bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of an Open Metadata Schema for Prospective Clinical Research (openPCR) in China
Authors: Guan Z. , Sun J. , Wang Z. , Geng Y. , Xu W. 
Published: December 2013

SummaryObjectives: In China, deployment of electronic data capture (EDC) and clinical data management system (CDMS) for clinical research (CR) is in its very early stage, and about 90% of clinical studies collected and submitted clinical data manually. This work aims to build an open metadata schema for Prospective Clinical Research (openPCR) in China based on openEHR archetypes, in order to help Chinese researchers easily create specific data entry templates for registration, study design and clinical data collection.Methods: Singapore Framework for Dublin Core Application Profiles (DCAP) is used to develop openPCR and four steps such as defining the core functional requirements and deducing the core metadata items, developing archetype models, defining metadata terms and creating archetype records, and finally developing implementation syntax are followed.Results: The core functional requirements are divided into three categories: requirements for research registration, requirements for trial design, and requirements for case report form (CRF). 74 metadata items are identified and their Chinese authority names are created. The minimum metadata set of openPCR includes 3 documents, 6 sections, 26 top level data groups, 32 lower data groups and 74 data elements. The top level container in openPCR is composed of public document, internal document and clinical document archetypes. A hierarchical structure of openPCR is established according to Data Structure of Electronic Health Record Architecture and Data Stand -ard of China (Chinese EHR Standard). Meta-data attributes are grouped into six parts: identification, definition, representation, relation, usage guides, and administration.Discussions and Conclusion: OpenPCR is an open metadata schema based on research registration standards, standards of the Clinical Data Interchange Standards Consortium (CDISC) and Chinese healthcare related stand -ards, and is to be publicly available throughout China. It considers future integration of EHR and CR by adopting data structure and data terms in Chinese EHR Standard. Archetypes in openPCR are modularity models and can be separated, recombined, and reused. The authors recommend that the method to develop openPCR can be referenced by other countries when designing metadata schema of clinical research. In the next steps, openPCR should be used in a number of CR projects to test its applicability and to continuously improve its coverage. Besides, metadata schema for research protocol can be developed to structurize and standardize protocol, and syntactical interoperability of openPCR with other related standards can be considered.
An Electronic Specimen Collection Protocol Schema (eSCPS)
Authors: Semjonow A. , Oezguer E. , Herden J. , Akbarov I. , Tok A. , Engelmann U. , Wille S. , Eminaga O. 
Published: December 2013

SummaryBackground: The integrity of collection protocols in biobanking is essential for a high-quality sample preparation process. However, there is not currently a well-defined universal method for integrating collection protocols in the biobanking information system (BIMS). Therefore, an electronic schema of the collection protocol that is based on Extensible Markup Language (XML) is required to maintain the integrity and enable the exchange of collection protocols.Materials and Methods: The development and implementation of an electronic specimen collection protocol schema (eSCPS) was performed at two institutions (Muenster and Cologne) in three stages. First, we analyzed the infrastructure that was already established at both the biorepository and the hospital information systems of these institutions and determined the requirements for the sufficient preparation of specimens and documentation. Second, we designed an eSCPS according to these requirements. Fi -nally, a prospective study was conducted to implement and evaluate the novel schema in the current BIMS.Results: We designed an eSCPS that provides all of the relevant information about collection protocols. Ten electronic collection protocols were generated using the supplementary Protocol Editor tool, and these protocols were successfully implemented in the existing BIMS. Moreover, an electronic list of collection protocols for the current studies being performed at each institution was included, new collection protocols were added, and the existing protocols were redesigned to be modifiable. The documentation time was significantly reduced after implementing the eSCPS (5 ± 2 min vs. 7 ± 3 min; p = 0.0002).Conclusion: The eSCPS improves the integrity and facilitates the exchange of specimen collection protocols in the existing open-source BIMS.
A Simplification and Implementation of Random-effects Meta-analyses Based on the Exact Distribution of Cochran’s Q
Authors: Preuß M. , Ziegler A. 
Published: December 2013

SummaryBackground: The random-effects (RE) model is the standard choice for meta-analysis in the presence of heterogeneity, and the stand ard RE method is the DerSimonian and Laird (DSL) approach, where the degree of heterogeneity is estimated using a moment-estimator. The DSL approach does not take into account the variability of the estimated heterogeneity variance in the estimation of Cochran’s Q. Biggerstaff and Jackson derived the exact cumulative distribution function (CDF) of Q to account for the variability of Ť 2.Objectives: The first objective is to show that the explicit numerical computation of the density function of Cochran’s Q is not required. The second objective is to develop an R package with the possibility to easily calculate the classical RE method and the new exact RE method.Methods: The novel approach was validated in extensive simulation studies. The different approaches used in the simulation studies, including the exact weights RE meta-analysis, the I 2 and T 2 estimates together with their confidence intervals were implemented in the R package metaxa.Results: The comparison with the classical DSL method showed that the exact weights RE meta-analysis kept the nominal type I error level better and that it had greater power in case of many small studies and a single large study. The Hedges RE approach had inflated type I error levels. Another advantage of the exact weights RE meta-analysis is that an exact confidence interval for T 2is readily available. The exact weights RE approach had greater power in case of few studies, while the restricted maximum likelihood (REML) approach was superior in case of a large number of studies. Differences between the exact weights RE meta-analysis and the DSL approach were observed in the re-analysis of real data sets. Application of the exact weights RE meta-analysis, REML, and the DSL approach to real data sets showed that conclusions between these methods differed.Conclusions: The simplification does not require the calculation of the density of Cochran’s Q, but only the calculation of the cumulative distribution function, while the previous approach required the computation of both the density and the cumulative distribution function. It thus reduces computation time, improves numerical stability, and reduces the approximation error in meta-analysis. The different approaches, including the exact weights RE meta-analysis, the I 2 and T 2estimates together with their confidence intervals are available in the R package metaxa, which can be used in applications.
Reply to the Commentary on "Graphite and its hidden superconductivity"
Authors: Esquinazi P. 
Published: December 2013

A Reply to the Commentary by E. M. Forgan [Pap. Phys. 5, 050008 (20013)].Received: 30 October 2013, Accepted: 4 November 2013; Edited by: S. A. Grigera; DOI: http://dx.doi.org/10.4279/10.4279/PIP.050009Cite as: P. Esquinazi, Papers in Physics 5, 050009 (2013)
Dipolarization and turbulence in the plasma sheet during a substorm: THEMIS observations and global MHD simulations
Authors: El‐Alaoui Mostafa , Richard Robert L. , Ashour‐Abdalla Maha , Goldstein Melvyn L. , Walker Raymond J. 
Published: December 2013

AbstractSpacecraft in the magnetotail have observed fluctuations in velocity and magnetic field that have the characteristics of fluid turbulence. We investigated the properties of these fluctuations during a substorm on 7 February 2009. During this event several spacecraft were observing the magnetotail. By using upstream observations performed by Wind, we conducted a global magnetohydrodynamic (MHD) simulation of the substorm. The simulation results were compared to time series of Time History of Events and Macroscale Interactions during Substorms (THEMIS) observations in the magnetotail, and it performed well as the spacecraft encountered dipolarizations and strong flows. Further, the power spectral densities and probability distribution functions observed in the magnetotail by THEMIS and in the MHD simulations were similar. Notable features of the event include a large dipolarization growing by accreting smaller earthward moving dipolarization fronts. The dipolarizations were associated with a strong channel of earthward flow and a large vortex. In the MHD simulation results, which are supported by the observations, strong narrow flow channels are a clear and persistent feature of magnetotail convection which exist at the driving scales for the turbulent spectra.
New approaches to removing cloud shadows and evaluating the 380 nm surface reflectance for improved aerosol optical thickness retrievals from the GOSAT/TANSO‐Cloud and Aerosol Imager
Authors: Fukuda Satoru , Nakajima Teruyuki , Takenaka Hideaki , Higurashi Akiko , Kikuchi Nobuyuki , Nakajima Takashi Y. , Ishida Haruma 
Published: December 2013

AbstractA satellite aerosol retrieval algorithm was developed to utilize a near‐ultraviolet band of the Greenhouse gases Observing SATellite/Thermal And Near infrared Sensor for carbon Observation (GOSAT/TANSO)‐Cloud and Aerosol Imager (CAI). At near‐ultraviolet wavelengths, the surface reflectance over land is smaller than that at visible wavelengths. Therefore, it is thought possible to reduce retrieval error by using the near‐ultraviolet spectral region. In the present study, we first developed a cloud shadow detection algorithm that uses first and second minimum reflectances of 380 nm and 680 nm based on the difference in Rayleigh scattering contribution for these two bands. Then, we developed a new surface reflectance correction algorithm, the modified Kaufman method, which uses minimum reflectance data at 680 nm and the NDVI to estimate the surface reflectance at 380 nm. This algorithm was found to be particularly effective at reducing the aerosol effect remaining in the 380 nm minimum reflectance; this effect has previously proven difficult to remove owing to the infrequent sampling rate associated with the three‐day recursion period of GOSAT and the narrow CAI swath of 1000 km. Finally, we applied these two algorithms to retrieve aerosol optical thicknesses over a land area. Our results exhibited better agreement with sun‐sky radiometer observations than results obtained using a simple surface reflectance correction technique using minimum radiances.
Skeletogenesis: Genetics
Authors: Wuelling Manuela , Vortkamp Andrea 
Published: December 2013

Abstract

The vertebrate skeleton is formed by two mechanisms – endochondral and intramembranous ossification. During intramembranous ossification, mesenchymal cells directly differentiate into osteoblasts. Endochondral ossification is a two‐step process during which bones are preformed as cartilage templates, which are subsequently replaced by bone. During this process, the inner cells of the cartilage condensation differentiate into chondrocytes, which proliferate and differentiate into hypertrophic chondrocytes producing a mineralised matrix. The outer cells differentiate into the perichondrium surrounding the cartilage template and later into osteoblasts, which produce a bone collar surrounding the hypertrophic region. Blood vessels from the bone collar invade the hypertrophic region in close association with bone‐resorbing osteoclasts and bone‐forming osteoblasts. The orchestrated formation, differentiation and degradation of cartilage and bone are regulated by a multitude of growth factors and transcriptional regulators, which will be discussed in this article.

Key Concepts:

During intramembranous ossification, mesenchymal progenitor cells differentiate directly into bone‐forming osteoblasts.

Endochondral ossification includes the formation of cartilage templates, which are subsequently replaced by bone and bone marrow.

Cells in the cartilage condensation represent bipotential osteochondroprogenitor cells that differentiate depending on their level of Sox9 into chondrocytes.

Ihh serves as a key regulator of endochondral ossification regulating chondrocyte proliferation, hypertrophic differentiation and ossification.

Ihh and Pthrp interact in a negative feedback mechanism to control the domain of columnar, high‐proliferating chondrocytes.

Pthrp negatively regulates cell cycle exit.

Runx2 and Mef2c activate chondrocyte differentiation.

Runx2 and Osterix are required to induce osteoblast differentiation.

The balance between Rankl and osteoprotegerin determines the differentiation of osteoclasts.

Chondrocyte differentiation is regulated by secreted growth factors, which activate distinct steps of the differentiation programme.
Language and Genes
Authors: Tomblin J Bruce , Mueller K L 
Published: December 2013

AbstractThe development of spoken language involves the acquisition of a complex system of knowledge and processing mechanisms that recruits a number of neural systems. These neural systems depend on numerous genetically influenced biological functions that provide for experience dependent learning. That language development and use entail genetic mechanisms is clear. A substantial literature shows that individual differences in language are partially heritable. This evidence of heritability has now motivated efforts to uncover specific genetics mechanisms using modern molecular genetics. To date, one gene,FOXP2, has been shown to be associated with speech and language. However, it is not appropriate to conclude thatFOXP2contains the human language faculty. Instead, it likely participates with many genetic systems to support language development. What these genetically influenced systems are is only beginning to be revealed.Key Concepts:There is considerable support for a role for genes in language development and function.Twin studies along with adoption studies show that individual differences in language are partially attributable to genetic factors.There is little evidence that vocabulary and grammar are differentially influenced by genetic factors.Heritability of language increases through childhood.Twin research suggests that the genetic influence on language development is shared with nonlanguage cognitive skills.Substantial evidence shows that FOXP2 plays an important role in the neurobiology of language via it regulation of the expression of other genes.CNTNAP2is a downstream regulatory target ofFOXP2that has been associated with developmental language impairment.Future progress in understanding a complex trait such as language may come from understanding genetic mechanisms controlling the expression levels of genes (eQTLs).
CFTR: TheCFGene and Its Regulation in Physiology and Disease
Authors: Davies Wayne IL 
Published: December 2013

AbstractCystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, which encodes an atypical transporter that functions as a chloride channel. The regulation of both the gene and the protein is highly complex, involving many novel regulatory mechanisms: these include differential usage of transcription start sites and upstream exons; alternative splicing and the production of unique polypeptide isoforms; and post‐transcriptional influences on transcript stability and protein levels. Together they mediate basal and tissue‐specificCFTRexpression in epithelial and nonepithelial tissues, such as the heart, under both normal physiological conditions and in the disease state.Key Concepts:Cystic fibrosis (CF) is one of the most well‐known and commonest monogenetic disorders in the Caucasian population.Nearly 2000 mutations have been identified in theCFTRgene.TheCFTRgene, also known asABCC7, contains 27 exons and encodes a chloride channel that is unique within the ABC transporter superfamily.Despite CF being primarily a disease of epithelial cells,CFTRexpression has also been identified in nonepithelial cells, for example, hypothalamic neurons and cardiomyocytes.Although relatively widespread,CFTRexpression shows tissue‐specific regulatory mechanisms that act at multiple levels, including transcription, post‐transcription and translation.Collectively, these control pathways yield distinct, tightly regulated transcripts that encode unique CFTR protein variants.The complexity ofCFTRexpression may be the main determining factor against the production of an effective cure for CF.Further study of these parallel tissue‐specific regulatory mechanisms, especially in organs that appear to be protected in CF, may provide insights into CF pathology and potential disease treatments.
Molecular Genetics of Primary Ciliary Dyskinesia
Authors: Horani Amjad , Ferkol Thomas W 
Published: December 2013

Abstract

Primary ciliary dyskinesia (PCD) is a genetic disease of the motile cilia, and is part of a rapidly expanding collection of disorders collectively known as ciliopathies. Our understanding of the complex genetics and functional phenotypes of these conditions has rapidly advanced over the past decade. A growing number of cilia‐related genes and mutations have been identified, which segregate into genes that encode axonemal motor proteins, structural and regulatory proteins within the cilium, as well as an emerging class of cytoplasmic proteins involved in ciliary assembly. These findings have yielded unexpected insights into the processes involved in the assembly, structure and function of a cilium, which will allow us to better understand the clinical heterogeneity of disease. Moreover, these discoveries have the potential to revolutionise testing for PCD, and lead to earlier diagnosis and treatment of affected individuals.

Key Concepts:

Cilia are complex organelles that are on the surface of many cell types and involved in diverse cellular functions.

Cilia are broadly classified as motile (motor) or primary (sensory), and the latter are important signalling organelles that sense the extracellular environment.

Motile cilia are critical for the intrinsic defence of the respiratory tract, including the middle ear, paranasal sinuses, and conducting airways.

Primary ciliary dyskinesia is an inherited disease that is characterised by impaired ciliary function and leads to diverse clinical manifestations, including chronic sinopulmonary disease, persistent middle ear effusions, laterality defects and infertility.

Mutations in different primary ciliary dyskinesia‐associated genes that encode proteins involved in ciliary assembly, structure and function can produce similar clinical phenotypes but different ultrastructural defects.
Assessing Genetic Variants of Uncertain Significance: The Example of Breast Cancer
Authors: Morris Gloria J 
Published: December 2013

Abstract

Mutations in the
BRCA1
or
2
genes can lead to an inherited increased risk of breast, ovarian and other cancers. Molecularly, these mutations manifest primarily as frameshift or nonsense mutations, leading to prematurely truncated proteins that would otherwise function as tumour suppressors. Up to 10–20% of all
BRCA
mutations are reported as variants of uncertain significance (VUS); these manifest as missense mutations (with resultant amino acid substitution), intronic variants with resultant effect on splicing capacity or in‐frame deletions and insertions, which may or may not change the reading frame of a gene. These variant sequences can confound rather than guide the risk assessment process in the genetic counselling of patients and family members, whether afflicted or not with an actual cancer. Several molecular methods are now able to discriminate those as yet unclassified variants between high and low risk for cancer development; databases have been generated accordingly and may allow some further prediction of the probability of deleterious behaviour.

This article aims to clarify the clinical relevance of BRCA VUS, to assimilate resources and make suggestions for estimating their clinical impact, and to highlight the need for further studies in this area.

Key Concepts:

There are limited guidelines for the specific management and surveillance of patients and their family members who harbour genetic variants of uncertain significance.

Integrated models to discriminate high‐risk from low‐risk variants have been generated.

Application of these models is considered.

Further clinical trials for risk management are advocated.

Up to 20% of BRCA 1 and 2 mutations can be missense mutations which amount to variants of uncertain significance, the deleterious nature of which are unclear in clinical practice.
Dental topography of platyrrhines and prosimians: Convergence and contrasts
Authors: Winchester Julia M. , Boyer Doug M. , St. Clair Elizabeth M. , Gosselin‐Ildari Ashley D. , Cooke Siobhán B. , Ledogar Justin A. 
Published: December 2013

ABSTRACTDental topographic analysis is the quantitative assessment of shape of three‐dimensional models of tooth crowns and component features. Molar topographic curvature, relief, and complexity correlate with aspects of feeding behavior in certain living primates, and have been employed to investigate dietary ecology in extant and extinct primate species. This study investigates whether dental topography correlates with diet among a diverse sample of living platyrrhines, and compares platyrrhine topography with that of prosimians. We sampled 111 lower second molars of 11 platyrrhine genera and 121 of 20 prosimian genera. For each tooth we calculated Dirichlet normal energy (DNE), relief index (RFI), and orientation patch count (OPCR), quantifying surface curvature, relief, and complexity respectively. Shearing ratios and quotients were also measured. Statistical analyses partitioned effects of diet and taxon on topography in platyrrhines alone and relative to prosimians. Discriminant function analyses assessed predictive diet models. Results indicate that platyrrhine dental topography correlates to dietary preference, and platyrrhine‐only predictive models yield high rates of accuracy. The same is true for prosimians. Topographic variance is broadly similar among platyrrhines and prosimians. One exception is that platyrrhines display higher average relief and lower relief variance, possibly related to lower relative molar size and functional links between relief and tooth longevity distinct from curvature or complexity. Explicitly incorporating phylogenetic distance matrices into statistical analyses of the combined platyrrhine‐prosimian sample results in loss of significance of dietary effects for OPCR and SQ, while greatly increasing dietary significance of RFI. Am J Phys Anthropol 153:29–44, 2014. © 2013 Wiley Periodicals, Inc.