bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective Catalytic Reduction of NO by NH3 over Mn–Cu Oxide Catalysts Supported by Highly Porous Silica Gel Powder: Comparative Investigation of Six Different Preparation Methods
Authors: Urbanas Davyd , Baltrėnaitė-Gedienė Edita
Published: June 2021

In this study, Mn-based catalysts supported by highly porous silica gel powder (SSA up to 470 m2·g−1 and total pore volume up to 0.8 cm3·g−1) were prepared by six different methods in liquid solutions (electroless metal deposition, stepwise addition of a reducing agent, wet impregnation, incipient wetness impregnation, urea hydrolysis, and ammonia evaporation) and tested for selective catalytic reduction of NOx with ammonia (NH3-SCR de-NOx). Prior to the activity test all the catalysts prepared were characterized by ICP-OES, SEM, EDX mapping, XPS, XRD and N2 adsorption techniques to provide the comprehensive information about their composition and morphology, investigate the dispersion of active components on the carrier surface, identify the chemical forms and structural properties of the catalytically active species of the catalysts prepared. The results revealed that all the methods applied for preparation of SCR de-NOx catalysts can ensure the uniform distribution of Mn species on the carrier surface, however as it is typical for preparation techniques in a liquid phase the significant reduction in SSA and pore volume along with increasing the loading was observed. Considering both the physicochemical properties and the catalytic performance of the catalysts the least effective preparation method was shown to be ammonia evaporation, while the most attractive techniques are incipient wetness impregnation and electroless metal deposition.
Deformity Reconstruction Surgery for Tibial Hemimelia
Authors: Chong David Y. , Paley Dror
Published: June 2021

Tibial hemimelia is a rare congenital deficiency with a wide spectrum of pathology and deformity. This paper aims to give a comprehensive review of tibial hemimelia, with a concise summary of the history, pathology, and clinical findings of tibial hemimelia, while providing treatment recommendations and a review of the current literature. Classifications and surgical treatments are discussed, including amputation, limb reconstruction, and lengthening. Type-specific treatments are also discussed, including staged distraction correction of joint contractures of knee and ankle, Weber patelloplasty, fibular centralization, knee and ankle arthrodesis, implantable articulated distractors, and the role of femoral shortening. Amputation is a simpler and easier solution for many patients; however, reconstruction options continue to evolve, improve, and provide better functional outcomes in many cases. Factors favoring surgical reconstruction include the presence of a knee joint/proximal tibia, and the presence of a patella and quadriceps mechanism.
Imaging Appropriateness in Pediatric Radiology during COVID-19 Pandemic: A Retrospective Comparison with No COVID-19 Period
Authors: Bottari Giampiero , Stellacci Giandomenico , Ferorelli Davide , Dell’Erba Alessandro , Aricò Maurizio , Benevento Marcello , Palladino Giuseppe , Solarino Biagio
Published: June 2021

During the COVID-19 pandemic, the number of accesses to the Pediatric Emergency Department (pED) in Italy sharply decreased by 30%. The purpose of this study is to evaluate how this novel setting impacted on management of children with trauma, and the use and appropriateness of imaging studies in such patients at the pED. All imaging studies performed in patients with trauma at the pED of a tertiary children’s Hospital during the first wave of the COVID-19 pandemic (between March and May 2020) were reviewed, in comparison with a control time interval (March to May 2019). In the pre-COVID control era, 669 imaging studies documented bone fractures in 145/568 children (25.5%). In the COVID-era, 79/177 (44.6%) pediatric patients showed bone fractures on 193 imaging studies. Comparative analysis shows a 71% decrease in imaging studies, and the proportion of negative imaging studies (with no evidence of bone fractures) dropped in 2020 by 19% compared to the 2019 control era (p < 0.001). The sharp decrease of negative studies suggests that the rate of appropriateness was higher during COVID-era, suggesting some attitude toward defensive medicine in the previous control year, as a result of some degree of imaging inappropriateness. The impact of a pandemic on emergency medicine may offer a unique opportunity to revisit diagnostic and therapeutic protocols in pediatrics.
Information Geometric Theory in the Prediction of Abrupt Changes in System Dynamics
Authors: Guel-Cortez Adrian-Josue , Kim Eun-jin
Published: June 2021

Detection and measurement of abrupt changes in a process can provide us with important tools for decision making in systems management. In particular, it can be utilised to predict the onset of a sudden event such as a rare, extreme event which causes the abrupt dynamical change in the system. Here, we investigate the prediction capability of information theory by focusing on how sensitive information-geometric theory (information length diagnostics) and entropy-based information theoretical method (information flow) are to abrupt changes. To this end, we utilise a non-autonomous Kramer equation by including a sudden perturbation to the system to mimic the onset of a sudden event and calculate time-dependent probability density functions (PDFs) and various statistical quantities with the help of numerical simulations. We show that information length diagnostics predict the onset of a sudden event better than the information flow. Furthermore, it is explicitly shown that the information flow like any other entropy-based measures has limitations in measuring perturbations which do not affect entropy.
A Novel Adaptive Control Approach Based on Available Headroom of the VSC-HVDC for Enhancement of the AC Voltage Stability
Authors: Huu Duc Nguyen
Published: June 2021

Increasing offshore wind farms are rapidly installed and planned. However, this will pose a bottle neck challenge for long-distance transmission as well as inherent variation of their generating power outputs to the existing AC grid. VSC-HVDC links could be an effective and flexible method for this issue. With the growing use of voltage source converter high-voltage direct current (VSC-HVDC) technology, the hybrid VSC-HVDC and AC system will be a next-generation transmission network. This paper analyzes the contribution of the multi VSC-HVDC system on the AC voltage stability of the hybrid system. A key contribution of this research is proposing a novel adaptive control approach of the VSC-HVDC as a so-called dynamic reactive power booster to enhance the voltage stability of the AC system. The core idea is that the novel control system is automatically providing a reactive current based on dynamic frequency of the AC system to maximal AC voltage support. Based on the analysis, an adaptive control method applied to the multi VSC-HVDC system is proposed to realize maximum capacity of VSC for reactive power according to the change of the system frequency during severe faults of the AC grid. A representative hybrid AC-DC network based on Germany is developed. Detailed modeling of the hybrid AC-DC network and its proposed control is derived in PSCAD software. PSCAD simulation results and analysis verify the effective performance of this novel adaptive control of VSC-HVDC for voltage support. Thanks to this control scheme, the hybrid AC-DC network can avoid circumstances that lead to voltage instability.
Framework to Facilitate Electricity and Flexibility Trading within, to, and from Local Markets
Authors: Annala Salla , Klein Lurian , Matos Luisa , Repo Sirpa , Kilkki Olli , Narayanan Arun , Honkapuro Samuli
Published: June 2021

Peer-to-peer (P2P) electricity sharing or trading can empower consumers and prosumers, incentivize the balancing of generation and demand locally, increase system resilience and reliability, and help in achieving societal goals, such as increasing renewable energy penetration. Nevertheless, the development of P2P trading in actual environments has been slow due to the unclear position of P2P markets in the power system. Recent developments in the European legislation are promising for the establishment of P2P markets and energy communities. Hence, the interplay between local trading and existing market structures needs to be addressed carefully. Furthermore, P2P trading with distributed resources presumes that electricity end users will become active players in the power system. This paper proposes a bidding and pricing mechanism for local markets, considering the external markets; a new approach to balance settlement and balance responsibility when local trading occurs; and an interface to promote end-user interest in, and interactions with, local energy trading. The proposed local market concept and interface solution promote the coupling between local and existing retail, wholesale and ancillary service markets, and can be seen as a step towards the establishment of local energy markets in real-life settings.
Comparative Study of Classical and MPC Control for Single-Phase MMC Based on V-HIL Simulations
Authors: Majstorovic Milovan , Rivera Marco , Ristic Leposava , Wheeler Patrick
Published: June 2021

The operation of single-phase Modular Multilevel Converter (MMC) is analyzed in the paper. A mathematical model of the converter is developed and described, based on which the structure and selection of parameters for Classical Control and Optimal Switching State Model Predictive Control (OSS-MPC) are defined. Additionally, the procedure for the determination of circuit parameters, such as submodule capacitance and arm inductance, is described and carried out. The listed control methods are designed and evaluated in Virtual Hardware-in-the-Loop together with single-phase MMC power circuit, regarding three control objectives: AC current control, voltage balancing control and circulating current control. Control methods are evaluated for both steady-state and transient performance and compared based on nine criteria: AC current reference tracking, THD of AC current and voltage, submodule capacitor voltage balancing, total submodule voltage control, circulating current magnitude and THD, number of control parameters and computational complexity. This is the first time that a fair comparison between Classical Control and MPC is considered in literature, resulting in superior performance of both control methods regarding four different criteria and the same performance regarding AC current reference tracking.
Multivariate Analysis of a Wind–PV-Based Water Pumping Hybrid System for Irrigation Purposes
Authors: Stoyanov Ludmil , Bachev Ivan , Zarkov Zahari , Lazarov Vladimir , Notton Gilles
Published: June 2021

The Green Deal and increased nutritional needs are driving factors in human activities nowadays. Agriculture is an essential economic sector that can profit from the application of renewable energy sources by the assimilation of off-grid, arid and barren terrains. Power supplied by hybrid systems for water pumping is a solution for overcoming the stochastic character of the renewable energy sources. This paper presents a sizing methodology for a hybrid system with wind and PV generation and water tank storage, based on the consideration of the entire energy conversion chain with energy models and a one-year operation simulation. The PV generator is modeled using a reduced Durisch’s model, while for the wind generator a piecewise interpolation is used. The methodology is applied for sites in Bulgaria with specific agricultural crops and meteorological data. Combinations of PV (different technologies) and wind (different types) generators and water tank capacities are considered and discussed. The combinations are compared on the basis of three criteria: the investment cost, the satisfaction of crop requirements and system oversizing. The possibility for the introduction of battery storage is also examined. The results show some trends in the hybrid system sizing and the possibility to apply the proposed methodology for various sites, generators and crops.
Relationship between the Toothbrushing Behavior and Hand Hygiene Practices of Korean Adolescents: A Study Focused on the 15th Korea Youth Risk Behavior Survey Conducted in 2019
Authors: Kim Eun-Jeong , Lee Hye-Ju
Published: June 2021

Hand hygiene is one of the most important measures available to prevent infectious diseases such as COVID-19, and it is recommended that individuals wash their hands periodically before and after meals, after using toilets, before preparing food at home, at schools, and in public places. The aim of this study was to investigate the relationship between oral hygiene and hand hygiene in Korean adolescents. Data from 57,303 adolescents who participated in the 2019 Korea Youth Risk Behavior web-based survey were analyzed to determine the relationship between oral hygiene and hand hygiene. A complex sample logistic regression analysis was performed to determine association between toothbrushing behavior and handwashing practices. According to the results of this study, adolescents who brushed their teeth after lunch were 1.48 times more likely to practice handwashing before lunch than were those who did not brush their teeth after lunch (p < 0.001). In addition, the odds ratios adjusted for gender, grade, school type, and residence were found to be 1.87 (p < 0.001). Moreover, these adjusted odds ratios were higher in students who received personal hygiene education (OR: 1.98, p < 0.001). Oral hygiene practices were found to be related to personal hygiene, as assessed by handwashing, in Korean adolescents. Additional studies are needed to develop ways of improving the hygiene and health of adolescents.
Identification of Explanatory Variables in Possession of the Ball in High-Performance Women’s Football
Authors: Maneiro Rubén , Losada José Luís , Casal Claudio A. , Ardá Antonio
Published: June 2021

Women’s football is a phenomenon that is experiencing an unstoppable increase in recent years. The objective of this study was to analyze how ball possessions are performed in high-performance women’s football. For this, the 52 matches played by all the national teams participating in the Women’s World Cup 2015 were analyzed. A total of 3740 ball possessions were examined. Using the “move outcome” variable as a reference criterion, a statistically significant relationship was found between possessions that ended in success and possessions that have failed. Specifically, the successful possessions were those that were made in the offensive zone, with a clear intention to progress towards the rival goal, with a low number of passes, and made in the second half of the matches. The results of the logistic regression showed that the proposed model is statistically significant, with an acceptable explanatory capacity. Finally, the results of the decision tree evidence the success of those possessions aiming at a quick completion, with very few passes and the offensive zone as a priority area for the possession.
Rural Social Participation through Osekkai during the COVID-19 Pandemic
Authors: Ohta Ryuichi , Yata Akiko , Arakawa Yuki , Maiguma Koichi , Sano Chiaki
Published: June 2021

We investigated the effects of enabling Osekkai, the traditional Japanese behavior of creating a helping culture, on social participation among rural people in rebuilding social connections that can be vital during the coronavirus diseases 2019 (COVID-19) pandemic. The subjects of this cross-sectional study were people interested in the Osekkai conference (control group) and those actively involved in Osekkai activities (exposure group). The primary outcome of social participation was measured as the frequency of meeting and the number of friends or acquaintances. The demographic data of the participants and process outcomes were measured using a questionnaire provided to all 287 registered participants. The effective response rate was 64.5% (185 responses). The involvement in Osekkai conferences was statistically associated with a high frequency and number of meetings with friends or acquaintances (p < 0.001 and 0.048, respectively). A health check was significantly associated with the number of friends or acquaintances met in the previous month, while high social support was significantly associated with loneliness. Thus, we confirm that Osekkai contributes to high social participation, although we see no relationship with loneliness. Future studies should investigate this cause-and-effect relationship and promote culturally sensitive activities to improve social and health outcomes in rural Japan.
Self-Management in Stroke Survivors: Development and Implementation of the Look after Yourself (LAY) Intervention
Authors: Fugazzaro Stefania , Denti Monica , Accogli Monia , Costi Stefania , Pagliacci Donatella , Calugi Simona , Cavalli Enrica , Taricco Mariangela , Bardelli Roberta ,   on behalf of Look after Yourself Project
Published: June 2021

Objective: Self-management is recommended in stroke rehabilitation. This report aims to describe timing, contents, and setting of delivery of a patient-centered, self-management program for stroke survivors in their early hospital rehabilitation phase: the Look After Yourself (LAY) intervention. Methods: After extensive literature search, the LAY intervention was developed by integrating the Chronic Disease Self-Management Program, based on the self-efficacy construct of social cognitive theory, with evidence-based key elements and input from stroke survivors. Results: the LAY intervention aims to implement self-management skills in stroke survivors, enabling them to be active in goal setting and problem solving using action plans and to facilitate the critical transition from hospital to community. It includes both group sessions to facilitate sharing of experiences, social comparison, vicarious learning, and increase motivation and one-to-one sessions focused on setting feasible action plans and on teaching personalized strategies to prevent falls. Standardization is ensured by manuals for facilitators and patients. Conclusion: The LAY intervention is the first Italian program to support early self-management in stroke rehabilitation; it has been experimented and its efficacy proven in improving self-efficacy, mental health, and activities of daily living, and detailed results have been published. The LAY intervention is described according to the TIDieR checklist.
Rodent-Related Zoonotic Pathogens at the Human–Animal–Environment Interface in Qatar: A Systematic Review and Meta-Analysis
Authors: Islam Md Mazharul , Farag Elmoubashar , Mahmoudi Ahmad , Hassan Mohammad Mahmudul , Mostafavi Ehsan , Enan Khalid A. , Al-Romaihi Hamad , Atta Muzzamil , El Hussein Abdel Rahim M. , Mkhize-Kwitshana Zilungile
Published: June 2021

Rodents are one of the most diversified terrestrial mammals, and they perform several beneficial activities in nature. These animals are also important as carriers of many pathogens with public health importance. The current systematic review was conducted to formulate a true depiction of rodent-related zoonoses in Qatar. Following systematic searches on PubMed, Scopus, Science Direct, and Web of Science and a screening process, a total of 94 published articles were selected and studied. The studied articles reported 23 rodent-related zoonotic pathogens that include nine bacterial, eleven parasitic, and three viral pathogens, from which the frequently reported pathogens were Mycobacterium tuberculosis (32 reports), Escherichia coli (23), and Salmonella spp. (16). The possible pathway of entry of the rodent-borne pathogens can be the land port, seaports, and airport of Qatar through carrier humans and animals, contaminated food, and agricultural products. The pathogens can be conserved internally by rodents, pets, and livestock; by agricultural production systems; and by food marketing chains. The overall estimated pooled prevalence of the pathogens among the human population was 4.27% (95%CI: 4.03–4.51%; p < 0.001) with significant heterogeneity (I2 = 99.50%). The top three highest prevalent pathogens were M.tuberculosis (30.90%; 22.75–39.04%; p < 0.001; I2 = 99.70%) followed by Toxoplasma gondii (21.93%; 6.23–37.61%; p < 0.001; I2 = 99.30%) and hepatitis E virus (18.29%; 11.72–24.86%; p < 0.001; I2 = 96.70%). However, there is a knowledge gap about the listed pathogens regarding the occurrence, transmission pathways, and rodent role in transmission dynamics at the human–animal–environment interface in Qatar. Further studies are required to explore the role of rodents in spreading zoonotic pathogens through the One Health framework, consisting of zoologists, ecologists, microbiologists, entomologists, veterinarians, and public health experts in this country.
The Health Behaviour of German Outpatient Caregivers in Relation to Their Working Conditions: A Qualitative Study
Authors: Mojtahedzadeh Natascha , Rohwer Elisabeth , Neumann Felix Alexander , Nienhaus Albert , Augustin Matthias , Zyriax Birgit-Christiane , Harth Volker , Mache Stefanie
Published: June 2021

Ongoing demographic change is leading to an increasingly older society and a rising proportion of people in need of care in the German population. Therefore, the professional group of outpatient caregivers is highly relevant. Their work is characterised not only by interacting with patients in a mobile setting but also by working in shifts. Health behaviour under these specific working conditions is crucial for ensuring long-term work ability and performance. Little is known about the health behaviour of German outpatient caregivers and its potential impact on their work. The aims of the study were (1) to examine health behavioural patterns (nutrition, exercise, smoking, regeneration) of outpatient caregivers, (2) to illuminate their personal health-promoting behaviours, and (3) to identify potential work-related factors influencing their health behaviour. Fifteen problem-centred interviews were conducted with outpatient caregivers working in Northern Germany in the period January–April 2020. Interviews were analysed by using qualitative content analysis. Outpatient caregivers reported improvable nutrition and hydration, with simultaneous high coffee consumption, low physical activity, poor regeneration (breaks and sleep quality), and good personal health-promoting behaviour (e.g., back-friendly habits), although the majority were smokers. Barriers to the implementation of health-promoting behaviours were a high perception of stress due to increased workload and time pressure, while aids to better health-promoting behaviour were described as being social support and personal resources. The respondents perceived their working conditions as potentially influencing their health behaviour. On the basis of their descriptions, various practice-relevant strategies were derived. The data explore a potential need for outpatient care services to develop interventions on behavioural and structural levels that can help create healthier working conditions for their employees so these caregivers can adopt better health behaviours.
Prioritising Risk Factors for Prescription Drug Overdose among Older Adults in South Korea: A Multi-Method Study
Authors: Lee Eun-Hae , Park Ju-Ok , Cho Joon-Pil , Lee Choung-Ah
Published: June 2021

Older adults are vulnerable to drug overdose. We used a multi-method approach to prioritise risk factors for prescription drug overdose among older adults. The study was conducted in two stages. First, risk factors for drug overdose were classified according to importance and changeability through literature review, determined through 2-phase expert surveys. Second, prescription drug overdose cases during 2011–2015 were selected from a national cohort; the prevalence of ‘more important’ or ‘more changeable’ factors determined in stage one was investigated. Scores were assigned according to the Basic Priority Rating Scale formula, reflecting the problem size and seriousness and intervention effectiveness. In the first stage, polypharmacy, old-old age, female sex, chronic disease, psychiatric disease, and low socioeconomic status (SES) were selected as risk factors. In the second stage, 93.9% of cases enrolled had chronic medical disease; 78.3% were using multiple drugs. Low SES was more prevalent than other risk factors. As per the scoring formula, chronic medical disease, polypharmacy, psychiatric disease, low SES, female sex, and old-old age were the most important risk factors in order of priority. Patients with chronic medical disease and those using multiple medications should be prioritised in overdose prevention interventions among older adults.
Gender Differences in the Quality of Life of Formal Workers
Authors: Louzado José Andrade , Lopes Cortes Matheus , Galvão Oliveira Marcio , Moraes Bezerra Vanessa , Mistro Sóstenes , Souto de Medeiros Danielle , Arruda Soares Daniela , Oliveira Silva Kelle , Nicolaevna Kochergin Clávdia , Honorato dos Santos de Carvalho Vivian Carla , Wildes Amorim Welma , Serrate Mengue Sotero
Published: June 2021

Background: This study aimed to assess the quality of life associated with gender inequalities in formal workers and to determine the effect of sociodemographic, clinical, and behavioral factors on the quality of life (QOL). Methods: This cross-sectional study involved 1270 workers. Quality of life was measured using the EUROHIS-QOL 8-Item and assessed in terms of psychological, environmental, social, and physical domains, while demographic, socioeconomic, behavioral, and clinical variables served as explanatory variables. Analyses were performed using an ordinal logistic regression model whose significance level was 5%. Results: Of the participants, 80.2% were men, and 19.8% were women; the mean age was 34 (standard deviation: ±10) and 32 (±9) years, respectively. In all prediction scenarios, men were more likely to have a higher quality of life, especially in the physical (odds ratio: 2.16; 95% confidence interval: 1.60–2.93) and psychological (odds ratio: 2.09; 95% confidence interval: 1.51–2.91) domains. Conclusions: Men and women had significantly different levels of quality of life, and sociodemographic, clinical, and behavioral variables partially clarified these differences, which were possibly established by a socio-historical process of construction of the work role determined by gender issues.
Smooth Muscle Specific Ablation of CXCL12 in Mice Downregulates CXCR7 Associated with Defective Coronary Arteries and Cardiac Hypertrophy
Authors: Ghadge Santhosh Kumar , Messner Moritz , Seiringer Herbert , Maurer Thomas , Staggl Simon , Zeller Tanja , Müller Christian , Börnigen Daniela , Weninger Wolfgang J. , Geyer Stefan H. , Sopper Sieghart , Krogsdam Anne , Pölzl Gerhard , Bauer Axel , Zaruba Marc-Michael
Published: June 2021

The chemokine CXCL12 plays a fundamental role in cardiovascular development, cell trafficking, and myocardial repair. Human genome-wide association studies even have identified novel loci downstream of the CXCL12 gene locus associated with coronary artery disease and myocardial infarction. Nevertheless, cell and tissue specific effects of CXCL12 are barely understood. Since we detected high expression of CXCL12 in smooth muscle (SM) cells, we generated a SM22-alpha-Cre driven mouse model to ablate CXCL12 (SM-CXCL12−/−). SM-CXCL12−/− mice revealed high embryonic lethality (50%) with developmental defects, including aberrant topology of coronary arteries. Postnatally, SM-CXCL12−/− mice developed severe cardiac hypertrophy associated with fibrosis, apoptotic cell death, impaired heart function, and severe coronary vascular defects characterized by thinned and dilated arteries. Transcriptome analyses showed specific upregulation of pathways associated with hypertrophic cardiomyopathy, collagen protein network, heart-related proteoglycans, and downregulation of the M2 macrophage modulators. CXCL12 mutants showed endothelial downregulation of the CXCL12 co-receptor CXCR7. Treatment of SM-CXCL12−/− mice with the CXCR7 agonist TC14012 attenuated cardiac hypertrophy associated with increased pERK signaling. Our data suggest a critical role of smooth muscle-specific CXCL12 in arterial development, vessel maturation, and cardiac hypertrophy. Pharmacological stimulation of CXCR7 might be a promising target to attenuate adverse hypertrophic remodeling.
Sex-Related Differences in Murine Models of Chemically Induced Pulmonary Fibrosis
Authors: Solopov Pavel , Colunga Biancatelli Ruben Manuel Luciano , Dimitropoulou Christiana , Catravas John D.
Published: June 2021

We developed two models of chemically induced chronic lung injury and pulmonary fibrosis in mice (intratracheally administered hydrochloric acid (HCl) and intratracheally administered nitrogen mustard (NM)) and investigated male–female differences. Female mice exhibited higher 30-day survival and less weight loss than male mice. Thirty days after the instillation of either HCl or NM, bronchoalveolar lavage fluid displayed a persistent, mild inflammatory response, but with higher white blood cell numbers and total protein content in males vs. females. Furthermore, females exhibited less collagen deposition, milder pulmonary fibrosis, and lower Ashcroft scores. After instillation of either HCl or NM, all animals displayed increased values of phosphorylated (activated) Heat Shock Protein 90, which plays a crucial role in the alveolar wound-healing processes; however, females presented lower activation of both transforming growth factor-β (TGF-β) signaling pathways: ERK and SMAD. We propose that female mice are protected from chronic complications of a single exposure to either HCl or NM through a lesser activation of TGF-β and downstream signaling. The understanding of the molecular mechanisms that confer a protective effect in females could help develop new, gender-specific therapeutics for IPF.
Metabolic Dysfunction in Spinal Muscular Atrophy
Authors: Deguise Marc-Olivier , Chehade Lucia , Kothary Rashmi
Published: June 2021

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder leading to paralysis, muscle atrophy, and death. Significant advances in antisense oligonucleotide treatment and gene therapy have made it possible for SMA patients to benefit from improvements in many aspects of the once devastating natural history of the disease. How the depletion of survival motor neuron (SMN) protein, the product of the gene implicated in the disease, leads to the consequent pathogenic changes remains unresolved. Over the past few years, evidence toward a potential contribution of gastrointestinal, metabolic, and endocrine defects to disease phenotype has surfaced. These findings ranged from disrupted body composition, gastrointestinal tract, fatty acid, glucose, amino acid, and hormonal regulation. Together, these changes could have a meaningful clinical impact on disease traits. However, it is currently unclear whether these findings are secondary to widespread denervation or unique to the SMA phenotype. This review provides an in-depth account of metabolism-related research available to date, with a discussion of unique features compared to other motor neuron and related disorders.
Lysophosphatidic Acid Accelerates Bovine In Vitro-Produced Blastocyst Formation through the Hippo/YAP Pathway
Authors: Yu Bo , van Tol Helena T. A. , Oei Christine H. Y. , Stout Tom A. E. , Roelen Bernard A. J.
Published: June 2021

The segregation of trophectoderm (TE) and inner cell mass in early embryos is driven primarily by the transcription factor CDX2. The signals that trigger CDX2 activation are, however, less clear. In mouse embryos, the Hippo-YAP signaling pathway is important for the activation of CDX2 expression; it is less clear whether this relationship is conserved in other mammals. Lysophosphatidic acid (LPA) has been reported to increase YAP levels by inhibiting its degradation. In this study, we cultured bovine embryos in the presence of LPA and examined changes in gene and protein expression. LPA was found to accelerate the onset of blastocyst formation on days 5 and 6, without changing the TE/inner cell mass ratio. We further observed that the expression of TAZ and TEAD4 was up-regulated, and YAP was overexpressed, in LPA-treated day 6 embryos. However, LPA-induced up-regulation of CDX2 expression was only evident in day 8 embryos. Overall, our data suggest that the Hippo signaling pathway is involved in the initiation of bovine blastocyst formation, but does not affect the cell lineage constitution of blastocysts.
Opa1 Deficiency Promotes Development of Retinal Vascular Lesions in Diabetic Retinopathy
Authors: Kim Dongjoon , Votruba Marcela , Roy Sayon
Published: June 2021

This study investigates whether reduced optic atrophy 1 (Opa1) level promotes apoptosis and retinal vascular lesions associated with diabetic retinopathy (DR). Four groups of mice: wild type (WT) control mice, streptozotocin (STZ)-induced diabetic mice, Opa1+/− mice, and diabetic Opa1+/− mice were used in this study. 16 weeks after diabetes onset, retinas were assessed for Opa1 and Bax levels by Western blot analysis, and retinal networks were examined for acellular capillaries (AC) and pericyte loss (PL). Apoptotic cells were detected in retinal capillaries using TUNEL assay, and caspase-3 activity was assessed using fluorometric analysis. Opa1 expression was significantly downregulated in retinas of diabetic and Opa1+/− mice compared with those of WT mice. Inducing diabetes further decreased Opa1 expression in retinas of Opa1+/− mice. Increased cytochrome c release concomitant with increased level of pro-apoptotic Bax and elevated caspase-3 activity were observed in retinas of diabetic and Opa1+/− mice; the number of TUNEL-positive cells and AC/PL was also significantly increased. An additional decrease in the Opa1 level in retinas of diabetic Opa1+/− mice exacerbated the development of apoptotic cells and AC/PL compared with those of diabetic mice. Diabetes-induced Opa1 downregulation contributes, at least in part, to the development of retinal vascular lesions characteristic of DR.
Current Strategies for the Regeneration of Skeletal Muscle Tissue
Authors: Alarcin Emine , Bal-Öztürk Ayca , Avci Hüseyin , Ghorbanpoor Hamed , Dogan Guzel Fatma , Akpek Ali , Yesiltas Gözde , Canak-Ipek Tuba , Avci-Adali Meltem
Published: June 2021

Traumatic injuries, tumor resections, and degenerative diseases can damage skeletal muscle and lead to functional impairment and severe disability. Skeletal muscle regeneration is a complex process that depends on various cell types, signaling molecules, architectural cues, and physicochemical properties to be successful. To promote muscle repair and regeneration, various strategies for skeletal muscle tissue engineering have been developed in the last decades. However, there is still a high demand for the development of new methods and materials that promote skeletal muscle repair and functional regeneration to bring approaches closer to therapies in the clinic that structurally and functionally repair muscle. The combination of stem cells, biomaterials, and biomolecules is used to induce skeletal muscle regeneration. In this review, we provide an overview of different cell types used to treat skeletal muscle injury, highlight current strategies in biomaterial-based approaches, the importance of topography for the successful creation of functional striated muscle fibers, and discuss novel methods for muscle regeneration and challenges for their future clinical implementation.
Structure and Thermal Stability of wtRop and RM6 Proteins through All-Atom Molecular Dynamics Simulations and Experiments
Authors: Arnittali Maria , Rissanou Anastassia N. , Amprazi Maria , Kokkinidis Michael , Harmandaris Vagelis
Published: June 2021

In the current work we study, via molecular simulations and experiments, the folding and stability of proteins from the tertiary motif of 4-α-helical bundles, a recurrent motif consisting of four amphipathic α-helices packed in a parallel or antiparallel fashion. The focus is on the role of the loop region in the structure and the properties of the wild-type Rop (wtRop) and RM6 proteins, exploring the key factors which can affect them, through all-atom molecular dynamics (MD) simulations and supporting by experimental findings. A detailed investigation of structural and conformational properties of wtRop and its RM6 loopless mutation is presented, which display different physical characteristics even in their native states. Then, the thermal stability of both proteins is explored showing RM6 as more thermostable than wtRop through all studied measures. Deviations from native structures are detected mostly in tails and loop regions and most flexible residues are indicated. Decrease of hydrogen bonds with the increase of temperature is observed, as well as reduction of hydrophobic contacts in both proteins. Experimental data from circular dichroism spectroscopy (CD), are also presented, highlighting the effect of temperature on the structural integrity of wtRop and RM6. The central goal of this study is to explore on the atomic level how a protein mutation can cause major changes in its physical properties, like its structural stability.
Identification of Three Type II Toxin-Antitoxin Systems in Model Bacterial Plant Pathogen Dickeya dadantii 3937
Authors: Boss Lidia , Górniak Marcin , Lewańczyk Alicja , Morcinek-Orłowska Joanna , Barańska Sylwia , Szalewska-Pałasz Agnieszka
Published: June 2021

Type II toxin-antitoxin (TA) systems are genetic elements usually encoding two proteins: a stable toxin and an antitoxin, which binds the toxin and neutralizes its toxic effect. The disturbance in the intracellular toxin and antitoxin ratio typically leads to inhibition of bacterial growth or bacterial cell death. Despite the fact that TA modules are widespread in bacteria and archaea, the biological role of these systems is ambiguous. Nevertheless, a number of studies suggests that the TA modules are engaged in such important processes as biofilm formation, stress response or virulence and maintenance of mobile genetic elements. The Dickeya dadantii 3937 strain serves as a model for pathogens causing the soft-rot disease in a wide range of angiosperm plants. Until now, several chromosome-encoded type II TA systems were identified in silico in the genome of this economically important bacterium, however so far only one of them was experimentally validated. In this study, we investigated three putative type II TA systems in D. dadantii 3937: ccdAB2Dda, phd-docDda and dhiTA, which represents a novel toxin/antitoxin superfamily. We provide an experimental proof for their functionality in vivo both in D. dadantii and Escherichia coli. Finally, we examined the prevalence of those systems across the Pectobacteriaceae family by a phylogenetic analysis.
Sulforaphane Impact on Reactive Oxygen Species (ROS) in Bladder Carcinoma
Authors: Xie Hui , Chun Felix K.-H. , Rutz Jochen , Blaheta Roman A.
Published: June 2021

Sulforaphane (SFN) is a natural glucosinolate found in cruciferous vegetables that acts as a chemopreventive agent, but its mechanism of action is not clear. Due to antioxidative mechanisms being thought central in preventing cancer progression, SFN could play a role in oxidative processes. Since redox imbalance with increased levels of reactive oxygen species (ROS) is involved in the initiation and progression of bladder cancer, this mechanism might be involved when chemoresistance occurs. This review summarizes current understanding regarding the influence of SFN on ROS and ROS-related pathways and appraises a possible role of SFN in bladder cancer treatment.
An Engineered sgsh Mutant Zebrafish Recapitulates Molecular and Behavioural Pathobiology of Sanfilippo Syndrome A/MPS IIIA
Authors: Douek Alon M. , Amiri Khabooshan Mitra , Henry Jason , Stamatis Sebastian-Alexander , Kreuder Florian , Ramm Georg , Änkö Minna-Liisa , Wlodkowic Donald , Kaslin Jan
Published: June 2021

Mucopolysaccharidosis IIIA (MPS IIIA, Sanfilippo syndrome type A), a paediatric neurological lysosomal storage disease, is caused by impaired function of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH) resulting in impaired catabolism of heparan sulfate glycosaminoglycan (HS GAG) and its accumulation in tissues. MPS IIIA represents a significant proportion of childhood dementias. This condition generally leads to patient death in the teenage years, yet no effective therapy exists for MPS IIIA and a complete understanding of the mechanisms of MPS IIIA pathogenesis is lacking. Here, we employ targeted CRISPR/Cas9 mutagenesis to generate a model of MPS IIIA in the zebrafish, a model organism with strong genetic tractability and amenity for high-throughput screening. The sgshΔex5−6 zebrafish mutant exhibits a complete absence of Sgsh enzymatic activity, leading to progressive accumulation of HS degradation products with age. sgshΔex5−6 zebrafish faithfully recapitulate diverse CNS-specific features of MPS IIIA, including neuronal lysosomal overabundance, complex behavioural phenotypes, and profound, lifelong neuroinflammation. We further demonstrate that neuroinflammation in sgshΔex5−6 zebrafish is largely dependent on interleukin-1β and can be attenuated via the pharmacological inhibition of Caspase-1, which partially rescues behavioural abnormalities in sgshΔex5−6 mutant larvae in a context-dependent manner. We expect the sgshΔex5−6 zebrafish mutant to be a valuable resource in gaining a better understanding of MPS IIIA pathobiology towards the development of timely and effective therapeutic interventions.
Alternate Roles of Sox Transcription Factors beyond Transcription Initiation
Authors: Zhang Yuli , Hou Linlin
Published: June 2021

Sox proteins are known as crucial transcription factors for many developmental processes and for a wide range of common diseases. They were believed to specifically bind and bend DNA with other transcription factors and elicit transcriptional activation or repression activities in the early stage of transcription. However, their functions are not limited to transcription initiation. It has been showed that Sox proteins are involved in the regulation of alternative splicing regulatory networks and translational control. In this review, we discuss the current knowledge on how Sox transcription factors such as Sox2, Sry, Sox6, and Sox9 allow the coordination of co-transcriptional splicing and also the mechanism of SOX4-mediated translational control in the context of RNA polymerase III.
A Glimpse into the Structural Properties of the Intermediate and Transition State in the Folding of Bromodomain 2 Domain 2 by Φ Value Analysis
Authors: Novak Leonore , Petrosino Maria , Santorelli Daniele , Chiaraluce Roberta , Consalvi Valerio , Pasquo Alessandra , Travaglini-Allocatelli Carlo
Published: June 2021

Bromodomains (BRDs) are small protein interaction modules of about 110 amino acids that selectively recognize acetylated lysine in histones and other proteins. These domains have been identified in a variety of multi-domain proteins involved in transcriptional regulation or chromatin remodeling in eukaryotic cells. BRD inhibition is considered an attractive therapeutic approach in epigenetic disorders, particularly in oncology. Here, we present a Φ value analysis to investigate the folding pathway of the second domain of BRD2 (BRD2(2)). Using an extensive mutational analysis based on 25 site-directed mutants, we provide structural information on both the intermediate and late transition state of BRD2(2). The data reveal that the C-terminal region represents part of the initial folding nucleus, while the N-terminal region of the domain consolidates its structure only later in the folding process. Furthermore, only a small number of native-like interactions have been identified, suggesting the presence of a non-compact, partially folded state with scarce native-like characteristics. Taken together, these results indicate that, in BRD2(2), a hierarchical mechanism of protein folding can be described with non-native interactions that play a significant role in folding.
Multifaced Roles of HDL in Sepsis and SARS-CoV-2 Infection: Renal Implications
Authors: Stasi Alessandra , Franzin Rossana , Fiorentino Marco , Squiccimarro Enrico , Castellano Giuseppe , Gesualdo Loreto
Published: June 2021

High-density lipoproteins (HDLs) are a class of blood particles, principally involved in mediating reverse cholesterol transport from peripheral tissue to liver. Omics approaches have identified crucial mediators in the HDL proteomic and lipidomic profile, which are involved in distinct pleiotropic functions. Besides their role as cholesterol transporter, HDLs display anti-inflammatory, anti-apoptotic, anti-thrombotic, and anti-infection properties. Experimental and clinical studies have unveiled significant changes in both HDL serum amount and composition that lead to dysregulated host immune response and endothelial dysfunction in the course of sepsis. Most SARS-Coronavirus-2-infected patients admitted to the intensive care unit showed common features of sepsis disease, such as the overwhelmed systemic inflammatory response and the alterations in serum lipid profile. Despite relevant advances, episodes of mild to moderate acute kidney injury (AKI), occurring during systemic inflammatory diseases, are associated with long-term complications, and high risk of mortality. The multi-faceted relationship of kidney dysfunction with dyslipidemia and inflammation encourages to deepen the clarification of the mechanisms connecting these elements. This review analyzes the multifaced roles of HDL in inflammatory diseases, the renal involvement in lipid metabolism, and the novel potential HDL-based therapies.
Gene Transfer Potential of Outer Membrane Vesicles of Gram-Negative Bacteria
Authors: Dell’Annunziata Federica , Folliero Veronica , Giugliano Rosa , De Filippis Anna , Santarcangelo Cristina , Izzo Viviana , Daglia Maria , Galdiero Massimiliano , Arciola Carla Renata , Franci Gianluigi
Published: June 2021

The increasing spread of multidrug-resistant pathogenic bacteria is one of the major threats to public health worldwide. Bacteria can acquire antibiotic resistance and virulence genes through horizontal gene transfer (HGT). A novel horizontal gene transfer mechanism mediated by outer membrane vesicles (OMVs) has been recently identified. OMVs are rounded nanostructures released during their growth by Gram-negative bacteria. Biologically active toxins and virulence factors are often entrapped within these vesicles that behave as molecular carriers. Recently, OMVs have been reported to contain DNA molecules, but little is known about the vesicle packaging, release, and transfer mechanisms. The present review highlights the role of OMVs in HGT processes in Gram-negative bacteria.
Single-Cell Transcriptome Analysis as a Promising Tool to Study Pluripotent Stem Cell Reprogramming
Authors: Kim Hyun Kyu , Ha Tae Won , Lee Man Ryul
Published: June 2021

Cells are the basic units of all organisms and are involved in all vital activities, such as proliferation, differentiation, senescence, and apoptosis. A human body consists of more than 30 trillion cells generated through repeated division and differentiation from a single-cell fertilized egg in a highly organized programmatic fashion. Since the recent formation of the Human Cell Atlas consortium, establishing the Human Cell Atlas at the single-cell level has been an ongoing activity with the goal of understanding the mechanisms underlying diseases and vital cellular activities at the level of the single cell. In particular, transcriptome analysis of embryonic stem cells at the single-cell level is of great importance, as these cells are responsible for determining cell fate. Here, we review single-cell analysis techniques that have been actively used in recent years, introduce the single-cell analysis studies currently in progress in pluripotent stem cells and reprogramming, and forecast future studies.