bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimized Manufacture of Lyophilized Dermal Fibroblasts for Next-Generation Off-the-Shelf Progenitor Biological Bandages in Topical Post-Burn Regenerative Medicine
Authors: Laurent Alexis , Scaletta Corinne , Abdel-Sayed Philippe , Michetti Murielle , Flahaut Marjorie , Simon Jeanne-Pascale , Roessingh Anthony de Buys , Raffoul Wassim , Hirt-Burri Nathalie , Applegate Lee Ann
Published: August 2021

Cultured fibroblast progenitor cells (FPC) have been studied in Swiss translational regenerative medicine for over two decades, wherein clinical experience was gathered for safely managing burns and refractory cutaneous ulcers. Inherent FPC advantages include high robustness, optimal adaptability to industrial manufacture, and potential for effective repair stimulation of wounded tissues. Major technical bottlenecks in cell therapy development comprise sustainability, stability, and logistics of biological material sources. Herein, we report stringently optimized and up-scaled processing (i.e., cell biobanking and stabilization by lyophilization) of dermal FPCs, with the objective of addressing potential cell source sustainability and stability issues with regard to active substance manufacturing in cutaneous regenerative medicine. Firstly, multi-tiered FPC banking was optimized in terms of overall quality and efficiency by benchmarking key reagents (e.g., medium supplement source, dissociation reagent), consumables (e.g., culture vessels), and technical specifications. Therein, fetal bovine serum batch identity and culture vessel surface were confirmed, among other parameters, to largely impact harvest cell yields. Secondly, FPC stabilization by lyophilization was undertaken and shown to maintain critical functions for devitalized cells in vitro, potentially enabling high logistical gains. Overall, this study provides the technical basis for the elaboration of next-generation off-the-shelf topical regenerative medicine therapeutic products for wound healing and post-burn care.
The Role of Circular RNAs in Keratinocyte Carcinomas
Authors: Meyer Thomas , Sand Michael , Schmitz Lutz , Stockfleth Eggert
Published: August 2021

Keratinocyte carcinomas (KC) include basal cell carcinomas (BCC) and cutaneous squamous cell carcinomas (cSCC) and represents the most common cancer in Europe and North America. Both entities are characterized by a very high mutational burden, mainly UV signature mutations. Predominately mutated genes in BCC belong to the sonic hedgehog pathway, whereas, in cSCC, TP53, CDKN2A, NOTCH1/2 and others are most frequently mutated. In addition, the dysregulation of factors associated with epithelial to mesenchymal transition (EMT) was shown in invasive cSCC. The expression of factors associated with tumorigenesis can be controlled in several ways and include non-coding RNA molecules, such as micro RNAs (miRNA) long noncoding RNAs (lncRNA) and circular RNAs (circRNA). To update findings on circRNA in KC, we reviewed 13 papers published since 2016, identified in a PubMed search. In both BCC and cSCC, numerous circRNAs were identified that were differently expressed compared to healthy skin. Some of them were shown to target miRNAs that are also dysregulated in KC. Moreover, some studies confirmed the biological functions of individual circRNAs involved in cancer development. Thus, circRNAs may be used as biomarkers of disease and disease progression and represent potential targets of new therapeutic approaches for KC.
Helicobacter pylori CagA Induces Cortactin Y-470 Phosphorylation-Dependent Gastric Epithelial Cell Scattering via Abl, Vav2 and Rac1 Activation
Authors: Tegtmeyer Nicole , Harrer Aileen , Rottner Klemens , Backert Steffen
Published: August 2021

The pathogen Helicobacter pylori is the first reported bacterial type-1 carcinogen playing a role in the development of human malignancies, including gastric adenocarcinoma. Cancer cell motility is an important process in this scenario, however, the molecular mechanisms are still not fully understood. Here, we demonstrate that H. pylori subverts the actin-binding protein cortactin through its type-IV secretion system and injected oncoprotein CagA, e.g., by inducing tyrosine phosphorylation of cortactin at Y-470, which triggers gastric epithelial cell scattering and motility. During infection of AGS cells, cortactin was discovered to undergo tyrosine dephosphorylation at residues Y-421 and Y-486, which is mediated through inactivation of Src kinase. However, H. pylori also profoundly activates tyrosine kinase Abl, which simultaneously phosphorylates cortactin at Y-470. Phosphorylated cortactin interacts with the SH2-domain of Vav2, a guanine nucleotide exchange factor for the Rho-family of GTPases. The cortactin/Vav2 complex then stimulates a previously unrecognized activation cascade including the small GTPase Rac1, to effect actin rearrangements and cell scattering. We hypothesize that injected CagA targets cortactin to locally open the gastric epithelium in order to get access to certain nutrients. This may disturb the cellular barrier functions, likely contributing to the induction of cell motility, which is important in gastric cancer development.
Emerging Principles in the Transcriptional Control by YAP and TAZ
Authors: Lopez-Hernandez Alejandro , Sberna Silvia , Campaner Stefano
Published: August 2021

Yes-associated protein (YAP) and TAZ are transcriptional cofactors that sit at the crossroad of several signaling pathways involved in cell growth and differentiation. As such, they play essential functions during embryonic development, regeneration, and, once deregulated, in cancer progression. In this review, we will revise the current literature and provide an overview of how YAP/TAZ control transcription. We will focus on data concerning the modulation of the basal transcriptional machinery, their ability to epigenetically remodel the enhancer–promoter landscape, and the mechanisms used to integrate transcriptional cues from multiple pathways. This reveals how YAP/TAZ activation in cancer cells leads to extensive transcriptional control that spans several hallmarks of cancer. The definition of the molecular mechanism of transcriptional control and the identification of the pathways regulated by YAP/TAZ may provide therapeutic opportunities for the effective treatment of YAP/TAZ-driven tumors.
The Role of Post-Translational Modifications of Chemokines by CD26 in Cancer
Authors: De Zutter Alexandra , Van Damme Jo , Struyf Sofie
Published: August 2021

Chemokines are a large family of small chemotactic cytokines that fulfill a central function in cancer. Both tumor-promoting and -impeding roles have been ascribed to chemokines, which they exert in a direct or indirect manner. An important post-translational modification that regulates chemokine activity is the NH2-terminal truncation by peptidases. CD26 is a dipeptidyl peptidase (DPPIV), which typically clips a NH2-terminal dipeptide from the chemokine. With a certain degree of selectivity in terms of chemokine substrate, CD26 only recognizes chemokines with a penultimate proline or alanine. Chemokines can be protected against CD26 recognition by specific amino acid residues within the chemokine structure, by oligomerization or by binding to cellular glycosaminoglycans (GAGs). Upon truncation, the binding affinity for receptors and GAGs is altered, which influences chemokine function. The consequences of CD26-mediated clipping vary, as unchanged, enhanced, and reduced activities are reported. In tumors, CD26 most likely has the most profound effect on CXCL12 and the interferon (IFN)-inducible CXCR3 ligands, which are converted into receptor antagonists upon truncation. Depending on the tumor type, expression of CD26 is upregulated or downregulated and often results in the preferential generation of the chemokine isoform most favorable for tumor progression. Considering the tight relationship between chemokine sequence and chemokine binding specificity, molecules with the appropriate characteristics can be chemically engineered to provide innovative therapeutic strategies in a cancer setting.
Highly Conductive n-Al0.65Ga0.35N Grown by MOCVD Using Low V/III Ratio
Authors: Zollner Christian J. , Yao Yifan , Wang Michael , Wu Feng , Iza Michael , Speck James S. , DenBaars Steven P. , Nakamura Shuji
Published: August 2021

Highly conductive silicon-doped AlGaN and ohmic contacts are needed for deep-UV LEDs and ultrawide bandgap electronics. We demonstrate improved n-Al0.65Ga0.35N films grown by metal–organic chemical vapor deposition (MOCVD) on sapphire substrates using a low V/III ratio (V/III = 10). A reduced V/III ratio improves repeatability and uniformity by allowing a wider range of silicon precursor flow conditions. AlxGa1−xN:Si with x > 0.5 typically has an electron concentration vs. silicon concentration trend that peaks at a particular “knee” value before dropping sharply as [Si] continues to increase (self-compensation). The Al0.65Ga0.35N:Si grown under the lowest V/III conditions in this study does not show the typical knee behavior, and instead, it has a flat electron concentration trend for [Si] > 3 × 1019 cm−3. Resistivities as low as 4 mΩ-cm were achieved, with corresponding electron mobility of 40 cm2/Vs. AFM and TEM confirm that surface morphology and dislocation density are not degraded by these growth conditions. Furthermore, we report vanadium-based ohmic contacts with a resistivity of 7 × 10−5 Ω-cm2 to AlGaN films grown using a low V/III ratio. Lastly, we use these highly conductive silicon-doped layers to demonstrate a 284 nm UV LED with an operating voltage of 7.99 V at 20 A/cm2, with peak EQE and WPE of 3.5% and 2.7%, respectively.
Prediction Model for Tumor Budding Status Using the Radiomic Features of F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Cervical Cancer
Authors: Chong Gun Oh , Park Shin-Hyung , Jeong Shin Young , Kim Su Jeong , Park Nora Jee-Young , Lee Yoon Hee , Lee Sang-Woo , Hong Dae Gy , Park Ji Young , Han Hyung Soo
Published: August 2021

Objective: To compare the radiomic features of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and intratumoral heterogeneity according to tumor budding (TB) status and to develop a prediction model for the TB status using the radiomic feature of 18F-FDG PET/CT in patients with cervical cancer. Materials and Methods: Seventy-six patients with cervical cancer who underwent radical hysterectomy and preoperative 18F-FDG PET/CT were included. We assessed the status of intratumoral budding (ITP) and peritumoral budding (PTB) in all available hematoxylin and eosin-stained specimens. Three conventional metabolic parameters and fifty-nine features were extracted and analyzed. Univariate analysis was used to identify significant metabolic parameters and radiomic findings for TB status. The prediction model for TB status was built using 3 machine learning classifiers (random forest, support vector machine, and neural network). Results: Univariate analysis led to the identification of 2 significant metabolic parameters and 12 significant radiomic features according to intratumoral budding (ITB) status. Among these parameters, following multivariate analysis for the ITB status, only compacity remained significant (odds ratio, 5.0047; 95% confidence interval, 1.1636–21.5253; p = 0.0305). Two conventional metabolic parameters and 25 radiomic features were selected by the Lasso regularization, and the prediction model for the ITB status had a mean area under the curve of 0.762 in the test dataset. Conclusion: Radiomic features of 18F-FDG PET/CT were associated with the ITB status. The prediction model using radiomic features successfully predicted the TB status in patients with cervical cancer. The prediction models for the ITB status may contribute to personalized medicine in the management of patients with cervical cancer.
Focal Myocarditis after Mild COVID-19 Infection in Athletes
Authors: Nedeljkovic Ivana P. , Giga Vojislav , Ostojic Marina , Djordjevic-Dikic Ana , Stojmenovic Tamara , Nikolic Ivan , Dikic Nenad , Nedeljkovic-Arsenovic Olga , Maksimovic Ruzica , Dobric Milan , Mujovic Nebojsa , Beleslin Branko
Published: August 2021

COVID-19 infection in athletes usually has a milder course, but in the case of complications, myocarditis and even sudden cardiac death may occur. We examined an athlete who felt symptoms upon returning to training after asymptomatic COVID-19 infection. Physical, laboratory, and echocardiography findings were normal. The cardiopulmonary exercise test was interrupted at submaximal effort due to severe dyspnea in the presence of reduced functional capacity in comparison to previous tests. Cardiac magnetic resonance (CMR) detected the focal myocarditis. After three months of recovery, CMR still revealed the presence of focal myocarditis and the persistence of decreased functional capacity. This case raises the question of screening athletes even after asymptomatic forms of COVID-19 infection.
Synthetic mRNAs; Their Analogue Caps and Contribution to Disease
Authors: Kyriakopoulos Anthony M. , McCullough Peter A.
Published: August 2021

The structure of synthetic mRNAs as used in vaccination against cancer and infectious diseases contain specifically designed caps followed by sequences of the 5′ untranslated repeats of β-globin gene. The strategy for successful design of synthetic mRNAs by chemically modifying their caps aims to increase resistance to the enzymatic deccapping complex, offer a higher affinity for binding to the eukaryotic translation initiation factor 4E (elF4E) protein and enforce increased translation of their encoded proteins. However, the cellular homeostasis is finely balanced and obeys to specific laws of thermodynamics conferring balance between complexity and growth rate in evolution. An overwhelming and forced translation even under alarming conditions of the cell during a concurrent viral infection, or when molecular pathways are trying to circumvent precursor events that lead to autoimmunity and cancer, may cause the recipient cells to ignore their differential sensitivities which are essential for keeping normal conditions. The elF4E which is a powerful RNA regulon and a potent oncogene governing cell cycle progression and proliferation at a post-transcriptional level, may then be a great contributor to disease development. The mechanistic target of rapamycin (mTOR) axis manly inhibits the elF4E to proceed with mRNA translation but disturbance in fine balances between mTOR and elF4E action may provide a premature step towards oncogenesis, ignite pre-causal mechanisms of immune deregulation and cause maturation (aging) defects.
Minimization of Output Voltage Ripple of Two-Phase Interleaved Buck Converter with Active Clamp
Authors: Yau Yeu-Torng , Hwu Kuo-Ing , Shieh Jenn-Jong
Published: August 2021

A control technique combining pulse width modulation (PWM) and pulse amplitude modulation (PAM) is presented herein to reduce the output voltage ripple of the converter as little as possible. Such a converter requires a two-stage cascaded structure. The first stage is the buck-boost converter, which is used to adjust the output voltage of the second power stage, whereas the second stage is the two-phase interleaved buck converter, which is used to reduce the output voltage ripple. In theory, the two phases of the second stage operate under the condition of individual duty cycles of 50% with a phase difference of 180° between the two, and hence, the currents in the two phases are cancelled for any period of time, thereby making the output voltage of the converter almost voltage-free. Moreover, in order to improve the overall efficiency further, the proposed soft-switching technique based on an active clamp is presented and applied to these two stages to render the main and auxiliary switches turned on with zero-voltage switching (ZVS). Finally, the operating principles and control strategies of the proposed converter are described, and then, their effectiveness is verified by experimental results.
Community Capacity-Building Mobilization towards Energy Transitions in the Era of Thailand 4.0: A Case Study on Biomass Power Plants
Authors: Homket Yuttana , Sutheravut Pongthep , Nima Sawpheeyah
Published: August 2021

In 2015, the National Energy Policy Council (NEPC) approved the latest Alternative Energy Development Plan (AEDP) 2015–2036, targeting electricity generation from biomass, biogas, and municipal solid waste by 2036 towards the Thailand 4.0 policy. The small biomass power plants are intensively promoted, contributing to many more public concerns. Therefore, this study provided new insight using the readiness and resilience in the communities near the biomass power plant generation in Southern Thailand. The community readiness model (CRM) and community health impact assessment (CHIA) were adopted using mixed methods during January–November 2019. A total of 999 respondents replied to the questionnaires, 153 informants were interviewed, and the panel was discussed and analyzed by descriptive statistics and content analysis. Findings illustrated that all stakeholder sectors strengthened community-driven development based on the average community readiness (3.01 ± 0.11) in a vague awareness stage, only with participation in information giving (75.38%) and having an impact pain point score of 7.64 ± 0.54, which was a highly intense level used to develop the public policy towards biomass power plants. Recent advanced community tools offered new insights for the first time about community strategic plans for sustainable biomass power generation, to achieve community security and values of democracy in Southern Thailand.
Effect of Type and Concentration of Carrier Material on the Encapsulation of Pomegranate Peel Using Spray Drying Method
Authors: Šavikin Katarina , Nastić Nataša , Janković Teodora , Bigović Dubravka , Miličević Borislav , Vidović Senka , Menković Nebojša , Vladić Jelena
Published: August 2021

This study aimed to establish a procedure for pomegranate peel (PP) valorization and attainment of stable extracts with preserved bioactive compounds. The technology applied was spray drying with carbohydrate-based (maltodextrin, MD) and protein-based (whey protein, WP) carrier materials in different concentrations (80, 100, and 120%). What was analyzed was the impact of the type and concentration of carrier material on the stability and quality of the final encapsulated powder. The best results were achieved when the PP extract was microencapsulated with the carbohydrate-based carrier (100%), where it had the highest encapsulation efficiency (EE) (88.63%), hygroscopicity (15.17%), and water solubility index (87.04%). The moisture content was in the range of 3.69–4.60% and 4.21–5.84% for MD and WP, respectively, indicating that both are suitable for long-term storage. It was observed that changes in carrier concentration significantly influenced most of the powders’ physicochemical properties. Microencapsulation using MD yielded a higher content of punicalin, punicalagin, gallic, and ellagic acid than those with WP. Overall results demonstrated that carbohydrate-based microencapsulation can be utilized efficiently for the protection of powder stability and phytochemical characteristics.
Expression of Piwi, MMP, TIMP, and Sox during Gut Regeneration in Holothurian Eupentacta fraudatrix (Holothuroidea, Dendrochirotida)
Authors: Dolmatov Igor Yu. , Kalacheva Nadezhda V. , Tkacheva Ekaterina S. , Shulga Alena P. , Zavalnaya Eugenia G. , Shamshurina Ekaterina V. , Girich Alexander S. , Boyko Alexey V. , Eliseikina Marina G.
Published: August 2021

Mesodermal cells of holothurian Eupentacta fraudatrix can transdifferentiate into enterocytes during the regeneration of the digestive system. In this study, we investigated the expression of several genes involved in gut regeneration in E. fraudatrix. Moreover, the localization of progenitor cells of coelomocytes, juvenile cells, and their participation in the formation of the luminal epithelium of the digestive tube were studied. It was shown that Piwi-positive cells were not involved in the formation of the luminal epithelium of the digestive tube. Ef-72 kDa type IV collagenase and Ef-MMP16 had an individual expression profile and possibly different functions. The Ef-tensilin3 gene exhibited the highest expression and indicates its potential role in regeneration. Ef-Sox9/10 and Ef-Sox17 in E. fraudatrix may participate in the mechanism of transdifferentiation of coelomic epithelial cells. Their transcripts mark the cells that plunge into the connective tissue of the gut anlage and give rise to enterocytes. Ef-Sox9/10 probably controls the switching of mesodermal cells to the enterocyte phenotype, while Ef-Sox17 may be involved in the regulation of the initial stages of transdifferentiation.
Evaluation of WNT Signaling Pathway Gene Variants WNT7B rs6519955, SFRP4 rs17171229 and RSPO2 rs611744 in Patients with Dupuytren’s Contracture
Authors: Samulėnas Gediminas , Smalinskienė Alina , Rimdeika Rytis , Braziulis Kęstutis , Fomkinas Mantas , Paškevičius Rokas
Published: August 2021

Dupuytren’s contracture (DC) represents a chronic fibroproliferative pathology of the palmar aponeurosis, which leads to flexion contractures of finger joints and hand disability. In recent decades, the WNT signaling pathway has been revealed to play a significant role in the manifestation and pathogenesis of DC. Our study aimed to evaluate the associations between Dupuytren’s contracture and WNT-related single-nucleotide polymorphisms: Wnt Family Member 7B (WNT7B) rs6519955 (G/T), Secreted Frizzled Related Protein 4 (SFRP4) rs17171229 (C/T) and R-spondin 2 (RSPO2) rs611744 (A/G). We enrolled 216 patients (113 DC cases and 103 healthy controls), and DNA samples were extracted from the peripheral blood. Genotyping of WNT7B rs6519955, SFRP4 rs17171229 and RSPO2 rs611744 was performed using the Real-Time PCR System 7900HT from Applied Biosystems. WNT7B rs6519955 genotype TT carriers were found to possess a higher prevalence of DC (OR = 3.516; CI = 1.624–7.610; p = 0.001), whereas RSPO2 rs611744 genotype GG appears to reduce the likelihood of the manifestation of DC nearly twofold (OR = 0.484, CI = 0.258–0.908, p = 0.024). In conclusion, SNPs WNT7B rs6519955 and RSPO2 rs611744 are associated with the development of Dupuytren’s contracture: WNT7B rs6519955 TT genotype increases the chances by 3.5-fold, and RSPO2 rs611744 genotype GG appears to attenuate the likelihood of the manifestation of DC nearly twofold. Findings of genotype distributions among DC patients and control groups suggest that SFRP4 rs17171229 is not significantly associated with development of the disease.
Nonelderly Adult Cancer Survivors in High Deductible Health Plan: Healthcare Expenditure, Utilization and Access
Authors: Mahashabde Ruchira , Li Chenghui
Published: August 2021

Background: To compare healthcare expenditure, utilization and access between nonelderly adult cancer survivors enrolled in a high deductible health plan with a health savings account (“HDHP+HSA”), HDHP without HSA (“HDHP alone”) and low deductible health plan (“LDHP”). Methods: 1735 cancer survivors, aged 18–64 years, with continuous private coverage identified from the 2012–2017 Medical Expenditure Panel Survey: HDHP alone (n = 353), HDHP+HSA (n = 242) and LDHP (n = 1140). Healthcare expenditures, utilization and inability/delay obtaining medical care were analyzed using generalized linear regressions with inverse propensity score weighting and doubly robust estimation. Results: HDHP alone group (23,255 USD) had significantly higher total healthcare expenditure compared to HDHP+HSA (15,580 USD, p = 0.012) and LDHP (16,261 USD, p = 0.016). HDHP alone (6089 USD; p = 0.002) and HDHP+HSA (5743 USD; p = 0.012) groups had significantly higher out-of-pocket (OOP) expenditure compared to LDHP (4853 USD). HDHP alone (17,128 USD, p = 0.010) and LDHP (12,645 USD, p = 0.045) had significantly higher private insurer payments compared to HDHP+HSA (9216 USD). No differences were found in utilization or inability/delay obtaining medical care across groups. Conclusions: Non-elderly adult cancer survivors with continuous coverage and comparable sociodemographic characteristics enrolled in HDHP with HSA displayed the lowest healthcare costs compared to HDHP without HSA and LDHP. HDHP+HSA had a significantly higher OOP expenditure than LDHP. No significant differences were observed in utilization or access among groups.
Longitudinal Effects of Excessive Weight and Obesity on Academic Performance of Primary School Boys in Different Socio-Economic Statuses: The NW-CHILD Study
Authors: Coetzee Dané , du Plessis Wilmarié , van Staden Deidré
Published: August 2021

Obesity affects millions of children worldwide and can often impact their academic performance. This longitudinal study, conducted over seven years, determines the effects of excessive weight and obesity on the academic performance of primary school boys, taking into account their socio-economic status (SES). The study forms part of a seven-year (2010–2016) longitudinal study, the North-West Child-Health-Integrated-Learning and Development (NW-CHILD) study, which includes a baseline measurement and two follow-up measurements of the 181 participants from varying areas in the North West Province. Two-way frequency tables, repeated measure ANOVA’s and Spearman rank order correlations were used to analyze the data. The Body Mass Index (BMI) of the participants reported an increase from 2010–2016. Nearly all of the school subjects reported small to large correlations between BMI and academic performance (r ≥ 0.1 and r ≥ 0.3), except for Afrikaans in 2013 (r = −0.06). Only two subjects (English and Language as tested with the ANA test) reported medium effects (r ≥ 0.3), whereas the other subjects only reported small effects (r ≥ 0.1). No statistically significant relationships (p ≥ 0.05) were observed between the BMI values and academic subjects, however SES and school subject scores reported several statistically significant relationships, especially regarding Language (English and First Additional Language) and Mathematics (p = 0.02). Overweight and obese primary school boys in the North West Province of South Africa reported a higher academic performance in comparison to boys of a normal weight, even when SES was taken into consideration. Further studies are recommended to verify current findings regarding weight, obesity and academic performance.
GSK-3β, FYN, and DYRK1A: Master Regulators in Neurodegenerative Pathways
Authors: Demuro Stefania , Di Martino Rita M. C. , Ortega Jose A. , Cavalli Andrea
Published: August 2021

Protein kinases (PKs) have been recognized as central nervous system (CNS)-disease-relevant targets due to their master regulatory role in different signal transduction cascades in the neuroscience space. Among them, GSK-3β, FYN, and DYRK1A play a crucial role in the neurodegeneration context, and the deregulation of all three PKs has been linked to different CNS disorders with unmet medical needs, including Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal lobar degeneration (FTLD), and several neuromuscular disorders. The multifactorial nature of these diseases, along with the failure of many advanced CNS clinical trials, and the lengthy approval process of a novel CNS drug have strongly limited the CNS drug discovery. However, in the near-decade from 2010 to 2020, several computer-assisted drug design strategies have been combined with synthetic efforts to develop potent and selective GSK-3β, FYN, and DYRK1A inhibitors as disease-modifying agents. In this review, we described both structural and functional aspects of GSK-3β, FYN, and DYRK1A and their involvement and crosstalk in different CNS pathological signaling pathways. Moreover, we outlined attractive medicinal chemistry approaches including multi-target drug design strategies applied to overcome some limitations of known PKs inhibitors and discover improved modulators with suitable blood–brain barrier (BBB) permeability and drug-like properties.
Extracellular DNA (eDNA). A Major Ubiquitous Element of the Bacterial Biofilm Architecture
Authors: Campoccia Davide , Montanaro Lucio , Arciola Carla Renata
Published: August 2021

After the first ancient studies on microbial slime (the name by which the biofilm matrix was initially indicated), multitudes of studies on the morphology, composition and physiology of biofilms have arisen. The emergence of the role that biofilms play in the pathogenesis of recalcitrant and persistent clinical infections, such as periprosthetic orthopedic infections, has reinforced scientific interest. Extracellular DNA (eDNA) is a recently uncovered component that is proving to be almost omnipresent in the extracellular polymeric substance (EPS) of biofilm. This macromolecule is eliciting unprecedented consideration for the critical impact on the pathogenesis of chronic clinical infections. After a systematic review of the literature, an updated description of eDNA in biofilms is presented, with a special focus on the latest findings regarding its fundamental structural role and the contribution it makes to the complex architecture of bacterial biofilms through interactions with a variety of other molecular components of the biofilm matrix.
Neuroblastoma GD2 Expression and Computational Analysis of Aptamer-Based Bioaffinity Targeting
Authors: Sabbih Godfred O. , Danquah Michael K.
Published: August 2021

Neuroblastoma (NB) is a neuroectodermal embryonic cancer that originates from primordial neural crest cells, and amongst pediatric cancers with high mortality rates. NB is categorized into high-, intermediate-, and low-risk cases. A significant proportion of high-risk patients who achieve remission have a minimal residual disease (MRD) that causes relapse. Whilst there exists a myriad of advanced treatment options for NB, it is still characterized by a high relapse rate, resulting in a reduced chance of survival. Disialoganglioside (GD2) is a lipo-ganglioside containing a fatty acid derivative of sphingosine that is coupled to a monosaccharide and a sialic acid. Amongst pediatric solid tumors, NB tumor cells are known to express GD2; hence, it represents a unique antigen for subclinical NB MRD detection and analysis with implications in determining a response for treatment. This article discusses NB MRD expression and analytical assays for GD2 detection and quantification as well as computational approaches for GD2 characterization based on high-throughput image processing and genomic data analysis.
Antisense Peptide Technology for Diagnostic Tests and Bioengineering Research
Authors: Štambuk Nikola , Konjevoda Paško , Pavan Josip
Published: August 2021

Antisense peptide technology (APT) is based on a useful heuristic algorithm for rational peptide design. It was deduced from empirical observations that peptides consisting of complementary (sense and antisense) amino acids interact with higher probability and affinity than the randomly selected ones. This phenomenon is closely related to the structure of the standard genetic code table, and at the same time, is unrelated to the direction of its codon sequence translation. The concept of complementary peptide interaction is discussed, and its possible applications to diagnostic tests and bioengineering research are summarized. Problems and difficulties that may arise using APT are discussed, and possible solutions are proposed. The methodology was tested on the example of SARS-CoV-2. It is shown that the CABS-dock server accurately predicts the binding of antisense peptides to the SARS-CoV-2 receptor binding domain without requiring predefinition of the binding site. It is concluded that the benefits of APT outweigh the costs of random peptide screening and could lead to considerable savings in time and resources, especially if combined with other computational and immunochemical methods.
Perioperative Management of Pheochromocytoma: From a Dogmatic to a Tailored Approach
Authors: Buscemi Salvatore , Di Buono Giuseppe , D’Andrea Rocco , Ricci Claudio , Alberici Laura , Querci Lorenzo , Selva Saverio , Minni Francesco , Citarrella Roberto , Romano Giorgio , Agrusa Antonino
Published: August 2021

Background: Perioperative management of pheochromocytoma (PCC) remains under debate. Methods: A bicentric retrospective study was conducted, including all patients who underwent laparoscopic adrenalectomy for PCC from 2000 to 2017. Patients were divided into two groups: Group 1 treated with alpha-blockade, and Group 2, without alfa-blockers. The primary end point was the major complication rate. The secondary end points were: the need for advanced intra-operative hemostasis, the admission to the intensive care unit (ICU), the length of stay (LOS), systolic (SBP), and diastolic blood pressure (DBP). Univariate and multivariate analysis was conducted. A p-value < 0.05 was considered statistically significant. Results: Major postoperative complications were similar (p = 0.49). Advanced hemostatic agents were 44.9% in Group 1 and 100% in Group 2 (p < 0.001). In Group 2, no patients were admitted to the ICU, while only 73.5% of Group 1 (p < 0.001) were admitted. The median length of stay was larger in Group 1 than in Group 2 (p = 0.026). At the induction, SBP was 130 mmHg in Group 1, and 115 mmHg (p < 0.001). The pre-surgery treatment was the only almost statistically significant variable at the multivariate analysis of DBP at the end of surgery. Conclusion: The preoperative use of alfa-blockers should be considered not a dogma in PCC.
Characterization of Risk Profiles for Diabetic Retinopathy Progression
Authors: Cunha-Vaz José , Mendes Luís
Published: August 2021

Diabetic retinopathy (DR) is a frequent complication of diabetes and, through its vision-threatening complications, i.e., macular edema and proliferative retinopathy, may lead to blindness. It is, therefore, of major relevance to identify the presence of retinopathy in diabetic patients and, when present, to identify the eyes that have the greatest risk of progression and greatest potential to benefit from treatment. In the present paper, we suggest the development of a simple to use alternative to the Early Treatment Diabetic Retinopathy Study (ETDRS) grading system, establishing disease severity as a necessary step to further evaluate and categorize the different risk factors involved in the progression of diabetic retinopathy. It needs to be validated against the ETDRS classification and, ideally, should be able to be performed automatically using data directly from the examination equipment without the influence of subjective individual interpretation. We performed the characterization of 105 eyes from 105 patients previously classified by ETDRS level by a Reading Centre using a set of rules generated by a decision tree having as possible inputs a set of metrics automatically extracted from Swept-source Optical Coherence Tomography (SS-OCTA) and Spectral Domain- OCT (SD-OCT) measured at different localizations of the retina. When the most relevant metrics were used to derive the rules to perform the organization of the full pathological dataset, taking into account the different ETDRS grades, a global accuracy equal to 0.8 was obtained. In summary, it is now possible to envision an automated classification of DR progression using noninvasive methods of examination, OCT, and SS-OCTA. Using this classification to establish the severity grade of DR, at the time of the ophthalmological examination, it is then possible to identify the risk of progression in severity and the development of vision-threatening complications based on the predominant phenotype.
Financial Inclusion through Digital Financial Services (DFS): A Study in Uganda
Authors: Ebong Jimmy , George Babu
Published: August 2021

This study unravels trends and momentum in banking and mobile money channels and uptake of select services and thereafter draws implications for enhancing financial inclusion through Digital Financial Services (DFS). The Rate of Change (ROC) approach was applied to analyze the growth momentum in banking and mobile money channels in Uganda. Implications for growth momentum in banking and mobile money channels for DFS and financial inclusion was drawn from observing and making informed interpretation of such observed trends and momentum. The findings of this study imply that banks must innovate to increase their contribution towards enhancing financial inclusion. Additional channel innovations, which may infuse banking and mobile money channels, are needed for banking to leverage on growth of mobile money and regain its role in enhancing financial inclusion. Leveraging the application of digital innovations in services such as payments and digitizing alternative channels such as agent banking are likely to increase efficiencies in physical channels and the provision of banking services and thereby increase overall reach and penetration of banking. The fast pace of mobile money penetration is good for speeding up financial inclusion. However, this calls for better regulatory approaches for DFS risk reduction, consumer protection, and protecting mobile money against integrity and financial crimes.
A Nature Tourism Route through GIS to Improve the Visibility of the Natural Resources of the Altar Volcano, Sangay National Park, Ecuador
Authors: Gavilanes Montoya Alex Vinicio , Esparza Parra José Fernando , Chávez Velásquez Carlos Renato , Tito Guanuche Paúl Eduardo , Parra Vintimilla Grace Maribel , Mestanza-Ramón Carlos , Vizuete Danny Daniel Castillo
Published: August 2021

Tourism in natural areas attracts people seeking contact with pristine ecosystems as opposed to a polluted urban habitat and a stressful pace of life. An adequate tourist route and itinerary guarantees a high level of tourist satisfaction. The objective of this study was to focus on the design of a tourist route and itinerary in the Altar Volcano, Sangay National Park, central Ecuador, by integrating tourist attractions and facilities. Within the methodological process, the main tourist attractions of the area were identified and georeferenced; then, a thematic map was elaborated using ArcGIS 10.5® software. Distances were determined by considering the transportation alternatives in relation to the base camps. Finally, the itinerary was structured by considering the possible tourist activities of each place or attraction. As a result, a tourist route was obtained that included 19 attractions and an itinerary that interacts with various activities in the study area. This research will strengthen tourism activities in the Altar Volcano, allowing for an increase in the number of visitors and the development of sustainable tourism thanks to proper planning in the use of a new tourist route.
Multimodal Approaches for Heritage and Second Language Instructor Training
Authors: Vasseur Raychel
Published: August 2021

This piece explores the need to provide better training to graduate student instructors by first conducting a needs analysis of current graduate students and recent graduate students regarding their conceptualizations of writing, multiliteracies, and second (L2) and heritage language (HL) pedagogies. Based on this survey, it is evident that with just one teaching methods course as the typical training graduate student instructors receive it behooves us to implement innovative pedagogy in other ways to develop graduate students’ abilities to navigate new technological tools and reconsider how they can teach writing in the L2/HL courses. Based on previous research as well as practical experience, this paper discusses several approaches for training and preparing graduate students to reconsider their preconceived notions of what it means to learn to write in an L2 or HL to include more focus on multiliteracies and technological skills to prepare students for 21st century communication.
Degradation and Characterisation of Electrospun Polycaprolactone (PCL) and Poly(lactic-co-glycolic acid) (PLGA) Scaffolds for Vascular Tissue Engineering
Authors: Bazgir Morteza , Zhang Wei , Zhang Ximu , Elies Jacobo , Saeinasab Morvarid , Coates Phil , Youseffi Mansour , Sefat Farshid
Published: August 2021

The current study aimed to evaluate the characteristics and the effects of degradation on the structural properties of Poly(lactic-co-glycolic acid) (PLGA)- and polycaprolactone (PCL)-based nanofibrous scaffolds. Six scaffolds were prepared by electrospinning, three with PCL 15% (w/v) and three with PLGA 10% (w/v), with electrospinning processing times of 30, 60 and 90 min. Both types of scaffolds displayed more robust mechanical properties with increased spinning times. The tensile strength of both scaffolds with 90-min electrospun membranes did not show a significant difference in their strengths, as the PCL and PLGA scaffolds measured at 1.492 MPa ± 0.378 SD and 1.764 MPa ± 0.7982 SD, respectively. All membranes were shown to be hydrophobic under a wettability test. A degradation behaviour study was performed by immersing all scaffolds in phosphate-buffered saline (PBS) solution at room temperature for 12 weeks and for 4 weeks at 37 °C. The effects of degradation were monitored by taking each sample out of the PBS solution every week, and the structural changes were investigated under a scanning electron microscope (SEM). The PCL and PLGA scaffolds showed excellent fibre structure with adequate degradation, and the fibre diameter, measured over time, showed slight increase in size. Therefore, as an example of fibre water intake and progressive degradation, the scaffold’s percentage weight loss increased each week, further supporting the porous membrane’s degradability. The pore size and the porosity percentage of all scaffolds decreased substantially over the degradation period. The conclusion drawn from this experiment is that PCL and PLGA hold great promise for tissue engineering and regenerative medicine applications.
The Vital Role of La2O3 on the La2O3-CaO-B2O3-SiO2 Glass System for Shielding Some Common Gamma Ray Radioactive Sources
Authors: Al-Ghamdi Hanan , Dong Mengge , Sayyed M. I. , Wang Chao , Almuqrin Aljawhara H. , Almasoud Fahad I.
Published: August 2021

The role La2O3 on the radiation shielding properties of La2O3-CaO-B2O3-SiO2 glass systems was investigated. The energies were selected between 0.284 and 1.275 MeV and Phy-X software was used for the calculations. BLa10 glass had the least linear attenuation coefficient (LAC) at all the tested energies, while BLa30 had the greatest, which indicated that increasing the content of La2O3 in the BLa-X glasses enhances the shielding performance of these glasses. The mass attenuation coefficient (MAC) of BLa15 decreases from 0.150 cm2/g to 0.054 cm2/g at energies of 0.284 MeV and 1.275 MeV, respectively, while the MAC of BLa25 decreases from 0.164 cm2/g to 0.053 cm2/g for the same energies, respectively. At all energies, the effective atomic number (Zeff) values follow the trend BLa10 < BLa15 < BLa20 < BLa25 < BLa30. The half value thickness (HVL) of the BLa-X glass shields were also investigated. The minimum HVL values are found at 0.284 MeV. The HVL results demonstrated that BLa30 is the most space-efficient shield. The tenth value layer (TVL) results demonstrated that the glasses are more effective attenuators at lower energies, while decreasing in ability at greater energies. These mean free path results proved that increasing the density of the glasses, by increasing the amount of La2O3 content, lowers MFP, and increases attenuation, which means that BLa30, the glass with the greatest density, absorbs the most amount of radiation.
Vegetarian Diets, Ayurveda, and the Case for an Integrative Nutrition Science
Authors: Purushotham Archana , Hankey Alex
Published: August 2021

Two recent studies of the health effects of vegetarian diets reported conflicting results: the EPIC-Oxford study reported a significant increase in strokes among vegetarians compared to meat-eaters among a predominantly Caucasian cohort, while another, performed on Taiwanese Buddhists, reported significantly lower incidence of strokes among vegetarians. This was doubly puzzling given the pronounced decrease in cardiovascular events among the EPIC-Oxford group. In this article, we make a detailed comparison of the actual dietary intake of various food groups by the cohorts in these studies. We then use the nutritional principles of Ayurveda—traditional Indian medicine—to show how these apparently contradictory results may be explained. Systems of traditional medicine such as Ayurveda possess profound knowledge of the effects of food on physiology. Ayurveda takes into account not just the type of food, but also multiple other factors such as taste, temperature, and time of consumption. Traditional cuisines have evolved hand in hand with such systems of medicine to optimize nutrition in the context of local climate and food availability. Harnessing the experiential wisdom of these traditional systems to create an integrative nutrition science would help fight the ongoing epidemic of chronic lifestyle diseases, and improve health and wellness.
Potent Acrylamide Determination in Food Products Using Ion-Selective Electrode Technique
Authors: Khalil Sabry , El-Beltagy Alaa , El-Sharnouby Mohamed
Published: August 2021

A potent selective acrylamide liquid sensor based on the reaction of acrylamide with 2-(5-Bromo-2-pyridylazo)-5-[N-n-Propyl-N-(3-Sulfopropyl) amino] aniline reagent is successfully designed. The characteristics slope (52.33 mV/decade), linearity usable range from 1.0 × 10−7–1.0 × 10−1 molar, limit of detection (1.6 × 10−8) molar, selectivity attitude to several inorganic cations, amino acids and sugars, time of response (8 s), lifetime (four months), pH effect on the electrode potential and the basic validation parameters were studied. The desirable pH applicable range was 3.0–6.5, and the restraint of the developed sensor is independent on this working pH range. The deployed electrode was effectively applied for rapid inexpensive analysis of acrylamide cations in food products with comparison to high-performance liquid chromatographic method and the results were agreeable with each other. The obtained data by the suggested electrode were treated statistically and compared with the various recently published acrylamide sensors.
Whole Genome Sequence Analysis of Brucella melitensis Phylogeny and Virulence Factors
Authors: Rabinowitz Peter , Zilberman Bar , Motro Yair , Roberts Marilyn C. , Greninger Alex , Nesher Lior , Ben-Shimol Shalom , Yagel Yael , Gdalevich Michael , Sagi Orly , Davidovitch Nadav , Kornspan David , Bardenstein Svetlana , Moran-Gilad Jacob
Published: August 2021

Brucellosis has a wide range of clinical severity in humans that remains poorly understood. Whole genome sequencing (WGS) analysis may be able to detect variation in virulence genes. We used Brucella melitensis sequences in the NCBI Sequence Read Archive (SRA) database to assemble 248 whole genomes, and additionally, assembled 27 B. melitensis genomes from samples of human patients in Southern Israel. We searched the 275 assembled genomes for the 43 B. melitensis virulence genes in the Virulence Factors of Pathogenic Bacteria Database (VFDB) and 10 other published putative virulence genes. We explored pan-genome variation across the genomes and in a pilot analysis, explored single nucleotide polymorphism (SNP) variation among the ten putative virulence genes. More than 99% of the genomes had sequences for all Brucella melitensis virulence genes included in the VFDB. The 10 other virulence genes of interest were present across all the genomes, but three of these genes had SNP variation associated with particular Brucella melitensis genotypes. SNP variation was also seen within the Israeli genomes obtained from a small geographic region. While the Brucella genome is highly conserved, this novel and large whole genome study of Brucella demonstrates the ability of whole genome and pan-genome analysis to screen multiple genomes and identify SNP variation in both known and novel virulence genes that could be associated with differential disease virulence. Further development of whole genome techniques and linkage with clinical metadata on disease outcomes could shed light on whether such variation in the Brucella genome plays a role in pathogenesis.