bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunoglobulin G levels can predict non‐diabetic renal disease in patients with type 2 diabetes mellitus
Authors: WENG Cheng‐Hao , HU Ching‐Chih , YU Chun‐Chen , LIN Ja‐Liang , YANG Chih‐Wei , HUNG Cheng‐Chieh , HSU Ching‐Wei , YEN Tzung‐Hai 
Published: December 2011

AbstractBackground:  Proteinuria in patients with diabetes mellitus (DM) is sometimes caused by glomerular diseases other than diabetic nephropathy. In patients with type 2 DM (T2DM), specific predictors for non‐diabetic renal disease (NDRD) are needed in addition to the traditional indicators for renal biopsy.Methods:  From 1 January 2000 to 31 March 2011, we retrospectively enrolled 54 T2DM patients with proteinuria who had undergone renal biopsies into the present study. Associations between NDRD and 20 potential biomarkers, including serum levels of Igs and proteins associated with kidney function, and urinary protein and red blood cell levels, and hepatitis virus carrier status, were analyzed by multivariate logistic regression.Results:  Multivariate logistic regression showed that reduced serum IgG (odds ratio [OR] 0.997; P = 0.006; 95% confidence interval [CI] 0.94–0.998) and creatinine (Cr; OR 0.587; P = 0.014; 95% CI 0.348–0.897) were predictors of NDRD. The area under the receiver operating characteristic curve (AUCROC) confirmed the good discriminatory power of IgG (AUCROC 0.857 ± 0.058; 95% CI 0.744–0.970; P < 0.001) and Cr (AUCROC 0.838 ± 0.054; 95% CI 0.732–0.943; P < 0.001). The IgG level below which the risk for NDRD increased, as calculated by obtaining the best Youden index, was 919.5 mg/dL (sensitivity 91.7%; specificity 83.3%), and the corresponding Cr level was 4.1 mg/dL (sensitivity 58.3%; specificity 96.7%).Conclusion:  Serum IgG levels <919.5 mg/dL and serum Cr levels <4.1 mg/dL are associated with NDRD in T2DM patients.
Tn
125
-Related Acquisition of
bla
NDM
-Like Genes in Acinetobacter baumannii
Authors: Poirel Laurent , Bonnin Rémy A. , Boulanger Anne , Schrenzel Jacques , Kaase Martin , Nordmann Patrice 
Published: December 2011

ABSTRACT

A multidrug-resistant
Acinetobacter baumannii
isolate recovered from a patient hospitalized in Switzerland after a transfer from Serbia produced the NDM-1 carbapenemase. The
bla
NDM-1
gene was part of a chromosomally located Tn
125
composite transposon bracketed by two copies of the same insertion sequence, IS
Aba125
. This transposon was also associated with the acquisition and expression of the
bla
NDM-2
gene in an
A. baumannii
isolate in Germany. Tn
125
appears to be the main vehicle for dissemination of
bla
NDM
genes in that species.
High Rates of Perinatal Group B Streptococcus Clindamycin and Erythromycin Resistance in an Upstate New York Hospital
Authors: Back Ephraim E. , O'Grady Elisa J. , Back Joshua D. 
Published: December 2011

ABSTRACT

The objective of this study was to evaluate the rates of clindamycin and erythromycin resistance among group B
Streptococcus
(GBS)-positive isolates cultured from pregnant women in an upstate New York community hospital. All GBS-positive perinatal rectovaginal cultures obtained from January 2010 through October 2011 were tested for resistance to erythromycin and clindamycin. Among the 688 GBS-positive cultures, clindamycin resistance was found in 38.4% and erythromycin resistance was found in 50.7%. Rates of GBS resistance to clindamycin and erythromycin are much higher than reported in earlier U.S. studies, suggesting both increasing resistance and regional variation in resistance. These findings lend strong support to the CDC and American College of Obstetricians and Gynecologists (ACOG) recommendations that clindamycin use for intrapartum antibiotic prophylaxis be restricted to penicillin-allergic women at high risk of anaphylaxis and that GBS isolates be tested for antibiotic resistance prior to the use of clindamycin in these women.
OmpT Outer Membrane Proteases of Enterohemorrhagic and Enteropathogenic Escherichia coli Contribute Differently to the Degradation of Human LL-37
Authors: Thomassin Jenny-Lee , Brannon John R. , Gibbs Bernard F. , Gruenheid Samantha , Le Moual Hervé 
Published: December 2011

ABSTRACT

Enterohemorrhagic
Escherichia coli
(EHEC) and enteropathogenic
E. coli
(EPEC) are food-borne pathogens that cause serious diarrheal diseases. To colonize the human intestine, these pathogens must overcome innate immune defenses such as antimicrobial peptides (AMPs). Bacterial pathogens have evolved various mechanisms to resist killing by AMPs, including proteolytic degradation of AMPs. To examine the ability of the EHEC and EPEC OmpT outer membrane (OM) proteases to degrade α-helical AMPs,
ompT
deletion mutants were generated. Determination of MICs of various AMPs revealed that both mutant strains are more susceptible than their wild-type counterparts to α-helical AMPs, although to different extents. Time course assays monitoring the degradation of LL-37 and C18G showed that EHEC cells degraded both AMPs faster than EPEC cells in an OmpT-dependent manner. Mass spectrometry analyses of proteolytic fragments showed that EHEC OmpT cleaves LL-37 at dibasic sites. The superior protection provided by EHEC OmpT compared to EPEC OmpT against α-helical AMPs was due to higher expression of the
ompT
gene and, in turn, higher levels of the OmpT protein in EHEC. Fusion of the EPEC
ompT
promoter to the EHEC
ompT
open reading frame resulted in decreased OmpT expression, indicating that transcriptional regulation of
ompT
is different in EHEC and EPEC. We hypothesize that the different contributions of EHEC and EPEC OmpT to the degradation and inactivation of LL-37 may be due to their adaptation to their respective niches within the host, the colon and small intestine, respectively, where the environmental cues and abundance of AMPs are different.
Employment status and work-related problems of gastrointestinal cancer patients at diagnosis: a cross-sectional study
Authors: de Boer A G E M , Bruinvels D J , Tytgat K M A J , Schoorlemmer A , Klinkenbijl J H G , Frings-Dresen M H W 
Published: December 2011

ObjectiveTo assess the employment status of patients with gastrointestinal cancer at diagnosis and to examine work-related problems of employed patients.DesignNew, consecutive patients were included at the Gastrointestinal Oncology Center Amsterdam, a one-stop, rapid access diagnostic assessment centre. Patients were interviewed on their employment status by a nurse. If (self-) employed, patients were asked to self-report on work-related problems, perceived distress (0–10), cancer-related problems, fatigue (MFI-20, range 4–20) and work ability (three WAI questions, range 0–10).ResultsOf all 333 included new consecutive patients (age range 32–89 years), 95 patients (28%) were (self-) employed at time of diagnosis, 179 (54%) were pensioners, and 59 were not working (18%). For the assessment of work-related problems, 45 (47%) of these 95 employed patients with cancer participated. Their mean age was 56 years, and patients had oesophageal/stomach (49%), colorectal (18%) or hepatic/pancreatic/biliary cancer (33%). Half of the employed patients (49%) were still at work, while 51% were on sick leave. The main reasons for sick leave were stress (35%), (scheduled) operation (26%), fatigue (17%) and pain (13%). Most patients on sick leave (70%) had no contact with their own occupational physician, although the majority (67%) would like to continue to work. Work-related problems were experienced by 73% of working patients. The mean work ability was 5.4, the mean general fatigue score was 11.5, and the mean distress score was 4.7. Employed patients on sick leave reported a lower work ability, more fatigue and higher distress but no more cancer-related problems compared with those still working.ConclusionA quarter of all patients with gastrointestinal cancer seen at an oncological centre are employed at time of diagnosis, and of these employed patients, 73% experience work-related problems. During diagnosis and treatment, information and support on work-related issues should be offered to patients with cancer as an essential part of high-quality oncological care.
Data-driven synthesis for object-oriented frameworks
Authors: Yessenov Kuat , Xu Zhilei , Solar-Lezama Armando 
Published: December 2011

Software construction today often involves the use of large frameworks. The challenge in this type of programming is that object-oriented frameworks tend to grow exceedingly intricate; they spread functionality among numerous classes, and any use of the framework requires knowledge of many interacting components. We present a system named MATCHMAKER that from a simple query synthesizes code that interacts with the framework. The query consists of names of two framework classes, and our system produces code enabling interaction between them. MATCHMAKER relies on a database of dynamic program traces called DELIGHT that uses novel abstraction-based indexing techniques to answer queries about the evolution of heap connectivity in a matter of seconds.
The paper evaluates the performance and effectiveness of MATCHMAKER on a number of benchmarks from the Eclipse framework. The paper also presents the results of a user study that showed a 49% average productivity improvement from the use of our tool.
Gradual typing for generics
Authors: Ina Lintaro , Igarashi Atsushi 
Published: December 2011

Gradual typing is a framework to combine static and dynamic typing in a single programming language. In this paper, we develop a gradual type system for class-based object-oriented languages with generics. We introduce a special type to denote dynamically typed parts of a program; unlike dynamic types introduced to C# 4.0, however, our type system allows for more seamless integration of dynamically and statically typed code.
We formalize a gradual type system for Featherweight GJ with a semantics given by a translation that inserts explicit run-time checks. The type system guarantees that statically typed parts of a program do not go wrong, even if it includes dynamically typed parts. We also describe a basic implementation scheme for Java and report preliminary performance evaluation.
Deriving Valid Population–Based Cancer Survival Estimates in the Presence of Nonnegligible Proportions of Cancers Notified by Death Certificates Only
Authors: Brenner Hermann , Holleczek Bernd 
Published: December 2011

Abstract
Background: Studies of cancer survival by population-based cancer registries are a key component in monitoring progress against cancer. Patients notified by death certificates only (DCO) are commonly excluded from such studies. The validity of this “exclude DCO” approach has been questioned and an alternative “correct for DCO” approach has been proposed.
Methods: We assess the validity of both the “exclude DCO” approach and the “correct for DCO” approach using model calculations. We illustrate implications for population-based cancer survival analyses by analyses of 5-year relative survival of cancer patients in Saarland, Germany.
Results: The “exclude DCO” approach provides (too) optimistic survival estimates and the “correct for DCO” approach provides (too) pessimistic survival estimates under plausible assumptions. For example, in case of true survival of 50%, underascertainment of 5% of surviving patients and of 15% of dying patients (yielding a proportion of DCO cases of 7.7%), the two approaches would provide survival rate estimates of 52.8% and 48.8%, respectively. The difference of survival estimates obtained with both approaches increases with incompleteness of registration and the proportion of DCO cases. Trace back of DCO cases shifts survival estimates from the former toward the latter estimate.
Conclusions: In case of nonnegligible DCO proportions, cancer survival studies should not be exclusively based on either the “exclude DCO” or the “correct for DCO” approach. A combination of estimates from both approaches may be useful to delineate a plausibility range for true survival.
Impact: Our results may help to enhance validity and comparability of population-based cancer survival estimates. Cancer Epidemiol Biomarkers Prev; 20(12); 2480–6. ©2011 AACR.
Applying Bourdieu’s theory to accounts of living with multimorbidity
Authors: Townsend Anne 
Published: December 2011

Objectives: Chronic illness is well researched. Broadly, empirical enquiry has focused on either determinants of behaviors or exploring lived experiences. This paper attempts to advance understandings of the lived experience of multimorbidity in broader cultural and structural settings. Methods: Twenty-three people in their early 50s were recruited from a community health survey in Scotland. The participants had 4 or more chronic illnesses and were interviewed twice. Key concepts of Bourdieu were applied to the data set Results: The analysis presented here is organized around 4 sections: 1) Habitus, capitals and the ill body; 2) Relational positioning; 3) Illness and symbolic violence; 4) The GP as dispenser of capitals. Applying Bourdieu’s theory to the accounts highlighted how broader cultural structures worked their way into personal illness narratives and illustrated how living with multimorbidity is a dialectic of structure and agency. Discussion: Interventions and support for those with multimorbidity need to take into account the tensions of opposing habitus underpinning medical encounters and the ongoing negotiation of structure and agency which is integral to living with chronic illness and underpins illness actions such as help-seeking and self-managing.
Management of Myelofibrosis
Authors: Vannucchi Alessandro M. 
Published: December 2011

AbstractMyelofibrosis (MF), either primary or arising from previous polycythemia vera (PV) or essential thrombocythemia (ET), is the worst among the chronic myeloproliferative neoplasms in terms of survival and quality of life. Patients with MF have to face several clinical issues that, because of the poor effectiveness of medical therapy, surgery or radiotherapy, represent largely unmet clinical needs. Powerful risk stratification systems, applicable either at diagnosis using the International Prognostic Scoring System (IPSS) or during the variable course of illness using the Dynamic International Prognostic Scoring System (DIPSS) and DIPSS Plus, allow recognition of categories of patients with survival times ranging from decades to < 2 years. These scores are especially important for therapeutic decisions that include allogeneic stem cell transplantation (allogeneic SCT), the only curative approach that still carries a nonnegligible risk of morbidity and mortality even with newest reduced intensity conditioning (RIC) regimens. Discovery of JAK2V617F mutation prompted the development of clinical trials using JAK2 inhibitors; these agents overall have resulted in meaningful symptomatic improvement and reduction of splenomegaly that were otherwise not achievable with conventional therapy. Intriguing differences in the efficacy and tolerability of JAK2 inhibitors are being recognized, which could lead to a nonoverlapping spectrum of activity/safety. Other agents that do not directly target JAK2 and have shown symptomatic efficacy in MF are represented by inhibitors of the mammalian target of rapamycin (mTOR) and histone deacetylases (HDACs). Pomalidomide appears to be particularly active against MF-associated anemia. However, because these agents are all poorly effective in reducing the burden of mutated cells, further advancements are needed to move from enhancing our ability to palliate the disease to arriving at an actual cure for MF.
Immunogenicity of panitumumab in combination chemotherapy clinical trials
Authors: Weeraratne Dohan , Chen Alin , Pennucci Jason J , Wu Chi-Yuan , Zhang Kathy , Wright Jacqueline , Pérez-Ruixo Juan José , Yang Bing-Bing , Kaliyaperumal Arunan , Gupta Shalini , Swanson Steven J , Chirmule Narendra , Starcevic Marta 
Published: December 2011

Abstract

Background
Panitumumab is a fully human antibody against the epidermal growth factor receptor that is indicated for the treatment of metastatic colorectal cancer (mCRC) after disease progression on standard chemotherapy. The purpose of this analysis was to examine the immunogenicity of panitumumab and to evaluate the effect of anti-panitumumab antibodies on pharmacokinetic and safety profiles in patients with mCRC receiving panitumumab in combination with oxaliplatin- or irinotecan-based chemotherapies.

Methods
Three validated assays (two screening immunoassays and a neutralizing antibody bioassay) were used to detect the presence of anti-panitumumab antibodies in serum samples collected from patients enrolled in four panitumumab combination chemotherapy clinical trials. The impact of anti-panitumumab antibodies on pharmacokinetic and safety profiles was analyzed using population pharmacokinetic analysis and descriptive statistics, respectively.

Results
Of 1124 patients treated with panitumumab in combination with oxaliplatin- or irinotecan-based chemotherapy with postbaseline samples available for testing, 20 (1.8%) patients developed binding antibodies and 2 (0.2%) developed neutralizing antibodies. The incidence of anti-panitumumab antibodies was similar in patients with tumors expressing wild-type or mutant KRAS and in patients receiving oxaliplatin- or irinotecan-based chemotherapies. No evidence of an altered pharmacokinetic or safety profile was found in patients who tested positive for anti-panitumumab antibodies.

Conclusions
The immunogenicity of panitumumab in the combination chemotherapy setting was infrequent and similar to the immunogenicity observed in the monotherapy setting. Panitumumab immunogenicity did not appear to alter pharmacokinetic or safety profiles. This low rate of immunogenicity may be attributed to the fully human nature of panitumumab.

Trial registration
ClinicalTrials.gov: NCT00339183 (study 20050181), NCT00411450 (study 20060277), NCT00332163 (study 20050184), and NCT00364013 (study 20050203).
The impact of phosphate scarcity on pharmaceutical protein production in S. cerevisiae: linking transcriptomic insights to phenotypic responses
Authors: Kazemi Seresht Ali , Palmqvist Eva Akke , Olsson Lisbeth 
Published: December 2011

Abstract

Background
The adaptation of unicellular organisms like Saccharomyces cerevisiae to alternating nutrient availability is of great fundamental and applied interest, as understanding how eukaryotic cells respond to variations in their nutrient supply has implications spanning from physiological insights to biotechnological applications.

Results
The impact of a step-wise restricted supply of phosphate on the physiological state of S. cerevisiae cells producing human Insulin was studied. The focus was to determine the changes within the global gene expression of cells being cultured to an industrially relevant high cell density of 33 g/l cell dry weight and under six distinct phosphate concentrations, ranging from 33 mM (unlimited) to 2.6 mM (limited). An increased flux through the secretory pathway, being induced by the PHO circuit during low Pi supplementation, proved to enhance the secretory production of the heterologous protein. The re-distribution of the carbon flux from biomass formation towards increased glycerol production under low phosphate led to increased transcript levels of the insulin gene, which was under the regulation of the TPI1 promoter.

Conclusions
Our study underlines the dynamic character of adaptive responses of cells towards a change in their nutrient access. The gradual decrease of the phosphate supply resulted in a step-wise modulated phenotypic response, thereby alternating the specific productivity and the secretory flux. Our work emphasizes the importance of reduced phosphate supply for improved secretory production of heterologous proteins.
Advanced glycation end products (AGEs) in relation to atherosclerotic lipid profiles in middle-aged and elderly diabetic patients
Authors: Chang Jin-Biou , Chu Nain-Feng , Syu Jhu-Ting , Hsieh An-Tsz , Hung Yi-Ren 
Published: December 2011

Abstract

Objectives
To evaluate the association between AGEs and atherosclerotic lipid profiles among aging diabetic patients in Taiwan.

Design and Methods
After age and gender matching, we selected 207 diabetic subjects and 174 diabetic subjects with proteinuria. Lipid profiles, including total cholesterol (TC), triglycerides (TG), high density cholesterol-lipoprotein (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were measured using standard methods. AGEs were measured with the immunoassay method.

Results
In general, males were heavier; however, females had higher AGEs, fasting glucose (GLU), TC, HDL-C and LDL-C levels than males, and had higher TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C ratios compared to males. AGEs were more strongly correlated with TG levels and TCL/LDL-C, LDL-C/HDL-C and TG/HDL-C ratios when compared to glucose or hemoglobin A1c. Subjects had higher AGEs levels (≧ 2.0 AU) with more adverse lipid profiles.

Conclusion
AGEs seem to be a good biomarker to evaluate the association between diabetes and atherosclerotic disorders in aging diabetes.
Zinc supplementation alters airway inflammation and airway hyperresponsiveness to a common allergen
Authors: Morgan Carrie I , Ledford John R , Zhou Ping , Page Kristen 
Published: December 2011

Abstract

Background
Zinc supplementation can modulate immunity through inhibition of NF-κB, a transcription factor that controls many immune response genes. Thus, we sought to examine the mechanism by which zinc supplementation tempers the response to a common allergen and determine its effect on allergic airway inflammation.

Methods
Mice were injected with zinc gluconate prior to German cockroach (GC) feces (frass) exposure and airway inflammation was assessed. Primary bone marrow-derived neutrophils and DMSO-differentiated HL-60 cells were used to assess the role of zinc gluconate on tumor necrosis factor (TNF)α expression. NF-κB:DNA binding and IKK activity were assessed by EMSA and in vitro kinase assay. Protein levels of A20, RIP1 and TRAF6 were assessed by Western blot analysis. Establishment of allergic airway inflammation with GC frass was followed by administration of zinc gluconate. Airway hyperresponsiveness, serum IgE levels, eosinophilia and Th2 cytokine production were assessed.

Results
Administration of zinc gluconate prior to allergen exposure resulted in significantly decreased neutrophil infiltration and TNFα cytokine release into the airways. This correlated with decreased NF-κB activity in the whole lung. Treatment with zinc gluconate significantly decreased GC frass-mediated TNFα production from bone-marrow derived neutrophils and HL-60 cells. We confirmed zinc-mediated decreases in NF-κB:DNA binding and IKK activity in HL-60 cells. A20, a natural inhibitor of NF-κB and a zinc-fingered protein, is a potential target of zinc. Zinc treatment did not alter A20 levels in the short term, but resulted in the degradation of RIP1, an important upstream activator of IKK. TRAF6 protein levels were unaffected. To determine the application for zinc as a therapeutic for asthma, we administered zinc following the establishment of allergic airway inflammation in a murine model. Zinc supplementation decreased airway hyperresponsiveness and serum IgE levels, but had no effect on Th2 cytokine expression.

Conclusions
This report suggests that the mechanism by which zinc supplementation alters NF-κB activity is via the alteration of A20 activity. In addition, this study provides evidence that supplementation of zinc to asthmatics may alter airway reactivity and serum IgE levels, suggesting zinc supplementation as a potential treatment for asthmatics.