bluuebunny/crossref_metadata_2025_split huggingface dataset:
Site of cochlear stimulation and its effect on electrically evoked compound action potentials using the MED-EL standard electrode array
Authors: Brill Stefan , Müller Joachim , Hagen Rudolf , Möltner Alexander , Brockmeier Steffi-Johanna , Stark Thomas , Helbig Silke , Maurer Jan , Zahnert Thomas , Zierhofer Clemens , Nopp Peter , Anderson Ilona , Strahl Stefan 
Published: December 2009

Abstract

Background
The standard electrode array for the MED-EL MAESTRO cochlear implant system is 31 mm in length which allows an insertion angle of approximately 720°. When fully inserted, this long electrode array is capable of stimulating the most apical region of the cochlea. No investigation has explored Electrically Evoked Compound Action Potential (ECAP) recordings in this region with a large number of subjects using a commercially available cochlear implant system. The aim of this study is to determine if certain properties of ECAP recordings vary, depending on the stimulation site in the cochlea.

Methods
Recordings of auditory nerve responses were conducted in 67 subjects to demonstrate the feasibility of ECAP recordings using the Auditory Nerve Response Telemetry (ART™) feature of the MED-EL MAESTRO system software. These recordings were then analyzed based on the site of cochlear stimulation defined as basal, middle and apical to determine if the amplitude, threshold and slope of the amplitude growth function and the refractory time differs depending on the region of stimulation.

Results
Findings show significant differences in the ECAP recordings depending on the stimulation site. Comparing the apical with the basal region, on average higher amplitudes, lower thresholds and steeper slopes of the amplitude growth function have been observed. The refractory time shows an overall dependence on cochlear region; however post-hoc tests showed no significant effect between individual regions.

Conclusions
Obtaining ECAP recordings is also possible in the most apical region of the cochlea. However, differences can be observed depending on the region of the cochlea stimulated. Specifically, significant higher ECAP amplitude, lower thresholds and steeper amplitude growth function slopes have been observed in the apical region. These differences could be explained by the location of the stimulating electrode with respect to the neural tissue in the cochlea, a higher density, or an increased neural survival rate of neural tissue in the apex.

Trial registration
The Clinical Investigation has the Competent Authority registration number DE/CA126/AP4/3332/18/05.
The protein tyrosine phosphatase receptor type R gene is an early and frequent target of silencing in human colorectal tumorigenesis
Authors: Menigatti Mirco , Cattaneo Elisa , Sabates-Bellver Jacob , Ilinsky Valery V , Went Philip , Buffoli Federico , Marquez Victor E , Jiricny Josef , Marra Giancarlo 
Published: December 2009

Abstract

Background
Tumor development in the human colon is commonly accompanied by epigenetic changes, such as DNA methylation and chromatin modifications. These alterations result in significant, inheritable changes in gene expression that contribute to the selection of tumor cells with enhanced survival potential.

Results
A recent high-throughput gene expression analysis conducted by our group identified numerous genes whose transcription was markedly diminished in colorectal tumors. One of these, the
p

rotein-

t

yrosine

p

hosphatase

r

eceptor type

R
(PTPRR) gene, was dramatically downregulated from the earliest stages of cellular transformation. Here, we show that levels of both major PTPRR transcript variants are markedly decreased (compared with normal mucosal levels) in precancerous and cancerous colorectal tumors, as well in colorectal cancer cell lines. The expression of the PTPRR-1 isoform was inactivated in colorectal cancer cells as a result of de novo CpG island methylation and enrichment of transcription-repressive histone-tail marks, mainly H3K27me3. De novo methylation of the PTPRR-1 transcription start site was demonstrated in 29/36 (80%) colorectal adenomas, 42/44 (95%) colorectal adenocarcinomas, and 8/8 (100%) liver metastases associated with the latter tumors.

Conclusions
Epigenetic downregulation of PTPRR seems to be an early alteration in colorectal cell transformation, which is maintained during the clonal selection associated with tumor progression. It may represent a preliminary step in the constitutive activation of the RAS/RAF/MAPK/ERK signalling, an effect that will later be consolidated by mutations in genes encoding key components of this pathway.
Human synthetic lethal inference as potential anti-cancer target gene detection
Authors: Conde-Pueyo Nuria , Munteanu Andreea , Solé Ricard V , Rodríguez-Caso Carlos 
Published: December 2009

AbstractBackgroundTwo genes are called synthetic lethal (SL) if mutation of either alone is not lethal, but mutation of both leads to death or a significant decrease in organism's fitness. The detection of SL gene pairs constitutes a promising alternative for anti-cancer therapy. As cancer cells exhibit a large number of mutations, the identification of these mutated genes' SL partners may provide specific anti-cancer drug candidates, with minor perturbations to the healthy cells. Since existent SL data is mainly restricted to yeast screenings, the road towards human SL candidates is limited to inference methods.ResultsIn the present work, we use phylogenetic analysis and database manipulation (BioGRID for interactions, Ensembl and NCBI for homology, Gene Ontology for GO attributes) in order to reconstruct the phylogenetically-inferred SL gene network for human. In addition, available data on cancer mutated genes (COSMIC and Cancer Gene Census databases) as well as on existent approved drugs (DrugBank database) supports our selection of cancer-therapy candidates.ConclusionsOur work provides a complementary alternative to the current methods for drug discovering and gene target identification in anti-cancer research. Novel SL screening analysis and the use of highly curated databases would contribute to improve the results of this methodology.
Cyclosporine Versus Tacrolimus in Immunosuppressive Maintenance Regimens in Renal Transplants in Brazil: Survival Analysis from 2000 to 2004
Authors: Guerra Augusto Afonso , Cesar Cibele Comini , Cherchiglia Mariângela Leal , Andrade Eli lola Gurgel , de Queiroz Odilon Vanni , Silva Grazielle D , de Assis Acurcio Francisco 
Published: December 2009

BACKGROUND In Brazil, the National Health System (SUS) is responsible for almost all renal transplants. SUS protocols recommend using cyclosporine, in association with azathioprine and corticosteroids, to maintain the immunosuppression that is essential for successful renal transplant. Alternatively, cyclosporine can be replaced by tacrolimus. OBJECTIVE To evaluate the effectiveness of therapeutic schema involving cyclosporine or tacrolimus after renal transplant during a 60-month follow-up period. METHODS A historical cohort study, from 2000 to 2004, was conducted using 5686 patients who underwent renal transplant and received cyclosporine or tacrolimus. Uni - and multivariate analyses were performed using the Cox model to examine factors associated with progression to treatment failure. RESULTS Most of the patients were male, aged 38 years or older, for whom the most frequent primary diagnosis of chronic renal failure (CRF) was glomerulonephritis/nephritis. Higher risk of treatment failure was associated with: therapeutic regimen (tacrolimus, HR 1.38, 95% CI 1.14 to 1.67), patient age at transplantation (additional year, HR 1.01, 95% CI 1.00 to 1.02), donor type (deceased, HR 1.60, 95% CI 1.35 to 1.89), median time of dialysis prior to transplantation (>24 mo, HR 1.29, 95% CI 1.09 to 1.52), and primary CRF diagnosis (diabetes, HR 1.54, 95% CI 1.09 to 2.17). CONCLUSIONS The risk of treatment failure of patients receiving tacrolimus was observed to be 1.38 times that of those receiving cyclosporine, after adjusting the model for possible confounding factors such as patient sex, patient age, graft origin, prior time of dialysis, and cause of CRF. Our results were obtained from an observational study, and further studies are necessary to evaluate whether compliance with SUS clinical protocols could result in more effective care for renal transplant recipients.
Effect of Rimonabant on Glycemic Control in Insulin-Treated Type 2 Diabetes: The ARPEGGIO Trial
Authors: Hollander Priscilla A. , Amod Aslam , Litwak León E. , Chaudhari Umesh ,   for the ARPEGGIO Study Group
Published: December 2009

OBJECTIVE
To examine the efficacy and safety of rimonabant, a selective cannabinoid receptor type-1 antagonist, in patients with type 2 diabetes receiving insulin monotherapy.

RESEARCH DESIGN AND METHODS
Patients (n = 368; A1C ≥7%) were randomized to 20 mg/day rimonabant or placebo in this 48-week, double-blind, placebo-controlled multicenter trial. Change in baseline A1C to week 48 (primary outcome) and changes in body weight, waist circumference, and lipid levels (secondary outcomes) were assessed.

RESULTS
Rimonabant significantly reduced baseline A1C versus placebo (−0.89 vs. −0.24%; P &lt; 0.0001), and significantly greater improvements were observed in cardiometabolic risk factors. More rimonabant patients achieved &gt;10% reduction in mean total daily insulin dose versus placebo (P = 0.0012), and fewer required rescue medication (P &lt; 0.0001). Hypoglycemia, nausea, dizziness, anxiety, and depression were more frequent with rimonabant.

CONCLUSIONS
Rimonabant improved glycemic control and cardiometabolic risk factors in patients with type 2 diabetes receiving insulin.
Patient Race/Ethnicity and Patient-Physician Race/Ethnicity Concordance in the Management of Cardiovascular Disease Risk Factors for Patients With Diabetes
Authors: Traylor Ana H. , Subramanian Usha , Uratsu Connie S. , Mangione Carol M. , Selby Joe V. , Schmittdiel Julie A. 
Published: December 2009

OBJECTIVE
Patient-physician race/ethnicity concordance can improve care for minority patients. However, its effect on cardiovascular disease (CVD) care and prevention is unknown. We examined associations of patient race/ethnicity and patient-physician race/ethnicity concordance on CVD risk factor levels and appropriate modification of treatment in response to high risk factor values (treatment intensification) in a large cohort of diabetic patients.

RESEARCH DESIGN AND METHODS
The study population included 108,555 adult diabetic patients in Kaiser Permanente Northern California in 2005. Probit models assessed the effect of patient race/ethnicity on risk factor control and treatment intensification after adjusting for patient and physician-level characteristics.

RESULTS
African American patients were less likely than whites to have A1C &lt;8.0% (64 vs. 69%, P &lt; 0.0001), LDL cholesterol &lt;100 mg/dl (40 vs. 47%, P &lt; 0.0001), and systolic blood pressure (SBP) &lt;140 mmHg (70 vs. 78%, P &lt; 0.0001). Hispanic patients were less likely than whites to have A1C &lt;8% (62 vs. 69%, P &lt; 0.0001). African American patients were less likely than whites to have A1C treatment intensification (73 vs. 77%, P &lt; 0.0001; odds ratio [OR] 0.8 [95% CI 0.7–0.9]) but more likely to receive treatment intensification for SBP (78 vs. 71%, P &lt; 0.0001; 1.5 [1.3–1.7]). Hispanic patients were more likely to have LDL cholesterol treatment intensification (47 vs. 45%, P &lt; 0.05; 1.1 [1.0–1.2]). Patient-physician race/ethnicity concordance was not significantly associated with risk factor control or treatment intensification.

CONCLUSIONS
Patient race/ethnicity is associated with risk factor control and treatment intensification, but patient-physician race/ethnicity concordance was not. Further research should investigate other potential drivers of disparities in CVD care.
Rapid Identification of Myocardial Infarction Risk Associated With Diabetes Medications Using Electronic Medical Records
Authors: Brownstein John S. , Murphy Shawn N. , Goldfine Allison B. , Grant Richard W. , Sordo Margarita , Gainer Vivian , Colecchi Judith A. , Dubey Anil , Nathan David M. , Glaser John P. , Kohane Isaac S. 
Published: December 2009

OBJECTIVE
To assess the ability to identify potential association(s) of diabetes medications with myocardial infarction using usual care clinical data obtained from the electronic medical record.

RESEARCH DESIGN AND METHODS
We defined a retrospective cohort of patients (n = 34,253) treated with a sulfonylurea, metformin, rosiglitazone, or pioglitazone in a single academic health care network. All patients were aged &gt;18 years with at least one prescription for one of the medications between 1 January 2000 and 31 December 2006. The study outcome was acute myocardial infarction requiring hospitalization. We used a cumulative temporal approach to ascertain the calendar date for earliest identifiable risk associated with rosiglitazone compared with that for other therapies.

RESULTS
Sulfonylurea, metformin, rosiglitazone, or pioglitazone therapy was prescribed for 11,200, 12,490, 1,879, and 806 patients, respectively. A total of 1,343 myocardial infarctions were identified. After adjustment for potential myocardial infarction risk factors, the relative risk for myocardial infarction with rosiglitazone was 1.3 (95% CI 1.1–1.6) compared with sulfonylurea, 2.2 (1.6–3.1) compared with metformin, and 2.2 (1.5–3.4) compared with pioglitazone. Prospective surveillance using these data would have identified increased risk for myocardial infarction with rosiglitazone compared with metformin within 18 months of its introduction with a risk ratio of 2.1 (95% CI 1.2–3.8).

CONCLUSIONS
Our results are consistent with a relative adverse cardiovascular risk profile for rosiglitazone. Our use of usual care electronic data sources from a large hospital network represents an innovative approach to rapid safety signal detection that may enable more effective postmarketing drug surveillance.
Carboxylation of Osteocalcin Affects Its Association With Metabolic Parameters in Healthy Children
Authors: Prats-Puig Anna , Mas-Parareda Marta , Riera-Pérez Elena , González-Forcadell Dolors , Mier Concepció , Mallol-Guisset Montserrat , Díaz Marta , Bassols Judit , de Zegher Francis , Ibáñez Lourdes , López-Bermejo Abel 
Published: December 2009

OBJECTIVE
Osteocalcin (OC), a bone-derived protein, was recently shown to regulate metabolic pathways in mice. Undercarboxylated OC (ucOC), but not carboxylated OC (cOC), increases adiponectin and insulin secretion. It is unclear if carboxylation of OC affects its association with metabolic parameters in humans.

RESEARCH DESIGN AND METHODS
The associations between ucOC, cOC, total and high-molecular-weight (HMW) adiponectin, and insulin secretion (homeostasis model assessment [HOMA]-β) were investigated in a population-based sample of healthy prepubertal children (n = 103; 49 boys and 54 girls).

RESULTS
Weight-dependent associations were observed between the different forms of OC and metabolic parameters. Higher cOC was related to lower HMW adiponectin (with a stronger association in leaner children; P &lt; 0.001). Higher ucOC-to-cOC ratio was associated with higher HOMA-β (P &lt; 0.01) in leaner children and associated with higher HMW adiponectin (P &lt; 0.001) in heavier children.

CONCLUSIONS
In a weight-dependent manner, cOC and the proportion of ucOC are differentially related to HMW adiponectin and insulin secretion in healthy children.
Approximation and asymptotics of eigenvalues of unbounded self-adjoint Jacobi matrices acting in l
2 by the use of finite submatrices
Authors: Malejki Maria 
Published: December 2009

Abstract
We consider the problem of approximation of eigenvalues of a self-adjoint operator J defined by a Jacobi matrix in the Hilbert space l
2(ℕ) by eigenvalues of principal finite submatrices of an infinite Jacobi matrix that defines this operator. We assume the operator J is bounded from below with compact resolvent. In our research we estimate the asymptotics (with n → ∞) of the joint error of approximation for the eigenvalues, numbered from 1 to N; of J by the eigenvalues of the finite submatrix J
n of order n × n; where N = max{k ∈ ℕ: k ≤ rn} and r ∈ (0; 1) is arbitrary chosen. We apply this result to obtain an asymptotics for the eigenvalues of J. The method applied in this research is based on Volkmer’s results included in [23].
Protonation mechanisms of Nickel Complexes Relevant to Industrial and Biological Catalysis
Authors: Henderson Richard A. 
Published: December 2009

The sites of protonation and the subsequent rearrangement reactions of simple nickel complexes containing hydride, thiolate and alkyl ligands are reviewed, and the relevance of these reactions to the action of certain nickelbased catalysts are discussed. Summary Protonation at the metal and ligand is central to the understanding of how both enzymes and industrial catalysts operate at the molecular level. The recurring theme in studies on the protonation of all metal complexes is that the ultimate residence of the proton is not necessarily the initial binding site, and the movement of proton between sites can occur by a variety of mechanisms. These features are also evident in the reactions of simple nickel complexes and mechanistic studies are revealing the subtle interplay between ligand and metal which are the basis of the kinetic and thermodynamic control of protonation reactions at these sites.
Clinical Features and Prognosis of Late-onset Systemic Lupus Erythematosus: Results from the 1000 Faces of Lupus Study
Authors: LALANI SHELIZA , POPE JANET , de LEON FAYE , PESCHKEN CHRISTINE 
Published: December 2009

Objective.There is controversy whether older-onset systemic lupus erythematosus (SLE) is associated with a different, more benign disease course than in younger-onset SLE. Our objective was to characterize the clinical features and prognosis of late-onset SLE in a large, multicenter cohort.Methods.We studied adult-onset lupus in the 1000 Canadian Faces of Lupus cohort (n = 1528) of whom 10.5% had onset at age ≥ 50 years versus a control group with onset at < 50 years.Results.Disease duration was different in early- and late-onset groups (15 yrs in early vs 9.3 yrs in late; p < 0.001). Caucasians were represented more in the later-onset SLE group (55.6% vs 74.5%), while Asians and Blacks were more prevalent in the younger group. Younger-onset SLE subjects fulfilled more American College of Rheumatology criteria for SLE (< 50 yrs: 5.98 ± 1.68; ≥ 50 yrs: 5.24 ± 1.44; p < 0.0001). Despite an equal prevalence of anti-dsDNA, the younger-onset group more often had positive anti-Smith autoantibody, ribonucleoprotein, and hypocomplementemia, and more nephritis, rash, and cytopenias than the older-onset group. However, disease activity and damage accrual were higher in the older-onset group. The older patients received less prednisone and immunosuppressives (current and ever-use). As expected, comorbidity was higher in the older-onset SLE group.Conclusion.This study suggests that older age-onset SLE is not benign. There may be an interaction between lupus and age in which, although there is less lupus nephritis in the elderly, more disease activity and damage are present.
Possible Reactivation of Potential Hepatitis B Virus Occult Infection by Tumor Necrosis Factor-α Blocker in the Treatment of Rheumatic Diseases
Authors: KIM YUN JUNG , BAE SANG-CHEOL , SUNG YOON-KYOUNG , KIM TAE-HWAN , JUN JAE-BUM , YOO DAE-HYUN , KIM TAE YEOB , SOHN JOO HYUN , LEE HYE-SOON 
Published: December 2009

Objective. To assess the safety of anti-tumor necrosis factor (TNF-α) therapy in patients with rheumatic diseases in terms of the reactivation of potential hepatitis B virus (HBV) occult infection.Methods. Patients who had taken anti-TNF-α for the treatment of rheumatic diseases from January 2002 to May 2008 were included in the study. In this patient group, we retrospectively investigated a series of serum aminotransferase levels, HBV serologic status, the type of anti-TNF-α therapy, duration of the anti-TNF-α treatment, and concurrent use of hepatotoxic drugs.Results. A total of 266 cases were documented using 3 serologic markers for HBV infection: HBV surface antigen (HBsAg), HBV surface antibody (HBsAb), and HBV core IgG Ab (HBcAb). Of these, 8 cases had chronic hepatitis B (HBsAg+), 170 cases were HBcAb-negative, and 88 cases were identified as having potential HBV occult infections represented by HBsAg-negative and HBcAb-positive, irrespective of the status of the HBsAb.The frequency of clinically significant (> 2 times normal value) and persistent increase (> 2 consecutive tests) of aminotransferase levels was significantly higher in the group with a potential HBV occult infection compared to the HBcAb-negative group. In the multiple logistic regression analysis controlling for various potential confounding factors such as prophylactic anti-tuberculosis medication, methotrexate, nonsteroidal antiinflammatory drugs, and the type of anti-TNF-α therapy, only potential HBV occult infection was a significant risk factor for abnormal liver function test (LFT).Conclusion. All rheumatic patients who plan to take anti-TNF-α treatment should undergo a test for HBV serology, including HBcAb, and have a close followup with an LFT test during therapy. Further prospective studies for hepatitis B viral load using HBV-polymerase chain reaction in patients who are HbcAb positive are needed to identify whether the abnormal LFT comes from the reactivation of occult HBV infection.
A General Approach for Fabricating Arc‐Shaped Composite Nanowire Arrays by Pulsed Laser Deposition
Authors: Shen Yue , Hong Jung‐Il , Xu Sheng , Lin Shisheng , Fang Hao , Zhang Su , Ding Yong , Snyder Robert L. , Wang Zhong Lin 
Published: December 2009

AbstractHere, a new method is demonstrated that uses sideways pulsed laser deposition to deliberately bend nanowires into a desired shape after growth and fabricate arc‐shaped composite nanowire arrays of a wide range of nanomaterials. The starting nanowires can be ZnO, but the materials to be deposited can be metallic, semiconductor, or ceramic depending on the application. This method provides a general approach for rational fabrication of a wide range of side‐by‐side or “core–shell” nanowire arrays with controllable degree of bending and internal strain. Considering the ZnO is a piezoelectric and semiconductive material, its electrical properties change when deformed. This technique has potential applications in tunable electronics, optoelectronics, and piezotronics.