bluuebunny/crossref_metadata_2025_split huggingface dataset:
An unsteady analysis of two-phase binding of drug in an asymmetric stenosed vessel
Authors: Biswas Sayantan , Sarifuddin  , Mandal Prashanta Kumar 
Published: November 2021

Abstract
In this paper, we investigate endovascular delivery to get a step ahead of the pharmacological limitations it has due to the complexity of dealing with a patient-specific vessel through a mathematical model. We divide the domain of computation into four sub-domains: the lumen, the lumen-tissue interface, the upper tissue and the lower tissue which are extracted from an asymmetric atherosclerotic image derived by the intravascular ultrasound (IVUS) technique. The injected drug at the luminal inlet is transported with the streaming blood which is considered Newtonian. An irreversible uptake kinetics of the injected drug at the lumen-tissue interface from the luminal side to the tissue domains is assumed. Subsequently, the drug is dispersed within the tissue followed by its retention in the extracellular matrix (ECM) and by receptor-mediated binding. The Marker and Cell (MAC) method has been leveraged to get a quantitative insight into the model considered. The effect of the wall absorption parameter on the concentration of all drug forms (free as well as two-phase bound) has been thoroughly investigated, and some other important factors, such as the averaged concentration, the tissue content, the fractional effect, the concentration variance and the effectiveness of drug have been graphically analyzed to gain a clear understanding of endovascular delivery. The simulated results predict that with increasing values of the absorption parameter, the averaged concentrations of all drug forms do decrease. An early saturation of binding sites takes place for smaller values of the absorption parameter, and also rapid saturation of ECM binding sites occurs as compared to receptor binding sites. Results also predict the influence of surface roughness as well as asymmetry of the domain about the centerline on the distribution and retention of drug. A thorough sensitivity analysis has been carried out to determine the influence of some parameters involved.
Southeast Asian expert perceptions of solar radiation management techniques and carbon dioxide removal approaches: caution, ambivalence, risk precaution, and research directions
Authors: Delina Laurence L 
Published: November 2021

Abstract
As the climate crisis intensifies in its impacts, discussions around the deployment of geoengineering solutions in case other interventions fail or prove insufficient have figured in research and have even been on the agenda of the United Nations. There have been calls for more investigation of geoengineering techniques to address the climate crisis. Yet, this response presents technological unknowns and economic, political, and ethical risks. Producing knowledge on these techniques has been pushed in many research institutes in the global North, especially in the United States, Europe, and Australia. Still, contributions from global South researchers, including those in Southeast Asia, remain scant. This paper describes the responses of seventeen climate and energy experts from southeast Asia on a purposively designed survey that collected expert opinions on two geoengineering techniques: solar radiation modification (SRM) and carbon dioxide removal (CDR), their risks, impacts, and governance as they pertain to their countries and region. Respondents showed ambivalence towards these techniques, with many supporting ‘natural’ CDR research and deployment while being cautious about ‘technological’ SRM and CDR research and deployment. Although respondents would welcome research on these technologies, especially their risks and impacts, they also identified critical barriers in research capacity development and funding availability.
Residual stress, distortion, and porosity analysis of LED heat sink printed by SLM process using machine learning
Authors: Thakur Sumit , Talla Gangadharudu , Verma Prakash 
Published: November 2021

Abstract
In recent years, Light-emitting diodes (LEDs) are dominating the traditional lighting system. Besides mercury-free, they have small size, good break resistance and long life. Although LEDs are cool to touch, they generate a lot of unnecessary heat inside the gadgets. It is important to remove the heat using efficient thermal management component such as heat sink. Instead of using a conventional manufacturing process, selective laser melting (SLM) process is used to manufacture the heat sink. The quick solidification and various thermal regimes of the material during the SLM process lead to the development of residual stresses that cause the part distortion and harm the mechanical properties of the component. The objective of the current study is to find the optimum value of laser power, scanning speed, and hatch spacing to bring down the residual stress and distortion in the SLM process to an acceptable range. Residual stress and distortion values of the heat sink are simulated using MSC Simufact additive and ANSYS Additive software. The conflicting nature between residual stress and porosity was observed. Hence, grey relation analysis was used to convert residual stress & porosity into a single objective. Optimum process parameters obtained were, laser power 80 (W), scanning speed 950 (mm s−1), and hatch spacing of 70

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The values of residual stress and porosity at optimum parameters were found to be 385.58 MPa and 12.21%. Multiple regressions algorithm of machine learning was used to form a relationship between residual stresses and porosity. It was also observed that the magnitude of residual stress and distortion were low at lower energy densities and high at higher energy densities and the residual stress and porosities were high in the z-direction.
Predicting protein–membrane interfaces of peripheral membrane proteins using ensemble machine learning
Authors: Chatzigoulas Alexios , Cournia Zoe 
Published: November 2021

AbstractAbnormal protein–membrane attachment is involved in deregulated cellular pathways and in disease. Therefore, the possibility to modulate protein–membrane interactions represents a new promising therapeutic strategy for peripheral membrane proteins that have been considered so far undruggable. A major obstacle in this drug design strategy is that the membrane-binding domains of peripheral membrane proteins are usually unknown. The development of fast and efficient algorithms predicting the protein–membrane interface would shed light into the accessibility of membrane–protein interfaces by drug-like molecules. Herein, we describe an ensemble machine learning methodology and algorithm for predicting membrane-penetrating amino acids. We utilize available experimental data from the literature for training 21 machine learning classifiers and meta-classifiers. Evaluation of the best ensemble classifier model accuracy yields a macro-averaged F1 score = 0.92 and a Matthews correlation coefficient = 0.84 for predicting correctly membrane-penetrating amino acids on unknown proteins of a validation set. The python code for predicting protein–membrane interfaces of peripheral membrane proteins is available at https://github.com/zoecournia/DREAMM.
Effect of minimally invasive mitral valve surgery compared to sternotomy on short- and long-term outcomes: a retrospective multicentre interventional cohort study based on Netherlands Heart Registration
Authors: Olsthoorn Jules R , Heuts Samuel , Houterman Saskia , Maessen Jos G , Sardari Nia Peyman ,   the Cardiothoracic Surgery Registration Committee of the Netherlands Heart Registration, Bramer S , van Boven W J P , Vonk A B A , Koene B M J A , Bekkers J A , Hoohenkerk G J F , Markou A L P , Weger A de , Segers P , Porta F , Speekenbrink R G H , Stooker W , Li W W L , Daeter E J , van der Kaaij N P , Vigano G 
Published: November 2021

Abstract

OBJECTIVES
Minimally invasive mitral valve surgery (MIMVS) has been performed increasingly for the past 2 decades; however, large comparative studies on short- and long-term outcomes have been lacking. This study aims to compare short- and long-term outcomes of patients undergoing MIMVS versus median sternotomy (MST) based on real-world data, extracted from the Netherlands Heart Registration.

METHODS
Patients undergoing mitral valve surgery, with or without tricuspid valve, atrial septal closure and/or rhythm surgery between 2013 and 2018 were included. Primary outcomes were short-term morbidity and mortality and long-term survival. Propensity score matching analyses were performed.

RESULTS
In total, 2501 patients were included, 1776 were operated through MST and 725 using an MIMVS approach. After propensity matching, no significant differences in baseline characteristics persisted. There were no between-group differences in 30-day mortality (1.1% vs 0.7%, P = 0.58), 1-year mortality (2.6% vs 2.1%, P = 0.60) or perioperative stroke rate (1.1% vs 0.6%, P = 0.25) between MST and MIMVS, respectively. An increased rate of postoperative arrhythmia was observed in the MST group (31.3% vs 22.4%, P &lt; 0.001). A higher repair rate was found in the MST group (80.9% vs 76.3%, P = 0.04). No difference in 5-year survival was found between the matched groups (95.0% vs 94.3%, P = 0.49). Freedom from mitral reintervention was 97.9% for MST and 96.8% in the MIMVS group (P = 0.01), without a difference in reintervention-free survival (P = 0.30).

CONCLUSIONS
The MIMVS approach is as safe as the sternotomy approach for the surgical treatment of mitral valve disease. However, it comes at a cost of a reduced repair rate and more reinterventions in the long term, in the real-world.
Real-life experience with compassionate use of cefiderocol for difficult-to-treat resistant Pseudomonas aeruginosa (DTR-P) infections
Authors: Meschiari Marianna , Volpi Sara , Faltoni Matteo , Dolci Giovanni , Orlando Gabriella , Franceschini Erica , Menozzi Marianna , Sarti Mario , Del Fabro Giovanni , Fumarola Benedetta , Guarneri Francesco , Lanza Paola , Lorenzotti Silvia , Saccani Barbara , Signorini Liana , Van Hauwermeiren Evelyn , Gatti Milo , Pea Federico , Castelli Francesco , Mussini Cristina 
Published: November 2021

Abstract

Objectives
To describe our real-life experience with cefiderocol in XDR and difficult-to-treat resistant Pseudomonas aeruginosa (DTR-P) infections without any other available treatment options.

Methods
We included patients with a proven infection due to an XDR/DTR-P, who had failed on previous regimens, and were treated with cefiderocol, following them prospectively to day 90 or until hospital discharge or death.

Results
Seventeen patients treated for &gt;72 h with cefiderocol were included: 14 receiving combination regimens (82.4%) and 3 receiving monotherapy (17.6%). Fourteen patients were males (82%) with a median age of 64 years (IQR 58–73). Fifteen patients (88.2%) were admitted to the ICU and five had septic shock (29%). Seven cases (41.2%) were ventilator-associated pneumonia, of which 71% (5/7) occurred in COVID-19 patients. Four were complicated intrabdominal infections, one ecthyma gangrenosum, one nosocomial pneumonia and one empyema, one osteomyelitis, one primary bacteraemia, and one nosocomial external ventricular drainage meningitis. Clinical cure and microbiological cure rates were 70.6% and 76.5%, respectively. There were six deaths (35.3%) after a median of 8 days (IQR 3–10) from the end of treatment, but only two of them (11.7%) were associated with P. aeruginosa infection progression.

Conclusions
Our experience collecting this large case series of DTR-P treated with cefiderocol may help clinicians consider this new option in this hard-to-manage setting. Our results are even more relevant in the current scenario of ceftolozane/tazobactam shortage. Importantly, this is the first study providing real-life data indicating adequate cefiderocol concentrations in CSF.
Development of 3D printed drug-eluting contact lenses
Authors: Mohamdeen Youssra Moustafa Gadelkareem , Tabriz Atabak Ghanizadeh , Tighsazzadeh Mohammad , Nandi Uttom , Khalaj Roxanne , Andreadis Ioannis , Boateng Joshua S , Douroumis Dennis 
Published: November 2021

Abstract

Objectives
The aim of the work was to introduce 3D printing technology for the design and fabrication of drug-eluting contact lenses (DECL) for the treatment of glaucoma. The development of 3D printed lenses can effectively overcome drawbacks of existing approaches by using biocompatible medical grade polymers that provide sustained drug release of timolol maleate for extended periods.

Methods
Hot melt extrusion was coupled with fusion deposition modelling (FDM) to produce printable filaments of ethylene-vinyl acetate copolymer–polylactic acid blends at various ratios loaded with timolol maleate. Physicochemical and mechanical characterisation of the printed filaments was used to optimise the printing of the contact lenses

Key findings
3D printed lenses with an aperture (opening) and specified dimensions could be printed using FDM technology. The lenses presented a smooth surface with good printing resolution while providing sustained release of timolol maleate over 3 days. The findings of this study can be used for the development of personalised DECL in the future.
Systemic BCGosis following intra-renal instillation of BCG: a case report
Authors: Schembri Higgans Jessica , Pace Keith , Sciberras John , Scicluna Warren 
Published: November 2021

Abstract
Bacillus Calmette-Guerin (BCG) immunotherapy is a mainstay of adjunctive therapy for non-muscle-invasive bladder cancer. The instillation of BCG in the upper urinary tract after complete tumour eradication has also been studied and used after kidney-sparing management. It is effective in increasing the length of remission. However, it is also associated with rare but severe local and systemic side effects which may potentially become life-threatening. We present a case report of a 37-year-old gentleman who developed BCGosis following intra-renal instillation of BCG immunotherapy. The patient presented with systemic symptoms of jaundice, fever, myalgia and arthralgia, rather than local symptoms. Mycobacterium bovis infection was confirmed on blood cultures. The patient also developed hepatosplenomegaly, dyspnoea and pancytopaenia. BCGosis following intravesical instillation has been well documented in literature; to the best of our knowledge, this is the first case report documenting BCGosis following intra-renal instillation.
The propagation of strong shocks into planetary and stellar atmospheres with graded density profiles
Authors: Remorov Andrey , Yalinewich Almog 
Published: November 2021

ABSTRACT
Previous works developed an analytic model for the propagation of shock waves into atmospheres with a uniform density. In this work, we generalized this formalism to account for graded density profiles. These waves can occur in a wide range of astrophysical events, such as collisions in planetary and stellar atmospheres, common envelope explosions, and peculiar type Ia supernovae. The behaviour of the shock wave and its evolution can be modelled using type II self-similar solutions. In such solutions, the evolution of the shock wave is determined by boundary conditions at the shock front and a singular point in the shocked region. We show how the evolution can be determined for different equations of state and density profiles, and compare these results to numerical simulations. We also demonstrate how these results can be applied to a wide range of problems in astrophysics.
On the evolution of vortex in locally isothermal self-gravitating discs: a parameter study
Authors: Tarczay-Nehéz D , Rozgonyi K , Regály Zs 
Published: November 2021

ABSTRACT
Gas-rich dusty circumstellar discs observed around young stellar objects are believed to be the birthplace of planets and planetary systems. Recent observations revealed that large-scale horseshoe-like brightness asymmetries are present in dozens of transitional protoplanetary discs. Theoretical studies suggest that these brightness asymmetries bf could be caused by large-scale anticyclonic vortices triggered by the Rossby wave Instability (RWI), which can be excited at the edges of the accretionally inactive region, the dead zone edge. Since vortices may play a key role in planet formation, investigating the conditions of the onset of RWI and the long-term evolution of vortices is inevitable. The aim of our work was to explore the effect of disc geometry (the vertical thickness of the disc), viscosity, the width of the transition region at the dead zone edge, and the disc mass on the onset, lifetime, strength and evolution of vortices formed in the disc. We performed a parametric study assuming different properties for the disc and the viscosity transition by running 1980 2D hydrodynamic simulations in the locally isothermal assumption with disc self-gravity included. Our results revealed that long-lived, large-scale vortex formation favours a shallow surface density slope and low- or moderate-disc masses with Toomre Q ≲ 1 h-1, where h is the geometric aspect ratio of the disc. In general, in low viscosity models, stronger vortices form. However, rapid vortex decay and re-formation is more widespread in these discs.
Radiative transfer of ionizing radiation through gas and dust: grain charging in star-forming regions
Authors: Glatzle Martin , Graziani Luca , Ciardi Benedetta 
Published: November 2021

ABSTRACT
The presence of charged dust grains is known to have a profound impact on the physical evolution of the multiphase interstellar medium (ISM). Despite its importance, this process is still poorly explored in numerical simulations due to its complex physics and the tight dependence on the environment. Here, we introduce a novel implementation of grain charging in the cosmological radiative transfer code crash. We first benchmark the code predictions on a series of idealized dusty H ii regions created by a single star, in order to assess the impact of grain properties on the resulting spatial distribution of charges. Secondly, we perform a realistic radiative transfer simulation of a star-forming region extracted from a dusty galaxy evolving in the Epoch of Reionization. We find that ∼13 per cent of the total dust mass gets negatively charged, mainly silicate and graphite grains of radius 10−3 $\mu$m. A complex spatial distribution of grain charges is also found, primarily depending on the exposure to stellar radiation and strongly varying along different lines of sight, as a result of radiative transfer effects. We finally assess the impact of grain properties (both chemical composition and size) on the resulting charge distribution. The new implementation described here will open up a wide range of possible studies investigating the physical evolution of the dusty ISM, nowadays accessible to observations of high- and low- redshift galaxies.
Structural basis of dimerization and nucleic acid binding of human DBHS proteins NONO and PSPC1
Authors: Knott Gavin J , Chong Yee Seng , Passon Daniel M , Liang Xue-hai , Deplazes Evelyne , Conte Maria R , Marshall Andrew C , Lee Mihwa , Fox Archa H , Bond Charles S 
Published: November 2021

Abstract
The Drosophila behaviour/human splicing (DBHS) proteins are a family of RNA/DNA binding cofactors liable for a range of cellular processes. DBHS proteins include the non-POU domain-containing octamer-binding protein (NONO) and paraspeckle protein component 1 (PSPC1), proteins capable of forming combinatorial dimers. Here, we describe the crystal structures of the human NONO and PSPC1 homodimers, representing uncharacterized DBHS dimerization states. The structures reveal a set of conserved contacts and structural plasticity within the dimerization interface that provide a rationale for dimer selectivity between DBHS paralogues. In addition, solution X-ray scattering and accompanying biochemical experiments describe a mechanism of cooperative RNA recognition by the NONO homodimer. Nucleic acid binding is reliant on RRM1, and appears to be affected by the orientation of RRM1, influenced by a newly identified ‘β-clasp’ structure. Our structures shed light on the molecular determinants for DBHS homo- and heterodimerization and provide a basis for understanding how DBHS proteins cooperatively recognize a broad spectrum of RNA targets.
Heavy particle non-decoupling in flavor-changing gravitational interactions
Authors: Inami Takeo , Kubota Takahiro 
Published: November 2021

Abstract
The flavor-changing gravitational process, d → s + graviton, is evaluated at the one-loop level in the standard electroweak theory with on-shell renormalization. The results that we present in the ’t Hooft–Feynman gauge are valid for on- and off-shell quarks and for all external and internal quark masses. We show that there exist non-decoupling effects of the internal heavy top quark in interactions with gravity. A naive argument taking account of the quark Yukawa coupling suggests that the amplitude of the process d → s + graviton in the large top quark mass limit would possibly acquire an enhancement factor $m_{t}^{2}/M_{W}^{2}$, where mt and MW are the top quark and the W-boson masses, respectively. In practice this leading enhancement is absent in the renormalized amplitude due to cancellation. Thus the non-decoupling of the internal top quark takes place at the ${\cal O}(1)$ level. The flavor-changing two- and three-point functions are shown to satisfy the Ward–Takahashi identity, which is used as a consistency check for the aforementioned cancellation of the ${\cal O}(m_{t}^{2}/M_{W}^{2})$ terms. Among the ${\cal O}(1)$ non-decoupling terms, we sort out those that can be regarded as due to the effective Lagrangian in which quark bilinear forms are coupled to the scalar curvature.
Definition of low disease activity state based on the SLE-DAS: derivation and validation in a multicentre real-life cohort
Authors: Assunção Helena , Jesus Diogo , Larosa Maddalena , Henriques Carla , Matos Ana , Le Guern Véronique , Rubiño Francisco , da Silva José A P , Rua-Figueroa Iñigo , Costedoat-Chalumeau Nathalie , Doria Andrea , Inês Luís S 
Published: November 2021

Abstract

Objectives
To derive and validate a definition of low disease activity (LDA) for SLE based on the SLE Disease Activity Score (SLE-DAS), in a real-life multicentre cohort of SLE patients.

Methods
Derivation was conducted using data from a monocentric cohort of SLE (Portugal), and validation was performed in a multicentre cohort (Italy, France and Spain). The Lupus Low Disease Activity State (LLDAS) was used as comparator. We applied receiver operating characteristics curve analysis against the LLDAS to determine the cut-off of SLE-DAS for LDA using bootstrap methodology. In a second step, we tested a definition of SLE-DAS LDA that included: (i) the statistically derived SLE-DAS upper threshold for LDA and (ii) prednisone dose ≤7.5 mg/day. In the multicentre validation cohort, we assessed the classification performance of this SLE-DAS LDA definition.

Results
We included 774 patients, 300 in the derivation and 474 in the validation cohort. In the derivation cohort, the optimal cut-off to identify patients in LLDAS was SLE-DAS ≤2.48, presenting an area under the curve of 0.965 (95% CI 0.935, 0.994). When applied to the multicentre validation cohort, the SLE-DAS LDA definition showed a sensitivity of 97.1% and a specificity of 97.7% for LLDAS and an almost perfect agreement (Cohen’s Kappa = 0.933; P &lt; 0.001). McNemar’s test found no significant differences between the two definitions (P = 0.092).

Conclusion
The SLE-DAS LDA is a validated, accurate and easy-to-use definition for classifying SLE patients in LDA state.