bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel electrospun poly-hydroxybutyrate scaffolds as carriers for the wound healing agents alkannins and shikonins
Authors: Arampatzis Athanasios S , Giannakoula Konstantina , Kontogiannopoulos Konstantinos N , Theodoridis Konstantinos , Aggelidou Eleni , Rat Angélique , Kampasakali Elli , Willems Anne , Christofilos Dimitrios , Kritis Aristeidis , Papageorgiou Vassilios P , Tsivintzelis Ioannis , Assimopoulou Andreana N 
Published: June 2021

Abstract
The aim of this study was to investigate the potential of novel electrospun fiber mats loaded with alkannin and shikonin (A/S) derivatives, using as carrier a highly biocompatible, bio-derived, eco-friendly polymer such as poly[(R)-3-hydroxybutyric acid] (PHB). PHB fibers containing a mixture of A/S derivatives at different ratios were successfully fabricated via electrospinning. Αs evidenced by scanning electron microscopy, the fibers formed a bead-free mesh with average diameters from 1.25 to 1.47 μm. Spectroscopic measurements suggest that electrospinning marginally increases the amorphous content of the predominantly crystalline PHB in the fibers, while a significant drug amount lies near the fiber surface for samples of high total A/S content. All scaffolds displayed satisfactory characteristics, with the lower concentrations of A/S mixture-loaded PHB fiber mats achieving higher porosity, water uptake ratios, and entrapment efficiencies. The in vitro dissolution studies revealed that all samples released more than 70% of the encapsulated drug after 72 h. All PHB scaffolds tested by cell viability assay were proven non-toxic for Hs27 fibroblasts, with the 0.15 wt.% sample favoring cell attachment, spreading onto the scaffold surface, as well as cell proliferation. Finally, the antimicrobial activity of PHB meshes loaded with A/S mixture was documented for Staphylococcus epidermidis and S. aureus.
Quantitative ultrasound to monitor the vascular response to tocilizumab in giant cell arteritis
Authors: Seitz Luca , Christ Lisa , Lötscher Fabian , Scholz Godehard , Sarbu Adela-Cristina , Bütikofer Lukas , Kollert Florian , Schmidt Wolfgang A , Reichenbach Stephan , Villiger Peter M 
Published: June 2021

Abstract

Objectives
To characterize the effect of ultra-short glucocorticoids followed by Tocilizumab monotherapy on the intima-media thickness (IMT) in GCA.

Methods
Eighteen GCA patients received 500 mg for 3 consecutive days (total of 1500mg) i.v. methylprednisolone on days 0–2, followed by i.v. Tocilizumab (8 mg/kg) on day 3 and thereafter weekly s.c. Tocilizumab injections (162 mg) over 52 weeks. US of temporal (TAs), axillary (AAs) and subclavian (SAs) arteries was performed at baseline, on days 2–3, and at weeks 4, 8, 12, 24 and 52. The largest IMT of all segments and IMT at landmarks of AA/SA were recorded. IMT was scaled by mean normal values and averaged. Each segment was classified according to diagnostic cut-offs.

Results
Of the 18 GCA patients, 16 patients had TA and 6 had extracranial large artery involvement. The IMT showed a sharp decline on day 2/3 in the TAs and AAs/SAs. In TAs, this was followed by an increase to baseline levels at week 4 and a subsequent slow decrease, which was paralleled by decreasing symptoms and achievement of clinical remission. The AAs/SAs showed a new signal of vasculitis at week 4 in three patients, with an IMT increase up to week 8.

Conclusion
Glucocorticoid pulse therapy induced a transient decrease of the IMT in TAs and AAs/SAs. Tocilizumab monotherapy resulted in a slow and steady decrease in IMT of the TAs and a smaller and delayed effect on the AAs/SAs. The data strongly support a remission-inducing effect of Tocilizumab and argue the case for US having an important role in monitoring disease activity in GCA.

Trial registration
ClinicalTrials.gov, www.clinicaltrials.gov, NCT03745586.
Species-Specific Urothelial Toxicity With an Anti-HIV Noncatalytic Site Integrase Inhibitor (NCINI) Is Related to Unusual pH-Dependent Physicochemical Changes
Authors: Roberts Ruth A , Campbell Richard A , Sikakana Phumzile , Sadler Claire , Osier Mark , Xu Yili , Feng Joy Y , Mitchell Michael , Sakowicz Roman , Chester Anne , Paoli Eric , Wang Jianhong , Burns-Naas Leigh Ann 
Published: June 2021

Abstract
GS-9695 and GS-9822 are next-generation noncatalytic site integrase inhibitors (NCINIs) with significantly improved potency against human immunodeficiency virus compared with previous drugs such as BI-224436. Development stopped due to vacuolation of the bladder urothelium seen in cynomolgus monkey but not in rat; this lesion was absent in equivalent preclinical studies with BI-224436 (tested in dog and rat). Lesions were unlikely to be attributable to target because NCINIs specifically target viral integrase protein and no mammalian homologue is known. Secondary pharmacology studies, mitochondrial toxicity studies, immunophenotyping, and analysis of proteins implicated in cell-cell interactions and/or bladder integrity (E-cadherin, pan-cytokeratin, uroplakins) failed to offer any plausible explanation for the species specificity of the lesion. Because it was characterized by inflammation and disruption of urothelial morphology, we investigated physicochemical changes in the bladder of cynomolgus monkey (urinary pH 5.5–7.4) that might not occur in the bladder of rats (urinary pH 7.3–8.5). In measurements of surface activity, GS-9822 showed an unusual transition from a monolayer to a bilayer at the air/water interface with decreasing pH, attributed to the strong association between drug molecules in adjacent bilayer leaflets and expected to be highly disruptive to the urothelium. Structural analysis of GS-9822 and GS-9695 showed zwitterionic characteristics over the range of pH expected in cynomolgus monkey but not rat urine. This exotic surface behavior is unlikely with BI-224436 since it would transition from neutral to cationic (never zwitterionic) with decreasing pH. These data provide useful insights to guide discovery and development of NCINIs, related compounds, and zwitterions.
Mechanistic Computational Model for Extrapolating In Vitro Thyroid Peroxidase (TPO) Inhibition Data to Predict Serum Thyroid Hormone Levels in Rats
Authors: Handa Sakshi , Hassan Iman , Gilbert Mary , El-Masri Hisham 
Published: June 2021

Abstract
High-throughput in vitro assays are developed to screen chemicals for their potential to inhibit thyroid hormones (THs) synthesis. Some of these experiments, such as the thyroid peroxidase (TPO) inhibition assay, are based on thyroid microsomal extracts. However, the regulation of thyroid disruption chemicals is based on THs in vivo serum levels. This necessitates the estimation of thyroid disruption chemicals in vivo tissue levels in the thyroid where THs synthesis inhibition by TPO takes place. The in vivo tissue levels of chemicals are controlled by pharmacokinetic determinants such as absorption, distribution, metabolism, and excretion, and can be described quantitatively in physiologically based pharmacokinetic (PBPK) models. An integrative computational model including chemical-specific PBPK and TH kinetics models provides a mechanistic quantitative approach to translate thyroidal high-throughput in vitro assays to in vivo measures of circulating THs serum levels. This computational framework is developed to quantitatively establish the linkage between applied dose, chemical thyroid tissue levels, thyroid TPO inhibition potential, and in vivo TH serum levels. Once this link is established quantitatively, the overall model is used to calibrate the TH kinetics parameters using experimental data for THs levels in thyroid tissue and serum for the 2 drugs, propylthiouracil and methimazole. The calibrated quantitative framework is then evaluated against literature data for the environmental chemical ethylenethiourea. The linkage of PBPK and TH kinetics models illustrates a computational framework that can be extrapolated to humans to screen chemicals based on their exposure levels and potential to disrupt serum THs levels in vivo.
Selection of Artificial Dermis for Shortening Treatment Period: Integra versus Pelnac
Authors: Kashimura Tsutomu , Nagasaki Keito , Horigome Michio , Yoshida Kotoku , Soejima Kazutaka 
Published: June 2021

Background:
Skin reconstruction of full-thickness skin defect wounds using artificial dermis is performed using secondary split-thickness skin grafting. For the selection of artificial dermis to shorten the treatment period, the waiting time until secondary skin grafting was investigated when the dermis-like tissue was constructed with Pelnac or Integra.

Methods:
We evaluated 26 patients who underwent secondary skin grafting after dermis reconstruction with Pelnac (18 patients) or Integra (8 patients) for full-thickness skin defects between 2006 and 2017. The waiting period from artificial dermis application to closure of the full-thickness skin defect with a secondary skin graft was investigated retrospectively.

Results:
Skin grafts survived well in all cases, and no complications of grafts or donors were observed. The mean waiting period was 17.5 ± 4.2 and 22.0 ± 4.6 days for the Pelnac and Integra groups, respectively (significantly shorter in the Pelnac group).

Conclusions:
The difference in waiting period is presumed to be due to the structural differences between the collagen sponge layer, which is the dermal replacement layer of Pelnac and Integra grafts. In cases where shortening the treatment period is important, Pelnac should be the first choice. In addition, in pediatric cases and widespread burns where it is difficult to control the infection during the waiting period, Pelnac is considered to be the first choice because the risk can be reduced by shortening the waiting period.
Serial Excision for Treatment of Non-melanoma Skin Cancer
Authors: Dekker Paige K. , Mishu Mark D. , Youn Richard , Baker Stephen B. 
Published: June 2021

Background:
Mohs micrographic surgery (MMS) has become the predominant modality of excision for non-melanoma skin cancers (NMSC). Patients are referred for MMS under the assumption that it is the most effective procedure for definitive removal of the cancer while also allowing for maximal tissue preservation to achieve optimal cosmesis. The objective of this study was to investigate outcomes of serial excision (SE) as an alternative excision modality for NMSC.

Methods:
Patients undergoing SE for basal cell carcinoma or squamous cell carcinoma by the senior author from 2009 to 2020 were retrospectively reviewed. Patient demographics, lesion characteristics, and excision characteristics were recorded. The primary outcome was the number of excisions required to achieve negative margins.

Results:
In total, 129 patients with 205 NMSC lesions were retrospectively reviewed. An estimated 69 lesions (33.7%) were located in high risk areas, as defined by the National Comprehensive Cancer Network. Negative margins were achieved in 191 (93.2%) lesions. In 88.3% of lesions (n = 181/205), negative margins were achieved in 2 or less excisions. 12 lesions (5.9%) were referred for MMS.

Conclusions:
Our results demonstrate that SE is an effective modality for definitive removal of NMSC. Recent research reveals that SE is much less expensive than MMS, and therefore places a smaller financial burden on the patient and the healthcare system as a whole. Relative to MMS, SE offers similar if not increased benefits for lower cost. Our findings highlight the need to critically reassess the select indications for MMS.
Arteriovenous Malformation of the Upper Eyelid: A Case Report
Authors: Alsabbagh Badriah M. , Alfaqeeh Faisal A. , Ajlan Abdulrazag M. , Yaghmoor Faris , Essbaiheen Fahad , Arab Khalid A. 
Published: June 2021

Summary:
Arteriovenous malformations (AVMs) are rare lesions formed by direct connection of arteries and veins bypassing capillary beds. AVM locations can vary; however, extracranial AVMs remain the least common. The vast majority of these malformations are congenital and can be triggered by hormonal changes. A 49-year-old woman presented with a progressive right-sided upper eyelid swelling over the past 12 years. The patient had mechanical ptosis and mild impairment of the right visual field. The swelling was compressible with a thrill, and bruits were heard. The patient was diagnosed with AVM using cerebral angiography. Preoperative endovascular embolization was not possible; however, surgical excision was successfully done with no complications. AVMs and fistulas are high-flow vascular lesions that usually occur during childhood and progress with time. Only a few cases of face and eyelid AVMs have been reported in the literature. Diagnosis of these anomalies is mostly made based on clinical presentation and radiographic imaging such as angiography. Treatment options remain controversial, and management should be individualized for each patient. Endovascular embolization followed by surgical excision is advisable in many cases. Due to its rare entity, information regarding the best management options for AVMs is limited. Reducing the risk of bleeding and achieving total resection is the goal of treatment. Long-term follow-up is required in these patients because recurrent cases of AVMs have been reported.
Three-dimensional Printing Technology for Deep Circumflex Iliac Artery Flap: From Recipient to Donor Sites
Authors: Zhu Wang-Yong , Choi Wing Shan , Su Yu-Xiong 
Published: June 2021

Summary
The deep circumflex iliac artery (DCIA) flap is one of the most commonly used vascularized free flaps for jaw reconstruction; however, its clinical application is limited by donor site complications. We aimed to describe a new technique of using 3-dimensionally (3D) printed patient-specific devices for mandibular reconstruction with DCIA flap and simultaneous dental implants, and for donor site restoration after harvesting the DCIA flap. One patient with mandible ameloblastoma underwent mandibular reconstruction using a DCIA flap with the “jaw-in-a-day” approach. The 3D-printed patient-specific devices included mandibular cutting guides, DCIA harvesting and dental implant guide, surgical plate, and iliac prosthesis. The postoperative 1-month accuracy measurement showed the mean distance deviations of the mandible, transferred bone grafts, dental implants and iliac prosthesis were 1.8 mm, 2.1 mm, 0.9 mm, and 1.2 mm, respectively. Three-dimensionally printed iliac prosthesis satisfactorily restored the contour of the iliac crest after DCIA flap harvesting. No complication of donor site was recorded during the follow-up of 12 months. We successfully used 3D-printed patient-specific implants in both donor and recipient sites for DCIA flap jaw reconstruction. Further studies with a larger sample size and long-term follow-up are needed.
Feasibility and safety of a rapid-access transient ischemic attack clinic
Authors: Hermanson Sarah , Vora Nirali , Blackmore C. Craig , Williams Barbara , Isenberg Nancy 
Published: June 2021

ABSTRACT

Background:
In the United States, patients with transient ischemic attacks (TIAs) are commonly admitted to the hospital despite evidence that low-risk TIA patients achieve improved outcomes at lower costs at specialized rapid-access TIA clinics (RATCs).

Local problem:
All patients experiencing TIAs at a hospital system in the Pacific Northwest were being admitted to the hospital. This project aimed to implement an RATC to relocate care for low-risk TIA patients, showing feasibility and safety.

Methods:
Following implementation of the RATC, a retrospective chart review was performed. Outcomes included days to RATC; days to magnetic resonance imaging (MRI); final diagnosis; stroke-related admissions and deaths within 90 days of the RATC visit.

Interventions:
From 2016 to 2018, implementation of an RATC included patient triage tools; multidisciplinary collaboration between departments; a direct scheduling pathway; and emphasis on stroke prevention.

Results:
Ninety-nine patients were evaluated in the RATC, 69% (69/99) were referred from the emergency department. Sixty-six percent of patients were seen in the TIA clinic in 2 days or less, 19% at 3 days, and 15% at 4 days or more. Mean days to TIA clinic was 2.5 days (SD 2.4). Mean days (SD) to MRI was 2.1 days (SD 2.3). Forty-eight percent (48/99) had a final diagnosis of probable TIA, followed by 32% (32/99) who had other diagnoses; 15% (15/99) migraine variant; 4% (4/99) with stroke. Two percent (2/99) of patients had a stroke-related admission within 90 days, another 2% (2/99) died of non–stroke-related causes within 90 days of the RATC visit.

Conclusions:
Utilization of RATCs is feasible and safe. Nurse practitioners are integral in delivering this innovative, cost-effective model of care.
Social inequalities in hostility toward vaccination against Covid-19
Authors: Spire Alexis , Bajos Nathalie , Silberzan Léna 
Published: June 2021

AbstractIn recent decades, France has appeared as a country particularly hostile to vaccination in general. When asked in November 2020 about the intention to take the Covid-19 vaccine, the French public showed, once again, reluctance. Therefore, France appeared as an ideal case study to analyze whether the hostility toward the Covid-19 vaccine has its own reasons or whether it is related to the reluctance to the principle of vaccination itself. Our objective was to determine the specificity of the social determinants of the intention to get the Covid-19 vaccine. Thanks to the use of a large random sample of the general population in France (86,000 individuals), the reluctant to Covid-19 vaccine could be clearly distinguished from the hesitant and the convinced, and thereby thoroughly analyzed. Our analysis highlighted a gendered reluctance toward vaccination in general but even more so regarding vaccination against Covid-19. It might refer to women being more concerned about the possible effects of an injection in their body, especially at the age of maternity and a differentiated socialization making them more sensitive than men to long-term risks and more apprehensive toward rapid technological change. We also found that people at the bottom of the social hierarchy, in terms of level of education, financial resources, and immigration status, were more likely to refuse the Covid-19 vaccine. Nevertheless, this reluctance was less prominent than for vaccination in general, reflecting the actual spread of the epidemic in various social milieux. Finally, our analysis showed that trust in the government’s actions was significantly associated with reluctance toward the Covid-19 vaccine, even more than toward vaccination in general.Specific campaigns should be thought beforehand to reach women and people at the bottom of the social hierarchy to avoid furthering social inequalities in terms of morbidity and mortality.
Evolutionary epidemiology consequences of trait-dependent control of heterogeneous parasites
Authors: Miele Leonardo , Evans R M L , Cunniffe Nik , Torres-Barcelo Clara , Bevacqua Daniele 
Published: June 2021

AbstractDisease control can induce both demographic and evolutionary responses in host-parasite systems. Foreseeing the outcome of control therefore requires knowledge of the eco-evolutionary feedback between control and system. Previous work has assumed that control strategies have a homogeneous effect on the parasite population. However, this is not true when control targets those traits that confer to the parasite heterogeneous levels of resistance, which can additionally be related to other key parasite traits, through evolutionary trade-offs. In this work, we develop a minimal model coupling epidemiological and evolutionary dynamics to explore possible trait-dependent effects of control strategies. Particularly, we consider a parasite expressing continuous levels of a trait determining resource exploitation, and a control treatment that can be either positively or negatively correlated with that trait. We demonstrate the potential of trait-dependent control by considering that the decision maker may want to minimise both the damage caused by the disease and the use of treatment, due to possible environmental or economic costs. We identify efficient strategies showing that the optimal type of treatment depends on the amount applied. Our results pave the way for the study of control strategies based on evolutionary constraints, such as collateral sensitivity and resistance costs, which are receiving increasing attention for both public health and agricultural purposes.
Prediction of the effect of pH on the aggregation and conditional folding of intrinsically disordered proteins with SolupHred and DispHred
Authors: Iglesias Valentín , Pintado-Grima Carlos , Santos Jaime , Fornt Marc , Ventura Salvador 
Published: June 2021

AbstractProteins microenvironments modulate their structures. Binding partners, organic molecules, or dissolved ions can alter the protein’s compaction, inducing aggregation or order-disorder conformational transitions. Surprisingly, bioinformatic platforms often disregard the protein context in their modeling. In recent work, we proposed that modeling how pH affects protein net charge and hydrophobicity might allow us to forecast pH-dependent aggregation and conditional disorder in intrinsically disordered proteins (IDPs). As these approaches showed remarkable success in recapitulating the available bibliographical data, we made these prediction methods available for the scientific community as two user-friendly web servers. SolupHred is the first dedicated software to predict pH-dependent aggregation, and DispHred is the first pH-dependent predictor of protein disorder. Here we dissect the features of these two software applications to train and assist scientists in studying pH-dependent conformational changes in IDPs.
Imaging flow cytometry challenges the usefulness of classically used EV labelling dyes and qualifies that of a novel dye, named Exoria™ for the labelling of MSC-EV preparations
Authors: Tertel Tobias , Schoppet Melanie , Stambouli Oumaima , Al-Jipouri Ali , James Patrick F. , Giebel Bernd 
Published: June 2021

AbstractExtracellular vesicles (EVs) are involved in mediating intercellular communication processes. An important goal within the EV field is the study of the biodistribution of EVs and the identification of their target cells. Considering that EV uptake is central for mediating the EVs role in intercellular communication processes, labelling with fluorescent dyes has emerged as a broadly distributed strategy for the identification of the EVs target cells and tissues. However, the accuracy and specificity of commonly utilized labelling dyes has not been sufficiently analyzed. By combining recent advancements in imaging flow cytometry for the phenotypic analysis of single EVs and aiming to identify target cells for EVs within therapeutically relevant MSC-EV preparations, we explored the EV labelling efficacy of various fluorescent dyes, specifically of CFDA-SE, Calcein AM, PKH67, BODIPY-TR-Ceramide and a novel lipid dye named Exoria. Our analyses qualified Exoria as the only dye which specifically labels EVs within our MSC-EV preparations. Furthermore, we demonstrate Exoria labelling does not interfere with the immunomodulatory properties of the MSC-EV preparations as tested in a multi-donor mixed lymphocyte reaction assay. Within this assay, labelled EVs were differentially taken-up by different immune cell types. Overall, our results qualify Exoria as an appropriate dye for the labelling of EVs derived from our MSC-EV preparations, this study also demonstrates the need for the development of next generation EV characterization tools which are able to localize and confirm specificity of EV labelling.