bluuebunny/crossref_metadata_2025 huggingface dataset:
Core Genome Allelic Profiles of Clinical Klebsiella pneumoniae Strains Using a Random Forest Algorithm Based on Multilocus Sequence Typing Scheme for Hypervirulence Analysis
Authors: Lan Peng , Shi Qiucheng , Zhang Ping , Chen Yan , Yan Rushuang , Hua Xiaoting , Jiang Yan , Zhou Jiancang , Yu Yunsong
Published: October 2019

Background

Hypervirulent Klebsiella pneumoniae (hvKP) infections can have high morbidity and mortality rates owing to their invasiveness and virulence. However, there are no effective tools or biomarkers to discriminate between hvKP and nonhypervirulent K. pneumoniae (nhvKP) strains. We aimed to use a random forest algorithm to predict hvKP based on core-genome data.

Methods

In total, 272 K. pneumoniae strains were collected from 20 tertiary hospitals in China and divided into hvKP and nhvKP groups according to clinical criteria. Clinical data comparisons, whole-genome sequencing, virulence profile analysis, and core genome multilocus sequence typing (cgMLST) were performed. We then established a random forest predictive model based on the cgMLST scheme to prospectively identify hvKP. The random forest is an ensemble learning method that generates multiple decision trees during the training process and each decision tree will output its own prediction results corresponding to the input. The predictive ability of the model was assessed by means of area under the receiver operating characteristic curve.

Results

Patients in the hvKP group were younger than those in the nhvKP group (median age, 58.0 and 68.0 years, respectively; P < .001). More patients in the hvKP group had underlying diabetes mellitus (43.1% vs 20.1%; P < .001). Clinically, carbapenem-resistant K. pneumoniae was less common in the hvKP group (4.1% vs 63.8%; P < .001), whereas the K1/K2 serotype, sequence type (ST) 23, and positive string tests were significantly higher in the hvKP group. A cgMLST-based minimal spanning tree revealed that hvKP strains were scattered sporadically within nhvKP clusters. ST23 showed greater genome diversification than did ST11, according to cgMLST-based allelic differences. Primary virulence factors (rmpA, iucA, positive string test result, and the presence of virulence plasmid pLVPK) were poor predictors of the hypervirulence phenotype. The random forest model based on the core genome allelic profile presented excellent predictive power, both in the training and validating sets (area under receiver operating characteristic curve, 0.987 and 0.999 in the training and validating sets, respectively).

Conclusions

A random forest algorithm predictive model based on the core genome allelic profiles of K. pneumoniae was accurate to identify the hypervirulent isolates.
Tolerance to nifurtimox and benznidazole in adult patients with chronic Chagas’ disease
Authors: Jackson Yves , Wyssa Baptiste , Chappuis François
Published: October 2019

Background

Current options for Chagas’ disease treatment are restricted to benznidazole and nifurtimox. To the best of our knowledge, no study has ever compared their tolerance in adults in a non-endemic country.

Objectives

To compare the completion rates and drug tolerance in a cohort of patients treated according to current guidelines.

Patients and methods

We analysed the medical records of all Chagas’ disease patients aged 18 years or over who started antiparasitic treatment at the Geneva University Hospitals, Switzerland, from 2008 to 2016. We recorded treatment duration and all adverse events.

Results

We included 176 patients, 92 and 84 of whom received benznidazole or nifurtimox, respectively. The overall treatment completion rate was 62.5%, without a significant difference between the groups (P=0.436). Most patients (89.8%) suffered at least one adverse event. Those receiving nifurtimox had more events (6.2 versus 3.5, P<0.001). Mucocutaneous symptoms predominated in the benznidazole group, whereas digestive symptoms were most frequent with nifurtimox. Neuropsychiatric events frequently occurred in both groups, most notably in patients receiving nifurtimox. Arthralgia, dyspnoea, sensitive neuropathy and pruritus were independent predictors of treatment interruption.

Conclusions

Currently recommended drug regimens for Chagas’ disease are not well tolerated and entail frequent treatment discontinuation irrespective of the drug used. This highlights the need to improve treatment tolerance in adults with Chagas’ disease with new therapeutic options.
International scope of the Japanese Anti-monopoly Act in cross-border cartel cases: a Japanese approach to ‘extraterritorial application’
Authors: Nishioka Kazuaki
Published: October 2019

Most states have a national anti-trust or competition law to regulate anti-competitive activities. There is no doubt that, in purely domestic cases, where an anti-competitive activity and its anti-competitive effects have occurred within a state, that state’s national competition authority can regulate the activity by applying its competition law. For cross-border cases such as where anti-competitive activities are carried out abroad but have anti-competitive effects on the domestic or internal market of that state or region, it has been gradually accepted that a state can apply its competition law to the activities on the basis of the effects within its territory. However, it should be noted that states have approached such cases differently. In 2017, the Supreme Court of Japan first decided the international scope of the Japanese Anti-Monopoly Act (JAMA) in cross-border cartel cases and clarified that the JAMA could apply to anti-competitive activities conducted outside of Japan if the activities in question disturbed the free competition economic order of Japan. The court did not mention the effects doctrine or the territorial principle. This article examines on what grounds and how far the JAMA can and should apply to cross-border cartel cases by analysing the Supreme Court judgement.
Interleukin-6 confers radio-resistance by inducing Akt mediated glycolysis and reducing mitochondrial damage in cells
Authors: Kumari Neeraj , Das Asmita , Bhatt Anant Narayan
Published: October 2019

Interleukin-6 (IL-6) induced glycolysis and therapeutic resistance is reported in some cell systems; however the mechanism of IL-6 induced glycolysis in radio-resistance is un-explored. Therefore to investigate, we treated Raw264.7 cells with IL-6 (1hr prior to irradiation) and examined the glycolytic flux. Increased expression of mRNA and protein levels of key glycolytic enzymes was observed after IL-6 treatment, which conferred glycolysis dependent resistance from radiation induced cell death. We further established that IL-6 induced glycolysis is activated by Akt signaling and knocking down Akt or inhibition of pan Akt phosphorylation significantly abrogated the IL-6 induced radio-resistance. Moreover, reduction of IL-6 induced pAkt level suppressed the expression of Hexokinase-2 and its translocation to the mitochondria, thereby inhibiting the glycolysis induced resistance to radiation. IL-6 induced glycolysis also minimized the radiation induced mitochondrial damage. These results suggest that IL-6 induced glycolysis observed in cells may be responsible for IL-6 mediated therapeutic radio-resistance in cancer cells, partly by activation of Akt signaling.
Quantifying the Efficacy of an Assessment-Based Pest Management (APM) Program for German Cockroach (L.) (Blattodea: Blattellidae) Control in Low-Income Public Housing Units
Authors: Miller Dini M , Smith Eric P
Published: October 2019

Over the last several decades, low-income public housing facilities have been known to be infested with particularly large German cockroach populations. These populations persist even though the housing pest control contracts often require, and pay for, IPM practices to be used in their facilities. When Virginia Tech researchers began reviewing public housing contracts in Virginia and North Carolina, it was easy to see why these ‘IPM programs’ were not successful. Many of these ‘low-bidder’ contracts do not allow the technician enough time in each apartment to assess the size of the pest population. In addition, these pest management contracts did not require German cockroach population monitoring, even though all IPM programs are based on assessments of the pest population. There was a clear need for an effective, easy to apply cockroach management program in U.S. public housing authorities. This study determined the long-term efficacy of an Assessment-based Pest Management (APM) program for German cockroach control in U.S. public housing facilities. Specifically, we evaluated an APM program where the residents were not asked to clean or prepare for treatment, and where overnight cockroach trap counts were used to determine the volume of gel bait that would be applied. The APM baiting program was conducted for 15 mo in three housing authorities. In all three housing authorities, cockroach populations in test units were typically reduced by >90%. German cockroach infestations were even eliminated from 49 of the 65 (75%) test units during this study.
Pediatric Trials for Cancer Therapies With Targets Potentially Relevant to Pediatric Cancers
Authors: Hwang Thomas J , Orenstein Liat , DuBois Steven G , Janeway Katherine A , Bourgeois Florence T
Published: October 2019

The Research to Accelerate Cures and Equity (RACE) for Children Act was enacted in 2017 to authorize the US Food and Drug Administration (FDA) to require pediatric studies for new cancer drugs that have a molecular target relevant to the growth or progression of a pediatric cancer. To assess the possible scope of this new policy, we examined all 78 adult cancer drugs approved by the FDA from 2007 to 2017. Only 17 (21.8%) drugs received any pediatric labeling information. Based on the FDA’s Pediatric Molecular Target List, we found that the RACE Act could have increased the proportion of cancer drugs potentially subject to pediatric study requirements from 0% to 78.2%. However, the actual effect of the legislation will depend on how often regulators require pediatric trials and on timely completion of such trials.
The effects of short-term calorie restriction on mutations in the spleen cells of infant-irradiated mice
Authors: Kakomi Saori , Nakayama Takafumi , Shang Yi , Tsuruoka Chizuru , Sunaoshi Masaaki , Morioka Takamitsu , Shimada Yoshiya , Kakinuma Shizuko , Tachibana Akira
Published: October 2019

The risk of cancer due to exposure to ionizing radiation is higher in infants than in adults. In a previous study, the effect of adult-onset calorie restriction (CR) on carcinogenesis in mice after early-life exposure to X-rays was examined (Shang, Y, Kakinuma, S, Yamauchi, K, et al. Cancer prevention by adult-onset calorie restriction after infant exposure to ionizing radiation in B6C3F1 male mice. Int J Cancer. 2014; 135: 1038-47). The results showed that the tumor frequency was reduced in the CR group. However, the mechanism of tumor suppression by CR is not yet clear. In this study, we examined the effects of CR on radiation-induced mutations using gpt delta mice, which are useful to analyze mutations in various tissues throughout the whole body. Infant male mice (1-week old) were exposed to 3.8 Gy X-rays and fed a control (95 kcal/week/mouse) or CR (65 kcal/week/mouse) diet from adult stage (7-weeks old). Mice were sacrificed at the age of 7 weeks, 8 weeks and 100 days, and organs (spleen, liver, lung, thymus) were harvested. Mutations at the gpt gene in the DNA from the spleen were analyzed by using a gpt assay protocol that detects primarily point mutations in the gpt gene. The results showed that mutation frequencies were decreased in CR groups compared with non-CR groups. Sequence analysis of the gpt gene in mutants revealed a reduction in the G:C to T:A transversion in CR groups. Since it is known that 8-oxoguanine could result in this base substitution and that CR has an effect of reducing oxidative stress, these results indicate that the suppression of oxidative stress by CR is the cause of the reduction of this transversion.
WUSCHEL-related homeobox gene PagWOX11/12a responds to drought stress by enhancing root elongation and biomass growth in poplar
Authors: Wang Liu-Qiang , Li Zhen , Wen Shuang-Shuang , Wang Jin-Nan , Zhao Shu-Tang , Lu Meng-Zhu
Published: October 2019

In plants, a large root system improves the uptake of water and nutrients and is important for responding to drought stress. The poplar WUSCHEL-related homeobox (WOX) transcription factor promotes adventitious rooting, but its regulation of root growth in response to drought stress remains elusive. In this study, we found that PagWOX11/12a from hybrid poplar 84K (Populus alba×Populus glandulosa) is expressed predominantly in the roots and is strongly induced by drought stress. Compared with nontransgenic 84K plants, transgenic poplar plants overexpressing PagWOX11/12a displayed increased root biomass and enhanced drought tolerance, while opposite phenotypes were observed for PagWOX11/12a dominant repression (DR) plants. PagWOX11/12a functions as a nuclear transcriptional activator with a transactivation domain at the C-terminus. In addition, PagERF35 was found to specifically bind to a dehydration-responsive element (DRE) within the PagWOX11/12a promoter and activate PagWOX11/12a gene expression. These results indicate that PagERF35 may activate PagWOX11/12a expression in response to drought stress by promoting root elongation and biomass, thereby increasing drought tolerance of poplar.
A Common Subject for Ethics
Authors: Schroeder Mark
Published: October 2019

The purpose of this paper is to conceptualize and explore what I shall call the Common Subject Problem for ethics. The problem is that there seems to be no good answer to what property everyone who makes moral claims could be talking and thinking about. The Common Subject Problem is not a new problem; on the contrary, I will argue that it is one of the central animating concerns in the history of both metaethics and normative theory. But despite its importance, the Common Subject Problem is essentially invisible on many contemporary ways of carving up the problems of metaethics and normative ethical theory.

My aim, therefore, is to make progress – in part by naming the problem, but also by beginning to sketch out the contours of what gives the problem its force, by distinguishing between different paths of response to the problem and assessing some of their chief merits, and finally, by distinguishing the Common Subject Problem from another problem with which it has come to be conflated. This nearby problem is the Moral Twin Earth Problem. Whereas the Common Subject Problem is a problem about what property ‘wrong’ could refer to, the Moral Twin Earth Problem is a problem about how ‘wrong’ could refer to it.

The upshot of the paper, therefore, is to rescue one of the historically significant problems in normative ethics and metaethics – a problem that is essentially about normative semantics – from the illusion that has persisted over the last twenty years that it is really, somehow, a problem about metasemantics. Once we have reclaimed this problem, we can see that it could still be a problem even if there are no distinctively metasemantic problems in metaethics at all, that it is a problem faced by a wider variety of views, and that the space of possible solutions is much wider and more interesting for normative theory, moral psychology, and moral epistemology.
On Westphalian Woodworms and Rhenish Missionaries: The Soest Conductus Fragments and Their Afterlife
Authors: Maschke Eva M
Published: October 2019

Examining the Soest conductus fragments, of which five single leaves have so far been rediscovered, this article analyses the different layers of use and reuse that can be deduced. First, a detailed account of the circumstances under which these manuscript fragments travelled with (or without) their respective host volumes is given. The music manuscript must have been discarded by the fifteenth century, as a bookbinder from the Dominican convent of Soest in Westphalia reused various leaves of it in a series of autographs written by Jacob of Soest, who died in 1438. After the dissolution of the convent’s library in the course of nineteenth-century secularization, further contexts of reuse and dismemberment pertaining to the fragments can be demonstrated. Secondly, the remnants of the original music manuscript are analysed. The use of the two-part conductus O crux ave spes unica (H4) as the opening piece of a fascicle can be connected to the dedication of the Soest Dominican house to the Holy Cross. In comparison to other fragmentary sources that made their way to the German-speaking area, as well as the long-known codices F, W1, and W2, the Soest music manuscript seems closest to W2. While, however, these two codices show significant parallels in terms of mise-en-page and copying process, the choice of repertory might have deliberately differed. This points to production in the same workshop, but for different commissioners.
Reflection spectra of thick accretion discs
Authors: Riaz Shafqat , Ayzenberg Dimitry , Bambi Cosimo , Nampalliwar Sourabh
Published: October 2019

Relativistic reflection features are commonly observed in the X-ray spectra of stellar-mass and supermassive black holes and originate from illumination of the inner part of the accretion disc by a hot corona. All the available relativistic reflection models assume that the disc is infinitesimally thin and the inner edge is at the innermost stable circular orbit or at a larger radius. However, we know that several sources, especially among supermassive black holes, have quite high-mass accretion rates. In such a case, the accretion disc becomes geometrically thick and the inner edge of the disc is expected to be inside the innermost stable circular orbit. In this work, we employ the Polish donut model to describe geometrically thick discs and we study the iron-line shapes from similar systems. We also simulate full reflection spectra and we analyse the simulated observations with a thin disc relativistic reflection model to determine the impact of the disc structure on the estimation of the model parameters, in particular in the case of tests of the Kerr hypothesis.
Sulphur-bearing and complex organic molecules in an infrared cold core
Authors: Beaklini Pedro P B , Mendoza Edgar , Canelo Carla M , Aleman Isabel , Merello Manuel , Kong Shuo , Navarete Felipe , Janot-Pacheco Eduardo , Abraham Zulema , Lépine Jacques R D , de Almeida Amaury A , Friaça Amâncio C S
Published: October 2019

Since the start of ALMA (Atacama Large Millimeter Array) observatory operation, new and important chemistry of infrared cold core was revealed. Molecular transitions at millimetre range are being used to identify and to characterize these sources. We have investigated the 231 GHz ALMA archive observations of the infrared dark cloud region C9, focusing on the brighter source that we called as IRDC-C9 Main. We report the existence of two substructures on the continuum map of this source: a compact bright spot with high chemistry diversity that we labelled as core, and a weaker and extended one, that we labelled as tail. In the core, we have identified lines of the molecules OCS(19−18), 13CS(5−4), and CH3CH2CN, several lines of CH3CHO and the k-ladder emission of 13CH3CN. We report two different temperature regions, while the rotation diagram of CH3CHO indicates a temperature of 25 K, the rotation diagram of 13CH3CN indicates a warmer phase at temperature of ∼450 K. In the tail, only the OCS(19−18) and 13CS(5−4) lines were detected. We used the nautilus and the radex codes to estimate the column densities and the abundances. The existence of hot gas in the core of IRDC-C9 Main suggests the presence of a protostar, which is not present in the tail.
ChiTaRS 5.0: the comprehensive database of chimeric transcripts matched with druggable fusions and 3D chromatin maps
Authors: Balamurali Deepak , Gorohovski Alessandro , Detroja Rajesh , Palande Vikrant , Raviv-Shay Dorith , Frenkel-Morgenstern Milana
Published: October 2019

Chimeric RNA transcripts are formed when exons from two genes fuse together, often due to chromosomal translocations, transcriptional errors or trans-splicing effect. While these chimeric RNAs produce functional proteins only in certain cases, they play a significant role in disease phenotyping and progression. ChiTaRS 5.0 (http://chitars.md.biu.ac.il/) is the latest and most comprehensive chimeric transcript repository, with 111 582 annotated entries from eight species, including 23 167 known human cancer breakpoints. The database includes unique information correlating chimeric breakpoints with 3D chromatin contact maps, generated from public datasets of chromosome conformation capture techniques (Hi–C). In this update, we have added curated information on druggable fusion targets matched with chimeric breakpoints, which are applicable to precision medicine in cancers. The introduction of a new section that lists chimeric RNAs in various cell-lines is another salient feature. Finally, using text-mining techniques, novel chimeras in Alzheimer's disease, schizophrenia, dyslexia and other diseases were collected in ChiTaRS. Thus, this improved version is an extensive catalogue of chimeras from multiple species. It extends our understanding of the evolution of chimeric transcripts in eukaryotes and contributes to the analysis of 3D genome conformational changes and the functional role of chimeras in the etiopathogenesis of cancers and other complex diseases.
RB, p130 and p107 differentially repress G1/S and G2/M genes after p53 activation
Authors: Schade Amy E , Fischer Martin , DeCaprio James A
Published: October 2019

Cell cycle gene expression occurs in two waves. The G1/S genes encode factors required for DNA synthesis and the G2/M genes contribute to mitosis. The Retinoblastoma protein (RB) and DREAM complex (DP, RB-like, E2F4 and MuvB) cooperate to repress all cell cycle genes during G1 and inhibit entry into the cell cycle. DNA damage activates p53 leading to increased levels of p21 and inhibition of cell cycle progression. Whether the G1/S and G2/M genes are differentially repressed by RB and the RB-like proteins p130 and p107 in response to DNA damage is not known. We performed gene expression profiling of primary human fibroblasts upon DNA damage and assessed the effects on G1/S and G2/M genes. Upon p53 activation, p130 and RB cooperated to repress the G1/S genes. In addition, in the absence of RB and p130, p107 contributed to repression of G1/S genes. In contrast, G2/M genes were repressed by p130 and p107 after p53 activation. Furthermore, repression of G2/M genes by p107 and p130 led to reduced entry into mitosis. Our data demonstrates specific roles for RB, p130-DREAM, and p107-DREAM in p53 and p21 mediated repression of cell cycle genes.
Electro-mechanically controlled assembly of reconfigurable 3D mesostructures and electronic devices based on dielectric elastomer platforms
Authors: Pang Wenbo , Cheng Xu , Zhao Haojie , Guo Xiaogang , Ji Ziyao , Li Guorui , Liang Yiming , Xue Zhaoguo , Song Honglie , Zhang Fan , Xu Zheng , Sang Lei , Huang Wen , Li Tiefeng , Zhang Yihui
Published: October 2019

The manufacture of 3D mesostructures is receiving rapidly increasing attention, because of the fundamental significance and practical applications across wide-ranging areas. The recently developed approach of buckling-guided assembly allows deterministic formation of complex 3D mesostructures in a broad set of functional materials, with feature sizes spanning nanoscale to centimeter-scale. Previous studies mostly exploited mechanically controlled assembly platforms using elastomer substrates, which limits the capabilities to achieve on-demand local assembly, and to reshape assembled mesostructures into distinct 3D configurations. This work introduces a set of design concepts and assembly strategies to utilize dielectric elastomer actuators as powerful platforms for the electro-mechanically controlled 3D assembly. Capabilities of sequential, local loading with desired strain distributions allow access to precisely tailored 3D mesostructures that can be reshaped into distinct geometries, as demonstrated by experimental and theoretical studies of ∼30 examples. A reconfigurable inductive–capacitive radio-frequency circuit consisting of morphable 3D capacitors serves as an application example.
Rethinking the economics of water: an assessment
Authors: Garrick Dustin E , Hanemann Michael , Hepburn Cameron
Published: October 2019

Water is rising on the policy agenda as population growth and climate change intensify scarcity, shocks, and access inequalities. The conventional economic policy recommendations—privatization, pricing, and property rights—have struggled due to a failure to account adequately for the politics of water and the associated distributional conflicts. We identify distinctive social and physical characteristics of water supply and demand, and explore their implications for three central areas of water policy: financing infrastructure, pricing, and property rights reform. Growing dependence on groundwater and non-networked water supplies exacerbates these challenges and reinforces the need to rethink the economics of water and tackle the political challenges head on. Meeting the water sustainable development goals would require institutional and technological innovations to supply, allocate, and manage water, as well as a sustained political and financial commitment to address those who might be left behind.
Distortion of magnetic fields in Barnard 68
Authors: Kandori Ryo , Tamura Motohide , Saito Masao , Tomisaka Kohji , Matsumoto Tomoaki , Kusakabe Nobuhiko , Kwon Jungmi , Nagayama Takahiro , Nagata Tetsuya , Tazaki Ryo , Tatematsu Ken’ichi
Published: October 2019

The magnetic field structure, kinematical stability, and evolutionary status of the starless dense core Barnard 68 (B68) are revealed based on the near-infrared polarimetric observations of background stars, measuring the dichroically polarized light produced by aligned dust grains in the core. After subtracting unrelated ambient polarization components, the magnetic fields pervading B68 are mapped using 38 stars and axisymmetrically distorted hourglass-like magnetic fields are obtained, although the evidence for the hourglass field is not very strong. On the basis of simple 2D and 3D magnetic field modeling, the magnetic inclination angles on the plane-of-sky and in the line-of-sight direction are determined to be 47° ± 5° and 20° ± 10°, respectively. The total magnetic field strength of B68 is obtained to be $26.1 \pm 8.7\, \mu \mbox{G}$. The critical mass of B68, evaluated using both magnetic and thermal/turbulent support, is $M_{\rm cr} = 2.30 \pm 0.20\, {M}_{\odot }$, which is consistent with the observed core mass of $M_{\rm core}=2.1\, M_{\odot }$, suggesting a nearly critical state. We found a relatively linear relationship between polarization and extinction up to AV ∼ 30 mag toward the stars with deepest obscuration. Further theoretical and observational studies are required to explain the dust alignment in cold and dense regions in the core.
Validating Self-Reported Turnout by Linking Public Opinion Surveys with Administrative Records
Authors: Enamorado Ted , Imai Kosuke
Published: October 2019

Although it is widely known that the self-reported turnout rates obtained from public opinion surveys tend to substantially overestimate actual turnout rates, scholars sharply disagree on what causes this bias. Some blame overreporting due to social desirability, whereas others attribute it to nonresponse bias and the accuracy of turnout validation. While we can validate self-reported turnout by directly linking surveys with administrative records, most existing studies rely on proprietary merging algorithms with little scientific transparency and report conflicting results. To shed light on this debate, we apply a probabilistic record linkage model, implemented via the open-source software package fastLink, to merge two major election studies—the American National Election Studies and the Cooperative Congressional Election Survey—with a national voter file of over 180 million records. For both studies, fastLink successfully produces validated turnout rates close to the actual turnout rates, leading to public-use validated turnout data for the two studies. Using these merged data sets, we find that the bias of self-reported turnout originates primarily from overreporting rather than nonresponse. Our findings suggest that those who are educated and interested in politics are more likely to overreport turnout. Finally, we show that fastLink performs as well as a proprietary algorithm.
The Elusive Likely Voter
Authors: Rentsch Anthony , Schaffner Brian F , Gross Justin H
Published: October 2019

Political commentators have offered evidence that the “polling misses” of 2016 were caused by a number of factors. This project focuses on one explanation: that likely-voter models—tools used by preelection pollsters to predict which survey respondents are most likely to make up the electorate and, thus, whose responses should be used to calculate election predictions—were flawed. While models employed by different pollsters vary widely, it is difficult to systematically study them because they are often considered part of pollsters’ methodological black box. In this study, we use Cooperative Congressional Election Study surveys since 2008 to build a probabilistic likely-voter model that takes into account not only the stated intentions of respondents to vote, but also other demographic variables that are consistently strong predictors of both turnout and overreporting. This model, which we term the Perry-Gallup and Demographics (PGaD) approach, shows that the bias and error created by likely-voter models can be reduced to a negligible amount. This likely-voter approach uses variables that pollsters already collect for weighting purposes and thus should be relatively easy to implement in future elections.
Power Doppler enhancement of accessory pulleys confirming disease localization in psoriatic dactylitis
Authors: Tinazzi Ilaria , McGonagle Dennis , Macchioni Pierluigi , Aydin Sibel Zehra
Published: October 2019

Objective

The digital accessory pulleys are highly mechanically stressed mini-entheses that are thickened in patients with a history of PsA-related dactylits. This study explored whether these pulleys are involved in PsA dactylitis as assessed by intra-pulley US power Doppler changes.

Methods

Fifty-eight PsA patients with dactylitis had US of the second to fourth digits for pulleys of the dactylitic and contralateral digits. The Leeds Dactylometer was used for thickness measurement. The presence of digital pain, tenderness, and swelling in the dactylitis finger and in the contralateral side was evaluated.

Results

We recruited 34 patients with acute and 24 patients with chronic dactylitis, 45/58 (77%) of which had tenderness on clinical assessment. Intra-pulley power Doppler was more frequently found in the dactylitic digits compared with contralateral sides and linked to A1, A2 and A4 pulleys thickening [power Doppler signals in A1 pulley (51%), A2 (22%) and A4 (12%) in dactylitic digit; compared with 1 A1, A2 and A4 pulleys each in the contralateral side (1.7%)]. Almost all cases had peri-tendinous oedema, and 82.6% of dactylitic digits had flexor tenosynovitis with power Doppler signals in 65.2% of flexor tendons.

Conclusion

Despite their small size and relatively avascular, the accessory pulleys exhibit power Doppler change in active Psoriatic dactylitis, supporting a pivotal role in dactylitis-related tenosynovitis and extra-tendinous disease.
Computers meet politics at wage structure: an analysis of the computer wage premium across rich countries
Authors: Kristal Tali , Edler Susanne
Published: October 2019

This article addresses an important question in the age of rapid spread of new computer technologies: how do institutions influence the computer wage premium? To identify institutional factors that account for differences in computers’ impact on wages, the authors estimate computer wage premiums for 20 countries classified into three national ‘varieties’ of capitalism and distinct forms of industrial relations and education systems. The analyses are based on unique international data from the Survey of Adult Skills, recently conducted by the Organisation for Economic Co-operation and Development. Results reveal that computer use at work is rewarded considerably higher in Liberal countries than in other countries—Nordic Coordinated countries above all. These results signify the centrality of coordinated markets, grounded in strong unions, centralized wage bargaining and publicly funded education and training, for lower computer wage gaps, hence for lower levels of wage inequality.
Inferring Tumor Proliferative Organization from Phylogenetic Tree Measures in a Computational Model
Authors: Scott Jacob G , Maini Philip K , Anderson Alexander R A , Fletcher Alexander G
Published: October 2019

We use a computational modeling approach to explore whether it is possible to infer a solid tumor’s cellular proliferative hierarchy under the assumptions of the cancer stem cell hypothesis and neutral evolution. We work towards inferring the symmetric division probability for cancer stem cells, since this is believed to be a key driver of progression and therapeutic response. Motivated by the advent of multiregion sampling and resulting opportunities to infer tumor evolutionary history, we focus on a suite of statistical measures of the phylogenetic trees resulting from the tumor’s evolution in different regions of parameter space and through time. We find strikingly different patterns in these measures for changing symmetric division probability which hinge on the inclusion of spatial constraints. These results give us a starting point to begin stratifying tumors by this biological parameter and also generate a number of actionable clinical and biological hypotheses regarding changes during therapy, and through tumor evolutionary time. [Cancer; evolution; phylogenetics.]
Predicting Outcome in Neonates with Possible Clinical Sepsis by Estimating an Early Score for Neonatal Acute Physiology-II (SNAP-II)
Authors: Pal Somalika , Jain Ashish , Garg Madhu , Sekhar Jerin C
Published: October 2019

Objectives

To determine role of Score for Neonatal Acute Physiology-II (SNAP-II) and its individual parameters assessed within 12 h of suspicion of neonatal sepsis in predicting outcomes; study its distribution across gestational ages and determine its relation with survival duration among expired neonates.

Methods

This prospective observational study conducted in a newborn unit of a tertiary care teaching hospital over 1 year included intramural neonates with birth weight ≥1000 g and gestation ≥28 weeks suspected with sepsis and assigned SNAP-II score within 12 h of suspicion. On day 14 of enrollment, they were categorized into three outcome groups: death (D), survival with organ dysfunction (SOD) and survival without organ dysfunction (SWOD).

Results

One hundred and ten neonates were enrolled and 100 analyzed. Mean SNAP-II score was 22 ± 22 (median: 13; interquartile range: 5–32.5). Seventy-six percent, 16% and 8% neonates belonged to SWOD, D and SOD groups, respectively. SNAP-II score and its individual parameters varied significantly among all outcome groups (p < 0.001). SNAP-II cutoffs of 44/115, 44/115, 38/115 and 33/115 were found to be highly predictive of D, D vs. SOD, D/SOD vs. SWOD and SWOD vs. SOD, respectively (sensitivity: 87.5–99%; specificity: 75–99%). The score was unaffected by gestational age (p = 0.80). Neonates with culture positive sepsis/meningitis had higher SNAP-II scores (p = 0.001).

Conclusions

SNAP-II and its individual parameters found to have high sensitivity and specificity in predicting outcomes in possible neonatal sepsis and may have a role in predicting severity of disease progression and rapidity of deterioration among non-survivors, pending validation in larger studies.
Comment on ‘Response to comment on ‘Valid molecular dynamics simulations of human hemoglobin require a surprisingly large box size’’
Authors: Gapsys Vytautas , Groot Bert L. de
Published: October 2019

We recently expressed three major concerns about a 2018 article of El Hage et al. about a claimed effect of the box size in molecular dynamics simulations of hemoglobin. In the response of the authors to our comment, none of these concerns have been addressed, yet the authors maintain their original conclusions. Here, we challenge those conclusions and provide additional data that reestablish our original concerns. In addition, we identified six additional flaws in the response from El Hage et al. as well as a number of technical concerns about the presented simulations and analyses. Taken together, we conclude that there is no basis to support the hypothesis of significant box size effects in MD simulations for the studied systems in the examined range.
Characterisation of a second gain of function EDAR variant, encoding EDAR380R, in East Asia
Authors: Riddell Jon , Mallick Chandana Basu , Jacobs Guy S. , Schoenebeck Jeffrey J. , Headon Denis J.
Published: October 2019

EDAR is a TNF receptor family member with roles in the development and growth of hair, teeth and glands. A derived allele of EDAR, single nucleotide variant rs3827760, encodes EDAR370A, a receptor with more potent signalling effects than the ancestral EDAR370V. This allele of rs3827760 is at very high frequency in modern East Asian and Native American populations as a result of ancient positive selection and has been associated with straighter, thicker hair fibres, alteration of tooth and ear shape, reduced chin protrusion and increased fingertip sweat gland density. Here we report the characterisation of another SNV in EDAR, rs146567337, encoding EDAR380R. The derived allele of this SNV is at its highest global frequency, of up to 5%, in populations of southern China, Vietnam, the Philippines, Malaysia and Indonesia. Using haplotype analyses, we find that the rs3827760 and rs146567337 SNVs arose on distinct haplotypes and that rs146567337 does not show the same signs of positive selection as rs3827760. From functional studies in cultured cells, we find that EDAR380R displays increased EDAR signalling output, at a similar level to that of EDAR370A. The existence of a second SNV with partly overlapping geographic distribution, the same in vitro functional effect and similar evolutionary age as the derived allele of rs3827760, but of independent origin and not exhibiting the same signs of strong selection, suggests a northern focus of positive selection on EDAR function in East Asia.
Diversity and complexity of the large surface protein family in the compacted genomes of variousPneumocystisspecies
Authors: Ma Liang , Chen Zehua , Huang Da Wei , Cissé Ousmane H. , Rothenburger Jamie L. , Latinne Alice , Bishop Lisa , Blair Robert , Brenchley Jason M. , Chabé Magali , Deng Xilong , Hirsch Vanessa , Keesler Rebekah , Kutty Geetha , Liu Yueqin , Margolis Daniel , Morand Serge , Pahar Bapi , Peng Li , Van Rompay Koen K.A. , Song Xiaohong , Song Jun , Sukura Antti , Thapar Sabrina , Wang Honghui , Weissenbacher-Lang Christiane , Xu Jie , Lee Chao-Hung , Jardine Claire , Lempicki Richard A. , Cushion Melanie T. , Cuomo Christina A. , Kovacs Joseph A.
Published: October 2019

Pneumocystis,a major opportunistic pathogen in patients with a broad range of immunodeficiencies, contains abundant surface proteins encoded by a multi-copy gene family, termed the major surface glycoprotein (Msg) gene superfamily. This superfamily has been identified in allPneumocystisspecies characterized to date, highlighting its important role inPneumocystisbiology. In this report, through a comprehensive and in-depth characterization of 459msggenes from 7Pneumocystisspecies, we demonstrate, for the first time, the phylogeny and evolution of conserved domains in Msg proteins, and provide detailed description of the classification, unique characteristics and phylogenetic relatedness of five Msg families. We further describe the relative expression levels of individualmsgfamilies in two rodentPneumocystisspecies, the substantial variability of themsgrepertoires inP. cariniifrom laboratory and wild rats, and the distinct features of the expression site for the classicmsggenes inPneumocystisfrom 8 mammalian host species. Our analysis suggests a wide variety of functions for this superfamily, not only conferring antigenic variation to allow immune evasion but also mediating life-stage development, optimizing cell mobility and adhesion, and adapting to specific host niches or environmental conditions. This study provides a rich source of information that lays the foundation for the continued experimental exploration of the functions of the Msg superfamily inPneumocystisbiology.
Interaction of contexts in context-dependent orientation estimation
Authors: Dekel Ron , Sagi Dov
Published: October 2019

The processing of a visual stimulus is known to be influenced by the statistics in recent visual history and by the stimulus’ visual surround. Such contextual influences lead to perceptually salient phenomena, such as the tilt aftereffect and the tilt illusion. Despite much research on the influence of an isolated context, it is not clear how multiple, possibly competing sources of contextual influence interact. Here, using psychophysical methods, we compared the combined influence of multiple contexts to the sum of the isolated context influences. The results showed large deviations from linear additivity for adjacent or overlapping contexts, and remarkably, clear additivity when the contexts were sufficiently separated. Specifically, for adjacent or overlapping contexts, the combined effect was often lower than the sum of the isolated component effects (sub-additivity), or was more influenced by one component than another (selection). For contexts that were separated in time (600 ms), the combined effect measured the exact sum of the isolated component effects (in degrees of bias). Overall, the results imply an initial compressive transformation during visual processing, followed by selection between the processed parts.

Highlights

Non-linear sub-additivity for increased context area or contrast

Non-linear selection between overlapping or adjacent, dissimilar contexts

Linear additivity for combinations of temporally separated contexts
jYCaMP: An optimized calcium indicator for two-photon imaging at fiber laser wavelengths
Authors: Mohr Manuel Alexander , Bushey Daniel , Aggarwal Abhi , Marvin Jonathan S. , Marquez Emiliano Jimenez , Liang Yajie , Patel Ronak , Macklin John J. , Lee Chi-Yu , Kim Douglas S. , Wong Allan M. , Looger Loren L. , Schreiter Eric R. , Podgorski Kaspar
Published: October 2019

State-of-the-art GFP-based calcium indicators do not undergo efficient two-photon excitation at wavelengths above 1000 nm, for which inexpensive and powerful industrial femtosecond lasers are available. Here we report jYCaMP1, a yellow variant of jGCaMP7 that outperforms its parent in mice and flies at excitation wavelengths above 1000 nm and enables improved two-color calcium imaging with RFP-based indicators.
Glucose homeostasis is impaired in mice deficient for the neuropeptide 26RFa (QRFP)
Authors: Mehdi Mouna El , Takhlidjt Saloua , Khiar Fayrouz , Prévost Gaëtan , Rego Jean-Luc do , Rego Jean-Claude do , Bénani Alexandre , Nedelec Emmanuelle , Godefroy David , Arabo Arnaud , Lefranc Benjamin , Leprince Jérôme , Anouar Youssef , Chartrel Nicolas , Picot Marie
Published: October 2019

Introduction

26RFa (QRFP) is a biologically active peptide that has been found to control feeding behaviour by stimulating food intake, and to regulate glucose homeostasis by acting as an incretin. The aim of the present study was thus to investigate the impact of 26RFa gene knockout on the regulation of energy and glucose metabolism.

Research design and methods

26RFa mutant mice were generated by homologous recombination, in which the entire coding region of prepro-26RFa was replaced by the iCre sequence. Energy and glucose metabolism was evaluated through measurement of complementary parameters. Morphological and physiological alterations of the pancreatic islets were also investigated.

Results

Our data do not reveal significant alteration of energy metabolism in the 26RFa-deficient mice except the occurrence of an increased basal metabolic rate. By contrast, 26RFa mutant mice exhibit an altered glycemic phenotype with an increased hyperglycemia after a glucose challenge associated with an impaired insulin production, and an elevated hepatic glucose production. 2D and 3D immunohistochemical experiments indicate that the insulin content of pancreatic β cells is much lower in the 26RFa-/- mice as compared to the wild-type littermates.

Conclusion

Disruption of the 26RFa gene induces substantial alteration in the regulation of glucose homeostasis with, in particular, a deficit in insulin production by the pancreatic islets. These findings further support the notion that 26RFa is an important regulator of glucose homeostasis.

Significance of this study

What is already known about this subject?

26RFa is a biologically active peptide produced in abundance in the gut and the pancreas. 26RFa has been found to regulate glucose homeostasis by acting as an incretin and by increasing insulin sensitivity.

What are the new findings?

Disruption of the 26RFa gene induces substantial alteration in the regulation of glucose homeostasis with, in particular, a deficit in insulin production by the pancreatic islets, assessing therefore the notion that 26RFa is an important regulator of glucose homeostasis.

How might these results change the focus of research or clinical practice?

Identification of a novel actor in the regulation of glucose homeostasis is crucial to better understand the general control of glucose metabolism in physiological and pathophysiological conditions, and opens new fields of investigation to develop innovative drugs to treat diabetes mellitus.
Essential Metabolic Routes as a Way to ESKAPE from Antibiotic Resistance
Authors: Barra Angélica Luana C. , Dantas Lívia de Oliveira C. , Galvão Morão Luana , Gutierrez Raíssa F. , Polikarpov Igor , Wrenger Carsten , Nascimento Alessandro S.
Published: October 2019

The antibiotic resistance is a worldwide concern that requires a concerted action from physicians, patients, governmental agencies and academia to prevent infections and the spread of resistance, to track resistant bacteria, to improve the use of current antibiotics and to develop new antibiotics. Despite the efforts spent so far, the current antibiotics in the market are restricted to only five general targets/pathways highlighting the need for basic research focusing on the discovery and evaluation of new potential targets. Here we interrogate two biosynthetic pathways as potentially druggable pathways in bacteria. The biosynthesis pathway for thiamine (vitamin B1), absent in humans, but found in many bacteria, including organisms in the group of the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa and Enterobacter species) and the biosynthesis pathway for pyridoxal 5’-phosphate and its vitamers (vitamin B6), found in S. aureus. Using current genomic data, we discuss the possibilities of inhibition of enzymes in the pathway and review the current state of the art in the scientific literature.