bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher-order Markov models for metagenomic sequence classification
Authors: Burks David J , Azad Rajeev K
Published: June 2020

Motivation

Alignment-free, stochastic models derived from k-mer distributions representing reference genome sequences have a rich history in the classification of DNA sequences. In particular, the variants of Markov models have previously been used extensively. Higher-order Markov models have been used with caution, perhaps sparingly, primarily because of the lack of enough training data and computational power. Advances in sequencing technology and computation have enabled exploitation of the predictive power of higher-order models. We, therefore, revisited higher-order Markov models and assessed their performance in classifying metagenomic sequences.

Results

Comparative assessment of higher-order models (HOMs, 9th order or higher) with interpolated Markov model, interpolated context model and lower-order models (8th order or lower) was performed on metagenomic datasets constructed using sequenced prokaryotic genomes. Our results show that HOMs outperform other models in classifying metagenomic fragments as short as 100 nt at all taxonomic ranks, and at lower ranks when the fragment size was increased to 250 nt. HOMs were also found to be significantly more accurate than local alignment which is widely relied upon for taxonomic classification of metagenomic sequences. A novel software implementation written in C++ performs classification faster than the existing Markovian metagenomic classifiers and can therefore be used as a standalone classifier or in conjunction with existing taxonomic classifiers for more robust classification of metagenomic sequences.

Availability and implementation

The software has been made available at https://github.com/djburks/SMM.

Contact

Rajeev.Azad@unt.edu

Supplementary information

Supplementary data are available at Bioinformatics online.
White Matter Development from Birth to 6 Years of Age: A Longitudinal Study
Authors: Stephens Rebecca L , Langworthy Benjamin W , Short Sarah J , Girault Jessica B , Styner Martin A , Gilmore John H
Published: June 2020

Human white matter development in the first years of life is rapid, setting the foundation for later development. Microstructural properties of white matter are linked to many behavioral and psychiatric outcomes; however, little is known about when in development individual differences in white matter microstructure are established. The aim of the current study is to characterize longitudinal development of white matter microstructure from birth through 6 years to determine when in development individual differences are established. Two hundred and twenty-four children underwent diffusion-weighted imaging after birth and at 1, 2, 4, and 6 years. Diffusion tensor imaging data were computed for 20 white matter tracts (9 left–right corresponding tracts and 2 commissural tracts), with tract-based measures of fractional anisotropy and axial and radial diffusivity. Microstructural maturation between birth and 1 year are much greater than subsequent changes. Further, by 1 year, individual differences in tract average values are consistently predictive of the respective 6-year values, explaining, on average, 40% of the variance in 6-year microstructure. Results provide further evidence of the importance of the first year of life with regard to white matter development, with potential implications for informing early intervention efforts that target specific sensitive periods.
One Hundred Days of Coronavirus Disease 2019 Prevention and Control in China
Authors: Zhou Lei , Wu Zunyou , Li Zhongjie , Zhang Yanping , McGoogan Jennifer M , Li Qun , Dong Xiaoping , Ren Ruiqi , Feng Luzhao , Qi Xiaopeng , Xi Jingjing , Cui Ying , Tan Wenjie , Shi Guoqing , Wu Guizhen , Xu Wenbo , Wang Xiaoqi , Ma Jiaqi , Su Xuemei , Feng Zijian , Gao George F
Published: June 2020

The epidemic of novel coronavirus disease was first reported in China in late December 2019 and was brought under control after some 2 months in China. However, it has become a global pandemic, and the number of cases and deaths continues to increase outside of China. We describe the emergence of the pandemic, detail the first 100 days of China’s response as a phase 1 containment strategy followed by phase 2 containment, and briefly highlight areas of focus for the future. Specific, simple, and pragmatic strategies used in China for risk assessment, prioritization, and deployment of resources are described. Details of implementation, at different risk levels, of the traditional public health interventions are shared. Involvement of society in mounting a whole country response and challenges experienced with logistics and supply chains are described. Finally, the methods China is employing to cautiously restart social life and economic activity are outlined.
On Setting Expectations for a Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine
Authors: Canaday David H , Gravenstein Stefan
Published: June 2020

The global coronavirus pandemic is unlike any other since 1918. A century of dramatic medical advances has produced a public expectation that the medical field will rapidly provide solutions to restore normalcy. In less than 6 months, since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified, the massive international effort to develop a SARS-CoV-2 vaccine has generated more than 140 vaccines in different stages of development, with 9 already recruiting into clinical trials posted on ClinicalTrials.gov. The long-term strategy to handle coronavirus disease 2019 (COVID-19) will almost certainly rely on vaccines. But what type of protection can we realistically expect to achieve from vaccines and when?
The Notion of Transparency Order, Revisited
Authors: Li Huizhong , Zhou Yongbin , Ming Jingdian , Yang Guang , Jin Chengbin
Published: June 2020

We revisit the definition of transparency order (TO) and that of modified transparency order (MTO) as well, which were proposed to measure the resistance of substitution boxes (S-boxes) against differential power analysis (DPA). We spot a definitional flaw in original TO, which is proved to significantly affect the soundness of TO. Regretfully, MTO overlooks this flaw, yet it happens to incur no bad effects on the correctness of MTO, even though the start point of this formulation is highly questionable. It is also this neglect that made MTO consider a variant of multi-bit DPA attack, which was mistakenly thought to appropriately serve as an alternative powerful attack. This implies the soundness of MTO is also more or less arguable. Therefore, we fix this definitional flaw and provide a revised definition named reVisited TO (VTO). For demonstrating validity and soundness of VTO, we present simulated and practical DPA attacks on implementations of $4\times 4$ and $8\times 8$ S-boxes. In addition, we also illustrate the soundness of VTO in masked S-boxes. Furthermore, as a concrete application of VTO, we present the distribution of VTO values of optimal affine equivalence classes of $4\times 4$ S-boxes and give some recommended guidelines on how to select $4\times 4$ S-boxes with higher DPA resistance at the identical level of implementation cost.
Reliability Analysis of Alternating Group Graphs and Split-Stars
Authors: Gu Mei-Mei , Hao Rong-Xia , Chang Jou-Ming
Published: June 2020

Given a connected graph $G$ and a positive integer $\ell $, the $\ell $-extra (resp. $\ell $-component) edge connectivity of $G$, denoted by $\lambda ^{(\ell )}(G)$ (resp. $\lambda _{\ell }(G)$), is the minimum number of edges whose removal from $G$ results in a disconnected graph so that every component has more than $\ell $ vertices (resp. so that it contains at least $\ell $ components). This naturally generalizes the classical edge connectivity of graphs defined in term of the minimum edge cut. In this paper, we proposed a general approach to derive component (resp. extra) edge connectivity for a connected graph $G$. For a connected graph $G$, let $S$ be a vertex subset of $G$ for $G\in \{\Gamma _{n}(\Delta ),AG_n,S_n^2\}$ such that $|S|=s\leq |V(G)|/2$, $G[S]$ is connected and $|E(S,G-S)|=\min \limits _{U\subseteq V(G)}\{|E(U, G-U)|: |U|=s, G[U]\ \textrm{is connected}\ \}$, then we prove that $\lambda ^{(s-1)}(G)=|E(S,G-S)|$ and $\lambda _{s+1}(G)=|E(S,G-S)|+|E(G[S])|$ for $s=3,4,5$. By exploring the reliability analysis of $AG_n$ and $S_n^2$ based on extra (component) edge faults, we obtain the following results: (i) $\lambda _3(AG_n)-1=\lambda ^{(1)}(AG_n)=4n-10$, $\lambda _4(AG_n)-3=\lambda ^{(2)}(AG_n)=6n-18$ and $\lambda _5(AG_n)-4=\lambda ^{(3)}(AG_n)=8n-24$; (ii) $\lambda _3(S_n^2)-1=\lambda ^{(1)}(S_n^2)=4n-8$, $\lambda _4(S_n^2)-3=\lambda ^{(2)}(S_n^2)=6n-15$ and $\lambda _5(S_n^2)-4=\lambda ^{(3)}(S_n^2)=8n-20$. This general approach maybe applied to many diverse networks.
Rethinking the Ethnography of Communication's Conception of Value in the Context of Globalization
Authors: Boromisza-Habashi David , Fang Yaqiong
Published: June 2020

As a key approach to the study of language and social interaction within the field of communication, the ethnography of communication (EC) posits that speech communities value communication resources for their functions in the process of competent use. We argue that this conception of value creates theoretical blind spots for other types of value that derive from other processes besides competent use, such as the exchange and acquisition of communication resources. Drawing on recent anthropological scholarship and our own cross-cultural comparative case study of United States and Chinese students' accounts of learning Anglo-American public speaking, we claim that, from an ethnographic perspective, a communication resource has value insofar as speakers interpret it as an object of desire due to its function as a means to other valued entities or focal values in the context of relevant social processes.
Screening for cardiovascular disease risk using traditional risk factor assessment or coronary artery calcium scoring: the ROBINSCA trial
Authors: van der Aalst Carlijn M , Denissen Sabine J A M , Vonder Marleen , Gratama Jan Willem C , Adriaansen Henk J , Kuijpers Dirkjan , Vliegenthart Rozemarijn , van Lennep Jeanine E Roeters , van der Harst Pim , Braam Richard L , van Dijkman Paul R M , van Bruggen Rykel , Oudkerk Matthijs , de Koning Harry J
Published: June 2020

Aims

Screening for a high cardiovascular disease (CVD) risk followed by preventive treatment can potentially reduce coronary heart disease-related morbidity and mortality. ROBINSCA (Risk Or Benefit IN Screening for CArdiovascular disease) is a population-based randomized controlled screening trial that investigates the effectiveness of CVD screening in asymptomatic participants using the Systematic COronary Risk Evaluation (SCORE) model or coronary artery calcium (CAC) scoring. This study describes the distributions in risk and treatment in the ROBINSCA trial.

Methods and results

Individuals at expected elevated CVD risk were randomized into screening arm A (n = 14 478; SCORE, 10-year fatal and non-fatal risk); or screening arm B (n = 14 450; CAC scoring). Preventive treatment was largely advised according to current Dutch guidelines. Risk and treatment differences between the screening arms were analysed. A total of 12 185 participants (84.2%) in arm A and 12 950 (89.6%) in arm B were screened. In total, 48.7% were women, and median age was 62 (interquartile range 10) years. SCORE screening identified 45.1% at low risk (SCORE < 10%), 26.5% at intermediate risk (SCORE 10–20%), and 28.4% at high risk (SCORE ≥ 20%). According to CAC screening, 76.0% were at low risk (Agatston < 100), 15.1% at high risk (Agatston 100–399), and 8.9% at very high risk (Agatston ≥ 400). CAC scoring significantly reduced the number of individuals indicated for preventive treatment compared to SCORE (relative reduction women: 37.2%; men: 28.8%).

Conclusion

We showed that compared to risk stratification based on SCORE, CAC scoring classified significantly fewer men and women at increased risk, and less preventive treatment was indicated.

Trial registration number

NTR6471.
On Theorizing International Organizations Law: Editors’ Introduction
Authors: Klabbers Jan , Sinclair Guy Fiti
Published: June 2020

This short article introduces a symposium on the intellectual history of international organizations law, which focuses on the contributions of six international lawyers: Henry G. (Hein) Schermers, Clarence Wilfred Jenks, Paul Reuter, Louis Sohn, Georges Abi-Saab and Hans Kelsen.
Targeting muscle-enriched long non-coding RNA H19 reverses pathological cardiac hypertrophy
Authors: Viereck Janika , Bührke Anne , Foinquinos Ariana , Chatterjee Shambhabi , Kleeberger Jan A , Xiao Ke , Janssen-Peters Heike , Batkai Sandor , Ramanujam Deepak , Kraft Theresia , Cebotari Serghei , Gueler Faikah , Beyer Andreas M , Schmitz Jessica , Bräsen Jan H , Schmitto Jan D , Gyöngyösi Mariann , Löser Alexandra , Hirt Marc N , Eschenhagen Thomas , Engelhardt Stefan , Bär Christian , Thum Thomas
Published: June 2020

Aims

Pathological cardiac remodelling and subsequent heart failure represents an unmet clinical need. Long non-coding RNAs (lncRNAs) are emerging as crucial molecular orchestrators of disease processes, including that of heart diseases. Here, we report on the powerful therapeutic potential of the conserved lncRNA H19 in the treatment of pathological cardiac hypertrophy.

Method and results

Pressure overload-induced left ventricular cardiac remodelling revealed an up-regulation of H19 in the early phase but strong sustained repression upon reaching the decompensated phase of heart failure. The translational potential of H19 is highlighted by its repression in a large animal (pig) model of left ventricular hypertrophy, in diseased human heart samples, in human stem cell-derived cardiomyocytes and in human engineered heart tissue in response to afterload enhancement. Pressure overload-induced cardiac hypertrophy in H19 knock-out mice was aggravated compared to wild-type mice. In contrast, vector-based, cardiomyocyte-directed gene therapy using murine and human H19 strongly attenuated heart failure even when cardiac hypertrophy was already established. Mechanistically, using microarray, gene set enrichment analyses and Chromatin ImmunoPrecipitation DNA-Sequencing, we identified a link between H19 and pro-hypertrophic nuclear factor of activated T cells (NFAT) signalling. H19 physically interacts with the polycomb repressive complex 2 to suppress H3K27 tri-methylation of the anti-hypertrophic Tescalcin locus which in turn leads to reduced NFAT expression and activity.

Conclusion

H19 is highly conserved and down-regulated in failing hearts from mice, pigs and humans. H19 gene therapy prevents and reverses experimental pressure-overload-induced heart failure. H19 acts as an anti-hypertrophic lncRNA and represents a promising therapeutic target to combat pathological cardiac remodelling.
Anti-EGFR therapy in metastatic colorectal cancer: mechanisms and potential regimens of drug resistance
Authors: Li Qing-Hai , Wang Ying-Zhao , Tu Jian , Liu Chu-Wei , Yuan Yu-Jie , Lin Run , He Wei-Ling , Cai Shi-Rong , He Yu-Long , Ye Jin-Ning
Published: June 2020

Cetuximab and panitumumab, as the highly effective antibodies targeting epidermal growth factor receptor (EGFR), have clinical activity in the patients with metastatic colorectal cancer (mCRC). These agents have good curative efficacy, but drug resistance also exists at the same time. The effects of KRAS, NRAS, and BRAF mutations and HER2 amplification on the treatment of refractory mCRC have been elucidated and the corresponding countermeasures have been put forward. However, the changes in EGFR and its ligands, the mutations or amplifications of PIK3CA, PTEN, TP53, MET, HER3, IRS2, FGFR1, and MAP2K1, the overexpression of insulin growth factor-1, the low expression of Bcl-2-interacting mediator of cell death, mismatch repair-deficient, and epigenetic instability may also lead to drug resistance in mCRC. Although the emergence of drug resistance has genetic or epigenetic heterogeneity, most of these molecular changes relating to it are focused on the key signaling pathways, such as the RAS/RAF/mitogen-activated protein kinase or phosphatidylinositol 3-kinase/Akt/mammalian target of the rapamycin pathway. Accordingly, numerous efforts to target these signaling pathways and develop the novel therapeutic regimens have been carried out. Herein, we have reviewed the underlying mechanisms of the resistance to anti-EGFR therapy and the possible implications in clinical practice.
State Power and ‘Everyday Criminality’ in the German Democratic Republic, 1961–1989
Authors: Millington Richard
Published: June 2020

Friedrich Engels claimed that the removal of the perceived causes of crime in a society—capitalist economic and societal conditions—would automatically lead to the eradication of crime. This did not prove to be the case in the German Democratic Republic (GDR), where instances of everyday criminality such as theft, robbery and assault never fell below 100,000 per annum throughout the period of the state’s existence, from 1949 to 1989. This article examines the ruling Socialist Unity Party’s (SED) perceptions of the causes of everyday criminality in the GDR. It shows that the SED concluded that crime persisted because citizens’ ‘socialist sense of legal right and wrong’ (sozialistisches Rechtsbewußtsein) was underdeveloped. The regime measured this by the extent to which citizens supported and participated in socialist society. Thus, crime could be eliminated by co-opting as many citizens as possible into the Party’s political project. The SED’s ideological tunnel vision on the causes of everyday criminality meant that it dismissed hints about the real causes of crime, such as poor supply and living conditions, identified by its analysts. Its failure to address these issues meant that citizens continued to break the law. Thus, the Party’s exercise of power contributed to the creation of limits to that power. Moreover, analysis of opinion polls on GDR citizens’ attitudes to criminality shows that they accepted crime as a part of everyday life.
The Importance of a Filament-like Structure in Aerial Dispersal and the Rarefaction Effect of Air Molecules on a Nanoscale Fiber: Detailed Physics in Spiders’ Ballooning
Authors: Cho Moonsung , Koref Iván Santibáñez
Published: June 2020

Synopsis

Many flying insects utilize a membranous structure for flight, which is known as a “wing.” However, some spiders use silk fibers for their aerial dispersal. It is well known that spiders can disperse over hundreds of kilometers and rise several kilometers above the ground in this way. However, little is known about the ballooning mechanisms of spiders, owing to the lack of quantitative data. Recently, Cho et al. discovered previously unknown information on the types and physical properties of spiders’ ballooning silks. According to the data, a crab spider weighing 20 mg spins 50–60 ballooning silks simultaneously, which are about 200 nm thick and 3.22 m long for their flight. Based on these physical dimensions of ballooning silks, the significance of these filament-like structures is explained by a theoretical analysis reviewing the fluid-dynamics of an anisotropic particle (like a filament or a high-slender body). (1) The filament-like structure is materially efficient geometry to produce (or harvest, in the case of passive flight) fluid-dynamic force in a low Reynolds number flow regime. (2) Multiple nanoscale fibers are the result of the physical characteristics of a thin fiber, the drag of which is proportional to its length but not to its diameter. Because of this nonlinear characteristic of a fiber, spinning multiple thin ballooning fibers is, for spiders, a better way to produce drag forces than spinning a single thick spider silk, because spiders can maximize their drag on the ballooning fibers using the same amount of silk dope. (3) The mean thickness of fibers, 200 nm, is constrained by the mechanical strength of the ballooning fibers and the rarefaction effect of air molecules on a nanoscale fiber, because the slip condition on a fiber could predominate if the thickness of the fiber becomes thinner than 100 nm.
Invariants of a General Branched Cover of P1
Authors: Bujokas Gabriel , Patel Anand
Published: June 2020

We investigate the resolution of a general branched cover $\alpha \colon C \to \mathbf{P}^1$ in its relative canonical embedding $C \subset \mathbf{P} E$. We conjecture that the syzygy bundles appearing in the resolution are balanced for a general cover, provided that the genus is sufficiently large compared to the degree. We prove this for the Casnati–Ekedahl bundle, or bundle of quadrics  $F$—the 1st bundle appearing in the resolution of the ideal of the relative canonical embedding. Furthermore, we prove the conjecture for all syzygy bundles in the resolution when the genus satisfies $g = 1 \mod d$.
On the Statistical Testing Methods for Single Laboratory Validation of Qualitative Microbiological Assays with a Paired Design
Authors: Wang Shizhen S
Published: June 2020

Background

There are several statistical methods for detecting a difference of detection rates between alternative and reference qualitative microbiological assays in a single laboratory validation study with a paired design.

Objective

We compared performance of eight methods including McNemar’s test, sign test, Wilcoxon signed-rank test, paired t-test, and the regression methods based on conditional logistic (CLOGIT), mixed effects complementary log-log (MCLOGLOG), mixed effects logistic (MLOGIT) models, and a linear mixed effects model (LMM).

Methods

We first compared the minimum detectable difference in the proportion of detections between the alternative and reference detection methods among these statistical methods for a varied number of test portions. We then compared power and type 1 error rates of these methods using simulated data.

Results

The MCLOGLOG and MLOGIT models had the lowest minimum detectable difference, followed by the LMM and paired t-test. The MCLOGLOG and MLOGIT models had the highest average power but were anticonservative when correlation between the pairs of outcome values of the alternative and reference methods was high. The LMM and paired t-test had mostly the highest average power when the correlation was low and the second highest average power when the correlation was high. Type 1 error rates of these last two methods approached the nominal value of significance level when the number of test portions was moderately large (n > 20).

Highlights

The LMM and paired t-test are better choices than other competing methods, and we provide an example using real data.
Should Denmark and Sweden Join the Banking Union?
Authors: Hougaard Jensen Svend E , Schoenmaker Dirk
Published: June 2020

An important policy discussion on joining the banking union is currently taking place in Denmark and Sweden. In this article we review the pros and cons of joining. The main rationale for joining the banking union is the importance of cross-border banking in the EU internal market. Reviewing the banking systems, we find that banks in Denmark and Sweden have the same cross-border characteristics as those in the euro area countries, suggesting a similar rationale for joining the banking union. Moreover, both countries have large banks which may be too big to save at country level, but not at the banking union level. Nevertheless, there are some governance concerns. While euro area countries have an automatic and full say in all banking union arrangements, the non-euro area countries (the ‘out’ countries) lack certain formal powers in ultimate decision-making; however, we find that this may be less of a problem in practice. If necessary, the ‘out’ countries would have the ‘nuclear option’ of leaving the banking union.
Systematic Review and STARD Scoring of Renal Cell Carcinoma Circulating Diagnostic Biomarker Manuscripts
Authors: Iafolla Marco A J , Picardo Sarah , Aung Kyaw , Hansen Aaron R
Published: June 2020

Background

No validated molecular biomarkers exist to help guide diagnosis of renal cell carcinoma (RCC) patients. We seek to evaluate the quality of published RCC circulating diagnostic biomarker manuscripts using the Standards for Reporting of Diagnostic Accuracy Studies (STARD) guidelines.

Methods

The phrase “(renal cell carcinoma OR renal cancer OR kidney cancer OR kidney carcinoma) AND circulating AND (biomarkers OR cell free DNA OR tumor DNA OR methylated cell free DNA OR methylated tumor DNA)” was searched in Embase, MEDLINE, and PubMed in March 2018. Relevant manuscripts were scored using 41 STARD subcriteria for a maximal score of 26 points. All tests of statistical significance were 2 sided.

Results

The search identified 535 publications: 27 manuscripts of primary research were analyzed. The median STARD score was 11.5 (range = 7-16.75). All manuscripts had appropriate abstracts, introductions, and distribution of alternative diagnoses. None of the manuscripts stated how indeterminant data were handled or if adverse events occurred from performing the index test or reference standard. Statistically significantly higher STARD scores were present in manuscripts reporting receiver operator characteristic curves (P < .001), larger sample sizes (P = .007), and after release of the original STARD statement (P = .005).

Conclusions

Most RCC circulating diagnostic biomarker manuscripts poorly adhere to the STARD guidelines. Future studies adhering to STARD guidelines may address this unmet need.
Logic fluidity: How frontline professionals use institutional logics in their day-to-day work
Authors: ten Dam Eline M , Waardenburg Maikel
Published: June 2020

This article aims to gain a better understanding on micro processes of how frontline professionals use institutional logics in their day-to-day work. It contributes to the growing literature on the dynamics between institutions and the professional frontline. To further develop this field of study, a conceptual framework is presented that integrates institutional logics, vocabularies of practice, and narratives as central concepts. By adopting a composite narrative approach and identifying vocabularies of practice, the article interprets how frontline professionals make use of different logics to make sense of a new principle introduced in their professional field. Findings are based on a case study of professional patient collaboration in healthcare. The article composes five narratives that act as vehicles through which healthcare professionals use five logics: a medical professional logic, managerial logic, commercial logic, consultation logic, and patient-centeredness logic. It argues that frontline professionals use vocabularies of practice to assemble narratives that help them to navigate between a plurality of logics. It further shows that professionals move fluently from one narrative to another, critiquing the ideas of adherence to a dominant logic and conflict solving. The article finalizes with a discussion that advocates for a process studies perspective and a stronger focus on micro processes in research on professional performance in the context of institutional plurality.
Modelling time variations of root diameter and elongation rate as related to assimilate supply and demand
Authors: Pagès Loïc , Bernert Marie , Pagès Guillaume
Published: June 2020

In a given root system, individual roots usually exhibit a rather homogeneous tip structure although highly different diameters and growth patterns, and this diversity is of prime importance in the definition of the whole root system architecture and foraging characteristics. In order to represent and predict this diversity, we built a simple and generic model at root tip level combining structural and functional knowledge on root elongation. The tip diameter, reflecting meristem size, is used as a driving variable of elongation. It varies, in response to the fluctuations of photo-assimilate availability, between two limits (minimal and maximal diameter). The elongation rate is assumed to be dependent on the transient value of the diameter. Elongation stops when the tip reaches the minimal diameter. The model could satisfactorily reproduce patterns of root elongation and tip diameter changes observed in various species at different scales. Although continuous, the model could generate divergent root classes as classically observed within populations of lateral roots. This model should help interpret the large plasticity of root elongation patterns which can be obtained in response to different combinations of endogenous and exogenous factors. The parameters could be used in phenotyping the root system.
The radio-loud narrow-line Seyfert 1 galaxy 1H 0323+342 in a galaxy merger
Authors: Doi Akihiro , Kino Motoki , Kawakatu Nozomu , Hada Kazuhiro
Published: June 2020

The supermassive black holes (SMBHs) of narrow-line Seyfert 1 galaxies (NLS1s) are at the lower end of the mass function of active galactic nuclei (AGNs) and reside preferentially in late-type host galaxies with pseudobulges, which are thought to be formed by internal secular evolution. On the other hand, the population of radio-loud NLS1s presents a challenge for the relativistic jet paradigm, which states that powerful radio jets are associated exclusively with very high mass SMBHs in elliptical hosts, which are built up through galaxy mergers. We investigated distorted radio structures associated with the nearest gamma-ray-emitting, radio-loud NLS1, 1H 0323+342. This provides supporting evidence for the merger hypothesis based on past optical/near-infrared observations of its host galaxy. The anomalous radio morphology consists of two different structures: the inner curved structure of the currently active jet and an outer linear structure of low-brightness relics. Such coexistence might be indicative of the stage of an established black hole binary with precession before the black holes coalesce in the galaxy merger process. 1H 0323+342 and other radio-loud NLS1s under galaxy interactions may be extreme objects on the evolutionary path from radio-quiet NLS1s to normal Seyfert galaxies with larger SMBHs in classical bulges through mergers and merger-induced jet phases.
The ALPINE−ALMA [C ii] Survey: on the nature of an extremely obscured serendipitous galaxy
Authors: Romano M , Cassata P , Morselli L , Lemaux B C , Béthermin M , Capak P , Faisst A , Le Fèvre O , Schaerer D , Silverman J , Yan L , Bardelli S , Boquien M , Cimatti A , Dessauges-Zavadsky M , Enia A , Fudamoto Y , Fujimoto S , Ginolfi M , Gruppioni C , Hathi N P , Ibar E , Jones G C , Koekemoer A M , Loiacono F , Mancini C , Riechers D A , Rodighiero G , Rodríguez-Muñoz L , Talia M , Vallini L , Vergani D , Zamorani G , Zucca E
Published: June 2020

We report the serendipitous discovery of a dust-obscured galaxy observed as part of the Atacama Large Millimeter Array (ALMA) Large Program to INvestigate [C ii] at Early times (ALPINE). While this galaxy is detected both in line and continuum emissions in ALMA Band 7, it is completely dark in the observed optical/near-infrared bands and only shows a significant detection in the UltraVISTA Ks band. We discuss the nature of the observed ALMA line, that is [C ii] at $z$ ∼ 4.6 or high-J CO transitions at $z$ ∼ 2.2. In the first case, we find a [C ii]/FIR luminosity ratio of $\mathrm{log}{(L_{[\mathrm{ C}\, \rm {\small {II}}]}/L_{\mathrm{ FIR}})} \sim -2.5$, consistent with the average value for local star-forming galaxies (SFGs). In the second case instead, the source would lie at larger CO luminosities than those expected for local SFGs and high-z submillimetre galaxies. At both redshifts, we derive the star formation rate (SFR) from the ALMA continuum and the physical parameters of the galaxy, such as the stellar mass (M*), by fitting its spectral energy distribution. Exploiting the results of this work, we believe that our source is a ‘main-sequence’, dusty SFG at $z$ = 4.6 (i.e. [C ii] emitter) with $\mathrm{log(SFR/M_{\odot }\, yr^{-1})}\sim 1.4$ and log(M*/M⊙) ∼ 9.9. As a support to this scenario our galaxy, if at this redshift, lies in a massive protocluster recently discovered at $z$ ∼ 4.57, at only ∼1 proper Mpc from its centre. This work underlines the crucial role of the ALPINE survey in making a census of this class of objects, in order to unveil their contribution to the global SFR density at the end of the Reionization epoch.
The fate of binary stars hosting planets upon interaction with Sgr A* black hole
Authors: Capuzzo-Dolcetta R , Davari N
Published: June 2020

Our Galaxy hosts a very massive object at its centre, often referred to as the supermassive black hole Sgr A*. Its gravitational tidal field is so intense that it can strip apart a binary star passing its vicinity and accelerate one of the components of the binary as hypervelocity star (HVS) and grab the other star as S-star. Taking into consideration that many binary star systems are known to host planets, in this paper we aim to broaden the study of the close interaction of binary stars and their planetary systems with Sgr A* massive object. Results are obtained via a high-precision N-body code including post-Newtonian approximation. We quantify the likelihood of capture and ejection of stars and planets after interaction with Sgr A*, finding that the fraction of stars captured around it is about three times that of the planets (∼49.4 per cent versus ∼14.5 per cent) and the fraction of hypervelocity planet ejection is about twice that of HVSs (∼21.7 per cent versus ∼9.0 per cent). The actual possibility of observational counterparts deserves further investigation.
Genome-wide CRISPR synthetic lethality screen identifies a role for the ADP-ribosyltransferase PARP14 in DNA replication dynamics controlled by ATR
Authors: Dhoonmoon Ashna , Schleicher Emily M , Clements Kristen E , Nicolae Claudia M , Moldovan George-Lucian
Published: June 2020

The DNA damage response is essential to maintain genomic stability, suppress replication stress, and protect against carcinogenesis. The ATR-CHK1 pathway is an essential component of this response, which regulates cell cycle progression in the face of replication stress. PARP14 is an ADP-ribosyltransferase with multiple roles in transcription, signaling, and DNA repair. To understand the biological functions of PARP14, we catalogued the genetic components that impact cellular viability upon loss of PARP14 by performing an unbiased, comprehensive, genome-wide CRISPR knockout genetic screen in PARP14-deficient cells. We uncovered the ATR-CHK1 pathway as essential for viability of PARP14-deficient cells, and identified regulation of DNA replication dynamics as an important mechanistic contributor to the synthetic lethality observed. Our work shows that PARP14 is an important modulator of the response to ATR-CHK1 pathway inhibitors.
Geographic and socioeconomic considerations for glioblastoma treatment in the elderly at a national level: a US perspective
Authors: Lu Victor M , Lewis Cole T , Esquenazi Yoshua
Published: June 2020

Background

Treatment for glioblastoma (GBM) in elderly (age > 65 years) patients can be affected by multiple geographic and socioeconomic parameters. Correspondingly, the aim of this study was to determine trends in treatment of elderly GBM patients in the United States.

Methods

All GBM patients in the U.S. National Cancer Database between 2005 and 2016 were retrospectively reviewed. Status of treatment by triple therapy (resection, chemotherapy, and radiation) were summarized and analyzed by U.S. Census region.

Results

There were 44 338 GBM patients included, with 21 573 (49%) elderly and 22 765 (51%) nonelderly patients with median ages 72 years (range, 65-90 years) and 47 years (range, 40-64 years), respectively. Compared to nonelderly patients, elderly patients had significantly lower odds of being treated by triple therapy (odds ratio, OR = 0.54) as a whole, and its individual elements of resection (OR = 0.78), chemotherapy (OR = 0.46), radiation therapy (OR = 0.52). This was reflected in each U.S. Census region, with the lowest odds of being treated with triple therapy, surgical resection, chemotherapy, and radiation therapy in New England (OR = 0.51) Mountain (OR = 0.66), West North Central (OR = 0.38), and the Middle Atlantic (OR = 0.44), respectively. Multivariable analysis revealed multiple socioeconomic parameters that significantly predicted lower odds of triple therapy in the elderly.

Conclusions

In the United States alone, there exists geographic disparity in the treatment outcomes of elderly GBM patients. Multiple socioeconomic parameters can influence access to treatment modalities for elderly patients compared to younger patients in different geographic regions, and public health initiatives targeting these aspects may prove beneficial conceptually to optimize and homogenize clinical outcomes.
Spatial multi-scaled chimera states of cerebral cortex network and its inherent structure-dynamics relationship in human brain
Authors: Huo Siyu , Tian Changhai , Zheng Muhua , Guan Shuguang , Zhou Changsong , Liu Zonghua
Published: June 2020

Human cerebral cortex displays various dynamics patterns under different states, however the mechanism how such diverse patterns can be supported by the underlying brain network is still not well understood. Human brain has a unique network structure with different regions of interesting to perform cognitive tasks. Using coupled neural mass oscillators on human cortical network and paying attention to both global and local regions, we observe a new feature of chimera states with multiple spatial scales and a positive correlation between the synchronization preference of local region and the degree of symmetry of the connectivity of the region in the network. Further, we use the concept of effective symmetry in the network to build structural and dynamical hierarchical trees and find close matching between them. These results help to explain the multiple brain rhythms observed in experiments and suggest a generic principle for complex brain network as a structure substrate to support diverse functional patterns.
A theory of status and coordination in organizations
Authors: Lam Wing Man Wynne
Published: June 2020

Firms can motivate workers by offering them social status. Much of the literature argues that a rise in status is a powerful work incentive while ignoring its impact on coordination. This article shows that when workers need to collaborate while having individual vested interests, status differences may reduce the organization value by distorting efforts from different workers. However, status differences can increase the organization value when status effects changes in both authority allocation and cost of taking actions amongst workers. These results have practical implications for human resource management and promotion policies.
Health-Related Quality of Life as Measured by the 12-Item Short-Form Survey Among Adults With Community-Acquired Bacterial Pneumonia who Received Either Lefamulin or Moxifloxacin in 2 Phase III Randomized, Double-Blind, Double-Dummy Clinical Trials
Authors: Lodise Thomas P , Colman Sam , Alexander Elizabeth , Stein Daniel S , Fitts David , Goldberg Lisa , Schranz Jennifer
Published: June 2020

Background

Interest in patient-reported outcomes (PROs) as part of benefit–risk assessment for new drug approvals is increasing. Lefamulin is the first intravenous (IV) and oral pleuromutilin antibiotic for treatment of adults with community-acquired bacterial pneumonia (CABP). Assessment of health-related quality of life (HRQoL) was prospectively incorporated in its CABP trials (Lefamulin Evaluation Against Pneumonia [LEAP] 1 and 2) via the 12-Item Short-Form Survey (SF-12), a widely used PRO that measures general health status in 8 domains.

Methods

HRQoL was evaluated by SF-12 at baseline and test of cure (TOC; 5–10 days after the last study drug dose) in patients who received lefamulin or moxifloxacin in LEAP 1 (IV/oral treatment) and LEAP 2 (oral-only treatment). SF-12 outcomes included the 8 domains, physical component and mental component summary scores, and the Short-Form Six-Dimension health utility score.

Results

Analysis included 1215 patients (lefamulin: n = 607; moxifloxacin: n = 608). At baseline, all mean SF-12 scores in both treatment groups were well below the United States reference mean. Clinically meaningful and significant improvements from baseline to TOC were observed in all SF-12 scores. No significant differences in mean score improvements from baseline to TOC between treatment groups were observed. SF-12 score improvements at TOC across predefined subgroups were comparable between treatment groups.

Conclusions

Results indicate that adults with CABP experienced comparable HRQoL improvements with lefamulin relative to moxifloxacin, and treatment with either agent resulted in returns to population norm HRQoL levels. These data suggest that lefamulin is a potential alternative to moxifloxacin for treatment of adults with CABP.
Low Serum Naproxen Concentrations Are Associated with Minimal Pain Relief: A Preliminary Study in Women with Dysmenorrhea
Authors: Oladosu Folabomi A , Tu Frank F , Garrison Ellen F , Dillane Katlyn E , Roth Genevieve E , Hellman Kevin M
Published: June 2020

Objective

Incomplete pain relief after administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is common, but it is unknown whether malabsorption or heightened metabolism contributes to NSAID resistance. To explain the etiology of NSAID resistance, we evaluated naproxen absorption and metabolism in relation to pain relief in a pilot study of women with dysmenorrhea.

Methods

During menses, participants completed before and after naproxen ingestion pain assessments. Analgesic effectiveness was calculated as a percent change in pain rating before and after naproxen administration. To evaluate the impact of malabsorption, the correlation between analgesic effectiveness and serum naproxen was analyzed. To identify whether hypermetabolism contributes to NSAID resistance, we also analyzed the metabolite O-desmethylnaproxen.

Results

Serum naproxen and O-desmethylnaproxen concentrations of the dysmenorrheic cohort (N = 23, 126 ± 10 µg/mL, 381 ± 56 ng/mL) and healthy controls (N = 12, 135 ± 8 µg/mL, 355 ± 58 ng/mL) were not significantly different (P > 0.05), suggesting that menstrual pain does not affect drug absorption and metabolism. However, nine dysmenorrhea participants had levels of analgesic effectiveness <30%. Among dysmenorrheic women, analgesic effectiveness was correlated with serum naproxen (r = 0.49, P = 0.019) and O-desmethylnaproxen (r = 0.45, P = 0.032) concentrations. After controlling for other gynecological diagnoses, a multivariate model analysis confirmed that lower serum naproxen concentrations were associated with reduced pain relief (P  = 0.038).

Conclusions

Our preliminary findings suggest that poor drug absorption contributes to ineffective pain relief in dysmenorrheic women. Future studies should explore whether malabsorption contributes to NSAID resistance for other pain conditions.
The Effectiveness of Stewardship Interventions to Reduce the Prescribing of Extended-Release Opioids for Acute Pain: A Systematic Review
Authors: Awadalla Rebecca , Gnjidic Danijela , Patanwala Asad , Sakiris Marissa , Penm Jonathan
Published: June 2020

Objective

To evaluate the effectiveness of stewardship interventions in reducing the prescribing of extended-release opioids for acute pain.

Design

Systematic review of randomized controlled trials, pre–post intervention studies, cohort studies and case–control studies.

Methods

A search was conducted using Medline, Scopus, Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts, and PsycINFO from inception to March 24, 2019. Search terms included opioids, interventions, extended-release, and acute pain. Included articles were original research articles outlining the impact of stewardship interventions on reducing the prescribing of extended-release opioids for acute pain.

Results

The search resulted in 1,264 articles after the removal of duplicates. Of these, 141 full texts were assessed, with three eligible for inclusion. One additional article was obtained via a manual search. Three studies explored forcing function interventions; two included prior authorization policies, which saw decreases in extended-release/long-acting scripts by 18–36%, while another evaluated order restrictions producing increased adherence to guidelines by 36%. One study explored the impact of education targeting prescribers and patients through a risk mitigation and evaluation strategy, which decreased extended-release/long-acting quarterly script volumes by 4.3%. All studies were performed at system levels. Forcing function interventions decreased extended-release/long-acting prescriptions and increased adherence to guidelines to a greater extent than less restrictive interventions such as education.

Conclusions

Forcing function interventions implemented at system levels show promise in decreasing the prescribing of extended-release opioids for acute pain. The current lack of literature warrants future research to increase understanding of the effectiveness of such interventions.
Variation after K-projection in antisymmetrized molecular dynamics for low-energy dipole excitations in 10Be and 16O
Authors: Shikata Yuki , Kanada-En’yo Yoshiko
Published: June 2020

A novel method of variation after $K$-projection is proposed to study dipole excitations in the framework of antisymmetrized molecular dynamics with the $\beta$-constraint. The method is applied to $^{10}$Be and $^{16}$O to describe low-energy dipole excitations. In the application to ${}^{10}\textrm{Be}$, two dipole states in the low-energy region are obtained. For ${}^{16}\textrm{O}$, the $1_1^-$ and $1_2^-$ states are obtained with remarkable dipole strength. The $1_1^-$ state is characterized by significant toroidal dipole (TD) strength and compressional dipole strength, whereas the $1_2^-$ state has significant TD strength and shows a developed $\alpha + {}^{12}\textrm{C}$ cluster structure. Dipole properties in $^{16}$O are discussed by analyzing the current densities of the dipole transitions.
Napping and cognitive performance during night shifts: a systematic review and meta-analysis
Authors: Dutheil Frédéric , Bessonnat Brice , Pereira Bruno , Baker Julien S , Moustafa Fares , Fantini Maria Livia , Mermillod Martial , Navel Valentin
Published: June 2020

Study Objectives

To examine the benefits of napping during night shifts on cognitive performance.

Methods

Medline, Cochrane Library, Science direct, and Embase databases were searched up to July 1, 2019. Cognitive performance during night shifts, both before and following napping or under control conditions (no nap), in working-aged adults, were analyzed by time and by type of cognitive function (executive function, attention, instrumental function, and memory). Estimates were pooled using random-effects meta-analysis.

Results

A total of 18 articles (6 in real-work and 12 in laboratory) with a total of 494 participants were included. The mean nap duration was 41.6 ± 28.3 min, occurring between 12.00 am and 4.10 am, with a mean time set at 2.12 am. Cognitive performance did not differ at baseline between the groups (effect size 0.02, 95% CI −0.09 to 0.13). There was an overall improvement in performance following a nap compared to the control condition without a nap (0.25, 0.10 to 0.41). Positioning naps early in the night and activity (simulated work tasks) tended to improve cognitive performance (−0.57, −1.16 to 0.002, and 0.082, −0.04 to 0.33, respectively). The improvements were primarily seen 30 min after awakening. Only memory deteriorated immediately after awakening without an overall change in global cognitive performance.

Conclusion

Napping during night shifts seems to improve cognitive performance. Napping early in the night and activity may benefit cognitive performance over time. Considering lack of data in real work environments, further studies are warranted before preconizing napping during night shifts as a preventive strategy (safety, health, and economic outcomes).