bluuebunny/crossref_metadata_2025_split huggingface dataset:
N-terminal pro-B-type Natriuretic Peptides’ Prognostic Utility Is Overestimated in Meta-analyses Using Study-specific Optimal Diagnostic Thresholds
Authors: Potgieter Danielle , Simmers Dale , Ryan Lisa , Biccard Bruce M. , Lurati-Buse Giovanna A. , Cardinale Daniela M. , Chong Carol P. W. , Cnotliwy Miloslaw , Farzi Sylvia I. , Jankovic Radmilo J. , Lim Wen Kwang , Mahla Elisabeth , Manikandan Ramaswamy , Oscarsson Anna , Phy Michael P. , Rajagopalan Sriram , Van Gaal William J. , Waliszek Marek , Rodseth Reitze N. 
Published: June 2015

AbstractAbstract
Meta-analysis of studies that made use of a study-specific optimal N-terminal fragment B-type natriuretic peptide threshold resulted in a larger risk point estimate for the prediction of the composite outcome of postoperative mortality and nonfatal myocardial infarction at 30 days after noncardiac surgery compared with using a single threshold across all studies. These data suggest that future biomarker studies should be evaluated as continuous variables rather than making use of post hoc study-specific optimal thresholds, and care should be taken when conducting meta-analysis on studies that have used study-specific optimal thresholds to evaluate biomarker prognostic ability, as it is likely that this methodology will overestimate biomarker predictive performance.

Background:

N-terminal fragment B-type natriuretic peptide (NT-proBNP) prognostic utility is commonly determined post hoc by identifying a single optimal discrimination threshold tailored to the individual study population. The authors aimed to determine how using these study-specific post hoc thresholds impacts meta-analysis results.

Methods:
The authors conducted a systematic review of studies reporting the ability of preoperative NT-proBNP measurements to predict the composite outcome of all-cause mortality and nonfatal myocardial infarction at 30 days after noncardiac surgery. Individual patient-level data NT-proBNP thresholds were determined using two different methodologies. First, a single combined NT-proBNP threshold was determined for the entire cohort of patients, and a meta-analysis conducted using this single threshold. Second, study-specific thresholds were determined for each individual study, with meta-analysis being conducted using these study-specific thresholds.

Results:
The authors obtained individual patient data from 14 studies (n = 2,196). Using a single NT-proBNP cohort threshold, the odds ratio (OR) associated with an increased NT-proBNP measurement was 3.43 (95% CI, 2.08 to 5.64). Using individual study-specific thresholds, the OR associated with an increased NT-proBNP measurement was 6.45 (95% CI, 3.98 to 10.46). In smaller studies (<100 patients) a single cohort threshold was associated with an OR of 5.4 (95% CI, 2.27 to 12.84) as compared with an OR of 14.38 (95% CI, 6.08 to 34.01) for study-specific thresholds.

Conclusions:

Post hoc identification of study-specific prognostic biomarker thresholds artificially maximizes biomarker predictive power, resulting in an amplification or overestimation during meta-analysis of these results. This effect is accentuated in small studies.
Hip Reconstruction in Children With Unilateral Cerebral Palsy and Hip Dysplasia
Authors: Abousamra Oussama , Er Mehmet S. , Rogers Kenneth J. , Nishnianidze Tristan , Dabney Kirk W. , Miller Freeman 
Published: June 2015

Background:
Highly functioning children with unilateral cerebral palsy (CP) who have hip involvement (type IV hemiplegia) may present with hip dysplasia during their adolescence. The aim of this report is to assess the outcomes of combined femoral and acetabular reconstruction in this population.

Methods:
This study is a retrospective review of all patients with unilateral CP, Gross Motor Function Classification System types I and II, who had hip reconstruction for unilateral dysplasia between 1989 and 2013. Clinical variables (pain and hip passive range of motion) were reviewed. Hip morphology was assessed radiographically according to Melbourne Cerebral Palsy Hip Classification System. Three-dimensional gait analyses were also reviewed to evaluate the effect of surgery on these patients’ gaits.

Results:
Twelve patients were included with a mean age at surgery of 14 years (range, 7 to 19 y) and follow-up mean of 4 years (range, 1 to 8 y). Nine hips were improved according to Melbourne Cerebral Palsy Hip Classification System. Migration percentage decreased significantly (P<0.001) from 45% (30% to 86%) to 15% (0% to 28%). Neck shaft angle decreased (P<0.001) from 144 degrees (range, 129 to 156 degrees) to 125 degrees (range, 114 to 139 degrees). Tonnis angle and Sharp angle also decreased significantly. All patients were pain free at the last visit. Overall level of gait function as measured by Gait Deviation Index and Gait Profile Score [78 (61 to 89) and 12 (8 to 16), respectively] for all patients was maintained without significant changes.

Conclusions:
In hemiplegic type IV CP, with high functional level (Gross Motor Function Classification System I and II), hip dysplasia is a rare occurrence during adolescent years. Combined hip reconstruction improves hip morphology, relieves pain, and maintains a high level of function.

Level of Evidence:
Level IV—therapeutic study.
Association Analysis of SLC6A20 Polymorphisms With Hirschsprung Disease
Authors: Lee Jin Sol , Oh Jung‐Tak , Kim Jeong‐Hyun , Seo Jeong‐Meen , Kim Dae‐Yeon , Park Kwi‐Won , Kim Hyun‐Young , Jung Kyuwhan , Park Byung Lae , Koh InSong , Shin Hyoung Doo 
Published: June 2015

ABSTRACTPurpose:Hirschsprung disease (HSCR) is a congenital and heterogeneous disorder, which is caused by no neuronal ganglion cells in part or all of distal gastrointestinal tract. Recently, our genome‐wide association study has identified solute carrier family 6, proline IMINO transporter, member 20 (SLC6A20) as one of the potential risk factors for HSCR development. This study performed a replication study for the association of SLC6A20 polymorphisms with HSCR and an extended analysis to investigate further associations for subgroups and haplotypes.Methods:For the replication study, a total of 40 single nucleotide polymorphisms (SNPs) of SLC6A20 were genotyped in 187 HSCR subjects composed of 121 short‐segment HSCR, 45 long‐segment HSCR (L‐HSCR), 21 total colonic aganglionosis, and 283 unaffected controls. Imputation was performed using genotype data from our genome‐wide association study and this replication study.Results:Imputed meta‐analysis revealed that 13 SLC6A20 SNPs (minimum P = 0.0002 at rs6770261) were significantly associated with HSCR even after correction for multiple comparisons using false discovery rate (FDR) (minimum PFDR = 0.005). In further subgroup analysis, SLC6A20 polymorphisms appeared to have increased associations with L‐HSCR. Moreover, haplotype analysis also showed significant associations between 2 haplotypes (BL3_ht2 and BL4_ht2) and HSCR susceptibility (PFDR < 0.05).Conclusions:Although further replications and functional evaluations are required, our results suggest that SLC6A20 may have roles in HSCR development and in the extent of aganglionic segment during enteric nervous system development.
Demographic superiority with increased logging in tropical understorey insectivorous birds
Authors: Srinivasan Umesh , Hines James E. , Quader Suhel 
Published: June 2015

Summary

Selective logging is pervasive in the tropics and is among the most urgent threats to tropical biodiversity. The vast areas of logged tropical forest are often vulnerable to relogging, clear‐felling, burning or conversion to plantations, despite evidence that logged forests retain a large proportion of tropical forest species at high abundances compared with alternate land uses. However, the demographic processes (e.g. survival, fecundity) that drive community or species properties (e.g. occurrence, density) in response to logging have never been examined.

We used a novel capture–recapture‐based sampling design to separate in situ reproduction from immigration‐fuelled recruitment to investigate the demographic vital rates of six forest‐dependent understorey insectivorous bird species along a logging continuum in the Eastern Himalaya Global Biodiversity Hotspot. We expected a positive relationship between forest intactness and reproductive rates, and that intact patches would contribute ‘excess’ individuals to logged patches from natal dispersal.

Contrary to our expectations, we found: (i) a positive relationship between logging intensity and reproduction, and (ii) evidence of natal dispersal from more logged to less logged and intact forest patches. Our results indicate that for certain forest‐dependent species in particular contexts, selectively logged habitats can have surprising and hitherto unrecognized demographic value that might be superior even to primary forest.

Synthesis and applications. In most tropical settings, logged forests can not only support a greater subset of forest biodiversity than other forms of land use (for instance, agriculture), but can also play an important role in supporting populations of certain forest‐dependent species. The ongoing conversion of large swathes of logged forest to non‐forest habitat (such as oil palm plantation) because of their perceived lack of importance for biodiversity is a cause for serious concern for the conservation of tropical biodiversity.
Relationship between cytokine expression patterns and clinical outcomes: two population‐based birth cohorts
Authors: Wu J. , Prosperi M. C. F. , Simpson A. , Hollams E. M. , Sly P. D. , Custovic A. , Holt P. G. 
Published: June 2015

SummaryBackgroundModels that incorporate patterns of multiple cytokine responses to allergens, rather than individual cytokine production, may better predict sensitization and asthma.ObjectiveTo characterize the patterns of peripheral blood mononuclear cells’ (PBMCs) cytokine responses to house dust mite (HDM) allergens among children from two population‐based birth cohorts using machine learning techniques.MethodsPBMCs collected at 8 years of age from the UK Manchester Asthma and Allergy Study (n = 268) and at 14 years of age from the Australian Raine Study (n = 1374) were cultured with HDM extract (10 μg/ml). Cytokine expression (IL‐13, IL‐5, IFN‐γ, and IL10) was measured in the supernatant. Cytokine patterns were identified using a Gaussian mixture model clustering, and classification stability was assessed by bootstrapping.ResultsA six‐class model indicated complex latent structure of cytokine expression. Based on the characteristics of each class, we designated them as follows: ‘Nonresponders’ (n = 905, 55%); ‘IL‐10 responders’ (n = 49, 3%); ‘IFN‐γ and IL‐13 medium responders’ (n = 56, 3.4%); ‘IL‐13 medium responders’ (n = 351, 21.4%); ‘IL‐5 and IL‐13 medium responders’ (n = 77, 4.7%); and ‘IL‐13 and IL‐5 high responders’ (n = 204, 12.4%). ‘IL‐13 and IL‐5 high responders’ were at much higher risk of HDM sensitization and asthma compared to all other classes, with 88% of children assigned to this class being sensitized and 28.5% having asthma.ConclusionUsing model‐based clustering, we identified several distinct patterns of cytokine response to HDM and observed interplay between cytokine expression level, cytokine patterns (especially IL‐13 and IL‐5), and clinical outcomes. ‘IL‐13 and IL‐5 high responders’ class was strongly associated with HDM sensitization. However, among HDM‐sensitized children, one‐third showed no PBMC response to HDM, and the majority of HDM‐sensitized children did not have asthma or wheeze. Our findings suggest that positive HDM ‘allergy tests’ and asthma are associated with a broad range of immunophenotypes, which may have important implications for the use of cytokine‐targeted treatment approaches.
Associations of epithelial c-kit expression in phyllodes tumours of the breast
Authors: Tawasil John , Go Edna May L , Tsang Julia Y S , Ni Yun-Bi , Ko Chun-Wai , Tse Gary M 
Published: June 2015

BackgroundMammary phyllodes tumours (PT) are rare biphasic neoplasms but have important clinical significance. Both epithelial and stromal components participate in PT development. Despite a number of studies on stromal c-kit in PT, little is known about the role of its epithelial expression.ObjectiveTo further evaluate the stromal and epithelial expression of c-kit in a cohort of patients with PT.Method and resultsExpression of c-kit in both epithelial and stromal components was examined and correlated with histological features in PT. Stromal c-kit expression was associated positively with stromal cellularity (median expression=10.0, 30.0 and 50.0 from mild to severe cellularity; p=0.019). Conversely, a significant negative trend between epithelial c-kit expression with stromal pleomorphism (median expression=55.0, 30.0 and 2.5 from mild to severe pleomorphism; p=0.043) and mitosis (median expression=70.0 and 20.0 for low and high mitosis respectively; p=0.003); and a trend of negative correlation with increased PT grade was found. Despite these reverse associations, epithelial and stromal c-kit expressions were positively correlated with each other. Notably, the correlation of stromal c-kit expression with malignant histological features appeared to be stronger in cases with low epithelial c-kit expression but not in those with high epithelial c-kit expression.ConclusionsThis study demonstrated the association of epithelial c-kit expression with stromal histological features and stromal c-kit. Interestingly, epithelial c-kit expression affected the strength of the correlation of stromal c-kit with these histological features. These findings provide further evidence of the interaction between the epithelial and stromal components in PT.
Predictors and prognostic value of left atrial remodelling after acute myocardial infarction
Authors: Kyhl Kasper , Vejlstrup Niels , Lønborg Jacob , Treiman Marek , Ahtarovski Kiril Aleksov , Helqvist Steffen , Kelbæk Henning , Holmvang Lene , Jørgensen Erik , Saunamäki Kari , Søholm Helle , Andersen Mads J , Møller Jacob E , Clemmensen Peter , Engstrøm Thomas 
Published: June 2015

PurposeLeft atrial (LA) volume is a strong prognostic predictor in patients following ST-segment elevation myocardial infarction (STEMI). However, the change in LA volume over time (LA remodelling) following STEMI has been scarcely studied. We sought to identify predictors for LA remodelling and to evaluate the prognostic importance of LA remodelling.MethodsThis is a subgroup analysis from a randomised clinical trial that evaluated the cardioprotective effect of exenatide treatment. A total of 160 patients with STEMI underwent a cardiovascular MR (CMR) 2 days after primary angioplasty and a second scan 3 months later. LA remodelling was defined as changes in LA volume or function from baseline to 3 months follow-up. Major adverse cardiac events were registered after a median of 5.2 years.ResultsAdverse LA minimum volume (LAmin) remodelling was correlated to the presence of hypertension, larger infarct size by CMR, higher peak troponin T, larger area at risk and adverse left ventricular (LV) remodelling. LA maximum volume (LAmax) remodelling was correlated to larger infarct size by CMR, higher peak troponin T, larger area at risk, larger LV mass, impaired LV function and adverse LV remodelling. Kaplan-Meier and Log Rank analyses showed that patients in the highest tertiles of LAmin or LAmax remodelling are at higher risk (0.030 and p=0.018).ConclusionsAfter a myocardial infarction, LA remodelling reflects a parallel ventricular-atrial remodelling. Infarct size is a major determinant of LA remodelling following STEMI and adverse LA remodelling is associated with an unfavourable prognosis.
Decitabine Enhances Lymphocyte Migration and Function and Synergizes with CTLA-4 Blockade in a Murine Ovarian Cancer Model
Authors: Wang Lei , Amoozgar Zohreh , Huang Jing , Saleh Mohammad H. , Xing Deyin , Orsulic Sandra , Goldberg Michael S. 
Published: June 2015

AbstractThe lack of second-line treatment for relapsed ovarian cancer necessitates the development of improved combination therapies. Targeted therapy and immunotherapy each confer clinical benefit, albeit limited as monotherapies. Ovarian cancer is not particularly responsive to immune checkpoint blockade, so combination with a complementary therapy may be beneficial. Recent studies have revealed that a DNA methyl transferase inhibitor, azacytidine, alters expression of immunoregulatory genes in ovarian cancer. In this study, the antitumor effects of a related DNA methyl transferase inhibitor, decitabine (DAC), were demonstrated in a syngeneic murine ovarian cancer model. Low-dose DAC treatment increases the expression of chemokines that recruit NK cells and CD8+ T cells, promotes their production of IFNγ and TNFα, and extends the survival of mice bearing subcutaneous or orthotopic tumors. While neither DAC nor immune checkpoint blockade confers durable responses as a monotherapy in this model, the efficacy of anti–CTLA-4 was potentiated by combination with DAC. This combination promotes differentiation of naïve T cells into effector T cells and prolongs cytotoxic lymphocyte responses as well as mouse survival. These results suggest that this combination therapy may be worthy of further consideration for improved treatment of drug-resistant ovarian cancer. Cancer Immunol Res; 3(9); 1030–41. ©2015 AACR.
Effect of a Procaspase-Activating Compound on the Catalytic Activity of Mature Caspase-3
Authors: Matsuo Takashi , Yamada Keita , Ishida Masaya , Miura Yoshiyuki , Yamanaka Masaru , Hirota Shun 
Published: June 2015

Abstract
Caspase-3, an apoptosis-executing enzyme with a dimeric structure, and its zymogen (procaspase-3) are target proteins in cancer chemotherapy using synthetic compounds. Previous work has shown that PAC-1 (1st procaspase-activating compound) affects the activation of procaspase-3 in cancerous cells through the Zn2+-chelation mechanism. However, we found that the compound also enhances the mature caspase-3 activity in the absence of Zn2+. The enhancement of the mature caspase-3 activity by PAC-1 followed a Michaelis–Menten-type saturation dependency with respect to the concentration of the compound. PAC-1 induced the change in the UV–vis spectrum of the mature caspase-3. From these findings, we propose a direct structural interaction of PAC-1 with the protein core. According to a molecular dynamics calculation for the complex of PAC-1 and mature caspase-3, PAC-1 is likely to bind to the interface between the dimeric structure in mature caspase-3. The interactions between PAC-1 and amino acid residues that affect the catalytic activity of mature caspase-3 are suggested. Throughout this work, diverse functions of the apoptosis-inducing compound are disclosed.
Frictional Pressure Losses of Fluids Flowing in Circular Conduits: A Review
Authors: Kamel Ahmed H. , Shaqlaih Ali S. 
Published: June 2015

SummaryFluids are pumped through circular conduits in various operations in the petroleum industry. These fluids may be Newtonian or non-Newtonian, clean or proppant-laden, polymer-based or surfactant-based, single-phase or multiphase, drag-reducing, and others. They are pumped through straight and coiled tubing under laminar- or turbulent-flow conditions. Calculation of frictional pressure losses for these circumstances is crucial for the success of the operation.A simple Darcy-Weisbach (Darcy 1857) equation is widely used to calculate frictional pressure losses in pipes. However, a unique term, friction factor, has to be determined. Enormous numbers of correlations are available to determine the friction factor. These correlations vary in complexity and applicability and have their own positive and negative features. In addition, several parameters included in the correlations have to be identified, and they vary from one correlation to another. The task at hand is determining the proper correlation. Estimating the friction factor is not an easy task, and it can be very confusing. Inaccurate estimation may lead to erroneous results and failure of operations.This study provides a comprehensive review of the friction-factor correlations and presents how to select the most-suitable correlation for specific conditions. It discusses the parameters involved in friction-factor calculation and how to define them. The authors compare and question the applicability, accuracy, and limitations of each correlation to propose the most-accurate ones. An innovative, user-friendly, and step-by-step code using the most widely used and accurate correlations can then be developed to predict the friction factor. The present study is an effort to simplify the friction-factor challenge. It aims at providing the most-accurate friction-factor correlations to overcome the complexity faced when calculating frictional pressure losses. In conclusion, it summarizes the state of the art in the field of fluids and hydraulics in the oil and gas industry.
The Physiological Basis of the Genetic Progress in Yield Potential of CIMMYT Spring Wheat Cultivars from 1966 to 2009
Authors: Aisawi K. A. B. , Reynolds M. P. , Singh R. P. , Foulkes M. J. 
Published: June 2015

ABSTRACTOur objective was to investigate the physiological basis of genetic progress in grain yield in CIMMYT spring wheat (Triticum aestivum L.) cultivars developed from 1966 to 2009 in irrigated, high‐potential conditions. Field experiments were conducted during three growing seasons in northwest Mexico (2008–2009, 2009–2010, and 2010–2011) examining 12 historic CIMMYT semidwarf spring wheat cultivars released from 1966 to 2009. The linear rate of genetic gain in grain yield was 30 kg ha−1 yr−1 (0.59% yr−1; R2 = 0.58, P = 0.01). Grain yield progress was associated with increased aboveground dry matter (AGDM) at harvest (R2 = 0.80, P < 0.001) and heavier grain weight (R2 = 0.46, P < 0.05). There was a positive linear association between AGDM and plant height (R2 = 0.43, P < 0.05) and between grain weight and the date of complete canopy senescence (CCS) among the 12 cultivars (R2 = 0.36, P < 0.05). There was no change in grains per square meter or harvest index (HI) with year of release (YoR). Grain weight was positively associated with potential grain weight (PGW), and PGW, in turn, was positively associated with rachis length per spikelet among the cultivars. Overall spike dry matter (DM) per square meter at anthesis (GS61) +7 d did not change with YoR. There was a trend for a linear increase in AGDM of fertile shoots (expressed as g m−2) at GS61 +7 d with YoR, but this was counteracted by spike partitioning decreasing overall during the 43‐yr period from 0.25 to 0.23. There was a linear increase in preanthesis flag‐leaf stomatal conductance with YoR (P < 0.05). There was no change in grain growth response to a degraining treatment imposed at GS61 +14 d (mean grain weight response +5.5%) indicating that the degree of source limitation to grain growth appeared to be small and unchanged in the older and modern cultivars. Generally, these results indicated that the rate of genetic progress in CIMMYT spring wheat has slowed but has not plateaued in recent decades, while genetic gains were associated with increase in both potential and final grain weight.