bluuebunny/crossref_metadata_2025 huggingface dataset:
SOCCOMAS: a FAIR web content management system that uses knowledge graphs and that is based on semantic programming
Authors: Vogt Lars , Baum Roman , Bhatty Philipp , Köhler Christian , Meid Sandra , Quast Björn , Grobe Peter
Published: May 2019

We introduce Semantic Ontology-Controlled application for web Content Management Systems (SOCCOMAS), a development framework for FAIR (‘findable’, ‘accessible’, ‘interoperable’, ‘reusable’) Semantic Web Content Management Systems (S-WCMSs). Each S-WCMS run by SOCCOMAS has its contents managed through a corresponding knowledge base that stores all data and metadata in the form of semantic knowledge graphs in a Jena tuple store. Automated procedures track provenance, user contributions and detailed change history. Each S-WCMS is accessible via both a graphical user interface (GUI), utilizing the JavaScript framework AngularJS, and a SPARQL endpoint. As a consequence, all data and metadata are maximally findable, accessible, interoperable and reusable and comply with the FAIR Guiding Principles. The source code of SOCCOMAS is written using the Semantic Programming Ontology (SPrO). SPrO consists of commands, attributes and variables, with which one can describe an S-WCMS. We used SPrO to describe all the features and workflows typically required by any S-WCMS and documented these descriptions in a SOCCOMAS source code ontology (SC-Basic). SC-Basic specifies a set of default features, such as provenance tracking and publication life cycle with versioning, which will be available in all S-WCMS run by SOCCOMAS. All features and workflows specific to a particular S-WCMS, however, must be described within an instance source code ontology (INST-SCO), defining, e.g. the function and composition of the GUI, with all its user interactions, the underlying data schemes and representations and all its workflow processes. The combination of descriptions in SC-Basic and a given INST-SCO specify the behavior of an S-WCMS. SOCCOMAS controls this S-WCMS through the Java-based middleware that accompanies SPrO, which functions as an interpreter. Because of the ontology-controlled design, SOCCOMAS allows easy customization with a minimum of technical programming background required, thereby seamlessly integrating conventional web page technologies with semantic web technologies. SOCCOMAS and the Java Interpreter are available from (https://github.com/SemanticProgramming).
RRAD mutation causes electrical and cytoskeletal defects in cardiomyocytes derived from a familial case of Brugada syndrome
Authors: Belbachir Nadjet , Portero Vincent , Al Sayed Zeina R , Gourraud Jean-Baptiste , Dilasser Florian , Jesel Laurence , Guo Hongchao , Wu Haodi , Gaborit Nathalie , Guilluy Christophe , Girardeau Aurore , Bonnaud Stephanie , Simonet Floriane , Karakachoff Matilde , Pattier Sabine , Scott Carol , Burel Sophie , Marionneau Céline , Chariau Caroline , Gaignerie Anne , David Laurent , Genin Emmanuelle , Deleuze Jean-François , Dina Christian , Sauzeau Vincent , Loirand Gervaise , Baró Isabelle , Schott Jean-Jacques , Probst Vincent , Wu Joseph C , Redon Richard , Charpentier Flavien , Le Scouarnec Solena
Published: May 2019

Aims

The Brugada syndrome (BrS) is an inherited cardiac disorder predisposing to ventricular arrhythmias. Despite considerable efforts, its genetic basis and cellular mechanisms remain largely unknown. The objective of this study was to identify a new susceptibility gene for BrS through familial investigation.

Methods and results

Whole-exome sequencing performed in a three-generation pedigree with five affected members allowed the identification of one rare non-synonymous substitution (p.R211H) in RRAD, the gene encoding the RAD GTPase, carried by all affected members of the family. Three additional rare missense variants were found in 3/186 unrelated index cases. We detected higher levels of RRAD transcripts in subepicardium than in subendocardium in human heart, and in the right ventricle outflow tract compared to the other cardiac compartments in mice. The p.R211H variant was then subjected to electrophysiological and structural investigations in human cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs). Cardiomyocytes derived from induced pluripotent stem cells from two affected family members exhibited reduced action potential upstroke velocity, prolonged action potentials and increased incidence of early afterdepolarizations, with decreased Na+ peak current amplitude and increased Na+ persistent current amplitude, as well as abnormal distribution of actin and less focal adhesions, compared with intra-familial control iPSC-CMs Insertion of p.R211H-RRAD variant in control iPSCs by genome editing confirmed these results. In addition, iPSC-CMs from affected patients exhibited a decreased L-type Ca2+ current amplitude.

Conclusion

This study identified a potential new BrS-susceptibility gene, RRAD. Cardiomyocytes derived from induced pluripotent stem cells expressing RRAD variant recapitulated single-cell electrophysiological features of BrS, including altered Na+ current, as well as cytoskeleton disturbances.
An Emergent Integrated Aging Process Conserved Across Primates
Authors: Wey Tina W , Roberge Émy , Legault Véronique , Kemnitz Joseph W , Ferrucci Luigi , Cohen Alan A
Published: May 2019

Aging is a complex process emerging from integrated physiological networks. Recent work using principal component analysis (PCA) of multisystem biomarkers proposed a novel fundamental physiological process, “integrated albunemia,” which was consistent across human populations and more strongly associated with age and mortality risk than individual biomarkers. Here we tested for integrated albunemia and associations with age and mortality across six diverse nonhuman primate species and humans. PCA of 13 physiological biomarkers recovered in all species a primary axis of variation (PC1) resembling integrated albunemia, which increased with age in all but one species but was less predictive of mortality risk. Within species, PC1 scores were often reliably recovered with a minimal biomarker subset and usually stable between sexes. Even among species, correlations in PC1 structure were often strong, but the effect of phylogeny was inconclusive. Thus, integrated albunemia likely reflects an evolutionarily conserved process across primates and appears to be generally associated with aging but not necessarily with negative impacts on survival. Integrated albunemia is unlikely to be the only conserved emergent physiological process; our findings hence have implications both for the evolution of the aging process and of physiological networks more generally.
Neighborhood Characteristics and Frailty: A Scoping Review
Authors: Fritz Heather , Cutchin Malcolm P , Gharib Jamil , Haryadi Neehar , Patel Meet , Patel Nandit
Published: May 2019

Background and Objectives

Frailty is highly prevalent in later life and associated with early mortality and adverse health outcomes. The neighborhood has been identified as an important contributor to individual health, and neighborhood characteristics may contribute to frailty development. A scoping review was conducted of the peer-reviewed literature to better understand how physical and social neighborhood characteristics contribute to frailty.

Research Design and Methods

Following an established scoping review methodology, we searched four peer-reviewed databases for relevant studies published from January 1, 2008, to December 31, 2018. Data extracted from studies included study characteristics, operationalization of neighborhood, the conceptual model of the neighborhood–frailty relationship, operationalization of frailty, and study findings for associations among neighborhood variables and frailty indicators.

Results

A total of 522 articles were identified and 13 articles were included in the final data charting. Existing studies suggest that neighborhood characteristics are associated with frailty in later life. Few studies articulated a conceptual model identifying exact mechanisms through which neighborhood factors affected frailty. Studies designs were mostly cross-sectional. Longitudinal studies did not measure neighborhood characteristics over time. Studies varied considerably in how they operationalized the neighborhood. Frailty was most commonly assessed using a 5-point phenotype or a frailty index approach.

Discussion and Implications

Findings indicate that research on the relationship between neighborhood characteristics and frailty is an emerging area of inquiry. Additional studies are needed to more definitely explicate mechanisms through which neighborhoods contribute to, or protect older adults from, frailty.
Single-cell transcriptomic landscape of nucleated cells in umbilical cord blood
Authors: Zhao Yi , Li Xiao , Zhao Weihua , Wang Jingwan , Yu Jiawei , Wan Ziyun , Gao Kai , Yi Gang , Wang Xie , Fan Bingbing , Wu Qinkai , Chen Bangwei , Xie Feng , Wu Jinghua , Zhang Wei , Chen Fang , Yang Huanming , Wang Jian , Xu Xun , Li Bin , Liu Shiping , Hou Yong , Liu Xiao
Published: May 2019

Background

For both pediatric and adult patients, umbilical cord blood (UCB) transplant is a therapeutic option for a variety of hematologic diseases, such as blood cancers, myeloproliferative disorders, genetic diseases, and metabolic disorders. However, the level of cellular heterogeneity and diversity of nucleated cells in UCB has not yet been assessed in an unbiased and systemic fashion. In the present study, nucleated cells from UCB were subjected to single-cell RNA sequencing to simultaneously profile the gene expression signatures of thousands of cells, generating a rich resource for further functional studies. Here, we report the transcriptomes of 17,637 UCB cells, covering 12 major cell types, many of which can be further divided into distinct subpopulations.

Results

Pseudotemporal ordering of nucleated red blood cells identifies wave-like activation and suppression of transcription regulators, leading to a polarized cellular state, which may reflect nucleated red blood cell maturation. Progenitor cells in UCB also comprise 2 subpopulations with activation of divergent transcription programs, leading to specific cell fate commitment. Detailed profiling of cytotoxic cell populations unveiled granzymes B and K signatures in natural killer and natural killer T-cell types in UCB.

Conclusions

Taken together, our data form a comprehensive single-cell transcriptomic landscape that reveals previously unrecognized cell types, pathways, and mechanisms of gene expression regulation. These data may contribute to the efficacy and outcome of UCB transplant, broadening the scope of research and clinical innovations.
A prototype knockoff filter for group selection with FDR control
Authors: Chen Jiajie , Hou Anthony , Hou Thomas Y
Published: May 2019

In many applications, we need to study a linear regression model that consists of a response variable and a large number of potential explanatory variables, and determine which variables are truly associated with the response. In Foygel Barber & Candès (2015, Ann. Statist., 43, 2055–2085), the authors introduced a new variable selection procedure called the knockoff filter to control the false discovery rate (FDR) and proved that this method achieves exact FDR control. In this paper, we propose a prototype knockoff filter for group selection by extending the Reid–Tibshirani (2016, Biostatistics, 17, 364–376) prototype method. Our prototype knockoff filter improves the computational efficiency and statistical power of the Reid–Tibshirani prototype method when it is applied for group selection. In some cases when the group features are spanned by one or a few hidden factors, we demonstrate that the Principal Component Analysis (PCA) prototype knockoff filter outperforms the Dai–Foygel Barber (2016, 33rd International Conference on Machine Learning (ICML 2016)) group knockoff filter. We present several numerical experiments to compare our prototype knockoff filter with the Reid–Tibshirani prototype method and the group knockoff filter. We have also conducted some analysis of the knockoff filter. Our analysis reveals that some knockoff path method statistics, including the Lasso path statistic, may lead to loss of power for certain design matrices and a specially designed response even if their signal strengths are still relatively strong.
The Brauer–Manin Obstruction for Zero-Cycles on K3 Surfaces
Authors: Ieronymou Evis
Published: May 2019

We study local–global principles for zero-cycles on $K3$ surfaces defined over number fields. We follow an idea of Liang to use the trivial fibration over the projective line.
From the Pipeline to the Bedside: Advances and Challenges in Clinical Metagenomics
Authors: Dulanto Chiang Augusto , Dekker John P
Published: May 2019

Next-generation sequencing (NGS) technologies have revolutionized multiple areas in the field of infectious diseases, from pathogen discovery to characterization of genes mediating drug resistance. Consequently, there is much anticipation that NGS technologies may be harnessed in the realm of diagnostic methods to complement or replace current culture-based and molecular microbiologic techniques. In this context, much consideration has been given to hypothesis-free, culture-independent tests that can be performed directly on primary clinical samples. The closest realizations of such universal diagnostic methods achieved to date are based on targeted amplicon and unbiased metagenomic shotgun NGS approaches. Depending on the exact details of implementation and analysis, these approaches have the potential to detect viruses, bacteria, fungi, parasites, and archaea, including organisms that were previously undiscovered and those that are uncultivatable. Shotgun metagenomics approaches additionally can provide information on the presence of virulence and resistance genetic elements. While many limitations to the use of NGS in clinical microbiology laboratories are being overcome with decreasing technology costs, expanding curated pathogen sequence databases, and better data analysis tools, there remain many challenges to the routine use and implementation of these methods. This review summarizes recent advances in applications of targeted amplicon and shotgun-based metagenomics approaches to infectious disease diagnostic methods. Technical and conceptual challenges are considered, along with expectations for future applications of these techniques.
Humoral Immune Correlates for Prevention of Postnatal Cytomegalovirus Acquisition
Authors: Saccoccio Frances M , Jenks Jennifer A , Itell Hannah L , Li Shuk Hang , Berry Madison , Pollara Justin , Casper Corey , Gantt Soren , Permar Sallie R
Published: May 2019

Background

Development of a cytomegalovirus (CMV) vaccine is a high priority. However, the ability of antibodies to protect against CMV infection is not well characterized. Studies of maternal antibodies in infants offer the potential to identify humoral correlates of protection against postnatal acquisition.

Methods

This hypothesis-generating study analyzed 29 Ugandan mother-infant pairs that were followed weekly for CMV acquisition. Seventeen mothers and no infants were infected with human immunodeficiency virus (HIV). We evaluated the association between CMV-specific immunoglobulin G (IgG) responses in mothers at the time of delivery and their infants’ CMV status at 6 months of age. We also assessed levels of CMV-specific IgG in infants at 6 weeks of age. CMV-specific IgG responses in the mother-infant pairs were then analyzed on the basis of perinatal HIV exposure.

Results

We found similar levels of multiple CMV glycoprotein–specific IgG binding specificities and functions in mothers and infants, irrespective of perinatal HIV exposure or infant CMV status at 6 months of age. However, the glycoprotein B–specific IgG titer, measured by 2 distinct assays, was higher in infants without CMV infection and was moderately associated with delayed CMV acquisition.

Conclusions

These data suggest that high levels of glycoprotein B–specific IgG may contribute to the partial protection against postnatal CMV infection afforded by maternal antibodies, and they support the continued inclusion of glycoprotein B antigens in CMV vaccine candidates.
Prevalence, Concordance, and Transmission of Human Papillomavirus Infection Among Heterosexual Couples in Liuzhou, China: An Observational Perspective Study
Authors: Su Yingying , Wei Feixue , Huang Xiumin , Li Yafei , Qiu Lingxian , Hu Fangfang , Yang Chaoqi , Zhang Yuejing , Yin Kai , Li Mingqiang , Wu Ting , Xia Ningshao , Zhang Jun
Published: May 2019

Background

Knowledge of human papillomavirus (HPV) transmission dynamics, which have important public health implications for designing HPV vaccination strategies, is scarce in undeveloped areas.

Methods

From May to July 2014, 390 couples were enrolled from the general population in Liuzhou, China. Exfoliated cells from male penis shaft/glans penis/coronary sulcus (PGC) and perianal/anal canal (PA) sites and from female vaginal, vulvar, and PA sites were collected biannually for 1 year.

Results

The HPV type-specific concordance rate between couples was 15.5% (95% confidence interval [CI], 8.5%–25.0%). For anogenital HPV transmission, the male-to-female transmission rate (11.5 [95% CI, 4.3–30.7] per 1000 person-months) was similar to the female-to-male transmission rate (11.3 [95% CI, 5.9–21.7] per 1000 person-months). The concordance rates between male PGC site and female vaginal, vulvar, and PA sites were 20.0%, 21.8%, and 14.9%, respectively, which were significantly higher than expected by chance. Infections transmitted from males to females seemed mainly originated from male genital sites, whereas for female-to-male transmission, the vaginal, vulvar, and PA sites might be all involved.

Conclusions

Among the heterosexual couples with relatively conservative sexual behavior, the anogenital HPV transmission rate for females to males is similar to that of males to females. In addition to the vagina and vulva, the female PA site is also an important reservoir for HPV transmission.
Enterococcus faecalis Escapes Complement-Mediated Killing via Recruitment of Complement Factor H
Authors: Ali Youssif M , Sim Robert B , Schwaeble Wilhelm , Shaaban Mona I
Published: May 2019

Background

Enterococcus faecalis is considered to be the most important species of enterococci responsible for blood stream infections in critically ill patients. In blood, the complement system is activated via the classical pathway (CP), the lectin pathway (LP), or the alternative pathway (AP), and it plays a critical role in opsonophagocytosis of bacteria including E faecalis.

Methods

In a mouse model of enterococcus peritonitis, BALB-C mice were challenged with a high dose of E faecalis 12 hours after intraperitoneal administration of anti-Factor H (FH) antibodies or isotype control. Four hours later, control mice developed higher bacterial burden in blood and organs compared with mice treated with anti-FH antibodies.

Results

We demonstrate that complement recognition molecules C1q, CL-11, and murine ficolin-A bind the enterococcus and drive the CP and the LP in human and mouse. We further describe that E faecalis evades the AP by recruitment of FH on its surface. Our results show a strong C3b deposition on E faecalis via both the CP and the LP but not through the AP.

Conclusions

These findings indicate that E faecalis avoids the complement phagocytosis by the AP via sequestering complement FH from the host blood.
First year of pre-exposure prophylaxis implementation in France with daily or on-demand tenofovir disoproxil fumarate/emtricitabine
Authors: Siguier M , Mera R , Pialoux G , Ohayon M , Cotte L , Valin N , Ghosn J , Cua E , Pintado C , Chas J , Barriere G , Durand F , Molina J M
Published: May 2019

Background

In January 2016, the French Medicine Agency initiated a Temporary Recommendation for Use (TRU) to allow the use of oral intake of tenofovir disoproxil fumarate and emtricitabine for pre-exposure prophylaxis (PrEP) in adults at high risk of HIV. We report the results of the first year of PrEP implementation in France.

Methods

Data were collected by physicians using a secured web subject-monitoring interface, with two forms: an initiation form, with patients’ baseline characteristics, and an HIV seroconversion form. Univariate and adjusted multivariate analysis using a logistic regression model were performed to identify baseline factors associated with on-demand PrEP regimen prescription.

Results

From 4 January 2016 to 28 February 2017, 3405 subjects were enrolled, with 2774 initiation forms completed; 98.1% were male and 96.9% were MSM. An on-demand regimen was prescribed to 57% of subjects. Older age (OR for participants older than 50 years = 1.76, 95% CI 1.35–2.3, P < 0.001) and site of prescription (OR of former IPERGAY sites = 2.28, 95% CI 1.84–2.83, P < 0.001) were associated with on-demand prescription. Those reporting sexually transmitted infection (STI) and condomless anal sex with at least two different partners were less likely to receive on-demand PrEP (OR = 0.68, 95% CI 0.57–0.82 and 0.75, 95% CI 0.57–0.98, respectively; P < 0.05 for all). Four breakthrough HIV infections were reported during the study, in the context of PrEP interruption or acute infection at the time of PrEP initiation.

Conclusions

In a real-life setting in France, PrEP was used, either daily or on-demand, mostly by MSM, with breakthrough infections being rare.
To Acclimate or Not to Acclimate? Simultaneous Positive and Negative Effects of Acclimation on Susceptibility of Tribolium confusum (Coleoptera: Tenebrionidae) and Oryzaephilus surinamensis (Coleoptera: Silvanidae) to Low Temperatures
Authors: Athanassiou Christos G , Arthur Frank H , Kavallieratos Nickolas G , Hartzer Kris L
Published: May 2019

Laboratory tests on acclimated and nonacclimated life stages of Tribolium confusum Jacquelin du Val (Coleoptera: Tenebrionidae) (adults, pupae, larvae, and eggs) and Oryzaephilus surinamensis (L.) (Coleoptera: Silvanidae) (adults, larvae, and eggs) were conducted at 0, –5, –10, and –15°C to evaluate effects of acclimation on susceptibility to cold treatment. Acclimation of all tested life stages for 7 d at 15°C affected susceptibility of both species to the cold temperatures. After 1 d exposures for ≥2 h, acclimated adults had a noticeable increase in cold tolerance compared with nonacclimated adults for both tested species. Nonacclimated pupae of T. confusum were equally susceptible to cold compared with acclimated pupae at short exposures to low temperatures. Exposure of nonacclimated life stages of T. confusum, at –10°C for 1 d gave 0% survival. Similarly, almost all (99.6%) nonacclimated individuals of O. surinamensis died at –10°C. At 0°C, nonacclimated larvae were more cold tolerant than acclimated larvae, but this trend was reversed when larvae were exposed to –5°C. Mixed results were obtained for larvae of O. surinamensis because in some of the combinations tested, nonacclimated larvae were more tolerant, even at temperatures that were lower than 0°C. In contrast to O. surinamensis, eggs of T. confusum that had not been exposed to cold were not affected by acclimation, while exposure to cold showed increased cold hardiness in acclimated eggs. Results show that individual stored-product insect species may have mixed susceptibility to cold temperatures, which must be taken into account when using cold treatment as a management strategy.
Drug ReposER: a web server for predicting similar amino acid arrangements to known drug binding interfaces for potential drug repositioning
Authors: Ab Ghani Nur Syatila , Ramlan Effirul Ikhwan , Firdaus-Raih Mohd
Published: May 2019

A common drug repositioning strategy is the re-application of an existing drug to address alternative targets. A crucial aspect to enable such repurposing is that the drug's binding site on the original target is similar to that on the alternative target. Based on the assumption that proteins with similar binding sites may bind to similar drugs, the 3D substructure similarity data can be used to identify similar sites in other proteins that are not known targets. The Drug ReposER (DRug REPOSitioning Exploration Resource) web server is designed to identify potential targets for drug repurposing based on sub-structural similarity to the binding interfaces of known drug binding sites. The application has pre-computed amino acid arrangements from protein structures in the Protein Data Bank that are similar to the 3D arrangements of known drug binding sites thus allowing users to explore them as alternative targets. Users can annotate new structures for sites that are similarly arranged to the residues found in known drug binding interfaces. The search results are presented as mappings of matched sidechain superpositions. The results of the searches can be visualized using an integrated NGL viewer. The Drug ReposER server has no access restrictions and is available at http://mfrlab.org/drugreposer/.
Is hypovitaminosis D associated with fibromyalgia? A systematic review
Authors: Martins Yandara A , Cardinali Camila A E F , Ravanelli Maria Ida , Brunaldi Kellen
Published: May 2019

Context

Recent findings have suggested a high prevalence of vitamin D deficiency or insufficiency in fibromyalgia (FM) patients despite the lack of clinical and pathophysiological evidence.

Objective

A systematic review was conducted to examine the association between vitamin D status and FM, including the effect of vitamin D supplementation.

Data source

PubMed, LILACS, Scopus, SciELO, Cochrane, and EMBASE were searched, from January 2000 to July 2018, using the descriptors “Fibromyalgia” and “Vitamin D.”

Study selection

Trials including FM patients in whom vitamin D levels were assessed were eligible for inclusion.

Data extraction

Data comprised age, gender, country, aims, bias, diagnosis criteria, cutoff point, and status of vitamin D, together with FM symptoms and vitamin D supplementation protocol.

Results

A total of 26 articles were selected. Most of the studies were found to present unreliable control groups and small samples. Experimental data on vitamin D supplementation indicated improvement in certain FM symptoms.

Conclusion

Prevalence of hypovitaminosis D in the FM population and the cause-effect relationship were inconclusive. Nevertheless, vitamin D supplementation may be considered as a co-adjuvant in FM therapy.
Interaction between molecular clouds and MeV–TeV cosmic-ray protons escaped from supernova remnants
Authors: Makino Ken , Fujita Yutaka , Nobukawa Kumiko K , Matsumoto Hironori , Ohira Yutaka
Published: May 2019

Recent discovery of the X-ray neutral iron line (Fe  i Kα at 6.40 keV) around several supernova remnants (SNRs) show that MeV cosmic-ray (CR) protons are distributed around the SNRs and are interacting with neutral gas there. We propose that these MeV CRs are the ones that have been accelerated at the SNRs together with GeV–TeV CRs. In our analytical model, the MeV CRs are still confined in the SNR when the SNR collides with molecular clouds. After the collision, the MeV CRs leak into the clouds and produce the neutral iron line emissions. On the other hand, GeV–TeV CRs had already escaped from the SNRs and emitted gamma-rays through interaction with molecular clouds surrounding the SNRs. We apply this model to the SNRs W 28 and W 44 and show that it can reproduce the observations of the iron line intensities and the gamma-ray spectra. This could be additional support of the hadronic scenario for the gamma-ray emissions from these SNRs.
A Solidaristic Approach to Workers’ Compensation Reform in Taiwan
Authors: Yeh Ming-Jui
Published: May 2019

The workers’ compensation system in Taiwan cannot provide sufficient coverage for all workers. This essay adopts a solidaristic approach to address this issue by analyzing the reasons why workers’ compensation is underdeveloped in Taiwan and what could be done to persuade more key actors to support the reform for a more just policy arrangement. First, through comparison with the healthcare system, it is argued that the lack of solidarity and the perception of relevant similarities could explain the underdevelopment of workers’ compensation. Second, the essay turns to the normative aspect of the issue. Compared with other normative political theories, Iris M. Young’s social connection model provides specific normative guidance that is useful for justifying the allocation of responsibility for a more just workers’ compensation reform.
Channel Flow Past A Near-Wall Body
Authors: Smith F T , Servini P
Published: May 2019

Near-wall behaviour arising when a finite sized body moves in a channel flow is investigated for high flow rates. This is over the interactive-flow length scale that admits considerable upstream influence. The focus is first on quasi-steady two-dimensional flow past a thin body in the outer reaches of one of the viscous wall layers. The jump conditions near the front of the body play an important part in the whole solution which involves an unusual multi-structured flow due to the presence of the body: flows above, below, ahead of and behind the body interact fully. Analytical solutions are presented and the repercussions for shorter and longer bodies are then examined. Second, implications are followed through for the movement of a free body in a dynamic fluid–body interaction. Particular key findings are that instability persists for all body lengths, the growth rate decreases like the $1/4$ power of distance as the body approaches the wall, and lift production on the body is dominated by high pressures from an unexpected flow region emerging on the front of the body.
Pairwise Kidney Exchange over the Blood Group Barrier
Authors: Andersson Tommy , Kratz Jörgen
Published: May 2019

Advances in medical technology have made kidney transplants over the blood group barrier feasible. This article investigates how such technology should be implemented when designing pairwise kidney exchange programs. The possibility to receive a kidney transplant from a blood group incompatible donor motivates an extension of the preference domain, allowing patients to distinguish between compatible donors and half-compatible donors (i.e. blood group incompatible donors that only become compatible after undergoing an immunosuppressive treatment). It is demonstrated that the number of transplants can be substantially increased by providing an incentive for patients with half-compatible donors to participate in kidney exchange programs. The results also suggest that the technology is beneficial for patient groups that are traditionally disadvantaged in kidney exchange programs (e.g. blood group O patients). The positive effect of allowing transplants over the blood group barrier is larger than the corresponding effects of including altruistic patient–donor pairs or of allowing three-way exchanges in addition to pairwise exchanges.
The relationship between patient acceptable symptom state and disease activity in patients with psoriatic arthritis
Authors: Fei Jeanie Z , Perruccio Anthony V , Ye Justine Y , Gladman Dafna D , Chandran Vinod
Published: May 2019

Objectives

The Psoriatic Arthritis Disease Activity Score (PASDAS) and Disease Activity Index for Psoriatic Arthritis (DAPSA) are composite PsA disease activity measures. We sought to identify the PASDAS and DAPSA cut-off points consistent with patient acceptable symptom state (PASS), the threshold of symptoms beyond which patients consider themselves well, and examine PASS across published PASDAS and DAPSA thresholds for low, moderate and high disease activity.

Methods

We used a standard protocol including physician assessment and patient-reported outcomes to prospectively record measures required to calculate PASDAS and DAPSA. We identified PASS thresholds for the PASDAS and DAPSA using receiver operating characteristics curve analyses. We assessed the frequency of reporting acceptable symptom state across disease activity thresholds for PASDAS and DAPSA scores.

Results

A total of 229 patients (58.5% male, mean age 55.5 years, mean disease duration 17.1 years) were recruited. The PASS threshold for the PASDAS was 3.79 [area under the curve (AUC) 0.86, sensitivity 0.75, specificity 0.82] and for the DAPSA was 11.10 (AUC 0.91, sensitivity 0.89, specificity 0.82). With the PASDAS, 90% of patients defined as having low disease activity considered their symptom state acceptable, compared with 55% and 17% among those with moderate and high disease activity, respectively. With the DAPSA, 98% of patients in disease remission considered their symptom state acceptable compared with 85, 22 and 18% among those with low, moderate and high disease activity, respectively.

Conclusion

We have defined PASS thresholds for PASDAS and DAPSA. The PASDAS target for low disease activity and DAPSA targets of low disease activity or remission align well with PASS.
People are neglected, not diseases: the relationship between disability and neglected tropical diseases
Authors: Hamill Louise Claire , Haslam Dominic , Abrahamsson Sofia , Hill Becks , Dixon Ruth , Burgess Heather , Jensen Kimberly , D’Souza Susan , Schmidt Elena , Downs Philip
Published: May 2019

People with disabilities and the neglected tropical diseases (NTDs) are separately receiving increased focus. In light of this positive development, and the similarities and intersections between the negative impacts experienced by both people with disabilities and people with NTDs, we believe now is the right time to focus attention on the overlap between the two. Both people with NTDs and people with disabilities experience a myriad of overlapping negative health, financial and socio-cultural consequences. Despite this, we believe that disability is not yet properly prioritised on the development agenda, and that there are multiple opportunities to make NTD programming more inclusive, to the benefit of those at this neglected intersection and beyond. There are both opportunities and need to scale up, integrate, and invest in inclusive, health system-focused NTD programming. Realisation of the Sustainable Development Goals, Universal Health Coverage, and the control and elimination of NTDs all rely on ensuring people with disabilities are not left behind.
A Turnip Mosaic Virus Determinant of Systemic Necrosis inNicotiana benthamianaand a Novel Resistance-Breaking Determinant in Chinese Cabbage Identified from Chimeric Infectious Clones
Authors: Kim Ik-Hyun , Ju Hye-Kyoung , Gong Junsu , Han Jae-Yeong , Seo Eun-Young , Cho Sang-Won , Hu Wen-Xing , Choi Su Ryun , Lim Yong Pyo , Domier Leslie L. , Hammond John , Lim Hyoun-Sub
Published: May 2019

Infectious clones of Korean turnip mosaic virus (TuMV) isolates KIH1 and HJY1 share 88.1% genomic nucleotides and 96.4% polyprotein amino acid identity, and they induce systemic necrosis or mild mosaic, respectively, in Nicotiana benthamiana. Chimeric constructs between these isolates exchanged the 5′, central, and 3′ domains of KIH1 (K) and HJY1 (H), where the order of the letters indicates the origin of these domains. KIH1 and chimeras KHH and KKH induced systemic necrosis, whereas HJY1 and chimeras HHK, HKK, and HKH induced mild symptoms, indicating the determinant of necrosis to be within the 5′ 3.9 kb of KIH1; amino acid identities of the included P1, Helper component protease, P3, 6K1, and cylindrical inclusion N-terminal domain were 90.06, 98.91, 93.80, 100, and 100%, respectively. Expression of P1 or P3 from a potato virus X vector yielded symptom differences only between P3 of KIH1 and HJY1, implicating a role for P3 in necrosis in N. benthamiana. Chimera KKH infected Brassica rapa var. pekinensis ‘Norang’, which was resistant to both KIH1 and HJY1, indicating that two separate TuMV determinants are required to overcome the resistance. Ability of diverse TuMV isolates, chimeras, and recombinants to overcome resistance in breeding lines may allow identification of novel resistance genes.
Bridging the Gap: Holistic Review to Increase Diversity in Graduate Medical Education
Authors: Aibana Omowunmi , Swails Jennifer L. , Flores Renee J. , Love LaTanya
Published: May 2019

Problem

Racial and ethnic disparities in health outcomes remain pervasive in the U.S. health care system. Increasing the diversity of the physician workforce is recognized as an important component of addressing these disparities. Holistic review, which gives balanced consideration to applicants’ academic metrics, experiences, and attributes, has gained popularity in undergraduate medical education and led to improvement in student diversity. Limited research has investigated how holistic review and other strategies can be implemented in graduate medical education to enhance diversity.

Approach

The internal medicine (IM) residency program of the John P. and Kathrine G. McGovern Medical School implemented a pilot intervention in academic years (AY) 2016–2017 and 2017–2018 aimed at increasing the number of matriculating residents who are underrepresented in medicine (URM). The intervention included (1) using holistic review in the process of selecting applicants for interview, (2) standardizing the interview encounters, and (3) explicitly highlighting the program’s commitment to diversity on interview days.

Outcomes

From AY 2015–2016 (preintervention) to AY 2017–2018, the percentage of URM applications reviewed increased from 14.1% (180/1,276) to 20.4% (183/897), the proportion of URM applicants interviewed rose from 16.0% (60/374) to 24.5% (95/388), and the proportion of URM residents matriculating increased from 12.5% (5/40) to 31.7% (13/41).

Next Steps

Further efforts are needed to expand the pool of URM applicants at McGovern and elsewhere and to identify how holistic review can be widely employed in other IM residency programs and in other specialties.
Oxygenation Impairment during Anesthesia
Authors: Hedenstierna Göran , Tokics Leif , Scaramuzzo Gaetano , Rothen Hans U. , Edmark Lennart , Öhrvik John
Published: May 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Anesthesia is increasingly common in elderly and overweight patients and prompted the current study to explore mechanisms of age- and weight-dependent worsening of arterial oxygen tension (Pao
2).

Methods

This is a primary analysis of pooled data in patients with (1) American Society of Anesthesiologists (ASA) classification of 1; (2) normal forced vital capacity; (3) preoxygenation with an inspired oxygen fraction (Fio
2) more than 0.8 and ventilated with Fio
2 0.3 to 0.4; (4) measurements done during anesthesia before surgery. Eighty patients (21 women and 59 men, aged 19 to 69 yr, body mass index up to 30 kg/m2) were studied with multiple inert gas elimination technique to assess shunt and perfusion of poorly ventilated regions (low ventilation/perfusion ratio [

JOURNAL/anet/04.03/00000542-201907000-00018/inline-graphic1/v/2024-12-03T192354Z/r/image-png

]) and computed tomography to assess atelectasis.

Results

Pao
2/Fio
2 was lower during anesthesia than awake (368; 291 to 470 [median; quartiles] vs. 441; 397 to 462 mm Hg; P = 0.003) and fell with increasing age and body mass index. Log shunt was best related to a quadratic function of age with largest shunt at 45 yr (r
2 =0.17, P = 0.001). Log shunt was linearly related to body mass index (r
2 = 0.15, P < 0.001). A multiple regression analysis including age, age2, and body mass index strengthened the association further (r
2 = 0.27). Shunt was highly associated to atelectasis (r
2 = 0.58, P < 0.001). Log low

JOURNAL/anet/04.03/00000542-201907000-00018/inline-graphic2/v/2024-12-03T192354Z/r/image-png

showed a linear relation to age (r
2 = 0.14, P = 0.001).

Conclusions

Pao
2/Fio
2 ratio was impaired during anesthesia, and the impairment increased with age and body mass index. Shunt was related to atelectasis and was a more important cause of oxygenation impairment in middle-aged patients, whereas low

JOURNAL/anet/04.03/00000542-201907000-00018/inline-graphic3/v/2024-12-03T192354Z/r/image-png

, likely caused by airway closure, was more important in elderly patients. Shunt but not low

JOURNAL/anet/04.03/00000542-201907000-00018/inline-graphic4/v/2024-12-03T192354Z/r/image-png

increased with increasing body mass index. Thus, increasing age and body mass index impaired gas exchange by different mechanisms during anesthesia.
Quantitative Research Methods in Medical Education
Authors: Ratelle John T. , Sawatsky Adam P. , Beckman Thomas J.
Published: May 2019

There has been a dramatic growth of scholarly articles in medical education in recent years. Evaluating medical education research requires specific orientation to issues related to format and content. Our goal is to review the quantitative aspects of research in medical education so that clinicians may understand these articles with respect to framing the study, recognizing methodologic issues, and utilizing instruments for evaluating the quality of medical education research. This review can be used both as a tool when appraising medical education research articles and as a primer for clinicians interested in pursuing scholarship in medical education.
Genetic Inheritance of Late-Onset, Down-Sloping Hearing Loss and Its Implications for Auditory Rehabilitation
Authors: Song Mee Hyun , Jung Jinsei , Rim John Hoon , Choi Hye Ji , Lee Hack June , Noh Byunghwa , Lee Jun Suk , Gee Heon Yung , Choi Jae Young
Published: May 2019

Objectives:

Late-onset, down-sloping sensorineural hearing loss has many genetic and nongenetic etiologies, but the proportion of this commonly encountered type of hearing loss attributable to genetic causes is not well known. In this study, the authors performed genetic analysis using next-generation sequencing techniques in patients showing late-onset, down-sloping sensorineural hearing loss with preserved low-frequency hearing, and investigated the clinical implications of the variants identified.

Design:

From a cohort of patients with hearing loss at a tertiary referral hospital, 18 unrelated probands with down-sloping sensorineural hearing loss of late onset were included in this study. Down-sloping hearing loss was defined as a mean low-frequency threshold at 250 Hz and 500 Hz less than or equal to 40 dB HL and a mean high-frequency threshold at 1, 2, and 4 kHz greater than 40 dB HL. The authors performed whole-exome sequencing and segregation analysis to identify the genetic causes and evaluated the outcomes of auditory rehabilitation in the patients.

Results:

There were nine simplex and nine multiplex families included, in which the causative variants were found in six of 18 probands, demonstrating a detection rate of 33.3%. Various types of variants, including five novel and three known variants, were detected in the MYH14, MYH9, USH2A, COL11A2, and TMPRSS3 genes. The outcome of cochlear and middle ear implants in patients identified with pathogenic variants was satisfactory. There was no statistically significant difference between pathogenic variant-positive and pathogenic variant-negative groups in terms of onset age, family history of hearing loss, pure-tone threshold, or speech discrimination scores.

Conclusions:

The proportion of patients with late-onset, down-sloping hearing loss identified with potentially causative variants was unexpectedly high. Identification of the causative variants will offer insights on hearing loss progression and prognosis regarding various modes of auditory rehabilitation, as well as possible concomitant syndromic features.
Mimics of axial spondyloarthritis
Authors: Merjanah Sali , Igoe Ann , Magrey Marina
Published: May 2019

Purpose of review

Axial spondyloarthritis (AxSpA) is a distinct clinical entity with characteristic clinical and radiographic features; however, a multitude of other metabolic, infectious and inflammatory disorders mimic it both clinically and radiographically.

Recent findings

We present in this review article recent updates about the various disease entities and conditions that may mimic AxSpA and how to differentiate among them. The sensitivity and specificity of MRI in diagnosing AxSpA has limitations and needs to be interpreted in the context of the clinical picture. Interestingly, some recent studies have highlighted that a relatively high prevalence of bone marrow edema on pelvic MRIs in healthy volunteers which could even be categorized as having a ‘positive MRI’ as defined by Assessment of Spondyloarthritis International Society. Another study revealed that a substantial proportion of patients with suspected sacroiliitis were more commonly diagnosed with diseases other than inflammatory sacroiliitis. On the basis of these reports, it is prudent to request MRIs in the appropriate clinical context and interpreted with caution taking into considerations the wide differential diagnosis of such MRI changes.

Highlighting the clinical pearls that differentiate disorders suspected of having sacroiliitis will lead to earlier and correct diagnosis and management; however, one must always take into considerations the radiographic and MRI findings in addition to the clinical presentations in order to make the appropriate diagnosis.
Effect of Side Struts on the Strength of Long Arm Plaster Splints: A Biomechanical Study
Authors: Thompson Samuel F. , McBride Conor , Conant Scott H. , Moore Marc C. , Lewis Thomas R.
Published: May 2019

Background:

There are multiple methods of achieving upper extremity immobilization after pediatric elbow injuries; however, no biomechanical study has established an optimal construct. The goal of this study was to compare the strength of commonly used long arm splints and to evaluate the effect of reinforcing plaster splints with side struts.

Methods:

Five categories of long arm posterior slab splints were tested: 4-inch plaster without side struts, 4-inch plaster with a medial side strut, 4-inch plaster with medial and lateral side struts, 5-inch plaster without side struts, and 4-inch fiberglass splint material without side struts. There were 4 splints in each group. As a control, 4 half fiberglass long arm casts were also tested. Each splint or cast was mounted on a single-column tensile tester and a 3-point bending load was applied to simulate an extension moment at the elbow. The maximum load before failure was measured and an ANOVA model was used to analyze the differences between groups. Additionally, a retrospective chart review was performed of pediatric patients who were immobilized postoperatively in a long arm plaster splint with side struts. We collected data on patient age, type of fracture, time from splint application in the operating room to removal in clinic, length of follow-up, and any complications.

Results:

The 4-inch plaster splints reinforced with 2 struts had the highest average maximum load to failure (731±143 N), which was significantly higher than the 4-inch plaster splints with one strut (505±48 N) (P=0.01) and the 4-inch plaster splints without struts (100±10 N) (P<0.001). The half fiberglass casts failed at an average maximum load of 655±96 N, however there was no statistically significant difference compared with 4-inch plaster splints with 2 struts (P=0.10). The 5-inch plaster splints without side struts failed at a greater average maximum load (341±110 N) compared with the splints constructed with fiberglass material without side struts (233±61 N) (P=0.03). A total of 140 patients were identified in the retrospective review. Splint-related complications occurred in 2 patients.

Conclusions:

The addition of both 1 and 2 side struts to a 4-inch long arm plaster splint significantly increased the load to failure. The strength of 4-inch plaster splints with 2 side struts was comparable to that of half fiberglass casts.

Level of Evidence:

NA (biomechanical study).