bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness of cardiac telerehabilitation in coronary artery disease and heart failure patients: systematic review of randomized controlled trials
Authors: Scherrenberg Martijn , Falter Maarten , Dendale Paul
Published: November 2020

This systematic review aims to assess the cost-effectiveness of cardiac telerehabilitation in comparison with centre-based cardiac rehabilitation (CR). Evidence of cost-effectiveness is an important step towards implementation and reimbursement of telerehabilitation services. Electronic databases were searched for economic evaluations of telerehabilitation programmes. Only randomized controlled trials (RCTs) published in English were eligible for inclusion. Study quality and risk of bias were assessed using the Consensus Health Economic Criteria (CHEC) list. A total of eight economic evaluations met the review inclusion criteria. The total sample size consisted of 751 patients ranging from a minimum of 46 patients to a maximum of 162 patients per study. Maximal follow-up was 5 years. A total of seven of the eight included studies demonstrated that telerehabilitation could lead to similar or lower long-term costs and are thus as cost-effective as traditional centre-based CR. There is significant heterogeneity between all included telerehabilitation interventions in duration, used technology, cost included and follow-up. Based on these small short duration trials, telerehabilitation may be as cost-effective as traditional centre-based approaches. However, more assessments of the value for money of telerehabilitation in larger and longer RCTs are needed both in high- as low-income countries.
Prediction of coronary artery calcium scoring from surface electrocardiogram in atherosclerotic cardiovascular disease: a pilot study
Authors: Farjo Peter D , Yanamala Naveena , Kagiyama Nobuyuki , Patel Heenaben B , Casaclang-Verzosa Grace , Nezarat Negin , Budoff Matthew J , Sengupta Partho P
Published: November 2020

Aims

Coronary artery calcium (CAC) scoring is an established tool for cardiovascular risk stratification. However, the lack of widespread availability and concerns about radiation exposure have limited the universal clinical utilization of CAC. In this study, we sought to explore whether machine learning (ML) approaches can aid cardiovascular risk stratification by predicting guideline recommended CAC score categories from clinical features and surface electrocardiograms.

Methods and results

In this substudy of a prospective, multicentre trial, a total of 534 subjects referred for CAC scores and electrocardiographic data were split into 80% training and 20% testing sets. Two binary outcome ML logistic regression models were developed for prediction of CAC scores equal to 0 and ≥400. Both CAC = 0 and CAC ≥400 models yielded values for the area under the curve, sensitivity, specificity, and accuracy of 84%, 92%, 70%, and 75%, and 87%, 91%, 75%, and 81%, respectively. We further tested the CAC ≥400 model to risk stratify a cohort of 87 subjects referred for invasive coronary angiography. Using an intermediate or higher pretest probability (≥15%) to predict CAC ≥400, the model predicted the presence of significant coronary artery stenosis (P = 0.025), the need for revascularization (P < 0.001), notably bypass surgery (P = 0.021), and major adverse cardiovascular events (P = 0.023) during a median follow-up period of 2 years.

Conclusion

ML techniques can extract information from electrocardiographic data and clinical variables to predict CAC score categories and similarly risk-stratify patients with suspected coronary artery disease.
Increased myocardial stiffness more than impaired relaxation function limits cardiac performance during exercise in heart failure with preserved ejection fraction: a virtual patient study
Authors: van Loon Tim , Knackstedt Christian , Cornelussen Richard , Reesink Koen D , Brunner La Rocca Hans-Peter , Delhaas Tammo , van Empel Vanessa , Lumens Joost
Published: November 2020

Aims

The relative impact of left ventricular (LV) diastolic dysfunction (LVDD) and impaired left atrial (LA) function on cardiovascular haemodynamics in heart failure with preserved ejection fraction (HFpEF) is largely unknown. We performed virtual patient simulations to elucidate the relative effects of these factors on haemodynamics at rest and during exercise.

Methods and results

The CircAdapt cardiovascular system model was used to simulate cardiac haemodynamics in wide ranges of impaired LV relaxation function, increased LV passive stiffness, and impaired LA function. Simulations showed that LV ejection fraction (LVEF) was preserved (>50%), despite these changes in LV and LA function. Impairment of LV relaxation function decreased E/A ratio and mildly increased LV filling pressure at rest. Increased LV passive stiffness resulted in increased E/A ratio, LA dilation and markedly elevated LV filling pressure. Impairment of LA function increased E/A ratio and LV filling pressure, explaining inconsistent grading of LVDD using echocardiographic indices. Exercise simulations showed that increased LV passive stiffness exerts a stronger exercise-limiting effect than impaired LV relaxation function does, especially with impaired LA function.

Conclusion

The CircAdapt model enabled realistic simulation of virtual HFpEF patients, covering a wide spectrum of LVDD and related limitations of cardiac exercise performance, all with preserved resting LVEF. Simulations suggest that increased LV passive stiffness, more than impaired relaxation function, reduces exercise tolerance, especially when LA function is impaired. In future studies, the CircAdapt model can serve as a valuable platform for patient-specific simulations to identify the disease substrate(s) underlying the individual HFpEF patient’s cardiovascular phenotype.
Immersive 3D virtual reality imaging in planning minimally invasive and complex adult cardiac surgery
Authors: Sadeghi Amir H , Bakhuis Wouter , Van Schaagen Frank , Oei Frans B S , Bekkers Jos A , Maat Alexander P W M , Mahtab Edris A F , Bogers Ad J J C , Taverne Yannick J H J
Published: November 2020

Aims

Increased complexity in cardiac surgery over the last decades necessitates more precise preoperative planning to minimize operating time, to limit the risk of complications during surgery and to aim for the best possible patient outcome. Novel, more realistic, and more immersive techniques, such as three-dimensional (3D) virtual reality (VR) could potentially contribute to the preoperative planning phase. This study shows our initial experience on the implementation of immersive VR technology as a complementary research-based imaging tool for preoperative planning in cardiothoracic surgery. In addition, essentials to set up and implement a VR platform are described.

Methods

Six patients who underwent cardiac surgery at the Erasmus Medical Center, Rotterdam, The Netherlands, between March 2020 and August 2020, were included, based on request by the surgeon and availability of computed tomography images. After 3D VR rendering and 3D segmentation of specific structures, the reconstruction was analysed via a head mount display. All participating surgeons (n = 5) filled out a questionnaire to evaluate the use of VR as preoperative planning tool for surgery.

Conclusion

Our study demonstrates that immersive 3D VR visualization of anatomy might be beneficial as a supplementary preoperative planning tool for cardiothoracic surgery, and further research on this topic may be considered to implement this innovative tool in daily clinical practice.

Lay summary

Over the past decades, surgery on the heart and vessels is becoming more and more complex, necessitating more precise and accurate preoperative planning. Nowadays, operative planning is feasible on flat, two-dimensional computer screens, however, requiring a lot of spatial and three-dimensional (3D) thinking of the surgeon. Since immersive 3D virtual reality (VR) is an upcoming imaging technique with promising results in other fields of surgery, we aimed in this study to explore the additional value of this technique in heart surgery. Our surgeons planned six different heart operations by visualizing computed tomography scans with a dedicated VR headset, enabling them to visualize the patient’s anatomy in an immersive and 3D environment. The outcomes of this preliminary study are positive, with a much more reality-like simulation for the surgeon. In such, VR could potentially be beneficial as a preoperative planning tool for complex heart surgery.
Automated lumen segmentation using multi-frame convolutional neural networks in intravascular ultrasound datasets
Authors: Ziemer Paulo G P , Bulant Carlos A , Orlando José I , Maso Talou Gonzalo D , Álvarez Luis A Mansilla , Guedes Bezerra Cristiano , Lemos Pedro A , García-García Héctor M , Blanco Pablo J
Published: November 2020

Aims

Assessment of minimum lumen areas in intravascular ultrasound (IVUS) pullbacks is time-consuming and demands adequately trained personnel. In this work, we introduce a novel and fully automated pipeline to segment the lumen boundary in IVUS datasets.

Methods and results

First, an automated gating is applied to select end-diastolic frames and bypass saw-tooth artefacts. Second, within a machine learning (ML) environment, we automatically segment the lumen boundary using a multi-frame (MF) convolutional neural network (MFCNN). Finally, we use the theory of Gaussian processes (GPs) to regress the final lumen boundary. The dataset consisted of 85 IVUS pullbacks (52 patients). The dataset was partitioned at the pullback-level using 73 pullbacks for training (20 586 frames), 6 pullbacks for validation (1692 frames), and 6 for testing (1692 frames). The degree of overlapping, between the ground truth and ML contours, median (interquartile range, IQR) systematically increased from 0.896 (0.874–0.933) for MF1 to 0.925 (0.911–0.948) for MF11. The median (IQR) of the distance error was also reduced from 3.83 (2.94–4.98)% for MF1 to 3.02 (2.25–3.95)% for MF11-GP. The corresponding median (IQR) in the lumen area error remained between 5.49 (2.50–10.50)% for MF1 and 5.12 (2.15–9.00)% for MF11-GP. The dispersion in the relative distance and area errors consistently decreased as we increased the number of frames, and also when the GP regressor was coupled to the MFCNN output.

Conclusion

These results demonstrate that the proposed ML approach is suitable to effectively segment the lumen boundary in IVUS scans, reducing the burden of costly and time-consuming manual delineation.
Many roads to bacterial generalism
Authors: Bell Terrence H , Bell Thomas
Published: November 2020

The fundamental niches of bacteria can be defined along many environmental axes, including temperature tolerance and resources consumed, while interactions with other organisms can constrain (e.g. competition) or enlarge (e.g. cross-feeding) realized niches. Organisms are often categorized as generalists or specialists, corresponding to broad or narrow niche requirements, which can then be linked to their functional role in an ecosystem. We show how these terms are applied to bacteria, make predictions about how the type and extent of generalism displayed by an organism relates to its functional potential and discuss the value of collecting different types of generalist bacteria. We believe that new approaches that take advantage of both high-throughput sequencing and environmental manipulation can allow us to understand the many types of generalism found within both cultivated and yet-to-be-cultivated bacteria.
Residential cluster design and potential improvement for maximum energy performance and outdoor thermal comfort on a hot summer in Thailand
Authors: Jareemit Daranee , Canyookt Parintorn
Published: November 2020

Thailand committed to achieving the Sustainable Development Goals to increase urban livability and reduce energy use in the building sector. However, the design information to achieve those challenge goals has been undefined. This study aimed to investigate and examine potential improvements for outdoor thermal comfort and energy efficiency in 136 designs of the two-type residential cluster in Pathum Thani, Thailand, via designs of building orientation, geometry and window-to-wall ratio (WWR). The daily cooling energy consumption in residential clusters was performed using eQuest under the modified weather data from the prior microclimate analysis. The energy-saving scenarios were calculated and compared to the acceptable outdoor thermal comfort hours. It is found that the row house cluster had the potential to be more sustainable than a single house. The row house clusters on orthogonal street orientation offered the highest percentage of hours in outdoor thermal comfort of 46% and energy efficiency below the new standard of Thailand. The cooling energy savings through increasing H/W with lowering WWR was up to 32%. This study’s results could provide urban planners and architects with the new design guidelines and improvement potentials to make cities more energy efficient and environmentally friendly for outdoor living in Thailand.
COVID-19: leadership on the frontline is what matters when we support healthcare workers
Authors: Obrien Niki , Flott Kelsey , Durkin Mike
Published: November 2020

The implications of severe acute respiratory syndrome coronavirus (SARS-CoV-2, henceforth described as COVID-19) on healthcare systems globally are proving to be immense, with unforeseen impacts that are still to fully emerge. Local and national healthcare systems, hospitals and healthcare workers have been overwhelmed by the needs of patients and limited by weaknesses in resources, staff capacity and distribution networks. These circumstances impact the ergonomic conditions within which healthcare staff work and subsequently their behavioural responses.In this commentary, we argue that urgent research is needed globally to bridge the evidence gap that exists on how best to support healthcare workers with the repercussions of working on the frontline of a pandemic. Leadership on the frontline is what matters. It is not only what policies, guidelines and checklists are in place to support nurses, doctors and healthcare workers, it is the actions and behaviours of their frontline and local leaders in implementing initiatives that really make the difference.Recognizing that the leadership style, organizational culture and model of successful implementation are inextricable is the first step to ensure sustainable interventions to support healthcare workers’ well-being will follow.
Transcriptional integration of plant responses to iron availability
Authors: Gao Fei , Dubos Christian
Published: November 2020

Iron is one of the most important micronutrients for plant growth and development. It functions as the enzyme cofactor or component of electron transport chains in various vital metabolic processes, including photosynthesis, respiration, and amino acid biosynthesis. To maintain iron homeostasis, and therefore prevent any deficiency or excess that could be detrimental, plants have evolved complex transcriptional regulatory networks to tightly control iron uptake, translocation, assimilation, and storage. These regulatory networks are composed of various transcription factors; among them, members of the basic helix-loop-helix (bHLH) family play an essential role. Here, we first review recent advances in understanding the roles of bHLH transcription factors involved in the regulatory cascade controlling iron homeostasis in the model plant Arabidopsis, and extend this understanding to rice and other plant species. The importance of other classes of transcription factors will also be discussed. Second, we elaborate on the post-translational mechanisms involved in the regulation of these regulatory networks. Finally, we provide some perspectives on future research that should be conducted in order to precisely understand how plants control the homeostasis of this micronutrient.
Growth and structure of multiphase gas in the cloud-crushing problem with cooling
Authors: Kanjilal Vijit , Dutta Alankar , Sharma Prateek
Published: November 2020

We revisit the problem of the growth of dense/cold gas in the cloud-crushing set-up with radiative cooling. The relative motion between the dense cloud and the diffuse medium produces a turbulent boundary layer of mixed gas with a short cooling time. This mixed gas may explain the ubiquity of the range of absorption/emission lines observed in various sources such as the circumgalactic medium and galactic/stellar/active galactic nucleus outflows. Recently, Gronke & Oh showed that the efficient radiative cooling of the mixed gas can lead to continuous growth of the dense cloud. They presented a threshold cloud size for the growth of dense gas that was contradicted by the more recent works of Li et al. & Sparre et al. These thresholds are qualitatively different as the former is based on the cooling time of the mixed gas whereas the latter is based on the cooling time of the hot gas. Our simulations agree with the threshold based on the cooling time of the mixed gas. We argue that the radiative cloud-crushing simulations should be run long enough to allow for the late-time growth of the dense gas due to cooling of the mixed gas but not so long that the background gas cools catastrophically. Moreover, the simulation domain should be large enough that the mixed gas is not lost through the boundaries. While the mixing layer is roughly isobaric, the emissivity of the gas at different temperatures is fundamentally different from an isobaric single-phase steady cooling flow.
A study of radial self-similar non-relativistic MHD outflow models: parameter space exploration and application to the water fountain W43A
Authors: Ceccobello C , Heemskerk M H M , Cavecchi Y , Vlemmings W H T , Tafoya D
Published: November 2020

Outflows, spanning a wide range of dynamical properties and spatial extensions, have now been associated with a variety of accreting astrophysical objects, from supermassive black holes at the core of active galaxies to young stellar objects. The role of such outflows is key to the evolution of the system that generates them, for they extract a fraction of the orbiting material and angular momentum from the region close to the central object and release them in the surroundings. The details of the launching mechanism and their impact on the environment are fundamental to understand the evolution of individual sources and the similarities between different types of outflow-launching systems. We solve semi-analytically the non-relativistic, ideal, magnetohydrodynamics equations describing outflows launched from a rotating disc threaded with magnetic fields using our new numerical scheme. We present here a parameter study of a large sample of new solutions. We study the different combinations of forces that lead to a successfully launched jet and discuss their global properties. We show how these solutions can be applied to the outflow of the water fountain W43A for which we have observational constraints on magnetic field, density and velocity of the flow at the location of two symmetrical water maser emitting regions.
A quantitative in-depth analysis of the prototype sdB+BD system SDSS J08205+0008 revisited in the Gaia era
Authors: Schaffenroth V , Casewell S L , Schneider D , Kilkenny D , Geier S , Heber U , Irrgang A , Przybilla N , Marsh T R , Littlefair S P , Dhillon V S
Published: November 2020

Subdwarf B stars are core-helium-burning stars located on the extreme horizontal branch (EHB). Extensive mass loss on the red giant branch is necessary to form them. It has been proposed that substellar companions could lead to the required mass loss when they are engulfed in the envelope of the red giant star. J08205+0008 was the first example of a hot subdwarf star with a close, substellar companion candidate to be found. Here, we perform an in-depth re-analysis of this important system with much higher quality data allowing additional analysis methods. From the higher resolution spectra obtained with ESO-VLT/XSHOOTER, we derive the chemical abundances of the hot subdwarf as well as its rotational velocity. Using the Gaia parallax and a fit to the spectral energy distribution in the secondary eclipse, tight constraints to the radius of the hot subdwarf are derived. From a long-term photometric campaign, we detected a significant period decrease of $-3.2(8)\times 10^{-12} \, \rm dd^{-1}$. This can be explained by the non-synchronized hot subdwarf star being spun up by tidal interactions forcing it to become synchronized. From the rate of period decrease we could derive the synchronization time-scale to be 4 Myr, much smaller than the lifetime on EHB. By combining all different methods, we could constrain the hot subdwarf to a mass of $0.39\!-\!0.50\, \rm M_\odot$ and a radius of $R_{\rm sdB}=0.194\pm 0.008\, \rm R_\odot$, and the companion to $0.061\!-\!0.071\rm \, M_\odot$ with a radius of $R_{\rm comp}=0.092 \pm 0.005\, \rm R_\odot$, below the hydrogen-burning limit. We therefore confirm that the companion is most likely a massive brown dwarf.
A new transient ultraluminous X-ray source in NGC 7090
Authors: Walton D J , Heida M , Bachetti M , Fürst F , Brightman M , Earnshaw H , Evans P A , Fabian A C , Grefenstette B W , Harrison F A , Israel G L , Lansbury G B , Middleton M J , Pike S , Rana V , Roberts T P , Rodriguez Castillo G A , Salvaterra R , Song X , Stern D
Published: November 2020

We report on the discovery of a new, transient ultraluminous X-ray source (ULX) in the galaxy NGC 7090. This new ULX, which we refer to as NGC 7090 ULX3, was discovered via monitoring with Swift during 2019–2020, and to date has exhibited a peak luminosity of LX ∼ 6 × 1039 erg s−1. Archival searches show that, prior to its recent transition into the ULX regime, ULX3 appeared to exhibit a fairly stable luminosity of LX ∼ 1038 erg s−1. Such strong long-time-scale variability may be reminiscent of the small population of known ULX pulsars, although deep follow-up observations with XMM–Newton and NuSTAR do not reveal any robust X-ray pulsation signals. Pulsations similar to those seen from known ULX pulsars cannot be completely excluded, however, as the limit on the pulsed fraction of any signal that remains undetected in these data is ≲20 per cent. The broad-band spectrum from these observations is well modelled with a simple thin disc model, consistent with sub-Eddington accretion, which may instead imply a moderately large black hole accretor (MBH ∼ 40 M⊙). Similarly, though, more complex models consistent with the super-Eddington spectra seen in other ULXs (and the known ULX pulsars) cannot be excluded given the limited signal-to-noise ratio of the available broad-band data. The nature of the accretor powering this new ULX therefore remains uncertain.
AstroVaDEr: astronomical variational deep embedder for unsupervised morphological classification of galaxies and synthetic image generation
Authors: Spindler Ashley , Geach James E , Smith Michael J
Published: November 2020

We present AstroVaDEr (Astronomical Variational Deep Embedder), a variational autoencoder designed to perform unsupervised clustering and synthetic image generation using astronomical imaging catalogues. The model is a convolutional neural network that learns to embed images into a low-dimensional latent space, and simultaneously optimizes a Gaussian Mixture Model (GMM) on the embedded vectors to cluster the training data. By utilizing variational inference, we are able to use the learned GMM as a statistical prior on the latent space to facilitate random sampling and generation of synthetic images. We demonstrate AstroVaDEr’s capabilities by training it on grey-scaled gri images from the Sloan Digital Sky Survey, using a sample of galaxies that are classified by Galaxy Zoo 2. An unsupervised clustering model is found that separates galaxies based on learned morphological features such as axial ratio, surface brightness profile, orientation, and the presence of companions. We use the learned mixture model to generate synthetic images of galaxies based on the morphological profiles of the Gaussian components. AstroVaDEr succeeds in producing a morphological classification scheme from unlabelled data, but unexpectedly places high importance on the presence of companion objects – demonstrating the importance of human interpretation. The network is scalable and flexible, allowing for larger data sets to be classified, or different kinds of imaging data. We also demonstrate the generative properties of the model, which allow for realistic synthetic images of galaxies to be sampled from the learned classification scheme. These can be used to create synthetic image catalogues or to perform image processing tasks such as deblending.
Testing general relativity on cosmological scales at redshift z ∼ 1.5 with quasar and CMB lensing
Authors: Zhang Yucheng , Pullen Anthony R , Alam Shadab , Singh Sukhdeep , Burtin Etienne , Chuang Chia-Hsun , Hou Jiamin , Lyke Brad W , Myers Adam D , Neveux Richard , Ross Ashley J , Rossi Graziano , Zhao Cheng
Published: November 2020

We test general relativity (GR) at the effective redshift $\bar{z} \sim 1.5$ by estimating the statistic EG, a probe of gravity, on cosmological scales $19 - 190\, h^{-1}{\rm Mpc}$. This is the highest redshift and largest scale estimation of EG so far. We use the quasar sample with redshifts 0.8 < z < 2.2 from Sloan Digital Sky Survey IV extended Baryon Oscillation Spectroscopic Survey Data Release 16 as the large-scale structure (LSS) tracer, for which the angular power spectrum $C_\ell ^{qq}$ and the redshift-space distortion parameter β are estimated. By cross-correlating with the Planck 2018 cosmic microwave background (CMB) lensing map, we detect the angular cross-power spectrum $C_\ell ^{\kappa q}$ signal at $12\, \sigma$ significance. Both jackknife resampling and simulations are used to estimate the covariance matrix (CM) of EG at five bins covering different scales, with the later preferred for its better constraints on the covariances. We find EG estimates agree with the GR prediction at $1\, \sigma$ level over all these scales. With the CM estimated with 300 simulations, we report a best-fitting scale-averaged estimate of $E_G(\bar{z})=0.30\pm 0.05$, which is in line with the GR prediction $E_G^{\rm GR}(\bar{z})=0.33$ with Planck 2018 CMB + BAO matter density fraction Ωm = 0.31. The statistical errors of EG with future LSS surveys at similar redshifts will be reduced by an order of magnitude, which makes it possible to constrain modified gravity models.
Tango for three: Sagittarius, LMC, and the Milky Way
Authors: Vasiliev Eugene , Belokurov Vasily , Erkal Denis
Published: November 2020

We assemble a catalogue of candidate Sagittarius stream members with 5D and 6D phase-space information, using astrometric data from Gaia DR2, distances estimated from RR Lyrae stars, and line-of-sight velocities from various spectroscopic surveys. We find a clear misalignment between the stream track and the direction of the reflex-corrected proper motions in the leading arm of the stream, which we interpret as a signature of a time-dependent perturbation of the gravitational potential. A likely cause of this perturbation is the recent passage of the most massive Milky Way satellite – the Large Magellanic Cloud (LMC). We develop novel methods for simulating the Sagittarius stream in the presence of the LMC, using specially tailored N-body simulations and a flexible parametrization of the Milky Way halo density profile. We find that while models without the LMC can fit most stream features rather well, they fail to reproduce the misalignment and overestimate the distance to the leading arm apocentre. On the other hand, models with an LMC mass in the range $(1.3\pm 0.3)\times 10^{11}\, \mathrm{M}_\odot$ rectify these deficiencies. We demonstrate that the stream can not be modelled adequately in a static Milky Way. Instead, our Galaxy is required to lurch toward the massive in-falling Cloud, giving the Sgr stream its peculiar shape and kinematics. By exploring the parameter space of Milky Way potentials, we determine the enclosed mass within 100 kpc to be $(5.6\pm 0.4)\times 10^{11}\, \mathrm{M}_\odot$, and the virial mass to be $(9.0\pm 1.3)\times 10^{11}\, \mathrm{M}_\odot$, and find tentative evidence for a radially-varying shape and orientation of the Galactic halo.
The effect of stellar multiplicity on protoplanetary discs: a near-infrared survey of the Lupus star-forming region
Authors: Zurlo Alice , Cieza Lucas A , Ansdell Megan , Christiaens Valentin , Pérez Sebastián , Lovell Josh , Mesa Dino , Williams Jonathan P , Gonzalez-Ruilova Camilo , Carraro Rosamaria , Ruíz-Rodríguez Dary , Wyatt Mark
Published: November 2020

We present results from a near-infrared (NIR) adaptive optics (AO) survey of pre-main-sequence stars in the Lupus molecular cloud with NACO at the Very Large Telescope (VLT) to identify (sub)stellar companions down to ∼20-au separation and investigate the effects of multiplicity on circumstellar disc properties. We observe for the first time in the NIR with AO a total of 47 targets and complement our observations with archival data for another 58 objects previously observed with the same instrument. All 105 targets have millimetre Atacama Large Millimetre/sub-millimetre Array (ALMA) data available, which provide constraints on disc masses and sizes. We identify a total of 13 multiple systems, including 11 doubles and 2 triples. In agreement with previous studies, we find that the most massive (Mdust > 50 M⊕) and largest (Rdust > 70 au) discs are only seen around stars lacking visual companions (with separations of 20–4800 au) and that primaries tend to host more massive discs than secondaries. However, as recently shown in a very similar study of >200 PMS stars in the Ophiuchus molecular cloud, the distributions of disc masses and sizes are similar for single and multiple systems for Mdust < 50 M⊕ and radii Rdust < 70 au. Such discs correspond to ∼80–90 per cent of the sample. This result can be seen in the combined sample of Lupus and Ophiuchus objects, which now includes more than 300 targets with ALMA imaging and NIR AO data, and implies that stellar companions with separations >20 au mostly affect discs in the upper 10${{\ \rm per\ cent}}$ of the disc mass and size distributions.
The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets
Authors: Szklarczyk Damian , Gable Annika L , Nastou Katerina C , Lyon David , Kirsch Rebecca , Pyysalo Sampo , Doncheva Nadezhda T , Legeay Marc , Fang Tao , Bork Peer , Jensen Lars J , von Mering Christian
Published: November 2020

Cellular life depends on a complex web of functional associations between biomolecules. Among these associations, protein–protein interactions are particularly important due to their versatility, specificity and adaptability. The STRING database aims to integrate all known and predicted associations between proteins, including both physical interactions as well as functional associations. To achieve this, STRING collects and scores evidence from a number of sources: (i) automated text mining of the scientific literature, (ii) databases of interaction experiments and annotated complexes/pathways, (iii) computational interaction predictions from co-expression and from conserved genomic context and (iv) systematic transfers of interaction evidence from one organism to another. STRING aims for wide coverage; the upcoming version 11.5 of the resource will contain more than 14 000 organisms. In this update paper, we describe changes to the text-mining system, a new scoring-mode for physical interactions, as well as extensive user interface features for customizing, extending and sharing protein networks. In addition, we describe how to query STRING with genome-wide, experimental data, including the automated detection of enriched functionalities and potential biases in the user's query data. The STRING resource is available online, at https://string-db.org/.
Using bio-orthogonally catalyzed lethality strategy to generate mitochondria-targeting anti-tumor metallodrugs in vitro and in vivo
Authors: Xue Xuling , Qian Chenggen , Tao Qin , Dai Yuanxin , Lv Mengdi , Dong Jingwen , Su Zhi , Qian Yong , Zhao Jing , Liu Hong-Ke , Guo Zijian
Published: November 2020

Synthetic lethality was proposed nearly a century ago by geneticists and recently applied to develop precision anti-cancer therapies. To exploit the synthetic lethality concept in the design of chemical anti-cancer agents, we developed a bio-orthogonally catalyzed lethality (BCL) strategy to generate targeting anti-tumor metallodrugs both in vitro and in vivo. Metallodrug Ru-rhein was generated from two non-toxic species Ru-N3 and rhein-alkyne via exclusive endogenous copper-catalyzed azide alkyne cycloaddition (CuAAC) reaction without the need of an external copper catalyst. The non-toxic species Ru-arene complex Ru-N3 and rhein-alkyne were designed to perform this strategy, and the mitochondrial targeting product Ru-rhein was generated in high yield (>83%) and showed high anti-tumor efficacy in vitro. This BCL strategy achieved a remarkable tumor suppression effect on the tumor-bearing mice models. It is interesting that the combination of metal-arene complexes with rhein via CuAAC reaction could transform two non-toxic species into a targeting anti-cancer metallodrug both in vitro and in vivo, while the product Ru-rhein was non-toxic towards normal cells. This is the first example that exclusive endogenous copper was used to generate metal-based anti-cancer drugs for cancer treatment. The anti-cancer mechanism of Ru-rhein was studied and autophagy was induced by increased reactive oxygen species and mitochondrial damage. The generality of this BCL strategy was also studied and it could be extended to other metal complexes such as Os-arene and Ir-arene complexes. Compared with the traditional methods for cancer treatment, this work presented a new approach to generating targeting metallodrugs in vivo via the BCL strategy from non-toxic species in metal-based chemotherapy.
Examining Market Trends in Smokeless Tobacco Sales in the United States: 2011–2019
Authors: Delnevo Cristine D , Hrywna Mary , Miller Lo Erin J , Wackowski Olivia A
Published: November 2020

Introduction

The smokeless tobacco (SLT) industry in the U.S. continues to transform with novel products amid an evolving regulatory environment. We report SLT sales trends in the U.S. by analyzing retail market scanner data from 2011 through 2019.

Methods

National SLT sales data were obtained from Nielsen's Convenience Track System for January 2011 to December 2019. UPC codes were used to classify products by attributes including type, parent company, brand, form, and flavor. Market share was calculated as percentage of total unit sales. Detailed product analysis was presented for moist snuff, snus, and tobacco-free nicotine products.

Results

SLT sales increased by 5.8% between 2011 and 2016 but declined by 3.9% from 2016 to 2019. Moist snuff sales increased by 8.1% between 2011 and 2016 and then declined 7.4% from 2016 to 2019 but still accounted for roughly 90% of the overall market annually. Between 2011 and 2019, snus sales consistently increased while sales of chew, dry snuff, and dissolvables decreased. Tobacco-free nicotine products emerged in 2016 and captured 4.0% of the market by 2019. Portion pouch packaging and flavors showed consistent growth although their popularity varied by the type of smokeless product.

Conclusion

This study extends our previous work on U.S. SLT market trends through 2019. Overall sales increased between 2011 and 2016 but there were signs of leveling off including declining sales of moist snuff. Newer products continue to gain market share. Continued monitoring of SLT sales is needed, particularly given the new modified risk status of several products.

Implications

This study analyzed the last 9 years of smokeless tobacco market data (2011–2019) to describe recent trends in sales. Overall, the smokeless product category is quite resilient although signs suggest downward trends among some product categories and features. New types of smokeless tobacco products (eg, snus and tobacco-free nicotine pouches) account for a growing share of the market.
Dioscorea Alata Tuber Proteome Analysis Uncovers Differentially Regulated Growth-associated Pathways of Tuber Development
Authors: Sharma Shruti , Deswal Renu
Published: November 2020

During its life cycle, the Dioscorea tuber undergoes multiple morphological and biochemical changes. To gain a better understanding of the metabolic changes associated with tuber growth, a stage-specific gel-free proteome analysis of four distinct morphological stages namely germinating tuber (S1), degrading tuber (S2), new tuber formation (S3) and tuber maturation (S4) was done and validated by principal component analysis. A comprehensive data set identifying 78.2% of the total 3,681 proteins was generated. PANTHER and KEGG MAPPER revealed both expected (carbohydrate metabolism and redox regulation) and novel biological processes (transcription factors and hormonal regulation) characteristic for each developmental stage. Higher abundance of the enzymes of ascorbate–glutathione cycle and carbohydrate metabolism was detected during tuber germination (S1) and tuber formation stages (S3) in comparison with the mature tuber. The presence of ethylene biosynthesis components during tuber formation hints toward its probable role in postharvest shelf life. The data set comprehensively describes the proteome of Dioscorea tuber and provides growth-specific markers for tuber germination (ascorbate peroxidase, monodehydroascorbate reductase, invertase) and tuber formation (sucrose synthase), which were validated by enzyme activity assays and Western blotting. The study provides information that may influence the direction of research for improving the productivity of this under-utilized and largely neglected crop.
Milton’s New Hero: Homeric Revisions in Paradise Regained
Authors: Péti Miklós
Published: November 2020

In this paper I propose an important, but hitherto unexplored connection between Milton’s Paradise Regained and Homer’s Odyssey. I argue at length that Paradise Regained is Milton’s critical revision of the story of Telemachus, the section of the Odyssey presenting the trials of Odysseus’s son. Recognizing Telemachus as Milton’s chief classical model for the Jesus of Paradise Regained provides solid grounding for earlier critics’ intuitions about Milton’s classicism, and it also sheds new light on Milton’s radically innovative poetic method.
The Role of ATP-Binding Cassette Transporters in Bacterial Phytopathogenesis
Authors: Zeng Yuan , Charkowski Amy O.
Published: November 2020

Bacteria use selective membrane transporting strategies to support cell survival in different environments. Of the membrane transport systems, ATP-binding cassette (ABC) transporters, which utilize the energy of ATP hydrolysis to deliver substrate across the cytoplasmic membrane, are the largest and most diverse superfamily. These transporters import nutrients, export molecules, and are required for diverse cell functions, including cell division and morphology, gene regulation, surface motility, chemotaxis, and interspecies competition. Phytobacterial pathogens encode numerous ABC transporter homologs compared with related nonphytopathogens, with up to 160 transporters per genome, suggesting that plant pathogens must be able to import or respond to a greater number of molecules compared with saprophytes or animal pathogens. Despite their importance, ABC transporters have been little examined in plant pathogens. To understand bacterial phytopathogenesis and evolution, we need to understand the roles that ABC transporters play in plant–microbe interactions. In this review, we outline a multitude of roles that bacterial ABC transporters play, using both plant and animal pathogens as examples, to emphasize the importance of exploring these transporters in phytobacteriology.
Genetic Diversity of the Fusarium oxysporum Complex Isolated from the Grassland Biome of South Africa
Authors: Nephalela-Mavhunga Mudzuli , Kwinda Grace T. , Summerell Brett A. , Venter Eduard , Jacobs Adriaana
Published: November 2020

The genetic diversity of pathogenic members of the Fusarium oxysporum species complex (FOSC) has been intensively studied worldwide, yet strains occurring in native soils with low anthropogenic disturbance remain poorly understood. This study focused on 355 F. oxysporum isolates from soils with low anthropogenic activity obtained from the grassland biome of South Africa. Analysis of the translation elongation factor 1-alpha (tef-1α) gene revealed high levels of sequence type diversity within the soil population in comparison with the global dataset. Phylogenetic relationships of the South African isolates revealed that four nested within FOSC clade 1. This is the first report of members of the basal clade recovered from ecosystems with low anthropogenic disturbance from Sub-Saharan Africa. The remaining strains nested within clades 2 to 5. This study contributes significantly to our understanding of the distribution of the FOSC in natural systems as we show that FOSC populations in the South African grassland biome are genetically diverse. This fills in our knowledge gap because previous studies reported only on the occurrence and diversity of the FOSC isolated from plant debris in South Africa. This is the first comprehensive survey of fusaria from grassland soils with low anthropogenic disturbance in South Africa.
Recent advances in targeted drug delivery for treatment of osteoarthritis
Authors: Mehta Shikhar , He Tengfei , Bajpayee Ambika G.
Published: November 2020

Purpose of review

Osteoarthritis is associated with severe joint pain, inflammation, and cartilage degeneration. Drugs injected directly into intra-articular joint space clear out rapidly providing only short-term benefit. Their transport into cartilage to reach cellular targets is hindered by the tissue's dense, negatively charged extracellular matrix. This has limited, despite strong preclinical data, the clinical translation of osteoarthritis drugs. Recent work has focused on developing intra-joint and intra-cartilage targeting drug delivery systems (DDS) to enable long-term therapeutic response, which is presented here.

Recent findings

Synovial joint targeting hybrid systems utilizing combinations of hydrogels, liposomes, and particle-based carriers are in consideration for pain-inflammation relief. Cartilage penetrating DDS target intra-cartilage constituents like aggrecans, collagen II, and chondrocytes such that drugs can reach their cellular and intra-cellular targets, which can enable clinical translation of disease-modifying osteoarthritis drugs including gene therapy.

Recent years have witnessed significant increase in both fundamental and clinical studies evaluating DDS for osteoarthritis. Steroid encapsulating polymeric microparticles for longer lasting pain relief were recently approved for clinical use. Electrically charged biomaterials for intra-cartilage targeting have shown promising disease-modifying response in preclinical models. Clinical trials evaluating safety of viral vectors are ongoing whose success can pave the way for gene therapy as osteoarthritis treatment.
Smoking Addiction and Strategies for Cessation
Authors: DiSilvio Briana , Baqdunes Mohammad , Alhajhusain Ahmad , Cheema Tariq
Published: November 2020

Cigarette smoking is the leading cause of chronic obstructive pulmonary disease (COPD) worldwide. Smoking cessation is thus integral to the treatment of COPD. Nicotine addiction is a disease dependent on the complex interactions of neurotransmitter pathways, conditioned behaviors, environmental cues, genetic predisposition, and personal life circumstances, which render some more susceptible to tobacco abuse than others. The most successful smoking cessation programs are individualized, comprehensive, and utilize combinations of clinician counseling, behavioral reinforcement, community resources, advanced technology support (eg, smartphone apps, and Internet Web sites), and pharmacotherapy (both nicotine-based and nonnicotine medications). E-cigarettes were introduced to the US market in 2006 and touted as a safer alternative to tobacco cigarette smoking. Unfortunately, over the last 5 to 10 years, recreational e-cigarette use, or “vaping,” has increased in popularity, especially among adolescents. This has introduced nicotine addiction to an entire generation of nonsmokers and resulted in numerous cases of acute lung disease, now known as e-cigarette or vape product use-associated lung injury (EVALI). In light of these adverse events, e-cigarettes and vape products are not currently recommended as a smoking cessation aid.
Lung Transplantation in COPD
Authors: Cheronis Nicholas , Rabold Erica , Singh Anil , Cheema Tariq
Published: November 2020

Chronic obstructive pulmonary disease (COPD) remains one of the leading causes of morbidity and mortality both in the United States and worldwide. Despite advances in medical treatment including smoking cessation, bronchodilator therapy, oxygen administration, and pulmonary rehabilitation, patients with advanced COPD still suffer significant debility. For select patients with severe COPD, there are additional surgical options including lung volume reduction surgery and ultimately lung transplantation.

This article discusses the history, clinical indications, selection of candidates, choice of procedure, and outcomes of lung transplantation in patients with advanced COPD. In addition, certain aspects of potential short- and long-term complications of transplantation will also be discussed.
MACULAR HOLE–RELATED RETINAL DETACHMENT COMPLICATING AUTOSOMAL RECESSIVE BESTROPHINOPATHY: CLINICAL FEATURES, MULTIMODAL IMAGING, AND SURGICAL OUTCOME
Authors: Abdullatif Abdussalam M.
Published: November 2020

Purpose:

To report a case of full-thickness macular–hole related retinal detachment in a patient with autosomal recessive bestrophinopathy.

Methods:

A 3-year-old boy presented for squint assessment. In the examination, there were typical features of autosomal recessive bestrophinopathy in the left eye and a macular hole–related retinal detachment in his right eye. Color fundus photography, autofluorescence, fundus fluorescence angiography, and spectral-domain optical coherence tomography were recorded.

Results:

Optical coherence tomography of the right eye showed a full-thickness macular hole retinal detachment. The retina showed retinoschisis affecting the inner and outer nuclear layer at the fovea and parafoveal region. Also, hyperreflective dots were seen at the hole and on the inner retinal surface. The left eye showed subretinal fluid with stalactite-like extensions into the subretinal space, and hyperreflective material seen above the retinal pigment epithelium. Fundus autofluorescence showed hyperautofluorescence at the fovea of the right eye and punctate hyperautofluorescent spots in the mid-periphery of the left eye. After pars plana vitrectomy and temporal internal limiting membrane flap, the hole was closed and all the schitic cavities collapsed at the sixth-week follow-up visit.

Conclusion:

A full-thickness macular hole–related retinal detachment can develop in autosomal recessive bestrophinopathy in the pediatric age group. Pars plana vitrectomy with temporal internal limiting membrane flap may be helpful for successful surgical repair.