bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic exposure following intravitreal administration of therapeutic agents: an integrated pharmacokinetic approach. 2. THR-687
Authors: Vanhove Marc , Wagner Jean-Marc , Noppen Bernard , Jonckx Bart , Vermassen Elke , Stitt Alan W. 
Published: July 2021

AbstractIntravitreal (IVT) injection remains the preferred administration route of pharmacological agents intended for the treatment of back of the eye diseases such as diabetic macular edema (DME) and neovascular age-related macular degeneration (nvAMD). The procedure enables drugs to be delivered locally at high concentrations whilst limiting whole body exposure and associated risk of systemic adverse events. Nevertheless, intravitreally-delivered drugs do enter the general circulation and achieving an accurate understanding of systemic exposure is pivotal for the evaluation and development of drugs administered in the eye. We report here the full pharmacokinetic properties of THR-687, a pan RGD integrin antagonist currently in clinical development for the treatment of DME, in both rabbit and minipig. Pharmacokinetic characterization included description of vitreal elimination, of systemic pharmacokinetics, and of systemic exposure following IVT administration. For the latter, we present a novel pharmacokinetic model that assumes clear partition between the vitreous humor compartment itself where the drug is administered and the central systemic compartment. We also propose an analytical solution to the system of differential equations that represent the pharmacokinetic model, thereby allowing data analysis with standard nonlinear regression analysis. The model accurately describes circulating levels of THR-687 following IVT administration in relevant animal models, and we suggest that this approach is relevant to a range of drugs and analysis of subsequent systemic exposure.
Are Functional Measures Sufficient to Capture Acceptance? A Qualitative Study on Lower Limb Exoskeleton Use for Older People
Authors: del Rio Carral Maria , Bourqui Vanlisa , Vuilleumier Noémie , Ortieb Amalric , Bouri Mohamed 
Published: July 2021

AbstractLower limb exoskeletons (LLE) are robotic devices developed to assist walk. In the field of healthcare, this technology has been available for almost a decade, yet it still faces important acceptance issues. While LLE were first developed for patients with spinal cord injuries, we expect their use to expand to everyday settings to benefit other populations, namely that of older people with reduced mobility (RM). We propose a qualitative approach to unearth key psychosocial themes on the acceptance of LLE in daily living for older people. The study analyses perceptions of older people with RM, as well as their entourage, including informal and professional caregivers. Using a grounded theory approach we analysed 12 semi-structured interviews with older people with RM; 2 focus groups with informal caregivers, and 2 focus groups with professional caregivers. LLE were introduced to participants through photo-elicitation. Older people with RM believed that LLE would increase their autonomy. They also perceived that using LLE would make them feel less of a burden for their entourage. Beyond these expected benefits, results captured participants’ ambivalence, dependent on their experiences of the ageing process and perceptions on the human–machine interaction. Informal caregivers highlighted that LLE could provide important relief related to the burden of care. Nonetheless, professional caregivers raised the fear of LLE leading to dehumanization of care. While each group had specific concerns on how LLE use would impact their lives, psychosocial considerations played a key role in LLE acceptance.
Upregulation of TCF21 inhibits migration of adrenocortical carcinoma cells
Authors: Kremer Jean Lucas , Auricino Thais Barabba , dos Santos Passaia Bárbara , Lotfi Claudimara Ferini Pacicco 
Published: July 2021

Abstract
Background
Adrenocortical carcinomas (ACC) are rare and aggressive cancer. Our previous study has revealed that the transcription factor 21, TCF21, is downregulated in ACC and regulates steroidogenic factor 1 (SF-1) binding to the SF-1 E-box promoter. In addition, it could be found that TCF21 is a predictor of overall survival (OS) in adult carcinomas.

Methods
In this study, it was investigated the correlation between TCF21 expression and the promoter methylation status in adrenocortical tumor cells, carcinomas and adenoma. The biological function and potential molecular mechanism of TCF21 restoration in migration and invasion of ACC cells was examined.

Results
We could be demonstrated a negative correlation between the level of TCF21 expression and methylation of its promoter in adenoma and carcinoma cells indicating the epigenetic control of TCF21 expression. It was also demonstrated that the expression of TCF21 inhibits migration and invasion in the ACC cell line, H295R cells, using plasmid transfection to express TCF21. Furthermore, it could be investigated the TCF21 function as tumor suppressor probably through Kisspeptin 1 (KISS-1) expression and epithelial–mesenchymal transition (EMT) reversion, as well as the modulation of several metalloproteinases in ACC cells.

Conclusions
Our results suggest that enhancement of TCF21 expression levels may be a potential strategy to revert invasive abilities in adrenocortical carcinomas.
Rapidly dissolving microneedle patch of amphotericin B for intracorneal fungal infections
Authors: Albadr Alyaa A. , Tekko Ismaiel A. , Vora Lalitkumar K. , Ali Ahlam A. , Laverty Garry , Donnelly Ryan F. , Thakur Raghu Raj Singh 
Published: July 2021

AbstractChronic fungal infection of the cornea could lead to blindness if not treated properly. Topical amphotericin B (AMP-B) is considered the first treatment of choice for ocular fungal infection. However, factors related to its poor solubility and penetration through intact cornea lead to poor bioavailability. Microneedles (MNs) are emerging as a minimally invasive method to enhance ocular drug delivery. This study aims to investigate the potential use of biodegradable poly(vinylpyrrolidone) (PVP) and hyaluronic acid (HA)–based rapidly dissolving MNs for delivery of AMP-B to treat fungal infection. The data obtained illustrates PVP/HA MN arrays’ reproducibility, good mechanical strength, and faster dissolution with 100% drug recovery. Multiphoton microscopic results revealed that MNs successfully penetrate the corneal tissue and enhance AMP-B permeation through corneal layers. Furthermore, PVP/HA MN arrays showed high solubility. Both PVP and HA successfully decreased AMP-B cytotoxicity when compared to free drug. More interestingly, the biocompatible MN formulations preserved the antifungal activity of AMP-B, as demonstrated by significant inhibition of fungal growth. Therefore, this study shows the feasibility of ocular delivery of the poorly soluble AMP-B using a fast-dissolving MN patch.
Graphical abstract
The Associations of Obstructive Sleep Apnea and Eye Disorders: Potential Insights into Pathogenesis and Treatment
Authors: Ahn Jeeyun , Gorin Michael B. 
Published: July 2021

Abstract
Purpose of Review
Obstructive sleep apnea (OSA) patients are at significantly increased risks for cardiovascular and cerebrovascular morbidities. Recently, there has been heightened interest in the association of OSA with numerous ocular diseases and possible improvement of these conditions with the initiation of OSA treatment. We reviewed the current evidence with an emphasis on the overlapping pathogeneses of both diseases.

Recent Findings
Currently available literature points to a substantial association of OSA with ocular diseases, ranging from those involving the eyelid to optic neuropathies and retinal vascular diseases. Since the retina is one of the highest oxygen-consuming tissues in the body, the intermittent hypoxia and hypercapnia ensuing in OSA can have deleterious effects on ocular function and health. Tissue hypoxia, autonomic dysfunction, microvascular dysfunction, and inflammation all play important roles in the pathogenesis of both OSA and ocular diseases. Whether OSA treatment is capable of reversing the course of associated ocular diseases remains to be determined. It is anticipated that future therapeutic approaches will target the common underlying pathophysiologic mechanisms and promote favorable effects on the treatment of known associated ocular diseases.

Summary
Emerging evidence supports the association of ocular diseases with untreated OSA. Future studies focusing on whether therapeutic approaches targeting the common pathophysiologic mechanisms will be beneficial for the course of both diseases are warranted.
Low and non-uniform illumination color image enhancement using weighted guided image filtering
Authors: Mu Qi , Wang Xinyue , Wei Yanyan , Li Zhanli 
Published: July 2021

AbstractIn the state of the art, grayscale image enhancement algorithms are typically adopted for enhancement of RGB color images captured with low or non-uniform illumination. As these methods are applied to each RGB channel independently, imbalanced inter-channel enhancements (color distortion) can often be observed in the resulting images. On the other hand, images with non-uniform illumination enhanced by the retinex algorithm are prone to artifacts such as local blurring, halos, and over-enhancement. To address these problems, an improved RGB color image enhancement method is proposed for images captured under non-uniform illumination or in poor visibility, based on weighted guided image filtering (WGIF). Unlike the conventional retinex algorithm and its variants, WGIF uses a surround function instead of a Gaussian filter to estimate the illumination component; it avoids local blurring and halo artifacts due to its anisotropy and adaptive local regularization. To limit color distortion, RGB images are first converted to HSI (hue, saturation, intensity) color space, where only the intensity channel is enhanced, before being converted back to RGB space by a linear color restoration algorithm. Experimental results show that the proposed method is effective for both RGB color and grayscale images captured under low exposure and non-uniform illumination, with better visual quality and objective evaluation scores than from comparator algorithms. It is also efficient due to use of a linear color restoration algorithm.
Das Versprechen der Architektur: Schaffen Multireligiöse Räume Toleranz?
Authors: Burchardt Marian , Häring Johanna 
Published: July 2021

ZusammenfassungWährend interreligiöse Dialoge durch ikonische architektonische Projekte eine größere öffentliche Sichtbarkeit und mediale Aufmerksamkeit erlangt haben, ist deren breitere gesellschaftliche Wahrnehmung und Wirkung weitestgehend unerforscht. Der Beitrag untersucht gruppenspezifische Wahrnehmungen interreligiöser Beziehungen und Positionierungen zu interreligiösen Dialogen. Im Zentrum der Analyse stehen dabei die Debatten zum BerlinerHouse of One, einem derzeit im Bau befindlichen multireligiösen Gebäude. Unter Rückgriff auf soziologische Konzeptualisierungen zum Verhältnis von Religion, Macht und Stadtraum untersucht der Beitrag, welche unterschiedlichen sozialen Positionen religiöser Akteur*innen (Protestant*innen, Alevit*innen und Muslim*innen) in den kulturellen Hierarchien urbaner Räume sich in solchen Wahrnehmungen dokumentieren. Wir argumentieren, dass die in diskursiven Aushandlungsprozessen zu interreligiösen Dialogen vorgenommenen Positionierungen solche kulturellen Hierarchien auf besondere Weise hervortreten lassen und damit auch auf blinde Flecken des Dialog-Paradigmas aufmerksam machen. Der Beitrag basiert auf Gruppendiskussionen und Einzelinterviews.
Eichhornia crassipes (Mart.) Solms (natural or carbonized) as biosorbent to remove pollutants in water
Authors: Lima Herbert de P. , Asencios Yvan J. O. 
Published: July 2021

AbstractThe prolific aquatic herbEichhornia crassipesconsidered a pest in many countries can cause damage such as obstruction of water flows and impair the locomotion of fishing boats. However,E. crassipesis renewable, inexpensive, and widely available in nature, and its ability to adsorb recalcitrant pollutants with mutagenic and carcinogenic properties, including synthetic dyes and heavy metals, has been extensively studied by the scientific community. This review paper analyzes previous reports concerning the use ofE. crassipes(in the natural and carbonized form) as an adsorbent for heavy metal cations and textile dye. The adsorptive capacity ofE. crassipes,the best conditions (adsorbent dosage, pH, and temperature) for the removal of these pollutants, the mechanism of adsorption, and the comparison between natural and carbonized forms (advantages and disadvantages) are discussed. All the results revised in this review indicated that the use ofE. crassipes(and its carbon derived) as adsorbent is promising and is an excellent material to be applied in the water treatment. It could be used in the actual technologies for the treatment of contaminated water by heavy metals and textile dyes; however, more studies need to be made on scale-up, economy projects, and related issues, to be finally implemented in wastewater treatment plants.
Structural insights into the role of DNA-PK as a master regulator in NHEJ
Authors: Chen Siyu , Lees-Miller James P. , He Yuan , Lees-Miller Susan P. 
Published: July 2021

AbstractDNA-dependent protein kinase catalytic subunit DNA-PKcs/PRKDC is the largest serine/threonine protein kinase of the phosphatidyl inositol 3-kinase-like protein kinase (PIKK) family and is the most highly expressed PIKK in human cells. With its DNA-binding partner Ku70/80, DNA-PKcs is required for regulated and efficient repair of ionizing radiation-induced DNA double-strand breaks via the non-homologous end joining (NHEJ) pathway. Loss of DNA-PKcs or other NHEJ factors leads to radiation sensitivity and unrepaired DNA double-strand breaks (DSBs), as well as defects in V(D)J recombination and immune defects. In this review, we highlight the contributions of the late Dr. Carl W. Anderson to the discovery and early characterization of DNA-PK. We furthermore build upon his foundational work to provide recent insights into the structure of NHEJ synaptic complexes, an evolutionarily conserved and functionally important YRPD motif, and the role of DNA-PKcs and its phosphorylation in NHEJ. The combined results identify DNA-PKcs as a master regulator that is activated by its detection of two double-strand DNA ends for a cascade of phosphorylation events that provide specificity and efficiency in assembling the synaptic complex for NHEJ.
Learning 2-Opt Heuristics for Routing Problems via Deep Reinforcement Learning
Authors: da Costa Paulo , Rhuggenaath Jason , Zhang Yingqian , Akcay Alp , Kaymak Uzay 
Published: July 2021

AbstractRecent works using deep learning to solve routing problems such as the traveling salesman problem (TSP) have focused on learning construction heuristics. Such approaches find good quality solutions but require additional procedures such as beam search and sampling to improve solutions and achieve state-of-the-art performance. However, few studies have focused on improvement heuristics, where a given solution is improved until reaching a near-optimal one. In this work, we propose to learn a local search heuristic based on 2-opt operators via deep reinforcement learning. We propose a policy gradient algorithm to learn a stochastic policy that selects 2-opt operations given a current solution. Moreover, we introduce a policy neural network that leverages a pointing attention mechanism, which can be easily extended to more generalk-opt moves. Our results show that the learned policies can improve even over random initial solutions and approach near-optimal solutions faster than previous state-of-the-art deep learning methods for the TSP. We also show we can adapt the proposed method to two extensions of the TSP: the multiple TSP and the Vehicle Routing Problem, achieving results on par with classical heuristics and learned methods.
Extracellular Matrix Remodeling in Chronic Liver Disease
Authors: Ortiz Cristina , Schierwagen Robert , Schaefer Liliana , Klein Sabine , Trepat Xavier , Trebicka Jonel 
Published: July 2021

Abstract
Purpose of the Review
This review aims to summarize the current knowledge of the extracellular matrix remodeling during hepatic fibrosis. We discuss the diverse interactions of the extracellular matrix with hepatic cells and the surrounding matrix in liver fibrosis, with the focus on the molecular pathways and the mechanisms that regulate extracellular matrix remodeling.

Recent Findings
The extracellular matrix not only provides structure and support for the cells, but also controls cell behavior by providing adhesion signals and by acting as a reservoir of growth factors and cytokines.

Summary
Hepatic fibrosis is characterized by an excessive accumulation of extracellular matrix. During fibrogenesis, the natural remodeling process of the extracellular matrix varies, resulting in the excessive accumulation of its components, mainly collagens. Signals released by the extracellular matrix induce the activation of hepatic stellate cells, which are the major source of extracellular matrix and most abundant myofibroblasts in the liver.

Graphical abstract
The Scott model of PCF in univalent type theory
Authors: de Jong Tom 
Published: July 2021

AbstractWe develop the Scott model of the programming language PCF in univalent type theory. Moreover, we work constructively and predicatively. To account for the non-termination in PCF, we use the lifting monad (also known as the partial map classifier monad) from topos theory, which has been extended to univalent type theory by Escardó and Knapp. Our results show that lifting is a viable approach to partiality in univalent type theory. Moreover, we show that the Scott model can be constructed in a predicative and constructive setting. Other approaches to partiality either require some form of choice or quotient inductive-inductive types. We show that one can do without these extensions.
Intranasal dexmedetomidine: the ideal drug for sedation in the pediatric echo lab?
Authors: Saudek David E , Walbergh Deborah , Bartz Peter , Shreve Sara , Schaal Amy , Lavoie Julie , Frommelt Peter C 
Published: July 2021

AbstractBackground:Intranasal dexmedetomidine is an attractive option for procedural sedation in pediatrics due to ease of administration and its relatively short half-life. This study sought to compare the safety and efficacy of intranasal dexmedetomidine to a historical cohort of pediatric patients sedated using chloral hydrate in a pediatric echo lab.Methods:Chart review was performed to compare patients sedated between September, 2017 and October, 2019 using chloral hydrate and intranasal dexmedetomidine. Vital signs, time to sedation, duration of sedation, need for second dose of medication, rate of failed sedation, and impact on vital signs were compared between groups. Subgroup analysis was performed for those with complex and cyanotic heart disease.Results:Chloral hydrate was used in 356 patients and intranasal dexmedetomidine in 376. Patient age, complexity of heart disease, and duration of sedation were similar. Rates of failed sedation were very low and similar. Average heart rate and minimum heart rate were lower for those receiving intranasal dexmedetomidine than chloral hydrate. Impact on vital signs was similar for those with complex and cyanotic heart disease. No adverse events occurred in either group.Conclusions:Sedation with intranasal dexmedetomidine is comparable to chloral hydrate in regards to safety and efficacy for children requiring echocardiography. Consistent with the mechanism of action, patients receiving intranasal dexmedetomidine have a lower heart rate without morbidity.
Neurocognitive functioning in young adults with congenital heart disease: insights from a case-control study
Authors: Schlosser Ladina , Kessler Nora , Feldmann Maria , Wehrle Flavia , Rometsch Sarah , Greutmann Matthias , Oxenius Angela , Brugger Peter , Latal Beatrice 
Published: July 2021

AbstractBackground:While there is evidence that cognitive impairment of children with congenital heart disease (CHD) may persist into adolescence, little is known about the spectrum of neurocognitive functioning of young adults with this disorder. The aim of this study was to assess neurocognitive functioning in a population of young adults with different types of CHD.Methods:Cross-sectional cohort study in young adults with CHD and a group-matched healthy control group. We assessed neurocognitive and general intellectual functioning with a comprehensive battery of standardised neuropsychological tests. In addition to task-based assessments, questionnaire data of executive dysfunctions in everyday life were measured with the Behaviour Rating Inventory of Executive Function – Adult Version.Results:A total of 67 patients (55% men) with CHD and 55 healthy controls (51% men) were included for analysis. Mean age at assessment was 26.9 (3.68) and 26.0 (3.32) years, respectively. The CHD group performed poorer in the domains of Executive Functions, Memory, Attention & Speed, and general intellectual functioning. Patients with a CHD of severe complexity were more affected than patients with simple or moderate complexity. Behaviour Rating Inventory of Executive Function – Adult Version scores indicated that patients’ self-rated deficits in behaviour regulation in everyday life was higher compared with healthy controls.Conclusion:Our findings indicate lower neurocognitive functioning in young adults with a CHD, particularly in those with severe defect complexity. In view of the potentially enhanced risk for cerebrovascular and neurodegenerative disease in this patient group as reported in the literature, systematic longitudinal monitoring of cognitive functioning is recommended.
Long-term results of percutaneous transluminal coronary balloon angioplasty in Kawasaki disease
Authors: Tsuda Etsuko , Takamuro Motoki , Yamamoto Kazuhiro 
Published: July 2021

AbstractWe report the long-term results of percutaneous transluminal coronary balloon angioplasty for early appearing localised stenosis of the left anterior descending artery caused by Kawasaki disease in two 2-year-olds. One patient had 50% restenosis and newly appearing aneurysm at 21-year-old, and the other had no restenosis at 16-year-old. They had no symptoms or cardiac events for 20 years. It is useful in the early localised stenosis without aneurysm.