bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the Quality of Mobile Health Applications for Burns Being Adequately Assessed?
Authors: Patel Benjamin , Edwards Tomos , Schrire Timothy , Barnard Katie , Sen Sankhya
Published: October 2021

High-quality mobile health applications (mHealth apps) have the potential to enhance the prevention, diagnosis, and treatment of burns. The primary aim of this study was to evaluate whether the quality of mHealth apps for burns care is being adequately assessed. The secondary aim was to determine whether these apps meet regulatory standards in the United Kingdom. We searched AMED, BNI, CINAHL, Cochrane Library, Embase, Emcare, Medline, and PsychInfo to identify studies assessing mHealth app quality for burns. The PRISMA reporting guideline was adhered to. Two independent reviewers screened abstracts to identify relevant studies. The quality of identified studies was assessed according to the framework proposed by Nouri et al, including design, information/content, usability, functionality, ethical issues, security/privacy, and user-perceived value. Of the 28 included studies, none assessed all seven domains of quality. Design was assessed in 4 of 28 studies; information/content in 26 of 28 studies; usability in 12 of 28 studies; functionality in 10 of 28 studies; ethical issues were never assessed in any studies; security/privacy was not assessed; subjective assessment was made in 9 of 28 studies. About 17 of 28 studies included apps that met the definition of “medical device” according to Medicines and Healthcare products Regulatory Agency guidance, yet only one app was appropriately certified with the UK Conformity Assessed mark. The quality of mHealth apps for burns is not being adequately assessed. The majority of apps should be considered medical devices according to UK standards, yet only one was appropriately certified. Regulatory bodies should support mHealth app developers, so as to improve quality control while simultaneously fostering innovation.
Evaluation of Voriconazole and Posaconazole Dosing in Patients With Thermal Burn Injuries
Authors: Musick Kaitlin L , Jones Savannah L , Norris Ashlyn M , Hochstetler Lauren J , Williams Felicia N , McKinzie Brian P
Published: October 2021

Fungal infections are a recognized cause of increased morbidity and mortality in thermal burn patients. Adequate treatment regimens remain a challenge due to unpredictable pharmacokinetic/pharmacodynamic changes caused by a hypermetabolic state and individual patient factors. A retrospective evaluation of adult thermal burn patients from April 2014 to April 2020 was conducted to assess voriconazole and posaconazole antifungal dosing regimens. The primary outcome was the incidence of attaining a therapeutic steady-state trough level on the patient’s initial voriconazole or posaconazole regimen. Of the 33 patients analyzed, 26 (78.8%) patients achieved a therapeutic level during azole therapy. However, only 11 (33.3%) patients achieved a therapeutic level on their first azole regimen. The median time to therapeutic level was 8.0 + 21.8 days from the start of azole therapy. Optimal dosing strategies for azole therapy in patients with thermal burns remain undefined. Further assessment is needed to delineate patient-specific factors that can contribute to subtherapeutic azole levels in thermal burn patients and the overall clinical impact of population-specific dosing regimens.
Finite element compatible matrix interpolation for parametric model order reduction of electrothermal microgripper
Authors: Roy Ananya , Nabi M , Rahman Najmur
Published: October 2021

Electrothermal microgrippers are nowadays commonly used as they are small in size, low cost, and easy to manufacture. The microgripper is modeled through partial differential equations, which are discretized by the finite element method (FEM), producing a large number of ordinary differential equations. This makes model order reduction (MOR) a fruitful proposition. Moreover, in design applications, the microgripper needs to be simulated repeatedly, with varying values of certain parameters. When these parameters are geometric in nature, matrix interpolation-based parametric model order reduction (pMOR) is the most suited method. However, in finite element applications, the sizes of the FE matrices change for varying geometrical parameters. The conventional matrix interpolation-based pMOR method becomes inapplicable for such cases, which remains a major drawback of this otherwise powerful algorithm. In this paper, this major hurdle is removed, and a new finite element compatible matrix interpolation (FEMI) for pMOR is proposed. A three-dimensional electrothermal microgripper is modeled parametrically using this proposed methodology. The effectiveness of the proposed method is shown through simulation results.
Dietary niches of creodonts and carnivorans of the late Eocene Cypress Hills Formation
Authors: Christison Brigid E , Gaidies Fred , Pineda-Munoz Silvia , Evans Alistair R , Gilbert Marisa A , Fraser Danielle
Published: October 2021

Modern North American carnivorous mammal assemblages consist of species from a single clade: the Carnivora. Carnivorans once coexisted with members of other meat-eating clades, including the creodonts (Hyaenodontida and Oxyaenida). Creodonts, however, went extinct in North America during the late Eocene and early Oligocene, potentially due to niche overlap and resource competition with contemporary carnivorans. In this study, we employ a community ecology approach to understand whether the dietary niches of coexisting creodonts and carnivorans overlapped during the late Eocene (Chadronian North American Land Mammal Age), a time when creodonts were dwindling and carnivorans were diversifying. We quantify niche overlap based on inferences of diet from carnassial tooth shape estimated using Orientation Patch Count, Dirichlet’s Normal Surface Energy, and linear dental measurements as well as from body mass for all species in the Calf Creek Local Fauna of Cypress Hills, Saskatchewan (Treaty 4 land). Although creodonts and carnivorans shared characteristics of their carnassial tooth shape, suggesting similar chewing mechanics and feeding habits, we find that marked differences in body size likely facilitated niche partitioning, at least between the largest creodonts and carnivorans. Calculations of prey focus masses and prey mass spectra indicate that only the smallest creodont may have experienced significant competition for prey with the coeval carnivorans. We suggest that the ultimate extinction of creodonts from North America during the late Eocene and Oligocene was unlikely to have been driven by factors related to niche overlap with carnivorans.
Effect of native and non-native snake scents on foraging activity of native rodents in Florida
Authors: Beckmann Sean , Avila Paloma , Farrell Terence
Published: October 2021

Rodents use direct and/or indirect cues of predators to assess predation risk. The responses to these cues are well studied with regard to mammalian predators, but less understood with regard to reptilian predators. These responses are of particular importance in tropical and subtropical regions where reptile diversity is high and the likelihood of establishment of invasive reptilian predators also is high. We hypothesized that rodents would respond to direct scent cues of snake predators and that rodents would show greater aversion to scents of native snake predators than non-native snake predators. To assess this, scents of three snake species, two native and one non-native, and a non-snake control odor were distributed in Sherman live traps using a randomized block design. A total of 69 rodents representing four species were captured. Responses varied by species reinforcing that some species utilize indirect cues to assess predation risk, whereas others use direct cues. Moreover, one species (Neotoma floridana) showed a preference for non-native Python scent, indicating a lack of the appropriate anti-predator behavior, suggesting that some native rodents are more at risk of attack from invasive snakes than other native rodents.
“There’s Nothing Wrong With You”: Pain-Related Stigma in Adolescents With Chronic Pain
Authors: Wakefield Emily O , Belamkar Vaishali , Litt Mark D , Puhl Rebecca M , Zempsky William T
Published: October 2021

Objective

Adolescents with chronic pain often experience symptom disbelief and social rejection by others secondary to “medically unexplained” symptoms. Although chronic pain is common in adolescents, limited research has conceptualized these social experiences as pain-related stigma in this population. The purpose of this study was to identify and describe pain-related stigma among adolescents with chronic pain and their parents using focus group methodology.

Methods

Five adolescent focus groups (N = 18; Age M = 15.33 years, SD = 1.28) and three parent focus groups (N = 9) were conducted. Directed content analysis was used to analyze focus group transcripts. Stigma categories were developed a priori (Felt Stigma, Anticipated Stigma, Internalized Stigma, Concealment, and Controllability) and new categories emerged during analysis. Two coders reached 87.16% agreement for all groups (adolescent group: 90.34%; Parent group: 79.55%) and consensus was achieved for discordant codes.

Results

Adolescents and their parents endorsed pain-related stigma across all social domains. Analyses revealed four main categories for both groups (a) Felt Stigma (subcategories: pain dismissal, faking or exaggerating, and mental health stigma), (b) Anticipated Stigma and Concealment, (c) Internalized Stigma, and (d) Sources of Pain-Related Stigma (subcategories: pain invisibility, lack of chronic pain knowledge, lack of understanding, and controllability).

Conclusions

Adolescents with chronic pain experience pain-related stigma from medical providers, school personnel, family members, and peers, which may have negative social and health implications. More research is needed to evaluate the link between pain-related stigma and health outcomes for adolescents with chronic pain. Clinical approaches targeting pain-related stigma are discussed.
Technical report and rare case description—patient-specific spacer made of bone cement for the revision of a PSI-TMJ fossa after screw fracture
Authors: Thiem Daniel G E , Al-Nawas Bilal , Kämmerer Peer W
Published: October 2021

Total alloplastic temporomandibular joint replacement (TMJ-TJR) has once again become the focus of therapy for end-stage destroyed joints. Although material quality has increased significantly in terms of service life and wear, problems occur even with patient-specific (PSI) prostheses. Here, mainly the ramus components are affected and an occurrence of screw loosening or fractures in the area of the fossa of stock joints is rare and has not yet been described for patient-specific (PSI) components. Although very rare, such events pose a great challenge to both practitioners and affected patients, especially in the case of PSI components, not least due to the long time required for new fabrication. The case report shows a non-described screw fracture of a PSI-TMJ fossa and the first description of a temporary revision using a PSI-TMJ fossa made of bone cement.
Micropapillary bladder cancer: an added indication to prophylactic urethrectomy
Authors: Mehrnoush Vahid , Ismail Asmaa , Zakaria Ahmed , Elmansy Hazem , Shahrour Walid , Prowse Owen , Kotb Ahmed
Published: October 2021

There is little research on the role of urethrectomy during cystectomy in patients with micropapillary bladder cancer (MPBC). We present two cases of MPBC cystectomy and suggest that urethrectomy be performed concurrently as a preventive measure. The first case involved a woman who had a mixed solid and papillary bladder tumour. An anterior pelvic exenteration was performed as well as a total urethrectomy. The T4a micropapillary variant tumour was confirmed by pathology. The second case involved a man with T1 MPBC who was treated with a BCG induction course. A recurrent muscle-invasive MPBC was discovered during follow-up. During the radical cystoprostatectomy, the urethra was spared. T2 MPBC was discovered through pathology. He had a urethrectomy 6 months later due to urethral bleeding, and the pathology revealed micropapillary cancer of the urethra.
Restricting emigration for their protection? Exit controls and the protection of (women) migrant workers
Authors: Lenard Patti Tamara
Published: October 2021

Abuse and exploitation of migrant workers in Gulf States is common and well-documented, and women domestic workers are at special risk. Sending states—often relatively poorer South Asian states—are limited in the ways that they can protect the rights of their citizens when they are labouring abroad. One strategy that sending states have deployed is the adoption of ‘emigration bans’ or ‘emigration conditions’. Emigration bans restrict citizens from taking up temporary labour market contracts, usually in specific states, but sometimes in general. ‘Emigration conditions’ require would-be migrants to meet specific requirements in order to be permitted, by the sending state, to take up a labour market contract abroad. In this article, I examine whether it is morally permissible for source countries to prohibit migration to countries where they risk being exploited or abused. I examine the reasons states give to justify emigration bans and conditions: the ‘structured vulnerability’ reason; the ‘gendered structured vulnerability’ reason; and the ‘gendered paternalism’ reason. Overall, I agree that the reasons motivating the bans and conditions are good ones—though I offer some criticism of the reasons I describe as ‘gendered paternalism’. But, since there is only limited evidence of the effectiveness of bans and conditions in achieving substantive benefit for labour migrants, and on the contrary evidence of the real harm they can sometimes generate, I argue that, absent positive evidence of success in achieving their objectives, they ought to be rejected in practice even if they are permissible in principle.
Are Bradycardic Donors More Likely to Have Adverse Outcomes During Blood Donation?
Authors: Broadwater Devin R , Krause Katherine A , Lynch David T , Kendelhardt Jason D
Published: October 2021

Introduction

In order to decrease adverse donor reactions during blood donation, volunteers are screened to safely donate according to the U.S. Food and Drug Administration standards. Volunteers must be normocardic, with a pulse between 50 and 100 beats per minute. Bradycardic volunteers with a pulse lower than 50 beats per minute who otherwise meet requirements may donate with physician approval. Blood donors in military settings tend to be younger and more physically fit than the average donor population, resulting in a higher percentage of bradycardic donors. The relationship between bradycardia and adverse donor reactions has not been well studied. Herein, we aim to compare post-donation adverse reactions and the ability to complete donation between normocardic and bradycardic donors.

Materials and Methods

Institutional review board approval was obtained. Records from a single blood donor center located on a large military installation in 2019 were retrospectively reviewed for vital signs, demographics, hemoglobin, and donor reactions. Donors were categorized as normocardic or bradycardic. The two groups were statistically compared using a χ2 test.

Results

Of the 1,601 donors in the study period, 1,514 qualified for donation. Mean age was 26.6 years (range, 17-72 years), with a male to female ratio of 2.1:1. Of these, 1,478 were normocardic and 26 were bradycardic. There was no significant difference in adverse reactions between the two groups (5.6% in bradycardic donors versus 3.6% in normocardic donors, n = 1,514, χ21 = 0.39, P = .53) or percentage of incomplete donations (5.9% in bradycardic and 5.65% in normocardic, n = 1,514, χ21 = 0.003, P = .96).

Conclusions

Donors with bradycardia are as safe to donate as normocardic donors. In the absence of comorbidities, blood donor centers should ensure their policies consider donation for volunteers with bradycardia.
Intrinsic alignments of galaxies around cosmic voids
Authors: d’Assignies D. William , Chisari Nora Elisa , Hamaus Nico , Singh Sukhdeep
Published: October 2021

The intrinsic alignments of galaxies, i.e. the correlation between galaxy shapes and their environment, are a major source of contamination for weak gravitational lensing surveys. Most studies of intrinsic alignments have so far focused on measuring and modelling the correlations of luminous red galaxies with galaxy positions or the filaments of the cosmic web. In this work, we investigate alignments around cosmic voids. We measure the intrinsic alignments of luminous red galaxies detected by the Sloan Digital Sky Survey around a sample of voids constructed from those same tracers and with radii in the ranges: [20–30; 30–40; 40–50] h−1 Mpc and in the redshift range z = 0.4−0.8. We present fits to the measurements based on a linear model at large scales, and on a new model based on the void density profile inside the void and in its neighbourhood. We constrain the free scaling amplitude of our model at small scales, finding no significant alignment at 1σ for either sample. We observe a deviation from the null hypothesis, at large scales, of 2σ for voids with radii between 20 and 30 h−1 Mpc, and 1.5σ for voids with radii between 30 and 40 h−1 Mpc and constrain the amplitude of the model on these scales. We find no significant deviation at 1σ for larger voids. Our work is a first attempt at detecting intrinsic alignments of galaxy shapes around voids and provides a useful framework for their mitigation in future void lensing studies.
Light-curve fingerprints: an automated approach to the extraction of X-ray variability patterns with feature aggregation – an example application to GRS 1915+105
Authors: Orwat-Kapola Jakub K , Bird Antony J , Hill Adam B , Altamirano Diego , Huppenkothen Daniela
Published: October 2021

Time series data mining is an important field of research in the era of ‘Big Data’. Next generation astronomical surveys will generate data at unprecedented rates, creating the need for automated methods of data analysis. We propose a method of light-curve characterization that employs a pipeline consisting of a neural network with a long-short term memory variational autoencoder architecture and a Gaussian mixture model. The pipeline performs extraction and aggregation of features from light-curve segments into feature vectors of fixed length that we refer to as light-curve ‘fingerprints’. This representation can be readily used as input of down-stream machine learning algorithms. We demonstrate the proposed method on a data set of Rossi X-ray Timing Explorer observations of the Galactic black hole X-ray binary GRS 1915+105, which was chosen because of its observed complex X-ray variability. We find that the proposed method can generate a representation that characterizes the observations and reflects the presence of distinct classes of GRS 1915+105 X-ray flux variability. We find that this representation can be used to perform efficient classification of light curves. We also present how the representation can be used to quantify the similarity of different light curves, highlighting the problem of the popular classification system of GRS 1915+105 observations, which does not account for intermediate class behaviour.
Measurement of redshift-space two- and three-point correlation of Lyα absorbers at 1.7 < z < 3.5: implications on evolution of the physical properties of IGM
Authors: Maitra Soumak , Srianand Raghunathan , Gaikwad Prakash
Published: October 2021

We present redshift-space two-point (ξ), three-point (ζ), and reduced three-point (Q) correlation of Lyα absorbers (Voigt profile components having H i column density, NH i > 1013.5 cm−2) over three redshift bins spanning 1.7 < z < 3.5 using high-resolution spectra of 292 quasars. We detect positive ξ up to 8 h−1 cMpc in all three redshift bins. The strongest detection of ζ = 1.81 ± 0.59 (with Q = 0.68 ± 0.23) is in $z$ = 1.7–2.3 bin at 1–2 h−1 cMpc. The measured ξ and ζ values show an increasing trend with NH i, while Q remains relatively independent of NH i. We find ξ and ζ to evolve strongly with redshift. Using simulations, we find that ξ and ζ seen in real space may be strongly amplified by peculiar velocities in redshift space. Simulations suggest that while feedback, thermal and pressure smoothing effects influence the clustering of Lyα absorbers at small scales, i.e. <0.5 h−1 cMpc, the H i photoionization rate (ΓH i) has a strong influence at all scales. The strong redshift evolution of ξ and ζ (for a fixed NH i cut-off) is driven by the redshift evolution of the relationship between NH i and baryon overdensity. Our simulation using best-fitting ΓH i($z$) measurements produces consistent clustering signals with observations at $z$ ∼ 2 but underpredicts the clustering at higher redshifts. One possible remedy is to have higher values of ΓH i at higher redshifts. Alternatively the discrepancy could be related to non-equilibrium and inhomogeneous conditions prevailing during He ii reionization not captured by our simulations.
Optical intensity interferometry lab tests in preparation of stellar diameter measurements at IACTs at GHz photon rates
Authors: Zmija Andreas , Vogel Naomi , Anton Gisela , Malyshev Dmitry , Michel Thilo , Zink Adrian , Funk Stefan
Published: October 2021

Astronomical intensity interferometry enables quantitative measurements of the source geometry by measuring the photon fluxes in individual telescopes and correlating them, rather than correlating the electromagnetic waves’ amplitudes. This simplifies the realization of large telescope baselines and high angular resolutions. Imaging Atmospheric Cherenkov Telescopes (IACTs), intended to detect the optical emission of γ-ray-induced air showers, are excellent candidates to perform intensity correlations in the optical at reasonable signal-to-noise ratios. The detected coherence time is on the scale of (10−12)–(10−15) s – depending on the optical bandwidth of the measurement – which challenges the detection system to work in a stable and accurate way. We developed an intensity interferometry set-up applicable to IACTs, which measures the photocurrents from photomultipliers and correlates them offline, and as such is designed to handle the very large photon rates provided by the telescopes. We present measurements in the lab simulating starlight using a xenon lamp and measured at different degrees of temporal and spatial coherence. Necessary calibration procedures are described with the goal of understanding the measurements quantitatively. Measured coherence times between $5\,$femtoseconds (corresponding signal-to-background ratio 5 × 10−7) and $110\,$femtoseconds (signal-to-background ratio 10−5) are in good agreement with expectations, and so are the noise levels in the correlations, reaching down to 6 × 10−8, after measurements between $30\,$min and $1\,$h.
PISCOLA: a data-driven transient light-curve fitter
Authors: Müller-Bravo Tomás E , Sullivan Mark , Smith Mathew , Frohmaier Chris , Gutiérrez Claudia P , Wiseman Philip , Zontou Zoe
Published: October 2021

Forthcoming time-domain surveys, such as the Rubin Observatory Legacy Survey of Space and Time, will vastly increase samples of supernovae (SNe) and other optical transients, requiring new data-driven techniques to analyse their photometric light curves. Here, we present the ‘Python for Intelligent Supernova-COsmology Light-curve Analysis’ (PISCOLA ), an open source data-driven light-curve fitter using Gaussian Processes that can estimate rest-frame light curves of transients without the need for an underlying light-curve template. We test PISCOLA  on large-scale simulations of type Ia SNe (SNe Ia) to validate its performance, and show it successfully retrieves rest-frame peak magnitudes for average survey cadences of up to 7 d. We also compare to the existing SN Ia light-curve fitter SALT2 on real data, and find only small (but significant) disagreements for different light-curve parameters. As a proof-of-concept of an application of PISCOLA , we decomposed and analysed the PISCOLA rest-frame light curves of SNe Ia from the Pantheon SN Ia sample with Non-Negative Matrix Factorization. Our new parametrization provides a similar performance to existing light-curve fitters such as SALT2. We further derived a SN Ia colour law from PISCOLA fits over ∼3500–7000 Å, and find agreement with the SALT2 colour law and with reddening laws with total-to-selective extinction ratio RV ≲ 3.1.
The halo light-cone catalogues of AbacusSummit
Authors: Hadzhiyska Boryana , Garrison Lehman H , Eisenstein Daniel , Bose Sownak
Published: October 2021

We describe a method for generating halo catalogues on the light-cone using the AbacusSummit suite of N-body simulations. The main application of these catalogues is the construction of realistic mock galaxy catalogues and weak lensing maps on the sky. Our algorithm associates the haloes from a set of coarsely spaced snapshots with their positions at the time of light-cone crossing by matching halo particles to on-the-fly light-cone particles. It then records the halo and particle information into an easily accessible product, which we call the AbacusSummit halo light-cone catalogues. Our recommended use of this product is in the halo mass regime of Mhalo > 2.1 × 1011 M⊙ h−1 for the base resolution simulations, i.e. haloes containing at least 100 particles, where the interpolated halo properties are most reliable. To test the validity of the obtained catalogues, we perform various visual inspections and consistency checks. In particular, we construct galaxy mock catalogues of emission-line galaxies (ELGs) at z ∼ 1 by adopting a modified version of the AbacusHOD script, which builds on the standard halo occupation distribution (HOD) method by including various extensions. We find that the multipoles of the autocorrelation function are consistent with the predictions from the full-box snapshot, implicitly validating our algorithm. In addition, we compute and output CMB convergence maps and find that the auto- and cross-power spectrum agrees with the theoretical prediction at the sub-per-cent level.

Halo light-cone catalogues for 25 base and 2 huge simulations at the fiducial cosmology are available at DOI:10.13139/OLCF/1825069
Zodiacal exoplanets in time (ZEIT) XII: a directly imaged planetary-mass companion to a young Taurus M dwarf star
Authors: Gaidos E , Hirano T , Kraus A L , Kuzuhara M , Zhang Z , Lee R A , Salama M , Berger T A , Grunblatt S K , Ansdell M , Liu M C , Harakawa H , Hodapp K W , Jacobson S , Konishi M , Kotani T , Kudo T , Kurokawa T , Nishikawa J , Omiya M , Serizawa T , Tamura M , Ueda A , Vievard S
Published: October 2021

We report the discovery of a resolved (0.9 arcsec) substellar companion to a member of the 1–5 Myr Taurus star-forming region. The host star (2M0437) is a single mid-M type (Teff ≈ 3100 K) dwarf with a position, space motion, and colour–magnitude that support Taurus membership, and possible affiliation with a ∼2.5-Myr-old subgroup. A comparison with stellar models suggests a 2–5 Myr age and a mass of 0.15–0.18M⊙. Although K2 detected quasi-periodic dimming from close-in circumstellar dust, the star lacks detectable excess infrared emission from a circumstellar disc and its H α emission is not commensurate with accretion. Astrometry based on 3 yr of AO imaging shows that the companion (2M0437b) is comoving, while photometry of two other sources at larger separation indicates that they are likely heavily reddened background stars. A comparison of the luminosity of 2M0437b with models suggests a mass of 3–5 MJUP, well below the deuterium burning limit, and an effective temperature of 1400–1500 K, characteristic of a late L spectral type. The H − K colour is redder than the typical L dwarf, but comparable to other directly detected young planets, e.g. those around HR 8799. The discovery of a super-Jupiter around a very young, very low-mass star challenges models of planet formation by either core accretion (which requires time) or disc instability (which requires mass). We also detected a second, comoving, widely separated (75 arcsec) object that appears to be a heavily extincted star. This is certainly a fellow member of this Taurus subgroup and statistically likely to be a bound companion.
The impact of photospheric brightness field on exoplanetary transit timings and the TTV excess of HD 189733 b
Authors: Baluev Roman V
Published: October 2021

We consider the issue of excessive TTV noise observed for the exoplanet HD 189733 b. Trying to explain it through the host star photospheric activity, we model the stellar surface brightness as a random field, then characterize statistical properties of the resulting transit signal perturbation and compute individual corrections to transit timings uncertainties. We find that possible effect of the photospheric brightness field can explain only a minor portion (∼10 s) of the observed (∼70 s) TTV excess of HD 189733, suggesting that the rest should be attributed to other sources. Regarding the photospheric pattern, we place an upper limit of ∼0.01 on the combination εcellrcell, where εcell is the relative magnitude of brightness variations, and rcell is the geometric cellularity scale (relative to star radius).
Laser communication with Proxima and Alpha Centauri using the solar gravitational lens
Authors: Marcy Geoffrey W , Tellis Nathaniel K , Wishnow Edward H
Published: October 2021

A search was conducted for laser signals, both sub-second pulses and continuous emission, from the regions of the sky opposite Proxima and Alpha Centauri. These regions are located at the foci of the gravitational lensing caused by the Sun, ideal for amplifying transmissions between our Solar system and those two nearest stellar neighbours. The search was conducted using two objective prism telescopes operating with exposure times of 0.25 s, enabling detection of sub-second laser pulses coming from the solar gravitational foci. During 6 months in 2020 and 2021, 88 000 exposures for Proxima Cen and 47 000 exposures for Alpha Cen were obtained. No evidence was detected of light pulses or continuous laser emission in the wavelength range of 380–950 nm. We would have detected a laser having a power of just 100 W, for a benchmark 1-m laser launcher that was diffraction-limited and located at the Sun’s gravitational focus 550 au away. To be detected, that beam must intercept Earth either by intention or, by accident, or if intended for a probe near Earth that is communicating with another one at the solar gravitational lens. These non-detections augment a previous non-detection of laser light coming directly from Proxima Centauri conducted with the HARPS spectrometer on the ESO 3.6-m telescope.
Star cluster ecology: revisiting the origin of iron and age complex clusters
Authors: Bastian Nate , Pfeffer Joel
Published: October 2021

Typical globular clusters (GCs – young and old) host stellar populations with little or no star-to-star variations in heavy elements (e.g. Ca, Fe) nor in age. Nuclear star clusters (NSCs), on the other hand, host complex stellar populations that show multimodal distributions in Fe and often in age, presumably due to their unique location at the centre of a large galactic potential well. However, recently a new class of clusters have been discovered, exemplified by the clusters Terzan 5 and Liller 1, two high mass, high metallicity clusters in the inner Galactic regions. It has been suggested that these are not true GCs, but rather represent left over fragments of the formation of the Galactic Bulge. Here, we critically assess this scenario and find that the role of dynamical friction likely makes it untenable and that the method used to estimate the initial masses of the clumps was invalid. Instead, it appears more likely that these clusters represent a relatively rare phenomenon of existing GCs accreting gas and forming a second generation, as has been previously suggested.
The real-world effectiveness of anti-RANKL antibody denosumab on the clinical fracture prevention in patients with rheumatoid arthritis: The ANSWER cohort study
Authors: Murata Koichi , Uozumi Ryuji , Hashimoto Motomu , Ebina Kosuke , Akashi Kengo , Onishi Akira , Nagai Koji , Yoshikawa Ayaka , Katayama Masaki , Son Yonsu , Amuro Hideki , Hara Ryota , Yamamoto Wataru , Watanabe Ryu , Murakami Kosaku , Tanaka Masao , Ito Hiromu , Morinobu Akio , Matsuda Shuichi
Published: October 2021

Objectives

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by localized and generalized bone loss. The risk of fractures is doubled in patients with RA. Denosumab, an anti-RANKL monoclonal antibody, is used for those with osteoporosis at high risk fracture and it has inhibitory effect of progressive bone erosion in patients with RA. While the increase in bone mineral density by denosumab has been reported in patients with RA, preventive effect of fracture by denosumab remains unknown. This study aimed to evaluate the efficacy of denosumab in treating clinical fracture risk in patients with RA.

Methods

Patients with RA who received denosumab treatment between 2013 and 2019 were retrospectively evaluated using the ANSWER (Kansai Consortium for the Well-Being of Rheumatic Disease Patients) cohort data. Fracture rates were evaluated between 0 and 6 months (reference period) versus > 6 months (post-reference period) of denosumab use.

Results

A total of 873 patients with RA received denosumab, and their characteristics were as follows: 88% females, mean age 68 years, and average disease duration 14.5 years. The hazard rates of all clinical fractures were 0.69 (per 100 person-years) in the reference period and 0.35 in the post-reference period, indicating a 49.2% decrease (p = 0.03).

Conclusions

Denosumab suppresses the risk of clinical fractures in patients with RA.
APPRIS: selecting functionally important isoforms
Authors: Rodriguez Jose Manuel , Pozo Fernando , Cerdán-Vélez Daniel , Di Domenico Tomás , Vázquez Jesús , Tress Michael L
Published: October 2021

APPRIS (https://appris.bioinfo.cnio.es) is a well-established database housing annotations for protein isoforms for a range of species. APPRIS selects principal isoforms based on protein structure and function features and on cross-species conservation. Most coding genes produce a single main protein isoform and the principal isoforms chosen by the APPRIS database best represent this main cellular isoform. Human genetic data, experimental protein evidence and the distribution of clinical variants all support the relevance of APPRIS principal isoforms. APPRIS annotations and principal isoforms have now been expanded to 10 model organisms. In this paper we highlight the most recent updates to the database. APPRIS annotations have been generated for two new species, cow and chicken, the protein structural information has been augmented with reliable models from the EMBL-EBI AlphaFold database, and we have substantially expanded the confirmatory proteomics evidence available for the human genome. The most significant change in APPRIS has been the implementation of TRIFID functional isoform scores. TRIFID functional scores are assigned to all splice isoforms, and APPRIS uses the TRIFID functional scores and proteomics evidence to determine principal isoforms when core methods cannot.
DiseaseMeth version 3.0: a major expansion and update of the human disease methylation database
Authors: Xing Jie , Zhai Ruiyang , Wang Cong , Liu Honghao , Zeng Jiaqi , Zhou Dianshuang , Zhang Mengyan , Wang Liru , Wu Qiong , Gu Yue , Zhang Yan
Published: October 2021

DNA methylation has a growing potential for use as a biomarker because of its involvement in disease. DNA methylation data have also substantially grown in volume during the past 5 years. To facilitate access to these fragmented data, we proposed DiseaseMeth version 3.0 based on DiseaseMeth version 2.0, in which the number of diseases including increased from 88 to 162 and High-throughput profiles samples increased from 32 701 to 49 949. Experimentally confirmed associations added 448 pairs obtained by manual literature mining from 1472 papers in PubMed. The search, analyze and tools sections were updated to increase performance. In particular, the FunctionSearch now provides for the functional enrichment of genes from localized GO and KEGG annotation. We have also developed a unified analysis pipeline for identifying differentially DNA methylated genes (DMGs) from the original data stored in the database. 22 718 DMGs were found in 99 diseases. These DMGs offer application in disease evaluation using two self-developed online tools, Methylation Disease Correlation and Cancer Prognosis & Co-Methylation. All query results can be downloaded and can also be displayed through a box plot, heatmap or network module according to whichever search section is used. DiseaseMeth version 3.0 is freely available at http://diseasemeth.edbc.org/.
The chromatin remodeler RSF1 coordinates epigenetic marks for transcriptional repression and DSB repair
Authors: Min Sunwoo , Lee Ho-Soo , Ji Jae-Hoon , Heo Yungyeong , Kim Yonghyeon , Chae Sunyoung , Choi Yong Won , Kang Ho-Chul , Nakanishi Makoto , Cho Hyeseong
Published: October 2021

DNA lesions impact on local transcription and the damage-induced transcriptional repression facilitates efficient DNA repair. However, how chromatin dynamics cooperates with these two events remained largely unknown. We here show that histone H2A acetylation at K118 is enriched in transcriptionally active regions. Under DNA damage, the RSF1 chromatin remodeling factor recruits HDAC1 to DSB sites. The RSF1-HDAC1 complex induces the deacetylation of H2A(X)-K118 and its deacetylation is indispensable for the ubiquitination of histone H2A at K119. Accordingly, the acetylation mimetic H2A-K118Q suppressed the H2A-K119ub level, perturbing the transcriptional repression at DNA lesions. Intriguingly, deacetylation of H2AX at K118 also licenses the propagation of γH2AX and recruitment of MDC1. Consequently, the H2AX-K118Q limits DNA repair. Together, the RSF1-HDAC1 complex controls the traffic of the DNA damage response and transcription simultaneously in transcriptionally active chromatins. The interplay between chromatin remodelers and histone modifiers highlights the importance of chromatin versatility in the maintenance of genome integrity.
Work participation is reduced during the development of RA, months before clinical arthritis manifests
Authors: Rogier Cleo , de Jong Pascal H P , van der Helm-van Mil Annette H M , van Mulligen Elise
Published: October 2021

Objectives

We investigated whether work participation is affected in patients with arthralgia during transition to RA. Arthralgia patients with symptom resolution and early RA patients at diagnosis were used as a reference.

Methods

Three groups of patients were studied: arthralgia patients converting to RA (n = 114), arthralgia patients with spontaneous symptom resolution (n = 57), and early RA patients (n = 617). Both presenteeism (i.e. working while sick, scale 0–10) and absenteeism (i.e. sick leave) were taken into account. Work ability 1 year prior to clinical arthritis was estimated (in absolute numbers). The course of work restriction over time was studied using linear mixed models (β coefficient; delta per month) within each patient group.

Results

One-year prior to the development of clinical arthritis, mean presenteeism was 7.0 (95% CI 5.8, 8.1) in patients with arthralgia, indicating 30% loss, and further worsened to 6.1 (95% CI 5.3, 6.6) at RA diagnosis, thus indicating 39% loss. In early RA patients, presenteeism improved over time after DMARD initiation (β 0.052 per month 95% CI 0.042, 0.061, P < 0.0001). Presenteeism also improved in arthralgia patients who achieved spontaneous symptom resolution (β 0.063 per month, 95% CI 0.024, 0.10, P = 0.002). Absenteeism did not change significantly in arthralgia patients, but did improve in RA after DMARD-start. ACPA stratification revealed similar results.

Conclusion

In the months preceding RA, presenteeism was already apparent, and it worsened further during progression to clinical arthritis and diagnosis. This underlines the relevance of the symptomatic pre-RA phase for patients. The observed reversibility in arthralgia patients with symptom resolution may suggest that intervention in pre-RA could improve work participation.
The TIPS Liquidity Premium
Authors: Andreasen Martin M , Christensen Jens H E , Riddell Simon
Published: October 2021

We introduce an arbitrage-free term structure model of nominal and real yields that accounts for liquidity risk in Treasury inflation-protected securities (TIPS). The novel feature of our model is to identify liquidity risk from individual TIPS prices by accounting for the tendency that TIPS, like most fixed-income securities, go into buy-and-hold investors’ portfolios as time passes. We find a sizable and countercyclical TIPS liquidity premium, which helps our model to match TIPS prices. Accounting for liquidity risk also improves the model’s ability to forecast inflation and match surveys of inflation expectations.
Assessment of the systemic toxicity ofLaghu vishagarbha taila, an Ayurvedic medicated oil formulation after dermal exposure
Authors: Wanjari Manish M , Yadav Mahendra , Dey Yadu Nandan , Sharma Deepti , Srivastava Bhavana , Jamdagni Shrirang B , Gaidhani Sudesh N , Jadhav Ankush D , Gautam Manish
Published: October 2021

Laghu vishagarbha taila (LVT) is a medicated oil preparation used in the Ayurvedic system of medicine and applied topically for the treatment of painful musculoskeletal and inflammatory disorders. It contains some mildly poisonous phytoconstituents which may show untoward effects upon application. The present study evaluated the toxicity of LVT in the acute, subacute, and subchronic dermal toxicity study in Wistar rats. LVT was tested for its compliance using physicochemical and analytical parameters as per standard methods prescribed in Ayurvedic Pharmacopoeia of India, while acute, subacute, and subchronic toxicity studies were carried out as per OECD 402, 410, and 411 guidelines, respectively. In the acute dermal toxicity study, a single dose of LVT (2000 mg/kg) was applied topically to rats, while in subacute and subchronic dermal toxicity study, the rats were topically applied LVT (1000 mg/kg) up to 28 and 90 days, respectively. LVT did not cause any alterations in clinical signs and no mortality or moribund stage was observed. The change in weekly body weight was insignificant compared with the vehicle control group. In subacute and subchronic dermal toxicity study, there were no significant changes in behavior, body weight, feed consumption, biochemical and hematological parameters, organ weight, and histological parameters compared with vehicle control rats. Topical application of single and repeated doses of LVT in rats did not exhibit adverse effects and suggests that the LD50 of LVT is more than 2000 mg/kg in the acute dose and NOAEL is more than 1000 mg/kg/day in repeated dose application.
SiO2-induced ferroptosis in macrophages promotes the development of pulmonary fibrosis in silicosis models
Authors: Liu Taiyang , Bao Rui , Wang Qiushi , Hao Wei , Liu Yaoyang , Chang Sirong , Wang Meng , Li Yuanyuan , Liu Zhihong , Sun Yue
Published: October 2021

Silicosis is a devastating disease that, without effective treatment, endangers the health of miners. Therefore, studies exploring the pathogenesis of SiO2-induced pulmonary fibrosis are necessary to develop treatments for silicosis. Although macrophages are known to play a pivotal role in SiO2-induced pulmonary fibrosis, the underlying mechanism remains unknown. Here, we explored whether ferroptosis was involved in SiO2-induced pulmonary fibrosis. To this end, C57BL/6 mice and mouse macrophage (RAW264.7) cells and mouse lung fibroblast (MLF) cells were subjected to iron content, cell viability, enzyme-linked immunosorbent assay, immunofluorescence staining, histological, western blotting, quantitative reverse transcription-PCR, reactive oxygen species, and lipid peroxidation analysis. In vivo, SiO2 was found to damage the lung alveolar structure, cause infiltration of inflammatory cells, and facilitate fibrosis. Additionally, it increased the iron concentration and lipid peroxidation as well as altered the expression of ferroptosis-related genes and the mitochondrial morphology in macrophages. In vitro, ferroptosis occurred in SiO2-treated RAW264.7 cells, which showed iron overload, lipid peroxidation, and gene alterations. Furthermore, ferrostatin-1 (Fer-1) attenuated ferroptosis in SiO2-treated RAW264.7 cells by inhibiting lipid peroxidation and cell death and regulating ferroptosis-related genes expression, in addition to attenuating the secretion of pro-fibrotic cytokines and fibrosis. Collectively, SiO2 induces ferroptosis in macrophages, which leads to the secretion of pro-fibrotic cytokines and fibrosis.
Evidence for the evolution of eusociality in stem ants and a systematic revision of †Gerontoformica (Hymenoptera: Formicidae)
Authors: Boudinot Brendon E , Richter Adrian , Katzke Julian , Chaul Júlio C M , Keller Roberto A , Economo Evan P , Beutel Rolf Georg , Yamamoto Shûhei
Published: October 2021

It is generally assumed that Cretaceous stem ants were obligately eusocial, because of the presence of wingless adult females, yet the available evidence is ambiguous. Here, we report the syninclusion of a pupa and adult of a stem ant species from Mid-Cretaceous amber. As brood are immobile, the pupa was likely to have been transported by an adult. Therefore, the fossil substantiates the hypothesis that wingless females were cooperators, thus these were true ‘workers’. Re-examination of all described Cretaceous ant species reveals that winged–wingless diphenism – hence a variable dispersal capacity – may have been ancestral to the total clade of the ants, and that highly specialized worker-specific phenotypes evolved in parallel between the stem and crown groups. The soft-tissue preservation of the fossil is exceptional, demonstrating the possibility of analysing the development of the internal anatomy in stem ants. Based on the highest-resolution µ-CT scans of stem ants to date, we describe †Gerontoformica sternorhabda sp. nov., redescribe †G. gracilis, redefine the species group classification of †Gerontoformica, and provide a key to the species of the genus. Our work clarifies the species boundaries of †Gerontoformica and renders fossils relevant to the discussion of eusocial evolution in a way that has heretofore been intractable.