bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher-order Hamilton–Jacobi perturbation theory for anisotropic heterogeneous media: dynamic ray tracing in ray-centred coordinates
Authors: Iversen Einar , Ursin Bjørn , Saksala Teemu , Ilmavirta Joonas , de Hoop Maarten V
Published: April 2021

Dynamic ray tracing is a robust and efficient method for computation of amplitude and phase attributes of the high-frequency Green’s function. A formulation of dynamic ray tracing in Cartesian coordinates was recently extended to higher orders. Extrapolation of traveltime and geometrical spreading was demonstrated to yield significantly higher accuracy—for isotropic as well as anisotropic heterogeneous 3-D models of an elastic medium. This is of value in mapping, modelling and imaging, where kernel operations are based on extrapolation or interpolation of Green’s function attributes to densely sampled 3-D grids. We introduce higher-order dynamic ray tracing in ray-centred coordinates, which has certain advantages: (1) such coordinates fit naturally with wave propagation; (2) they lead to a reduction of the number of ordinary differential equations; (3) the initial conditions are simple and intuitive and (4) numerical errors due to redundancies are less likely to influence the computation of the Green’s function attributes. In a 3-D numerical example, we demonstrate that paraxial extrapolation based on higher-order dynamic ray tracing in ray-centred coordinates yields results highly consistent with those obtained using Cartesian coordinates. Furthermore, in a 2-D example we show that interpolation of dynamic ray tracing quantities along a wavefront can be done with much better consistency in ray-centred coordinates than in Cartesian coordinates. In both examples we measure consistency by means of constraints on the dynamic ray tracing quantities in the 3-D position space and in the 6-D phase space.
Extracting surface wave dispersion curves from asynchronous seismic stations: method and application
Authors: Rao Hao , Luo Yinhe , Zhao Kaifeng , Yang Yingjie
Published: April 2021

Correlation of the coda of Empirical Green's functions (EGFs) from ambient noise can be used to reconstruct EGFs between two seismic stations deployed different periods of time. However, such method requires a number of source stations deployed in the area surrounding a pair of asynchronous stations, which limit its applicability in cases where there are not so many available source stations. Here, we propose an alternative method, called two-station C2 method, which uses one single station as a virtual source to retrieve surface wave phase velocities between a pair of asynchronous stations. Using ambient noise data from USArray as an example, we obtain the interstation C2 functions using our C2 method and the traditional cross-correlation functions (C1 functions). We compare the differences between the C1 and C2 functions in waveforms, dispersion measurements, and phase velocity maps. Our results show that our C2 method can obtain reliable interstation phase velocity measurements, which can be used in tomography to obtain reliable phase velocity maps. Our method can significantly improve ray path coverage from asynchronous seismic arrays and enhance the resolution in ambient noise tomography for areas between asynchronous seismic arrays.
RNA kinase CLP1/Cbc regulates meiosis initiation in spermatogenesis
Authors: Wu Jianbo , Li Xin , Gao Zhiyang , Pang Lin , Liu Xian , Huang Xiahe , Wang Yingchun , Wang Zhaohui
Published: April 2021

CLP1, TSEN complex, and VCP are evolutionarily conserved proteins whose mutations are associated with neurodegenerative diseases. In this study, we have found that they are also involved in germline differentiation. To optimize both quantity and quality in gametes production, germ cells expand themselves through limited mitotic cycles prior to meiosis. Stemming from our previous findings on the correlation between mRNA 3′-processing and meiosis entry, here we identify that the RNA kinase Cbc, the Drosophila member of the highly conserved CLP1 family, is a component of the program regulating the transition from mitosis to meiosis. Using genetic manipulations in Drosophila testis, we demonstrate that nuclear Cbc is required to promote meiosis entry. Combining biochemical and genetic methods, we reveal that Cbc physically and/or genetically intersects with Tsen54 and TER94 (VCP ortholog) in this process. The C-terminal half of Tsen54 is both necessary and sufficient for its binding with Cbc. Further, we illustrate the functional conservation between Cbc and mammalian CLP1 in the assays of subcellular localization and Drosophila fertility. As CLP1, TSEN complex, and VCP have also been identified in neurodegenerations of animal models, a mechanism involving these factors seems to be shared in gametogenesis and neurogenesis.
Vedolizumab Clinical Decision Support Tool Predicts Efficacy of Vedolizumab But Not Ustekinumab in Refractory Crohn’s Disease
Authors: Alric Hadrien , Amiot Aurélien , Kirchgesner Julien , Tréton Xavier , Allez Mathieu , Bouhnik Yoram , Beaugerie Laurent , Carbonnel Franck , Meyer Antoine
Published: April 2021

Introduction

Vedolizumab clinical decision support tool (VDZ-CDST) predicts response to vedolizumab, but whether this tool also predicts efficacy of other drugs in Crohn’s disease (CD) is unknown. This study aimed to assess the value of VDZ-CDST to predict vedolizumab and ustekinumab efficacy in patients with CD.

Patients and methods

We included consecutive CD patients refractory or intolerant to anti-TNF who started either vedolizumab or ustekinumab in 5 university hospitals between May 2014 and August 2018. The main end points were the rates of clinical remission and steroid-free clinical remission (SFCR) in each group of VDZ-CDST at week 48.

Results

One hundred eighty patients were included; 94 received vedolizumab (VDZ-CDST ≤13: 32; VDZ-CDST >13 and ≤19: 52; VDZ-CDST >19: 10), and 86 received ustekinumab (VDZ-CDST ≤13: 16; VDZ-CDST >13 and ≤19: 60; VDZ-CDST >19: 10). At week 48 in the vedolizumab group, clinical remission and SFCR were reached in 9.4% with a VDZ-CDST ≤13, in 38.5% and 28.8% with a VDZ-CDST >13 and ≤19, respectively, and in 80.0% with a VDZ-CDST >19 (P < 0.0001 and P < 0.0001, respectively). In the ustekinumab cohort, clinical remission and SFCR were reached in 43.8% and 37.5% with a VDZ-CDST ≤13, in 55.0% and 50.0% with a VDZ-CDST >13 and ≤19, and 50.0% with a VDZ-CDST >19, respectively (P = 0.65 and P = 0.46, respectively). VDZ-CDST identified SFCR with an area under the curve of 0.69 (95% CI, 0.57–0.82) for vedolizumab and 0.52 (95% CI, 0.40–0.65) for ustekinumab.

Conclusion

The VDZ-CDST predicts clinical remission and SFCR at week 48 for vedolizumab but not for ustekinumab in CD patients refractory or intolerant to anti-TNF.
Glucocentric Metabolism in Ultra-Endurance Sled Dogs
Authors: Davis Michael S
Published: April 2021

The total energy expenditure of a racing sled dog can exceed 500 kcal/kg bodyweight during typical events spanning a week or more. Based on early research, as well as practical considerations, modern commercial diets are formulated to meet these energy requirements using fat and protein. However, more recent research provides a clear picture of a canine athlete with glucocentric metabolism, including many conditioning-induced adaptations oriented toward sustaining submaximal exercise with glucose as the primary metabolic fuel despite the consumption of fat as the primary dietary energy source. The specific strategies used by racing sled dogs to maintain a robust supply of glucose during exercise, as well as the possible role of fat in facilitating that metabolic priority, is the subject of ongoing research.
Continuous Galerkin schemes for semiexplicit differential-algebraic equations
Authors: Altmann Robert , Herzog Roland
Published: April 2021

This paper studies a new class of integration schemes for the numerical solution of semiexplicit differential-algebraic equations of differentiation index 2 in Hessenberg form. Our schemes provide the flexibility to choose different discretizations in the differential and algebraic equations. At the same time they are designed to have a property called variational consistency, i.e., the choice of the discretization of the constraint determines the discretization of the Lagrange multiplier. For the case of linear constraints we prove convergence of order $r+1$, both for the state and the multiplier if piecewise polynomials of order $r$ are used. These results are also verified numerically.
The antibiogram: key considerations for its development and utilization
Authors: Truong William R , Hidayat Levita , Bolaris Michael A , Nguyen Lee , Yamaki Jason
Published: April 2021

The antibiogram is an essential resource for institutions to track changes in antimicrobial resistance and to guide empirical antimicrobial therapy. In this Viewpoint, data and examples from literature are presented that suggest institutions have not completely adopted the standardized approach in developing antibiograms, as variations in the development methodologies of antibiograms exist despite consensus guidelines (M39) published by CLSI. We emphasize developing antibiograms in line with the M39 recommendations will help ensure that they are accurate, reliable and valid, and highlight that understanding the limitations of antibiogram data is critical to ensuring appropriate interpretation and application to clinical decision-making. We also stress the importance of easy accessibility and education on antibiogram use, to allow for prescribers to select the most optimal empirical treatment regimens and propose the creation of an abbreviated antibiogram for frontline users. Multidisciplinary antimicrobial stewardship programmes are vital to accomplishing these goals.
Evaluation of the GENE-UP® EHEC Detection Method for the Detection of Enterohemorrhagic E. coli in Select Foods: Collaborative Study: First Action Method 2020.06
Authors: Johnson Ronald , Mills John , Pittet Jean-Louis , Rannou Maryse , Bird Patrick
Published: April 2021

Background

The GENE-UP® EHEC assay (Performance Tested MethodSM 121806) is a real-time PCR molecular detection method that utilizes fluorescence resonance energy transfer proprietary hybridization probes for the rapid detection of enterohemorrhagic Escherichia coli (EHEC) in select foods.

Objective

The purpose of this validation was to evaluate the method’s interlaboratory performance and submit the results to AOAC INTERNATIONAL for adoption as a First Action Official Method of AnalysisSM for the detection of EHEC in select foods.

Method

The GENE-UP method was evaluated in a multi-laboratory study as part of the MicroVal VALIDATION certification process using unpaired test portions for one food matrix, raw ground beef (85% lean). Collaborators evaluated the candidate method using either an automated or manual lysis procedure. The candidate method was compared to the ISO/TS 13136:2012 method. Data from 17 participants from 15 laboratories throughout the European Union were evaluated. Three levels of contamination were evaluated: a non-inoculated control level (0 CFU/test portion), a low contamination level (∼1 CFU/test portion), and a high contamination level (∼10 CFU/test portion). Data from the study were analyzed according to the probability of detection (POD) statistical model.

Results

The difference in laboratory probability of detection (dLPODC) values with 95% confidence interval between the candidate and reference method results were –0.01 (–0.04, 0.02), 0.23 (0.07, 0.39), and 0.06 (0.01, 0.12) for the non-inoculated, low, and high contamination levels, respectively.

Conclusions

For the candidate method, values obtained for repeatability and reproducibility were similar to the reference method and indicated minimal variation between samples or between laboratories. No discrepant results (false positive or false negative) were observed for each contamination. A statistical difference was calculated between the candidate and reference method at the low and high inoculation levels, with the candidate method detecting a higher number of positive samples indicating a higher sensitivity than the reference method. No differences in the recovery of the target analyte were observed between the manual and automated lysis procedures.

Highlights

The GENE-UP EHEC Detection Method provides end users a rapid, easy-to-use workflow for the detection of EHEC in food matrixes.
Changes in nutrient balance, methane emissions, physiologic biomarkers and production performance in goats fed different forage-to-concentrate ratios during lactation
Authors: Fernández Carlos , Hernández Alberto , Gomis-Tena Julio , Loor Juan J
Published: April 2021

The objective was to determine the effect forage to concentrate (F:C) ratio and stage of lactation on methane emissions, digestibility, nutrient balance, lactation performance, and metabolic responses in lactating goats. Twenty Murciano-Granadina dairy goats were used in an experiment divided into three periods: early (30 d), mid (100 d) and late (170 d) lactation. All goats were fed a diet with 35:65 F:C (FCL) during early-lactation. Then, one group (n = 10 goats) remained on FCL through mid and late-lactation while the other group (n = 10 goats) was fed a diet with 50:50 F:C at mid-lactation (FCM) and 65:35 (FCH) at late lactation. A greater proportion of concentrate in the diet was associated with greater overall intake and digestibility (P < 0.05). Energy balance was negative in early-lactation (-77 kJ/kg of BW 0.75, on average) and positive for FCL at mid and late-lactation (13 and 35 kJ/kg of BW 0.75, respectively). Goats fed FCM and FCH maintained negative energy balance throughout lactation. Plasma concentrations of non-esterified fatty acids (NEFA) at mid-lactation were greater for FCM than FCL (680 mEq/L), and at late-lactation concentrations were greater for FCH and FCL (856 mEq/L). A similar response was detected for plasma ß-Hydroxybutyrate (BHB). Methane emission was greater (P < 0.05) for FCM than FCH (1.7 g CH4/d). This study demonstrated that differences in F:C across stages of lactation lead to distinct metabolic responses at the level of the rumen and tissues.
Direct and biometrical estimates of the closing force of major claws of the sand fiddler crab Leptuca pugilator (Bosc, 1801) (Decapoda: Brachyura: Ocypodidae): Support for the weakening combatant hypothesis
Authors: Levinton Jeffrey S , Arena Brooke
Published: April 2021

Many conclusions concerning the functional biology of crab claws rely upon biometrical estimates of closing force, based upon measures of muscle cross-sectional area and mechanical advantage. Fiddler crab closing force patterns show variation with body size, claw size, location of the opposing claw tips, and physiological condition, so we have measured closing force of the sand fiddler crab Leptuca pugilator (Bosc, 1801) as a function of claw size, force exerted at claw tips, and at the commonly well-developed pollex tooth. Leptuca pugilator has an elongated claw with gracile dactyl and pollex. As predicted by biometrical proportions, closing force is greater at the pollex tooth than at the claw tip. The pollex tooth does shift with increasing claw size in relative position toward the claw hinge. Mechanical advantage at the pollex tooth and dactyl tip both decline with increasing claw length. But there is no difference in slope of log closing force as a function of log claw length between the pollex position and terminus of the dactyl, which demonstrates that force exerted at the pollex tooth has no impact on proportional change in closing force with increasing claw size. The log-log slope is ~0.9, reflecting the proportionally decreasing muscle cross-sectional area and lowering mechanical advantage with increasing claw size. For both the pollex tooth and the claw tip, mechanical advantage decreases very slightly with increasing claw size, but closing force proportionally decreases with increasing claw size, supporting the weakening combatant hypothesis for this species.
Alternative Formulations of Trap Lures for Operational Detection, Population Monitoring, and Outbreak Forecasting of Southern Pine Beetle in the United States
Authors: Sullivan Brian T , Shepherd William P , Nowak John T , Clarke Stephen R , Merten Paul R , Billings Ronald F , Upton William W , Riggins John J , Brownie Cavell
Published: April 2021

The southern pine beetle, Dendroctonus frontalis Zimmermann (Coleoptera: Curculionidae: Scolytinae) is a major destructive pest of Pinus L. In the southeastern United States, numbers of this species and a major predator, Thanasimus dubius (Fabricius) (Coleoptera: Cleridae), captured during an annual springtime trapping survey are used to make forecasts of the likelihood and severity of an outbreak during the following summer. We investigated responses by both species to six lure formulations to evaluate their suitability for the survey and allow integration of historical data sets produced with differing lure compositions. Trapping trials were performed at four locations across three states (Louisiana, Mississippi, and Alabama) during spring, and at these and one additional location (North Carolina) in fall 2016. All lures included the pheromone component frontalin. Southern pine beetle preferred lures that additionally included the pheromone component endo-brevicomin and turpentine as a source of host odors (rather than a 7:3 mixture of monoterpenes alpha- and beta-pinene). Thanasimus dubius displayed little discrimination among lure compositions. Lure preferences by southern pine beetle did not differ significantly among locations in spring but were influenced by season. Gas chromatography (GC)-electroantennographic detection analyses with southern pine beetle and GC-mass spectrometry identified numerous known and potential semiochemicals that distinguished volatiles released by the tested host odor devices. The lure combination that included endo-brevicomin and alpha/beta-pinene is recommended for the trapping survey because of its high sensitivity for southern pine beetle and potential for greater data integrity resulting from its reproducible composition.
A Special Collection: Drones to Improve Insect Pest Management
Authors: Moses-Gonzales Nathan , Brewer Michael J
Published: April 2021

The Special Collection Drones to Improve Insect Pest Management presents research and development of unmanned (or uncrewed) aircraft system (UAS, or drone) technology to improve insect pest management. The articles bridge from more foundational studies (i.e., evaluating and refining abilities of drones to detect pest concerns or deliver pest management materials) to application-oriented case studies (i.e., evaluating opportunities and challenges of drone use in pest management systems). The collection is composed of a combination of articles presenting information first-time published, and a selection of articles previously published in Journal of Economic Entomology (JEE). Articles in the Collection, as well as selected citations of articles in other publications, reflect the increase in entomology research using drones that has been stimulated by advancement in drone structural and software engineering such as autonomous flight guidance; in- and post-flight data storage and processing; and companion advances in spatial data management and analyses including machine learning and data visualization. The Collection is also intended to stimulate discussion on the role of JEE as a publication venue for future articles on drones as well as other cybernectic-physical systems, big data analyses, and deep learning processes. While these technologies have their genesis in fields arguably afar from the discipline of entomology, we propose that interdisciplinary collaboration is the pathway for applications research and technology transfer leading to an acceleration of research and development of these technologies to improve pest management.
Big Data in Conservation Genomics: Boosting Skills, Hedging Bets, and Staying Current in the Field
Authors: Schweizer Rena M , Saarman Norah , Ramstad Kristina M , Forester Brenna R , Kelley Joanna L , Hand Brian K , Malison Rachel L , Ackiss Amanda S , Watsa Mrinalini , Nelson Thomas C , Beja-Pereira Albano , Waples Robin S , Funk W Chris , Luikart Gordon
Published: April 2021

A current challenge in the fields of evolutionary, ecological, and conservation genomics is balancing production of large-scale datasets with additional training often required to handle such datasets. Thus, there is an increasing need for conservation geneticists to continually learn and train to stay up-to-date through avenues such as symposia, meetings, and workshops. The ConGen meeting is a near-annual workshop that strives to guide participants in understanding population genetics principles, study design, data processing, analysis, interpretation, and applications to real-world conservation issues. Each year of ConGen gathers a diverse set of instructors, students, and resulting lectures, hands-on sessions, and discussions. Here, we summarize key lessons learned from the 2019 meeting and more recent updates to the field with a focus on big data in conservation genomics. First, we highlight classical and contemporary issues in study design that are especially relevant to working with big datasets, including the intricacies of data filtering. We next emphasize the importance of building analytical skills and simulating data, and how these skills have applications within and outside of conservation genetics careers. We also highlight recent technological advances and novel applications to conservation of wild populations. Finally, we provide data and recommendations to support ongoing efforts by ConGen organizers and instructors—and beyond—to increase participation of underrepresented minorities in conservation and eco-evolutionary sciences. The future success of conservation genetics requires both continual training in handling big data and a diverse group of people and approaches to tackle key issues, including the global biodiversity-loss crisis.
Tarski’s Undefinability Theorem and the Diagonal Lemma
Authors: Salehi Saeed
Published: April 2021

We prove the equivalence of the semantic version of Tarski’s theorem on the undefinability of truth with the semantic version of the diagonal lemma and also show the equivalence of a syntactic version of Tarski’s undefinability theorem with a weak syntactic diagonal lemma. We outline two seemingly diagonal-free proofs for these theorems from the literature and show that the syntactic version of Tarski’s theorem can deliver Gödel–Rosser’s incompleteness theorem.
Outcomes of salvage fractionated re-irradiation combined with bevacizumab for recurrent high-grade gliomas that progressed after bevacizumab treatment**
Authors: Yonezawa Hajime , Ohno Makoto , Igaki Hiroshi , Miyakita Yasuji , Takahashi Masamichi , Tamura Yukie , Shima Satoshi , Matsushita Yuko , Ichimura Koichi , Narita Yoshitaka
Published: April 2021

Background

There is no standard treatment for patients with recurrent high-grade gliomas who progress after bevacizumab treatment. We evaluated the outcomes of re-irradiation combined with bevacizumab for patients refractory to bevacizumab.

Methods

Between January 2015 and September 2019, patients with progression after bevacizumab treatment were treated with re-irradiation combined with bevacizumab (25 Gy in five fractions).

Results

Fourteen patients [glioblastoma, isocitrate dehydrogenase (IDH) wild type (N = 6), glioblastoma, IDH mutant (N = 4), anaplastic astrocytoma, IDH wild type (N = 1), anaplastic astrocytoma, IDH mutant (N = 1), glioblastoma, not otherwise specified (N = 1) and radiologically diagnosed brainstem glioma (N = 1)] were included in this study. The median survival and progression-free survival times after re-irradiation combined with bevacizumab were 6.1 and 3.8 months, respectively. The 6-month survival and progression-free survival rates were 54.5 and 15.7%, respectively. Patients with a Karnofsky performance status of ≥70 tended to have longer median survival time (9.3 vs. 5.4 months, respectively; P = 0.058) and had a significantly longer median progression-free survival time (4.2 vs. 3.7 months, respectively; P = 0.046) than those with a Karnofsky performance status of <70. Four patients (28.6%) achieved a complete or partial radiological response, and three patients (21.4%) had an improved Karnofsky performance status after re-irradiation combined with bevacizumab. Grade 3/4 toxicities included leukopenia in four patients (28.6%), hypertension in three (21.4%), proteinuria in one (7.1%) and gastrointestinal hemorrhage in one (7.1%).

Conclusions

Re-irradiation combined with bevacizumab for patients with recurrent high-grade gliomas who progress after bevacizumab treatment was feasible. Re-irradiation combined with bevacizumab is a potential treatment option, especially for patients with a Karnofsky performance status of ≥70.
The stellar mass function and evolution of the density profile of galaxy clusters from the Hydrangea simulations at 0 < z < 1.5
Authors: Ahad Syeda Lammim , Bahé Yannick M , Hoekstra Henk , van der Burg Remco F J , Muzzin Adam
Published: April 2021

Galaxy clusters are excellent probes to study the effect of environment on galaxy formation and evolution. Along with high-quality observational data, accurate cosmological simulations are required to improve our understanding of galaxy evolution in these systems. In this work, we compare state-of-the-art observational data of massive galaxy clusters ($\gt 10^{14}\, \textrm {M}_{\odot }$) at different redshifts (0 < z < 1.5) with predictions from the Hydrangea suite of cosmological hydrodynamic simulations of 24 massive galaxy clusters ($\gt 10^{14}\, \textrm {M}_{\odot }$ at z = 0). We compare three fundamental observables of galaxy clusters: the total stellar mass-to-halo mass ratio, the stellar mass function, and the radial mass density profile of the cluster galaxies. In the first two of these, the simulations agree well with the observations, albeit with a slightly too high abundance of $M_\star \lesssim 10^{10} \, \mathrm{M}_\odot$ galaxies at z ≳ 1. The Navarro–Frenk–White concentrations of cluster galaxies increase with redshift, in contrast to the decreasing dark matter (DM) halo concentrations. This previously observed behaviour is therefore due to a qualitatively different assembly of the smooth DM halo compared to the satellite population. Quantitatively, we, however, find a discrepancy in that the simulations predict higher stellar concentrations than observed at lower redshifts (z < 0.3), by a factor of ≈2. This may be due to selection bias in the simulations, or stem from shortcomings in the build-up and stripping of their inner satellite halo.
Unearthing LTR Retrotransposon gag Genes Co-opted in the Deep Evolution of Eukaryotes
Authors: Wang Jianhua , Han Guan-Zhu
Published: April 2021

LTR retrotransposons comprise a major component of the genomes of eukaryotes. On occasion, retrotransposon genes can be recruited by their hosts for diverse functions, a process formally referred to as co-option. However, a comprehensive picture of LTR retrotransposon gag gene co-option in eukaryotes is still lacking, with several documented cases exclusively involving Ty3/Gypsy retrotransposons in animals. Here, we use a phylogenomic approach to systemically unearth co-option of retrotransposon gag genes above the family level of taxonomy in 2,011 eukaryotes, namely co-option occurring during the deep evolution of eukaryotes. We identify a total of 14 independent gag gene co-option events across more than 740 eukaryote families, eight of which have not been reported previously. Among these retrotransposon gag gene co-option events, nine, four, and one involve gag genes of Ty3/Gypsy, Ty1/Copia, and Bel-Pao retrotransposons, respectively. Seven, four, and three co-option events occurred in animals, plants, and fungi, respectively. Interestingly, two co-option events took place in the early evolution of angiosperms. Both selective pressure and gene expression analyses further support that these co-opted gag genes might perform diverse cellular functions in their hosts, and several co-opted gag genes might be subject to positive selection. Taken together, our results provide a comprehensive picture of LTR retrotransposon gag gene co-option events that occurred during the deep evolution of eukaryotes and suggest paucity of LTR retrotransposon gag gene co-option during the deep evolution of eukaryotes.
Reverse Plasticity Underlies Rapid Evolution by Clonal Selection within Populations of Fibroblasts Propagated on a Novel Soft Substrate
Authors: Purkayastha Purboja , Pendyala Kavya , Saxena Ayush S , Hakimjavadi Hesamedin , Chamala Srikar , Dixit Purushottam , Baer Charles F , Lele Tanmay P
Published: April 2021

Mechanical properties such as substrate stiffness are a ubiquitous feature of a cell’s environment. Many types of animal cells exhibit canonical phenotypic plasticity when grown on substrates of differing stiffness, in vitro and in vivo. Whether such plasticity is a multivariate optimum due to hundreds of millions of years of animal evolution, or instead is a compromise between conflicting selective demands, is unknown. We addressed these questions by means of experimental evolution of populations of mouse fibroblasts propagated for approximately 90 cell generations on soft or stiff substrates. The ancestral cells grow twice as fast on stiff substrate as on soft substrate and exhibit the canonical phenotypic plasticity. Soft-selected lines derived from a genetically diverse ancestral population increased growth rate on soft substrate to the ancestral level on stiff substrate and evolved the same multivariate phenotype. The pattern of plasticity in the soft-selected lines was opposite of the ancestral pattern, suggesting that reverse plasticity underlies the observed rapid evolution. Conversely, growth rate and phenotypes did not change in selected lines derived from clonal cells. Overall, our results suggest that the changes were the result of genetic evolution and not phenotypic plasticity per se. Whole-transcriptome analysis revealed consistent differentiation between ancestral and soft-selected populations, and that both emergent phenotypes and gene expression tended to revert in the soft-selected lines. However, the selected populations appear to have achieved the same phenotypic outcome by means of at least two distinct transcriptional architectures related to mechanotransduction and proliferation.
Transcriptome Analysis in Yeast Reveals the Externality of Position Effects
Authors: Gui Qian , Deng Shuyun , Zhou ZhenZhen , Cao Waifang , Zhang Xin , Shi Wenjun , Cai Xiujuan , Jiang Wenbing , Cui Zifeng , Hu Zheng , Chen Xiaoshu
Published: April 2021

The activity of a gene newly integrated into a chromosome depends on the genomic context of the integration site. This “position effect” has been widely reported, although the other side of the coin, that is, how integration affects the local chromosomal environment, has remained largely unexplored, as have the mechanism and phenotypic consequences of this “externality” of the position effect. Here, we examined the transcriptome profiles of approximately 250 Saccharomyces cerevisiae strains, each with GFP integrated into a different locus of the wild-type strain. We found that in genomic regions enriched in essential genes, GFP expression tended to be lower, and the genes near the integration site tended to show greater expression reduction. Further joint analysis with public genome-wide histone modification profiles indicated that this effect was associated with H3K4me2. More importantly, we found that changes in the expression of neighboring genes, but not GFP expression, significantly altered the cellular growth rate. As a result, genomic loci that showed high GFP expression immediately after integration were associated with growth disadvantages caused by elevated expression of neighboring genes, ultimately leading to a low total yield of GFP in the long run. Our results were consistent with competition for transcriptional resources among neighboring genes and revealed a previously unappreciated facet of position effects. This study highlights the impact of position effects on the fate of exogenous gene integration and has significant implications for biological engineering and the pathology of viral integration into the host genome.
A unified computational view of DNA duplex, triplex, quadruplex and their donor–acceptor interactions
Authors: Park Gyuri , Kang Byunghwa , Park Soyeon V , Lee Donghwa , Oh Seung Soo
Published: April 2021

DNA can assume various structures as a result of interactions at atomic and molecular levels (e.g., hydrogen bonds, π–π stacking interactions, and electrostatic potentials), so understanding of the consequences of these interactions could guide development of ways to produce elaborate programmable DNA for applications in bio- and nanotechnology. We conducted advanced ab initio calculations to investigate nucleobase model structures by componentizing their donor-acceptor interactions. By unifying computational conditions, we compared the independent interactions of DNA duplexes, triplexes, and quadruplexes, which led us to evaluate a stability trend among Watson–Crick and Hoogsteen base pairing, stacking, and even ion binding. For a realistic solution-like environment, the influence of water molecules was carefully considered, and the potassium-ion preference of G-quadruplex was first analyzed at an ab initio level by considering both base-base and ion-water interactions. We devised new structure factors including hydrogen bond length, glycosidic vector angle, and twist angle, which were highly effective for comparison between computationally-predicted and experimentally-determined structures; we clarified the function of phosphate backbone during nucleobase ordering. The simulated tendency of net interaction energies agreed well with that of real world, and this agreement validates the potential of ab initio study to guide programming of complicated DNA constructs.
Single-molecule imaging of epigenetic complexes in living cells: insights from studies on Polycomb group proteins
Authors: Brown Kyle , Andrianakos Haralambos , Ingersoll Steven , Ren Xiaojun
Published: April 2021

Chromatin-associated factors must locate, bind to, and assemble on specific chromatin regions to execute chromatin-templated functions. These dynamic processes are essential for understanding how chromatin achieves regulation, but direct quantification in living mammalian cells remains challenging. Over the last few years, live-cell single-molecule tracking (SMT) has emerged as a new way to observe trajectories of individual chromatin-associated factors in living mammalian cells, providing new perspectives on chromatin-templated activities. Here, we discuss the relative merits of live-cell SMT techniques currently in use. We provide new insights into how Polycomb group (PcG) proteins, master regulators of development and cell differentiation, decipher genetic and epigenetic information to achieve binding stability and highlight that Polycomb condensates facilitate target-search efficiency. We provide perspectives on liquid-liquid phase separation in organizing Polycomb targets. We suggest that epigenetic complexes integrate genetic and epigenetic information for target binding and localization and achieve target-search efficiency through nuclear organization.
Diagnostic accuracy and clinical impact of [18F]FET PET in childhood CNS tumors
Authors: Marner Lisbeth , Lundemann Michael , Sehested Astrid , Nysom Karsten , Borgwardt Lise , Mathiasen René , Wehner Peder S , Henriksen Otto M , Thomsen Carsten , Skjøth-Rasmussen Jane , Broholm Helle , Østrup Olga , Forman Julie L , Højgaard Liselotte , Law Ian
Published: April 2021

Background

Central nervous system (CNS) tumors cause the highest death rates among childhood cancers, and survivors frequently have severe late effects. Magnetic resonance imaging (MRI) is the imaging modality of choice, but its specificity can be challenged by treatment-induced signal changes. In adults, O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) PET can assist in interpreting MRI findings. We assessed the clinical impact and diagnostic accuracy of adding [18F]FET PET to MRI in children with CNS tumors.

Methods

A total of 169 [18F]FET PET scans were performed in 97 prospectively and consecutively included patients with known or suspected childhood CNS tumors. Scans were performed at primary diagnosis, before or after treatment, or at relapse.

Results

Adding [18F]FET PET to MRI impacted clinical management in 8% [95% confidence interval (CI): 4%-13%] of all scans (n = 151) and in 33% [CI: 17%-53%] of scans deemed clinically indicated due to difficult decision making on MRI alone (n = 30). Using pathology or follow-up as reference standard, the addition of [18F]FET PET increased specificity (1.00 [0.82-1.00] vs 0.48 [0.30-0.70], P = .0001) and accuracy (0.91 [CI: 0.87-0.96] vs 0.81 [CI: 0.75-0.89], P = .04) in 83 treated lesions and accuracy in 58 untreated lesions (0.96 [CI: 0.91-1.00] vs 0.90 [CI: 0.82-0.92], P < .001). Further, in a subset of patients (n = 15) [18F]FET uptake correlated positively with genomic proliferation index.

Conclusions

The addition of [18F]FET PET to MRI helped discriminate tumor from non-tumor lesions in the largest consecutive cohort of pediatric CNS tumor patients presented to date.
Postmarket American Experience With Woven EndoBridge Device: Adjudicated Multicenter Case Series
Authors: Cherian Jacob , Chen Stephen R , Puri Ajit , Vakharia Kunal , Levy Elad , Eshraghi Sheila , Howard Brian M , Tong Frank C , Cawley C Michael , Gross Bradley , Alexander Matthew D , Grandhi Ramesh , Srinivasan Visish M , Burkhardt Jan-Karl , Johnson Jeremiah N , Kan Peter
Published: April 2021

BACKGROUND

The Woven EndoBridge (WEB) device was granted premarket approval in the United States following results of the Woven EndoBridge Intrasaccular Therapy (WEB-IT) study. WEB-IT reported excellent adequate angiographic occlusion of treated aneurysms with a high safety profile. These results were achieved, however, in the context of a prospective study with strict inclusion criteria and rigorous training support.

OBJECTIVE

To review early as-practiced clinical experience with the WEB device in the United States.

METHODS

Retrospective review across 6 institutions identified 91 patients undergoing 92 treatment sessions for WEB device placement in treatment of 91 intracranial aneurysms. Details regarding demographics, aneurysm characteristics, treatment considerations, clinical outcomes, and aneurysm occlusion were obtained and analyzed in a multicenter database. Angiograms from the index procedure and follow-up studies were reviewed by a blinded and independent adjudicator.

RESULTS

The middle cerebral, anterior communicating, and basilar artery complexes were the commonly treated locations. Eight patients presented with ruptured aneurysms. A mean of 1.2 devices were introduced per case. Technical failure without deployment of a WEB device occurred in 2% (2/92) of sessions. Complete aneurysm occlusion for patients with imaging follow-up was 49% (mean follow-up of 8 mo). Four aneurysms were retreated. 90% of patients had modified Rankin Scale ≤ 2 at last clinical follow-up with no mortalities.

CONCLUSION

Immediate postmarket experience with the WEB device, newly introduced at American centers, confirms safe procedural use, but long-term efficacy remains unclear. Early challenges include accurate sizing and device selection.
HSE Management Standards and burnout dimensions among rehabilitation professionals
Authors: Carpi M , Bruschini M , Burla F
Published: April 2021

Background

The Health & Safety Executive Indicator Tool (HSE-IT) is a standard-based questionnaire commonly used to assess work-related stress in organizations. Although the HSE-IT validity has been well documented and significant relationships have been observed between its scales and several work-related outcomes, to date there is no evidence concerning the relationships between the HSE-IT and burnout among healthcare workers.

Aims

To investigate the relationships between the HSE-IT subscales and burnout dimensions as measured by the Maslach Burnout Inventory (MBI) in a sample of Italian rehabilitation professionals employed in healthcare institutions.

Methods

An anonymous cross-sectional questionnaire was administered to a sample of Italian rehabilitation professionals including physical therapists, occupational therapists, psychiatric rehabilitation technicians and developmental psychomotor therapists. Associations between the HSE-IT and the MBI were analysed with multiple linear regression models.

Results

A total of 432 rehabilitation professionals completed the questionnaire and 14% of them showed high levels of burnout risk. Significant differences in the HSE-IT scores were found between workers at high risk of burnout and workers at low risk of burnout. Hierarchical regressions showed an association between the HSE-IT scales and the MBI factors: emotional exhaustion was associated with ‘demands’ and ‘role’, and both depersonalization and personal accomplishment were associated with ‘control’ and ‘role’.

Conclusions

This preliminary study showed the HSE-IT subscales are sensitive to burnout risk as measured by the MBI. The association found between the HSE-IT ‘demands’, ‘role’ and ‘control’ subscales and the MBI dimensions is significant but small. These findings might inform targeted burnout prevention.
Progressive Response to Repeat Application of Capsaicin 179 mg (8% w/w) Cutaneous Patch in Peripheral Neuropathic Pain: Comprehensive New Analysis and Clinical Implications
Authors: Freynhagen Rainer , Argoff Charles , Eerdekens Mariëlle , Engelen Sylvia , Perrot Serge
Published: April 2021

Objective

To investigate the efficacy of repeated application of capsaicin 179 mg cutaneous patch in nonresponders to the first application.

Design

Post hoc, as-treated analysis of two prospective trials (STRIDE and PACE) with 52-week follow-up.

Blinding

Open-label.

Setting

Multicenter clinical trial.

Subjects

STRIDE: nondiabetic neuropathic pain; PACE: painful diabetic peripheral neuropathy.

Methods

Patients were divided according to number of applications needed before attainment of a ≥30% reduction in average pain intensity (question 5 of the Brief Pain Inventory [BPI-Q5]). We assessed the change from baseline in average pain intensity (BPI-Q5), mean “interference with sleep” score, Patient Global Impression of Change, quality of life (QOL) via the EuroQol 5-dimension, and Self-Assessment of Treatment.

Results

In STRIDE and PACE, respectively, n = 306 and n = 313 received the capsaicin patch; n = 60 and n = 96 had a response after the first application, n = 33 and n = 68 after the second, and n = 11 and n = 43 after the third. Among patients without a ≥30% reduction in pain intensity at 3 months, in STRIDE and PACE, respectively, 23.3% and 28.1% achieved a ≥30% reduction at 6 months, increasing to 33.9% and 45.7% at 12 months. Similar results were obtained when a decrease of ≥50% was used as the responder definition. Progressive improvements in pain intensity in slower responders reached levels similar to those in early responders at month 12 and were accompanied by improvements in sleep, QOL, and patient satisfaction.

Conclusions

Although some patients with peripheral neuropathic pain experience rapid improvements with a single treatment of capsaicin 179 mg patch, some may require two or three treatments before an initial response is observed. Similar benefits for pain, sleep, and QOL can be achieved in early and late responders.
High-efficacy, high-manufacturability human VH domain antibody therapeutics from transgenic sources
Authors: Bélanger Kasandra , Tanha Jamshid
Published: April 2021

Interest in single-domain antibodies (sdAbs) stems from their unique structural/pronounced, hence therapeutically desirable, features. From the outset—as therapeutic modalities—human antibody heavy chain variable domains (VHs) attracted a particular attention compared with ‘naturally-occurring’ camelid and shark heavy-chain-only antibody variable domains (VHHs and VNARs, respectively) due to their perceived lack of immunogenicity. However, they have not quite lived up to their initial promise as the VH hits, primarily mined from synthetic VH phage display libraries, have too often been plagued with aggregation tendencies, low solubility and low affinity. Largely unexplored, synthetic camelized human VH display libraries appeared to have remediated the aggregation problem, but the low affinity of the VH hits still persisted, requiring undertaking additional, laborious affinity maturation steps to render VHs therapeutically feasible. A wholesome resolution has recently emerged with the development of non-canonical transgenic rodent antibody discovery platforms that appear to facilely and profusely generate high affinity, high solubility and aggregation-resistant human VHs.
Metonymies, metaphors and/or language reconsiderations for sustainability during COVID-19
Authors: Kahambing Jan Gresil S
Published: April 2021

Pandemic discussions employ language metaphors and metonymies to make sense of the coronavirus disease 2019 crisis. From commenting and proposing to revise terms such as social distancing, the war against the virus, to viewing mother nature as a killer, there are language reconsiderations to be made to avoid some disturbing mental imageries to picture a sustainable future. The Anthropocene geologic time and the improved environmental quality situate this backdrop. Language interventions make up as a vanishing mediation that will prompt a deeper understanding of the environment and nature as a whole.
The Politics of Alignment and the ‘Quiet Transgender Revolution’ in Fortune 500 Corporations, 2008 to 2017
Authors: Ghosh Apoorva
Published: April 2021

This study shows that when social movements achieve a general acceptance for the legitimacy of their cause in the institutional environment, they may start pursuing further demands by challenging their target entities through the ‘politics of alignment,’ meaning engaging these entities in professionally developed programs and demanding specific outcomes by introducing timed interventions in them. This study exemplifies this politics using the case of American LGBT workplace movement which used its Corporate Equality Index (CEI) program to extend reputational and economic benefits to its target entities—the Fortune 500 corporations—but also added an intervention to this program in 2011 to demand the adoption of gender transition-related health benefits by these corporations as a specific movement outcome which, if not met, would make these corporations lose the benefits they had been deriving through their performance in the CEI program. A longitudinal study of 456 Fortune 500 corporations from 2008 to 2017 conducted through hazard rate analysis indicates that corporations affected by this intervention, as well as by other movement factors, were the most likely to adopt these health benefits for their employees. Further quantitative analysis—using QCA—shows that early adoptions were explained largely by the LGBT workplace movement forces and the later adoptions by insider activism and isomorphic diffusion. These findings highlight that an incisive understanding of organizational change can be best gathered by examining social movements and institutional forces together.