bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antineutrophil cytoplasmic antibody-positive conversion and microscopic polyangiitis development in patients with idiopathic pulmonary fibrosis
Authors: Kagiyama Naho , Takayanagi Noboru , Kanauchi Tetsu , Ishiguro Takashi , Yanagisawa Tsutomu , Sugita Yutaka 
Published: January 2015

BackgroundIncreasing evidence indicates that antineutrophil cytoplasmic antibody (ANCA)-positive conversion occurs in patients initially diagnosed with idiopathic pulmonary fibrosis (IPF) and as a result, some of these patients develop microscopic polyangiitis (MPA). However, the incidence density of these patients is not well known.ObjectivesTo explore the incidence of ANCA-positive conversion and development of MPA during the disease course in patients with IPF and to evaluate whether corticosteroid therapy reduces MPA development in patients with IPF with myeloperoxidase (MPO)-ANCA positivity at diagnosis or who later acquire MPO-ANCA positivity.MethodsWe retrospectively analysed the medical records of 504 Asian patients with IPF treated at our institution in Saitama, Japan.ResultsOf the 504 patients with IPF, 20 (4.0%) had MPO-ANCA and 16 (3.2%) had PR-3-ANCA when first evaluated. In 264 of 504 patients with IPF, ANCA was measured repeatedly and seroconversion to MPO-ANCA and PR3-ANCA occurred in 15 (5.7%) and 14 (5.3%) patients, respectively, and 9 of 35 patients who were either MPO-ANCA positive at IPF diagnosis or who subsequently seroconverted developed MPA. None of the nine patients who developed MPA had been previously treated with steroids. The incidence of MPA tended to be lower in patients treated than not treated with corticosteroids although this was not statistically significant.ConclusionsSome patients with IPF with MPO-ANCA positivity at IPF diagnosis or with MPO-ANCA-positive conversion during follow-up developed MPA. Clinical trials to determine whether corticosteroid therapy can reduce MPA development and prolong survival in MPO-ANCA-positive patients with IPF should be considered.
Health service use, out-of-pocket payments and catastrophic health expenditure among older people in India: The WHO Study on global AGEing and adult health (SAGE)
Authors: Brinda Ethel Mary , Kowal Paul , Attermann Jørn , Enemark Ulrika 
Published: January 2015

BackgroundHealthcare financing through out-of-pocket payments and inequities in healthcare utilisation are common in low and middle income countries (LMICs). Given the dearth of pertinent studies on these issues among older people in LMICs, we investigated the determinants of health service use, out-of-pocket and catastrophic health expenditures among older people in one LMIC, India.MethodsWe accessed data from a nationally representative, multistage sample of 2414 people aged 65 years and older from the WHO's Study on global Ageing and adult health in India. Sociodemographic characteristics, health profiles, health service utilisation and out-of-pocket health expenditure were assessed using standard instruments. Multivariate zero-inflated negative binomial regression models were used to evaluate the determinants of health service visits. Multivariate Heckman sample selection regression models were used to assess the determinants of out-of-pocket and catastrophic health expenditures.ResultsOut-of-pocket health expenditures were higher among participants with disability and lower income. Diabetes, hypertension, chronic pulmonary disease, heart disease and tuberculosis increased the number of health visits and out-of-pocket health expenditures. The prevalence of catastrophic health expenditure among older people in India was 7% (95% CI 6% to 8%). Older men and individuals with chronic diseases were at higher risk of catastrophic health expenditure, while access to health insurance lowered the risk.ConclusionsReducing out-of-pocket health expenditure among older people is an important public health issue, in which social as well as medical determinants should be prioritised. Enhanced public health sector performance and provision of publicly funded insurance may protect against catastrophic health expenses and healthcare inequities in India.
Performance characteristics of methods for quantifying spontaneous intracerebral haemorrhage: data from the Efficacy of Nitric Oxide in Stroke (ENOS) trial
Authors: Krishnan Kailash , Mukhtar Siti F , Lingard James , Houlton Aimee , Walker Elizabeth , Jones Tanya , Sprigg Nikola , Cala Lesley A , Becker Jennifer L , Dineen Robert A , Koumellis Panos , Adami Alessandro , Casado Ana M , Bath Philip M W , Wardlaw Joanna M 
Published: January 2015

BackgroundPoor prognosis after intracerebral haemorrhage (ICH) is related to haemorrhage characteristics. Along with developing therapeutic interventions, we sought to understand the performance of haemorrhage descriptors in large clinical trials.MethodsClinical and neuroimaging data were obtained for 548 participants with ICH from the Efficacy of Nitric Oxide in Stroke (ENOS) trial. Independent observers performed visual categorisation of the largest diameter, measured volume using ABC/2, modified ABC/2, semiautomated segmentation (SAS), fully automatic measurement methods; shape, density and intraventricular haemorrhage were also assessed. Intraobserver and interobserver reliability were determined for these measures.ResultsICH volume was significantly different among standard ABC/2, modified ABC/2 and SAS: (mean) 12.8 (SD 16.3), 8.9 (9.2), 12.8 (13.1) cm3, respectively (p<0.0001). There was excellent agreement for haemorrhage volume (n=193): ABC/2 intraobserver intraclass correlation coefficient (ICC) 0.96–0.97, interobserver ICC 0.88; modified ABC/2 intraobserver ICC 0.95–0.97, interobserver ICC 0.91; SAS intraobserver ICC 0.95–0.99, interobserver ICC 0.93; largest diameter: (visual) interadjudicator ICC 0.82, (visual vs measured) adjudicator vs observer ICC 0.71; shape intraobserver ICC 0.88 interobserver ICC 0.75; density intraobserver ICC 0.86, interobserver ICC 0.73. Graeb score (mean 3.53) and modified Graeb (5.22) scores were highly correlated. Using modified ABC/2, ICH volume was underestimated in regular (by 2.2-2.5 cm3, p<0.0001) and irregular-shaped haemorrhages (by 4.8-4.9 cm3, p<0.0001). Fully automated measurement of haemorrhage volume was possible in only 5% of cases.ConclusionsFormal measurement of haemorrhage characteristics and visual estimates are reproducible. The standard ABC/2 method is superior to the modified ABC/2 method for quantifying ICH volume.Clinical trial registrationISRCTN9941422.
Mitigating Prefetcher-Caused Pollution Using Informed Caching Policies for Prefetched Blocks
Authors: Seshadri Vivek , Yedkar Samihan , Xin Hongyi , Mutlu Onur , Gibbons Phillip B. , Kozuch Michael A. , Mowry Todd C. 
Published: January 2015

Many modern high-performance processors prefetch blocks into the on-chip cache. Prefetched blocks can potentially pollute the cache by evicting more useful blocks. In this work, we observe that both accurate and inaccurate prefetches lead to cache pollution, and propose a comprehensive mechanism to mitigate prefetcher-caused cache pollution.
First, we observe that over 95% of useful prefetches in a wide variety of applications are not reused after the first demand hit (in secondary caches). Based on this observation, our first mechanism simply demotes a prefetched block to the lowest priority on a demand hit. Second, to address pollution caused by inaccurate prefetches, we propose a self-tuning prefetch accuracy predictor to predict if a prefetch is accurate or inaccurate. Only predicted-accurate prefetches are inserted into the cache with a high priority.
Evaluations show that our final mechanism, which combines these two ideas, significantly improves performance compared to both the baseline LRU policy and two state-of-the-art approaches to mitigating prefetcher-caused cache pollution (up to 49%, and 6% on average for 157 two-core multiprogrammed workloads). The performance improvement is consistent across a wide variety of system configurations.
Heterogeneity of DNA Distribution Pattern in Renal Tumours
Authors: Nenning Hans , Raßler Jörg , Minh Do Hoan 
Published: January 2015

The presence of intratumoural heterogeneity in DNA distribution patterns has been accepted. However, most previous studies have not taken this fact into consideration. The value of DNA cytometry depends on its reproducibility. This could be influenced by heterogeneity failure. The aim of the present study is to evaluate intratumoural heterogeneity in renal cell cancer.A sample of 22 tumours of the kidney was investigated by means of static DNA cytometry: 21 tumours were carcinomas, one was an angiomyolipoma. Probes from seven different locations of each tumour were Feulgen‐stained and measured. The variability of DNA features was determined and correlated with histological grade and type and with tumour size.There was considerable intratumoural heterogeneity with respect to DNA distribution pattern in 45% of the tumours. Additional non‐diploid tumour‐stemlines and deviation of computed DNA features could be found in several cases by measuring more than one slide per tumour. A correlation between tumour heterogeneity, grading or typing, and tumour size could not be found.Because these DNA parameters could serve as the foundation of a risk‐adapted treatment, tumour heterogeneity could have clinical consequences. Based on the results of this study we suggest measuring at least three slides per tumour to avoid misinterpretation of DNA measurements in renal cell cancer.
Chromatin Texture from Hematoxylin Stained Thyroid Lesions
Authors: Ferrer-Roca Olga , Pérez Gómez José A. , Estévez Maritza 
Published: January 2015

Quantitative aspects of cytology and histology should be considered in diagnostic standardisation processes. The present paper summarises the cytological differences detected in 75 thyroid lesions using a computerized textural analysis.Cells stained with progressive hematoxylin and taken from paraffin blocks were overlaid with the extracted texture. This technique was based on the lineal detection of a grey level gradient of the common logarithm of the integrated optical density (IOD) of each nucleus.Diffuse and nodular goiters (36 cases) were demonstrated to be composed of small cells containing high density texture that, on microscopical visual inspection, gave a “salt and pepper” appearance. The adenomatous goiters (2 cases) and adenomas (26 cases) were composed of low texture cells with a visual “blurry or smudgy” chromatin, while the atypical adenomas with capsular invasion (4 cases) were characterised by a “woodworm” nuclear appearance that produced the highest texture of the series. Finally, encapsulated folliculo‐papillary carcinomas (3 cases) were composed of large clear nuclei with high IOD, low texture, and scattered lines that resulted in an “empty grape skin” aspect.Our findings seam to confirm the suitability of computerized textural techniques that aid in recognizing cell microscopic features objectively. The one used in the present work, based on a mathematical function of the DNA content of each individual nucleus (IOD), fulfills all microscopy detection criteria.
A Telepathology Based Virtual Reference and Certification Centre for DNA Image Cytometry
Authors: Haroske G. , Giroud Francoise , Kunze K. D. , Meyer W. 
Published: January 2015

An increasing need for flexible consultation between pathologists, including the application of fast evolving supplementary technologies, has been identified during the last years. Although pathology is already one of the most advanced application of telemedicine there is more to come from the fast evolution towards computerized microscope image analysis: A reproducible quantification of measurable descriptors of the lesions in cells and tissues (so‐called biological markers) is an indispensable adjunct to routine diagnostic application. Among such quantitative methods DNA image cytometry is increasingly applied by pathologists for assistance in diagnostics.As for other pathological issues, too, a reference center for the clinical application of DNA image cytometry might be therefore of utmost value for pathologists using that method.Based on advanced telematic technologies, a Virtual Reference and Certification Center (VRCC) could be installed for certifying the cytometry hardware and software, the analytical procedures, and the basic interpretation of the results. It will be designed to be operated as a non‐attended service, based on quantification servers accessible via Internet round the clock. The VRCC will supply appropriate standardization and normalization materials and run a GroupWare platform for consensus making by experts.
Analysis of Erythrocyte Glycophorin‐A Variants by Flow Cytometry in Lung Disease Patients Detects the Effect of Tobacco Smoke
Authors: Neri Monica , Geido Elio , Filiberti Rosangela , Orecchia Roberto , Di Vinci Angela , Cafferata Mara , Tassara Elisabetta , Puntoni Riccardo , Giaretti Walter 
Published: January 2015

The glycophoryn A (GPA) assay evaluates somatic in vivo mutations. It is considered a cumulative biodosimeter for genotoxic exposures and is under evaluation in cancer risk assessment.GPA, a polymorphic membrane protein of the erythrocytes, determines the MN blood groups. The N0 and NN variant frequencies (VF) may be detected in MN subjects (about 50% of the population) by flow cytometry using two differently labelled antibodies.We explored if GPA N0 and NN VF might be relevant to the assessment of individual lung cancer risk and susceptibility, in a small population with a high prevalence of heavy tobacco smokers: 8 lung cancer patients and 16 subjects with non‐malignant lung diseases associated with increased risk of lung cancer.There was a wide interindividual variability and complete overlap between non‐neoplastic and neoplastic patients. A significant positive correlation was seen with smoking duration in N0 VF (p=0.04, age‐adjusted). Current smokers (n=12) displayed higher N0 values than never (n=1) or ex‐smokers (n=11), 36.3±18.2 and 21.0±13.2, respectively (p < 0:01). No association was shown with occupational exposure.The present exploratory study suggests that assessment of individual lung cancer risk and susceptibility by the GPA assay does not seem to be feasible. The assay appears to provide a biomarker of longterm exposure to tobacco smoke.
How Could Static Telepathology Improve Diagnosis in Neuropathology?
Authors: Remmelinck Myriam , Lopes M. Beatriz S. , Nagy Nathalie , Rorive Sandrine , Rombaut Katja , Decaestecker Christine , Kiss Robert , Salmon Isabelle 
Published: January 2015

The present paper reports our experience with, and our opinion of static telepathology as applied to neuropathology by means of the PHAROS acquisition system and conventional telephone data transmission (modem). The classical procedure of expert consultation based on surface mailing of histological slides is routinely performed, especially in highly specialized fields of pathology. Telepathology is an easy means of sharing scientific expertise at international level and could thus improve diagnosis particularly in neuropathology, where certain tumor types are very rare and complex to diagnose. Dynamic telepathology allows the referring pathologist to capture by himself images supporting their diagnosis. Using static telepathology the pathologist could be limited in diagnosis by problems in fields selection.We devoted a whole year to collecting all the technical parameters characterizing the use of digitized neuropathological data files in order to investigate the feasibility of telepathology and the extent to which its use could improve diagnoses. Our results on a series of 38 histological brain examinations illustrate how we successfully established an international connection between two departments of pathology in Belgium and the USA. The referring pathologists gave diagnoses in 35 cases and deferred only 3. Despite a time‐consuming procedure for the telepathology session of a few cases, this tool provides easy access to expert diagnosis and real‐time discussion, both of which are of considerable interest and offer significant improvements in neuropathology.
Reliability of Telepathology for Frozen Section Service
Authors: Wellnitz Uwe , Binder Bernd , Fritz Peter , Friedel Godehard , Schwarzmann Peter 
Published: January 2015

One of the most promising applications of telepathology (pathology at a distance by electronic transmission of images in pathology) is frozen section diagnosis, especially because by means of this tool operations requiring an intraoperative histopathological diagnosis are feasible at hospitals without a pathologist on‐site. For the introduction of this diagnostic tool into pathologist′s daily practice the evidence of its diagnostic accuracy comparable to that of the conventional frozen section diagnosis is crucial.For this purpose the literature on the diagnostic accuracy of telepathological frozen section diagnosis was reviewed. In a metaanalysis these studies and reports, in which a total of more than 1290 cases had been examined, showed a slightly lower overall diagnostic accuracy (of the telepathological frozen section diagnosis) of about 0.91 than the conventional frozen section diagnosis with an average accuracy of about 0.98 found in an analysis of several studies (on frozen section diagnosis of different organs). This difference is at least predominantly caused by a higher rate of deferred and false negative frozen section diagnoses in the telepathological method, while the specificity of both methods, each more than 0.99 was not significantly different.In conclusion, the introduction of a telepathological frozen section diagnosis for hospitals without an acceptable access to a pathologist is justifiable already at the current state of the technological development especially when considering the advantages (time saving, reduction in costs) compared to the alternative of surgical interventions without access to an intraoperative diagnosis.
VHLGenetic Alteration in CCRCC Does Not Determine De-Regulation of HIF, CAIX, hnRNP A2/B1 and Osteopontin
Authors: Nyhan Michelle J. , El Mashad Shereen M. , O’Donovan Tracey R. , Ahmad Sarfraz , Collins Chris , Sweeney Paul , Rogers Eamonn , O’Sullivan Gerald C. , McKenna Sharon L. 
Published: January 2015

Background: von Hippel–Lindau (VHL) tumour suppressor gene inactivation is associated with clear cell renal cell carcinoma (CCRCC) development. The VHL protein (pVHL) has been proposed to regulate the expression of several proteins including Hypoxia Inducible Factor-α (HIF-α), carbonic anhydrase (CA)IX, heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 and osteopontin. pVHL has been characterized in vitro, however, clinical studies are limited. We evaluated the impact of VHL genetic alterations on the expression of several pVHL protein targets in paired normal and tumor tissue.Methods: TheVHLgene was sequenced in 23 CCRCC patients andVHLtranscript levels were evaluated by real-time RT-PCR. Expression of pVHL’s protein targets were determined by Western blotting in 17 paired patient samples.Results: VHL genetic alterations were identified in 43.5% (10/23) of CCRCCs. HIF-1α, HIF-2α and CAIX were up-regulated in 88.2% (15/17), 100% (17/17) and 88.2% (15/17) of tumors respectively and their expression is independent ofVHLstatus. hnRNP A2/B1 and osteopontin expression was variable in CCRCCs and had no association withVHLgenetic status.Conclusion: As expression of these proposed pVHL targets can be achieved independently ofVHLmutation (and possibly by hypoxia alone), these data suggests that other pVHL targets may be more crucial in renal carcinogenesis.
Activating Mutation (V617F) in the Tyrosine Kinase JAK2 is Absent in Locally-Confined or Castration-Resistant Prostate Cancer
Authors: Gu Lei , Zhu Xian-Hua , Visakorpi Tapio , Alanen Kalle , Mirtti Tuomas , Edmonston Tina Bocker , Nevalainen Marja T. 
Published: January 2015

Background: Transcription factor Stat5a/b is highly critical for the viability of human prostate cancer cells in vitro and for prostate tumor growthin vivo. Stat5 is constitutively active in clinical prostate cancers but not in the normal human prostate epithelium. Moreover, Stat5a/b activation in prostate cancer is associated with high histological grade of prostate cancer. However, the molecular mechanisms underlying constitutive activation of Stat5a/b in prostate cancer are unclear. The receptor-associated tyrosine kinase Jak2 is a known key activator of Stat5a/b in prostate cancer cells in response to ligand stimulation. Recently, a single gain-of-function point mutation ofJAK2was described in myeloproliferative diseases leading to constitutive Jak2 kinase activity, subsequent Stat5a/b activation and involvement of V617F Jak2 in the pathogenesis of myeloproliferative disorders.Materials and Methods: We determined whetherJAK2undergoes the V617F activating mutation during clinical progression of human prostate cancer using a highly sensitive assay (amplification refractory mutation system) and a unique material of fresh specimens from organ-confined or castration-resistant prostate cancers.Results: TheJAK2V617F mutation was not found in any of the normal or malignant prostate samples analyzed in this study.Conclusions: Future work should focus on determining the molecular mechanisms other than V617F mutation of Jak2 resulting in continuous Stat5 activation in clinical prostate cancers.
Ultra-Fast Processing of Gigapixel Tissue MicroArray Images Using High Performance Computing
Authors: Wang Yinhai , McCleary David , Wang Ching-Wei , Kelly Paul , James Jackie , Fennell Dean A. , Hamilton Peter 
Published: January 2015

Background: Tissue MicroArrays (TMAs) are a valuable platform for tissue based translational research and the discovery of tissue biomarkers. The digitised TMA slides or TMA Virtual Slides, are ultra-large digital images, and can contain several hundred samples. The processing of such slides is time-consuming, bottlenecking a potentially high throughput platform.Methods: A High Performance Computing (HPC) platform for the rapid analysis of TMA virtual slides is presented in this study. Using an HP high performance cluster and a centralised dynamic load balancing approach, the simultaneous analysis of multiple tissue-cores were established. This was evaluated on Non-Small Cell Lung Cancer TMAs for complex analysis of tissue pattern and immunohistochemical positivity.Results: The automated processing of a single TMA virtual slide containing 230 patient samples can be significantly speeded up by a factor of circa 22, bringing the analysis time to one minute. Over 90 TMAs could also be analysed simultaneously, speeding up multiplex biomarker experiments enormously.Conclusion: The methodologies developed in this paper provide for the first time a genuine high throughput analysis platform for TMA biomarker discovery that will significantly enhance the reliability and speed for biomarker research. This will have widespread implications in translational tissue based research.