bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-Dimensional Unsteady Aerodynamic Analysis of a Rigid-Framed Delta Kite Applied to Airborne Wind Energy
Authors: Castro-Fernández Iván , Borobia-Moreno Ricardo , Cavallaro Rauno , Sánchez-Arriaga Gonzalo
Published: December 2021

The validity of using a low-computational-cost model for the aerodynamic characterization of Airborne Wind Energy Systems was studied by benchmarking a three-dimensional Unsteady Panel Method (UnPaM) with experimental data from a flight test campaign of a two-line Rigid-Framed Delta kite. The latter, and a subsequent analysis of the experimental data, provided the evolution of the tether tensions, the full kinematic state of the kite (aerodynamic velocity and angular velocity vectors, among others), and its aerodynamic coefficients. The history of the kinematic state was used as input for UnPaM that provided a set of theoretical aerodynamic coefficients. Disparate conclusions were found when comparing the experimental and theoretical aerodynamic coefficients. For a wide range of angles of attack and sideslip angles, the agreement in the lift and lateral force coefficients was good and moderate, respectively, considering UnPaM is a potential flow tool. As expected, UnPaM predicts a much lower drag because it ignores viscous effects. The comparison of the aerodynamic torque coefficients is more delicate due to uncertainties on the experimental data. Besides fully non-stationary simulations, the lift coefficient was also studied with UnPaM by assuming quasi-steady and steady conditions. It was found that for a typical figure-of-eight trajectory there are no significant differences between unsteady and quasi-steady approaches allowing for fast simulations.
Climate Risks and the Realized Volatility Oil and Gas Prices: Results of an Out-of-Sample Forecasting Experiment
Authors: Gupta Rangan , Pierdzioch Christian
Published: December 2021

We extend the widely-studied Heterogeneous Autoregressive Realized Volatility (HAR-RV) model to examine the out-of-sample forecasting value of climate-risk factors for the realized volatility of movements of the prices of crude oil, heating oil, and natural gas. The climate-risk factors have been constructed in recent literature using techniques of computational linguistics, and consist of daily proxies of physical (natural disasters and global warming) and transition (U.S. climate policy and international summits) risks involving the climate. We find that climate-risk factors contribute to out-of-sample forecasting performance mainly at a monthly and, in some cases, also at a weekly forecast horizon. We demonstrate that our main finding is robust to various modifications of our forecasting experiment, and to using three different popular shrinkage estimators to estimate the extended HAR-RV model. We also study longer forecast horizons of up to three months, and we account for the possibility that policymakers and forecasters may have an asymmetric loss function.
A CMOS Active Rectifier with Efficiency-Improving and Digitally Adaptive Delay Compensation for Wireless Power Transfer Systems
Authors: Zhang Yichen , Ma Junye , Tang Xian
Published: December 2021

A CMOS active rectifier with digitally adaptive delay compensation for power efficiency improvement is presented in this work. The power transistors are turned on and turned off in advance under the control of the regenerated compensation signals, which are generated by the proposed compensation control circuit; therefore, the reverse current is eliminated, and the efficiency is increased. Simulation results in a standard 0.18 μm CMOS process show that the turn-on and turn-off delay of the rectifier is effectively compensated. The power efficiency is up to 90.6% when the proposed rectifier works at the operation frequency of 13.56 MHz.
Assessment of Structural Differences between Water-Extracted and Non-Extracted Hydro-Thermally Treated Spruce Wood by NIR Spectroscopy
Authors: Popescu Carmen-Mihaela , Zeniya Nanami , Endo Kaoru , Genkawa Takuma , Matsuo-Ueda Miyuki , Obataya Eiichi
Published: December 2021

Sitka spruce wood samples were subjected to different conditions of hydro-thermal treatment by varying the relative humidity (RH) and period of exposure at a constant temperature of 120 °C. Near infrared (NIR) spectroscopy, principal component analysis (PCA) and two dimensional correlation spectroscopy (2D-COS) were employed to examine the structural changes which occur in the wood samples during the applied treatment conditions and to quantify the differences between non-extracted and water-extracted wood specimens after the treatment. Modifications were dependent on the amount of water molecules present the medium and also on treatment time. Higher variations were observed for samples treated at higher RH values and for longer periods. At the same time, it was also observed that during the hydro-thermal treatment a high amount of extractives remain in the wood structure, extractives which vary in quantity and composition. PCA and 2D-COS made it possible to discriminate modifications in the wood samples according to treatment time and relative humidity. Non-extracted and water-extracted samples were also examined to identify the sequential order of band modification.
Adsorption Equilibrium and Thermodynamics of Tea Theasinensins on HP20—A High-Efficiency Macroporous Adsorption Resin
Authors: Zhang Jianyong , Cui Hongchun , Xue Jinjin , Wang Wei , Wang Weiwei , Le Ting , Chen Lin , Engelhardt Ulrich H. , Jiang Heyuan
Published: December 2021

The separation and preparation of theasinensins have been hot spots in the field of tea chemistry in recent years. However, information about the mechanism of efficient adsorption of tea theasinensins by resin has been limited. In this study, the adsorption equilibrium and thermodynamics of tea theasinensins by a high-efficiency macroporous adsorption HP20 resin were evaluated. The adsorption of theasinensin A, theasinensin B, and theasinensin C on HP20 resin were spontaneous physical reaction processes. Adsorption processes were exothermic processes, and lowering the temperature was beneficial to the adsorption. The Freundlich model was more suitable to describe the adsorption of tea theasinensins. The adsorption equilibrium constant and maximum adsorption capacity of theasinensin A were significantly higher than theasinensin B and theasinensin C, which indicated that the adsorption affinity of theasinensin A was stronger than that of theasinensin B and theasinensin C. The phenolic hydroxyl groups and intramolecular hydrogen bonds of theasinensin A were more than those of theasinensin B and theasinensin C, which might be the key to the resin’s higher adsorption capacity for theasinensin A. The HP20 resin was very suitable for efficient adsorption of theasinensin A.
Growth and Biochemical Composition Characteristics of Arthrospira platensis Induced by Simultaneous Nitrogen Deficiency and Seawater-Supplemented Medium in an Outdoor Raceway Pond in Winter
Authors: Wu Hualian , Li Tao , Lv Jinting , Chen Zishuo , Wu Jiayi , Wang Na , Wu Houbo , Xiang Wenzhou
Published: December 2021

Arthrospira platensis, a well-known cyanobacterium, is widely applied not only in human and animal nutrition but also in cosmetics for its high amounts of active products. The biochemical composition plays a key role in the application performance of the Arthrospira biomass. The present study aimed to evaluate the growth and biochemical composition characteristics of A. platensis, cultured with a nitrogen-free and seawater-supplemented medium in an outdoor raceway pond in winter. The results showed that the biomass yield could achieve 222.42 g m−2, and the carbohydrate content increased by 247% at the end of the culture period (26 d), compared with that of the starter culture. The daily and annual areal productivities were 3.96 g m−2 d−1 and 14.44 ton ha−1 yr−1 for biomass and 2.88 g m−2 d−1 and 10.53 ton ha−1 yr−1 for carbohydrates, respectively. On the contrary, a profound reduction was observed in protein, lipid, and pigment contents. Glucose, the main monosaccharide in the A. platensis biomass, increased from 77.81% to 93.75% of total monosaccharides. Based on these results, large-scale production of carbohydrate-rich A. platensis biomass was achieved via a low-cost culture, involving simultaneous nitrogen deficiency and supplementary seawater in winter.
A Qualitative Study of Pictorial Health Warnings on Malaysian Cigarette Packs: How Do the Adults Understand Them?
Authors: Hamzah Ainun Mardhiah , Saub Roslan , Marhazlinda Jamaludin
Published: December 2021

The WHO recommended pictorial health warnings (PHWs) on cigarette packs in 2003 to educate and warn the public of smoking effects. Malaysia too has implemented this policy since 2009. This study explored the public’s understanding of the gazetted PHWs depicted on cigarette packs available in Malaysia. A qualitative study using four focus group discussions (FGDs) was conducted among smokers and non-smokers aged 18–40 in Malacca, Peninsular Malaysia. Thematic analyses were performed using the Atlas Ti version 8.0 software. Six themes have emerged reflecting the public’s understanding of the existing PHWs in Malaysia, namely, (i) awareness and exposures, (ii) recall and attention, (iii) perceived goals, (iv) perceived target groups, (v) attitude in understanding, and (vi) knowledge and meaning of PHWs. All participants were aware of the PHWs depicted on legal cigarettes but not seen on most illicit cigarettes. PHWs were perceived to give awareness and warning about the smoking effects targeting smokers and non-smokers. Participants understood the lung and oral health-related images easily than other body parts such as gangrene foot, miscarriages, etc. Besides enforcement on illicit cigarettes without PHWs, policymakers or relevant authorities should emphasize creating relevant and clear pictorial messages in educating the public to avoid confusion affecting the public’s understanding of the PHWs.
Spirituality in Coping with Pain in Cancer Patients: A Cross-Sectional Study
Authors: Oliveira Sharon Shyrley Weyll , Vasconcelos Rayzza Santos , Amaral Verônica Rabelo Santana , Sousa Hélder Fernando Pedrosa e , Dinis Maria Alzira Pimenta , Vidal Diogo Guedes , Sá Katia Nunes
Published: December 2021

Spirituality has been identified as an adaptive coping strategy and a predictor of better quality of life in cancer patients. Despite the relevance of spirituality in the health–disease process, it is noted that the assessment of the impact of spirituality in coping with pain is still incipient. The objective of this study is to assess the impact of spirituality in coping with pain in cancer patients. This quantitative cross-sectional study was carried out in a medium-sized hospital and a cancer patient support institution located in northeastern Brazil. A questionnaire with sociodemographic and clinical variables was used and the following instruments were applied: Visual Analogue Scale (VAS); Short-Form McGill Pain Questionnaire (SF-MPQ); Neuropathic Pain 4 Questions (DN4); Spiritual Wellbeing Scale (SWBS); WHOQOL Spirituality, Religiousness and Personal Beliefs (WHOQOL-SRPB). Most people with no pain had higher scores on the SWBS. Neuropathic pain was identified in 23 patients and was associated with the highest level of spirituality used as a way of coping with pain. As faith increases, pain decreases in intensity by 0.394 points. On the other hand, as inner peace increases, pain increases by 1.485 points. It is concluded that faith is a strategy for coping with pain, in particular neuropathic pain, minimizing its intensity. On the other hand, greater levels of inner peace allow to increase the awareness of the painful sensation. It is expected that these findings may be useful to integrate spirituality care in healthcare facilities as a resource for positive coping for people in the process of becoming ill, contributing to the therapeutic path and favouring a new meaning to the experience of the disease.
Genetic Analyses of Resistance to Fusarium Basal Rot in Onion
Authors: Straley Elizabeth , Colcol Marzu Jen , Havey Michael J.
Published: December 2021

Fusarium basal rot (FBR) is a serious disease of onion (Allium cepa). We identified sources of FBR resistance, assessed efficacy of selection for increased resistance, and investigated its genetic control. Onion accessions were evaluated for FBR resistance, and percentage survival ranged from 0% to 78%. Survivors were intercrossed, and progenies from one cycle of selection showed increased survival by 18% to 52%. Selections were crossed to male-sterile lines, and hybrids showed specific combining ability for FBR resistance. Segregating families were produced, and quantitative trait loci (QTLs) were identified on chromosomes 2 and 4 conditioning FBR resistance. A second QTL on chromosome 4 was identified that decreased FBR resistance. Plants from families with different genotypes across the 1.5 logarithm of odds (LOD) regions on chromosomes 2 and 4 were self-pollinated, and resulting families were evaluated for FBR survival. Genomic regions on chromosomes 2 and 4 associated with resistance were validated at p = 0.05 and 0.10, respectively. The region on chromosome 4 associated with increased susceptibility was validated at p = 0.05. These results are in agreement with previous studies reporting high heritability and specific combining ability for FBR resistance and should be useful for selection of FBR-resistant onion.
Effective Categorization of Tolerance to Salt Stress through Clustering Prunus Rootstocks According to Their Physiological Performances
Authors: Toro Guillermo , Pimentel Paula , Salvatierra Ariel
Published: December 2021

The effects of climate change on traditional stone fruit producing areas, together with the generation of new varieties with lower chilling requirements that allow the cultivation of previously unexplored areas, are setting up a challenging scenario for the establishment of productive orchards that must be more efficient in their capacity to adapt to new edaphoclimatic conditions. In this context, the rootstock breeding programs are a key piece in the agronomic strategy to achieve this adaptation through the development of rootstocks compatible with the new varieties and capable of transferring their tolerance to stress. An effective categorization of phenotypes within the germplasm involved in a plant breeding program is of utmost importance. Through the measurement of physiological parameters in both roots and leaves, tolerance to saline stress (120 mM NaCl) was evaluated in seven Prunus rootstocks whose genetic background included representatives of the subgenera Prunus, Cerasus, and Amygdalus. To group the genotypes according to their physiological performance under salt stress, an agglomerative hierarchical clustering was applied. The genotypes were grouped into three clusters containing rootstocks very sensitive (‘Mazzard F12/1’), moderately tolerant (‘Maxma 60’, ‘Cab6P’ and ‘AGAF 0204-09’), and tolerant (‘Mariana 2624’, ‘Garnem’ and ‘Colt’) to salt stress. ‘Mariana 2624’, a plum-based rootstock, was identified as the most tolerant Prunus rootstock. The information reported is valuable both in the productive context, for the selection of the most appropriate rootstocks to establish an orchard, and in the context of plant breeding programs, when choosing parents with outstanding traits to obtain progenies tolerant to salt stress.
Stevia rebaudiana Bertoni: The Interaction of Night Interruption on Gas Exchange, Flowering Delay, and Steviol Glycosides Synthesis
Authors: Rivera-Avilez Jesús Antonio , Jarma-Orozco Alfredo , Pompelli Marcelo F.
Published: December 2021

The Stevia market is estimated to be USD 1.14 billion in 2028 due to its acceptance in the food and beverage industry. Stevia rebaudiana and its two more relevant edulcorants: stevioside (St) and rebaudioside A (Reb-A) can reach 450-fold sweeter than sucrose. The species is considered a long night plant, promoting flowering and shortening vegetative growth. Thus, to increase the leaf area and St and Reb-A increase, we broke the long night with a short light pulse, here called night interruption (NI). In this study, three NI times and two S. rebaudiana genotypes were tested to promote larger vegetative growth, flowering delay, and higher synthesis of steviol glycosides (SvGly). The main goal of this study was to demonstrate that NI increased net photosynthesis (9% to 20%), the internode length (59%), the leaf area (25%), while delays in 4 to 10 days of the flowering phase, impacting in 17% to 25% more St and Reb-A, respectively. Here we describe an inexpensive flowering delay, elongation of vegetative growth, allowing extended harvesting, which could yield four to five annual harvesting of leaves, increasing the production in 21% to 24% more St and Reb-A yield (kg ha−1).
Assessment of Dietary Folate Intake and Pill Burden among Saudi Patients on Maintenance Hemodialysis
Authors: Sales Ibrahim , Bawazeer Ghada , Tarakji Ahmad R. , Ben Salha Feriel K. , Al-Deaiji Nourah H. , Saeed Marwah , Idris Rawan S. , Aljawadi Mohammad H. , Aljohani Majidah A. , Mahmoud Mansour Adam , Syed Wajid
Published: December 2021

The aim of this study was to assess the adequacy of dietary folate intake and perceptions of pill burden among Saudi patients on maintenance hemodialysis (MHD). This was a cross-sectional study of adults (>18 years) on MHD (>3 months) attending the dialysis unit at King Saud University Medical City. Patient demographics, dietary folic acid intake, and perceptions of pill burden were collected. Fifty-four patients met the eligibility criteria, with a mean age of 57 ± 15.5 years. The majority were females (63%), and the most prevalent comorbidities were diabetes (43%) and hypertension (76%). The average number of medications/patients was 11 ± 2.9, and most patients were receiving folate supplementation (68.5%). The average dietary folate intake was 823 ± 530 mcg/day. Pill burden was bothersome, primarily due to taking too many medications (57%) while taking medications at the workplace was the least bothersome burden (17%). The reported high pill burden and adequate dietary folate intake by Saudi patients on MHD indicates that the omission of folate supplementation may be advantageous for this special population.
Occupational Exposure to Ultrafine Particles and Placental Histopathological Lesions: A Retrospective Study about 130 Cases
Authors: Pasquiou Anaïs , Pelluard Fanny , Manangama Guyguy , Brochard Patrick , Audignon Sabyne , Sentilhes Loïc , Delva Fleur
Published: December 2021

Ultrafine particles (UFPs) are particles smaller than 100 nanometers that are produced unintentionally during human activities or natural phenomena. They have a higher biological reactivity than bigger particles and can reach the placenta after maternal exposure. One study has shown an association between maternal occupational exposure to UFPs and fetal growth restriction. Yet few studies have focused on the effects of UFP exposure on placental histopathological lesions. The aim of this study was to investigate the association between maternal occupational exposure to UFPs and histopathological lesions of their placenta. The analyses were based on data from the ARTEMIS Center. A job-exposure matrix was used to assess occupational exposure to UFPs. The histopathological placental exam was performed by two pathologists who were blinded to the exposure of each subject. The examination was conducted in accordance with the recommendations of the Amsterdam consensus. The study sample included 130 placentas (30 exposed, 100 unexposed). Maternal occupational exposure to UFPs during pregnancy is significantly associated with placental hypoplasia (the phenomenon affected 61% of the exposed patients and 34% of the unexposed ones, p < 0.01). Further research is needed to explain its pathophysiological mechanisms.
hGLUTEN Tool: Measuring Its Social Impact Indicators
Authors: Moreno Antonia , Sanz Guillermo , Garcia-Zapirain Begonya
Published: December 2021

hGLUTEN is a technological solution capable of detecting gluten and spoiled food. We measured the social impact of the hGLUTEN tool using two Likert scale surveys with two groups: professionals (engineers/chefs) and end-users. These data have been assessed in accordance with the social impact indicators defined for the Key Impact Pathways introduced by the European Commission for Horizon Europe and the criteria of the Social Impact Open Repository (SIOR). A total of 85% of users, 100% of engineers and 68% of professional chefs consider it very relevant to participate and give their opinion in research projects, which shows the increasingly high level of involvement of the general population. A total of 88% of users were unaware of other applications that detect gluten and were more dependent on guidelines provided by allergy associations and expiry dates of foodstuffs. In addition, only 5% of professional chefs said they were aware of other technology capable of detecting gluten in food, which may indicate a large economic market and good commercialisation possibilities for the tool in the future. Finally, the inclusion of tools to motivate users to promote it has been identified as an area for improvement, which could mean that it should be made more visible in the media to increase its impact and influence.
Insights into Factors Affecting Traffic Accident Severity of Novice and Experienced Drivers: A Machine Learning Approach
Authors: Chen Shuaiming , Shao Haipeng , Ji Ximing
Published: December 2021

Traffic accidents have significant financial and social impacts. Reducing the losses caused by traffic accidents has always been one of the most important issues. This paper presents an effort to investigate the factors affecting the accident severity of drivers with different driving experience. Special focus was placed on the combined effect of driving experience and age. Based on our dataset (traffic accidents that occurred between 2005 and 2021 in Shaanxi, China), CatBoost model was applied to deal with categorical feature, and SHAP (Shapley Additive exPlanations) model was used to interpret the output. Results show that accident cause, age, visibility, light condition, season, road alignment, and terrain are the key factors affecting accident severity for both novice and experienced drivers. Age has the opposite impact on fatal accident for novice and experienced drivers. Novice drivers younger than 30 or older than 55 are prone to suffer fatal accident, but for experienced drivers, the risk of fatal accident decreases when they are young and increases when they are old. These findings fill the research gap of the combined effect of driving experience and age on accident severity. Meanwhile, it can provide useful insights for practitioners to improve traffic safety for novice and experienced drivers.
Longitudinal Changes in Swiss Adolescent’s Mental Health Outcomes from before and during the COVID-19 Pandemic
Authors: Ertanir Beyhan , Kassis Wassilis , Garrote Ariana
Published: December 2021

This study aimed to explore changes in mental health outcomes (depression, anxiety, home, and school stress) from before the first COVID-19 wave (autumn 2019) to the later stages of the same wave (autumn 2020) in a sample of N = 377 Swiss adolescents (Mage = 12.67; 47% female). It also examined whether students’ background characteristics (gender, immigrant status, and socio-economic status) and reported COVID-19 burden predicted students’ outcomes and their intra-individual changes. Student’s mental health, background characteristics, and reported COVID-19 burden were assessed by a self-report questionnaire. The intra-individual changes in students’ scores were estimated using random coefficients regression analyses, with time points nested in individuals. To examine the effects of predictors (students’ background characteristics and the reported COVID-19 burden) on outcome scores and changes, multilevel intercepts-and-slopes-as-outcomes models were used. The results showed that the expected impact of the pandemic on mental health was not noticeable in the later stages of the first COVID-19 wave. Only two effects were demonstrated in terms of intra-individual changes, namely, an effect of gender on depression and anxiety symptoms and an effect of reported COVID-19 burden on school stress symptoms. Moreover, few associations were found for selected predictors and students’ mean level scores, averaged across both time points.
Deep Learning for Toponym Resolution: Geocoding Based on Pairs of Toponyms
Authors: Fize Jacques , Moncla Ludovic , Martins Bruno
Published: December 2021

Geocoding aims to assign unambiguous locations (i.e., geographic coordinates) to place names (i.e., toponyms) referenced within documents (e.g., within spreadsheet tables or textual paragraphs). This task comes with multiple challenges, such as dealing with referent ambiguity (multiple places with a same name) or reference database completeness. In this work, we propose a geocoding approach based on modeling pairs of toponyms, which returns latitude-longitude coordinates. One of the input toponyms will be geocoded, and the second one is used as context to reduce ambiguities. The proposed approach is based on a deep neural network that uses Long Short-Term Memory (LSTM) units to produce representations from sequences of character n-grams. To train our model, we use toponym co-occurrences collected from different contexts, namely textual (i.e., co-occurrences of toponyms in Wikipedia articles) and geographical (i.e., inclusion and proximity of places based on Geonames data). Experiments based on multiple geographical areas of interest—France, United States, Great-Britain, Nigeria, Argentina and Japan—were conducted. Results show that models trained with co-occurrence data obtained a higher geocoding accuracy, and that proximity relations in combination with co-occurrences can help to obtain a slightly higher accuracy in geographical areas with fewer places in the data sources.
Genes and Pathways Associated with Skeletal Sagittal Malocclusions: A Systematic Review
Authors: Gershater Elizabeth , Li Chenshuang , Ha Pin , Chung Chun-Hsi , Tanna Nipul , Zou Min , Zheng Zhong
Published: December 2021

Skeletal class II and III malocclusions are craniofacial disorders that negatively impact people’s quality of life worldwide. Unfortunately, the growth patterns of skeletal malocclusions and their clinical correction prognoses are difficult to predict largely due to lack of knowledge of their precise etiology. Inspired by the strong inheritance pattern of a specific type of skeletal malocclusion, previous genome-wide association studies (GWAS) were reanalyzed, resulting in the identification of 19 skeletal class II malocclusion-associated and 53 skeletal class III malocclusion-associated genes. Functional enrichment of these genes created a signal pathway atlas in which most of the genes were associated with bone and cartilage growth and development, as expected, while some were characterized by functions related to skeletal muscle maturation and construction. Interestingly, several genes and enriched pathways are involved in both skeletal class II and III malocclusions, indicating the key regulatory effects of these genes and pathways in craniofacial development. There is no doubt that further investigation is necessary to validate these recognized genes’ and pathways’ specific function(s) related to maxillary and mandibular development. In summary, this systematic review provides initial insight on developing novel gene-based treatment strategies for skeletal malocclusions and paves the path for precision medicine where dental care providers can make an accurate prediction of the craniofacial growth of an individual patient based on his/her genetic profile.
Residue Folding Degree—Relationship to Secondary Structure Categories and Use as Collective Variable
Authors: Sladek Vladimir , Harada Ryuhei , Shigeta Yasuteru
Published: December 2021

Recently, we have shown that the residue folding degree, a network-based measure of folded content in proteins, is able to capture backbone conformational transitions related to the formation of secondary structures in molecular dynamics (MD) simulations. In this work, we focus primarily on developing a collective variable (CV) for MD based on this residue-bound parameter to be able to trace the evolution of secondary structure in segments of the protein. We show that this CV can do just that and that the related energy profiles (potentials of mean force, PMF) and transition barriers are comparable to those found by others for particular events in the folding process of the model mini protein Trp-cage. Hence, we conclude that the relative segment folding degree (the newly proposed CV) is a computationally viable option to gain insight into the formation of secondary structures in protein dynamics. We also show that this CV can be directly used as a measure of the amount of α-helical content in a selected segment.
Structural Characterization of the Interaction of Hypoxia Inducible Factor-1 with Its Hypoxia Responsive Element at the −964G > A Variation Site of the HLA-G Promoter Region
Authors: Alves Cinthia C. , Donadi Eduardo A. , Giuliatti Silvana
Published: December 2021

Human Antigen Leukocyte-G (HLA-G) gene encodes an immune checkpoint molecule that has restricted tissue expression in physiological conditions; however, the gene may be induced in hypoxic conditions by the interaction with the hypoxia inducible factor-1 (HIF1). Hypoxia regulatory elements (HRE) located at the HLA-G promoter region and at exon 2 are the major HIF1 target sites. Since the G allele of the −964G > A transversion induces higher HLA-G expression when compared to the A allele in hypoxic conditions, here we analyzed HIF1-HRE complex interaction at the pair-atom level considering both −964G > A polymorphism alleles. Mouse HIF2 dimer crystal (Protein Data Bank ID: 4ZPK) was used as template to perform homology modelling of human HIF1 quaternary structure using MODELLER v9.14. Two 3D DNA structures were built from 5′GCRTG’3 HRE sequence containing the −964G/A alleles using x3DNA. Protein-DNA docking was performed using the HADDOCK v2.4 server, and non-covalent bonds were computed by DNAproDB server. Molecular dynamic simulation was carried out per 200 ns, using Gromacs v.2019. HIF1 binding in the HRE containing −964G allele results in more hydrogen bonds and van der Waals contact formation than HRE with −964A allele. Protein-DNA complex trajectory analysis revealed that HIF1-HRE-964G complex is more stable. In conclusion, HIF1 binds in a more stable and specific manner at the HRE with G allele.
An Update on Graphene-Based Nanomaterials for Neural Growth and Central Nervous System Regeneration
Authors: Tupone Maria Grazia , Panella Gloria , d’Angelo Michele , Castelli Vanessa , Caioni Giulia , Catanesi Mariano , Benedetti Elisabetta , Cimini Annamaria
Published: December 2021

Thanks to their reduced size, great surface area, and capacity to interact with cells and tissues, nanomaterials present some attractive biological and chemical characteristics with potential uses in the field of biomedical applications. In this context, graphene and its chemical derivatives have been extensively used in many biomedical research areas from drug delivery to bioelectronics and tissue engineering. Graphene-based nanomaterials show excellent optical, mechanical, and biological properties. They can be used as a substrate in the field of tissue engineering due to their conductivity, allowing to study, and educate neural connections, and guide neural growth and differentiation; thus, graphene-based nanomaterials represent an emerging aspect in regenerative medicine. Moreover, there is now an urgent need to develop multifunctional and functionalized nanomaterials able to arrive at neuronal cells through the blood-brain barrier, to manage a specific drug delivery system. In this review, we will focus on the recent applications of graphene-based nanomaterials in vitro and in vivo, also combining graphene with other smart materials to achieve the best benefits in the fields of nervous tissue engineering and neural regenerative medicine. We will then highlight the potential use of these graphene-based materials to construct graphene 3D scaffolds able to stimulate neural growth and regeneration in vivo for clinical applications.
Development of Polyvinyl Alcohol/Kaolin Sponges Stimulated by Marjoram as Hemostatic, Antibacterial, and Antioxidant Dressings for Wound Healing Promotion
Authors: Tamer Tamer M. , Alsehli Mosa H. , Omer Ahmed M. , Afifi Tarek H. , Sabet Maysa M. , Mohy-Eldin Mohamed S. , Hassan Mohamed A.
Published: December 2021

The predominant impediments to cutaneous wound regeneration are hemorrhage and bacterial infections that lead to extensive inflammation with lethal impact. We thus developed a series of composite sponges based on polyvinyl alcohol (PVA) inspired by marjoram essential oil and kaolin (PVA/marjoram/kaolin), adopting a freeze–thaw method to treat irregular wounds by thwarting lethal bleeding and microbial infections. Microstructure analyses manifested three-dimensional interconnected porous structures for PVA/marjoram/kaolin. Additionally, upon increasing marjoram and kaolin concentrations, the pore diameters of the sponges significantly increased, recording a maximum of 34 ± 5.8 µm for PVA-M0.5-K0.1. Moreover, the porosity and degradation properties of PVA/marjoram/kaolin sponges were markedly enhanced compared with the PVA sponge with high swelling capacity. Furthermore, the PVA/marjoram/kaolin sponges exerted exceptional antibacterial performance against Escherichia coli and Bacillus cereus, along with remarkable antioxidant properties. Moreover, PVA/marjoram/kaolin sponges demonstrated significant thrombogenicity, developing high thrombus mass and hemocompatibility, in addition to their remarkable safety toward fibroblast cells. Notably, this is the first study to our knowledge investigating the effectiveness of marjoram in a polymeric carrier for prospective functioning as a wound dressing. Collectively, the findings suggest the prospective usage of the PVA-M0.5-K0.1 sponge in wound healing for hemorrhage and bacterial infection control.
Limitations and Possibilities of Transarterial Chemotherapeutic Treatment of Hepatocellular Carcinoma
Authors: Ebeling Barbier Charlotte , Heindryckx Femke , Lennernäs Hans
Published: December 2021

Because diagnostic tools for discriminating between hepatocellular carcinoma (HCC) and advanced cirrhosis are poor, HCC is often detected in a stage where transarterial chemoembolization (TACE) is the best treatment option, even though it provides a poor survival gain. Despite having been used worldwide for several decades, TACE still has many limitations. First, there is a vast heterogeneity in the cellular composition and metabolism of HCCs as well as in the patient population, which renders it difficult to identify patients who would benefit from TACE. Often the delivered drug does not penetrate sufficiently selectively and deeply into the tumour and the drug delivery system is not releasing the drug at an optimal clinical rate. In addition, therapeutic effectiveness is limited by the crosstalk between the tumour cells and components of the cirrhotic tumour microenvironment. To improve this widely used treatment of one of our most common and deadly cancers, we need to better understand the complex interactions between drug delivery, local pharmacology, tumour targeting mechanisms, liver pathophysiology, patient and tumour heterogeneity, and resistance mechanisms. This review provides a novel and important overview of clinical data and discusses the role of the tumour microenvironment and lymphatic system in the cirrhotic liver, its potential response to TACE, and current and possible novel DDSs for locoregional treatment.
Targeting Mediators of Inflammation in Heart Failure: A Short Synthesis of Experimental and Clinical Results
Authors: Szabo Timea Magdolna , Frigy Attila , Nagy Előd Ernő
Published: December 2021

Inflammation has emerged as an important contributor to heart failure (HF) development and progression. Current research data highlight the diversity of immune cells, proteins, and signaling pathways involved in the pathogenesis and perpetuation of heart failure. Chronic inflammation is a major cardiovascular risk factor. Proinflammatory signaling molecules in HF initiate vicious cycles altering mitochondrial function and perturbing calcium homeostasis, therefore affecting myocardial contractility. Specific anti-inflammatory treatment represents a novel approach to prevent and slow HF progression. This review provides an update on the putative roles of inflammatory mediators involved in heart failure (tumor necrosis factor-alpha; interleukin 1, 6, 17, 18, 33) and currently available biological and non-biological therapy options targeting the aforementioned mediators and signaling pathways. We also highlight new treatment approaches based on the latest clinical and experimental research.
Emerging Role of TCA Cycle-Related Enzymes in Human Diseases
Authors: Kang Woojin , Suzuki Miki , Saito Takako , Miyado Kenji
Published: December 2021

The tricarboxylic acid (TCA) cycle is the main source of cellular energy and participates in many metabolic pathways in cells. Recent reports indicate that dysfunction of TCA cycle-related enzymes causes human diseases, such as neurometabolic disorders and tumors, have attracted increasing interest in their unexplained roles. The diseases which develop as a consequence of loss or dysfunction of TCA cycle-related enzymes are distinct, suggesting that each enzyme has a unique function. This review aims to provide a comprehensive overview of the relationship between each TCA cycle-related enzyme and human diseases. We also discuss their functions in the context of both mitochondrial and extra-mitochondrial (or cytoplasmic) enzymes.
A Comparative Transcriptomic Meta-Analysis Revealed Conserved Key Genes and Regulatory Networks Involved in Drought Tolerance in Cereal Crops
Authors: Baldoni Elena , Frugis Giovanna , Martinelli Federico , Benny Jubina , Paffetti Donatella , Buti Matteo
Published: December 2021

Drought affects plant growth and development, causing severe yield losses, especially in cereal crops. The identification of genes involved in drought tolerance is crucial for the development of drought-tolerant crops. The aim of this study was to identify genes that are conserved key players for conferring drought tolerance in cereals. By comparing the transcriptomic changes between tolerant and susceptible genotypes in four Gramineae species, we identified 69 conserved drought tolerant-related (CDT) genes that are potentially involved in the drought tolerance of all of the analysed species. The CDT genes are principally involved in stress response, photosynthesis, chlorophyll biogenesis, secondary metabolism, jasmonic acid signalling, and cellular transport. Twenty CDT genes are not yet characterized and can be novel candidates for drought tolerance. The k-means clustering analysis of expression data highlighted the prominent roles of photosynthesis and leaf senescence-related mechanisms in differentiating the drought response between tolerant and sensitive genotypes. In addition, we identified specific transcription factors that could regulate the expression of photosynthesis and leaf senescence-related genes. Our analysis suggests that the balance between the induction of leaf senescence and maintenance of photosynthesis during drought plays a major role in tolerance. Fine-tuning of CDT gene expression modulation by specific transcription factors can be the key to improving drought tolerance in cereals.
A Dystrophin Exon-52 Deleted Miniature Pig Model of Duchenne Muscular Dystrophy and Evaluation of Exon Skipping
Authors: Echigoya Yusuke , Trieu Nhu , Duddy William , Moulton Hong M. , Yin HaiFang , Partridge Terence A. , Hoffman Eric P. , Kornegay Joe N. , Rohret Frank A. , Rogers Christopher S. , Yokota Toshifumi
Published: December 2021

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive disorder caused by mutations in the DMD gene and the subsequent lack of dystrophin protein. Recently, phosphorodiamidate morpholino oligomer (PMO)-antisense oligonucleotides (ASOs) targeting exon 51 or 53 to reestablish the DMD reading frame have received regulatory approval as commercially available drugs. However, their applicability and efficacy remain limited to particular patients. Large animal models and exon skipping evaluation are essential to facilitate ASO development together with a deeper understanding of dystrophinopathies. Using recombinant adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer, we generated a Yucatan miniature pig model of DMD with an exon 52 deletion mutation equivalent to one of the most common mutations seen in patients. Exon 52-deleted mRNA expression and dystrophin deficiency were confirmed in the skeletal and cardiac muscles of DMD pigs. Accordingly, dystrophin-associated proteins failed to be recruited to the sarcolemma. The DMD pigs manifested early disease onset with severe bodywide skeletal muscle degeneration and with poor growth accompanied by a physical abnormality, but with no obvious cardiac phenotype. We also demonstrated that in primary DMD pig skeletal muscle cells, the genetically engineered exon-52 deleted pig DMD gene enables the evaluation of exon 51 or 53 skipping with PMO and its advanced technology, peptide-conjugated PMO. The results show that the DMD pigs developed here can be an appropriate large animal model for evaluating in vivo exon skipping efficacy.
Finding Central Vertices and Community Structure via Extended Density Peaks-Based Clustering
Authors: Meng Yuanyuan , Liu Xiyu
Published: December 2021

Community detection is a significant research field of social networks, and modularity is a common method to measure the division of communities in social networks. Many classical algorithms obtain community partition by improving the modularity of the whole network. However, there is still a challenge in community division, which is that the traditional modularity optimization is difficult to avoid resolution limits. To a certain extent, the simple pursuit of improving modularity will cause the division to deviate from the real community structure. To overcome these defects, with the help of clustering ideas, we proposed a method to filter community centers by the relative connection coefficient between vertices, and we analyzed the community structure accordingly. We discuss how to define the relative connection coefficient between vertices, how to select the community centers, and how to divide the remaining vertices. Experiments on both real and synthetic networks demonstrated that our algorithm is effective compared with the state-of-the-art methods.
Long-Term Incidence of Total Knee Arthroplasty after Open Reduction and Internal Fixation of Proximal Tibial and Distal Femoral Fractures: A Nationwide Cohort Study
Authors: Yeh Kuang-Ting , Wu Wen-Tien , Lee Ru-Ping , Wang Chen-Chie , Wang Jen-Hung , Chen Ing-Ho
Published: December 2021

Knee fractures often require open reduction internal fixation (ORIF) for knee function recovery. More than one fifth of patients with knee fractures subsequently develop posttraumatic arthritis, and over 5% of them need total knee arthroplasty (TKA). We conducted this nationwide retrospective cohort study using the data of 2,000,000 people in the general population who received TKA and were followed up in the 17-year period 2001–2017, through random sampling of the Taiwan National Health Insurance Research Database. We matched the ORIF and non-fracture groups by a propensity score, based on age, sex, index date of surgery, and comorbidities enrolled in CCI calculated at a 1:1 ratio. The average proportion of subjects receiving TKA after ORIF for distal femoral or proximal tibial fractures was 2.0 per 1000 person-years, which was significantly higher than that in the non-fracture group. Patients aged 20–65 years and males represented a significantly higher proportion of subjects receiving TKA after ORIF than that in the non-fracture group. The proportion of subjects receiving TKA for the 20–65-year subgroup of the ORIF group was 4%, and that for the male subgroup was 1.5%; both rates increased over the 17-year follow-up period. More aggressive intraoperative and postoperative adjuvant therapies may be necessary for these subgroups.
Portal Vein Thrombosis Is Associated with an Increased Incidence of Depression and Anxiety Disorders
Authors: Gairing Simon Johannes , Galle Peter Robert , Schattenberg Jörn M. , Kostev Karel , Labenz Christian
Published: December 2021

Portal vein thrombosis (PVT) is a severe disease that adversely affects patients’ well-being. Data on the influence of PVT on the occurrence of depression or anxiety disorders are lacking. This study aimed to explore the impact of PVT on the incidence of depression and anxiety disorders diagnoses in a large German primary care cohort over a ten-year period. Patients with PVT were matched to non-PVT individuals by age, sex, yearly consultation frequency, index year and comorbidities in a 1:5 ratio. The primary outcome of the study was the incidence of depression and anxiety disorders. The relationship between PVT and both depression and anxiety disorders was investigated using Cox regression models. We compared 547 patients with PVT with 2735 matched individuals without PVT. Within 5 years of the index date, 17.4% of patients with PVT and 9.3% of non-PVT individuals were diagnosed with depression (p < 0.001). Anxiety disorders were diagnosed in 5.5% and 3.0% of patients with PVT and non-PVT individuals, respectively (p = 0.002). On regression analyses, PVT was positively associated with incident depression (HR 2.01, 95% CI 1.53–2.64, p < 0.001) as well as anxiety disorders (HR 2.16, 95% CI 1.35–3.46, p = 0.001). Regarding depression, this association remained significant in women as well as in men. There was no association between PVT and the incidence of anxiety disorders in women. In conclusion, PVT is associated with the development of depression and anxiety disorders. However, further prospective studies are needed to confirm our findings before definitive recommendations can be made.
HTR for Greek Historical Handwritten Documents
Authors: Tsochatzidis Lazaros , Symeonidis Symeon , Papazoglou Alexandros , Pratikakis Ioannis
Published: December 2021

Offline handwritten text recognition (HTR) for historical documents aims for effective transcription by addressing challenges that originate from the low quality of manuscripts under study as well as from several particularities which are related to the historical period of writing. In this paper, the challenge in HTR is related to a focused goal of the transcription of Greek historical manuscripts that contain several particularities. To this end, in this paper, a convolutional recurrent neural network architecture is proposed that comprises octave convolution and recurrent units which use effective gated mechanisms. The proposed architecture has been evaluated on three newly created collections from Greek historical handwritten documents that will be made publicly available for research purposes as well as on standard datasets like IAM and RIMES. For evaluation we perform a concise study which shows that compared to state of the art architectures, the proposed one deals effectively with the challenging Greek historical manuscripts.