bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reverse Electrical Remodeling by Cardiac Resynchronization Therapy: Prevalence and Clinical Impact
Authors: SEBAG FREDERIC A. , MARTINS RAPHAEL P. , DEFAYE PASCAL , HIDDEN‐LUCET FRANÇOISE , MABO PHILIPPE , DAUBERT JEAN‐CLAUDE , LECLERCQ CHRISTOPHE 
Published: May 2012

Intrinsic QRS Narrowing with CRT. Background: Cardiac resynchronization therapy (CRT) improves left ventricular ejection fraction (LVEF) in patients with congestive heart failure, LV systolic dysfunction, and a wide QRS complex. Previous reports suggest that CRT may also induce electrical remodeling but the impact on clinical outcome remains unknown.Objective: We sought to determine (1) if chronic CRT induces a relevant shortening of the intrinsic QRS (iQRS), (2) whether changes in the native conduction system correlate with clinical or echocardiographic response to CRT, and (3) to identify predictors of iQRS width shortening.Methods: We prospectively included 85 consecutive patients with left bundle‐branch block who received a CRT device in 3 French centers. NYHA class, iQRS duration, LVEF, and left ventricular volumes were assessed before and 1 year after CRT implantation. Clinical and echocardiographic CRT responders were defined respectively as NYHA class improvement >1 class without heart failure hospitalization and an increase of LVEF by ≥10% and/or a decrease in LVESV by ≥15%. Electrocardiographic responders were defined as a decrease in iQRS duration by ≥20 ms.Results: Baseline and 1‐year follow‐up mean iQRS durations were, respectively, 168.0 ± 19.7 ms and 149.6 ± 31.6 ms (P < 0.0001). Electrocardiographic response, observed in 43/85 patients (51%), was associated with a greater rate of clinical (P = 0.035) and echocardiographic (P = 0.023) response. Younger age, male gender, and longer baseline QRS width were independent predictors of electrocardiographic response.Conclusion: CRT decreases iQRS duration. A reduction of at least 20 ms in iQRS duration is associated with better clinical and echocardiographic response. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1219–1227, November 2012)
Childbirth attendance strategies and their impact on maternal mortality and morbidity in low‐income settings: a systematic review
Authors: PYONE THIDAR , SORENSEN BJARKE LUND , TELLIER SIRI 
Published: May 2012

AbstractObjective. To review quantitative evidence of the effect on maternal health of different childbirth attendance strategies in low‐income settings. Design. Systematic review. Methods. Studies using quantitative methods, referring to the period 1987–2011, written in English and reporting the impact of childbirth attendance strategies on maternal mortality or morbidity in low‐income settings were included. Guidelines developed by the Cochrane collaboration and the Centre for Review and Dissemination, University of York were followed. The included articles were read and sorted by category of strategy that emerged from the reading. Results. The search criteria yielded 29 articles. The following three main categories of strategy emerged: (i) those primarily intended to improve quality of care; (ii) “centrifugal strategies,” which sought to bring services to the women; and (iii) “centripetal strategies,” which sought to bring the women to the services. Few of the studies had a design that provided strong evidence for the impact of the strategy concerned. Conclusions. The evidence emerging from the studies was difficult to compare, because concepts were not defined in a consistent manner (such as “skilled birth attendance”) and many studies examined the impact of a package of interventions without ferreting out the impact of individual components. Yet, some studies described individual aspects with great promise (such as cost, transport, outreach‐friendly drugs or targeted training). There is a need for clearer conceptual frameworks, including some which permit assessment of packages of interventions.
Inherited platelet disorders and oral health
Authors: Valera Marie‐Cécile , Kemoun Philippe , Cousty Sarah , Sie Pierre , Payrastre Bernard 
Published: May 2012

J Oral Pathol Med (2013)42: 115–124Platelets play a key role in thrombosis and hemostasis. Accumulation of platelets at the site of vascular injury is the first step in the formation of hemostatic plugs, which play a pivotal role in preventing blood loss after injury. Platelet adhesion at sites of injury results in spreading, secretion, recruitment of additional platelets, and formation of platelet aggregates. Inherited platelet disorders are rare causes of bleeding syndromes, ranging from mild bruising to severe hemorrhage. The defects can reflect deficiency or dysfunction of platelet surface glycoproteins, granule contents, cytoskeletal proteins, platelet pro‐coagulant function, and signaling pathways. For instance, Bernard–Soulier syndrome and Glanzmann thrombasthenia are attributed to deficiencies of glycoprotein Ib/IX/V and GPIIb/IIIa, respectively, and are rare but severe platelet disorders. Inherited defects that impair platelet secretion and/or signal transduction are among the most common forms of mild platelet disorders and include gray platelet syndrome, Hermansky–Pudlak syndrome, and Chediak–Higashi syndrome. When necessary, desmopressin, antifibrinolytic agents, and transfusion of platelets remain the most common treatment of inherited platelet disorders. Alternative therapies such as recombinant activated factor VII are also available for a limited number of situations. In this review, we will discuss the management of patients with inherited platelet disorders in various clinical situations related to dental cares, including surgical intervention.
The electroneutral Na+:HCO3− cotransporter NBCn1 is a major pHi regulator in murine duodenum
Authors: Chen Mingmin , Praetorius Jeppe , Zheng Wen , Xiao Fang , Riederer Brigitte , Singh Anurag Kumar , Stieger Nicole , Wang Jian , Shull Gary E. , Aalkjaer Christian , Seidler Ursula 
Published: May 2012

Key points
The mucosa of the proximal duodenum is regularly exposed to the strong acid of gastric juice, and acid damage causes peptic ulceration and bleeding.
The epithelial cells of the duodenum protect themselves against acid‐induced chemical damage by secreting bicarbonate into the lumen and by regulating their intracellular pH, but the molecular mechanisms of duodenal pHi control are incompletely understood.
We have found a high expression of the electroneutral sodium bicarbonate transporter Slc4a7 (NBCn1) in the basolateral membrane of duodenal villous enterocytes.
Genetic knockout of Slc4a7 resulted in a strong defect in duodenocyte pHi recovery from acid loads, and reduced bicarbonate secretory rates.
This suggests that the electroneutral sodium bicarbonate cotransporter Slc4a7 is a major import mechanism for HCO3− from the blood into the duodenal epithelial cells. Defects in this transporter may severely endanger duodenal mucosal integrity
Abstract  Duodenocyte pHi control and HCO3− secretion protects the proximal duodenum against damage by gastric acid. The molecular details of duodenocyte pH control are not well understood. A selective duodenal expression (within the upper GI tract) has been reported for the electroneutral Na+:HCO3− cotransporter NBCn1 (Slc4a7). We aimed to determine the role of NBCn1 and NBCe2 in duodenocyte intracellular pH regulation as well as basal and agonist‐stimulated duodenal bicarbonate secretion (JHCO3−), exploiting mouse models of genetic slc4a7 and slc4a5 disruption. Basal and forskolin (FSK)‐stimulated JHCO3− was measured by single‐pass perfusion in the duodenum of slc4a7−/− and slc4a7+/+ as well as slc4a5−/− and slc4a5+/+ mice in vivo, and by pH‐stat titration in isolated duodenal mucosa in vitro. Duodenocyte HCO3− uptake rates were fluorometrically assessed after acidification of intact villi and of isolated duodenocytes. Slc4a7−/− mice displayed significantly lower basal and FSK‐stimulated duodenal HCO3− secretion than slc4a7+/+ littermates in vivo. FSK‐stimulated HCO3− secretion was significantly reduced in slc4a7−/− isolated duodenal mucosa. Na+‐ and HCO3−‐dependent base uptake rates were significantly decreased in slc4a7−/− compared with slc4a7+/+ villus duodenocytes when measured in intact villi. Carbonic anhydrase (CA)‐mediated CO2 hydration played no apparent role as a HCO3− supply mechanism for basal or FSK‐stimulated secretion in the slc4a7+/+ duodenum, but was an important alternative HCO3− supply mechanism in the slc4a7−/− duodenum. NBCe2 (Slc4a5) displayed markedly lower duodenal mRNA expression levels, and its disruption did not interfere with duodenal HCO3− secretion. The electroneutral Na+:HCO3− cotransporter NBCn1 (slc4a7) is a major duodenal HCO3− importer that supplies HCO3− during basal and FSK‐stimulated HCO3− secretion.
Dinitroazetidines Are a Novel Class of Anticancer Agents and Hypoxia-Activated Radiation Sensitizers Developed from Highly Energetic Materials
Authors: Ning Shoucheng , Bednarski Mark , Oronsky Bryan , Scicinski Jan , Saul Gordon , Knox Susan J. 
Published: May 2012

Abstract
In an effort to develop cancer therapies that maximize cytotoxicity, while minimizing unwanted side effects, we studied a series of novel compounds based on the highly energetic heterocyclic scaffold, dinitroazetidine. In this study, we report the preclinical validation of 1-bromoacetyl-3,3-dinitroazetidine (ABDNAZ), a representative lead compound currently in a phase I clinical trial in patients with cancer. In tumor cell culture, ABDNAZ generated reactive free radicals in a concentration- and time-dependent manner, modulating intracellular redox status and triggering apoptosis. When administered to mice as a single agent, ABDNAZ exhibited greater cytotoxicity than cisplatin or tirapazamine under hypoxic conditions. However, compared with cisplatin, ABDNAZ was better tolerated at submaximal doses, yielding significant tumor growth inhibition in the absence of systemic toxicity. Similarly, when combined with radiation, ABDNAZ accentuated antitumor efficacy along with the therapeutic index. Toxicity studies indicated that ABDNAZ was not myelosuppressive and no dose-limiting toxicity was apparent following daily administration for 14 days. Taken together, our findings offer preclinical proof-of-concept for ABDNAZ as a promising new anticancer agent with a favorable toxicity profile, either as a chemotherapeutic agent or a radiosensitizer. Cancer Res; 72(10); 2600–8. ©2012 AACR.
A Comprehensive Survey of Ras Mutations in Cancer
Authors: Prior Ian A. , Lewis Paul D. , Mattos Carla 
Published: May 2012

Abstract
All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras, that promote oncogenesis when they are mutationally activated at codon 12, 13, or 61. Although there is a high degree of similarity among the isoforms, K-Ras mutations are far more frequently observed in cancer, and each isoform displays preferential coupling to particular cancer types. We examined the mutational spectra of Ras isoforms curated from large-scale tumor profiling and found that each isoform exhibits surprisingly distinctive codon mutation and amino-acid substitution biases. These findings were unexpected given that these mutations occur in regions that share 100% amino-acid sequence identity among the 3 isoforms. Of importance, many of these mutational biases were not due to differences in exposure to mutagens, because the patterns were still evident when compared within specific cancer types. We discuss potential genetic and epigenetic mechanisms, as well as isoform-specific differences in protein structure and signaling, that may promote these distinct mutation patterns and differential coupling to specific cancers. Cancer Res; 72(10); 2457–67. ©2012 AACR.
Using Germline Genomics to Individualize Pediatric Cancer Treatments
Authors: Pinto Navin , Cohn Susan L. , Dolan M. Eileen 
Published: May 2012

Abstract
The amazing successes in cure rates for children with cancer over the last century have come in large part from identifying clinical, genetic, and molecular variables associated with response to therapy in large cooperative clinical trials and stratifying therapies according to the predicted risk of relapse. There is an expanding interest in identifying germline genomic variants, as opposed to genetic variants within the tumor, that are associated with susceptibility to toxicity and for risk of relapse. This review highlights the most important germline pharmacogenetic and pharmacogenomic studies in pediatric oncology. Incorporating germline genomics into risk-adapted therapies will likely lead to safer and more effective treatments for children with cancer. Clin Cancer Res; 18(10); 2791–800. ©2012 AACR.
Multiple SNP testing improves risk prediction of first venous thrombosis
Authors: de Haan Hugoline G. , Bezemer Irene D. , Doggen Carine J. M. , Le Cessie Saskia , Reitsma Pieter H. , Arellano Andre R. , Tong Carmen H. , Devlin James J. , Bare Lance A. , Rosendaal Frits R. , Vossen Carla Y. 
Published: May 2012

Abstract
There are no risk models available yet that accurately predict a person's risk for developing venous thrombosis. Our aim was therefore to explore whether inclusion of established thrombosis-associated single nucleotide polymorphisms (SNPs) in a venous thrombosis risk model improves the risk prediction. We calculated genetic risk scores by counting risk-increasing alleles from 31 venous thrombosis-associated SNPs for subjects of a large case-control study, including 2712 patients and 4634 controls (Multiple Environmental and Genetic Assessment). Genetic risk scores based on all 31 SNPs or on the 5 most strongly associated SNPs performed similarly (areas under receiver-operating characteristic curves [AUCs] of 0.70 and 0.69, respectively). For the 5-SNP risk score, the odds ratios for venous thrombosis ranged from 0.37 (95% confidence interval [CI], 0.25-0.53) for persons with 0 risk alleles to 7.48 (95% CI, 4.49-12.46) for persons with more than or equal to 6 risk alleles. The AUC of a risk model based on known nongenetic risk factors was 0.77 (95% CI, 0.76-0.78). Combining the nongenetic and genetic risk models improved the AUC to 0.82 (95% CI, 0.81-0.83), indicating good diagnostic accuracy. To become clinically useful, subgroups of high-risk persons must be identified in whom genetic profiling will also be cost-effective.
Global attractivity for fractional order delay partial integro-differential equations
Authors: Abbas Saïd , Baleanu Dumitru , Benchohra Mouffak 
Published: May 2012

Abstract
Our aim in this work is to study the existence and the attractivity of solutions for a system of delay partial integro-differential equations of fractional order. We use the Schauder fixed point theorem for the existence of solutions, and we prove that all solutions are locally asymptotically stable.

AMS (MOS) Subject Classifications: 26A33.
CytoITMprobe: a network information flow plugin for Cytoscape
Authors: Stojmirović Aleksandar , Bliskovsky Alexander , Yu Yi-Kuo 
Published: May 2012

Abstract

Background
Cytoscape is a well-developed flexible platform for visualization, integration and analysis of network data. Apart from the sophisticated graph layout and visualization routines, it hosts numerous user-developed plugins that significantly extend its core functionality. Earlier, we developed a network information flow framework and implemented it as a web application, called ITM Probe. Given a context consisting of one or more user-selected nodes, ITM Probe retrieves other network nodes most related to that context. It requires neither user restriction to subnetwork of interest nor additional and possibly noisy information. However, plugins for Cytoscape with these features do not yet exist. To provide the Cytoscape users the possibility of integrating ITM Probe into their workflows, we developed CytoITMprobe, a new Cytoscape plugin.

Findings

CytoITMprobe maintains all the desirable features of ITM Probe and adds additional flexibility not achievable through its web service version. It provides access to ITM Probe either through a web server or locally. The input, consisting of a Cytoscape network, together with the desired origins and/or destinations of information and a dissipation coefficient, is specified through a query form. The results are shown as a subnetwork of significant nodes and several summary tables. Users can control the composition and appearance of the subnetwork and interchange their ITM Probe results with other software tools through tab-delimited files.

Conclusions
The main strength of CytoITMprobe is its flexibility. It allows the user to specify as input any Cytoscape network, rather than being restricted to the pre-compiled protein-protein interaction networks available through the ITM Probe web service. Users may supply their own edge weights and directionalities. Consequently, as opposed to ITM Probe web service, CytoITMprobe can be applied to many other domains of network-based research beyond protein-networks. It also enables seamless integration of ITM Probe results with other Cytoscape plugins having complementary functionality for data analysis.
Updated Analysis of SWOG-Directed Intergroup Study 0116: A Phase III Trial of Adjuvant Radiochemotherapy Versus Observation After Curative Gastric Cancer Resection
Authors: Smalley Stephen R. , Benedetti Jacqueline K. , Haller Daniel G. , Hundahl Scott A. , Estes Norman C. , Ajani Jaffer A. , Gunderson Leonard L. , Goldman Bryan , Martenson James A. , Jessup J. Milburn , Stemmermann Grant N. , Blanke Charles D. , Macdonald John S. 
Published: May 2012

Purpose Surgical resection of gastric cancer has produced suboptimal survival despite multiple randomized trials that used postoperative chemotherapy or more aggressive surgical procedures. We performed a randomized phase III trial of postoperative radiochemotherapy in those at moderate risk of locoregional failure (LRF) following surgery. We originally reported results with 4-year median follow-up. This update, with a more than 10-year median follow-up, presents data on failure patterns and second malignancies and explores selected subset analyses. Patients and Methods In all, 559 patients with primaries ≥ T3 and/or node-positive gastric cancer were randomly assigned to observation versus radiochemotherapy after R0 resection. Fluorouracil and leucovorin were administered before, during, and after radiotherapy. Radiotherapy was given to all LRF sites to a dose of 45 Gy. Results Overall survival (OS) and relapse-free survival (RFS) data demonstrate continued strong benefit from postoperative radiochemotherapy. The hazard ratio (HR) for OS is 1.32 (95% CI, 1.10 to 1.60; P = .0046). The HR for RFS is 1.51 (95% CI, 1.25 to 1.83; P < .001). Adjuvant radiochemotherapy produced substantial reduction in both overall relapse and locoregional relapse. Second malignancies were observed in 21 patients with radiotherapy versus eight with observation (P = .21). Subset analyses show robust treatment benefit in most subsets, with the exception of patients with diffuse histology who exhibited minimal nonsignificant treatment effect. Conclusion Intergroup 0116 (INT-0116) demonstrates strong persistent benefit from adjuvant radiochemotherapy. Toxicities, including second malignancies, appear acceptable, given the magnitude of RFS and OS improvement. LRF reduction may account for the majority of overall relapse reduction. Adjuvant radiochemotherapy remains a rational standard therapy for curatively resected gastric cancer with primaries T3 or greater and/or positive nodes.
Human Epidermal Growth Factor Receptor 2 Status and Interval Breast Cancer in a Population-Based Cancer Registry Study
Authors: Musolino Antonino , Michiara Maria , Conti Giovanni Maria , Boggiani Daniela , Zatelli Marella , Palleschi Dario , Bella Maria Angela , Sgargi Paolo , Di Blasio Beatrice , Ardizzoni Andrea 
Published: May 2012

Purpose To determine whether human epidermal growth factor receptor 2 (HER2) –positive status is associated with risk of breast cancer diagnosis in the interval between mammographic screening, we estimated the distribution of features of aggressive tumor behavior in a general population with newly diagnosed breast cancer and known screening status. Patients and Methods We evaluated all invasive breast cancers (N = 641) that were systematically collected by the Parma Province Cancer Registry and diagnosed in women age 50 to 69 years from 2004 to 2007. From this population, 292 screen-detected cancers and 48 interval cases with negative screening mammograms on expert rereading (true interval cancers) were selected for study purposes. Unconditional logistic regression adjusted for age and tumor size was used to determine whether interval cancers were associated with selected clinicobiologic characteristics. Results Tumors with a high histologic grade (odds ratio [OR], 1.8; 95% CI, 1.2 to 3.8), high proliferative rate (OR, 2.4; 95% CI, 1.2 to 4.5), negative estrogen receptor status (OR, 1.6; 95% CI, 1.1 to 3.1), or HER2-positive status (OR, 3.4; 95% CI, 1.7 to 7.1) were more likely to be diagnosed in the interval between screening. Women age less than 60 years with HER2-positive breast cancer were four times more likely to be diagnosed in the interval between screening compared with only a two-fold increased risk for older women. Conclusion This population-based cancer registry study demonstrated that HER2-positive tumors account for a substantial proportion of mammographic screening failure. The distribution of biologic characteristics in screen-detected cancers differs from that observed in interval cancers and may account in part for the more aggressive behavior of interval-detected cases.
Strukturelle Entfremdung als Kategorie der Wirtschaftsethik
Authors: Henning Tim 
Published: May 2012

Abstract
This paper argues that a certain kind of alienation from labour can be analyzed and explained in the theoretical framework that is dominant in current economics. Given a neoclassical model of a labour market, the intrinsic value that different kinds of labour may have for people can be represented as a source of utility (in the technical sense). It can then be shown that in capitalist economies, basing one’s supply decisions on this intrinsic value is predictably costly. So in the long run, rational agents can be – and will be – expected to make their labour supply decisions based only on considerations of income and leisure time. In the resulting picture, rational agents are indifferent with regard to different qualitatively specific kinds of labour. I draw on the theory of efficiency wages to show that this picture lies at the root of contemporary problems such as involuntary unemployment and injustice.
Formatives Assessment in offenen, informellen, vernetzten Lernszenarien
Authors: Herding Daniel , Schroeder Ulrik , Stalljohann Patrick , Chatti Mohamed Amine 
Published: May 2012

Summary
While assessment with closed questions is supported by current Learning Management Systems, there are still shortcomings in formative feedback regarding open-ended tasks. Furthermore, new types of interaction and collaboration in online learning environments have emerged in the last years. This contribution discusses three research questions that have to be answered in order to embed the new forms of assessment in institutional education.
E-Learning an Hochschulen – Vom Projekt zum Prozessmanagement
Authors: Trahasch Stephan , Kandzia Paul-Thomas 
Published: May 2012

Summary
Since 20 years universities are establishing new departments for e-learning services. Nowadays the question is not “if“ anymore, but “how” to shape e-learning departments. We propose to change the focus from organizational structure to a more process oriented approach similar to the process management view on companies.