bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Evolution of Ecological Specialisation: Genomic Insights from the Diversification of Murine Rodents
Authors: Roycroft Emily , Achmadi Anang , Callahan Colin M , Esselstyn Jacob A , Good Jeffrey M , Moussalli Adnan , Rowe Kevin C
Published: May 2021

Adaptive radiations are characterized by the diversification and ecological differentiation of species, and replicated cases of this process provide natural experiments for understanding the repeatability and pace of molecular evolution. During adaptive radiation, genes related to ecological specialization may be subject to recurrent positive directional selection. However, it is not clear to what extent patterns of lineage-specific ecological specialization (including phenotypic convergence) are correlated with shared signatures of molecular evolution. To test this, we sequenced whole exomes from a phylogenetically dispersed sample of 38 murine rodent species, a group characterized by multiple, nested adaptive radiations comprising extensive ecological and phenotypic diversity. We found that genes associated with immunity, reproduction, diet, digestion, and taste have been subject to pervasive positive selection during the diversification of murine rodents. We also found a significant correlation between genome-wide positive selection and dietary specialization, with a higher proportion of positively selected codon sites in derived dietary forms (i.e., carnivores and herbivores) than in ancestral forms (i.e., omnivores). Despite striking convergent evolution of skull morphology and dentition in two distantly related worm-eating specialists, we did not detect more genes with shared signatures of positive or relaxed selection than in a nonconvergent species comparison. Although a small number of the genes we detected can be incidentally linked to craniofacial morphology or diet, protein-coding regions are unlikely to be the primary genetic basis of this complex convergent phenotype. Our results suggest a link between positive selection and derived ecological phenotypes, and highlight specific genes and general functional categories that may have played an integral role in the extensive and rapid diversification of murine rodents.
Age, Sex, and BMI Influence on Copper, Zinc, and Their Major Serum Carrier Proteins in a Large European Population Including Nonagenarian Offspring From MARK-AGE Study
Authors: Piacenza Francesco , Giacconi Robertina , Costarelli Laura , Basso Andrea , Bürkle Alexander , Moreno-Villanueva María , Dollé Martijn E T , Jansen Eugène , Grune Tilman , Weber Daniela , Stuetz Wolfgang , Gonos Efstathios S , Schön Christiane , Bernhardt Jürgen , Grubeck-Loebenstein Beatrix , Sikora Ewa , Toussaint Olivier , Debacq-Chainiaux Florence , Franceschi Claudio , Capri Miriam , Hervonen Antti , Hurme Mikko , Slagboom Eline , Breusing Nicolle , Mocchegiani Eugenio , Malavolta Marco
Published: May 2021

The analysis of copper (Cu) and zinc (Zn) along with their major serum carriers, albumin (Alb) and ceruloplasmin (Cp), could provide information on the capacity of humans to maintain homeostasis of metals (metallostasis). However, their relationship with aging, sex, body mass index, as well as with nutritional and inflammatory markers was never investigated in a large-scale study. Here, we report results from the European large-scale cross-sectional study MARK-AGE in which Cu, Zn, Alb, Cp, as well as nutritional and inflammatory parameters were determined in 2424 age-stratified participants (35–75 years), including the general population (RASIG), nonagenarian offspring (GO), a well-studied genetic model of longevity, and spouses of GO (SGO). In RASIG, Cu to Zn ratio and Cp to Alb ratio were higher in women than in men. Both ratios increased with aging because Cu and Cp increased and Alb and Zn decreased. Cu, Zn, Alb, and Cp were found associated with several inflammatory as well as nutritional biomarkers. GO showed higher Zn levels and higher Zn to Alb ratio compared to RASIG, but we did not observe significant differences with SGO, likely as a consequence of the low sample size of SGO and the shared environment. Our results show that aging, sex, body mass index, and GO status are characterized by different levels of Cu, Zn, and their serum carrier proteins. These data and their relationship with inflammatory biomarkers support the concept that loss of metallostasis is a characteristic of inflammaging.
Long-Term Effectiveness of Oral Ferric Maltol vs Intravenous Ferric Carboxymaltose for the Treatment of Iron-Deficiency Anemia in Patients With Inflammatory Bowel Disease: A Randomized Controlled Noninferiority Trial
Authors: Howaldt Stefanie , Domènech Eugeni , Martinez Nicholas , Schmidt Carsten , Bokemeyer Bernd
Published: May 2021

Background

Iron-deficiency anemia is common in inflammatory bowel disease, requiring oral or intravenous iron replacement therapy. Treatment with standard oral irons is limited by poor absorption and gastrointestinal toxicity. Ferric maltol is an oral iron designed for improved absorption and tolerability.

Methods

In this open-label, phase 3b trial (EudraCT 2015-002496-26 and NCT02680756), adults with nonseverely active inflammatory bowel disease and iron-deficiency anemia (hemoglobin, 8.0-11.0/12.0 g/dL [women/men]; ferritin, <30 ng/mL/<100 ng/mL with transferrin saturation <20%) were randomized to oral ferric maltol 30 mg twice daily or intravenous ferric carboxymaltose given according to each center’s standard practice. The primary endpoint was a hemoglobin responder rate (≥2 g/dL increase or normalization) at week 12, with a 20% noninferiority limit in the intent-to-treat and per-protocol populations.

Results

For the intent-to-treat (ferric maltol, n = 125/ferric carboxymaltose, n = 125) and per-protocol (n = 78/88) analyses, week 12 responder rates were 67% and 68%, respectively, for ferric maltol vs 84% and 85%, respectively, for ferric carboxymaltose. As the confidence intervals crossed the noninferiority margin, the primary endpoint was not met. Mean hemoglobin increases at weeks 12, 24, and 52 were 2.5 vs 3.0 g/dL, 2.9 vs 2.8 g/dL, and 2.7 vs 2.8 g/dL with ferric maltol vs ferric carboxymaltose. Treatment-emergent adverse events occurred in 59% and 36% of patients, respectively, and resulted in treatment discontinuation in 10% and 3% of patients, respectively.

Conclusions

Ferric maltol achieved clinically relevant increases in hemoglobin but did not show noninferiority vs ferric carboxymaltose at week 12. Both treatments had comparable long-term effectiveness for hemoglobin and ferritin over 52 weeks and were well tolerated.
Fecal Diversion for Perianal Crohn Disease in the Era of Biologic Therapies: A Multicenter Study
Authors: McCurdy Jeffrey D , Reid Jacqueline , Yanofsky Russell , Sinnathamby Vigigah , Medawar Edgar , Williams Lara , Bessissow Talat , Rosenfeld Greg
Published: May 2021

Background

The natural history of perianal Crohn disease (PCD) after fecal diversion in the era of biologics is poorly understood. We assessed clinical and surgical outcomes after fecal diversion for medically refractory PCD and determined the impact of biologics.

Methods

We performed a retrospective, multicenter study from 1999 to 2020. Patients who underwent fecal diversion for refractory PCD were stratified by diversion type (ostomy with or without proctectomy). Times to clinical and surgical outcomes were estimated using Kaplan-Meier methods, and the association with biologics was assessed using multivariable Cox proportional hazards models.

Results

Eighty-two patients, from 3 academic institutions, underwent a total of 97 fecal diversions: 68 diversions without proctectomy and 29 diversions with proctectomy. Perianal healing occurred more commonly after diversion with proctectomy than after diversion without proctectomy (83% vs 53%; P = 0.021). Among the patients who had 68 diversions without proctectomy, with a median follow-up of 4.9 years post-diversion (interquartile range, 1.66-10.19), 37% had sustained healing, 31% underwent surgery to restore bowel continuity, and 22% underwent proctectomy. Ostomy-free survival occurred in 21% of patients. Biologics were independently associated with avoidance of proctectomy (hazard ratio, 0.32; 95% confidence interval, 0.11-0.98) and surgery to restore bowel continuity (hazard ratio, 3.10; 95% confidence interval, 1.02-9.37), but not fistula healing.

Conclusions

In this multicenter study, biologics were associated with bowel restoration and avoidance of proctectomy after fecal diversion without proctectomy for PCD; however, a minority of patients achieved sustained fistula healing after initial fecal diversion or after bowel restoration. These results highlight the refractory nature of PCD.
Russian News Media, Digital Media, Informational Learned Helplessness, and Belief in COVID-19 Misinformation
Authors: Nisbet Erik C , Kamenchuk Olga
Published: May 2021

The COVID-19 pandemic has been paired with a global misinformation “infodemic.” Citizens in authoritarian countries, where most media is state controlled, often do not have access to credible information sources to help combat misinformation. In fact, the news media in these countries may be the primary drivers of misinformation while digital media may be sources of more accurate information. We test how news and digital media in an authoritarian context are associated with endorsing misinformation while introducing the concept of informational learned helplessness as an additional factor driving inaccurate beliefs. We test our hypotheses employing data from a nationally representative telephone survey of the Russian public (N = 1600) and discuss the implications of our findings for Russian attitudes about COVID-19 vaccination.
Error estimate of a decoupled numerical scheme for the Cahn–Hilliard–Stokes–Darcy system
Authors: Chen Wenbin , Wang Shufen , Zhang Yichao , Han Daozhi , Wang Cheng , Wang Xiaoming
Published: May 2021

We analyze a fully discrete finite element numerical scheme for the Cahn–Hilliard–Stokes–Darcy system that models two-phase flows in coupled free flow and porous media. To avoid a well-known difficulty associated with the coupling between the Cahn–Hilliard equation and the fluid motion, we make use of the operator-splitting in the numerical scheme, so that these two solvers are decoupled, which in turn would greatly improve the computational efficiency. The unique solvability and the energy stability have been proved in Chen et al. (2017, Uniquely solvable and energy stable decoupled numerical schemes for the Cahn–Hilliard–Stokes–Darcy system for two-phase flows in karstic geometry. Numer. Math., 137, 229–255). In this work, we carry out a detailed convergence analysis and error estimate for the fully discrete finite element scheme, so that the optimal rate convergence order is established in the energy norm, i.e., in the $\ell ^{\infty } (0, T; H^1) \cap \ell ^2 (0, T; H^2)$ norm for the phase variables, as well as in the $\ell ^{\infty } (0, T; H^1) \cap \ell ^2 (0, T; H^2)$ norm for the velocity variable. Such an energy norm error estimate leads to a cancelation of a nonlinear error term associated with the convection part, which turns out to be a key step to pass through the analysis. In addition, a discrete $\ell ^2 (0;T; H^3)$ bound of the numerical solution for the phase variables plays an important role in the error estimate, which is accomplished via a discrete version of Gagliardo–Nirenberg inequality in the finite element setting.
MicroRNAs: immune modulators in cancer immunotherapy
Authors: Xing Yun , Wang Zhiqiang , Lu Zhou , Xia Jie , Xie Zhangjuan , Jiao Mengxia , Liu Ronghua , Chu Yiwei
Published: May 2021

MicroRNA (miRNA) is a class of endogenous small non-coding RNA of 18–25 nucleotides and plays regulatory roles in both physiological and pathological processes. Emerging evidence support that miRNAs function as immune modulators in tumors. MiRNAs as tumor suppressors or oncogenes are also found to be able to modulate anti-tumor immunity or link the crosstalk between tumor cells and immune cells surrounding. Based on the specific regulating function, miRNAs can be used as predictive, prognostic biomarkers, and therapeutic targets in immunotherapy. Here, we review new findings about the role of miRNAs in modulating immune responses, as well as discuss mechanisms underlying their dysregulation, and their clinical potentials as indicators of tumor prognosis or to sensitize cancer immunotherapy.
Introduction: Electronic Medicine in Immunology Special Issue Part 1
Authors: Tracey Kevin J , Chavan Sangeeta , Murakami Masaaki
Published: May 2021

Electronic Medicine in Immunology.
Targeted ordering of investigations reduces costs of treatment for surgical inpatients
Authors: Adhikari Ashim Nath , Beck Matthew Dylan , Wykes James Justin , Ashford Bruce Graham
Published: May 2021

Background

Laboratory testing forms an important part of diagnostic investigation in modern medicine; however, the overuse of ‘routine blood tests’ can result in significant potential harm and financial cost to the patient and the healthcare system. In 2018, a new protocol targeting the ordering of investigations was implemented within the General Surgical Teams of Wollongong Hospital in New South Wales, an Australian tertiary referral hospital, to reduce the number of ‘routine blood tests’ as a quality improvement initiative.

Objective

To identify whether there was a reduction in the number of ‘routine blood tests’ and associated costs following implementation of the new protocol.

Methods

The protocol involved regular review of the laboratory investigations being ordered for the following day with a senior team member. The medical records of all patients admitted under the general surgery service at Wollongong Hospital were retrospectively reviewed over two 10-week periods in 2017 and 2018 (control and study, respectively). The casemix was categorized into Minor, Intermediate, Major or Unscored, depending on case complexity coding.

Results

A total of 838 patients were identified during the control period (2017) and 805 patients were identified during the study period (2018). Ten thousand and thirty tests were included in the control period, compared to 8610 over the study period, resulting in a 16% (or greater) reduction in ‘routine blood tests’ per patient, per day of admission and a 6% reduction in costs in the study group (P < 0.001).

Conclusion

Targeted ordering of investigations with personalized education and feedback to junior staff during review of clinical status of each patient as a part of normal workflow can reduce inappropriate ordering of ‘routine blood tests’ and associated costs to the patient and the healthcare system.
Beyond Methodological Axioms
Authors: Blum Jason
Published: May 2021

Since nearly the field’s birth, religious studies has been plagued by the question of how to deal with claims concerning the supernatural. Strategies for addressing the issue typically take the form of one or another methodological axiom, typically either methodological atheism or methodological agnosticism. Although each axiom answers legitimate concerns about how to address supernatural claims, each is also vulnerable to substantial objections. I therefore argue that these approaches to solving religious studies’ central methodological dilemma is flawed. Eschewing the search for methodological axioms, I advocate that we return to a basic standard of academic work: public evidence. When paired with a distinction between the analytical tasks of interpretation and explanation, this approach resolves the central problems that have vexed both methodological atheism and methodological agnosticism, avoiding the theoretical pitfalls generated by each while providing the necessary guidance and discipline for research on religion.
The use of continuous electronic prescribing data to infer trends in antimicrobial consumption and estimate the impact of stewardship interventions in hospitalized children
Authors: Channon-Wells S. , Kwok M. , Booth J. , Bamford A. , Konstanty P. , Hatcher J. , Dixon G. , Diggle P. J. , Standing J. F. , Irwin A. D.
Published: May 2021

Background

Understanding antimicrobial consumption is essential to mitigate the development of antimicrobial resistance, yet robust data in children are sparse and methodologically limited. Electronic prescribing systems provide an important opportunity to analyse and report antimicrobial consumption in detail.

Objectives

We investigated the value of electronic prescribing data from a tertiary children’s hospital to report temporal trends in antimicrobial consumption in hospitalized children and compare commonly used metrics of antimicrobial consumption.

Methods

Daily measures of antimicrobial consumption [days of therapy (DOT) and DDDs] were derived from the electronic prescribing system between 2010 and 2018. Autoregressive moving-average models were used to infer trends and the estimates were compared with simulated point prevalence surveys (PPSs).

Results

More than 1.3 million antimicrobial administrations were analysed. There was significant daily and seasonal variation in overall consumption, which reduced annually by 1.77% (95% CI 0.50% to 3.02%). Relative consumption of meropenem decreased by 6.6% annually (95% CI −3.5% to 15.8%) following the expansion of the hospital antimicrobial stewardship programme. DOT and DDDs exhibited similar trends for most antimicrobials, though inconsistencies were observed where changes to dosage guidelines altered consumption calculation by DDDs, but not DOT. PPS simulations resulted in estimates of change over time, which converged on the model estimates, but with much less precision.

Conclusions

Electronic prescribing systems offer significant opportunities to better understand and report antimicrobial consumption in children. This approach to modelling administration data overcomes the limitations of using interval data and dispensary data. It provides substantially more detailed inferences on prescribing patterns and the potential impact of stewardship interventions.
Shutting the gate before the horse has bolted: is it time for a conversation about SARS-CoV-2 and antiviral drug resistance?
Authors: Hiscox Julian A. , Khoo Saye H. , Stewart James P. , Owen Andrew
Published: May 2021

This article provides a brief overview of drug resistance to antiviral therapy as well as known and emergent variability in key SARS-CoV-2 viral sequences. The purpose is to stimulate deliberation about the need to consider drug resistance prior to widespread roll-out of antivirals for SARS-CoV-2. Many existing candidate agents have mechanisms of action involving drug targets likely to be critical for future drug development. Resistance emerged quickly with monotherapies deployed for other pulmonary viruses such as influenza virus, and in HIV mutations in key drug targets compromised efficacy of multiple drugs within a class. The potential for drug resistance in SARS-CoV-2 has not yet been rigorously debated or assessed, and we call for more academic and industry research on this potentially important future threat prior to widespread roll-out of monotherapies for COVID-19 treatment and prevention.
Accessibility evaluation of COVID-19 vaccine registration websites across the United States
Authors: Alismail Sarah , Chipidza Wallace
Published: May 2021

This exploratory study investigated the web accessibility of 54 official COVID-19 vaccine registration websites in the US and their concordance with the WCAG 2.0 and 2.1 guidelines. We employed AChecker, WAVE, and SortSite web accessibility evaluation tools to conduct automated analyses of these websites. The results showed suboptimal compliance with WCAG 2.0 and 2.1 guidelines, as determined using the AChecker, WAVE, and SortSite tools. These shortcomings in compliance may pose difficulties to users with disabilities as they access information on the websites. Based on our findings, we offered recommendations for states and other authorities to improve the accessibility of their websites to ensure that users with disabilities can independently schedule vaccination appointments.
Tooth bending strength of gears with a progressive curved path of contact
Authors: Zorko Damijan , Duhovnik Jože , Tavčar Jože
Published: May 2021

The article presents a comprehensive study on the tooth bending strength of spur gears with a progressive curved path of contact, or so-called S-gears. Systematic gear meshing simulations were conducted to study the effects of S-gear geometry parameters on tooth bending strength. Different S-gear geometries were analysed in a systematically organized manner, and a comparison was made against a standard 20° pressure angle involute shape. Furthermore, different material combinations, e.g. polymer/polymer, steel/polymer, and steel/steel, of both drive and driven gear were analysed within a meaningful range of loads. The gear profile shape, material combination of the drive and the driven gear, and the transmitted load were found as the main parameters affecting gear tooth bending stress. Complex, non-linear relations between the recognized effects and the corresponding root stress were observed. Based on the numerical results, a shape factor, which considers the above-mentioned effects, was introduced, and a model for root strength control of S-gears was proposed and verified employing the finite element method (FEM).
Underground heterosis for yield improvement in melon
Authors: Dafna Asaf , Halperin Ilan , Oren Elad , Isaacson Tal , Tzuri Galil , Meir Ayala , Schaffer Arthur A , Burger Joseph , Tadmor Yaakov , Buckler Edward S , Gur Amit
Published: May 2021

Heterosis, the superiority of hybrids over their parents, is a major genetic force associated with plant fitness and crop yield enhancement. We investigated root-mediated yield heterosis in melons (Cucumis melo) by characterizing a common variety grafted onto 190 hybrid rootstocks, resulting from crossing 20 diverse inbreds in a diallel-mating scheme. Hybrid rootstocks improved yield by more than 40% compared with their parents, and the best hybrid yield outperformed the reference commercial variety by 65% under both optimal and minimal irrigation treatments. To characterize the genetics of underground heterosis we conducted whole genome re-sequencing of the 20 founder lines, and showed that parental genetic distance was no predictor for the level of heterosis. Through inference of the 190 hybrid genotypes from their parental genomes, followed by genome-wide association analysis, we mapped multiple quantitative trait loci for root-mediated yield. Yield enhancement of the four best-performing hybrid rootstocks was validated in multiple experiments with four different scion varieties. Our grafting approach is complementary to the common roots genetic approach that focuses mainly on variation in root system architecture, and is a step towards discovery of candidate genes involved in root function and yield enhancement.
Distribution and genotypic analysis of Enterocytozoon bieneusi from wild boars in Korea
Authors: Lee Haeseung , Seo Min-Goo , Lee Seung-Hun , Oem Jae-Ku , Kim Seon-Hee , Jeong Hyesung , Kim Yongkwan , Jheong Weon-Hwa , Kwon Oh-Deog , Kwak Dongmi
Published: May 2021

Enterocytozoon bieneusi, an important microsporidian fungus, causes chronic diarrhea in humans and animals worldwide. Out of the 502 fecal samples from wild boars, 13 were positive for the E. bieneusi internal transcribed spacer region, with a prevalence of 2.6%. Six E. bieneusi genotypes, D, EbpC, and four novel KWB1–KWB4, were identified with zoonotic potential. Genotypes D (subgroup 1a) and EbpC (subgroup 1d) were first reported in Korean swine and Korea, respectively; KWB1–KWB4 (subgroup 1e) were most prevalent in this study. Because zoonotic genotypes have been identified, E. bieneusi transmission through wild boars must be closely monitored for proper prevention and treatment, despite their low prevalence.

Lay Summary

Enterocytozoon bieneusi is an important microsporidian fungus. Its sequences from wild boars were identified with zoonotic potential. Genotypes D and EbpC were first reported in Korean swine and Korea, respectively. E. bieneusi should be closely monitored to properly prevent and treat animals.
Observable spectral and angular distributions of γ-rays from extragalactic ultrahigh energy cosmic ray accelerators: the case of extreme TeV blazars
Authors: Khalikov Emil V , Dzhatdoev Timur A
Published: May 2021

Ultrahigh energy protons and nuclei from extragalactic cosmic ray sources initiate intergalactic electromagnetic cascades, resulting in observable fluxes of γ-rays in the GeV–TeV energy domain. The total spectrum of such cascade γ-rays of hadronic nature is significantly harder than the one usually expected from blazars. The spectra of some sources known as ‘extreme TeV blazars’ could be well-described by this ‘intergalactic hadronic cascade model’ (IHCM). We calculate the shape of the observable point-like spectrum, as well as the observable angular distibution of γ-rays, for the first time taking into account the effect of primary proton deflection in filaments and galaxy clusters of the extragalactic magnetic field assuming the model of Dolag et al. (2005). We present estimates of the width of the observable γ-ray angular distribution derived from simple geometrical considerations. We also employ a hybrid code to compute the observable spectral and angular distributions of γ-rays. The observable point-like spectrum at multi-TeV energies is much softer than the one averaged over all values of the observable angle. The presence of a high-energy cutoff in the observable spectra of extreme TeV blazars in the framework of the IHCM could significantly facilitate future searches of new physics processes that enhance the apparent γ-ray transparency of the Universe (for instance, γ → ALP oscillations). The width of the observable angular distribution is greater than or comparable to the extent of the point spread function of next-generation γ-ray telescopes.
TLDR: time lag/delay reconstructor
Authors: Anderson M D , Baron F , Bentz M C
Published: May 2021

We present the time lag/delay reconstructor (TLDR), an algorithm for reconstructing velocity delay maps in the maximum a posteriori framework for reverberation mapping. Reverberation mapping is a tomographical method for studying the kinematics and geometry of the broad-line region of active galactic nuclei at high spatial resolution. Leveraging modern image reconstruction techniques, including total variation and compressed sensing, TLDR applies multiple regularization schemes to reconstruct velocity delay maps using the alternating direction method of multipliers. Along with the detailed description of the TLDR algorithm we present test reconstructions from TLDR applied to synthetic reverberation mapping spectra as well as a preliminary reconstruction of the Hβ feature of Arp 151 from the 2008 Lick Active Galactic Nuclei Monitoring Project.
Morphological classification of compact and extended radio galaxies using convolutional neural networks and data augmentation techniques
Authors: Maslej-Krešňáková Viera , El Bouchefry Khadija , Butka Peter
Published: May 2021

Machine-learning techniques have been increasingly used in astronomical applications and have proven to successfully classify objects in image data with high accuracy. The current work uses archival data from the Faint Images of the Radio Sky at Twenty Centimeters (FIRST) to classify radio galaxies into four classes: Fanaroff–Riley Class I (FRI), Fanaroff–Riley Class II (FRII), Bent-Tailed (BENT), and Compact (COMPT). The model presented in this work is based on Convolutional Neural Networks (CNNs). The proposed architecture comprises three parallel blocks of convolutional layers combined and processed for final classification by two feed-forward layers. Our model classified selected classes of radio galaxy sources on an independent testing subset with an average of 96 per cent for precision, recall, and F1 score. The best selected augmentation techniques were rotations, horizontal or vertical flips, and increase of brightness. Shifts, zoom, and decrease of brightness worsened the performance of the model. The current results show that model developed in this work is able to identify different morphological classes of radio galaxies with a high efficiency and performance.
Local Volume Late-Type Galaxies with an Extreme Ratio of Hα-to-FUV Star-Formation Rates
Authors: Karachentsev I D , Kaisina E I , Kaisin S S
Published: May 2021

Using a currently most representative sample of 477 late-type galaxies within 11 Mpc of the Milky Way with measured star-formation rates (SFRs) from the far ultraviolet (FUV) and Hα emission line fluxes, we select galaxies with the extreme ratios: SFR(Hα)/SFR(FUV) > 2 and SFR(Hα)/SFR(FUV) < 1/20. Each subsample amounts to ∼5% of the total number and consists of dwarf galaxies with the stellar masses M*/M⊙ = (5.5 − 9.5) dex. In spite of a huge difference in their SFR(Hα) activity on a scale of ∼10  Myr, the temporarily “excited” and temporarily “quiescent” galaxies follow one and the same relation between SFR(FUV) and M* on a scale of ∼100 Myr. Their average specific star-formation rate log [SFR(FUV)/M*] = −10.1 ± 0.1 (yr−1) coinsides with the Hubble parameter log (H0) = −10.14 (yr−1). On a scale of t ∼ 10 Myr, variations of SFR have a moderate flash amplitude of less than 1 order above the main-sequence and a fading amplitude to 2 orders below the average level. In general, both temporarily excited and temporarily quiescent galaxies have almost similar gas fractions as normal main-sequence galaxies, being able to maintain the current rate of star-formation on another Hubble time scale. Ranging the galaxies according to the density contrast produced by the nearest massive neighbor exhibits only a low average excess of SFR caused by tidal interactions.
Modeling of two CoRoT solar analogues constrained by seismic and spectroscopic analysis
Authors: Castro M , Baudin F , Benomar O , Samadi R , Morel T , Barban C , do Nascimento J D , Lebreton Y , Boumier P , Marques J P , da Costa J S
Published: May 2021

Solar analogues are important stars to study for understanding the properties of the Sun. Combined with seismic and spectroscopic analysis, evolutionary modelling becomes a powerful method to characterize stellar intrinsic parameters, such as mass, radius, metallicity and age. However, these characteristics, relevant for other aspects of astrophysics or exoplanetary system physics, for example, are difficult to obtain with high precision and/or accuracy. The goal of this study is to characterize the two solar analogues, HD 42618 and HD 43587, observed by CoRoT. In particular, we aim to infer their precise mass, radius and age, using evolutionary modelling constrained by spectroscopic, photometric and seismic analysis. These stars show evidence of being older than the Sun but with a relatively large lithium abundance. We present the seismic analysis of HD 42618, and the modelling of the two solar analogues, HD 42618 and HD 43587 using the cestam stellar evolution code. Models were computed to reproduce the spectroscopic (effective temperature and metallicity) and seismic (mode frequency) data, and the luminosity of the stars, based on Gaia parallaxes. We infer very similar values of mass and radius for both stars compared with the literature, within the uncertainties, and we reproduce correctly the seismic constraints. The modelling shows that HD 42618 is slightly less massive and older than the Sun, and that HD 43587 is more massive and older than the Sun, in agreement with previous results. The use of chemical clocks improves the reliability of our age estimates.
The origin of the orbital parameter distribution of merging haloes
Authors: Benson Andrew J
Published: May 2021

We describe a simple model that explains the qualitative and (approximate) quantitative features of the distribution of orbital velocities of merging pairs of dark matter haloes. Our model considers a primary dark matter halo as a perturber in a background of secondary haloes with velocities described by linear theory. By evaluating the ensemble of secondary haloes on orbits within the perturbing halo’s ‘loss cone’ we derive the distribution of orbital parameters of these captured haloes. This model is able provide qualitative explanations for the features of this distribution as measured from N-body simulations, and is in approximate quantitative agreement with those measurements. As the velocity dispersion of the background haloes is larger on smaller scales our model predicts an overall increase in the characteristic velocities of merging haloes, relative to the virial velocities of those haloes, in lower mass systems. Our model also provides a simple explanation for the measured independence of the orbital velocity distribution function on redshift when considered at fixed peak height. By connecting the orbital parameter distribution to the underlying power spectrum our model also allows for estimates to be made of the effect of modifying that power spectrum, for example by including a truncation at large wavenumber. For plausible warm dark matter models, we find that this truncation has only a small effect on the predicted distributions.
Human MettL3-MettL14 RNA adenine methyltransferase complex is active on double-stranded DNA containing lesions
Authors: Yu Dan , Horton John R , Yang Jie , Hajian Taraneh , Vedadi Masoud , Sagum Cari A , Bedford Mark T , Blumenthal Robert M , Zhang Xing , Cheng Xiaodong
Published: May 2021

MettL3-MettL14 methyltransferase complex has been studied widely for its role in RNA adenine methylation. This complex is also recruited to UV- and X-ray exposed DNA damaged sites, and its methyltransfer activity is required for subsequent DNA repair, though in theory this could result from RNA methylation of short transcripts made at the site of damage. We report here that MettL3-MettL14 is active in vitro on double-stranded DNA containing a cyclopyrimidine dimer – a major lesion of UV radiation-induced products – or an abasic site or mismatches. Furthermore, N6-methyladenine (N6mA) decreases misincorporation of 8-oxo-guanine (8-oxoG) opposite to N6mA by repair DNA polymerases. When 8-oxoG is nevertheless incorporated opposite N6mA, the methylation inhibits N6mA excision from the template (correct) strand by the adenine DNA glycosylase (MYH), implying that the methylation decreases inappropriate misrepair. Finally, we observed that the N6mA reader domain of YTHDC1, which is also recruited to sites of DNA damage, binds N6mA that is located across from a single-base gap between two canonical DNA helices. This YTHDC1 complex with a gapped duplex is structurally similar to DNA complexes with FEN1 and GEN1 – two members of the nuclease family that act in nucleotide excision repair, mismatch repair and homologous recombination, and which incise distinct non-B DNA structures. Together, the parts of our study provide a plausible mechanism for N6mA writer and reader proteins acting directly on lesion-containing DNA, and suggest in vivo experiments to test the mechanisms involving methylation of adenine.
Skull Base Tumors: Neuropathology and Clinical Implications
Authors: Bi Wenya Linda , Santagata Sandro
Published: May 2021

Tumors that arise in and around the skull base comprise a wide range of common and rare entities. Recent studies have advanced our understanding of their pathogenesis, which in some cases, have significantly influenced clinical practice. The genotype of meningiomas is strongly associated with their phenotype, including histologic subtype and tumor location, and clinical outcome. A single molecular alteration, NAB2-STAT6 fusion, has redefined the category of solitary fibrous tumors to include the previous entity hemangiopericytomas. Schwannomas, both sporadic and familial, are characterized by near ubiquitous alterations inNF2, with additional mutations inSMARCB1orLZTR1in schwannomatosis. In pituitary adenohypophyseal tumors, cell lineage transcription factors such as SF-1, T-PIT, and PIT-1 are now essential for classification, providing a more rigorous taxonomy for tumors that were previously considered null cell adenomas. The pituicyte lineage transcription factor TTF-1 defines neurohypophyseal tumors, which may represent a single nosological entity with a spectrum of morphologic manifestations (ie, granular cell tumor, pituicytoma, and spindle cell oncocytoma). Likewise, the notochord cell lineage transcription factor brachyury defines chordoma, discriminating them from chondrosarcomas. The identification of nonoverlapping genetic drivers of adamantinomatous craniopharyngiomas and papillary craniopharyngiomas indicates that these are distinct tumor entities and has led to successful targeted treatment of papillary craniopharyngiomas using BRAF and/or mitogen–activated protein kinase inhibitors. Similarly, dramatic therapeutic responses have been achieved in patients with Langerhans cell histiocytosis, both withBRAF-mutant andBRAF-wildtype tumors. Familiarity with the pathology of skull base tumors, their natural history, and molecular features is essential for optimizing patient care.
Borrowing in Music
Authors: Sallis Friedemann
Published: May 2021

This text examines the idea and practice of musical borrowing in the composition of art music in two distinct historical contexts: the age of music conceived as oration (ca. 1600–1800) and the age of the strong work concept (ca. 1800 to the present). It shows that the idea of musical borrowing is an evolving, historical concept that needs to be examined contextually in order to understand what it meant in the period within which the music in question was composed, as well as for the specific composer. The text also briefly examines related topics: authorship, plagiarism, imitation vs. emulation, music conceived as oration, and the strong work concept.
People With Hematological Malignancies Treated With Bone Marrow Transplantation Have Improved Function, Quality of Life, and Fatigue Following Exercise Intervention: A Systematic Review and Meta-Analysis
Authors: Abo Shaza , Denehy Linda , Ritchie David , Lin Kuan-Yin , Edbrooke Lara , McDonald Cassie , Granger Catherine L
Published: May 2021

Objective

For people with hematological malignancies treated with bone marrow transplantation (BMT), this systematic review aimed to identify, evaluate, and synthesize the evidence examining the effect of exercise training on the outcomes of exercise capacity, health-related quality of life (HRQoL), and hospital length of stay (LOS) and to identify any difference in the effect on people treated with allogeneic versus autologous transplantation.

Methods

Five electronic databases were systematically searched from inception to December 5, 2020. Prospective studies with a comparator group, with or without randomization, were included if they investigated the effects of an exercise intervention compared with usual care or another intervention in adults who had a hematological malignancy and were undergoing BMT. Primary outcomes of interest were functional exercise capacity and HRQoL; secondary outcomes included strength, fatigue, hospital LOS, and feasibility. Only randomized controlled trials were included in the meta-analyses. Risk of bias was evaluated using the Physiotherapy Evidence Database or Newcastle-Ottawa Scale; the quality of evidence for meta-analyses was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

Results

Twenty-four randomized controlled trials and 3 prospective nonrandomized experimental trials were included (n = 2432). There was moderate-quality evidence that exercise improves functional exercise capacity (mean difference [MD] = 29 m; 95% CI = 12.59 to 45.4), global HRQoL (MD = 3.38 points; 95% CI = 0.37 to 6.39), and fatigue (MD = 2.52 points; 95% CI = 0.42 to 4.63) and low-quality evidence for reduced hospital LOS (MD = 2.07 days; 95% CI = 0.43 to 3.72). These effects were more pronounced in recipients of allogeneic transplantation. No serious adverse events were associated directly with exercise in the included studies.

Conclusion

Exercise is safe and improves outcomes, including functional exercise capacity, HRQoL, and hospital LOS in adults undergoing BMT.

Impact

The results of this systematic review support the implementation of exercise programs in adults undergoing BMT, particularly recipients of allogeneic transplantation.
The role of TNFRSF11B in development of osteoarthritic cartilage
Authors: Rodríguez Ruiz Alejandro , Tuerlings Margo , Das Ankita , Coutinho de Almeida Rodrigo , Suchiman H Eka D , Nelissen Rob G H H , Ramos Yolande F M , Meulenbelt Ingrid
Published: May 2021

Objectives

OA is a complex genetic disease with different risk factors contributing to its development. One of the genes, TNFRSF11B, previously identified with gain-of-function mutation in a family with early-onset OA with chondrocalcinosis, is among the highest upregulated genes in lesioned OA cartilage (RAAK-study). Here, we determined the role of TNFRSF11B overexpression in development of OA.

Methods

Human primary articular chondrocytes (9 donors RAAK study) were transduced using lentiviral particles with or without TNFRSF11B. Cells were cultured for 1 week in a 3 D in-vitro chondrogenic model. TNFRSF11B overexpression was confirmed by RT-qPCR, immunohistochemistry and ELISA. Effects of TNFRSF11B overexpression on cartilage matrix deposition, matrix mineralization, and genes highly correlated to TNFRSF11B in RNA-sequencing dataset (r >0.75) were determined by RT-qPCR. Additionally, glycosaminoglycans and collagen deposition were visualized with Alcian blue staining and immunohistochemistry (COL1 and COL2).

Results

Overexpression of TNFRSF11B resulted in strong upregulation of MMP13, COL2A1 and COL1A1. Likewise, mineralization and osteoblast characteristic markers RUNX2, ASPN and OGN showed a consistent increase. Among 30 genes highly correlated to TNFRSF11B, expression of only eight changed significantly, with BMP6 showing the highest increase (9-fold) while expression of RANK and RANKL remained unchanged indicating previously unknown downstream pathways of TNFRSF11B in cartilage.

Conclusion

Results of our 3D in vitro chondrogenesis model indicate that upregulation of TNFRSF11B in lesioned OA cartilage may act as a direct driving factor for chondrocyte to osteoblast transition observed in OA pathophysiology. This transition does not appear to act via the OPG/RANK/RANKL triad common in bone remodeling.
Pulmonary fibrosis in relation to genetic loci in an inception cohort of patients with early rheumatoid arthritis from northern Sweden
Authors: Jönsson Elias , Ljung Lotta , Norrman Eva , Freyhult Eva , Ärlestig Lisbeth , Dahlqvist Johanna , Rantapää-Dahlqvist Solbritt
Published: May 2021

Objectives

Pulmonary manifestations in RA are common comorbidities. Interstitial lung disease (ILD), both idiopathic and in RA, has been associated with several genetic variants. We assessed pulmonary fibrosis (PF) in an inception cohort of RA patients in relation to genetic variants and disease-related factors.

Methods

A total of 1466 early RA patients were consecutively included and followed prospectively from the index date until death or 31 December 2016. Clinical and laboratory data and treatment were continuously registered according to the Swedish Rheumatology Quality Register. DNA was available from 1184 patients and 571 151 genome-wide single-nucleotide polymorphisms (SNPs) were analysed. Thirteen identified genetic variants were extracted. At follow-up, the patients answered a questionnaire regarding disease progression and lung involvement that was validated by reviewing medical records and analysing radiological examinations.

Results

The prevalence of PF was 5.6% and the annualized incidence rate was 5.0/1000 (95% CI 3.80, 6.54). Four SNPs were associated with PF in RA: rs35705950 [MUC5B; OR 2.5 (95% CI 1.5, 4.0), adjusted P-value = 0.00016, q-value = 0.0021]; rs111521887 [TOLLIP; OR 1.9 (95% CI 1.3, 2.8), adjusted P-value = 0.0014, q-value = 0.0092]; rs2609255 [FAM13A; OR 1.7 (95% CI 1.1, 2.5), adjusted P-value = 0.013, q-value = 0.055] and rs2736100 [TERT; OR 1.5 (95% CI 1.0, 2.2), adjusted P-value = 0.046, q-value = 0.15]. Older age and RF positivity were associated with increased risk, while MTX treatment was associated with a lower risk of PF.

Conclusions

Development of PF in an inception cohort of RA patients was associated with 4 of 12 ILD risk genes. RA-related factors except for age at diagnosis and RF positivity were of limited importance in PF development.
Evaluating the Interrater Agreement and Acceptability of a New Reference Tool for Assessing Respiratory Rate in Children under Five with Cough and/or Difficulty Breathing
Authors: Stratil Ann-Sophie , Ward Charlotte , Habte Tedila , Maurel Alice , Antson Max , Naydenova Elina , Baker Kevin
Published: May 2021

Background

Manual assessment of respiratory rate (RR) in children is unreliable, but remains the main method to diagnose pneumonia in low-resource settings. While automated RR counters offer a potential solution, there is currently no gold standard to validate these diagnostic aids. A video-based reference tool is proposed that allows users to annotate breaths and distortions including movement periods, allowing the exclusion of distortions from the computation of RR measures similar to how new diagnostic aids account for distortions automatically. This study evaluated the interrater agreement and acceptability of the new reference tool.

Methods

Annotations were based on previously recorded reference videos of children under five years old with cough and/or difficulty breathing (n = 50). Five randomly selected medical experts from a panel of ten annotated each video. RR measures (breaths per minute, bpm) were computed as the number of annotated certain breaths divided by the length of calm periods after removing annotated distorted periods.

Results

Reviewers showed good interrater agreement on continuous RR {standard error of measurement (SEM) [4.8 (95%CI 4.4–5.3)]} and substantial agreement on classification of fast breathing (Fleiss kappa, κ 0.71). Agreement was lowest in the youngest age group [< 2 months: SEM 6.2 (5.4–7.4) bpm, κ 0.48; 2–11 months: 4.7 (4.0–5.8) bpm, κ 0.84; 12–59 months: 2.6 (2.2–3.1) bpm, κ 0.8]. Reviewers found the functionalities of the tool helpful in annotating breaths, but remained uncertain about the validity of their annotations.

Conclusions

Before the new tool can be considered a reference standard for RR assessments, interrater agreement in children younger than 2 months must be improved.