bluuebunny/crossref_metadata_2025 huggingface dataset:
Accelerometer-derived physical activity and risk of atrial fibrillation
Authors: Khurshid Shaan , Weng Lu-Chen , Al-Alusi Mostafa A , Halford Jennifer L , Haimovich Julian S , Benjamin Emelia J , Trinquart Ludovic , Ellinor Patrick T , McManus David D , Lubitz Steven A
Published: April 2021

Aims

Physical activity may be an important modifiable risk factor for atrial fibrillation (AF), but associations have been variable and generally based on self-reported activity.

Methods and results

We analysed 93 669 participants of the UK Biobank prospective cohort study without prevalent AF who wore a wrist-based accelerometer for 1 week. We categorized whether measured activity met the standard recommendations of the European Society of Cardiology, American Heart Association, and World Health Organization [moderate-to-vigorous physical activity (MVPA) ≥150 min/week]. We tested associations between guideline-adherent activity and incident AF (primary) and stroke (secondary) using Cox proportional hazards models adjusted for age, sex, and each component of the Cohorts for Heart and Aging Research in Genomic Epidemiology AF (CHARGE-AF) risk score. We also assessed correlation between accelerometer-derived and self-reported activity. The mean age was 62 ± 8 years and 57% were women. Over a median of 5.2 years, 2338 incident AF events occurred. In multivariable adjusted models, guideline-adherent activity was associated with lower risks of AF [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75–0.89; incidence 3.5/1000 person-years, 95% CI 3.3–3.8 vs. 6.5/1000 person-years, 95% CI 6.1–6.8] and stroke (HR 0.76, 95% CI 0.64–0.90; incidence 1.0/1000 person-years, 95% CI 0.9–1.1 vs. 1.8/1000 person-years, 95% CI 1.6–2.0). Correlation between accelerometer-derived and self-reported MVPA was weak (Spearman r = 0.16, 95% CI 0.16–0.17). Self-reported activity was not associated with incident AF or stroke.

Conclusions

Greater accelerometer-derived physical activity is associated with lower risks of AF and stroke. Future preventive efforts to reduce AF risk may be most effective when targeting adherence to objective activity thresholds.
High-fat diet–induced activation of SGK1 promotes Alzheimer’s disease–associated tau pathology
Authors: Elahi Montasir , Motoi Yumiko , Shimonaka Shotaro , Ishida Yoko , Hioki Hiroyuki , Takanashi Masashi , Ishiguro Koichi , Imai Yuzuru , Hattori Nobutaka
Published: April 2021

Type 2 diabetes mellitus (T2DM) has long been considered a risk factor for Alzheimer’s disease (AD). However, the molecular links between T2DM and AD remain obscure. Here, we reported that serum-/glucocorticoid-regulated kinase 1 (SGK1) is activated by administering a chronic high-fat diet (HFD), which increases the risk of T2DM, and thus promotes Tau pathology via the phosphorylation of tau at Ser214 and the activation of a key tau kinase, namely, GSK-3ß, forming SGK1-GSK-3ß-tau complex. SGK1 was activated under conditions of elevated glucocorticoid and hyperglycemia associated with HFD, but not of fatty acid–mediated insulin resistance. Elevated expression of SGK1 in the mouse hippocampus led to neurodegeneration and impairments in learning and memory. Upregulation and activation of SGK1, SGK1-GSK-3ß-tau complex were also observed in the hippocampi of AD cases. Our results suggest that SGK1 is a key modifier of tau pathology in AD, linking AD to corticosteroid effects and T2DM.
Deep Learning for Reintegrating Biology
Authors: Müller Rolf , Han Jin-Ping , Chandrasekaran Sriram , Bogdan Paul
Published: April 2021

The goal of this vision paper is to investigate the possible role that advanced machine learning techniques, especially deep learning (DL), could play in the reintegration of various biological disciplines. To achieve this goal, a series of operational, but admittedly very simplistic, conceptualizations have been introduced: Life has been taken as a multidimensional phenomenon that inhabits three physical dimensions (time, space, and scale) and biological research as establishing connection between different points in the domain of life. Each of these points hence denotes a position in time, space, and scale at which a life phenomenon of interest takes place. Using these conceptualizations, fragmentation of biology can be seen as the result of too few and especially too short-ranged connections. Reintegrating biology could then be accomplished by establishing more, longer ranged connections. DL methods appear to be very well suited for addressing this particular need at this particular time. Notwithstanding the numerous unsubstantiated claims regarding the capabilities of AI, DL networks represent a major advance in the ability to find complex relationships inside large data sets that would have not been accessible with traditional data analytic methods or to a human observer. In addition, ongoing advances in the automation of taking measurements from phenomena on all levels of biological organization continue to increase the number of large quantitative data sets that are available. These increasingly common data sets could serve as anchor points for making long-range connections by virtue of DL. However, connections within the domain of life are likely to be structured in a highly nonuniform fashion and hence it is necessary to develop methods, for example, theoretical, computational, and experimental, to determine linkage of biological data sets most likely to provide useful insights on a biological problem using DL. Finally, specific DL approaches and architectures should be developed to match the needs of reintegrating biology.
The Role of the Tail or Lack Thereof in the Evolution of Tetrapod Aquatic Propulsion
Authors: Fish Frank E , Rybczynski Natalia , Lauder George V , Duff Christina M
Published: April 2021

Secondary aquatic vertebrates exhibit a diversity of swimming modes that use paired limbs and/or the tail. Various secondarily aquatic tetrapod clades, including amphibians, reptiles, and mammals use transverse undulations or oscillations of the tail for swimming. These movements have often been classified according to a kinematic gradient that was established for fishes but may not be appropriate to describe the swimming motions of tetrapods. To understand the evolution of movements and design of the tail in aquatic tetrapods, we categorize the types of tails used for swimming and examine swimming kinematics and hydrodynamics. From a foundation of a narrow, elongate ancestral tail, the tails used for swimming by aquatic tetrapods are classified as tapered, keeled, paddle, and lunate. Tail undulations are associated with tapered, keeled, and paddle tails for a diversity of taxa. Propulsive undulatory waves move down the tail with increasing amplitude toward the tail tip, while moving posteriorly at a velocity faster than the anterior motion of the body indicating that the tail is used for thrust generation. Aquatic propulsion is associated with the transfer of momentum to the water from the swimming movements of the tail, particularly at the trailing edge. The addition of transverse extensions and flattening of the tail increases the mass of water accelerated posteriorly and affects vorticity shed into the wake for more aquatically adapted animals. Digital Particle Image Velocimetry reveals that the differences were exhibited in the vortex wake between the morphological and kinematic extremes of the alligator with a tapering undulating tail and the dolphin with oscillating wing-like flukes that generate thrust. In addition to exploring the relationship between the shape of undulating tails and the swimming performance across aquatic tetrapods, the role of tail reduction or loss of a tail in aquatic-tetrapod swimming was also explored. For aquatic tetrapods, the reduction would have been due to factors including locomotor and defensive specializations and phylogenetic and physiological constraints. Possession of a thrust-generating tail for swimming, or lack thereof, guided various lineages of secondarily aquatic vertebrates into different evolutionary trajectories for effective aquatic propulsion (i.e., speed, efficiency, and acceleration).
The Degenerate Tale of Ascidian Tails
Authors: Fodor Alexander C A , Powers Megan M , Andrykovich Kristin , Liu Jiatai , Lowe Elijah K , Brown C Titus , Di Gregorio Anna , Stolfi Alberto , Swalla Billie J
Published: April 2021

Ascidians are invertebrate chordates, with swimming chordate tadpole larvae that have distinct heads and tails. The head contains the small brain, sensory organs, including the ocellus (light) and otolith (gravity) and the presumptive endoderm, while the tail has a notochord surrounded by muscle cells and a dorsal nerve cord. One of the chordate features is a post-anal tail. Ascidian tadpoles are nonfeeding, and their tails are critical for larval locomotion. After hatching the larvae swim up toward light and are carried by the tide and ocean currents. When competent to settle, ascidian tadpole larvae swim down, away from light, to settle and metamorphose into a sessile adult. Tunicates are classified as chordates because of their chordate tadpole larvae; in contrast, the sessile adult has a U-shaped gut and very derived body plan, looking nothing like a chordate. There is one group of ascidians, the Molgulidae, where many species are known to have tailless larvae. The Swalla Lab has been studying the evolution of tailless ascidian larvae in this clade for over 30 years and has shown that tailless larvae have evolved independently several times in this clade. Comparison of the genomes of two closely related species, the tailed Molgula oculata and tailless Molgula occulta reveals much synteny, but there have been multiple insertions and deletions that have disrupted larval genes in the tailless species. Genomics and transcriptomics have previously shown that there are pseudogenes expressed in the tailless embryos, suggesting that the partial rescue of tailed features in their hybrid larvae is due to the expression of intact genes from the tailed parent. Yet surprisingly, we find that the notochord gene regulatory network is mostly intact in the tailless M. occulta, although the notochord does not converge and extend and remains as an aggregate of cells we call the “notoball.” We expect that eventually many of the larval gene networks will become evolutionarily lost in tailless ascidians and the larval body plan abandoned, with eggs developing directly into an adult. Here we review the current evolutionary and developmental evidence on how the molgulids lost their tails.
The transport of images method: computing all zeros of harmonic mappings by continuation
Authors: Sète Olivier , Zur Jan
Published: April 2021

We present a continuation method to compute all zeros of a harmonic mapping $\,f$ in the complex plane. Our method works without any prior knowledge of the number of zeros or their approximate location. We start by computing all solutions of $f(z) = \eta $ with $\lvert \eta \rvert{}$ sufficiently large and then track all solutions as $\eta $ tends to $0$ to finally obtain all zeros of $f$. Using theoretical results on harmonic mappings we analyze where and how the number of solutions of $f(z) = \eta $ changes and incorporate this into the method. We prove that our method is guaranteed to compute all zeros, as long as none of them is singular. In our numerical examples the method always terminates with the correct number of zeros, is very fast compared to general purpose root finders and is highly accurate in terms of the residual. An easy-to-use MATLAB implementation is freely available online.
Always Available, Always Attached: A Relational Perspective on the Effects of Mobile Phones and Social Media on Subjective Well-Being
Authors: Taylor Samuel Hardman , Bazarova Natalya N
Published: April 2021

In this study, we examine the effects of the near-constant use of digital media in everyday life on well-being in the context of close relationships. Building on media multiplexity and attachment perspectives, we argue that communication over a dyad’s media ecosystem, including face-to-face, text messaging, cellphone calls, e-mail, and instant messaging, creates connected availability. Connected availability is the perception that a partner is at a continuous (digital) arm’s reach offering protection and security. Using longitudinal dyadic data of cohabitating romantic partners, we track the effects of media multiplexity on well-being by factoring in both partners’ perspectives to untangle the security offered through partner’s availability from the stress of maintaining one’s own constant availability to a partner. The results support salutary effects of media use on well-being because of increased connected availability, with limited evidence for adverse impacts of maintaining constant availability with a close partner.

The always-on, always-available nature of digital life means almost constant connection and availability between romantic partners, family members, and close friends. Being tethered to one another can give people a sense of security, while simultaneously causing more stress. In this article, we find that keeping a romantic partner constantly within a (digital) arm’s reach promotes better well-being for oneself. In addition, keeping a romantic partner always available also predicted better well-being for the romantic partner. Further, the analysis did not show added stress for the partner.
Neonicotinoid Exposures that Stimulate Predatory Stink Bug, Podisus maculiventris (Hemiptera: Pentatomidae), Reproduction Do Not Inhibit Its Behavior
Authors: Rix R R , Cutler G C
Published: April 2021

Exposure to sublethal amounts of pesticide can compromise life-history traits and behavior of natural enemies thereby reducing their effectiveness as predators. However, sublethal exposures to pesticides and other stressors may also stimulate insects, a dose–response phenomenon known as hormesis. We previously reported stimulatory effects on reproduction in the beneficial insect predator Podisus maculiventris (Say) (Hemiptera: Pentatomidae) following exposure to sublethal concentrations of imidacloprid. Here we examined whether these same treatments stimulated behavior and/or predation of P. maculiventris. Stimulation of some behaviors occurred at a reproductively hormetic concentration and two additional sublethal concentrations, depending upon bioassay design and sex. We observed no substantial inhibition of behavior or predation at a reproductively hormetic concentration, demonstrating that reproductive fitness in P. maculiventris may be stimulated without compromising behaviors important in its effectiveness as a natural enemy.
The significance of biopsy scar excision at the time of skin- or nipple-sparing mastectomy with immediate breast reconstruction
Authors: Ozaki Yuri , Yoshimura Akiyo , Sawaki Masataka , Hattori Masaya , Kotani Haruru , Adachi Yayoi , Kataoka Ayumi , Sugino Kayoko , Horisawa Nanae , Endo Yuka , Nozawa Kazuki , Sakamoto Shoko , Takatsuka Daiki , Okumura Seiko , Maruyama Yoko , Iwata Hiroji
Published: April 2021

Background

Neoplastic seeding (NS) can occur after tissue biopsy, which is a clinical issue especially in mastectomy with immediate reconstruction. This is because postoperative radiation is not usually given and local recurrence of preserved skin flap may increase. The purpose of this study is to investigate the importance of preoperative evaluation of NS and the validity of biopsy scar excision.

Patients and methods

We retrospectively analysed 174 cases of mastectomy with immediate breast reconstruction. The primary endpoint is the frequency of clinical and pathological NS and the secondary endpoint is the problem of excision of needle biopsy site.

Results

Three cases (1.7%) had preoperative clinical findings of NS. Pathological examination revealed NS in all three cases. Biopsy scars could be excised in 115 cases among 171 cases without clinical NS. Pathological NS was found in 1 of 66 (1.5%) cases of which pathological examination was performed. Biopsy scars could not be excised in the remaining 56 cases: the biopsy scar could not be identified in 41 cases, and there was concern about a decrease in flap blood flow after excision in 15 cases. In 12 of these 15 cases, the scars were close to the skin incision; excision of these scars might have triggered skin necrosis between the incision and the biopsy scar excision site. No postoperative complications were observed.

Conclusions

It is important to preoperatively evaluate clinical NS, and biopsy scars should be excised in clinical NS cases. Even in cases without clinical NS, biopsy scar excision should be considered. It is also important to perform a biopsy in consideration of the incision design for reconstructive surgery.
Angiofibromatoid histiosarcoma of the pulmonary artery
Authors: Farag James , McNamara Nicholas , Yan Tristan D
Published: April 2021

We describe the surgical management of a rare pulmonary angiomatoid fibrous histiosarcoma (AFH). A 62-year-old lady presented with shortness of breath and found to have a large left main pulmonary artery defect that was positron emission tomography-avid.

Following discussion in a thoracic multidisciplinary team meeting it was deemed unsafe to biopsy considering its intravascular position. The patient proceeded to theatre for a left pneumonectomy. She was successfully discharged home by Day 7. On follow-up the patient is well, and free of malignancy.

AFH is an incredibly rare form of sarcoma, and in particular in the thoracic region. We have demonstrated successful oncological resection of a rare intravascular lesion in the pulmonary artery.
Innocent until proven guilty: acute on chronic tubal torsion mimicking pelvic inflammatory disease
Authors: Taylor Scott , Lee Hong , Singh Rajeev
Published: April 2021

Acute pelvic pain is a common complaint in reproductive age women and has a large differential diagnosis. Decision for conservative vs. surgical management is often dependent on clinical, biochemical and imaging findings. Isolated tubal torsion is a rare cause of pelvic pain that requires prompt diagnosis and surgical management to avoid morbidity. Here, we report non-pregnant women of reproductive age presenting with acute lower abdominal pain. Raised inflammatory markers and ultrasound findings prompted management for Pelvic Inflammatory Disease. Despite some improvement with antibiotics, the patient had ongoing symptoms. At surgery, bilateral para-tubal cysts and a left sided hydrosalpinx were found, along with an isolated left tubal torsion. Isolated tubal torsion most commonly occurs in reproductive aged women, and risk factors include intrinsic tubal pathology and extrinsic lesions. Clinically, biochemically and radiographically, it is often indistinguishable from other pelvic pathology, potentially leading to diagnostic delay, and necrosis of the tube.
Orchestral manoeuvres in the light: crosstalk needed for regulation of the Chlamydomonas carbon concentration mechanism
Authors: Santhanagopalan Indu , Wong Rachel , Mathur Tanya , Griffiths Howard
Published: April 2021

The inducible carbon concentration mechanism (CCM) in Chlamydomonas reinhardtii has been well defined from a molecular and ultrastructural perspective. Inorganic carbon transport proteins, and strategically located carbonic anhydrases deliver CO2 within the chloroplast pyrenoid matrix where Rubisco is packaged. However, there is little understanding of the fundamental signalling and sensing processes leading to CCM induction. While external CO2 limitation has been believed to be the primary cue, the coupling between energetic supply and inorganic carbon demand through regulatory feedback from light harvesting and photorespiration signals could provide the original CCM trigger. Key questions regarding the integration of these processes are addressed in this review. We consider how the chloroplast functions as a crucible for photosynthesis, importing and integrating nuclear-encoded components from the cytoplasm, and sending retrograde signals to the nucleus to regulate CCM induction. We hypothesize that induction of the CCM is associated with retrograde signals associated with photorespiration and/or light stress. We have also examined the significance of common evolutionary pressures for origins of two co-regulated processes, namely the CCM and photorespiration, in addition to identifying genes of interest involved in transcription, protein folding, and regulatory processes which are needed to fully understand the processes leading to CCM induction.
Disposition of posaconazole after single oral administration in large falcons (Falco spp): Effect of meal and dosage and a non-compartmental model to predict effective dosage
Authors: Azmanis Panagiotis , Pappalardo Lucia , Sara Ziad A J , Silvanose Christudas , Naidoo Vinny
Published: April 2021

Posaconazole has been used anecdotally to treat aspergillosis in falcons resistant to voriconazole. In human medicine, it is used prophylactically in immunosuppressed human subjects with invasive pulmonary aspergillosis. So far, no studies have been performed in birds. The aim of this study was to evaluate the in-vivo pharmacokinetic behavior of oral posaconazole after a single administration in six large falcons (i.e gyrfalcons, saker falcons). Posaconazole oral suspension (Noxafil, 40 mg/ml, Schering-Plough) was administered per os without meal in a single dosage of 12.5 mg/kg in 3 falcons. A comparison was done in two more falcons, one with a natural fatty meal at the same single dose, and one with a natural fatty meal and a higher dosage (20 mg/kg). Finally, six falcons received posaconazole pre-dissolved in corn oil with a natural low-fat meal in the higher single dose (20 mg/kg). No side effects were observed in the falcons in any of the experiments. In starved state posaconazole was poorly absorbed, more so than in other species. As expected, absorption of posaconazole was higher with the administration of meal or in the presence of plant (corn) oil, with a fourfold increase in apparent bioavailability. Despite the preferential absorption in the presence of fat, for both dosing schemes the AUC24 : MIC ratio was lower than described in human medicine to achieve a therapeutic effect. The AUCinf : MIC which is an indicator of efficacy after steady-state, while variable, did indicate that the drug is worth trying when susceptibility testing shows to be the only effective drug.

Lay Abstract

The focus of this work is to determine the pharmacokinetic parameters of oral posaconazole in large falcons for the first time after a single dose. Posaconazole has higher bioavailability when administered with meal and fatty components. No adverse reactions have been observed. The ratio of the area under the curve (AUC24) to minimum inhibitory concentration was lower compared to the therapeutic level in human.
New unexpected flow patterns in the problem of the stellar wind interaction with the interstellar medium: stationary ideal-MHD solutions
Authors: Korolkov Sergey , Izmodenov Vladislav
Published: April 2021

The astropause (heliopause for the Sun) is the tangential discontinuity separating the stellar wind from the interstellar plasma. The global shape of the heliopause is a matter of debates. Two types of the shape are under discussion: comet-like and tube-like. In the second type, the two-jets oriented towards the stellar rotation axis are formed by the action of azimuthal component of the stellar magnetic field. We explore a simplified global astrosphere in which (1) the surrounding and moving with respect to the star circumstellar medium is fully ionized, (2) the interstellar magnetic field is neglected, (3) the radial component of the stellar magnetic field is neglected as compared with the azimuthal component, and (4) the stellar wind outflow is spherically symmetric and supersonic. We present the results of numerical 3D MHD modelling and explore how the global structure depends on the gas-dynamic Mach number of the interstellar flow, M∞, and the Alfvenic Mach number in the stellar wind. It is shown that the astropause has a tube-like shape for small values of M∞. The wings of the tube are distorted towards the tail as larger as larger the Mach number is. The new (to our knowledge) result is the reverse interstellar flow in the vicinity of the astropause in the tail. The larger the interstellar Mach number is the narrower the reverse flow is. At some values of the Mach number, the stellar wind overcomes the reverse interstellar flow and moves out in downwind. In this regime, the astropause changes its topology from tube-like to sheet-like.
Observing relativistic features in large-scale structure surveys – II. Doppler magnification in an ensemble of relativistic simulations
Authors: Coates Louis , Adamek Julian , Bull Philip , Guandalin Caroline , Clarkson Chris
Published: April 2021

The standard cosmological model is inherently relativistic, and yet a wide range of cosmological observations can be predicted accurately from essentially Newtonian theory. This is not the case on ‘ultralarge’ distance scales, around the cosmic horizon size, however, where relativistic effects can no longer be neglected. In this paper, we present a novel suite of 53 fully relativistic simulations generated using the gevolution code, each covering the full sky out to z ≈ 0.85, and approximately 1930 deg2 out to z ≈ 3.55. These include a relativistic treatment of massive neutrinos, as well as the gravitational potential that can be used to exactly calculate observables on the past light cone. The simulations are divided into two sets, the first being a set of 39 simulations of the same fiducial cosmology (based on the Euclid Flagship 2 cosmology) with different realizations of the initial conditions, and the second that fixes the initial conditions, but varies each of seven cosmological parameters in turn. Taken together, these simulations allow us to perform statistical studies and calculate derivatives of any relativistic observable with respect to cosmological parameters. As an example application, we compute the cross-correlation between the Doppler magnification term in the convergence, κv, and the CDM + baryon density contrast, δcb, which arises only in a (special) relativistic treatment. We are able to accurately recover this term as predicted by relativistic perturbation theory, and study its sample variance and derivatives with respect to cosmological parameters.
The characteristic momentum of radiatively cooling energy-driven galactic winds
Authors: Lochhaas Cassandra , Thompson Todd A , Schneider Evan E
Published: April 2021

Energy injection by supernovae may drive hot supersonic galactic winds in rapidly star-forming galaxies, driving metal-enriched gas into the circumgalactic medium and potentially accelerating cool gas. If sufficiently mass-loaded, such flows become radiative within the wind-driving region, reducing the overall mass outflow rate from the host galaxy. We show that this sets a maximum on the total outflow momentum for hot energy-driven winds. For a spherical wind of Solar metallicity driven by continuous star formation, $\dot{p}_\mathrm{max} \simeq 1.9\times 10^4\ M_\odot \ \mathrm{yr}^{-1}\ \mathrm{km\ s}^{-1}(\alpha /0.9)^{0.86}\left[R_\star /(300\ \mathrm{pc})\right]^{0.14}[\dot{M}_\star /(20\ M_\odot \ \mathrm{yr}^{-1})]^{0.86},$ where α is the fraction of supernova energy that thermalizes the wind, and $\dot{M}_\star$ and R⋆ are the star formation rate and radius of the wind-driving region. This maximum momentum for hot winds can also apply to cool, ionized outflows that are typically observed in starburst galaxies, if the hot wind undergoes bulk radiative cooling or if the hot wind transfers mass and momentum to cool clouds within the flow. We show that requiring the hot wind to undergo single-phase cooling on large scales sets a minimum on the total outflow momentum rate. These maximum and minimum outflow momenta have similar values, setting a characteristic momentum rate of hot galactic winds that can become radiative on large scales. We find that most observations of photoionized outflow wind momentum fall below the theoretical maximum and thus may be signatures of cooling hot flows. On the other hand, many systems fall below the minimum momentum required for bulk cooling, indicating that perhaps the cool material observed has instead been entrained in or mixed with the hot flow.
Cosmic voids in modified gravity models with massive neutrinos
Authors: Contarini Sofia , Marulli Federico , Moscardini Lauro , Veropalumbo Alfonso , Giocoli Carlo , Baldi Marco
Published: April 2021

Cosmic voids are progressively emerging as a new viable cosmological probe. Their abundance and density profiles are sensitive to modifications of gravity, as well as to dark energy and neutrinos. The main goal of this work is to investigate the possibility of exploiting cosmic void statistics to disentangle the degeneracies resulting from a proper combination of f(R) modified gravity and neutrino mass. We use N-body simulations to analyse the density profiles and size function of voids traced by both dark matter particles and haloes. We find clear evidence of the enhancement of gravity in f(R) cosmologies in the void density profiles at z = 1. However, these effects can be almost completely overridden by the presence of massive neutrinos because of their thermal free streaming. Despite the limited volume of the analysed simulations does not allow us to achieve a statistically relevant abundance of voids larger than 40 Mpc h−1, we find that the void size function at high redshifts and for large voids is potentially an effective probe to disentangle these degenerate cosmological models, which is key in the prospective of the upcoming wide-field redshift surveys.
PyTorchDIA: a flexible, GPU-accelerated numerical approach to Difference Image Analysis
Authors: Hitchcock James A , Hundertmark Markus , Foreman-Mackey Daniel , Bachelet Etienne , Dominik Martin , Street Rachel , Tsapras Yiannis
Published: April 2021

We present a GPU-accelerated numerical approach for fast kernel and differential background solutions. The model image proposed in the Bramich Difference Image Analysis (DIA) algorithm is analogous to a very simple convolutional neural network (CNN), with a single convolutional filter (i.e. the kernel) and an added scalar bias (i.e. the differential background). Here, we do not solve for the discrete pixel array in the classical, analytical linear least-squares sense. Instead, by making use of PyTorch tensors (GPU compatible multidimensional matrices) and associated deep learning tools, we solve for the kernel via an inherently massively parallel optimization. By casting the DIA problem as a GPU-accelerated optimization that utilizes automatic differentiation tools, our algorithm is both flexible to the choice of scalar objective function, and can perform DIA on astronomical data sets at least an order of magnitude faster than its classical analogue. More generally, we demonstrate that tools developed for machine learning can be used to address generic data analysis and modelling problems.
KIC 5950759: a high-amplitude δ Sct star with amplitude and frequency modulation near the terminal age main sequence
Authors: Bowman D M , Hermans J , Daszyńska-Daszkiewicz J , Holdsworth D L , Tkachenko A , Murphy S J , Smalley B , Kurtz D W
Published: April 2021

Among the intermediate mass pulsating stars known as δ Sct stars is a subset of high-amplitude and predominantly radial-mode pulsators known as high-amplitude δ Sct (HADS) stars. From more than 2000 δ Sct stars observed by the Kepler space mission, only two HADS stars were detected. We investigate the more perplexing of these two HADS stars, KIC 5950759. We study its variability using ground- and space-based photometry, determine its atmospheric parameters from spectroscopy and perform asteroseismic modelling to constrain its mass and evolutionary stage. From spectroscopy, we find that KIC 5950759 is a metal-poor star, which is in agreement with the inferred metallicity needed to reproduce its pulsation mode frequencies from non-adiabatic pulsation models. Furthermore, we combine ground-based WASP and Kepler space photometry, and measure a linear change in period of order $\dot{P}/P \simeq 10^{-6}$ yr−1 for both the fundamental and first overtone radial modes across a time base of several years, which is at least two orders of magnitude larger than predicted by evolution models, and is the largest measured period change in a δ Sct star to date. Our analysis indicates that KIC 5950759 is a metal-poor HADS star near the short-lived contraction phase and the terminal-age main sequence, with its sub-solar metallicity making it a candidate SX Phe star. KIC 5950759 is a unique object among the thousands of known δ Sct stars and warrants further study to ascertain why its pulsation modes are evolving remarkably faster than predicted by stellar evolution.
OxDNA.org: a public webserver for coarse-grained simulations of DNA and RNA nanostructures
Authors: Poppleton Erik , Romero Roger , Mallya Aatmik , Rovigatti Lorenzo , Šulc Petr
Published: April 2021

OxDNA and oxRNA are popular coarse-grained models used by the DNA/RNA nanotechnology community to prototype, analyze and rationalize designed DNA and RNA nanostructures. Here, we present oxDNA.org, a graphical web interface for running, visualizing and analyzing oxDNA and oxRNA molecular dynamics simulations on a GPU-enabled high performance computing server. OxDNA.org automatically generates simulation files, including a multi-step relaxation protocol for structures exported in non-physical states from DNA/RNA design tools. Once the simulation is complete, oxDNA.org provides an interactive visualization and analysis interface using the browser-based visualizer oxView to facilitate the understanding of simulation results for a user’s specific structure. This online tool significantly lowers the entry barrier of integrating simulations in the nanostructure design pipeline for users who are not experts in the technical aspects of molecular simulation. The webserver is freely available at oxdna.org.
Is time a healer? Course of demands during the COVID-19 pandemic in long-term care: a repeated cross-sectional survey in Germany
Authors: Hower Kira Isabel , Pfaff Holger , Pförtner Timo-Kolja
Published: April 2021

In the course of the coronavirus disease 2019 pandemic, long-term nursing care facilities are faced with general and pandemic-specific demands. In our study, we examined their burden from the perspective of managers in long-term nursing care facilities and how it differed in outpatient and inpatient settings. A cross-sectional online survey of long-term care managers was conducted in April 2020 (n = 503) and December 2020/January 2021 (n = 294). Burdens have increased over the course of the pandemic especially for outpatient facilities and in terms of general demands referring to staff (e.g. (staff shortages and overload) and work organization (e.g. compliance with regulations on working hours or staffing ratio). Concerns about infections of people in need of care and of employees remain the highest burden in the course of the pandemic. This knowledge helps us to draw implications from the pandemic and to prepare for future crises.
The extent of infectious SARS-CoV-2 shedding in an Argentinean cohort
Authors: Blanco Sebastián , Aguilar Juan Javier , Konigheim Brenda Salomé , Diaz Luis Adrian , Spinsanti Lorena , Beranek Mauricio , Collino César ,   Lab Central Córdoba working group, Diaz Miguel , Barbás María Gabriela , Gallego Sandra Verónica
Published: April 2021

Background

To analyze the infectious extent of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in different settings where prevention strategies are critical to limit infection spread, we evaluated SARS-COV-2 viability to guide public health policies regarding isolation criteria and infection control.

Methods

We attempted viral isolation in 82 nasopharyngeal swabs from 72 patients with confirmed SARS-COV-2 infection. Study population was divided into four groups: (i) Patients during the first week of symptoms; (ii) Patients with prolonged positive PCR; (iii) Healthcare workers from a hospital participating of an outbreak investigation, with SARS-COV-2 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) and (iv) Recipients of convalescent immune plasma (CIP).

Vero Cl76 cell-line (ATCC CRL-587) was used in assays for virus isolation. Plasma samples of CIP recipients were also tested with plaque-reduction neutralization test.

Results

We obtained infectious SARS-COV-2 isolates from 15/84 nasopharyngeal swabs. The virus could not be isolated from upper respiratory tract samples collected 10-day after onset of symptoms (AOS) in patients with mild–moderate disease.

Conclusion

The knowledge of the extent of SARS-CoV-2 infectivity AOS is relevant for effective prevention measures. This allows to discuss criteria for end isolation despite persistence of positive PCR and improve timing for hospital discharge with consequent availability of critical beds.
Northern Ireland’s New Offence of Domestic Abuse
Authors: McQuigg Ronagh J A
Published: April 2021

A specific offence of domestic abuse was introduced in Northern Ireland in March 2021 under section 1 of the Domestic Abuse and Civil Proceedings Act (Northern Ireland) 2021. This represents a crucial development in Northern Ireland’s response to domestic abuse. The new legislation has the effect of criminalizing coercive and controlling behaviour, therefore bringing Northern Ireland into line with the other jurisdictions within the United Kingdom and Ireland, and also with relevant human rights standards. Being the final jurisdiction within the United Kingdom and Ireland to criminalize such behaviour has enabled Northern Ireland’s approach to be informed by the legislation enacted in the other jurisdictions and, in some respects, has allowed Northern Ireland to ‘cherry pick’ the best aspects of the approaches of these jurisdictions. There are also aspects of Northern Ireland’s domestic abuse offence which differ from the approaches in any of the other jurisdictions in question. However, although the enactment of the domestic abuse offence is certainly a very positive development, this will not constitute a complete panacea to the problem of domestic violence in Northern Ireland. Legislation in itself is insufficient as regards addressing domestic abuse, and further sustained efforts are necessary to tackle this issue.
Molecular phylogeny and revised classification of the Buccinoidea (Neogastropoda)
Authors: Kantor Yuri I , Fedosov Alexander E , Kosyan Alisa R , Puillandre Nicolas , Sorokin Pavel A , Kano Yasunori , Clark Roger , Bouchet Philippe
Published: April 2021

The superfamily Buccinoidea is distributed across the oceans of the world from the Arctic Ocean to the Antarctic and from intertidal to abyssal depths. It encompasses 3351 recent species in 337 genera. The latest taxonomic account recognized eight full families. For the first time, the monophyly of the superfamily and the relationships among the families are tested with molecular data supplemented by anatomical and radula data. Five genetic markers were used: fragments of mitochondrial COI, 16S rRNA, 12S rRNA and nuclear Histone 3 (H3) and 28S rRNA genes (for 225 species of 117 genera). Our analysis recovered Buccinoidea monophyletic in Bayesian analyses. The relationships between the formerly recognized families and subfamilies are drastically revised and a new classification of the superfamily is here proposed, now including 20 taxa of family rank and 23 subfamilies. Five new families (Chauvetiidae, Dolicholatiridae, Eosiphonidae, Prodotiidae and Retimohniidae) and one subfamily of Nassariidae (Tomliniinae) are described. Austrosiphonidae and Tudiclidae are resurrected from synonymy and employed in a new taxonomical extension. All but 40 recent genera are reclassified. Our results demonstrate that anatomy is rather uniform within the superfamily. With exceptions, the rather uniform radular morphology alone does not allow the allocation of genera to a particular family without additional molecular data.
The evolving treatment paradigm of advanced hepatocellular carcinoma: putting all the pieces back together
Authors: D’Alessio Antonio , Cammarota Antonella , Prete Maria Giuseppina , Pressiani Tiziana , Rimassa Lorenza
Published: April 2021

Purpose of review

The therapeutic landscape of advanced hepatocellular carcinoma (HCC) has become notably complex in recent years. With this review, we aimed to put the most recent findings in perspective and tried to delineate the rapidly changing treatment algorithm.

Recent findings

The combination of atezolizumab and bevacizumab has become the new first-line standard of care treatment for unresectable HCC after the positive results of the phase 3 IMbrave150 study. Nivolumab monotherapy failed to demonstrate advantage versus sorafenib in the CheckMate 459 trial, while two different therapeutic strategies (sintilimab and bevacizumab biosimilar and donafenib) outperformed sorafenib in two phase 2/3 studies conducted in the Chinese population. Several immunotherapy combinations are currently under study in large phase 3 trials after promising results in earlier phase studies. About further lines of treatment, the combination of ipilimumab and nivolumab was approved for sorafenib-pretreated patients after the positive results of the phase 1/2 CheckMate 040 study and apatinib was proven effective in the Chinese population in a phase 2/3 study, while pembrolizumab as monotherapy did not show statistically significant superiority when compared with placebo in the KEYNOTE-240 study.

Because of the growing complexity of advanced HCC treatment, the implementation of predictive biomarkers of response is eagerly needed.
New treatments in advanced gastrointestinal stromal tumor
Authors: Serrano César
Published: April 2021

Purpose of review

The current article revisits the most recent advances that occurred in the field of gastrointestinal stromal tumor (GIST) therapeutics.

Recent findings

GIST is driven by the oncogenic activation of KIT or PDGFRA receptor tyrosine kinases, and agents targeting these receptors lead to substantial benefit throughout the entire course of the disease. Two new drugs were approved in 2020. On one hand, ripretinib obtained the regulatory approval for the treatment of GIST patients after progression to all standard treatments. On the other hand, avapritinib became the first agent ever displaying activity in GIST driven by the multiresistant PDGFRA D842V mutation. The addition of both drugs to GIST therapeutics constitutes a remarkable milestone, particularly considering that the last agent approved was back in 2012. Similarly, the recent identification of neurotrophic tyrosine receptor kinase (NTRK) fusions in a subset of KIT/PDGFRA wild-type GISTs led to an open window for tailored treatment using specific NTRK inhibitors. Finally, multiple efforts have been made toward the clinical implementation of circulating tumor DNA evaluation to guide clinical decisions in GIST.

GIST has been consolidated over the years as a paradigmatic model in personalized medicine for the successful development of novel therapeutic strategies through targeted inhibition of oncogenic drivers.
Interventions to Improve Adherence to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia
Authors: Heiney Sue P. , Sorrell McKenzie , Sheng Jingxi , Adams Swann A. , Nelson Kathy , Nguyen Lan A. , Edwards Amy , Wickersham Karen E.
Published: April 2021

Background:

Lack of adherence to tyrosine kinase inhibitors (TKIs) is a significant problem resulting in incomplete cytogenetic response and increased mortality in patients with chronic myeloid leukemia (CML). Few studies have been conducted on interventions to improve adherence. The authors conducted a systematic review to explore studies that examined the impact of strategies to improve TKI adherence among individuals with CML.

Methods:

The first 2 authors completed a systematic literature review according to the guidelines in Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Studies (n=2633) conducted between 1980 and 2019 were identified through 3 databases and examined for inclusion/exclusion criteria.

Results:

Fourteen studies were identified which met the eligibility criteria. The studies only examined adherence to imatinib, dasatinib, or nilotinib. Ten of the 14 used large data sets (commercial health insurance plans or Surveillance Epidemiology and End Results [SEER] data) for analysis. The majority of the studies used a cohort design. Adherence was defined and measured in a variety of ways with most studies using 80% or higher as adequate adherence. Strategies not focused on health care costs used a multidisciplinary team approach.

Conclusion:

Development of evidence to improve treatment adherence to TKIs for CML have relied on large data sets rather than prospective trials. Current studies lack patient focused interventions.
The impact of submucosal fatty tissue during colon endoscopic submucosal dissection in a western center
Authors: Ramos-Zabala Felipe , Parra-Blanco Adolfo , Beg Sabina , Rodríguez-Pascual Jesús , Cárdenas Rebollo José Miguel , Cardozo-Rocabado Rocío , Moreno-Almazán Luis
Published: April 2021

Objectives

Obesity is associated with submucosal fatty tissue. The main aim of this study was to assess the impact of submucosal fatty tissue on the success of colonic endoscopic submucosal dissection (C-ESD) in a western population.

Methods

This was a retrospective analysis of 125 consecutive C-ESDs performed between October 2015 and July 2017. Fatty tissue sign was defined as positive when the submucosal layer was covered with fatty tissue. The complexity of performing an ESD was assessed by the performing endoscopist, defined by the occurrence of intraprocedural perforation, inability to complete an en-bloc resection or a procedure time exceeding 180 min.

Results

Fatty tissue sign positive was present in 44.8% of the procedures. There were 28 (22.4%) c-ESD defined as complex. Factors associated with complex ESD included; fatty tissue sign [odds ratio (OR) 12.5; 95% confidence interval (CI), 1.9–81.9; P = 0.008], severe fibrosis (OR 148.6; 95% CI, 6.6–3358.0; P = 0.002), poor maneuverability (OR 267.4; 95% CI, 11.5–6212.5; P < 0.001) and polyp size ≥35 mm (OR 17.2; 95% CI, 2.6–113.8; P = 0.003). In patients demonstrating the fatty tissue sign, BMI and waist-to-height ratio (WHtR) were higher (27.8 vs. 24.7; P < 0.001 and 0.56 vs. 0.49; P < 0.001, respectively) and en-bloc resection was achieved less frequently (76.8 vs. 97.1%, P = 0.001). Multivariate analysis revealed higher risk of fatty tissue sign positive associated with WHtR ≥0.52 (OR 26.10, 95% CI, 7.63–89.35, P < 0.001).

Conclusion

This study demonstrates that the fatty tissue sign contributes to procedural complexity during C-ESD. Central obesity correlates with the likelihood of submucosal fatty tissue and as such should be taken into account when planning procedures.