bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Play? Video Games and the Historical Imaginary
Authors: Denning Andrew
Published: February 2021

Video games earned $43.8 billion in revenue in 2018, and many of the most popular and enduring games in recent years are set in historical environments. They are a form of popular art that sheds light on the mentalité of our era. As this article argues, the act of participating in history in virtual forums frames the public’s view of history. This article examines how recent video games focused on the Nazis shape public understanding of the Third Reich, as well as how they stage who and what matters in history and assume how historical change occurs. Historical video games connect the past to present, shaping historical memory and contemporary political debates simultaneously. Video games are a form of “deep play” that build knowledge of the past and present, but that knowledge must be broadened through historians’ attention to structural forces and disadvantaged groups. Historians should understand how video games shape the wider public’s knowledge and philosophy of history, and they should develop strategies to bring the virtues of play into their own research and teaching.
International Law and Regional Norm Smuggling: How the EU and ASEAN Redefined the Global Regime on Human Trafficking
Authors: Jovanovic Marija
Published: February 2021

The European Union (EU) and the Association of Southeast Asian Nations (ASEAN) have developed fundamentally different regional regimes to address human trafficking despite both drawing on the framework established by the U.N. Palermo Protocol. These regimes have been deployed to achieve different missions: crime control animates the European framework whereas migration management informs the ASEAN regime. These different regional agendas have led to all central elements of the respective antitrafficking regimes being addressed differently including, the legal authority of the regional regime over domestic legislation, the allocation of responsibility between “sending” and “receiving” countries, their approaches to subjects of human trafficking, and the connectedness of each antitrafficking instrument to the wider regional regimes. The two regional responses challenge general assumptions about the universality and coherence of the growing international legal framework on human trafficking.
Genozip: a universal extensible genomic data compressor
Authors: Lan Divon , Tobler Ray , Souilmi Yassine , Llamas Bastien
Published: February 2021

We present Genozip, a universal and fully featured compression software for genomic data. Genozip is designed to be a general-purpose software and a development framework for genomic compression by providing five core capabilities—universality (support for all common genomic file formats), high compression ratios, speed, feature-richness and extensibility. Genozip delivers high-performance compression for widelyused genomic data formats in genomics research, namely FASTQ, SAM/BAM/CRAM, VCF, GVF, FASTA, PHYLIP and 23andMe formats. Our test results show that Genozip is fast and achieves greatly improved compression ratios, even when the files are already compressed. Further, Genozip is architected with a separation of the Genozip Framework from file-format-specific Segmenters and data-type-specific Codecs. With this, we intend for Genozip to be a general-purpose compression platform where researchers can implement compression for additional file formats, as well as new codecs for data types or fields within files, in the future. We anticipate that this will ultimately increase the visibility and adoption of these algorithms by the user community, thereby accelerating further innovation in this space.

Availability and implementation

Genozip is written in C. The code is open-source and available on http://www.genozip.com. The package is free for non-commercial use. It is distributed through the Conda package manager, github, and as a Docker container on DockerHub. Genozip is tested on Linux, Mac and Windows.

Supplementary information

Supplementary data are available at Bioinformatics online.
Effects of quercetin on exercise performance, physical activity and blood supply in a novel model of sustained hind-limb ischaemia
Authors: Phie J , Krishna S M , Kinobe R , Moxon J V , Andrade-Lima A , Morton S K , Lazzaroni S M , Huynh P , Golledge J
Published: February 2021

Background

There are currently few effective drugs to treat the leg symptoms of peripheral arterial disease (PAD). Previous studies have suggested that the nutraceutical, quercetin, can improve exercise performance and reduce pain sensitivity in healthy mice and improve blood supply in a rodent model of acute hind-limb ischaemia. These models may not be relevant to people with PAD. The aim of this study was to examine the effect of quercetin on exercise performance, physical activity and blood supply in a novel mouse model of sustained hind-limb ischaemia.

Methods

Hind-limb ischaemia was induced in 6-month-old male apolipoprotein E-deficient mice using a novel two-stage surgical procedure. Five days after induction of ischaemia, mice were allocated to commence dietary quercetin or a control diet for 4 weeks. The primary outcome was exercise performance evaluated using a treadmill test. Other outcomes included physical activity, estimated by an open field test, and hind-limb blood supply, assessed by laser Doppler monitoring.

Results

A sustained reduction in relative limb blood supply (P < 0.001) was achieved consistently in all 48 mice before allocation to a control (n = 24) or quercetin (n = 24) diet. Quercetin did not improve exercise performance (P = 0.785), physical activity (P = 0.151) or relative limb blood supply (P = 0.954) over the 4-week assessment period.

Conclusion

These data suggest that quercetin does not improve exercise performance, physical activity or limb blood supply in mice with sustained hind-limb ischaemia, and therefore is unlikely be an effective treatment for PAD.
Cardiac rehabilitation and all-cause mortality in patients with heart failure: a retrospective cohort study
Authors: Buckley Benjamin J R , Harrison Stephanie L , Fazio-Eynullayeva Elnara , Underhill Paula , Sankaranarayanan Rajiv , Wright David J , Thijssen Dick H J , Lip Gregory Y H
Published: February 2021

Aims 

Despite the benefits of exercise training in the secondary prevention of cardiovascular disease, there are conflicting findings for the impact of exercise-based cardiac rehabilitation (CR) on mortality for patients with heart failure (HF). The aim of this study was therefore to investigate the association of exercise-based CR with all-cause mortality, hospitalisation, stroke, and atrial fibrillation in patients with heart failure.

Methods and results

A retrospective cohort study was conducted which utilized a global federated health research network, primarily in the USA. Patients with a diagnosis of HF were compared between those with and without an electronic medical record of CR and/or exercise programmes within 6 months of an HF diagnosis. Patients with HF undergoing exercise-based CR were propensity score matched to HF patients without exercise-based CR by age, sex, race, comorbidities, medications, and procedures (controls). We ascertained 2-year incidence of all-cause mortality, hospitalization, stroke, and atrial fibrillation. Following propensity score matching, a total of 40 364 patients with HF were identified. Exercise-based CR was associated with 42% lower odds of all-cause mortality [odds ratio 0.58, 95% confidence interval (CI): 0.54–0.62], 26% lower odds of hospitalization (0.74, 95% CI 0.71–0.77), 37% lower odds of incident stroke (0.63, 95% CI 0.51–0.79), and 53% lower odds of incident atrial fibrillation (0.47, 95% CI 0.4–0.55) compared to controls, after propensity score matching. The beneficial association of CR and exercise on all-cause mortality was consistent across all subgroups, including patients with HFrEF (0.52, 95% CI 0.48–0.56) and HFpEF (0.65, 95% CI 0.60–0.71).

Conclusion 

Exercise-based CR was associated with lower odds of all-cause mortality, hospitalizations, incident stroke, and incident atrial fibrillation at 2-year follow-up for patients with HF (including patients with HFrEF and HFpEF).
The Effect of Mismatch Repair and Heteroduplex Formation on Sexual Isolation in Bacillus
Authors: Majewski Jacek , Cohan Frederick M
Published: February 2021

In Bacillus transformation, sexual isolation is known to be an exponential function of the sequence divergence between donor and recipient. Here, we have investigated the mechanism under which sequence divergence results in sexual isolation. We tested the effect of mismatch repair by comparing a wild-type strain and an isogenic mismatch-repair mutant for the relationship between sexual isolation and sequence divergence. Mismatch repair was shown to contribute to sexual isolation but was responsible for only a small fraction of the sexual isolation observed. Another possible mechanism of sexual isolation is that more divergent recipient and donor DNA strands have greater difficulty forming a heteroduplex because a region of perfect identity between donor and recipient is required for initiation of the heteroduplex. A mathematical model showed that this heteroduplex-resistance mechanism yields an exponential relationship between sexual isolation and sequence divergence. Moreover, this model yields an estimate of the size of the region of perfect identity that is comparable to independent estimates for Escherichia coli. For these reasons, and because all other mechanisms of sexual isolation may be ruled out, we conclude that resistance to heteroduplex formation is predominantly responsible for the exponential relationship between sexual isolation and sequence divergence in Bacillus transformation.
Genetic Evaluation by Best Linear Unbiased Prediction Using Marker and Trait Information in a Multibreed Population
Authors: Wang T , Fernando R L , Grossman M
Published: February 2021

Genetic evaluation by best linear unbiased prediction (BLUP) requires modeling genetic means, variances, and covariances. This paper presents theory to model means, variances, and covariances in a multibreed population, given marker and breed information, in the presence of gametic disequilibrium between the marker locus (ML) and linked quantitative trait locus (MQTL). Theory and algorithms are presented to construct the matrix of conditional covariances between relatives (Gv) for the MQTL effects in a multibreed population and to obtain the inverse of Gv efficiently. Theory presented here accounts for heterogeneity of variances among pure breeds and for segregation variances between pure breeds. A numerical example was used to illustrate how the theory and algorithms can be used for genetic evaluation by BLUP using marker and trait information in a multibreed population.
Mapping Quantitative Trait Loci Using Multiple Families of Line Crosses
Authors: Xu Shizhong
Published: February 2021

To avoid a loss in statistical power as a result of homozygous individuals being selected as parents of a mapping population, one can use multiple families of line crosses for quantitative trait genetic linkage analysis. Two strategies of combining data are investigated: the fixed-model and the random-model strategies. The fixed-model approach estimates and tests the average effect of gene substitution for each parent, while the random-model approach treats each effect of gene substitution as a random variable and directly estimates and tests the variance of gene substitution. Extensive Monte Carlo simulations verify that the two strategies perform equally well, although the random model is preferable in combining data from a large number of families. Simulations also show that there may be an optimal sampling strategy (number of families vs. number of individuals per family) in which QTL mapping reaches its maximum power and minimum estimation error. Deviation from the optimal strategy reduces the efficiency of the method.
Patterns of Y and X Chromosome DNA Sequence Divergence During the Felidae Radiation
Authors: Slattery Jill Pecon , O'Brien Stephen J
Published: February 2021

The 37 species of modern cats have evolved from approximately eight phylogenetic lineages within the past 10 to 15 million years. The Felidae family has been described with multiple measures of morphologic and molecular evolutionary methods that serve as a framework for tracking gene divergence during brief evolutionary periods. In this report, we compare the mode and tempo of evolution of noncoding sequences of a large intron within Zfy (783 bp) and Zfx (854 bp), homologous genes located on the felid Y and X chromosomes, respectively. Zfy sequence variation evolves at about twice the rate of Zfx, and both gene intron sequences track feline hierarchical topologies accurately. As homoplasies are infrequent in patterns of nucleotide substitution, the Y chromosome sequence displays a remarkable degree of phylogenetic consistency among cat species and provides a highly informative glimpse of divergence of sex chromosome sequences in Felidae.
Substitutions in the Pheromone-Responsive Gβ Protein of Saccharomyces cerevisiae Confer a Defect in Recovery from Pheromone Treatment
Authors: Li E , Meldrum Eric , Stratton Holly F , Stone David E
Published: February 2021

The pheromone-responsive Gα protein of Saccharomyces cerevisiae, Gpa1p, stimulates an adaptive mechanism that downregulates the mating signal. In a genetic screen designed to identify signaling elements required for Gpa1p-mediated adaptation, a large collection of adaptive-defective (Adp−) mutants were recovered. Of the 49 mutants characterized thus far, approximately three-quarters exhibit a dominant defect in the negative regulation of the pheromone response. Eight of the dominant Adp− mutations showed tight linkage to the gene encoding the pheromone-responsive Gβ, STE4. Sequence analysis of the STE4 locus in the relevant mutant strains revealed seven novel STE4 alleles, each of which was shown to disrupt proper regulation of the pheromone response. Although the STE4 mutations had only minor effects on basal mating pathway activity, the mutant forms of Gβ dramatically affected the ability of the cell to turn off the mating response after exposure to pheromone. Moreover, the signaling activity of the aberrant Gβγ subunits was suppressed by G322E, a mutant form of Gpa1p that blocks the pheromone response by sequestering Gβγ, but not by E364K, a hyperadaptive form of Gpa1p. On the basis of these observations, we propose that Gpa1p-mediated adaptation involves the binding of an unknown negative regulator to Gβγ.
Transient and Heritable Mutators in Adaptive Evolution in the Lab and in Nature
Authors: Rosenberg Susan M , Thulin Carl , Harris Reuben S
Published: February 2021

Major advances in understanding the molecular mechanism of recombination-dependent stationary-phase mutation in Escherichia coli occurred this past year. These advances are reviewed here, and we also present new evidence that the mutagenic state responsible is transient. We find that most stationary-phase mutants do not possess a heritable stationary-phase mutator phenotype, although a small proportion of heritable mutators was found previously. We outline similarities between this well-studied system and several recent examples of adaptive evolution associated with heritable mutator phenotype in a similarly small proportion of survivors of selection in nature and in the lab. We suggest the following: (1) Transient mutator states may also be a predominant source of adaptive mutations in these latter systems, the heritable mutators being a minority (Rosenberg 1997); (2) heritable mutators may sometimes be a product of, rather than the cause of, hypermutation that gives rise to adaptive mutations.
Mutagenesis and More: umuDC and the Escherichia coli SOS Response
Authors: Smith Bradley T , Walker Graham C
Published: February 2021

The cellular response to DNA damage that has been most extensively studied is the SOS response of Escherichia coli. Analyses of the SOS response have led to new insights into the transcriptional and posttranslational regulation of processes that increase cell survival after DNA damage as well as insights into DNA-damage-induced mutagenesis, i.e., SOS mutagenesis. SOS mutagenesis requires the recA and umuDC gene products and has as its mechanistic basis the alteration of DNA polymerase III such that it becomes capable of replicating DNA containing miscoding and noncoding lesions. Ongoing investigations of the mechanisms underlying SOS mutagenesis, as well as recent observations suggesting that the umuDC operon may have a role in the regulation of the E. coli cell cycle after DNA damage has occurred, are discussed.
Early Effect of Inbreeding as Revealed by Microsatellite Analyses on Ostrea edulis Larvae
Authors: Bierne Nicolas , Launey Sophie , Naciri-Graven Yamama , Bonhomme François
Published: February 2021

This paper reports new experimental evidence on the effect of inbreeding on growth and survival in the early developmental phase of a marine bivalve, the flat oyster Ostrea edulis. Two crosses between full sibs were analyzed using four microsatellite markers. Samples of 96 individuals were taken just after spawning (day 1), at the end of the larval stage before metamorphosis (day 10) and at the postlarval stage (day 70). Significant departure from Mendelian expectation was observed at two loci in the first cross and two loci in the second. Departure from 1:1 segregation occured in one parent of the first cross at three loci and genotypic selection, which resulted in highly significant heterozygote excesses, was recorded at three out of four loci in cross C1 and at two out of three loci in cross C2. Across the four markers, there were similar significant excesses of multilocus heterozygosity, and significant multilocus heterozygosity–growth correlations were recorded for both crosses at all stages. These results suggest that microsatellite markers, often assumed to be neutral, cosegregated with fitness-associated genes, the number of which is estimated to be between 15 and 38 in the whole genome, and that there is a potentially high genetic load in Ostrea edulis genome. This load provides a genetic basis for heterosis in marine bivalves.
Factors Affecting Transposition of the Himar1 mariner Transposon in Vitro
Authors: Lampe David J , Grant Theresa E , Robertson Hugh M
Published: February 2021

Mariner family transposable elements are widespread in animals, but their regulation is poorly understood, partly because only two are known to be functional. These are particular copies of the Dmmar1 element from Drosophila mauritiana, for example, Mos1, and the consensus sequence of the Himar1 element from the horn fly, Haematobia irritans. An in vitro transposition system was refined to investigate several parameters that influence the transposition of Himar1. Transposition products accumulated linearly over a period of 6 hr. Transposition frequency increased with temperature and was dependent on Mg2+ concentration. Transposition frequency peaked over a narrow range of transposase concentration. The decline at higher concentrations, a phenomenon observed in vivo with Mos1, supports the suggestion that mariners may be regulated in part by “overproduction inhibition.” Transposition frequency decreased exponentially with increasing transposon size and was affected by the sequence of the flanking DNA of the donor site. A noticeable bias in target site usage suggests a preference for insertion into bent or bendable DNA sequences rather than any specific nucleotide sequences beyond the TA target site.
Intron Loss and Gain During Evolution of the Catalase Gene Family in Angiosperms
Authors: Frugoli Julia A , McPeek Mark A , Thomas Terry L , McClung C Robertson
Published: February 2021

Angiosperms (flowering plants), including both monocots and dicots, contain small catalase gene families. In the dicot, Arabidopsis thaliana, two catalase (CAT) genes, CAT1 and CAT3, are tightly linked on chromosome 1 and a third, CAT2, which is more similar to CAT1 than to CAT3, is unlinked on chromosome 4. Comparison of positions and numbers of introns among 13 angiosperm catalase genomic sequences indicates that intron positions are conserved, and suggests that an ancestral catalase gene common to monocots and dicots contained seven introns. Arabidopsis CAT2 has seven introns; both CAT1 and CAT3 have six introns in positions conserved with CAT2, but each has lost a different intron. We suggest the following sequence of events during the evolution of the Arabidopsis catalase gene family. An initial duplication of an ancestral catalase gene gave rise to CAT3 and CAT1. CAT1 then served as the template for a second duplication, yielding CAT2. Intron losses from CAT1 and CAT3 followed these duplications. One subclade of monocot catalases has lost all but the 5′-most and 3′-most introns, which is consistent with a mechanism of intron loss by replacement of an ancestral intron-containing gene with a reverse-transcribed DNA copy of a fully spliced mRNA. Following this event of concerted intron loss, the Oryza sativa (rice, a monocot) CAT1 lineage acquired an intron in a novel position, consistent with a mechanism of intron gain at proto-splice sites.
Medicinal plants from the Himalayan region for potential novel antimicrobial and anti-inflammatory skin treatments
Authors: Heinrich Michael , Jiang Haiping , Scotti Francesca , Booker Anthony , Walt Heinrich , Weckerle Caroline , Maake Caroline
Published: February 2021

Background and Objectives

Adequate treatment of wounds remains one of the major medical needs globally, most notably in the regions with poor or limited access to health care. In many local and traditional systems of medicine, plants are often widely used for treating infected wounds.

Aim and objectives

The overarching aim of this project was selection of potential species for use in a future treatment by combining with plant resources with aspects of antimicrobial photodynamic therapy (aPDT). Specifically, we focussed on species used locally in the Himalayan region for the treatment of skin disorders and then assessed the existing pharmacological evidence for key species based on the published evidence available.

Methods

Database searches were performed to identify relevant publications describing local and traditional uses of plants in the Himalayan region of Bhutan, PR China, India, Nepal and Pakistan. Using the Global Biodiversity Information Facility (GBIF), species were researched in terms of their distribution including in different climatic regions, focussing on species mostly found in higher climatic zones (based on the Köppen–Geiger climate classification). For species used in three or more countries and restricted to the higher altitudes, data on safety, pharmacology, as it relates to dermatological conditions, and phytochemistry were retrieved.

Key findings

The study identified a total of 606 species that are used in the treatment of various skin conditions often associated with infections reported in 84 articles. Common weeds like Ageratum conyzoides and Bidens pilosa, widely used and cultivated species like Centealla asiatiaca and Prunus armenica were excluded. This ultimately led to the identification of a core group of five widely used species restricted to the Himalayan region (Cedrus deodara, Nardostachys jatamansi, Pinus wallichiana, Pinus roxburghii and Valeriana jatamansi).

Conclusions

Here we apply a novel approach comprising an assessment of the published information on the use of medicinal plants (i.e. local and traditional knowledge) in the context of their potential to be used in a biomedical form of clinical treatment – aPDT. Then, once sustainable sourcing based on access and benefit-sharing arrangements is in place, these species are investigated for their potential in wound treatment. Ultimately, the goal is to develop a new baseline for primary health care in some of the regions of the world with poor or limited access to health care.
Absolute parameters of young stars: V puppis
Authors: Budding E , Love T , Blackford M G , Banks T , Rhodes M J
Published: February 2021

New spectrometric data on V Pup are combined with satellite photometry [HIPPARCOS and recent Transiting Exoplanet Survey Satellite (TESS)] to allow a revision of the absolute parameters with increased precision. We find: M1 = 14.0 ± 0.5, M2 = 7.3 ± 0.3 (M⊙); R1  = 5.48 ± 0.18, R2  = 4.59 ± 0.15 (R⊙); T1 26 000 ± 1000, T2 24 000 ± 1000 (K), age 5 ± 1 (Myr), photometric distance 320 ± 10 (pc). The TESS photometry reveals low-amplitude (∼0.002 mag) variations of the β Cep kind, consistent with the deduced evolutionary condition and age of the optical primary. This fact provides independent support to our understanding of the system as in a process of Case A type interactive evolution that can be compared with μ1 Sco. The ∼10 M⊙ amount of matter shed by the overluminous present secondary must have been mostly ejected from the system rather than transferred, thus taking angular momentum out of the orbit and keeping the pair in relative close proximity. New times of minima for V Pup have been studied and the results compared with previous analyses. The implied variation of period is consistent with the Case A evolutionary model, though we offer only a tentative sketch of the original arrangement of this massive system. We are not able to confirm the previously reported cyclical variations having a 5.47-yr period with the new data, though a direct comparison between the HIPPARCOS and TESS photometry points to the presence of third light from a star that is cooler than those of the close binary, as mentioned in previous literature.
Star formation in ‘the Brick’: ALMA reveals an active protocluster in the Galactic centre cloud G0.253+0.016
Authors: Walker Daniel L , Longmore Steven N , Bally John , Ginsburg Adam , Diederik Kruijssen J M , Zhang Qizhou , Henshaw Jonathan D , Lu Xing , Alves João , Barnes Ashley T , Battersby Cara , Beuther Henrik , Contreras Yanett A , Gómez Laura , Ho Luis C , Jackson James M , Kauffmann Jens , Mills Elisabeth A C , Pillai Thushara
Published: February 2021

G0.253+0.016, aka ‘the Brick’, is one of the most massive (>105 M⊙) and dense (>104 cm−3) molecular clouds in the Milky Way’s Central Molecular Zone. Previous observations have detected tentative signs of active star formation, most notably a water maser that is associated with a dust continuum source. We present ALMA Band 6 observations with an angular resolution of 0.13 arcsec (1000 AU) towards this ‘maser core’ and report unambiguous evidence of active star formation within G0.253+0.016. We detect a population of eighteen continuum sources (median mass ∼2 M⊙), nine of which are driving bi-polar molecular outflows as seen via SiO (5–4) emission. At the location of the water maser, we find evidence for a protostellar binary/multiple with multidirectional outflow emission. Despite the high density of G0.253+0.016, we find no evidence for high-mass protostars in our ALMA field. The observed sources are instead consistent with a cluster of low-to-intermediate-mass protostars. However, the measured outflow properties are consistent with those expected for intermediate-to-high-mass star formation. We conclude that the sources are young and rapidly accreting, and may potentially form intermediate- and high-mass stars in the future. The masses and projected spatial distribution of the cores are generally consistent with thermal fragmentation, suggesting that the large-scale turbulence and strong magnetic field in the cloud do not dominate on these scales, and that star formation on the scale of individual protostars is similar to that in Galactic disc environments.
De novo3D models of SARS-CoV-2 RNA elements from consensus experimental secondary structures
Authors: Rangan Ramya , Watkins Andrew M , Chacon Jose , Kretsch Rachael , Kladwang Wipapat , Zheludev Ivan N , Townley Jill , Rynge Mats , Thain Gregory , Das Rhiju
Published: February 2021

The rapid spread of COVID-19 is motivating development of antivirals targeting conserved SARS-CoV-2 molecular machinery. The SARS-CoV-2 genome includes conserved RNA elements that offer potential small-molecule drug targets, but most of their 3D structures have not been experimentally characterized. Here, we provide a compilation of chemical mapping data from our and other labs, secondary structure models, and 3D model ensembles based on Rosetta's FARFAR2 algorithm for SARS-CoV-2 RNA regions including the individual stems SL1-8 in the extended 5′ UTR; the reverse complement of the 5′ UTR SL1-4; the frameshift stimulating element (FSE); and the extended pseudoknot, hypervariable region, and s2m of the 3′ UTR. For eleven of these elements (the stems in SL1–8, reverse complement of SL1–4, FSE, s2m and 3′ UTR pseudoknot), modeling convergence supports the accuracy of predicted low energy states; subsequent cryo-EM characterization of the FSE confirms modeling accuracy. To aid efforts to discover small molecule RNA binders guided by computational models, we provide a second set of similarly prepared models for RNA riboswitches that bind small molecules. Both datasets (‘FARFAR2-SARS-CoV-2’, https://github.com/DasLab/FARFAR2-SARS-CoV-2; and ‘FARFAR2-Apo-Riboswitch’, at https://github.com/DasLab/FARFAR2-Apo-Riboswitch’) include up to 400 models for each RNA element, which may facilitate drug discovery approaches targeting dynamic ensembles of RNA molecules.
A Tribute to H. George Fredrickson
Authors: Dubnick Melvin J , Guy Mary E , Kettl Donald F , Kim Pan Suk , O’Leary Rosemary
Published: February 2021

During his 50-year career, H. George Frederickson contributed on multiple fronts: to better government, to a more thoughtful and rigorous public administration field, to better scholarship, to a network of scholars, and to collaborative interaction among practitioners and scholars. He was the founding Editor of the Journal of Public Administration Research and Theory as well as the Journal of Public Administration Education. He was one of the founders of the Public Management Research Association (PMRA) and was instrumental in establishing the world headquarters of PMRA at the University of Kansas School of Public Affairs, where he was the Edwin O. Stene Distinguished Professor. He was President of Eastern Washington University. A gifted writer and thinker who excelled in both breadth and depth, George published important articles and books, and won many awards for his scholarship. Most importantly, he was a catalyst for establishing social equity as the “third pillar” of public administration. In this article, five public administration scholars pay tribute to H. George Frederickson’s most influential scholarly works, with an emphasis on social equity and accountability. George’s impact outside of the United States, especially in South Korea, also is highlighted.
The true orthodoxy of trusts law
Authors: Coumas Michael
Published: February 2021

Trusts evolved over time in a process of cyclical development. Legal drafters have repeatedly devised new versions of existing forms to achieve their clients’ objectives. Legislatures and courts have then recognised, or rejected, the legal validity of these innovations. Their responses prompt further innovatory moves by drafters, and so the rules governing validity and drafting practices have developed hand in hand. There is nothing new about the way commercial parties have put trust structures to new uses. Opposing their innovations on the ground that these depart from trust law ‘orthodoxy’ is to misunderstand the true orthodoxy of trusts law.
Age Differences in the Mediating Effects of Parenting Stress on the Relationship Between Cyanotic Congenital Heart Disease and Externalizing Problems in Children and Adolescents
Authors: Chang Ling-Yin , Wang Chia-Ching , Weng Wen-Chin , Chiu Shuenn-Nan , Chang Hsing-Yi
Published: February 2021

Background

Cyanotic congenital heart disease (CHD) has detrimental effects on behavioral function in children and adolescents. However, few study authors have examined the underlying mechanisms of these effects.

Objective

The aims of this study were to investigate the mediating effects of parenting stress in the association between cyanotic CHD and externalizing problems and to explore whether age moderated these mediating effects.

Methods

A total of 697 children and adolescents (aged 2–17 years) with CHD (252 with cyanotic CHD and 445 with acyanotic CHD) in Taiwan were enrolled. The Child Behavior Checklist and the Parenting Stress Index were used to assess externalizing problems and parenting stress, respectively. Mediation analysis was performed to determine the mediating effects of parenting stress in the association between cyanotic CHD and externalizing problems. A moderated mediation model was used to investigate the moderating effect of age on the observed mediating effects.

Results

Parenting stress significantly mediated the relationship between cyanotic CHD and externalizing problems (unstandardized coefficient B = 0.98; 95% bootstrap confidence interval, 0.23–1.78). Children's age further moderated the mediating effects, with greater effects in older children. Age also moderated the association between cyanotic CHD and parenting stress, such that the effects were only significant in children older than 5.7 years.

Conclusions

Our study revealed that age affected the mediating effects of parenting stress in the relationship between cyanotic CHD and externalizing problems. Efforts to reduce externalizing problems in children and adolescents with cyanotic CHD by targeting parenting stress may be more effective when age differences are considered.
Amblyopia and Refractive Status in Congenital Ptosis
Authors: Wu Xusheng , Zhang Jiaying , Ding Xia , Cao Yuan , Zhu Xiaowei , Li Rui , Li Lin , Lin Ming , Li Jin
Published: February 2021

Purpose

The aim of this study was to explore the effect of congenital ptosis on the visual function of patients and observe the improvement in visual function after the correction of ptosis at different surgical times.

Methods

We performed a retrospective study of 265 patients (346 eyes) with congenital ptosis at the same hospital. Each patient underwent an ophthalmic examination, including optometry and measurement of the affected palpebral fissure height and upper eyelid margin reflex distance. Preoperative clinical and morphologic data were compared with postoperative data.

Results

The refractive error of the patient population was significantly different from that of the general population (P < 0.01). The rates of strabismus and amblyopia were 12.45% and 36.98%, respectively, in the ptosis patients, both of which are higher than the rates in the general population (P < 0.01), especially for unilaterally affected patients and patients with the optical axis covered. The refractive error of patients younger than 5 years was improved postoperatively (P < 0.05). The number of cases of amblyopia and strabismus was reduced, as was the percentage of cases of with-the-rule astigmatism (P < 0.05).

Conclusion

Congenital ptosis can result in refractive error, strabismus, and amblyopia, which could seriously impair the visual function of patients. The impairment is more pronounced in unilaterally affected patients. Surgery is conducive to the recovery of visual function, especially in patients younger than 5 years. Satisfactory curative effects can be obtained before the age of 3 years; thus, unilaterally affected patients, severely affected patients, and patients with impaired visual function should undergo surgery as soon as possible.
Course Review
Authors: Teklay Samuel , Dhillon Dharminder
Published: February 2021

Plastic surgery is niche surgical speciality that is not very well covered in curricula of many medical schools around the world. Junior doctors often feel underprepared and unskilled to deal with basic plastic surgery trauma that commonly presents to the emergency department. Most junior doctors have had very limited or no exposure to common plastic surgery procedures. Simulation training would be one effective way of preparing for such placements.

The Mid Yorkshire Plastic Surgery Course, accredited by the British Association of Plastic, Reconstructive, and Aesthetic Surgeons, is an interactive 2-day course that takes place in Wakefield, UK. The Mid Yorkshire Plastic Surgery Course provides delegates with learning opportunities via short, concise lectures followed by longer practical workshops enabling application of theory into immediate practice. It focuses on fundamental plastic surgery skills required to perform key index operating procedures required for entry into higher specialist surgical training. A comprehensive evaluation of this course is conducted in this review.
Preservation of the Implant in Nipple-Sparing Mastectomies: A Retrospective Cohort Study
Authors: Le Nicole K. , Soni Sara E. , Smith Paul D. , Kumar Ambuj , Dayicioglu Deniz
Published: February 2021

Background

Mastectomies are an integral part of breast cancer treatment for many patients.
1
Of those patients, a significant number have previously undergone breast augmentation before being diagnosed with breast cancer. Therefore, we developed the novel technique of performing nipple- and implant-sparing mastectomies (NISMs) for women with prior breast augmentations. This study will assess the plausibility of using NISMs versus nipple-sparing mastectomies (NSMs) in this subgroup of patients by comparing the complication rates.

Methods

Data were collected on age, tumor size, tumor grade, receptors, and the interval between mastectomy and implant exchange for both groups. Descriptive statistics were used to summarize patient characteristics. Independent samples t tests, χ2 tests, and Fisher exact tests were used to compare the NISM and NSM cohorts. Logistic regression was used to assess the association between complications and mastectomy type and was summarized as an odds ratio with a 95% confidence interval.

Results

Fifteen patients underwent an NISM and 35 patients underwent an NSM. The overall rate of complications was less in NISM cases than in NSM cases (20% vs 27%). However, this difference was not statistically significant (odds ratio, 0.54; 95% confidence interval, 0.18–1.64; P = 0.278).

Conclusions

The overall complication rate was lower with NISMs compared with NSMs. Nipple- and implant-sparing mastectomy is a novel, viable, and safe option for patients with breast cancer and a history of submuscular breast augmentation.
Bicarbonate, carbon dioxide and pH sensing via mammalian bicarbonate-regulated soluble adenylyl cyclase
Authors: Rossetti Tom , Jackvony Stephanie , Buck Jochen , Levin Lonny R.
Published: February 2021

Soluble adenylyl cyclase (sAC; ADCY10) is a bicarbonate (HCO3−)-regulated enzyme responsible for the generation of cyclic adenosine monophosphate (cAMP). sAC is distributed throughout the cell and within organelles and, as such, plays a role in numerous cellular signalling pathways. Carbonic anhydrases (CAs) nearly instantaneously equilibrate HCO3−, protons and carbon dioxide (CO2); because of the ubiquitous presence of CAs within cells, HCO3−-regulated sAC can respond to changes in any of these factors. Thus, sAC can function as a physiological HCO3−/CO2/pH sensor. Here, we outline examples where we have shown that sAC responds to changes in HCO3−, CO2or pH to regulate diverse physiological functions.
Stomatal responses to carbon dioxide and light require abscisic acid catabolism in
Arabidopsis
Authors: Movahedi Mahsa , Zoulias Nicholas , Casson Stuart A. , Sun Peng , Liang Yun-Kuan , Hetherington Alistair M. , Gray Julie E. , Chater Caspar C. C.
Published: February 2021

In plants, stomata control water loss and CO
2
uptake. The aperture and density of stomatal pores, and hence the exchange of gases between the plant and the atmosphere, are controlled by internal factors such as the plant hormone abscisic acid (ABA) and external signals including light and CO
2
. In this study, we examine the importance of ABA catabolism in the stomatal responses to CO
2
and light. By using the ABA 8′-hydroxylase-deficient
Arabidopsis thaliana
double mutant
cyp707a1 cyp707a3
, which is unable to break down and instead accumulates high levels of ABA, we reveal the importance of the control of ABA concentration in mediating stomatal responses to CO
2
and light. Intriguingly, our experiments suggest that endogenously produced ABA is unable to close stomata in the absence of CO
2
. Furthermore, we show that when plants are grown in short day conditions ABA breakdown is required for the modulation of both elevated [CO
2
]-induced stomatal closure and elevated [CO
2
]-induced reductions in leaf stomatal density. ABA catabolism is also required for the stomatal density response to light intensity, and for the full range of light-induced stomatal opening, suggesting that ABA catabolism is critical for the integration of stomatal responses to a range of environmental stimuli.
Associations between movement behaviors and emotional changes in toddlers and preschoolers during early stages of the COVID-19 pandemic in Chile
Authors: Aguilar-Farias Nicolas , Toledo-Vargas Marcelo , Miranda-Marquez Sebastian , Cortinez-O’Ryan Andrea , Martino-Fuentealba Pia , Cristi-Montero Carlos , Rodriguez-Rodriguez Fernando , Guarda-Saavedra Paula , del Pozo Cruz Borja , Okely Anthony D.
Published: February 2021

Background

There is limited evidence about emotional and behavioral responses in toddlers and preschoolers during the coronavirus disease (COVID-19) pandemic, particularly in Latin America.

Objective

To assess associations between changes in movement behaviors (physical activity, screen time and sleeping) and emotional changes in toddlers and preschoolers during early stages of the pandemic in Chile.

Methods

A cross-sectional study conducted from March 30th to April 27th, 2020. Main caregivers of 1-to 5-year-old children living in Chile answered an online survey that included questions about sociodemographic characteristics, changes in the child’s emotions and behaviors, movement behaviors and caregivers’ stress during the pandemic. Multiple linear regressions were used to assess the association between different factors and emotional changes in toddlers and preschoolers.

Results

In total, 1727 caregivers provided complete data on emotional changes for children aged 2.9±1.36 years old, 47.9% girls. A large proportion of toddlers and preschoolers in Chile experienced emotional and behavioral changes. Most caregivers reported that children were ‘more affectionate’ (78.9%), ‘more restless’ (65.1%), and ‘more frustrated’ (54.1%) compared with pre-pandemic times. Apart from changes in movement behaviors, factors such as child age, caregivers’ age and stress, and residential area (urban/rural) were consistently associated with changes in emotions and behaviors.

Conclusion

The pandemic substantially affected the emotions and behaviors of toddlers and preschoolers in Chile. Mental health promotion programs should consider multilevel approaches in which the promotion of movement behaviors and support for caregivers should be essential pieces for future responses.
A New Hematological Prognostic Index For Covid-19 Severity
Authors: Hammadi Abdulmajeed A. , Jubouri Adnan M. Al , Ahmed Ghassan , Hayyawi Ali H. , Kareem Khalil , Gorial Faiq I. , Salman Muhammed Waheeb , Ghanim Mohammed , Jameel Basil F. , Jawad Ali M. , Abbas Hassan M. , Al-Gharawi Ali A. , Al-shareef Jawad I , Ali Chasib L. , Nasser Kawthar F. , Abdulrazaq Mohammad Y.
Published: February 2021

Background

severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or Covid-19 is a nationwide public health emergency with significant impact on human life.

Objective

To develop a new simple hematological prognostic index for Covid-19 severity state.

Patients and methods

This observational cross sectional study was conducted on 250 patients with Covid-19 disease. Age, gender, and severity of Covid −19 were recorded. Complete blood count and lactate dehydrogenase were measured.

New index: COVID-19 severity-Iraqi-index = CSI index to predict COVID-19 severity.

CSI index is monocyte/lymphocyte absolute counts multiplied by LDH (lactate dehydrogenase)/upper normal reference laboratory range of LDH value.

Results

Mean age of patients was 50.4 + 15.1 years. Majority of patients were Males 148 (59.2%)..Most of patients were in stage 2 and 3 (> 94%). There was a significant difference between means of White Blood Cells, lymphocytes and Monocytes among the different stages of the disease (P = 0.0001, 0.036, 0.012). There was a significant moderate correlation between the prognostic index and the stage of the disease (r=0.41, p=0.0001).

Conclusions

CSI index is a new simple predictor of clinical outcome in patients with covid-19 during early stage of the disease.
Accumulation of somatic mutations leads to genetic mosaicism in Cannabis
Authors: Adamek Kristian , Jones Andrew Maxwell Phineas , Torkamaneh Davoud
Published: February 2021

Cannabis is typically propagated using stem cuttings taken from mother plants to produce genetically uniform propagules. However, producers anecdotally report that clonal lines deteriorate over time and eventually produce clones with less vigour and lower cannabinoid levels than the original mother plant. While the cause of this deterioration has not been investigated, one potential contributor is the accumulation of somatic mutations within the plant. To test this, we used deep sequencing of whole genomes (>50x) to compare the variability within an individualCannabis sativacv. “Honey Banana” plant sampled at the bottom, middle and top. We called over 6 million sequence variants based on a reference genome and found that the top had the most by a sizable amount. Comparing the variants among the samples uncovered that nearly 600K (34%) were unique to the top while the bottom only contained 148K (12%) and middle with 77K (9%) unique variants. Bioinformatics tools were used to identify mutations in critical cannabinoid/terpene biosynthesis pathways. While none were identified as high impact, four genes contained more than double the average level of nucleotide diversity (π) in or near the gene. Two genes code for essential enzymes required for the cannabinoid pathway while the other two are in the terpene pathways, demonstrating that mutations were accumulating within these pathways and could influence their function. Overall, a measurable number of intra-plant genetic diversity was discovered that could impact long-term genetic fidelity of clonal lines and potentially contribute to the observed decline in vigour and cannabinoid content.