bluuebunny/crossref_metadata_2025 huggingface dataset:
Clustering tennis players’ anthropometric and individual features helps to reveal performance fingerprints
Authors: Cui Yixiong , Gómez Miguel‐Ángel , Gonçalves Bruno , Sampaio Jaime
Published: February 2019

The study was aimed to explore distinct players’ groups according to their anthropometric and individual features, and to identify the key performance indicators that discriminate player groups. Match statistics, anthropometric and personal features of 1188 male players competing during 2015–2017 main draw Grand Slam singles events were collected. Height, weight, experience, handedness and backhand style were used to automatically classify players into different clusters through unsupervised learning model. Afterwards, 29 match variables were analysed through MANOVA and discriminant analysis in order to evaluate the different match performance among player groups and to identify the key performance indicators that best differentiate player clusters in each Grand Slam. The analysis revealed the existence of four clusters, they were classified as Big‐sized Right Two‐handed Players (n = 387), Medium‐sized Right One‐handed Players (n = 265), Small‐sized Right Two‐handed Players (n = 414), and Left Two‐handed Players (n = 122). Serve, winner, net and physical performance‐related indicators (Structure Coefficient ≥ |0.30|) were showed to be the maximum contributors to the group separation. Left‐handed players were the most homogenous group in performance. Taller players outperformed their peers in all Slams except for Roland Garros, where left‐handed players demonstrated certain advantage playing on slow‐pace surface. In Wimbledon and US Open, Medium‐sized Right One‐handed Players showed better net and physical performance. The advantage of left‐handed player is over‐represented at elite level. Current findings promote a better understanding of match‐play from distinct player groups and offer information on evaluating contextual variability for achieving better performances.
Building on Dewaele’s (2018) L1 versus LX Dichotomy: The Language-Usage-Identity State Model
Authors: Thomas Nathan , Osment Christopher
Published: February 2019

In this brief contribution, we will summarize the main arguments in Dewaele’s (2018) ‘Why the Dichotomy “L1 versus LX User” is Better than “Native versus Non-native Speaker”’ and discuss our Language-Usage-Identity State Model, showing how it builds on the core features of Dewaele’s proposal.
PhenoPro: a novel toolkit for assisting in the diagnosis of Mendelian disease
Authors: Li Zixiu , Zhang Feng , Wang Yukai , Qiu Yue , Wu Yang , Lu Yulan , Yang Lin , Qu William J , Wang Huijun , Zhou Wenhao , Tian Weidong
Published: February 2019

Motivation

Whole-exome sequencing (WES) is now being used in clinical practice for the diagnosis of the causal genes of Mendelian diseases. In order to make the diagnosis, however, the clinical phenotypes [e.g. Human Phenotype Ontology (HPO) terms] of a patient are needed for prioritizing the variants called from the WES data of the patient. Computational tools are therefore needed to standardize and accelerate this process.

Results

Here, we introduce a tool named PhenoPro for prioritizing the causal gene of Mendelian disease given both the HPO terms assigned to and the variants called from the WES data of a patient. PhenoPro has been benchmarked using both simulated patients and 287 real diagnosed patients of Chinese ancestry, and shows significant improvements over five previous tools. Moreover, the addition of an internal variant data of Chinese ancestry and the variant data from the patients’ parents can further improve PhenoPro’s performance. To make PhenoPro a fully automated tool, we also include a natural language processing component for automated HPO term assignment from clinical reports, and demonstrate that the natural language processing is as effective as manual HPO assignment using real clinical reports. In conclusion, PhenoPro can be used as a pre-screening tool to assist in the diagnosis of Mendelian disease genes.

Availability and implementation

The web server of PhenoPro is freely available at http://app.tianlab.cn.

Supplementary information

Supplementary data are available at Bioinformatics online.
Driver network as a biomarker: systematic integration and network modeling of multi-omics data to derive driver signaling pathways for drug combination prediction
Authors: Huang Lei , Brunell David , Stephan Clifford , Mancuso James , Yu Xiaohui , He Bin , Thompson Timothy C , Zinner Ralph , Kim Jeri , Davies Peter , Wong Stephen T C
Published: February 2019

Motivation

Drug combinations that simultaneously suppress multiple cancer driver signaling pathways increase therapeutic options and may reduce drug resistance. We have developed a computational systems biology tool, DrugComboExplorer, to identify driver signaling pathways and predict synergistic drug combinations by integrating the knowledge embedded in vast amounts of available pharmacogenomics and omics data.

Results

This tool generates driver signaling networks by processing DNA sequencing, gene copy number, DNA methylation and RNA-seq data from individual cancer patients using an integrated pipeline of algorithms, including bootstrap aggregating-based Markov random field, weighted co-expression network analysis and supervised regulatory network learning. It uses a systems pharmacology approach to infer the combinatorial drug efficacies and synergy mechanisms through drug functional module-induced regulation of target expression analysis. Application of our tool on diffuse large B-cell lymphoma and prostate cancer demonstrated how synergistic drug combinations can be discovered to inhibit multiple driver signaling pathways. Compared with existing computational approaches, DrugComboExplorer had higher prediction accuracy based on in vitro experimental validation and probability concordance index. These results demonstrate that our network-based drug efficacy screening approach can reliably prioritize synergistic drug combinations for cancer and uncover potential mechanisms of drug synergy, warranting further studies in individual cancer patients to derive personalized treatment plans.

Availability and implementation

DrugComboExplorer is available at https://github.com/Roosevelt-PKU/drugcombinationprediction.

Supplementary information

Supplementary data are available at Bioinformatics online.
Choice of species affects phylogenetic stability of deep nodes: an empirical example in Terrabacteria
Authors: Superson Ashley A , Phelan Doug , Dekovich Allyson , Battistuzzi Fabia U
Published: February 2019

Motivation

The promise of higher phylogenetic stability through increased dataset sizes within tree of life (TOL) reconstructions has not been fulfilled. Among the many possible causes are changes in species composition (taxon sampling) that could influence phylogenetic accuracy of the methods by altering the relative weight of the evolutionary histories of each individual species. This effect would be stronger in clades that are represented by few lineages, which is common in many prokaryote phyla. Indeed, phyla with fewer taxa showed the most discordance among recent TOL studies. We implemented an approach to systematically test how the identity of taxa among a larger dataset and the number of taxa included affected the accuracy of phylogenetic reconstruction.

Results

Utilizing an empirical dataset within Terrabacteria we found that even within scenarios consisting of the same number of taxa, the species used strongly affected phylogenetic stability. Furthermore, we found that trees with fewer species were more dissimilar to the tree produced from the full dataset. These results hold even when the tree is composed by many phyla and only one of them is being altered. Thus, the effect of taxon sampling in one group does not seem to be buffered by the presence of many other clades, making this issue relevant even to very large datasets. Our results suggest that a systematic evaluation of phylogenetic stability through taxon resampling is advisable even for very large datasets.

Availability and implementation

https://github.com/BlabOaklandU/PATS.git.

Supplementary information

Supplementary data are available at Bioinformatics online.
G2P: a Genome-Wide-Association-Study simulation tool for genotype simulation, phenotype simulation and power evaluation
Authors: Tang You , Liu Xiaolei
Published: February 2019

Motivation

Plenty of Genome-Wide-Association-Study (GWAS) methods have been developed for mapping genetic markers that associated with human diseases and agricultural economic traits. Computer simulation is a nice tool to test the performances of various GWAS methods under certain scenarios. Existing tools are either inefficient in terms of computation and memory efficiency or inconvenient to use to simulate big, realistic genotype data and phenotype data to evaluate available GWAS methods.

Results

Here, we present a GWAS simulation tool named G2P that can be used to simulate genotype data, phenotype data and perform power evaluation of GWAS methods. G2P is a user-friendly tool with all functions is provided in both graphical user interface and pipeline manners and it is available for Windows, Mac and Linux environments. Furthermore, G2P achieves maximum efficiency in terms of both memory usage and simulation speed; with G2P, the simulation of genotype data that includes 1 000 000 samples and 2 000 000 markers can be accomplished in 5 h.

Availability and implementation

The G2P software, user manual, and example datasets are freely available at GitHub: https://github.com/XiaoleiLiuBio/G2P.

Supplementary information

Supplementary data are available at Bioinformatics online.
Social Work Research with Industry: A Systematic Literature Review of Engagement and Impact
Authors: Zuchowski Ines , Miles Debra , Gair Susan , Tsey Komla
Published: February 2019

Current research agendas in developed countries focus on academics engaging collaboratively with communities and industry partners to achieve research outcomes that demonstrate reach and significance. Social work academics are in a prime position to undertake collaborative research that has specific project benefits and wider social impacts. This article reports on a systematic literature review of articles in social work journals that reported on academic industry partnerships. The review aimed to analyse publications documenting the engagement of social work academic researchers with industry partners, to examine the nature of the research undertaken through this engagement and to ascertain the reported impact. Findings highlight that collaborative research processes could be described in greater detail, further explicit detail on collaboration and impact is needed, and while project level impacts are described in reviewed publications, most are not presenting broader societal impacts.
High baseline soluble urokinase plasminogen activator receptor (suPAR) serum levels indicate adverse outcome after resection of pancreatic adenocarcinoma
Authors: Loosen Sven H , Tacke Frank , Püthe Niklas , Binneboesel Marcel , Wiltberger Georg , Alizai Patrick H , Kather Jakob N , Paffenholz Pia , Ritz Thomas , Koch Alexander , Bergmann Frank , Trautwein Christian , Longerich Thomas , Roderburg Christoph , Neumann Ulf P , Luedde Tom
Published: February 2019

Surgical resection represents the only potentially curative therapy for patients with pancreatic adenocarcinoma (PDAC), an aggressive malignancy with a very limited 5-year survival rate. However, even after complete tumor resection, many patients are still facing an unfavorable prognosis underlining the need for better preoperative stratification algorithms. Here, we explored the role of the secreted glycoprotein soluble urokinase plasminogen activator receptor (suPAR) as a novel circulating biomarker for patients undergoing resection of PDAC. Serum levels of suPAR were measured by enzyme-linked immunosorbent assay (ELISA) in an exploratory as well as a validation cohort comprising a total of 127 PDAC patients and 75 healthy controls. Correlating with a cytoplasmic immunohistochemical expression of uPAR in PDAC tumor cells, serum levels of suPAR were significantly elevated in PDAC patients compared to healthy controls and patient with PDAC precursor lesions. Importantly, patients with high preoperative suPAR levels above a calculated cutoff value of 5.956 ng/ml showed a significantly reduced overall survival after tumor resection. The prognostic role of suPAR was further corroborated by uni- and multivariate Cox-regression analyses including parameters of systemic inflammation, liver and kidney function as well as clinico-pathological patients’ characteristics. Moreover, high baseline suPAR levels identified those patients particularly susceptible to acute kidney injury and surgical complications after surgery. In conclusion, our data suggest that circulating suPAR represents a novel prognostic marker in PDAC patients undergoing tumor resection that might be a useful addition to existing preoperative stratification algorithms for identifying patients that particularly benefit from extended tumor resection.
Changes in Functional Connectivity Predict Outcome of Repetitive Transcranial Magnetic Stimulation Treatment of Major Depressive Disorder
Authors: Corlier Juliana , Wilson Andrew , Hunter Aimee M , Vince-Cruz Nikita , Krantz David , Levitt Jennifer , Minzenberg Michael J , Ginder Nathaniel , Cook Ian A , Leuchter Andrew F
Published: February 2019

Repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder (MDD) is associated with changes in brain functional connectivity (FC). These changes may be related to the mechanism of action of rTMS and explain the variability in clinical outcome. We examined changes in electroencephalographic FC during the first rTMS treatment in 109 subjects treated with 10 Hz stimulation to left dorsolateral prefrontal cortex. All subjects subsequently received 30 treatments and clinical response was defined as ≥40% improvement in the inventory of depressive symptomatology-30 SR score at treatment 30. Connectivity change was assessed with coherence, envelope correlation, and a novel measure, alpha spectral correlation (αSC). Machine learning was used to develop predictive models of outcome for each connectivity measure, which were compared with prediction based upon early clinical improvement. Significant connectivity changes were associated with clinical outcome (P < 0.001). Machine learning models based on αSC yielded the most accurate prediction (area under the curve, AUC = 0.83), and performance improved when combined with early clinical improvement measures (AUC = 0.91). The initial rTMS treatment session produced robust changes in FC, which were significant predictors of clinical outcome of a full course of treatment for MDD.
Inherited Interleukin 2–Inducible T-Cell (ITK) Kinase Deficiency in Siblings With Epidermodysplasia Verruciformis and Hodgkin Lymphoma
Authors: Youssefian Leila , Vahidnezhad Hassan , Yousefi Mehdi , Saeidian Amir Hossein , Azizpour Arghavan , Touati Andrew , Nikbakht Neda , Hesari Kambiz Kamyab- , Adib-Sereshki Mohammad Mahdi , Zeinali Sirous , Mansoori Behzad , Jazayeri Ali , Karamzadeh Razieh , Fortina Paolo , Jouanguy Emmanuelle , Casanova Jean-Laurent , Uitto Jouni
Published: February 2019

Biallelic mutations in the ITK gene cause a T-cell primary immunodeficiency with Epstein-Barr virus (EBV)–lymphoproliferative disorders. We describe a novel association of a homozygous ITK mutation with β–human papillomavirus (HPV)–positive epidermodysplasia verruciformis. Thus, loss of function in ITK can result in broad dysregulation of T-cell responses to oncogenic viruses, including β-HPV and EBV.
Dental root development associated with treatments by rapid maxillary expansion/reverse headgear and slow maxillary expansion
Authors: Seker Elif Dilara , Yagci Ahmet , Kurt Demirsoy Kevser
Published: February 2019

Objectives

To assess dental root development in two groups of paediatric patients who received treatments with reverse headgear and rapid maxillary expansion and slow maxillary dental arch expansion.

Materials and methods

The 20 subjects (13 girls, 7 boys; mean age: 8.9 ± 1.3 years) in the first group were treated with a Petit-type reverse headgear attached to a full-coverage bonded rapid maxillary expander via elastics (RME&RHg group). The 20 subjects included in the second group (9 girls, 11 boys; mean age: 9.1 ± 2.2 years) were selected among patients who were treated with Hawley appliances for slow maxillary expansion (SME group). Digitized panoramic radiographs were used. A total of 960 permanent teeth (maxillary–mandibular incisors, canines, premolars, and first molars) were measured quantitatively for pre-treatment and post-treatment.

Results

No significant increase was found except for the right and left maxillary and mandibular second premolars and left mandibular and first premolar in the RME&RHg group (P < 0.05). Teeth length values increased significantly in all maxillary and mandibular teeth except maxillary first molars and mandibular incisors in the SME group (P < 0.05). Inter-group comparisons showed that statistically significant differences were observed in maxillary and mandibular incisors, left maxillary first premolar, and molar teeth (P > 0.05).

Limitation

A limitation of this study is the use of two-dimensional radiographic images for root length measurement. However, ethical obligations limit the dental cone beam computed tomography imaging application for protection of paediatric patients from harm.

Conclusions

RME&RHg therapy inhibits root development of maxillary and mandibular teeth in the early period. However, further studies should be performed to determine whether this effect on root development is reversible or irreversible.
C-type natriuretic peptide co-ordinates cardiac structure and function
Authors: Moyes Amie J , Chu Sandy M , Aubdool Aisah A , Dukinfield Matthew S , Margulies Kenneth B , Bedi Kenneth C , Hodivala-Dilke Kairbaan , Baliga Reshma S , Hobbs Adrian J
Published: February 2019

Aims

C-type natriuretic peptide (CNP) is an essential endothelium-derived signalling species that governs vascular homoeostasis; CNP is also expressed in the heart but an intrinsic role for the peptide in cardiac function is not established. Herein, we employ unique transgenic strains with cell-specific deletion of CNP to define a central (patho)physiological capacity of CNP in maintaining heart morphology and contractility.

Methods and results

Cardiac structure and function were explored in wild type (WT), cardiomyocyte (cmCNP−/−), endothelium (ecCNP−/−), and fibroblast (fbCNP−/−)—specific CNP knockout mice, and global natriuretic peptide receptor (NPR)-B−/−, and NPR-C−/− animals at baseline and in experimental models of myocardial infarction and heart failure (HF). Endothelium-specific deletion of CNP resulted in impaired coronary responsiveness to endothelium-dependent- and flow-mediated-dilatation; changes mirrored in NPR-C−/− mice. Ex vivo, global ischaemia resulted in larger infarcts and diminished functional recovery in cmCNP−/− and NPR-C−/−, but not ecCNP−/−, vs. WT. The cardiac phenotype of cmCNP−/−, fbCNP−/−, and NPR-C−/− (but not ecCNP−/− or NPR-B−/−) mice was more severe in pressure overload- and sympathetic hyperactivation-induced HF compared with WT; these adverse effects were rescued by pharmacological CNP administration in WT, but not NPR-C−/−, mice. At a molecular level, CNP/NPR-C signalling is impaired in human HF but attenuates activation of well-validated pro-hypertrophic and pro-fibrotic pathways.

Conclusion

C-type natriuretic peptide of cardiomyocyte, endothelial and fibroblast origins co-ordinates and preserves cardiac structure, function, and coronary vasoreactivity via activation of NPR-C. Targeting NPR-C may prove an innovative approach to treating HF and ischaemic cardiovascular disorders.
Elevated high-density lipoprotein in adolescents with Type 1 diabetes is associated with endothelial dysfunction in the presence of systemic inflammation
Authors: Chiesa Scott T , Charakida Marietta , McLoughlin Eve , Nguyen Helen C , Georgiopoulos Georgios , Motran Laura , Elia Yesmino , Marcovecchio M Loredana , Dunger David B , Dalton R Neil , Daneman Denis , Sochett Etienne , Mahmud Farid H , Deanfield John E
Published: February 2019

Aims

High-density lipoprotein (HDL) function may be altered in patients with chronic disease, transforming the particle from a beneficial vasoprotective molecule to a noxious pro-inflammatory equivalent. Adolescents with Type 1 diabetes often have elevated HDL, but its vasoprotective properties and relationship to endothelial function have not been assessed.

Methods and results

Seventy adolescents with Type 1 diabetes (age 10–17 years) and 30 age-matched healthy controls supplied urine samples for the measurement of early renal dysfunction (albumin:creatinine ratio; ACR), blood samples for the assessment of cardiovascular risk factors (lipid profiles, HDL functionality, glycaemic control, and inflammatory risk score), and had their conduit artery endothelial function tested using flow-mediated dilation (FMD). HDL-c levels (1.69 ± 0.41 vs. 1.44 ± 0.29mmol/L; P < 0.001), and glycated haemoglobin (HbA1c) (8.4 ± 1.2 vs. 5.4 ± 0.2%; P < 0.001) were increased in all patients compared with controls. However, increased inflammation and HDL dysfunction were evident only in patients who also had evidence of early renal dysfunction (mean ± standard deviation for high-ACR vs. low-ACR and healthy controls: inflammatory risk score 11.3 ± 2.5 vs. 9.5 ± 2.4 and 9.2 ± 2.4, P < 0.01; HDL-mediated nitric-oxide bioavailability 38.0 ± 8.9 vs. 33.3 ± 7.3 and 25.0 ± 7.7%, P < 0.001; HDL-mediated superoxide production 3.71 ± 3.57 vs. 2.11 ± 3.49 and 1.91 ± 2.47nmol O2 per 250 000 cells, P < 0.05). Endothelial function (FMD) was impaired only in those who had both a high inflammatory risk score and high levels of HDL-c (P < 0.05).

Conclusion

Increased levels of HDL-c commonly observed in individuals with Type 1 diabetes may be detrimental to endothelial function when accompanied by renal dysfunction and chronic inflammation.
Do sociodemographic characteristics associated with the use of CAM differ by chronic disease?
Authors: Drieskens Sabine , Tafforeau Jean , Demarest Stefaan
Published: February 2019

Background

Complementary and alternative medicine (CAM) is oftenused to alleviate the discomfort, disability and pain involved in many chronic diseases. Besides this, females, middle-aged and higher educated people are also known to use CAM the most. This study explores whether the sociodemographic characteristics associated with CAM use differ by type of disease.

Methods

The following data were taken from the Belgian Health Interview Survey 2013 for the individuals aged 15+ years (n = 8942): sociodemographic characteristics, past 12-month diseases (using a list) and contact with a homeopath, chiropractor, acupuncturist and/or osteopath (CAM-therapists) in the past year. The association between CAM use and disease, controlled for gender, age, education and conventional medicine use, was assessed through logistic regressions. When interactions with the sociodemographic characteristics were found, stratified regressions were conducted.

Results

People with musculoskeletal diseases [odds ratio (OR) = 2.6], allergy (OR = 1.4) and severe headache (OR = 1.5) had higher odds of using CAM in the past year with statistical significance. For musculoskeletal diseases, the odds of using CAM was higher, with statistical significance, for every sociodemographic subclass. For allergy, CAM use was higher among men, people aged 45+ years and lower educated people, while for severe headache CAM use was higher among women, people aged 45+ years and higher educated people, all with statistical significance.

Conclusions

Sociodemographic characteristics associated with CAM use differ by diseases. The role of CAM in disease management cannot be ignored. Making physicians aware for which disease CAM is used and by whom, may facilitate disease management.
Social Work Practice with Medical Assistance in Dying: A Case Study
Authors: Antifaeff Kelsey
Published: February 2019

Medical assistance in dying (MAiD) recently became legal in Canada, and social workers have an integral role providing psychosocial care to those considering this end-of-life care option. Research has found that most requests for assisted dying have a psychosocial dimension. Social workers are uniquely equipped to understand the personal and contextual factors informing the choice for MAiD and offer supports. A case example highlights practice opportunities for social workers throughout the MAiD process.
Actual Anti-TNF Trough Levels Relate to Serum IL-10 in Drug-Responding Patients With Crohn’s Disease
Authors: Zapater Pedro , Almenara Susana , Gutiérrez Ana , Sempere Laura , García Marifé , Laveda Raquel , Martínez Antonio , Scharl Michael , Cameo José I , Linares Raquel , González-Navajas José M , Wiest Reiner , Rogler Gerhard , Francés Rubén
Published: February 2019

Background

Patients with Crohn’s disease (CD) responding to anti–tumor necrosis factor (anti-TNF) show great variability in serum drug levels, even within the therapeutic range. We aimed at exploring the role of inflammatory, genetic, and bacterial variables in relation to anti-TNF through levels in CD patients.

Methods

Consecutive CD patients receiving stable doses of infliximab or adalimumab were included. Clinical and analytical parameters were recorded. Cytokine response, bacterial DNA translocation, and several immune-related genes’ genotypes were evaluated, along with serum through anti-TNF drug levels. A linear regression analysis controlled by weight and drug regimen was performed.

Results

One hundred nineteen patients were initially considered. Five patients on infliximab and 2 on adalimumab showed antidrug antibodies in serum and were excluded. One hundred twelve patients were finally included (62 on infliximab, 50 on adalimumab). Fourteen patients on infliximab and 15 on adalimumab (22.6% vs 30%, P = 0.37) were receiving an intensified drug regimen. C-reactive protein (CRP), fecal calprotectin, Crohn’s Disease Activity Index, leukocyte count, and albumin levels in plasma were not significantly associated with infliximab or adalimumab levels in the multivariate analysis. Serum interleukin-10 (IL-10) levels were directly related to infliximab (Beta = 0.097, P < 0.0001) and adalimumab levels (Beta = 0.069, P = 0.0241). The best multivariate regression model explaining the variability of serum infliximab and adalimumab levels included IL-10. Predicted drug levels by this model robustly fitted with actual drug levels (R2 = 0.841 for infliximab, R2 = 0.733 for adalimumab).

Conclusion

Serum IL-10 is significantly related to serum anti-TNF levels in CD patients, showing how the disposition of anti-TNF drugs is significantly influenced by the degree of immunological activation.
Feasibility of planning coronary artery bypass grafting based only on coronary computed tomography angiography and CT-derived fractional flow reserve: a pilot survey of the surgeons involved in the randomized SYNTAX III Revolution trial
Authors: Sonck Jeroen , Miyazaki Yosuke , Collet Carlos , Onuma Yoshinobu , Asano Taku , Takahashi Kuniaki , Kogame Norihiro , Katagiri Yuki , Modolo Rodrigo , Serruys Patrick W , Bartorelli Antonio L , Andreini Daniele , Doenst Torsten , Maureira Juan Pablo , Plass Andre , La Meir Mark , Pompillio Giulio
Published: February 2019

OBJECTIVES

Invasive coronary angiography has been the preferred diagnostic method to guide the decision-making process between coronary artery bypass grafting (CABG) and percutaneous coronary intervention and plan a surgical revascularization procedure. Guidelines recommend a heart team approach and assessment of coronary artery disease (CAD) complexity, objectively quantified by the anatomical SYNTAX score. Coronary computed tomography angiography (CCTA) and CT-derived fractional flow reserve (FFRCT) are emerging technologies in the diagnosis of stable CAD. In this study, data from patients with left main or 3-vessel CAD who underwent CABG were evaluated to assess the feasibility of developing a surgical plan based on CCTA integrated with FFRCT. The primary objective was to assess the theoretical feasibility of surgical decision-making and treatment planning based only on non-invasive imaging.

METHODS

This study represents a survey of surgeons involved in the SYNTAX III Revolution trial. In this trial, heart teams were randomized to make treatment decisions using CTA. CCTAs and FFRCT results of 20 patients were presented to 5 cardiac surgeons.

RESULTS

Surgical treatment decision-making based on CCTA with FFRCT was considered feasible by a panel of surgeons in 84% of the cases with an excellent agreement on the number of anastomoses to be made in each patient (intraclass correlation coefficient 0.77, 95% confidence interval 0.35–0.96).

CONCLUSIONS

Using non-invasive imaging only in patients with left main or 3-vessel CAD, an excellent agreement on treatment planning and the number of anastomoses was found among cardiac surgeons. Thus, CABG planning based on non-invasive imaging appears feasible. Further investigation is warranted to determine the safety and feasibility in clinical practice.
Proof of the Cluckers–Veys Conjecture on Exponential Sums for Polynomials With Log-Canonical Threshold at Most a Half
Authors: Chambille Saskia , Nguyen Kien Huu
Published: February 2019

In this paper, we will give two proofs of the Cluckers–Veys conjecture on exponential sums for the case of polynomials in ${{\mathbb{Z}}}[x_{1},\ldots ,x_{n}]$ having log-canonical thresholds at most one-half. In particular, these results imply Igusa’s conjecture and Denef–Sperber’s conjecture under the same restriction on the log-canonical threshold.
A New Proof of Raynaud–Gruson’s Flattening Theorem
Authors: Guignard Quentin
Published: February 2019

We give a new proof of Raynaud–Gruson’s theorem regarding flattening by blow-ups. The proof is direct, by working directly on the inverse limit of all admissible blow-ups, which is a valuative space similar to the classical Zariski–Riemann space. These valuative spaces are defined in a broader context and always have an analogous flattening property; this yields a generalization of Raynaud–Gruson’s theorem.
Energy Minimizing Beltrami Fields on Sasakian 3-Manifolds
Authors: Peralta-Salas Daniel , Slobodeanu Radu
Published: February 2019

We study on which compact Sasakian 3-manifolds the Reeb field, which is a Beltrami field with eigenvalue $2$, is an energy minimizer in its adjoint orbit under the action of volume-preserving diffeomorphisms. This minimization property for Beltrami fields is relevant because of its connections with the phenomenon of magnetic relaxation and the hydrodynamic stability of steady Euler flows. We characterize the Sasakian manifolds where the Reeb field is a minimizer in terms of the 1st positive eigenvalue of the curl operator and show that for $a>a_0$ (a constant that depends on the Sasakian structure) the Reeb field of the $\mathcal{D}$-homothetic deformation of the manifold with constant $a$ (which is still Sasakian) is an unstable critical point of the energy and hence not even a local minimizer. We also provide some examples of Sasakian manifolds where the Reeb field is a minimizer, highlighting the case of the weighted 3-spheres, on which another minimization problem (for the quartic Skyrme–Faddeev energy) is shown to admit exact solutions.
Can menstrual health apps selected based on users’ needs change health-related factors? A double-blind randomized controlled trial
Authors: Lee Jisan , Kim Jeongeun
Published: February 2019

Objective

Most healthcare providers are reluctant to use health apps for healthcare because there is no rigorous way of choosing the best app for their patient or consumer. Accordingly, we developed a new method of app selection that fully considers target users’ needs. This study verified whether health apps selected based on target users’ needs can influence health-related factors.

Materials and Methods

We conducted a randomized control trial of women with dysmenorrhea and premenstrual syndrome using App A (the best app selected using the new method) and App B (the app with the highest number of users worldwide). The intervention was performed over 4 months to include at least 3 menstrual cycles.

Results

Sixty-one app users completed the 16-week intervention. While users rated both apps as higher in quality than previously used menstrual apps, only App A users showed significant improvements in overall satisfaction, app outcome expectancy, the number of days with records, app social influence, intent to recommend, and the possibility of behavioral or cognitive changes in their symptom management. The number of menus used increased over time. While the app self-efficacy and the number of relief methods did not significantly differ between groups, they still showed an increase in App A users.

Conclusions

When a menstrual app reflected users’ needs, they recorded their symptoms more often and reported higher app quality, satisfaction, and intention to recommend. This study can not only benefit the selection of menstrual apps, but also confirm that mobile health apps can improve health-related factors.
Racial and ethnic disparities in use of a personal health record by veterans living with HIV
Authors: Javier Sarah J , Troszak Lara K , Shimada Stephanie L , McInnes D Keith , Ohl Michael E , Avoundjian Tigran , Erhardt Taryn A , Midboe Amanda M
Published: February 2019

Objective

To examine sociodemographic characteristics associated with use of My HealtheVet (MHV) by veterans living with HIV.

Materials and Methods

Veterans Health Administration administrative data were used to identify a cohort of veterans living with HIV in fiscal years 2011–2017. Descriptive analyses were conducted to examine demographic characteristics and racial/ethnic differences in MHV registration and tool use. Chi-Square tests were performed to assess associations between race/ethnicity and MHV registration and tool use.

Results

The highest proportion of registrants were non-Hispanic White veterans living with HIV (59%), followed by Hispanic/Latino (55%) and Black veterans living with HIV (40%). Chi-Square analyses revealed that: (1) MHV account registration was significantly lower for both Black and Hispanic/Latino veterans in comparison to White veterans and (2) Black MHV registrants were less likely to utilize any MHV tool compared with White MHV registrants including Blue Button record download, medication refills, secure messaging, lab, and appointment views.

Discussion

In line with prior research on personal health record (PHR) use among non-veteran populations, these findings show racial and ethnic inequities in MHV use among veterans living with HIV. Racial and ethnic minorities may be less likely to use PHRs for a myriad of reasons, including PHR privacy concerns, decreased educational attainment, and limited access to the internet.

Conclusion

This is the first study to examine racial and ethnic disparities in use of MHV tools by veterans living with HIV and utilizing Veterans Health Administration health care. Future research should examine potential moderating factors linked to decreased PHR use among racial and ethnic minority veterans, which could inform strategies to increase PHR use among vulnerable populations.
Morelloflavone as a novel inhibitor of mitotic kinesin Eg5
Authors: Ogunwa Tomisin Happy , Taii Kenichi , Sadakane Kei , Kawata Yuka , Maruta Shinsaku , Miyanishi Takayuki
Published: February 2019

Among 40 plant-derived biflavonoids with inhibitory potential against Eg5, morelloflavone from Garcinia dulcis leaves was selected for further testing based on in silico analysis of binding modes, molecular interactions, binding energies and functional groups that interact with Eg5. Computational models predicted that morelloflavone binds the putative allosteric pocket of Eg5, within the cavity surrounded by amino acid residues of Ile-136, Glu-116, Glu-118, Trp-127, Gly-117, Ala-133, Glu-215, Leu-214 and Tyr-211. Binding energy was −8.4 kcal/mol, with a single hydrogen bond formed between morelloflavone and Tyr-211. The binding configuration was comparable to that of a reference inhibitor, S-trityl-L-cysteine. Subsequent biochemical analysis in vitro confirmed that morelloflavone inhibited both the basal and microtubule-activated ATPase activity of Eg5 in a manner that does not compete with ATP binding. Morelloflavone also suppressed Eg5 gliding along microtubules. These results suggest that morelloflavone binds the allosteric binding site in Eg5 and thereby inhibits ATPase activity and motor function of Eg5.
Why Serious International Crimes Might Not Seem ‘Manifestly Unlawful’ to Low-level Perpetrators
Authors: Smeulers Alette
Published: February 2019

Article 33 of the International Criminal Court Statute allows low-ranking perpetrators to — in exceptional cases — rely on the defence of superior orders. By doing so, Article 33 might be seen as an acknowledgement that within a specific context orders to commit international crimes might not always be manifest unlawful. Article 33(2), however, restricts the possibility to rely on this defence to perpetrators of war crimes and denies perpetrators of crimes against humanity and genocide a similar defence, since according to Article 33(2), such orders are considered always to be manifestly unlawful. This contribution questions whether such a distinction should be made. Many low-ranking perpetrators involved in such crimes by following superior orders seem to genuinely believe that they were doing the ‘right thing’. This article seeks to explain how these perpetrators might have come to such a belief, and the challenge this might represent to the core principles which underpin the concept of individual criminal responsibility.
The contribution of nanostructures towards the wing patterning of yellow Catopsilia pomona. How it differs from the lime?
Authors: Mishra Monalisa , Rathore Varsha , Sahu Swetapadma , sahoo Harekrushna
Published: February 2019

Polyphenism, an adaptation to survive throughout the year, is shown by many butterflies including Catopsilia pomona. With the variation of seasons, different morphs were found. Among all the morphs, lime exists throughout the year whereas the yellow one is available only in the winter season. The current study deciphers the colouration mechanism of yellow morph using various microscopic and spectroscopic techniques. The scanning electron microscopy analysis reveals various types of scales on the dorsal as well as the ventral side. The shape of the cover scale varies from region to region. The fine structural arrangement of the scale like window, ridge, microrib, crossrib and pigments vary throughout the wing. The pigment present in the wing is pterin as evidenced from the shape and its isolation technique. Absorption spectroscopy further confirms the presence of various types of pterin within the wing. Scanning electron microscopy discloses the dense amount of pigments within the wing. The fine structural arrangement of the wing of yellow C. pomona is compared with the yellow region of the lime C. pomona. All together, the current study describes the fine structural arrangement of the wing of yellow C. pomona and the various types of pterin which contribute towards the wing colouration. The advantage of yellow morph over lime is also discussed in this paper.
Intraoperative Monitoring of Heparin: Comparison of Activated Coagulation Time and Whole Blood Heparin Measurements by Different Point-of-Care Devices with Heparin Concentration by Laboratory-Performed Plasma Anti-Xa Assay
Authors: Thompson Thomas Z , Kunak Rebecca L , Savage Natasha M , Agarwal Shvetank , Chazelle Jennifer , Singh Gurmukh
Published: February 2019

Background

Cardiac surgical interventions, extracorporeal membrane oxygenation, transcutaneous coronary-artery angioplasty, and stenting are carried out while patients are being treated with the anticoagulation drug heparin. Monitoring the level and reversal of heparinization during and at the conclusion of medical and surgical procedures is a critical issue in patient care.

Methods

We performed parallel testing of the ACCRIVA Hemochron Signature Elite ACT+ and Hemochron Response analyzer, iSTAT platform, and 2 Hepcon Hemostasis Management System (HMS) Plus analyzers for monitoring intraoperative heparin treatment. Laboratory anti-Xa assay was used as the criterion standard for heparin measurement.

Results

Poor correlation between the 2 Hemochron analyzers was identified at 0.78. Correlation between the analyzers on the i-STAT platform was 0.97. Regression analysis revealed that i-STAT values were generally lower, by 43 seconds, than Hemochron values. The correlation between Hepcon and i-STAT activated clotting time (ACT) results was 0.94. The i-STAT ACT results were generally 23 seconds lower than the Hepcon ACT values. Correlation coefficients on comparing Hepcon ACT and i-STAT ACT using laboratory anti-Xa assay were 0.83 and 0.87, respectively. The correlation between Hepcon heparin concentration and anti-Xa results was 0.85.

Conclusions

ACT monitoring with iSTAT offers good correlation between instruments and with the Hepcon ACT. Hepcon occupies a specific niche in cardiac operating departments because of its ability to provide additional information regarding heparin concentration; however, lack of suitable proficiency testing may impair its use. The iSTAT is a more reliable platform for broader, hospital-wide application.
Despite the Holocaust: Rebuilding Jewish Life in Germany after 1945*
Authors: Sinn Andrea A
Published: February 2019

In 1945, the return of Jewish life to Germany was by no means a foregone conclusion. Aiming to understand the developments that laid the groundwork for a long-term continuation of Jewish life in post-Holocaust Germany, this paper discusses the difficult process of rebuilding Jewish institutions in ‘the land of the perpetrators’ during the first two decades after the Second World War. Particularly significant are the essential contributions of two high-profile representatives of this minority to the process of renewing Jewish life in Germany following the Holocaust. By creating a sense of unity among the different Jewish groups and securing financial and practical support essential to the revival of Jewish life in the Federal Republic, the first General Secretary of the Zentralrat der Juden in Deutschland (Central Council of Jews in Germany), Dr Hendrik G. van Dam, and the journalist and chief editor of the German-Jewish newspaper known today as Jüdische Allgemeine, Karl Marx, played a key role in establishing Jewish institutions. These helped to convey a sense of permanency—a central factor for ensuring a continuation of Jewish life in the years and decades to come.
Antifungal drugs: What brings the future?
Authors: Van Daele Ruth , Spriet Isabel , Wauters Joost , Maertens Johan , Mercier Toine , Van Hecke Sam , Brüggemann Roger
Published: February 2019

The high burden and growing prevalence of invasive fungal infections (IFIs), the toxicity and interactions associated with current antifungal drugs, as well as the increasing resistance, ask for the development of new antifungal drugs, preferably with a novel mode of action. Also, the availability of oral or once-weekly alternatives would enable ambulatory treatment resulting in an improved patient's comfort and therapy adherence. However, only one new azole and two new posaconazole-formulations were marketed over the last decade. This review focuses on the antifungal drugs in the pipeline undergoing clinical evaluation. First, the newest azole, isavuconazole, with its improved safety profile and reduction in DDIs, will be discussed. Moreover, there are two glucan synthase inhibitors (GSIs) in the antifungal pipeline: rezafungin (CD101), a long-acting echinocandin with an improved stability that enables once weekly administration, and SCY-078, an orally available GSI with efficacy against azole- and echinocandin resistant isolates. A new oral formulation of amphotericin B will also be presented. Moreover, the first representative of a new antifungal class, the orotomides, with a broad spectrum and no cross-resistance with current antifungal classes, will be discussed. Finally, an overview of other antifungals that are still in earlier clinical development phases, is provided.
Recognition of M-type stars in the unclassified spectra of LAMOST DR5 using a hash-learning method
Authors: Guo Y-X , Luo A-L , Zhang S , Du B , Wang Y-F , Chen J-J , Zuo F , Kong X , Hou Y-H
Published: February 2019

Our study aims to recognize M-type stars which are classified as ‘UNKNOWN’ due to poor quality in the Large sky Area Multi-Object fiber Spectroscopic Telescope (LAMOST) DR5 V1. A binary nonlinear hashing algorithm based on Multi-Layer Pseudo-Inverse Learning (ML-PIL) is proposed to effectively learn spectral features for M-type-star detection, which can overcome the bad fitting problem of template matching, particularly for low S/N spectra. The key steps and the performance of the search scheme are presented. A positive data set is obtained by clustering the existing M-type spectra to train the ML-PIL networks. By employing this new method, we find 11 410 M-type spectra out of 642 178 ‘UNKNOWN’ spectra, and provide a supplemental catalogue. Both the supplemental objects and released M-type stars in DR5 V1 are composed of a whole M-type sample, which will be released in the official DR5 to the public in June 2019. All the M-type stars in the data set are classified as giants and dwarfs by two suggested separators: (1) a colour diagram of H versus J − K from 2MASS, (2) line indices CaOH versus CaH1, and the separation is validated with the Hertzsprung–Russell diagram (HRD) derived from Gaia DR2. The magnetic activities and kinematics of M dwarfs are also provided with the equivalent width (EW) of the Hα emission line and the astrometric data from Gaia DR2 respectively.
Patterns and Mechanisms of Diminishing Returns from Beneficial Mutations
Authors: Wei Xinzhu , Zhang Jianzhi
Published: February 2019

Diminishing returns epistasis causes the benefit of the same advantageous mutation smaller in fitter genotypes and is frequently observed in experimental evolution. However, its occurrence in other contexts, environment dependence, and mechanistic basis are unclear. Here, we address these questions using 1,005 sequenced segregants generated from a yeast cross. Under each of 47 examined environments, 66–92% of tested polymorphisms exhibit diminishing returns epistasis. Surprisingly, improving environment quality also reduces the benefits of advantageous mutations even when fitness is controlled for, indicating the necessity to revise the global epistasis hypothesis. We propose that diminishing returns originates from the modular organization of life where the contribution of each functional module to fitness is determined jointly by the genotype and environment and has an upper limit, and demonstrate that our model predictions match empirical observations. These findings broaden the concept of diminishing returns epistasis, reveal its generality and potential cause, and have important evolutionary implications.