bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of co-evolution analysis through phylogenetic profiling reveals pathway-specific signals
Authors: Bloch Idit , Sherill-Rofe Dana , Stupp Doron , Unterman Irene , Beer Hodaya , Sharon Elad , Tabach Yuval 
Published: April 2020

Abstract

Summary
The exponential growth in available genomic data is expected to reach full sequencing of a million genomes in the coming decade. Improving and developing methods to analyze these genomes and to reveal their utility is of major interest in a wide variety of fields, such as comparative and functional genomics, evolution and bioinformatics. Phylogenetic profiling is an established method for predicting functional interactions between proteins based on similarities in their evolutionary patterns across species. Proteins that function together (i.e. generate complexes, interact in the same pathways or improve adaptation to environmental niches) tend to show coordinated evolution across the tree of life. The normalized phylogenetic profiling (NPP) method takes into account minute changes in proteins across species to identify protein co-evolution. Despite the success of this method, it is still not clear what set of parameters is required for optimal use of co-evolution in predicting functional interactions. Moreover, it is not clear if pathway evolution or function should direct parameter choice. Here, we create a reliable and usable NPP construction pipeline. We explore the effect of parameter selection on functional interaction prediction using NPP from 1028 genomes, both separately and in various value combinations. We identify several parameter sets that optimize performance for pathways with certain biological annotation. This work reveals the importance of choosing the right parameters for optimized function prediction based on a biological context.

Availability and implementation
Source code and documentation are available on GitHub: https://github.com/iditam/CompareNPPs.

Contact
yuvaltab@ekmd.huji.ac.il

Supplementary information
Supplementary data are available at Bioinformatics online.
Impact of Revised Infectious Diseases Society of America and Society for Healthcare Epidemiology of America Clinical Practice Guidelines on the Treatment of Clostridium difficile Infections in the United States
Authors: Clancy Cornelius J , Buehrle Deanna , Vu Michelle , Wagener Marilyn M , Nguyen M Hong 
Published: April 2020

Abstract

Background
Our objective was to determine if oral vancomycin, fidaxomicin, and oral metronidazole use in the United States changed after publication of revised clinical practice guidelines for Clostridium difficile infection (CDI) in February 2018.

Methods
We obtained US antibiotic prescription data (IQVIA) from 2006–August 2019 and used guideline-recommended dosing regimens to estimate monthly numbers of 10-day treatment courses of vancomycin, fidaxomicin and metronidazole. Interrupted time-series analyses were performed, adjusted by month. We compared linear trends for monthly numbers of treatment courses in different time periods.

Results
Cumulative treatment courses of oral vancomycin and fidaxomicin increased by 54% (n = 226 166) and 48% (n = 18 518), respectively, in 18 months following guidelines compared with 18 months before; those of oral metronidazole decreased by 3% (n = 238 372). Monthly vancomycin and fidaxomicin use significantly increased throughout the period following revised guidelines (P &lt; .0001 and P = .0002, respectively), whereas that of metronidazole decreased significantly (P &lt; .0001). Monthly vancomycin use increased and metronidazole use decreased to a significantly greater extent after publication of revised guidelines than after publication of clinical trials establishing superiority of vancomycin over metronidazole (P &lt; .0001).

Conclusions
Revised practice guidelines have had a significant impact on CDI treatment in the US. Clinical trial data used for the revised guidelines were available since 2007–2014 and 2011–2012 for oral vancomycin and fidaxomicin, respectively. Guidelines or guidance documents for treating CDI and other infections should be updated in more timely fashion.
Profile of Immunoglobulin G and IgM Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Authors: Qu Jiuxin , Wu Chi , Li Xiaoyong , Zhang Guobin , Jiang Zhaofang , Li Xiaohe , Zhu Qing , Liu Lei 
Published: April 2020

Abstract
We profiled the serological responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein and spike (S) glycoprotein. The majority of the patients developed robust antibody responses between 17 and 23 days after illness onset. Delayed, but stronger, antibody responses were observed in critical patients.
BET bromodomain-containing epigenetic reader proteins regulate vascular smooth muscle cell proliferation and neointima formation
Authors: Dutzmann Jochen , Haertlé Marco , Daniel Jan-Marcus , Kloss Frederik , Musmann Robert-Jonathan , Kalies Katrin , Knöpp Kai , Pilowski Claudia , Sirisko Mirja , Sieweke Jan-Thorben , Bauersachs Johann , Sedding Daniel G , Gegel Simona 
Published: April 2020

Abstract

Aims
Recent studies revealed that the bromodomain and extra-terminal (BET) epigenetic reader proteins resemble key regulators in the underlying pathophysiology of cancer, diabetes, or cardiovascular disease. However, whether they also regulate vascular remodelling processes by direct effects on vascular cells is unknown. In this study, we investigated the effects of the BET proteins on human smooth muscle cell (SMC) function in vitro and neointima formation in response to vascular injury in vivo.

Methods and results
Selective inhibition of BETs by the small molecule (+)-JQ1 dose-dependently reduced proliferation and migration of SMCs without apoptotic or toxic effects. Flow cytometric analysis revealed a cell cycle arrest in the G0/G1 phase in the presence of (+)-JQ1. Microarray- and pathway analyses revealed a substantial transcriptional regulation of gene sets controlled by the Forkhead box O (FOXO1)1-transcription factor. Silencing of the most significantly regulated FOXO1-dependent gene, CDKN1A, abolished the antiproliferative effects. Immunohistochemical colocalization, co-immunoprecipitation, and promoter-binding ELISA assay data confirmed that the BET protein BRD4 directly binds to FOXO1 and regulates FOXO1 transactivational capacity. In vivo, local application of (+)-JQ1 significantly attenuated SMC proliferation and neointimal lesion formation following wire-induced injury of the femoral artery in C57BL/6 mice.

Conclusion
Inhibition of the BET-containing protein BRD4 after vascular injury by (+)-JQ1 restores FOXO1 transactivational activity, subsequent CDKN1A expression, cell cycle arrest and thus prevents SMC proliferation in vitro and neointima formation in vivo. Inhibition of BET epigenetic reader proteins might thus represent a promising therapeutic strategy to prevent adverse vascular remodelling.
Management of patients with combined arterial hypertension and aortic valve stenosis: a consensus document from the Council on Hypertension and Council on Valvular Heart Disease of the European Society of Cardiology, the European Association of Cardiovascular Imaging (EACVI), and the European Association of Percutaneous Cardiovascular Interventions (EAPCI)
Authors: Mancusi Costantino , de Simone Giovanni , Brguljan Hitij Jana , Sudano Isabella , Mahfoud Felix , Parati Gianfranco , Kahan Thomas , Barbato Emanuele , Pierard Luc A , Garbi Madalina , Flachskampf Frank A , Gerdts Eva 
Published: April 2020

Abstract
Aortic valve stenosis (AS) is the third most common cardiovascular disease. The prevalence of both AS and arterial hypertension increases with age, and the conditions therefore often co-exist. Co-existence of AS and arterial hypertension is associated with higher global left ventricular (LV) pressure overload, more abnormal LV geometry and function, and more adverse cardiovascular outcome. Arterial hypertension may also influence grading of AS, leading to underestimation of the true AS severity. Current guidelines suggest re-assessing patients once arterial hypertension is controlled. Management of arterial hypertension in AS has historically been associated with prudence and concerns, mainly related to potential adverse consequences of drug-induced peripheral vasodilatation combined with reduced stroke volume due to the fixed LV outflow obstruction. Current evidence suggests that patients should be treated with antihypertensive drugs blocking the renin–angiotensin–aldosterone system, adding further drug classes when required, to achieve similar target blood pressure (BP) values as in hypertensive patients without AS. The introduction of transcatheter aortic valve implantation has revolutionized the management of patients with AS, but requires proper BP management during and following valve replacement. The purpose of this document is to review the recent evidence and provide practical expert advice on management of hypertension in patients with AS.
The Justification of Privilege in International Investment Law: Preferential Treatment of Foreign Investors as a Problem of Legitimacy
Authors: Alvik Ivar 
Published: April 2020

Abstract
A fundamental feature of international investment law is that it only applies to foreign investment. This has historical reasons and is connected to deep-rooted principles of international law. It has also been a historical cause of controversy because it requires states to treat foreign investors better than they treat their own nationals. This article shows how the international minimum standard for treatment of foreigners nevertheless developed in a dialogue with such a concern for equality. The article argues that the way in which international investment law has developed in recent years into an effective remedial mechanism that can be invoked by individual foreign investors against host states ignores this historical lesson and now poses a particular challenge to its legitimacy. It privileges foreign investors as a select group worthy of more effective legal protection than ordinarily provided under municipal law, challenging the ideal of equality before the law as a basic constitutional value. The article discusses possible justifications of such privilege, arguing that only a more traditional international minimum standard rationale provides a convincing justification of special treatment of foreign investment. This has important implications for the reform of the current investment regime, suggesting that it should be redesigned to adopt a more supplementary role and deferential attitude to domestic law and courts – for example, through a requirement to exhaust local remedies.
Epigenetic Clock and Leukocyte Telomere Length Are Associated with Vitamin D Status but not with Functional Assessments and Frailty in the Berlin Aging Study II
Authors: Vetter Valentin Max , Spira Dominik , Banszerus Verena Laura , Demuth Ilja 
Published: April 2020

Abstract
DNA methylation (DNAm) age acceleration, a parameter derived via the epigenetic clock, has recently been suggested as a biomarker of aging. We hypothesized that accelerated biological aging, measured by both this new and the established biomarker of aging, relative leukocyte telomere length (rLTL), are associated with vitamin D deficiency. Moreover, we tested for an association between rLTL/DNAm age acceleration and different clinical assessments for functional capacity, including the Fried frailty score. Cross-sectional data of 1,649 participants of the Berlin Aging Study II was available (~50% female, age: 22–37 and 60–84 years). A seven cytosine-phosphate-guanine clock was estimated to calculate the DNAm age acceleration. rLTL was measured by quantitative real-time polymerase chain reaction (PCR). 25-hydroxyvitamin D (25(OH)D) serum levels &lt;25 nmol/L was defined as vitamin D deficiency and &lt;50 nmol/L as vitamin D insufficiency. Vitamin D-sufficient individuals had a 1.4 years lower mean DNAm age acceleration (p &lt; .05, analysis of variance [ANOVA]) and a 0.11 longer rLTL (p &lt; .001, ANOVA) than vitamin D-deficient participants. Likewise, vitamin D-sufficient participants had lower DNAm age acceleration (β = 1.060, p = .001) and longer rLTL (β = −0.070; p &lt; .001) than vitamin D nonsufficient subjects in covariate-adjusted analysis. Neither DNAm age acceleration nor rLTL were significantly associated with the Fried frailty score or the functional assessments. Only the clock drawing test was associated with DNAm age acceleration (subgroup of older men: β = 1.898, p = .002). Whether the analyzed biomarkers of aging can be used to predict an individual’s functional capacity or will be associated with frailty in the advanced course of aging, will be clarified by future longitudinal analyses.
Bayesian trans-dimensional full waveform inversion: synthetic and field data application
Authors: Guo Peng , Visser Gerhard , Saygin Erdinc 
Published: April 2020

SUMMARYSeismic full waveform inversion (FWI) is a state-of-the-art technique for estimating subsurface physical models from recorded seismic waveform, but its application requires care because of high non-linearity and non-uniqueness. The final outcome of global convergence from conventional FWI using local gradient information relies on an informative starting model. Bayesian inference using Markov chain Monte Carlo (MCMC) sampling is able to remove such dependence, by a direct extensive search of the model space. We use a Bayesian trans-dimensional MCMC seismic FWI method with a parsimonious dipping layer parametrization, to invert for subsurface velocity models from pre-stack seismic shot gathers that contain mainly reflections. For the synthetic study, we use a simple four-layer model and a modified Marmousi model. A recently collected multichannel off-shore seismic reflection data set, from the Lord Howe Rise (LHR) in the east of Australia, is used for the field data test. The trans-dimensional FWI method is able to provide model ensembles for describing posterior distribution, when the dipping-layer model assumption satisfies the observed data. The model assumption requires narrow models, thus only near-offset data to be used. We use model stitching with lateral and depth constraints to create larger 2-D models from many adjacent overlapping submodel inversions. The inverted 2-D velocity model from the Bayesian inference can then be used as a starting model for the gradient-based FWI, from which we are able to obtain high-resolution subsurface velocity models, as demonstrated using the synthetic data. However, lacking far-offset data limits the constraints for the low-wavenumber part of the velocity model, making the inversion highly non-unique. We found it challenging to apply the dipping-layer based Bayesian FWI to the field data. The approximations in the source wavelet and forward modelling physics increase the multimodality of the posterior distribution; the sampled velocity models clearly show the trade-off between interface depth and velocity. Numerical examples using the synthetic and field data indicate that trans-dimensional FWI has the potential for inverting earth models from reflection waveform. However, a sparse model parametrization and far offset constraints are required, especially for field application.
Ocean acidification induces carry-over effects on the larval settlement of the New Zealand abalone,Haliotis iris
Authors: Espinel-Velasco Nadjejda , Lamare Miles , Kluibenschedl Anna , Moss Graeme , Cummings Vonda 
Published: April 2020

AbstractLarval settlement is a key process in the lifecycle of benthic marine organisms; however, little is known on how it could change in reduced seawater pH and carbonate saturation states under future ocean acidification (OA). This is important, as settlement ensures species occur in optimal environments and, for commercially important species such as abalone, reduced settlement could decrease future population success. We investigated how OA could affect settlement success in the New Zealand abalone Haliotis iris by examining: (1) direct effects of seawater at ambient (pHT 8.05) and reduced pHT (7.65) at the time of settlement, (2) indirect effects of settlement substrates (crustose coralline algae, CCA) preconditioned at ambient and reduced pHT for 171 days, and (3) carry-over effects, by examining settlement in larvae reared to competency at ambient and reduced pHT (7.80). We found no effects of seawater pH or CCA incubation on larval settlement success. OA-induced carry-over effects were evident, with lower settlement in larvae reared at reduced pH. Understanding the mechanisms behind these responses is key to fully comprehend the extent to which OA will affect marine organisms and the industries that rely on them.
Phenotypic and genotypic quinolone resistance in Escherichia coli underlining GyrA83/87 mutations as a target to detect ciprofloxacin resistance
Authors: Muggeo Anaëlle , Cambau Emmanuelle , Amara Marlène , Micaëlo Maïté , Pangon Béatrice , Bajolet Odile , Benmansour Hanaa , de Champs Christophe , Guillard Thomas 
Published: April 2020

Abstract

Background
Quinolone resistance (QR) is one component of the MDR emerging in Escherichia coli and is of particular concern given the widespread use of fluoroquinolones.

Objectives
To characterize the QR phenotypes and genotypes in E. coli responsible for bloodstream infections and to propose molecular determinants that could be targeted to predict ciprofloxacin resistance.

Methods
E. coli isolates from blood cultures in three French hospitals were studied for quinolone MICs and characterization of genotypic QR determinants (QRg).

Results
Among 507 isolates tested for MICs, 148 (29.2%) were resistant to quinolones based on EUCAST breakpoints and 143 (28.2%) harboured at least one QRg. QRg were mainly mutations in the QRDR (138 isolates, 27.2%), with 55.8% of these isolates carrying at least three QRDR mutations. gyrA mutations predominated (92.8%) followed by parC (61.6%), parE (32.6%) and gyrB (1.4%) mutations. Only 4.7% of the isolates harboured a plasmid-mediated quinolone resistance (PMQR) gene: aac(6′)-Ib-cr (60.0%) or qnr (qnrS, qnrB) (32.0%). For the first time in France, we reported the qepA4 allele of the plasmid-encoded efflux pump QepA. Only five isolates carried PMQR without a QRDR mutation. The positive predictive value (PPV) for ciprofloxacin resistance was 100% for any QRg and 99.2% for gyrA mutations specifically.

Conclusions
QR observed in E. coli isolates involved in bloodstream infections is still mainly due to QRDR mutations, especially at codons GyrA83/87, which could be used as a molecular target to rapidly detect resistance.
Assessing New Tools for Management of the Pepper Weevil (Coleoptera: Curculionidae) in Greenhouse and Field Pepper Crops
Authors: Labbé Roselyne M , Gagnier Dana , Rizzato Rebecca , Tracey Amanda , McCreary Cara 
Published: April 2020

Abstract
The pepper weevil, Anthonomus eugenii Cano, is an economically important pest of field and greenhouse pepper crops in North America. In this study, a series of insecticides covering a broad-spectrum of insecticidal modes of action were assessed for their potential in managing the pepper weevil under laboratory and greenhouse conditions. To accomplish this, laboratory mini-spray tower and greenhouse cage trials were conducted that evaluated the efficacy of 16 conventional, reduced-risk, and microbial insecticides. In laboratory trials, adult weevils were sprayed with insecticides, placed on treated leaves within a cup cage, and were monitored for their survival over 10 d. Of the 16 insecticides tested, 8 provided greater than 60% weevil control, a threshold considered necessary for including products in further greenhouse testing. In greenhouse trials, adult weevil mortality, bud and foliar damage, bud and fruit abortion, and subsequent weevil offspring emergence were measured following each of three weekly insecticide applications. The most efficacious insecticides included kaolin clay and mineral oil, which performed as well as the thiamethoxam-positive control, and incurred 70 and 55% of adult weevil mortality, respectively. Additionally, kaolin clay and mineral oil reduced offspring weevil emergence by 59 and 54%, respectively, compared with untreated controls. Despite the clear challenge that controlling this pest represents, this study has identified useful new tools for the integrated management of the pepper weevil, which may accelerate the rate at which these become available for use in greenhouse and field pepper production.
A phase I/II trial of intraoperative breast radiotherapy in an Asian population: 10-year results with critical evaluation
Authors: Kawamura Mariko , Itoh Yoshiyuki , Kamomae Takeshi , Sawaki Masataka , Kikumori Toyone , Tsunoda Nobuyuki , Ito Junji , Shimoyama Yoshie , Satake Hiroko , Naganawa Shinji 
Published: April 2020

Abstract
Although phase III trials have been published comparing whole breast irradiation (WBI) with accelerated partial breast irradiation (APBI) using intraoperative radiotherapy (IORT), long-term follow-up results are lacking. We report the 10-year follow-up results of a prospective phase I/II clinical trial of IORT. The inclusion criteria were as follows: (i) tumor size &lt;2.5 cm, (ii) desire for breast-conserving surgery, (iii) age &gt;50 years, (iv) negative margins after resection and (v) sentinel lymph node-negative disease. A single dose of IORT (19–21 Gy) was delivered to the tumor bed in the operation room just after wide local excision of the primary breast cancer using a 6–12 MeV electron beam. Local recurrence was defined as recurrence or new disease within the treated breast and was evaluated annually using mammography and ultrasonography. A total of 32 patients were eligible for evaluation. The median patient age was 65 years and the median follow-up time was 10 years. Two patients experienced local recurrence just under the nipple, out of the irradiated field, after 8 years of follow-up. Three patients had contralateral breast cancer and one patient experienced bone metastasis after 10 years of follow-up. No patient experienced in-field recurrence nor breast cancer death. Eight patients had hypertrophic scarring at the last follow-up. There were no lung or heart adverse effects. This is the first report of 10-year follow-up results of IORT as APBI. The findings suggest that breast cancer with extended intraductal components should be treated with great caution.
Flavonoids are indispensable for complete male fertility in rice
Authors: Wang Lanxiang , Ying Lam Lydia Pui , Lui Andy C W , Zhu Fu-Yuan , Chen Mo-Xian , Liu Hongjia , Zhang Jianhua , Lo Clive 
Published: April 2020

AbstractFlavonoids are essential for male fertility in some but not all plant species. In rice (Oryza sativa), the chalcone synthase mutant oschs1 produces flavonoid-depleted pollen and is male sterile. The mutant pollen grains are viable with normal structure, but they display reduced germination rate and pollen-tube length. Analysis of oschs1/+ heterozygous lines shows that pollen flavonoid deposition is a paternal effect and fertility is independent of the haploid genotypes (OsCHS1 or oschs1). To understand which classes of flavonoids are involved in male fertility, we conducted detailed analysis of rice mutants for branch-point enzymes of the downstream flavonoid pathways, including flavanone 3-hydroxylase (OsF3H; flavonol pathway entry enzyme), flavone synthase II (CYP93G1; flavone pathway entry enzyme), and flavanone 2-hydroxylase (CYP93G2; flavone C-glycoside pathway entry enzyme). Rice osf3h and cyp93g1 cyp93g2 CRISPR/Cas9 mutants, and cyp93g1 and cyp93g2 T-DNA insertion mutants showed altered flavonoid profiles in anthers, but only the osf3h and cyp93g1 cyp93g2 mutants displayed reduction in seed yield. Our findings indicate that flavonoids are essential for complete male fertility in rice and a combination of different classes (flavanones, flavonols, flavones, and flavone C-glycosides) appears to be important, as opposed to the essential role played primarily by flavonols that has been previously reported in several plant species.