bluuebunny/crossref_metadata_2025 huggingface dataset:
Hashin–Shtrikman bounds of periodic linear elastic media with cubic symmetry
Authors: Mejak George
Published: February 2020

Based on the Hashin–Shtrikman variational principle, novel bounds on the effective shear moduli of a two-phase periodic composite are derived. The composite constituents are assumed to be isotropic, while the microstructure is assumed to exhibit cubic symmetry. A solution of the subsidiary boundary value problem is expressed as a double contraction of a fourth-order cubic tensor with the applied macroscopic strain. The bounds for cubic shear moduli are new, while the bounds for the bulk modulus are equal to the classical ones. The new bounds are verified for composites with the cubic, frame, octet and cubic + octet structures. It is shown that they are nearly attained for the cubic, octet and cubic + octet structures.
Integrating Social Dynamics Into Modeling Cigarette and E-Cigarette Use
Authors: Chu Kar-Hai , Shensa Ariel , Colditz Jason B. , Sidani Jaime E. , Hoffman Beth L. , Sinclair David , Krauland Mary G. , Primack Brian A.
Published: February 2020

Background. The use of electronic cigarettes (e-cigarette) offers potential to facilitate cigarette smoking cessation, yet potentially increases risk of cigarette smoking initiation. This relationship has been primarily modeled in mathematical ways that often do not represent real-world complexities, which could inform decisions regarding local prevention programs or policies. Aims. To develop a model of cigarette and e-cigarette use that combines current research on tobacco use and incorporates real-world geographic and demographic data. Method. We used a platform for developing agent-based models with demographic information representative of the population in Pennsylvania. We developed three models of cigarette and e-cigarette use. The primary outcome for each was the total number of users for cigarette, e-cigarette, and total nicotine. The first model applied current cigarette and e-cigarette data, the second tested the effect of implementing a program of e-cigarette education and policies, and the third considered a social contagion factor, where local schools functioned as a transmission vector. Results. The baseline and social contagion models found an overall decline in cigarette use but an increase in e-cigarette and total nicotine use. The education/policies model had declines in all categories. Sensitivity analysis suggested the importance of nuanced e-cigarette/cigarette interactions when modeling tobacco use. Discussion. Public health campaigns that focus on reducing youth e-cigarette usage can have a large effect. Social contagion should be strongly considered when studying e-cigarette spread. Conclusion. Targeted public health campaigns focused on reducing school prevalence of e-cigarette use may be particularly valuable.
Systematic Review of Criminal and Legal Involvement After Substance Use and Mental Health Treatment Among Veterans: Building Toward Needed Research
Authors: Timko Christine , Nash Amia , Owens Mandy D , Taylor Emmeline , Finlay Andrea K
Published: February 2020

Evidence indicates that substance use and mental health treatment is often associated with reduced criminal activity. The present systematic review examined this association among military veterans, and aimed to provide a comprehensive summary of needed research to further contribute to reduced criminal activity among veterans. This systematic review was derived from a scoping review that mapped existing research on justice-involved veterans’ health. For the current systematic review, a subset of 20 publications was selected that addressed the question of whether criminal activity declines among veterans treated for substance use and mental health disorders. Generally, veterans improved on criminal outcomes from pre- to post-treatment for opioid use, other substance use, or mental health conditions, and more sustained treatment was associated with better outcomes. This occurred despite high rates of criminal involvement among veterans prior to entering treatment. Needed are substance use and mental health treatment studies that include women justice-involved veterans, follow criminally-active veterans for longer periods of time, and use validated and reliable measures of criminal activity with fully transparent statistical procedures. Future randomized trials should evaluate new treatments against evidence-based treatments (versus no-treatment control conditions). Subsequent studies should examine how to link veterans to effective treatments, facilitate sustained treatment engagement, and ensure the availability of effective treatments, and examine mechanisms (mediators and moderators) that explain the association of treatment with reduced criminal activity among veterans. Best practices are needed for reducing criminal activity among the minority of justice-involved veterans who do not have diagnosed substance use and/or mental health disorders.
Prognostic role of intrathecal IgM synthesis in multiple sclerosis: Results from a clinical series
Authors: Fonderico Mattia , Biagioli Tiziana , Lanzilao Luisa , Bellinvia Angelo , Fratangelo Roberto , Pastò Luisa , Prestipino Elio , Razzolini Lorenzo , Tudisco Laura , Ginestroni Andrea , Vuolo Luisa , Fainardi Enrico , Ballerini Clara , Portaccio Emilio , Amato Maria Pia
Published: February 2020

Background:

There is emerging evidence that intrathecal IgM synthesis (ITMS) is a risk factor for conversion to clinically defined multiple sclerosis (CDMS) in clinically isolated syndrome (CIS) patients.

Objectives:

The objective of this study is to verify the prognostic role of ITMS as a risk factor for the second clinical attack in patients after the first demyelinating event.

Methods:

Monocentric observational study performed on prospectively acquired clinical data and retrospective evaluation of magnetic resonance imaging (MRI) data. ITMS was assessed according to Reiber’s non-linear function. We compared time to the second attack by using Kaplan–Meier curves and performed adjustment by Cox regression analysis.

Results:

Demographics and clinical data were collected prospectively in a cohort of 68 patients. ITMS occurred in 40% (27/68) of patients who had a higher T1-hypointense lesion load at brain MRI ( p = 0.041). In multivariate Cox regression analysis (adjusted for age, sex, baseline Expanded Disability Status Scale, IgG oligoclonal bands and disease-modifying treatment exposure), relapsing-remitting multiple sclerosis (MS) patients with ITMS were at higher risk to experience a second clinical attack (adjusted hazard ratio (aHR) = 6.3, 95% confidence interval (CI) = 2.1–18.4, p = 0.001).

Conclusion:

Together with previous studies, our findings support the role of ITMS as a prognostic biomarker in MS.
Educationalisation of youth unemployment through lifelong learning policies in Europe
Authors: Valiente Oscar , Capsada-Munsech Queralt , G de Otero Jan Peter
Published: February 2020

In the aftermath of the 2008 Global Financial Crisis, European authorities reinforced the economic objectives of European lifelong learning policy, promoting employability solutions to address youth unemployment, and increasing their political influence on the implementation of national lifelong learning reforms. This article investigates to what extent these supranational policy orientations have been translated into concrete national lifelong learning initiatives. Although European countries were not equally affected in terms of time and intensity by the rise in youth unemployment rates, the political responses from their governments shared a central focus on employability solutions to youth unemployment in lifelong learning policy reforms. Our comparative analysis shows how different lifelong learning policy initiatives managed to ‘educationalise’ a structural economic problem (i.e. youth unemployment) into an individual educational concern (i.e. lack of education and skills). We argue that the ‘educationalisation’ of youth unemployment through lifelong learning policies is a crisis management strategy, which has allowed governments to focus on the individual symptoms of the problem while avoiding offering solutions to the underlying structural causes of young people’s poor labour market prospects.
Facilitators and Barriers to Developing, Implementing, and Evaluating Healthy Vending Policies in Four Cities
Authors: Green Sarah , Glanz Karen , Bromberg Julie
Published: February 2020

Vending machines are a common source of low-nutrient, energy-dense snacks, and beverages. Many cities are beginning to adopt healthy vending policies in public areas, but evidence regarding best practices for developing, implementing, and evaluating these healthy vending polices is limited. This study used a mixed-methods, multiple case study design to examine healthy vending policies and initiatives in four cities. Data were collected between August 2017 and December 2017. Research staff worked with a designated contact person to coordinate site visits to each city where observations of the vending machines were conducted. Semistructured interviews were conducted with multiple stakeholders from each site and documents, including policies, vendor contracts, and nutrition standards, were reviewed. The following elements were identified as being essential to a healthy vending policy or initiative: having a champion and support from leadership, internal and external partnerships, and clear communication. Conducting regular compliance checks of the vending machines and the ability to obtain sales data, especially pre– and post–healthy vending policy sales data, continues to be a challenge. Stakeholders across all cities reported that concerns about profit–loss from the vendor and city revenue and procurement departments are barriers to adopting healthy vending policies. More research and evaluation are needed, as results are mixed regarding the impact on overall revenue/profits. This study yielded a variety of resources and “lessons learned” from those who have developed and implemented healthy vending policies and initiatives. This information should be used by others looking to influence healthier snacking behaviors through vending machines.
Differential contribution of sensory transient receptor potential channels in response to the bioactive lipid sphingosine-1-phosphate
Authors: Kittaka Hiroki , DeBrecht Jennifer , Mishra Santosh K
Published: February 2020

Somatosensation encompasses a wide range of sensations including pain, itch, touch, and temperature and is essential for the detection of environmental stimuli, ultimately allowing an organism to escape, communicate, and adapt to its environment. Such sensations are detected by primary sensory neurons whose nerve endings are located in the skin. Compared to external stimuli, mechanisms underlying endogenous stimulation of primary sensory neurons, such as by lipids, are still largely unknown. Here, we focus on one of the endogenous bioactive lipids, sphingosine-1-phosphate (S1P), to investigate the physiological roles of S1P in pain and itch. We showed that S1P-induced calcium responses in sensory neurons through S1P receptors. Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) are nonselective calcium-permeable ion channels that are known to be involved in pain and itch. Neurons that respond to S1P show reduced responsiveness when treated with antagonists that block either TRPA1 or TRPV1 alone or in combination. In addition, using single and double knockout mice (TRPA1; TRPV1; TRPA1/TRPV1) with loss of function of these channels, we demonstrated that both TRP channels are involved in S1P-induced neuronal responses in vitro. Next, we examined the effects of S1P on pain and itch responsiveness in freely behaving mice post-S1P injection into the cheek, neck, and hind paw. Our findings reveal that S1P induces both pain and itch in vivo and that these responses are partially dependent upon the TRPV1, but not TRPA1 channels.
Synthesis, characterization, and biological properties of oxidovanadium(IV) complexes of acetylsalicylhydroxamic acid (N-acetyloxy-2-hydroxybenzamide) as potential antimicrobials
Authors: Priya Bhanu , Kumar Abhishek , Sharma Neeraj
Published: February 2020

New oxidovanadium(IV) complexes of composition [VO(AcSHA)2] 1 and [VO(acac)(AcSHA)] 2 are synthesized by reactions of VOSO4.5H2O and [VO(acac)2] with acetylsalicylhydroxamic acid AcSH2A (C6H4(OH)(CONHOCOCH3)) in a 1:2 molar ratio in absolute ethanol. The compounds are characterized by the Fourier-transform infrared spectroscopy, ultraviolet–visible spectroscopy, electron spin resonance, and mass spectrometry along with elemental analyses, molar conductivity, and magnetic moment measurements. The infrared spectra of the complexes suggest bonding through carbonyl and phenolic oxygen atoms (O,O coordination). The magnetic moment, electron spin resonance, and mass spectra of the complexes indicate that both exist as monomers, and a distorted square pyramidal geometry around vanadium is proposed. The thermal behavior of the complexes is studied by thermogravimetry and differential thermal analysis techniques under an N2 atmosphere, yielding VO2 as the decomposition product. The in vitro antimicrobial assays against pathogenic Gram-positive bacteria, Gram-negative bacteria, and fungi (minimum inhibitory concentration method) show the appreciable antimicrobial potential relative to the respective standard drugs, tetracycline hydrochloride, and fluconazole.
Comparison of Swiss and European risk algorithms for cardiovascular prevention in Switzerland
Authors: Beuret Hadrien , Hausler Nadine , Nanchen David , Méan Marie , Marques-Vidal Pedro , Vaucher Julien
Published: February 2020

Background

In Switzerland, two distinct algorithms are recommended for cardiovascular prevention: (a) Arbeitsgruppe Lipide und Atherosklerose (AGLA); and (b) European Society of Cardiology (ESC). We validated and determined which algorithm better predicts incident atherosclerotic cardiovascular disease and assessed statin eligibility in Switzerland.

Design

A prospective population-based cohort.

Methods

We employed longitudinal data of the CoLaus study involving 6733 individuals, aged 35–75 years, with a 10-year follow-up. Using discrimination and calibration, we evaluated the predictive performance of the AGLA and ESC algorithms for the prediction of atherosclerotic cardiovascular disease.

Results

From the 6733 initial participants, 5529 were analysed with complete baseline and follow-up data. Mean age (SD) was 52.4 (10.6) years and 54% were women. During an average follow-up (SD) of 10.2 years (1.7), 370 (6.7%) participants developed an incident atherosclerotic cardiovascular disease. The sensitivity of AGLA and ESC algorithms to predict atherosclerotic cardiovascular disease was 51.6% (95% confidence interval (CI) 46.4–56.8) and 58.6% (53.4–63.7), respectively. Discrimination and calibration were similar between the AGLA and ESC algorithms, with area under the receiver operating characteristic curve values of 0.78 (95% CI 0.76–0.80) and 0.79 (0.76–0.81), and Brier scores of 0.059 and 0.041, respectively. Among 370 individuals developing incident atherosclerotic cardiovascular disease, only 278 (75%) were eligible for statin therapy at baseline, including 210 (57%) according to both algorithms, 4 (1%) to AGLA only and 64 (17%) to ESC only.

Conclusion

AGLA and ESC algorithms presented similar accuracy to predict atherosclerotic cardiovascular disease in Switzerland. A quarter of adults developing atherosclerotic cardiovascular disease were not identified by preventive algorithms to be eligible for statin therapy.
The Asymmetric Influence of Financial Development on Economic Growth in Kenya: Evidence From NARDL
Authors: Chen Hao , Hongo Duncan O. , Ssali Max William , Nyaranga Maurice Simiyu , Nderitu Consolata Wairimu
Published: February 2020

This study analyzed the asymmetric effects of financial development on economic growth using a model augmented with inflation and government expenditure asymmetries to inform model specification. The research question used entails, Do their asymmetry changes significantly influence growth? Using the nonlinear auto-regressive distributive lag (NARDL), the most significant results posit that positive shocks in financial development in the short run and its negative shocks in the long run increase and decrease economic growth, respectively. Regarding inflation, its positive (negative) shocks in both runs, respectively, reduce (increase) economic growth. In comparison, positive shocks in financial development that spur growth in the short run and negative shocks in financial development (government expenditure) that increase (reduce) growth are the most domineering effects as the rest of the shocks insignificantly affect growth. Results clearly demonstrate to an environment steered by stable and sustainable inflation that regulated government expenditure and comprehensive financial system deepening would positively cause economic growth. Therefore, appropriate policies that favor low inflation and reduced government spending, expansion of feasibly reformed financial institutions, capital accumulation, and increased resource mobilization should be instituted if real growth is to positively happen.
Exploring Variations in Corporations’ Communication After a CA Versus CSR Crisis: A Semantic Network Analysis of Sustainability Reports
Authors: Park Keonyoung , Kim Hyejin , Rim Hyejoon
Published: February 2020

The study attempts to understand corporations’ efforts to communicate their values and commitment to stakeholders after a crisis. Specifically, the study explores the characteristics of communication efforts that may differ depending on the reputational crisis types: corporate ability (CA) and corporate social responsibility (CSR) crises. Employing a series of semantic network analyses, the study examined the sustainability annual reports of two Korean airlines (i.e., Korean Air and Asiana Airlines) published before and after their recent crises. Results showed how sustainability reports’ central keywords, social issues the companies support, and prioritized stakeholders varied in response to the different types of crises. Word frequency results showed that there was an increasing trend in emphasizing the word “safety” after both types of crisis, while a noticeable decrease in emphasis on the word “ethics” was observed after CA crisis. The results of semantic network analyses showed that Korean Air’s sustainability reports seemed to focus more on aspects of the relationship with stakeholders after the CSR crisis, while Asiana Airlines appeared to place more emphasis on business-related notions after the CA crisis. Theoretical and practical implications are discussed.
Scaffolding Clinical Reasoning of Health Care Students: A Qualitative Exploration of Clinicians’ Perceptions on an Interprofessional Obstetric Ward
Authors: Visser Cora LF , Wouters Anouk , Croiset Gerda , Kusurkar Rashmi A
Published: February 2020

Purpose:

Interprofessional education (IPE) on a ward supports students to generate interprofessional patient care plans as a means to learn about the roles, responsibilities, and clinical reasoning of other professions. We investigated how clinicians guide the clinical reasoning of students from their own and other professions and whether clinicians from nursing, midwifery, and medicine could scaffold students from all professions, that is, by providing just-in-time and tailored support.

Methods:

Nine supervising clinicians from medicine, nursing, and midwifery were interviewed and a repeat interview held 3 to 15 weeks later; one nurse supervisor was interviewed only once. Using conventional content analysis, themes were identified inductively. Next, we applied an existing scaffolding framework to conceptualise how clinicians supported the clinical reasoning in an IPE setting.

Results:

Themes were clinicians’ interventions and intentions, results of interventions and of IPE, characteristics of students and clinicians, interactions between clinicians and students, and logistics. Clinicians applied various interventions and expressed several intentions to guide the learning of students from all professions. Clinicians stimulated students’ clinical reasoning by structuring meetings, asking students to explain their thoughts to each other and through giving group assignments. Thus, clinicians used peer-assisted learning for the students. By collaborating with other supervising clinicians regarding the form and amount of guidance to give to the students, clinicians applied peer-assisted learning for themselves as well.

Conclusion:

Clinicians can learn to scaffold the clinical reasoning of students from different professions, when they are provided with training, good examples, and structures. An existing scaffolding framework can serve as an overview of aims and interventions to provide just-in-time guidance to students from all professions. The scaffolding framework is useful for training clinicians and for depicting the pedagogical approach for IPE wards.
Challenges to the European automotive industry in securing critical raw materials for electric mobility: the case of rare earths
Authors: Schmid Marc
Published: February 2020

Critical raw materials (CRMs) are crucial for the transformation towards low carbon mobility. However, their production is often highly concentrated in a few countries, which leads to supply risks. Exemplified by the case of rare earth elements (REEs) and based on in-depth interviews with corporate executives from companies along the automotive supply chain, this contribution provides insights into the strategies of the European automotive industry to cope with these supply risks. Results show a lack of awareness of REE criticality studies and their outcomes in the past, the decisive role of price competitiveness when pursuing mitigation strategies and a lack of willingness or ability to engage in rare earth (RE) projects to get access to production output and secure supply. Overall, affected companies struggle to pursue long-term oriented strategies to secure their need for REEs. These findings are discussed with regard to the new demand for CRMs due to the shift to electric mobility and the specific challenges that the automotive industry faces.
Prognostic factors for VTE and bleeding in hospitalized medical patients: a systematic review and meta-analysis
Authors: Darzi Andrea J. , Karam Samer G. , Charide Rana , Etxeandia-Ikobaltzeta Itziar , Cushman Mary , Gould Michael K. , Mbuagbaw Lawrence , Spencer Frederick A. , Spyropoulos Alex C. , Streiff Michael B. , Woller Scott , Zakai Neil A. , Germini Federico , Rigoni Marta , Agarwal Arnav , Morsi Rami Z. , Iorio Alfonso , Akl Elie A. , Schünemann Holger J.
Published: February 2020

There may be many predictors of venous thromboembolism (VTE) and bleeding in hospitalized medical patients, but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify prognostic factors for VTE and bleeding in hospitalized medical patients and searched Medline and EMBASE from inception through May 2018. We considered studies that identified potential prognostic factors for VTE and bleeding in hospitalized adult medical patients. Reviewers extracted data in duplicate and independently and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. Of 69 410 citations, we included 17 studies in our analysis: 14 that reported on VTE, and 3 that reported on bleeding. For VTE, moderate-certainty evidence showed a probable association with older age; elevated C-reactive protein (CRP), D-dimer, and fibrinogen levels; tachycardia; thrombocytosis; leukocytosis; fever; leg edema; lower Barthel Index (BI) score; immobility; paresis; previous history of VTE; thrombophilia; malignancy; critical illness; and infections. For bleeding, moderate-certainty evidence showed a probable association with older age, sex, anemia, obesity, low hemoglobin, gastroduodenal ulcers, rehospitalization, critical illness, thrombocytopenia, blood dyscrasias, hepatic disease, renal failure, antithrombotic medication, and presence of a central venous catheter. Elevated CRP, a lower BI, a history of malignancy, and elevated heart rate are not included in most VTE risk assessment models. This study informs risk prediction in the management of hospitalized medical patients for VTE and bleeding; it also informs guidelines for VTE prevention and future research.
proMAD: semiquantitative densitometric measurement of protein microarrays
Authors: Jaeschke Anna , Eckert Hagen , Bray Laura J.
Published: February 2020

Background

Protein microarrays are a versatile and widely used tool for analyzing complex protein mixtures. Membrane arrays utilize antibodies which are captured on a membrane to specifically immobilize several proteins of interest at once. Using detection antibodies, the bound protein-antibody-complex is converted into visual signals, which can be quantified using densitometry. The reliability of such densitometric assessments depends on a variety of factors, not only sample preparation and the choice of acquisition device but also the selected analysis software and the algorithms used for readout and processing data. Currently available software packages use a single image of a membrane at an optimal exposure time selected for that specific experimental framework. This selection is based on a user’s best guess and is subject to inter-user variability or the acquisition device algorithm. With modern image acquisition systems proving the capacity to collect signal development over time, this information can be used to improve densitometric measurements. Here we introduce proMAD, a toolkit for protein microarray analysis providing a novel systemic approach for the quantification of membrane arrays based on the kinetics of the analytical reaction.

Results

Briefly, our toolkit ensures an exact membrane alignment, utilizing basic computer vision techniques. It also provides a stable method to estimate the background light level. Finally, we model the light production over time, utilizing the knowledge about the reaction kinetics of the underlying horseradish peroxidase-based signal detection method.

Conclusion

proMAD incorporates the reaction kinetics of the enzyme to model the signal development over time for each membrane creating an individual, self-referencing concept. Variations of membranes within a given experimental set up can be accounted for, allowing for a better comparison of such. While the open-source library can be implemented in existing workflows and used for highly user-tailored analytic setups, the web application, on the other hand, provides easy platform-independent access to the core algorithm to a wide range of researchers. proMAD’s inherent flexibility has the potential to cover a wide range of use-cases and enables the automation of data analytic tasks.
Pre- and post-sequencing recommendations for functional annotation of human fecal metagenomes
Authors: Treiber Michelle L. , Taft Diana H. , Korf Ian , Mills David A. , Lemay Danielle G.
Published: February 2020

Background

Shotgun metagenomes are often assembled prior to annotation of genes which biases the functional capacity of a community towards its most abundant members. For an unbiased assessment of community function, short reads need to be mapped directly to a gene or protein database. The ability to detect genes in short read sequences is dependent on pre- and post-sequencing decisions. The objective of the current study was to determine how library size selection, read length and format, protein database, e-value threshold, and sequencing depth impact gene-centric analysis of human fecal microbiomes when using DIAMOND, an alignment tool that is up to 20,000 times faster than BLASTX.

Results

Using metagenomes simulated from a database of experimentally verified protein sequences, we find that read length, e-value threshold, and the choice of protein database dramatically impact detection of a known target, with best performance achieved with longer reads, stricter e-value thresholds, and a custom database. Using publicly available metagenomes, we evaluated library size selection, paired end read strategy, and sequencing depth. Longer read lengths were acheivable by merging paired ends when the sequencing library was size-selected to enable overlaps. When paired ends could not be merged, a congruent strategy in which both ends are independently mapped was acceptable. Sequencing depths of 5 million merged reads minimized the error of abundance estimates of specific target genes, including an antimicrobial resistance gene.

Conclusions

Shotgun metagenomes of DNA extracted from human fecal samples sequenced using the Illumina platform should be size-selected to enable merging of paired end reads and should be sequenced in the PE150 format with a minimum sequencing depth of 5 million merge-able reads to enable detection of specific target genes. Expecting the merged reads to be 180-250 bp in length, the appropriate e-value threshold for DIAMOND would then need to be more strict than the default. Accurate and interpretable results for specific hypotheses will be best obtained using small databases customized for the research question.
Assessing stationary distributions derived from chromatin contact maps
Authors: Segal Mark R. , Fletez-Brant Kipper
Published: February 2020

Background

The spatial configuration of chromosomes is essential to various cellular processes, notably gene regulation, while architecture related alterations, such as translocations and gene fusions, are often cancer drivers. Thus, eliciting chromatin conformation is important, yet challenging due to compaction, dynamics and scale. However, a variety of recent assays, in particular Hi-C, have generated new details of chromatin structure, spawning a number of novel biological findings. Many findings have resulted from analyses on the level of native contact data as generated by the assays. Alternatively, reconstruction based approaches often proceed by first converting contact frequencies into distances, then generating a three dimensional (3D) chromatin configuration that best recapitulates these distances. Subsequent analyses can enrich contact level analyses via superposition of genomic attributes on the reconstruction. But, such advantages depend on the accuracy of the reconstruction which, absent gold standards, is inherently difficult to assess. Attempts at accuracy evaluation have relied on simulation and/or FISH imaging that typically features a handful of low resolution probes. While newly advanced multiplexed FISH imaging offers possibilities for refined 3D reconstruction accuracy evaluation, availability of such data is limited due to assay complexity and the resolution thereof is appreciably lower than the reconstructions being assessed. Accordingly, there is demand for new methods of reconstruction accuracy appraisal.

Results

Here we explore the potential of recently proposed stationary distributions, hereafter StatDns, derived from Hi-C contact matrices, to serve as a basis for reconstruction accuracy assessment. Current usage of such StatDns has focussed on the identification of highly interactive regions (HIRs): computationally defined regions of the genome purportedly involved in numerous long-range intra-chromosomal contacts. Consistent identification of HIRs would be informative with respect to inferred 3D architecture since the corresponding regions of the reconstruction would have an elevated number ofknearest neighbors (kNNs). More generally, we anticipate a monotone decreasing relationship between StatDn values andkNN distances. After initially evaluating the reproducibility of StatDns across replicate Hi-C data sets, we use this implied StatDn -kNN relationship to gauge the utility of StatDns for reconstruction validation, making recourse to both real and simulated examples.

Conclusions

Our analyses demonstrate that, as constructed, StatDns donotprovide a suitable measure for assessing the accuracy of 3D genome reconstructions. Whether this is attributable to specific choices surrounding normalization in defining StatDns or to the logic underlying their very formulation remains to be determined.
Macroevolutionary bursts and constraints generate a rainbow in a clade of tropical birds
Authors: Merwin Jon T. , Seeholzer Glenn F. , Smith Brian Tilston
Published: February 2020

Background

Bird plumage exhibits a diversity of colors that serve functional roles ranging from signaling to camouflage and thermoregulation. However, birds must maintain a balance between evolving colorful signals to attract mates, minimizing conspicuousness to predators, and optimizing adaptation to climate conditions. Examining plumage color macroevolution provides a framework for understanding this dynamic interplay over phylogenetic scales. Plumage evolution due to a single overarching process, such as selection, may generate the same macroevolutionary pattern of color variation across all body regions. In contrast, independent processes may partition plumage and produce region-specific patterns. To test these alternative scenarios, we collected color data from museum specimens of an ornate clade of birds, the Australasian lorikeets, using visible-light and UV-light photography, and comparative methods. We predicted that the diversification of homologous feather regions, i.e., patches, known to be involved in sexual signaling (e.g., face) would be less constrained than patches on the back and wings, where new color states may come at the cost of crypsis. Because environmental adaptation may drive evolution towards or away from color states, we tested whether climate more strongly covaried with plumage regions under greater or weaker macroevolutionary constraint.

Results

We found that alternative macroevolutionary models and varying rates best describe color evolution, a pattern consistent with our prediction that different plumage regions evolved in response to independent processes. Modeling plumage regions independently, in functional groups, and all together showed that patches with similar macroevolutionary models clustered together into distinct regions (e.g., head, wing, belly), which suggests that plumage does not evolve as a single trait in this group. Wing patches, which were conserved on a macroevolutionary scale, covaried with climate more strongly than plumage regions (e.g., head), which diversified in a burst.

Conclusions

Overall, our results support the hypothesis that the extraordinary color diversity in the lorikeets was generated by a mosaic of evolutionary processes acting on plumage region subsets. Partitioning of plumage regions in different parts of the body provides a mechanism that allows birds to evolve bright colors for signaling and remain hidden from predators or adapt to local climatic conditions.
GSAlign: an efficient sequence alignment tool for intra-species genomes
Authors: Lin Hsin-Nan , Hsu Wen-Lian
Published: February 2020

Background

Personal genomics and comparative genomics are becoming more important in clinical practice and genome research. Both fields require sequence alignment to discover sequence conservation and variation. Though many methods have been developed, some are designed for small genome comparison while some are not efficient for large genome comparison. Moreover, most existing genome comparison tools have not been evaluated the correctness of sequence alignments systematically. A wrong sequence alignment would produce false sequence variants.

Results

In this study, we present GSAlign that handles large genome sequence alignment efficiently and identifies sequence variants from the alignment result. GSAlign is an efficient sequence alignment tool for intra-species genomes. It identifies sequence variations from the sequence alignments. We estimate performance by measuring the correctness of predicted sequence variations. The experiment results demonstrated that GSAlign is not only faster than most existing state-of-the-art methods, but also identifies sequence variants with high accuracy.

Conclusions

As more genome sequences become available, the demand for genome comparison is increasing. Therefore an efficient and robust algorithm is most desirable. We believe GSAlign can be a useful tool. It exhibits the abilities of ultra-fast alignment as well as high accuracy and sensitivity for detecting sequence variations.
The Oxidoreductase DsbA1 negatively influences 2,4-diacetylphloroglucinol biosynthesis by interfering the function of Gcd in Pseudomonas fluorescens 2P24
Authors: Zhang Bo , Zhao Hui , Wu Xiaogang , Zhang Li-Qun
Published: February 2020

Background

The polyketide antibiotic 2,4-diacetylphloroglucinol (2,4-DAPG), produced by Pseudomonas fluorescens 2P24, is positively regulated by the GacS-GacA two-component system.

Results

Here we reported on the characterization of DsbA1 (disulfide oxidoreductase) as novel regulator of biocontrol activity in P. fluorescens. Our data showed that mutation of dsbA1 caused the accumulation of 2,4-DAPG in a GacA-independent manner. Further analysis indicated that DsbA1 interacts with membrane-bound glucose dehydrogenase Gcd, which positively regulates the production of 2,4-DAPG. Mutation of cysteine (C)-235, C275, and C578 of Gcd, significantly reduced the interaction with DsbA1, enhanced the activity of Gcd and increased 2,4-DAPG production.

Conclusions

Our results suggest that DsbA1 regulates the 2,4-DAPG concentration via fine-tuning the function of Gcd in P. fluorescens 2P24.
A simulation study to compare different estimation approaches for network meta-analysis and corresponding methods to evaluate the consistency assumption
Authors: Kiefer Corinna , Sturtz Sibylle , Bender Ralf
Published: February 2020

Background

Network meta-analysis (NMA) is becoming increasingly popular in systematic reviews and health technology assessments. However, there is still ambiguity concerning the properties of the estimation approaches as well as for the methods to evaluate the consistency assumption.

Methods

We conducted a simulation study for networks with up to 5 interventions. We investigated the properties of different methods and give recommendations for practical application. We evaluated the performance of 3 different models for complex networks as well as corresponding global methods to evaluate the consistency assumption. The models are the frequentist graph-theoretical approach netmeta, the Bayesian mixed treatment comparisons (MTC) consistency model, and the MTC consistency model with stepwise removal of studies contributing to inconsistency identified in a leverage plot.

Results

We found that with a high degree of inconsistency none of the evaluated effect estimators produced reliable results, whereas with moderate or no inconsistency the estimator from the MTC consistency model and the netmeta estimator showed acceptable properties. We also saw a dependency on the amount of heterogeneity. Concerning the evaluated methods to evaluate the consistency assumption, none was shown to be suitable.

Conclusions

Based on our results we recommend a pragmatic approach for practical application in NMA. The estimator from the netmeta approach or the estimator from the Bayesian MTC consistency model should be preferred. Since none of the methods to evaluate the consistency assumption showed satisfactory results, users should have a strong focus on the similarity as well as the homogeneity assumption.
Disentangling the genetics of sarcopenia: prioritization of NUDT3 and KLF5 as genes for lean mass & HLA-DQB1-AS1 for hand grip strength with the associated enhancing SNPs & a scoring system
Authors: Singh Abhishek Narain , Gasman Bili
Published: February 2020

Background

Sarcopenia is a skeletal muscle disease of clinical importance that occurs commonly in old age and in various disease sub-categories. Widening the scope of knowledge of the genetics of muscle mass and strength is important because it may allow to identify patients with an increased risk to develop a specific musculoskeletal disease or condition such as sarcopenia based on genetic markers.

Methods

We used bioinformatics tools to identify gene loci responsible for regulating muscle strength and lean mass, which can then be a target for downstream lab experimentation validation. Single nuclear polymorphisms (SNPs) associated with various disease traits of muscles and specific genes were chosen according to their muscle phenotype associationp-value, as traditionally done in Genome Wide Association Studies, GWAS. We’ve developed and applied a combination of expression quantitative trait loci (eQTLs) and GWAS summary information, to prioritize causative SNP and point out the unique genes associated in the tissues of interest (muscle).

Results

We foundNUDT3andKLF5for lean mass andHLA-DQB1-AS1for hand grip strength as candidate genes to target for these phenotypes. The associated regulatory SNPs are rs464553, rs1028883 and rs3129753 respectively.

Conclusion

Transcriptome Wide Association Studies, TWAS, approaches of combining GWAS and eQTL summary statistics proved helpful in statistically prioritizing genes and their associated SNPs for the disease phenotype of study, in this case, Sarcopenia. Potentially regulatory SNPs associated with these genes, and the genes further prioritized by a scoring system, can be then wet lab verified, depending on the phenotype it is hypothesized to affect.
Atypical presentation of acute post-infectious glomerulonephritis in patients with sickle cell disease: report of two cases
Authors: de Menezes Neves Precil Diego Miranda , Reichert Bernardo Vergara , Bridi Ramaiane Aparecida , Yu Luis , Dias Cristiane Bitencourt , Pinheiro Rafaela Brito Bezerra , de Abreu Testagrossa Leonardo , Cavalcante Lívia Barreira , Malheiros Denise Maria Avancini Costa , Jorge Lectícia Barbosa , Woronik Viktoria
Published: February 2020

Background

Sickle cell disease (SCD) is a highly prevalent genetic disease worldwide. In the natural evolution of SCD, glomerular lesions can develop, presenting histopathological patterns of segmental or focal membranoproliferative glomerulosclerosis, with or without thrombotic microangiopathy. We report two cases of acute post-infectious glomerulonephritis (APIGN), with atypical presentations, in patients with SCD.

Case presentation

Case 1: An 18-year-old female with SCD presented with a 21-day history of progressive oedema, accompanied by dyspnoea, productive cough, fever, and chest pain. Blood tests showed the following: haemoglobin 6.1 g/dl; leucocytes 18,820 cells/mm3; and creatinine 0.49 mg/dl. A urine sample evidenced leucocyturia and haematuria. The 24-h proteinuria was 8.99 g, serum albumin level was 1.2 g/dl, low serum C3 levels and high levels of anti-streptolysin O. Renal biopsy was consistent with APIGN. The patient was treated with diuretic and anti-proteinuric agents, subsequently evolving to reversal of the renal alterations. Case 2: A 12-year-old male with SCD presented with a 20-day history of a non-productive cough and progressive oedema, together with hypertension. The serum creatinine concentration was 0.48 mg/dl. A urine sample evidenced leukocyturia and haematuria. The 24-h proteinuria was 12.5 g, and the serum albumin level was 2.6 g/dl. The levels of C3 and C4 were normal. Renal biopsy revealed APIGN. The patient was treated with diuretic and anti-proteinuric agents, subsequently evolving reversal of the renal alterations.

Conclusions

The presentation of the two cases reported here are not typical of SCD-related kidney injury. Analysis of the renal biopsy specimens elucidated the diagnosis, affecting the prognosis, because that of APIGN is highly favourable, unlike that of nephrotic syndrome associated with SCD glomerulopathy.
Validation of the Spanish version of the migraine disability assessment questionnaire (MIDAS) in university students with migraine
Authors: Rodríguez-Almagro Daniel , Achalandabaso Alexander , Rus Alma , Obrero-Gaitán Esteban , Zagalaz-Anula Noelia , Lomas-Vega Rafael
Published: February 2020

Background

The Migraine Disability Assessment (MIDAS) questionnaire is widely used to determine the degree of migraine-related disability of subjects. So far, and to the best of our knowledge, no Spanish version of this tool has been validated. The questionnaire comprises seven items, with the first five constituting the main scale while the sixth and seventh items referring, respectively, to the frequency and intensity of headache. The present study aims to analyze the clinimetric properties of the Spanish version of the MIDAS questionnaire in a population of university students.

Methods

We performed a cross-sectional study of validation for this measuring instrument. A total of 153 subjects participated in the study. We analyzed construct validity using factor analysis, test-retest reliability by the Intraclass Correlation Coeficient (ICC), internal consistency, and concurrent validity with respect to the 12-Item Short Form Health Survey (SF-12).

Results

Factor analysis revealed a two-factor structure. The questionnaire has good reliability for the MIDAS main-scale score ([ICC = 0.81; 95% CI: 0.63–0.90]), excellent reliability for headache frequency (ICC = 0.90; 95%; CI: [0.79–0.95]), and moderately good reliability for headache intensity (ICC = 0.63; 95% CI: [0.34–0.80]). The analysis also yielded good internal consistency results (α Cronbach = 0.797) and a moderate correlation between MIDAS-main scale and the physical component summary of SF-12 (Rho = − 0.326; p <  0.001).

Conclusions

The Spanish version of the MIDAS questionnaire is a valid and reliable tool to measure migraine-related disability in university subjects. The two additional items provide information that could help clinicians in making decisions.
Mutation screening of the USH2A gene reveals two novel pathogenic variants in Chinese patients causing simplex usher syndrome 2
Authors: He Chenhao , Liu Xinyu , Zhong Zilin , Chen Jianjun
Published: February 2020

Background

Usher syndrome (USH) is the most prevalent cause of the human genetic deafness and blindness. USH type II (USH2) is the most common form of USH, and USH2A is the major pathogenic gene for USH2. For expanding the spectrum of USH2A mutations and further revealing the role of USH2A in USH2, we performed the USH2A gene variant screening in Chinese patients with USH2.

Methods

Genomic DNA was extracted from peripheral blood of unrelated Chinese USH2 patients, we designed specific primers for amplifying the coding region (exons 2–72) of the USH2A gene. Sanger sequencing was used to study alleles. Silico prediction tools were used to predict the pathogenicity of the variants identified in these patients.

Results

Five heterozygous pathogenic variants were detected in four patients. Two patients were found to have two-mutations and two patients only have one. Two novel variants c.4217C > A (p.Ser1406X) and c.11780A > G (p.Asp3927Gly)) were predicted deleterious by computer prediction algorithms. In addition, three reported mutations (c.8559-2A > G, c.8232G > C and c.11389 + 3A > T) were also found in this study.

Conclusions

We identified five heterozygous pathogenic variants in the USH2A gene in Chinese patients diagnosed with Usher syndrome type 2, two of which were not reported. It expands the spectrum of USH2A variants in USH.