bluuebunny/crossref_metadata_2025_split huggingface dataset:
S100A6 expression in cutaneous smooth muscle neoplasms
Authors: Idriss Munir H. , Elston Dirk M. 
Published: August 2015

The S100A6 protein is expressed in a variety of tissues and distinct staining patterns in S100A6 immunohistochemistry may be useful in the differential diagnosis of difficult lesions. We evaluated the staining pattern of the S100A6 antibody in 22 cases each of pilar leiomyoma (LM), angioleiomyoma (ALM), and cutaneous leiomyosarcoma (LMS). S100A6 labeled both the nucleus and cytoplasm of myocytes in positive cases. About 64% of LM and 86% ALM had positive staining to the S100A6 antibody but predominantly in a weak staining pattern. In contrast, 95% of the LMS exhibited moderate to strong staining with the S100A6 antibody. The difference in the frequency of positive cases was statistically significant in the LM vs LMS comparison (p = 0.025), but we found intensity of staining to be of greatest practical utility. Analysis between the groups taking in to consideration differences in intensity of staining using the nonparametric rank sum (Mann–Whitney U test) demonstrated that there was a statistically significant difference between LM and LMS and between ALM and LMS. Weak or absent S100A6 staining supports a diagnosis of LM, whereas strong positive staining supports a diagnosis of LMS.
Liver injury is associated with mortality in sickle cell disease
Authors: Feld J. J. , Kato G. J. , Koh C. , Shields T. , Hildesheim M. , Kleiner D. E. , Taylor J. G. , Sandler N. G. , Douek D. , Haynes‐Williams V. , Nichols J. S. , Hoofnagle J. H. , Jake Liang T. , Gladwin M. T. , Heller T. 
Published: August 2015

SummaryBackgroundIncreased life expectancy in sickle cell disease (SCD) has resulted in greater recognition of the consequences of repeated intravascular vaso‐occlusion and chronic haemolysis to multiple organ systems.AimTo report the long‐term consequences of liver dysfunction in SCD.MethodsA cohort of SCD patients was prospectively evaluated at the National Institutes of Health (NIH) Clinical Center. The association of mortality with liver enzymes, parameters of liver synthetic function and iron overload was evaluated using Cox regression.ResultsExactly, 247 SCD patients were followed up for 30 months of whom 22 (9%) died. After controlling for predictors, increased direct bilirubin (DB), ferritin, alkaline phosphatase and decreased albumin were independently associated with mortality. In a multivariable model, only high DB and ferritin remained significant. Ferritin correlated with hepatic iron content and total blood transfusions but not haemolysis markers. Forty patients underwent liver biopsies and 11 (28%) had fibrosis. Twelve of 26 patients (48%) had portal hypertension by hepatic venous pressure gradient (HVPG) measurements. All patients with advanced liver fibrosis had iron overload; however, most patients (69%) with iron overload were without significant hepatic fibrosis. Ferritin did not correlate with left ventricular dysfunction by echocardiography. DB correlated with bile acid levels suggesting liver pathology. Platelet count and soluble CD14 correlated with HVPG indicating portal hypertension.ConclusionsFerritin and direct bilirubin are independently associated with mortality in sickle cell disease. Ferritin likely relates to transfusional iron overload, while direct bilirubin suggests impairment of hepatic function, possibly impairing patients’ ability to tolerate systemic insults.
A Permutation Approach for Selecting the Penalty Parameter in Penalized Model Selection
Authors: Sabourin Jeremy A. , Valdar William , Nobel Andrew B. 
Published: August 2015

Summary
We describe a simple, computationally efficient, permutation-based procedure for selecting the penalty parameter in LASSO-penalized regression. The procedure, permutation selection, is intended for applications where variable selection is the primary focus, and can be applied in a variety of structural settings, including that of generalized linear models. We briefly discuss connections between permutation selection and existing theory for the LASSO. In addition, we present a simulation study and an analysis of real biomedical data sets in which permutation selection is compared with selection based on the following: cross-validation (CV), the Bayesian information criterion (BIC), scaled sparse linear regression, and a selection method based on recently developed testing procedures for the LASSO.
Deductive Derivation and Turing-Computerization of Semiparametric Efficient Estimation
Authors: Frangakis Constantine E. , Qian Tianchen , Wu Zhenke , Diaz Ivan 
Published: August 2015

SummaryResearchers often seek robust inference for a parameter through semiparametric estimation. Efficient semiparametric estimation currently requires theoretical derivation of the efficient influence function (EIF), which can be a challenging and time-consuming task. If this task can be computerized, it can save dramatic human effort, which can be transferred, for example, to the design of new studies. Although the EIF is, in principle, a derivative, simple numerical differentiation to calculate the EIF by a computer masks the EIF's functional dependence on the parameter of interest. For this reason, the standard approach to obtaining the EIF relies on the theoretical construction of the space of scores under all possible parametric submodels. This process currently depends on the correctness of conjectures about these spaces, and the correct verification of such conjectures. The correct guessing of such conjectures, though successful in some problems, is a nondeductive process, i.e., is not guaranteed to succeed (e.g., is not computerizable), and the verification of conjectures is generally susceptible to mistakes. We propose a method that can deductively produce semiparametric locally efficient estimators. The proposed method is computerizable, meaning that it does not need either conjecturing, or otherwise theoretically deriving the functional form of the EIF, and is guaranteed to produce the desired estimates even for complex parameters. The method is demonstrated through an example.
Quantile Regression Analysis of Censored Longitudinal Data with Irregular Outcome-Dependent Follow-Up
Authors: Sun Xiaoyan , Peng Limin , Manatunga Amita , Marcus Michele 
Published: August 2015

Summary
In many observational longitudinal studies, the outcome of interest presents a skewed distribution, is subject to censoring due to detection limit or other reasons, and is observed at irregular times that may follow a outcome-dependent pattern. In this work, we consider quantile regression modeling of such longitudinal data, because quantile regression is generally robust in handling skewed and censored outcomes and is flexible to accommodate dynamic covariate-outcome relationships. Specifically, we study a longitudinal quantile regression model that specifies covariate effects on the marginal quantiles of the longitudinal outcome. Such a model is easy to interpret and can accommodate dynamic outcome profile changes over time. We propose estimation and inference procedures that can appropriately account for censoring and irregular outcome-dependent follow-up. Our proposals can be readily implemented based on existing software for quantile regression. We establish the asymptotic properties of the proposed estimator, including uniform consistency and weak convergence. Extensive simulations suggest good finite-sample performance of the new method. We also present an analysis of data from a long-term study of a population exposed to polybrominated biphenyls (PBB), which uncovers an inhomogeneous PBB elimination pattern that would not be detected by traditional longitudinal data analysis.
The novel atypical retinoid ST5589 down‐regulates Aurora Kinase A and has anti‐tumour activity in lymphoma pre‐clinical models
Authors: Bernasconi Elena , Gaudio Eugenio , Kwee Ivo , Rinaldi Andrea , Cascione Luciano , Tarantelli Chiara , Mensah Afua Adjeiwaa , Stathis Anastasios , Zucca Emanuele , Vesci Loredana , Giannini Giuseppe , Bertoni Francesco 
Published: August 2015

SummaryDespite the marked improvements in the treatment of lymphomas, there is still a need for new therapeutic agents. Synthetic retinoids represent a class of compounds with anti‐cancer activity. Here, we report the preclinical activity of a new member of this class, the ST1926‐derivative ST5589, in lymphomas. ST5589 presented a dose‐dependent anti‐proliferative activity in almost all of the 25 lymphoma cell lines analysed, with a median 50% inhibitory concentration of 433 nM. Apoptosis was observed in 8/11 cell lines. ST5589 induced changes in the gene expression profiles of the cell lines, including the down‐regulation of Aurora Kinase A (AURKA). Specific gene expression signatures were associated with a higher sensitivity to the compound and combination of ST5589 with carfilzomib revealed the importance of proteasome activity in mediating the anti‐tumour activity of ST5589. In conclusion, we have identified a new mechanism of action of atypical retinoids as anti‐cancer compounds, and the encouraging results obtained with the new ST1926‐derivative ST5589 provide the basis for further developments of the compound.
Epithelioid Glioblastomas and Anaplastic Epithelioid Pleomorphic Xanthoastrocytomas—Same Entity or First Cousins?
Authors: Alexandrescu Sanda , Korshunov Andrey , Lai Siang Hui , Dabiri Salma , Patil Sushama , Li Rong , Shih Chie‐Schin , Bonnin Jose M. , Baker Jonathan A. , Du Emma , Scharnhorst David W. , Samuel David , Ellison David W. , Perry Arie 
Published: August 2015

AbstractEpithelioid glioblastoma (eGBM) and pleomorphic xanthoastrocytoma (PXA) with anaplastically transformed foci (ePXA) show overlapping features. Eleven eGBMs and 5 ePXAs were reviewed and studied immunohistochemically. Fluorescence in situ hybridization for EGFR amplification, PTEN deletion and ODZ3 deletion was also performed, with Ilumina 450 methylome analysis obtained in five cases. The average age for eGBM was 30.9 (range 2–79) years, including five pediatric cases and a M : F ratio of 4.5. The ePXA patients had a M : F ratio of 4 and averaged 21.2 (range 10–38) years in age, including two pediatric cases. Six eGBMs and two ePXAs recurred (median recurrence interval of 12 and 3.3 months, respectively). All tumors were composed of solid sheets of loosely cohesive, “melanoma‐like” cells with only limited infiltration. ePXAs showed lower grade foci with classic features of PXA. Both tumor types showed focal expression of epithelial and glial markers, retained INI1 and BRG1 expression, occasional CD34 positivity, and lack of mutant IDH1 (R132H) immunoreactivity. BRAF V600E mutation was present in four eGBMs and four ePXAs. ODZ3 deletion was detected in seven eGBMs and two ePXAs. EGFR amplification was absent. Methylome analysis showed that one ePXA and one eGBM clustered with PXAs, one eGBM clustered with low‐grade gliomas, and two eGBMs clustered with pediatric‐type glioblastomas. Common histologic, immunohistochemical, molecular and clinical features found in eGBM and ePXA suggest that they are closely related or the same entity. If the latter is true, the nomenclature and WHO grading remains to be resolved.
Deformation of a young salt giant: regional topography of the Red Sea Miocene evaporites
Authors: Mitchell Neil C. , Ligi Marco , Feldens Peter , Hübscher Christian 
Published: August 2015

AbstractThe deformational behaviour of ‘salt giants’ during and shortly after their deposition is difficult to decipher in ocean margin settings where the original evaporites have been deeply buried and strongly mobilized. Here, we examine seismic reflection data from the Red Sea, where evaporites deposited until the end of the Miocene (~5.3 Ma), are generally covered by only 200–300 m of low‐density sediments and where the presence of an axial spreading centre allows us to observe how they have responded to a varied configuration of underlying basement. The regional morphology of the S‐reflection, representing the evaporite surface, is mapped out from seismic data from 13 cruises. The S‐reflection is locally rugged and commonly angular. It is either underlain by layered reflectivity, suggestive of layered evaporite beds, or by more transparent seismic character, suggestive of massive halite. On average, the depth of the reflection on the flanks of the axial rift systematically declines from 700 to 1100 m below sea level (mbsl) going northwards from 16 to 23°N. In the central Red Sea, the S‐reflection has 100‐ to 200‐m‐deep depressions, extending towards the coasts in places. In the southern Red Sea, the S‐reflection forms a surface at 300–800 mbsl that appears less disrupted. We suggest that the evaporites originally had a flat, horizontal surface at the end of the Miocene and have subsequently been distorted by isostatic effects and axial rifting, which in turn promoted evaporite flowage. Off‐axis evaporite depressions correspond with flows identified with multibeam sonar. Furthermore, across‐rift lows in Bouguer gravity anomalies represent valleys in the underlying basement. The off‐axis evaporite depressions overlie those valleys, as would be expected if halokinetic movements were greatest where the evaporites are locally thick, leading to deflation of the evaporite surface. The thickness of post‐Miocene sediment, also mapped out as part of this procedure, confirms the generally pelagic nature of this interval and increases on average from ~250 to 300 m from the central to the southern Red Sea, mimicking the variation in pelagic productivity observed in the present water column.
Human leukocyte antigen class II DRB1*1302 allele protects against cervical cancer: At which step of multistage carcinogenesis?
Authors: Matsumoto Koji , Maeda Hiroo , Oki Akinori , Takatsuka Naoyoshi , Yasugi Toshiharu , Furuta Reiko , Hirata Ranko , Mitsuhashi Akira , Kawana Kei , Fujii Takuma , Iwata Takashi , Hirai Yasuo , Yokoyama Masatoshi , Yaegashi Nobuo , Watanabe Yoh , Nagai Yutaka , Yoshikawa Hiroyuki ,   the Japan HPV and Cervical Cancer (JHACC) Study Group
Published: August 2015

We investigated the role of human leukocyte antigen (HLA) class II alleles in multistage cervical carcinogenesis. Cross‐sectional analysis for HLA association with cervical cancer included 1253 Japanese women: normal cytology (NL, n = 341), cervical intraepithelial neoplasia grade 1 (CIN1, n = 505), CIN grade 2 or 3 (CIN2/3, n = 96), or invasive cervical cancer (ICC, n = 311). The HLA class II allele frequencies were compared by Fisher's exact test or the χ2‐test. The Bonferroni adjustment corrected for multiple comparisons. Among the study subjects, 454 women with low‐grade squamous intraepithelial lesion cytology were prospectively monitored by cytology and colposcopy every 3–4 months to analyze cumulative risk of CIN3 within the next 10 years in relation to HLA class II alleles. HLA class II DRB1*1302 allele frequency was similar between women with NL (11.7%) and CIN1 (11.9%), but significantly decreased to 5.2% for CIN2/3 and 5.8% for ICC (P = 0.0003). Correction for multiple testing did not change this finding. In women with low‐grade squamous intraepithelial lesion cytology, the cumulative risk of CIN3 diagnosed within 10 years was significantly reduced among DRB1*1302‐positive women (3.2% vs. 23.7%, P = 0.03). In conclusion, the two different types of analysis in this single study showed the protective effect of the DRB1*1302 allele against progression from CIN1 to CIN2/3.
Early sustained unresponsiveness after short‐course egg oral immunotherapy: a randomized controlled study in egg‐allergic children
Authors: Escudero C. , Rodríguez del Río P. , Sánchez‐García S. , Pérez‐Rangel I. , Pérez‐Farinós N. , García‐Fernández C. , Ibáñez M. D. 
Published: August 2015

SummaryBackgroundNo studies have evaluated the potential of egg oral immunotherapy (egg‐OIT) to induce sustained unresponsiveness after discontinuing therapy following short‐term treatments.ObjectiveWe assessed the efficacy of short‐course egg‐OIT to induce sustained unresponsiveness.MethodsSixty‐one egg‐allergic children, 5 to 17 years old, with positive double‐blind placebo‐controlled food challenge (DBPCFC) to dehydrated egg white (EW) were randomized to receive egg‐OIT (OITG) for 3 months (maintenance dose one undercooked egg every 48 hours) or to continue egg avoidance diet (control group, CG) for 4 months. Children who completed egg‐OIT avoided egg for 1 month. At 4 months, both groups underwent a DBPCFC. OITG participants who passed this challenge were instructed to add egg to their diet ad libitum. Immune markers were studied at different time points.ResultsNinety‐three percent (28/30) of OITG children were desensitized in a median of 32.5 days (IQR, 14 days). At 4 months, 1/31 (3%) in CG passed DBPCFC and 11/30(37%) of OITG (95% CI, 14 to 51%; P = 0.003), all of them were consuming egg at 36 months. A decrease in EW, OVA and OVM skin test results and OVA‐specific IgE (sIgE) levels was observed on OITG at 4 months (P = 0.001). EW‐, OVA‐ and OVM‐sIgE levels prior to the start of egg avoidance diet were lower in OITG children who passed DBPCFC at 4 months than in those who did not pass it. EW‐ and OVM‐sIgE showed the best diagnostic performance in predicting DBPCFC result at 4 months. Levels above optimal EW‐sIgE cut‐off of 7.1 kU/L indicated 90% probability of failing DBPCFC.ConclusionThis is the first demonstration of sustained unresponsiveness with a three‐month egg‐OIT protocol. Almost all treated subjects were desensitized and 37% achieved sustained unresponsiveness. EW‐sIgE levels at the end of treatment predicted sustained unresponsiveness. This protocol shows a new approach to OIT for egg‐allergic children.
Implication of circulating memory B cells in late‐onset myasthenia gravis
Authors: Murai Hiroyuki 
Published: August 2015

AbstractMyasthenia gravis is a heterogeneous disease, and it presents various clinical differences according to the age of onset. Immunological backgrounds that cause these differences are not well understood. Kubota et al. investigated subsets of circulating T and B lymphocytes using various markers. They argued that a reduced percentage of memory B cells seems to be a characteristic of late‐onset myasthenia gravis.
Intravenous immunoglobulin and suppression of the production of matrix metalloproteinase‐9
Authors: Matsuo Hidenori 
Published: August 2015

AbstractMatrix metalloproteinase‐9 is a biomarker and therapeutic target in multiple sclerosis. Okada and Adachi reported the matrix metalloproteinase‐9/tissue inhibitor of metalloproteinase‐1 imbalance was a predisposition in patients with multiple sclerosis, and human immunoglobulin G restored it in vitro, supporting the potential of intravenous immunoglobulin therapy in multiple sclerosis.
Debate on the pathogenesis of paraneoplastic cerebellar degeneration with anti‐Yo antibody: T‐cell mediated or antibody mediated?
Authors: Tanaka Keiko 
Published: August 2015

AbstractIt is widely believed that paraneoplastic neurological syndromes with antibodies against intracellular antigens are a cytotoxic T‐cell‐mediated disease triggered in the process of cancer immunity. During this process, coactivation of a humoral immune mechanism is elicited, and autoantibodies against onconeural antigens are produced. These onconeural proteins are usually located in the neuronal cytoplasm or nucleus, and are not targets of antibody‐mediated neuronal damage. Greenlee et al. asserted that the anti‐Yo antibody had a direct effect on Purkinje cell apoptosis, which conflicts with the commonly believed view.
NAPB – a novel SNARE‐associated protein for early‐onset epileptic encephalopathy
Authors: Conroy J. , Allen N.M. , Gorman K. M. , Shahwan A. , Ennis S. , Lynch S.A. , King M.D. 
Published: August 2015

ABSTRACTNext‐generation sequencing has accelerated the identification of disease genes in many rare genetic disorders including early‐onset epileptic encephalopathies (EOEEs). While many of these disorders are caused by neuronal channelopathies, the role of synaptic and related neuronal proteins are increasingly being described. Here, we report a 6‐year‐old girl with unexplained EOEE characterized by multifocal seizures and profound global developmental delay. Recessive inheritance was considered due to parental consanguinity and Irish Traveller descent. Exome sequencing was performed. Variant prioritization identified a homozygous nonsense variant in the N‐ethylmaleimide‐sensitive factor attachment protein, beta (NAPB) gene resulting in a premature stop codon and 46% loss of the protein. NAPB plays a role in soluble N‐ethylmaleimide‐sensitive fusion attachment protein receptor (SNARE)‐complex dissociation and recycling (synaptic vesicle docking). Knockout mouse models of the murine ortholog Napb have been previously reported. These mice develop recurrent post‐natal epileptic seizures in the absence of structural brain changes. The identification of a disease‐causing variant in NAPB further recognizes the importance of the SNARE complex in the development of epilepsy and suggests that this gene should be considered in patients with unexplained EOEE.
Improving Performance of Image Retrieval Based on Fuzzy Colour Histograms by Using Hybrid Colour Model and Genetic Algorithm
Authors: Ljubovic V. , Supic H. 
Published: August 2015

AbstractA hybrid colour model is a colour descriptor formed by combining channels from several different colour models. Although rarely used in computer graphics applications due to redundancy, hybrid colour models may be of interest for the Content‐Based Image Retrieval (CBIR). Best features of each colour model can be combined to obtain optimal retrieval performance. This paper evaluates several approaches to the construction of a hybrid colour model that is used to construct a fuzzy colour histogram of image as a compact feature for retrieval. By evaluating each channel separately, a colour model named HSY is proposed. Various parameters of fuzzy histogram are further improved using Genetic algorithm (GA). Using standard data sets and the Average Normalized Modified Retrieval Rank (ANMRR) as a metric for retrieval performance, it is shown that this novel approach can give an improved retrieval performance.
Global Illumination Using Well‐Separated Pair Decomposition
Authors: Bus N. , Mustafa N. H. , Biri V. 
Published: August 2015

AbstractInstant radiosity methods rely on using a large number of virtual point lights (VPLs) to approximate global illumination. Efficiency considerations require grouping the VPLs into a small number of clusters that are treated as individual lights with respect to each point to be shaded. Two examples of clustering algorithms are Lightcuts [WFA*05] and LightSlice [OP11]. In this work, we use the notion of geometric separatedness of point sets as a basis for a data structure for pre‐computing and compactly storing a set of candidate VPL clusterings. Our data structure is created prior to rendering, is view‐independent and relies only on geometric and radiometric information. For any point to be shaded, we show that a suitable clustering of the VPLs can be efficiently extracted from this data structure. We develop the above framework into an accurate and efficient clustering algorithm based on well‐separated pair decompositions which outperforms earlier work in speed and/or quality for diffuse scenes.