differential activity of decitabine in distinct chromosome regions. Hypermethylation occurred much less frequently than hypomethylation and was associated with low CpG content regions. Decitabine-related methylation changes were concordant with those previously reported in distinct genes. In summary, our study supports the feasibility of methylome analyses as a pharmacodynamic endpoint for hypomethylating therapies.
Brentuximab vedotin for relapsed or refractory CD30+ hematologic malignancies: the German Hodgkin Study Group experience
Authors: Rothe Achim , Sasse Stephanie , Goergen Helen , Eichenauer Dennis A. , Lohri Andreas , Jäger Ulrich , Bangard Christopher , Böll Boris , von Bergwelt Baildon Michael , Theurich Sebastian , Borchmann Peter , Engert Andreas 
Published: July 2012

Abstract
The CD30-targeting Ab-drug conjugate brentuximab vedotin (SGN-35) was recently approved for the treatment of relapsed Hodgkin lymphoma and anaplastic large-cell lymphoma by the Food and Drug Administration. In the present study, we report the experience of the German Hodgkin Study Group with brentuximab vedotin as single agent in 45 patients with refractory or relapsed CD30+ Hodgkin lymphoma who were treated either in a named patient program (n = 34) or in the context of a safety study associated with the registration program of this drug. In these very heavily pretreated patients, an objective response rate of 60%, including 22% complete remissions, could be documented. The median duration of response was 8 months. This retrospective analysis supports the previously reported excellent therapeutic efficacy of brentuximab vedotin in heavily pretreated CD30+ malignancies. This trial was registered at www.clinicaltrials.gov with identifier NCT01026233.
The sums of the reciprocals of Fibonacci polynomials and Lucas polynomials
Authors: Wu Zhengang , Zhang Wenpeng 
Published: July 2012

Abstract
In this article, we consider infinite sums derived from the reciprocals of the Fibonacci polynomials and Lucas polynomials, and infinite sums derived from the reciprocals of the square of the Fibonacci polynomials and Lucas polynomials. Then applying the floor function to these sums, we obtain several new equalities involving the Fibonacci polynomials and Lucas polynomials.

Mathematics Subject Classification (2010): Primary, 11B39.
Colon cancer associated genes exhibit signatures of positive selection at functionally significant positions
Authors: Morgan Claire C , Shakya Kabita , Webb Andrew , Walsh Thomas A , Lynch Mark , Loscher Christine E , Ruskin Heather J , O’Connell Mary J 
Published: July 2012

Abstract

Background
Cancer, much like most human disease, is routinely studied by utilizing model organisms. Of these model organisms, mice are often dominant. However, our assumptions of functional equivalence fail to consider the opportunity for divergence conferred by ~180 Million Years (MY) of independent evolution between these species. For a given set of human disease related genes, it is therefore important to determine if functional equivalency has been retained between species. In this study we test the hypothesis that cancer associated genes have different patterns of substitution akin to adaptive evolution in different mammal lineages.

Results
Our analysis of the current literature and colon cancer databases identified 22 genes exhibiting colon cancer associated germline mutations. We identified orthologs for these 22 genes across a set of high coverage (>6X) vertebrate genomes. Analysis of these orthologous datasets revealed significant levels of positive selection. Evidence of lineage-specific positive selection was identified in 14 genes in both ancestral and extant lineages. Lineage-specific positive selection was detected in the ancestral Euarchontoglires and Hominidae lineages for STK11, in the ancestral primate lineage for CDH1, in the ancestral Murinae lineage for both SDHC and MSH6 genes and the ancestral Muridae lineage for TSC1.

Conclusion
Identifying positive selection in the Primate, Hominidae, Muridae and Murinae lineages suggests an ancestral functional shift in these genes between the rodent and primate lineages. Analyses such as this, combining evolutionary theory and predictions - along with medically relevant data, can thus provide us with important clues for modeling human diseases.
Antibiotic prescribing in two private sector hospitals; one teaching and one non-teaching: A cross-sectional study in Ujjain, India
Authors: Sharma Megha , Eriksson Bo , Marrone Gaetano , Dhaneria Suryaprakash , Lundborg Cecilia Stålsby 
Published: July 2012

AbstractBackgroundThe worldwide increase in antibiotic resistant bacteria is of great concern. One of the main causes is antibiotic use which is likely to be high but is poorly described in India. The aim was to analyze and compare antibiotic prescribing for inpatients, in two private sector tertiary care hospitals; one Teaching and one Non-teaching, in Ujjain, India.MethodsA cross-sectional study with manual data collection was carried out in 2008. Antibiotic prescribing was recorded for all inpatients throughout their hospital stay. Demographic profile of inpatients and prescribed antibiotics were compared. WHO Anatomical Therapeutic Chemical (ATC) classifications for antibiotics was used and Defined Daily Doses (DDD) were calculated per patient day.ResultsA total of 8385 inpatients were admitted during the study period. In the Teaching hospital (TH) 82% of 3004 and in the Non-teaching hospital (NTH) 79% of 5381 patients were prescribed antibiotics. The most commonly prescribed antibiotic groups were; fluoroquinolones and aminoglycosides in the TH and, 3rd generation cephalosporins and combination of antibiotics in the NTH. Of the prescriptions, 51% in the TH and 87% in the NTH (p<0.001) were for parenteral route administration. Prescribing by trade name was higher in the NTH (96%) compared with the TH (63%, p<0.001).ConclusionsThe results from both hospitals show extensive antibiotic prescribing. High use of combinations of antibiotics in the NTH might indicate pressure from pharmaceutical companies. There is a need to formulate and implement; based on local prescribing and resistance data; contextually appropriate antibiotic prescribing guidelines and a local antibiotic stewardship program.
Implementation of automated reporting of estimated glomerular filtration rate among Veterans Affairs laboratories: a retrospective study
Authors: Hall Rasheeda K , Wang Virginia , Jackson George L , Hammill Bradley G , Maciejewski Matthew L , Yano Elizabeth M , Svetkey Laura P , Patel Uptal D 
Published: July 2012

Abstract

Background
Automated reporting of estimated glomerular filtration rate (eGFR) is a recent advance in laboratory information technology (IT) that generates a measure of kidney function with chemistry laboratory results to aid early detection of chronic kidney disease (CKD). Because accurate diagnosis of CKD is critical to optimal medical decision-making, several clinical practice guidelines have recommended the use of automated eGFR reporting. Since its introduction, automated eGFR reporting has not been uniformly implemented by U. S. laboratories despite the growing prevalence of CKD. CKD is highly prevalent within the Veterans Health Administration (VHA), and implementation of automated eGFR reporting within this integrated healthcare system has the potential to improve care. In July 2004, the VHA adopted automated eGFR reporting through a system-wide mandate for software implementation by individual VHA laboratories. This study examines the timing of software implementation by individual VHA laboratories and factors associated with implementation.

Methods
We performed a retrospective observational study of laboratories in VHA facilities from July 2004 to September 2009. Using laboratory data, we identified the status of implementation of automated eGFR reporting for each facility and the time to actual implementation from the date the VHA adopted its policy for automated eGFR reporting. Using survey and administrative data, we assessed facility organizational characteristics associated with implementation of automated eGFR reporting via bivariate analyses.

Results
Of 104 VHA laboratories, 88% implemented automated eGFR reporting in existing laboratory IT systems by the end of the study period. Time to initial implementation ranged from 0.2 to 4.0 years with a median of 1.8 years. All VHA facilities with on-site dialysis units implemented the eGFR software (52%, p<0.001). Other organizational characteristics were not statistically significant.

Conclusions
The VHA did not have uniform implementation of automated eGFR reporting across its facilities. Facility-level organizational characteristics were not associated with implementation, and this suggests that decisions for implementation of this software are not related to facility-level quality improvement measures. Additional studies on implementation of laboratory IT, such as automated eGFR reporting, could identify factors that are related to more timely implementation and lead to better healthcare delivery.
Cisplatin and ultra-violet-C synergistically down-regulate receptor tyrosine kinases in human colorectal cancer cells
Authors: Kawaguchi Junji , Adachi Seiji , Yasuda Ichiro , Yamauchi Takahiro , Nakashima Masanori , Ohno Tomohiko , Shimizu Masahito , Yoshioka Takashi , Itani Masahiko , Kozawa Osamu , Moriwaki Hisataka 
Published: July 2012

Abstract

Background
Platinum-containing anti-cancer drugs such as cisplatin are widely used for patients with various types of cancers, however, resistance to cisplatin is observed in some cases. Whereas we have recently reported that high dose UV-C (200 J/m²) induces colorectal cancer cell proliferation by desensitization of EGFR, which leads oncogenic signaling in these cells, in this study we investigated the combination effect of low dose cisplatin (10 μM) and low dose UV-C (10 J/m²) on cell growth and apoptosis in several human colorectal cancer cells, SW480, DLD-1, HT29 and HCT116.

Results
The combination inhibited cell cycle and colony formation, while either cisplatin or UV-C alone had little effect. The combination also induced apoptosis in these cells. In addition, the combination caused the downregulation of EGFR and HER2. Moreover, UV-C alone caused the transient internalization of the EGFR, but with time EGFR recycled back to the cell surface, while cisplatin did not affect its localization. Surprisingly, the combination caused persistent internalization of the EGFR, which results in the lasting downregulation of the EGFR.

Conclusions
The combination of low dose cisplatin and low dose UV-C synergistically exerted anti-cancer effect by down-regulating RTK, such as EGFR and HER2. These findings may provide a novel strategy for the treatment of patients with colorectal cancer.
Proteomic analysis of the effects of exogenous calcium on hypoxic-responsive proteins in cucumber roots
Authors: He Lizhong , Lu Xiaomin , Tian Jing , Yang Yanjuan , Li Bin , Li Jing , Guo Shirong 
Published: July 2012

Abstract

Background
Hypoxia acts as a plant stress factor, particularly in cucumbers plants under hydroponic culture. Calcium is involved in stress signal transmission and in the growth of plants. To determine the effect of exogenous calcium on hypoxic-responsive proteins in cucumber (Cucumis sativus L. cv. Jinchun No.2) roots, proteomic analysis was performed using two-dimensional electrophoresis (2-DE) and mass spectrometry.

Results
Cucumber roots were used to analyze the influence of hypoxia on plants. The expressions of 38 protein spots corresponding to enzymes were shown to change in response to hypoxia. Of these, 30 spots were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF/TOF MS analysis). The proteins were categorized according to functional groups, including glycolysis, the tricarboxylic acid (TCA) cycle, fermentative metabolism, nitrogen metabolism, energy metabolism, protein synthesis and defense against stress. Exogenous calcium appeared to alleviate hypoxic stress via these metabolic and physiological systems. Western blotting was used to analyze the accumulation of alcohol dehydrogenase (ADH) and pyruvate decarboxylase (PDC); calcium further increased the expression of ADH and PDC under hypoxia. In addition, semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to assess the transcript levels of differentially expressed proteins.

Conclusions
Exogenous calcium enhanced the expression of enzymes involved in glycolysis, the TCA cycle, fermentative metabolism, nitrogen metabolism, and reactive oxygen species (ROS) defense in plants under hypoxia. Calcium appears to induce hypoxic tolerance of cucumber seedlings. These phenomena have prompted us to further investigate the mechanisms by which cucumbers respond to exogenous calcium under hypoxia.
On the solutions of second order generalized difference equations
Authors: Manuel M MariaSusai , Kılıçman Adem , Xavier G BrittoAntony , Pugalarasu R , Dilip DS 
Published: July 2012

Abstract
In this article, the authors discuss

ℓ

2
(
ℓ
)

and

c

0
(
ℓ
)

solutions of the second order generalized difference equation

Δ
ℓ
2

u
(
k
)
+
f

(
k
,
u
(
k
)
)

=
0
,

k
∈
[
a
,
∞
)
,
a
>
0

and we prove the condition for non existence of non-trivial solution where

Δ
ℓ

u
(
k
)
=
u
(
k
+
ℓ
)
−
u
(
k
)

for

ℓ
>
0

. Further we present some formulae and examples to find the values of finite and infinite series in number theory as application of

Δ
ℓ

.

MSC:39A12, 39A70, 47B39, 39B60.
Antiviral activity of Bifidobacterium adolescentisSPM1005-A on human papillomavirus type 16
Authors: Cha Min-Kyeong , Lee Do-Kyung , An Hyang-Mi , Lee Si-Won , Shin Seon-Hee , Kwon Jeong-Hyun , Kim Kyung-Jae , Ha Nam-Joo 
Published: July 2012

Abstract

Background
Probiotic lactic acid bacteria (LAB) support a functional and balanced immune system, and contribute to immune modulatory effects in combatting microbial pathogens, including viruses. Most cervical cancers are associated with anogenital region infection with high-risk (HR) human papillomavirus (HPV). In this study, we analyzed the antiviral activity of Bifidobacterium adolescentis SPM1005-A in the SiHa cervical cancer cell line expressing HPV type 16.

Methods
We assessed the cellular toxicity of B. adolescentis SPM1005-A in SiHa cells by the Trypan blue dye exclusion assay. Cells (3.6 × 105) in culture plates with or without B. adolescentis SPM1005-A in the same type of medium, were incubated with HPV type 16 at a concentration of 5.1 × 107 cfu/ml. For antiviral analysis, we performed quantitative real-time PCR (qRT-PCR) for E6 and E7 oncogene expressions and observed protein levels by immunoblotting.

Results
The qRT-PCR results showed that E6 and E7 mRNA levels decreased simultaneously. Western blot analysis revealed that the E6 protein expression slightly decreased after 24 and 48 h, but the level of E7 protein expression appear unaffected compared with that in the control. Decreased HPV16 E6 and E7 mRNA transcript and protein levels were not associated with cell morphology or significant cytotoxic effects.

Conclusions
This study showed that B. adolescentis SPM1005-A had antiviral activity through suppression E6 and E7 oncogene expression. The results suggest that B. adolescentis SPM1005-A could be potential applications of HPV-associated cervical cancer prevention.