bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Evaluation of Blood and Serum Samples in Rapid Immunochromatographic Tests for Visceral Leishmaniasis
Authors: Kumar Dinesh , Khanal Basudha , Tiwary Puja , Mudavath Shyam Lal , Tiwary Narendra K. , Singh Rupa , Koirala Kanika , Boelaert Marleen , Rijal Suman , Sundar Shyam 
Published: September 2013

ABSTRACT

Rapid diagnostic tests (RDTs) based on the detection of specific antibodies in serum are commonly used for the diagnosis of visceral leishmaniasis (VL). Several commercial kits are available, and some of them allow the use of whole-blood samples instead of serum. An RDT is much more user-friendly for blood samples than for serum samples. In this study, we examined the sensitivities and specificities of six different commercially available immunochromatographic tests for their accuracy in detecting
Leishmania
infection in whole blood and serum of parasitologically confirmed VL cases. This study was performed in areas of India and Nepal where VL is endemic. A total of 177 confirmed VL cases, 208 healthy controls from areas of endemicity (EHCs), 26 malaria patients (MP), and 37 tuberculosis (TB) patients were enrolled. The reproducibilities of the blood and serum results and between-reader and between-laboratory results were tested. In India, the sensitivities of all the RDTs ranged between 94.7 and 100.0%, with no significant differences between whole blood and serum. The specificities ranged between 92.4 and 100.0%, except for the specificity of the Onsite
Leishmania
Ab RevB kit, which was lower (33.6 to 42.0%). No differences in specificities were observed for blood and serum. In Nepal, the sensitivities of all the test kits, for whole-blood as well as serum samples, ranged between 96.3 and 100.0%, and the specificities ranged between 90.1 and 96.1%, again with the exception of that of the Onsite
Leishmania
Ab RevB test, which was markedly lower (48.7 to 49.3%). The diagnostic accuracies of all the tests, except for one brand, were excellent for the whole-blood and serum samples. We conclude that whole blood is an adequate alternative for serum in RDTs for VL, with sensitivities and specificities comparable to those obtained in serum samples, provided that the test kit is of overall good quality.
BK Polyomavirus Subtype III in a Pediatric Renal Transplant Patient with Nephropathy
Authors: Kapusinszky Beatrix , Chen Sharon F. , Sahoo Malaya K. , Lefterova Martina I. , Kjelson Lynn , Grimm Paul C. , Kambham Neeraja , Concepcion Waldo , Pinsky Benjamin A. 
Published: September 2013

ABSTRACT
BK polyomavirus (BKV) is an emerging pathogen in immunocompromised individuals. BKV subtype III is rarely identified and has not previously been associated with disease. Here we provide the whole-genome sequence of a subtype III BKV from a pediatric kidney transplant patient with polyomavirus-associated nephropathy.
PC61 (Anti-CD25) Treatment Inhibits Influenza A Virus-Expanded Regulatory T Cells and Severe Lung Pathology during a Subsequent Heterologous Lymphocytic Choriomeningitis Virus Infection
Authors: Kraft Anke R. M. , Wlodarczyk Myriam F. , Kenney Laurie L. , Selin Liisa K. 
Published: September 2013

ABSTRACTPrior immunity to influenza A virus (IAV) in mice changes the outcome to a subsequent lymphocytic choriomeningitis virus (LCMV) infection and can result in severe lung pathology, similar to that observed in patients that died of the 1918 H1N1 pandemic. This pathology is induced by IAV-specific memory CD8+T cells cross-reactive with LCMV. Here, we discovered that IAV-immune mice have enhanced CD4+Foxp3+T-regulatory (Treg) cells in their lungs, leading us to question whether a modulation in the normal balance of Treg and effector T-cell responses also contributes to enhancing lung pathology upon LCMV infection of IAV-immune mice. Treg cell and interleukin-10 (IL-10) levels remained elevated in the lungs and mediastinal lymph nodes (mLNs) throughout the acute LCMV response of IAV-immune mice. PC61 treatment, used to decrease Treg cell levels, did not change LCMV titers but resulted in a surprising decrease in lung pathology upon LCMV infection in IAV-immune but not in naive mice. Associated with this decrease in pathology was a retention of Treg in the mLN and an unexpected partial clonal exhaustion of LCMV-specific CD8+T-cell responses only in IAV-immune mice. PC61 treatment did not affect cross-reactive memory CD8+T-cell proliferation. These results suggest that in the absence of IAV-expanded Treg cells and in the presence of cross-reactive memory, the LCMV-specific response was overstimulated and became partially exhausted, resulting in a decreased effector response. These studies suggest that Treg cells generated during past infections can influence the characteristics of effector T-cell responses and immunopathology during subsequent heterologous infections. Thus, in humans with complex infection histories, PC61 treatment may lead to unexpected results.
Predicting the likelihood of additional lymph node metastasis in sentinel lymph node positive breast cancer: validation of the Memorial Sloan-Kettering Cancer Centre (MSKCC) nomogram
Authors: Chue Koy Min , Yong Wei Sean , Thike Aye Aye , Ahmed Syed Salahuddin , Li Hui Hua , Wong Chow Yin , Ho Gay Hui , Madhukumar Preetha , Tan Benita Kiat Tee , Ong Kong Wee , Tan Puay Hoon 
Published: September 2013

AimTo identify important clinicopathological parameters that are most helpful in predicting additional non-sentinel lymph node (SLN) metastasis among patients with a positive SLN biopsy in the Singapore breast cancer population.MethodsA total of 1409 patients who underwent SLN biopsy were reviewed over a 5 year period from July 2004 to October 2009. A Singapore General Hospital (SGH) nomogram was developed from predictors in the Memorial Sloan-Kettering Cancer Centre (MSKCC) nomogram using 266 patients with primary invasive breast cancer and a positive SLN biopsy who subsequently had an axillary lymph node dissection. The SGH nomogram was calibrated using bootstrapped data, while the MSKCC nomogram was calibrated using SGH data. The performance of these two nomograms was compared with the calculation of the area under the receiver–operator characteristics curve and adequacy indices.ResultsThe MSKCC nomogram achieved an area under the curve (AUC) of 0.716 (range 0.653–0.779) in our study population, while the SGH nomogram, which used only three pathological parameters, lymphovascular invasion, number of positive and negative SLN biopsies, achieved an AUC of 0.750 (range 0.691–0.808). The SGH nomogram with a higher adequacy index (0.969) provided better estimates compared with the MSKCC nomogram (0.689).ConclusionsThe use of the MSKCC nomogram was validated in our local patient population. The SGH nomogram showed promise to be equally, if not, more predictive as a model in our own population, while using only three pathological parameters.
Republished: Instigating change: trainee doctors' perspective
Authors: Parvizi Nassim , Shahaney Sumera , Martin Guy , Ahmad Ahmir , Moghul Masood 
Published: September 2013

Abstract
In the 21st century, the core skills of trainee doctors are evolving as clinicians, leaders and innovators. Leadership skills are an essential tool for all doctors and need to be an integral part of their training and learning as set out in the General Medical Council's Good Medical Practice. It is essential to develop these skills at an early stage and continually improve them. A group of junior doctors participated in a pilot programme for leadership with the aim of executing a quality improvement (QI) project. This article describes our experiences of both the course itself and the project undertaken by our group. As part of the process of implementing change, we faced a number of challenges which contributed to our learning. These have been explored as well as potential ways to overcome them to enable the swift and smooth development of future QI projects. Using an example of a QI project looking at handover, this article demonstrates how a trainee doctor can implement their project for both professional and institutional improvement.
Validation of a Proliferation-Based Expression Signature as Prognostic Marker in Early Stage Lung Adenocarcinoma
Authors: Wistuba Ignacio I. , Behrens Carmen , Lombardi Francesca , Wagner Susanne , Fujimoto Junya , Raso M. Gabriela , Spaggiari Lorenzo , Galetta Domenico , Riley Robyn , Hughes Elisha , Reid Julia , Sangale Zaina , Swisher Steven G. , Kalhor Neda , Moran Cesar A. , Gutin Alexander , Lanchbury Jerry S. , Barberis Massimo , Kim Edward S. 
Published: September 2013

Abstract
Purpose: New prognostic markers to guide treatment decisions in early stage non–small cell lung cancer are necessary to improve patient outcomes. In this report, we assess the utility of a predefined mRNA expression signature of cell-cycle progression genes (CCP score) to define 5-year risk of lung cancer–related death in patients with early stage lung adenocarcinoma.
Experimental Design: A CCP score was calculated from the mRNA expression levels of 31 proliferation genes in stage I and stage II tumor samples from two public microarray datasets [Director's Consortium (DC) and GSE31210]. The same gene set was tested by quantitative PCR in 381 formalin-fixed paraffin-embedded (FFPE) primary tumors. Association of the CCP score with outcome was assessed by Cox proportional hazards analysis.
Results: In univariate analysis, the CCP score was a strong predictor of cancer-specific survival in both the Director's Consortium cohort (P = 0.00014; HR = 2.08; 95% CI, 1.43–3.02) and GSE31210 (P = 0.0010; HR = 2.25; 95% CI, 1.42–3.56). In multivariate analysis, the CCP score remained the dominant prognostic marker in the presence of clinical variables (P = 0.0022; HR = 2.02; 95% CI, 1.29–3.17 in Director's Consortium, P = 0.0026; HR = 2.16; 95% CI, 1.32–3.53 in GSE31210). On a quantitative PCR platform, the CCP score maintained highly significant prognostic value in FFPE-derived mRNA from clinical samples in both univariate (P = 0.00033; HR = 2.10; 95% CI, 1.39–3.17) and multivariate analyses (P = 0.0071; HR = 1.92; 95% CI, 1.18–3.10).
Conclusions: The CCP score is a significant predictor of lung cancer death in early stage lung adenocarcinoma treated with surgery and may be a valuable tool in selecting patients for adjuvant treatment. Clin Cancer Res; 19(22); 6261–71. ©2013 AACR.
Partial deletion of the αC-domain in the Fibrinogen Perth variant is associated with thrombosis, increased clot strength and delayed fibrinolysis
Authors: Duval Cédric , Philippou Helen , Brown Rebecca , Lee Kurtis R. , Murden Sherina L. , Phillips Emma , Reilly-Stitt Christopher , Whalley Daniel , Ariëns Robert A. , Mumford Andrew D. , Westbury Sarah K. 
Published: September 2013

SummaryGenetic fibrinogen (FGN) variants that are associated with bleeding or thrombosis may be informative about fibrin polymerisation, structure and fibrinolysis. We report a four generation family with thrombosis and heritable dysfibrinogenaemia segregating with a c.[1541delC];[=] variation in FGA (FGN-Perth). This deletion predicts a truncated FGN αC-domain with an unpaired terminal Cys at residue 517 of FGN-Aα. In keeping with this, SDS-PAGE of purified FGN-Perth identified a truncated FGN-Aα chain with increased co-purification of albumin, consistent with disulphide bonding to the terminal Cys of the variant FGN-Aα. Clot visco-elastic strength in whole blood containing FGN-Perth was greater than controls and tPA-mediated fibrinolysis was delayed. In FGN-Perth plasma and in purified FGN-Perth, there was markedly reduced final turbidity after thrombin-mediated clot generation. Consistent with this, FGN-Perth formed tighter, thinner fibrin fibres than controls indicating defective lateral aggregation of protofibrils. Clots generated with thrombin in FGN-Perth plasma were resistant to tPA-mediated fibrinolysis. FGN-Perth clot also displayed impaired tPA-mediated plasmin generation but incorporated α2-anti-plasmin at a similar rate to control. Impaired fibrinolysis because of defective plasmin generation potentially explains the FGN-Perth clinical phenotype. These findings highlight the importance of the FGN αC-domain in the regulation of clot formation and fibrinolysis.
Interplay of Electrical Wavefronts as Determinant of the Response to Cardiac Resynchronization Therapy in Dyssynchronous Canine Hearts
Authors: Strik Marc , van Middendorp Lars B. , Houthuizen Patrick , Ploux Sylvain , van Hunnik Arne , Kuiper Marion , Auricchio Angelo , Prinzen Frits W. 
Published: September 2013

Background—
The relative contribution of electromechanical synchronization and ventricular filling to the optimal hemodynamic effect in cardiac resynchronization therapy (CRT) during adjustment of stimulation-timings is incompletely understood. We investigated whether optimal hemodynamic effect in CRT requires collision of pacing-induced and intrinsic activation waves and optimal filling of the left ventricle (LV).

Methods and Results—

CRT was performed in dogs with chronic left bundle–branch block (n=8) or atrioventricular (AV) block (n=6) through atrial (A), right ventricular (RV) apex, and LV-basolateral pacing. A 100 randomized combinations of A-LV/A-RV intervals were tested. Total activation time (TAT) was calculated from >100 contact mapping electrodes. Mechanical interventricular dyssynchrony was determined as the time delay between upslopes of LV and RV pressure curves. Settings providing an increase in LVdP/dt
max
(maximal rate of rise of left ventricular pressure) of ≥90% of the maximum LVdP/dt
max
value were defined as optimal (CRT
opt
). Filling was assessed by changes in LV end-diastolic volume (EDV; conductance catheter technique). In all hearts, CRT
opt
was observed during multiple settings, providing an average LVdP/dt
max
increase of ≈15%. In AV-block hearts, CRT
opt
exclusively depended on interventricular-interval and not on AV-interval. In left bundle–branch block hearts, CRT
opt
occurred at A-LV intervals that allowed fusion of LV-pacing–derived activation with right bundle–derived activation. In all animals, CRT
opt
occurred at settings resulting in the largest decrease in TAT and mechanical interventricular dyssynchrony, whereas LV EDV hardly changed.

Conclusions—
In left bundle–branch block and AV-block hearts, optimal hemodynamic effect of CRT depends on optimal interplay between pacing-induced and intrinsic activation waves and the corresponding mechanical resynchronization rather than filling.
Characterization and Space–Time Downscaling of the Inundation Extent over the Inner Niger Delta Using GIEMS and MODIS Data
Authors: Aires Filipe , Papa Fabrice , Prigent Catherine , Crétaux Jean-François , Berge-Nguyen Muriel 
Published: September 2013

Abstract
The objective in this work is to develop downscaling methodologies to obtain a long time record of inundation extent at high spatial resolution based on the existing low spatial resolution results of the Global Inundation Extent from Multi-Satellites (GIEMS) dataset. In semiarid regions, high-spatial-resolution a priori information can be provided by visible and infrared observations from the Moderate Resolution Imaging Spectroradiometer (MODIS). The study concentrates on the Inner Niger Delta where MODIS-derived inundation extent has been estimated at a 500-m resolution. The space–time variability is first analyzed using a principal component analysis (PCA). This is particularly effective to understand the inundation variability, interpolate in time, or fill in missing values. Two innovative methods are developed (linear regression and matrix inversion) both based on the PCA representation. These GIEMS downscaling techniques have been calibrated using the 500-m MODIS data. The downscaled fields show the expected space–time behaviors from MODIS. A 20-yr dataset of the inundation extent at 500 m is derived from this analysis for the Inner Niger Delta. The methods are very general and may be applied to many basins and to other variables than inundation, provided enough a priori high-spatial-resolution information is available. The derived high-spatial-resolution dataset will be used in the framework of the Surface Water Ocean Topography (SWOT) mission to develop and test the instrument simulator as well as to select the calibration validation sites (with high space–time inundation variability). In addition, once SWOT observations are available, the downscaled methodology will be calibrated on them in order to downscale the GIEMS datasets and to extend the SWOT benefits back in time to 1993.
Comparing Evaporative Sources of Terrestrial Precipitation and Their Extremes in MERRA Using Relative Entropy
Authors: Dirmeyer Paul A. , Wei Jiangfeng , Bosilovich Michael G. , Mocko David M. 
Published: September 2013

Abstract
A quasi-isentropic, back-trajectory scheme is applied to output from the Modern-Era Retrospective Analysis for Research and Applications (MERRA) and a land-only replay with corrected precipitation to estimate surface evaporative sources of moisture supplying precipitation over every ice-free land location for the period 1979–2005. The evaporative source patterns for any location and time period are effectively two-dimensional probability distributions. As such, the evaporative sources for extreme situations like droughts or wet intervals can be compared to the corresponding climatological distributions using the method of relative entropy. Significant differences are found to be common and widespread for droughts, but not wet periods, when monthly data are examined. At pentad temporal resolution, which is more able to isolate floods and situations of atmospheric rivers, values of relative entropy over North America are typically 50%–400% larger than at monthly time scales. Significant differences suggest that moisture transport may be a key factor in precipitation extremes. Where evaporative sources do not change significantly, it implies other local causes may underlie the extreme events.
An interesting case of new-onset ketosis-prone diabetes in a Scottish teaching hospital
Authors: Gardiner Ann , George Priya S , Pearson Ewan , McCrimmon Rory J 
Published: September 2013

Background: Clinical teaching for many years has been to assume that diabetic ketoacidosis is pathognomic of type 1 diabetes. However, this dogma is now increasingly questioned as increasing numbers of people are admitted with diabetic ketoacidosis without the typical features of autoimmune type 1 diabetes. Such individuals are increasingly diagnosed with ketosis-prone diabetes, a heterogenous syndrome where individuals present with diabetic ketoacidosis or unprovoked ketosis but are usually autoantibody negative and have no residual β-cell function. Classification of ketosis-prone diabetes using the Aβ system can aid in diagnosis and treatment decisions. Case report: An Afro-Caribbean male presented with hyperglycaemic ketosis. Initially diagnosed with type 1 diabetes and treated with a basal-bolus regimen, he was able to stop insulin completely within one month of presentation following rapid improvements in glycaemic control and repeated hypoglycaemia. Clinical investigation revealed he was negative for β-cell autoantibodies and had a stimulated C-peptide of >0.5 pmol/ml, suggesting preserved β-cell function. A diagnosis of ketosis-prone diabetes (A-β+) was made. Discussion: A high index of suspicion for ketosis-prone diabetes should arise when someone presents with diabetic ketoacidosis, who is obese, middle-aged, male and with a strong family history of type 2 diabetes and from a Black or Hispanic population. There is currently limited evidence on the pathophysiology of this transient β-cell defect, with suggestions that it may be related to glucotoxicity.
Extension of theCaenorhabditis elegansPharyngeal M1 Neuron Axon Is Regulated by Multiple Mechanisms
Authors: Refai Osama , Rohs Patricia , Mains Paul E , Gaudet Jeb 
Published: September 2013

AbstractThe guidance of axons to their correct targets is a critical step in development. The C. elegans pharynx presents an attractive system to study neuronal pathfinding in the context of a developing organ. The worm pharynx contains relatively few cells and cell types, but each cell has a known lineage and stereotyped developmental patterns. We found that extension of the M1 pharyngeal axon, which spans the entire length of the pharynx, occurs in two distinct phases. The first proximal phase does not require genes that function in axon extension (unc-34, unc-51, unc-115, and unc-119), whereas the second distal phase does use these genes and is guided in part by the adjacent g1P gland cell projection. unc-34, unc-51, and unc-115 had incompletely penetrant defects and appeared to act in conjunction with the g1P cell for distal outgrowth. Only unc-119 showed fully penetrant defects for the distal phase. Mutations affecting classical neuronal guidance cues (Netrin, Semaphorin, Slit/Robo, Ephrin) or adhesion molecules (cadherin, IgCAM) had, at best, weak effects on the M1 axon. None of the mutations we tested affected the proximal phase of M1 elongation. In a forward genetic screen, we isolated nine mutations in five genes, three of which are novel, showing defects in M1, including axon overextension, truncation, or ectopic branching. One of these mutations appeared to affect the generation or differentiation of the M1 neuron. We conclude that M1 axon extension is a robust process that is not completely dependent on any single guidance mechanism.
A critical look at the Wallace-Bott hypothesis in fault-slip analysis
Authors: Lisle Richard J. 
Published: September 2013

AbstractThe assumption is widely made that slip on faults occurs in the direction of maximum resolved shear stress, an assumption known as the Wallace-Bott hypothesis. This assumption is used to theoretically predict slip directions from known in situ stresses, and also as the basis of palaeostress inversion from fault-slip data. This paper examines different situations in relation to the appropriateness of this assumption. Firstly, it is shown that the magnitude of the shear stress resolved within a plane is a function with a poorly defined maximum direction, so that shear stress values greater than 90% of the maximum occur within a wide angular range (± 26°) degrees. The situation of simultaneous movement on pairs of faults requires slip on each fault to be parallel to their mutual line of intersection. However, the resolved shear stresses arising from a homogeneous state of stress do not accord with such a slip arrangement except in the case of pairs of perpendicular faults. Where fault surfaces are non-planar, the directions of resolved shear stress in general give, according to the Wallace-Bott hypothesis, a set of slip directions of rigid fault blocks, which is generally kinematically incompatible. Finally, a simple model of a corrugated fault suggests that any anisotropy of the shear strength of the fault such as that arising from fault surface topography, can lead to a significant angular difference between the directions of maximum shear stress and the slip direction.These findings have relevance to the design of procedures used to estimate palaeostresses and the amount of data required for this type of analysis.