bluuebunny/crossref_metadata_2025 huggingface dataset:
Reinvestigating the Parabolic-Shaped Eddy Viscosity Profile for Free Surface Flows
Authors: Absi Rafik
Published: August 2021

The flow in rivers is turbulent. The main parameter related to turbulence in rivers is the eddy viscosity, which is used to model a turbulent flow and is involved in the determination of both velocities and sediment concentrations. A well-known and largely used vertical distribution of eddy viscosity in free surface flows (open channels and rivers) is given by the parabolic profile that is based on the logarithmic velocity profile assumption and is valid therefore only in the log-law layer. It was improved thanks to the log-wake law velocity profile. These two eddy viscosities are obtained from velocity profiles, and the main shortcoming of the log-wake profile is the empirical Coles’ parameter. A more rigorous and reliable analytical eddy viscosity model is needed. In this study, we present two analytical eddy viscosity models based on the concepts of velocity and length scales, which are related to the exponentially decreasing turbulent kinetic energy (TKE) function and mixing length, namely, (1) the exponential-type profile of eddy viscosity and (2) an eddy viscosity based on an extension of von Karman’s similarity hypothesis. The eddy viscosity from the second model is Re*-independent, while the eddy viscosity from the first model is Re*-dependent (where Re* is the friction Reynolds number). The proposed analytical models were validated through computation of velocity profiles, obtained from the resolution of the momentum equation and comparisons to experimental data. With an additional correction function related to the damping effect of turbulence near the free surface, both models are similar to the log-wake-modified eddy viscosity profile but with different values of the Coles’ parameter, i.e., Π=0.2 for the first model and Π=0.15 for the second model. These values are similar to those found in open-channel flow experiments. This provides an explanation about the accuracy of these two analytical models in the outer part of free surface flows. For large values of Re* (Re* > 2000), the first model becomes Re* independent, and the two coefficients reach asymptotic values. Finally, the two proposed eddy viscosity models are validated by experimental data of eddy viscosity.
ArcDrain: A GIS Add-In for Automated Determination of Surface Runoff in Urban Catchments
Authors: Manchado Cristina , Roldán-Valcarce Alejandro , Jato-Espino Daniel , Andrés-Doménech Ignacio
Published: August 2021

Surface runoff determination in urban areas is crucial to facilitate ex ante water planning, especially in the context of climate and land cover changes, which are increasing the frequency of floods, due to a combination of violent storms and increased imperviousness. To this end, the spatial identification of urban areas prone to runoff accumulation is essential, to guarantee effective water management in the future. Under these premises, this work sought to produce a tool for automated determination of urban surface runoff using a geographic information systems (GIS). This tool, which was designed as an ArcGIS add-in called ArcDrain, consists of the discretization of urban areas into subcatchments and the subsequent application of the rational method for runoff depth estimation. The formulation of this method directly depends on land cover type and soil permeability, thereby enabling the identification of areas with a low infiltration capacity. ArcDrain was tested using the city of Santander (northern Spain) as a case study. The results achieved demonstrated the accuracy of the tool for detecting high runoff rates and how the inclusion of mitigation measures in the form of sustainable drainage systems (SuDS) and green infrastructure (GI) can help reduce flood hazards in critical zones.
Delirium in Critical Illness Patients and the Potential Role of Thiamine Therapy in Prevention and Treatment: Findings from a Scoping Review with Implications for Evidence-Based Practice
Authors: Lange Sandra , Mędrzycka-Dąbrowska Wioletta , Friganovic Adriano , Oomen Ber , Krupa Sabina
Published: August 2021

Introduction: Thiamine is a water-soluble vitamin and is necessary for energy metabolism. Critically ill patients are at particular risk of developing thiamine deficiency and related complications. One of the complications that can occur is delirium. Delirium is a disorder that affects the body’s response to treatment, length of stay in the ward, mortality, long-term cognitive impairment, and significantly increases treatment costs. In addition, studies show that delirium medication is more effective in preventing than in treating delirium. Given its low cost, availability, and minimal risk of side effects, thiamine supplementation could prove to be a relevant strategy in the prevention and treatment of delirium. Methods: PubMed, Cochrane Library, Ovid, and ClinicalTrials.gov databases were searched using relevant keywords that focus on the use of thiamine to prevent or treat delirium in critically ill patients. Results: Seven articles were included in the analysis. Conclusion: The small number of studies and considerable heterogeneity prevent conclusions supporting the use of thiamine as an adjuvant in the prevention and treatment of delirium among critically ill patients. There is a need for high-quality, large-scale randomized clinical trials to confirm the beneficial effects of thiamine in the prevention and treatment of delirium.
Societal Age Stereotypes in the U.S. and U.K. from a Media Database of 1.1 Billion Words
Authors: Ng Reuben
Published: August 2021

Recently, 194 World Health Organization member states called on the international organization to develop a global campaign to combat ageism, citing its alarming ubiquity, insidious threat to health, and prevalence in the media. Existing media studies of age stereotypes have mostly been single-sourced. This study harnesses a 1.1-billion-word media database comprising the British National Corpus and Corpus of Contemporary American English—with genres including spoken/television, fiction, magazines, newspapers—to provide a comprehensive view of ageism in the United Kingdom and United States. The US and UK were chosen as they are home to the largest media conglomerates with tremendous power to shape public opinion. The most commonly used synonym of older adults was identified, and its most frequently used descriptors were analyzed for valence. Such computational linguistics techniques represent a new advance in studying aging narratives. The key finding is consistent, though no less alarming: Negative descriptions of older adults outnumber positive ones by six times. Negative descriptions tend to be physical, while positive ones tend to be behavioral. Magazines contain the highest levels of ageism, followed by the spoken genre, newspapers, and fiction. Findings underscore the need to increase public awareness of ageism and lay the groundwork to design targeted societal campaigns to tackle ageism—one of our generation’s most pernicious threats.
Social Support and Cognitive Impairment: Results from a Portuguese 4-Year Prospective Study
Authors: Pais Ricardo , Ruano Luís , Moreira Carla , Fraga Sílvia , P. Carvalho Ofélia , Barros Henrique
Published: August 2021

(1) Background: In an ageing society, social relationships may benefit cognitive performance with an impact on the health of older people. This study aims to estimate the effect of different social support sources on the risk of cognitive impairment in a sample of older Portuguese people. (2) Methods: From the Portuguese EpiPorto cohort study, we followed a sample of participants with 60 to 85 years (N = 656) between 2009 and 2015 (4.63 mean years of follow-up). The participants’ perception of social support from family, friends and significant others was evaluated. Cox’s regression models were used to investigate the association between this and sociodemographic variables. (3) Results: It was found that social support from friends reduces the risk of cognitive impairment. Men, participants aged 60 to 64 and those not married have a lower risk of cognitive impairment after adjusting for other variables. Participants between 80 and 85 years old (p = 0.021), those with less than four years of education (p < 0.001), and those with cognitive impairment (p = 0.007) have perception of less social support from friends. (4) Conclusions: A social support network from friends reduces the risk of cognitive impairment for older people.
Effect of Unmeasured Time Hours on Occupational Noise Exposure Assessment in the Shipbuilding Process in Korea
Authors: Shin Jaewoo , Lee Seokwon , Lee Kyoungho , Kim Hyunwook
Published: August 2021

Occupational noise is known to be one of the most hazardous risk factors, frequently exceeding the exposure limit thus causing hearing loss and other health outcomes among many field workers in various industries and workplaces. This study aims to characterize the levels of occupational noise exposure during the daily working hours and break periods (sampling preparation and lunch break), identify work-related characteristics affecting the noise exposure levels when including or excluding the break periods and finally determine the most effective approach for occupational noise exposure assessment by using the Korean and U.S. OSHA’s guidelines. A total of 1575 workers employed by a large shipbuilding company participated in this study, and the historical exposure datasets of noise dosimeters, collected from 2016 to 2018, were classified by characteristics. A threshold level (TL) for the noise dosimeter was set as a value of 80 dBA during the break periods, including the preparation time for sampling instruments and one hour for the lunch break. The shipbuilding workers were exposed to high levels of occupational noise during the break periods, especially for those working in heating, grinding, and power processes in the painting-related departments. Out of 1575 samples, most cases were related to the preparation time (N = 1432, 90.9%) and lunch break (N = 1359, 86.9%). During the break time, the levels of noise exposure were measured depending on task-specific characteristics. When including the break time, the noise levels increased by approximately 1 dBA during the break, combining 0.8 dBA in the lunch hours and 0.2 dBA for the preparation of the sampling instrument. When excluding the break time, the levels of noise exposure collected using a Korean Occupational Safety and Health Administration (KOSHA) guide tended to be underestimated compared to those using the U.S. OSHA method. When including the break times, the proportion of noise exposure levels exceeding the compliance exposure limit declined from 37.9% to 34.5%, indicating that the break times might affect the decrease in the noise exposure levels. Taken together, shipbuilding workers could possibly be exposed to much greater amounts of noise exposure during break times in the shipbuilding processes, and the noise exposure levels in the department of painting were high. Therefore, it is recommended that industrial hygienists collect exposure monitoring data of occupational noise one hour after their job tasks begin and then consecutively monitor the noise exposure levels for at least 6 h including the break periods for each day.
The Association between the Self-Management of Mild Symptoms and Quality of Life of Elderly Populations in Rural Communities: A Cross-Sectional Study
Authors: Ohta Ryuichi , Sato Mikiya , Kitayuguchi Jun , Maeno Tetsuhiro , Sano Chiaki
Published: August 2021

Maintaining people’s health based on their help-seeking behavior (HSB) regarding mild symptoms is essential. An effective HSB, especially self-management, can facilitate the attainment of appropriate healthcare resources and affect health outcomes such as quality of life (QOL). However, clear evidence regarding the relationship between self-management, mild symptoms, and QOL is unavailable. Therefore, this cross-sectional study investigated this association in a rural elderly population. The participants, aged over 65 years, were living in rural communities. The primary outcome of QOL was examined using the EuroQol 5-Dimension 5-Level (EQ-5D-5L). After adjusting for propensity score matching, 298 participants in the self-management usage group were matched with 298 in the group not using self-management. The most frequent HSB trend was consulting with primary care physicians, followed by self-care, consulting with families, utilizing home medicines, and buying medicines. The EQ-5D-5L scores were statistically higher in the self-management usage group than in the other group. The HSBs with a trend of using self-management were related to a high QOL. Self-management of symptoms along with other HSBs can improve elderly HSBs in rural contexts. Educational interventions and system development for HSBs in rural contexts could be effective in enhancing the QOL of rural elderly populations.
Comparison of Aerobic Capacity Changes as a Result of a Polarized or Block Training Program among Trained Mountain Bike Cyclists
Authors: Hebisz Paulina , Hebisz Rafał , Drelak Maja
Published: August 2021

This study compared the effectiveness of a block training program and a polarized training program in developing aerobic capacity in twenty trained mountain bike cyclists. The cyclists were divided into two groups: the block training program group (BT) and the polarized training program group (PT). The experiment lasted 8 weeks. During the experiment, the BT group alternated between 17-day blocks consisting of dominant low-intensity training (LIT) and 11-day blocks consisting of sprint interval training (SIT), and high-intensity interval training (HIIT), while the PT group performed SIT, HIIT, and LIT simultaneously. Before and after the experiment, the cyclists performed incremental tests during which maximal oxygen uptake (VO2max), maximal aerobic power (Pmax), power achieved at the first ventilatory threshold (PVT1), and at the second ventilatory threshold (PVT2) were measured. VO2max increased in BT group (from 3.75 ± 0.67 to 4.00 ± 0.75 L∙min−1) and PT group (from 3.66 ± 0.73 to 4.20 ± 0.89 L∙min−1). In addition, Pmax, PVT1, and PVT2 increased in both groups to a similar extent. In conclusion, the polarized training program was more effective in developing the VO2max compared to the block program. In terms of developing other parameters characterizing the cyclists’ aerobic capacity, the block and polarized program induced similar results.
Preschoolers’ and Mothers Dietary Practices and Compliance with the 24-h Movement Guidelines: Results of Oman’s National Nutrition Survey
Authors: Almaamary Salima , Al Shammakhi Saleh , Alghamari Ibtisam , Jabbour Jana , Al-Jawaldeh Ayoub
Published: August 2021

Introduction: Little is known on the nutritional and lifestyle variables of preschool children in Oman. This study analyzed data of the 2017 Oman National Nutrition Survey to assess the prevalence and interrelationships between dietary and movement variables among preschool children, aged 2–5 years. Methods: Household visits of a nationally representative sample evaluated mothers and children’s dietary, sleep and physical activity practices; media exposure; and anthropometric and sociodemographic variables. Results: Dyads of mothers and pre-school children aged 2–5 years (n = 1771) were assessed. Childhood overweight/obesity was prevalent in 2% of the sample. Over 54% of children consumed sweetened items and/or French fries or chips at least once daily. Over 65% of children had fruits and/or vegetables once daily or less. Mothers had healthier dietary and movement habits compared to their offspring. Compliance with media exposure was the lowest among mothers and children. Multivariate regression revealed children’s increased sweet intake was the only significant predictor of excess weight in children. Conclusion: This study revealed a low prevalence of overweight/obesity among preschool children in Oman. Children had an acceptable compliance with sleeping recommendations, yet limited adherence to media exposure, activity, added sugar and fruits and vegetables guidelines.
Electronic Games, Television, and Psychological Wellbeing of Adolescents: Mediating Role of Sleep and Physical Activity
Authors: Khan Asaduzzaman , Burton Nicola W.
Published: August 2021

This study investigated the associations between two common recreational screen activities and the psychological wellbeing of adolescents, and whether this association was mediated by sleep duration or physical activity frequency. This study used nationally representative cross-sectional survey data from 2946 adolescents (mean age 16.9 [0.38] years; 49% female) in the Longitudinal Study of Australian Children (LSAC). Adolescents provided information on daily time spent for each of the following: playing electronic games and watching television, time of sleep onset and wakeup, and number of days/week doing ≥60 min/day of physical activity. Psychological wellbeing was assessed by the Strengths and Difficulties Questionnaire (SDQ). Generalized estimating equations were used to examine the associations, and a contemporary multiple mediation analysis was used to examine the mediation effects. One fifth (20%) of adolescents were categorized as having poor wellbeing (SDQ total ≥17) with a significant sex difference (males: 16%; females: 24%; p < 0.001). Playing electronic games was inversely associated with psychological wellbeing for both male and female adolescents (p < 0.001). Watching television was inversely associated with psychological wellbeing for female adolescents (p < 0.001). Sleep duration and physical activity frequency were found to partially mediate the relationships between playing electronic games and the psychological wellbeing of male and female adolescents. Physical activity frequency partially mediated the association between television watching and wellbeing among female adolescents. Longitudinal studies are required to determine the causal pathway between screen-based activities and the wellbeing of adolescents, and to inform intervention strategies.
The Anaerobic Power Assessment in CrossFit® Athletes: An Agreement Study
Authors: Ponce-García Tomás , Benítez-Porres Javier , García-Romero Jerónimo Carmelo , Castillo-Domínguez Alejandro , Alvero-Cruz José Ramón
Published: August 2021

Anaerobic power and capacity are considered determinants of performance and are usually assessed in athletes as a part of their physical capacities’ evaluation along the season. For that purpose, many field tests have been created. The main objective of this study was to analyze the agreement between four field tests and a laboratory test. Nineteen CrossFit® (CF) athletes were recruited for this study (28.63 ± 6.62 years) who had been practicing CF for at least one year. Tests performed were: (1) Anaerobic Squat Test at 60% of bodyweight (AST60); (2) Anaerobic Squat Test at 70% of bodyweight (AST70); (3) Repeated Jump Test (RJT); (4) Assault Bike Test (ABT); and (5) Wingate Anaerobic Test on a cycle ergometer (WG). All tests consisted of 30 s of max effort. The differences among methods were tested using a repeated-measures analysis of variance (ANOVA) and effect size. Agreement between methods was performed using Bland–Altman analysis. Analysis of agreement showed systematic bias in all field test PP values, which varied between −110.05 (AST60PP—WGPP) and 463.58 (ABTPP—WGPP), and a significant proportional error in ABTPP by rank correlation (p < 0.001). Repeated-measures ANOVA showed significant differences among PP values (F(1.76,31.59) = 130.61, p =< 0.001). In conclusion, since to our knowledge, this is the first study to analyze the agreement between various methods to estimate anaerobic power in CF athletes. Apart from ABT, all tests showed good agreement and can be used interchangeably in CF athletes. Our results suggest that AST and RJT are good alternatives for measuring the anaerobic power in CF athletes when access to a laboratory is not possible.
Bioaccumulation of Macronutrients in Edible Mushrooms in Various Habitat Conditions of NW Poland—Role in the Human Diet
Authors: Malinowski Ryszard , Sotek Zofia , Stasińska Małgorzata , Malinowska Katarzyna , Radke Patrycja , Malinowska Alicja
Published: August 2021

Recently, the interest in mushroom consumption has been growing, since their taste and low calorific value are appreciated, but also due to their nutritional value. In determining the usefulness of mushrooms in the human diet, it is important to consider the conditions of their occurrence to perform the assessment of bioaccumulation of minerals. The aim of the study was: (a) to determine the content of selected macronutrients (P, K, Ca, Mg, Na) in fruiting bodies of Boletus edulis, Imleria badia, Leccinum scabrum and the soils, (b) to determine their bioaccumulation potential taking into account the habitat conditions, and (c) an attempt to estimate their role in covering the requirement for macronutrients of the human organism. The research material was obtained in the NW of Poland: Uznam and Wolin, the Drawa Plain and the Ińsko Lakeland. In the soil, we determined the content of organic matter, pH, salinity and the content of absorbable and general forms of macronutrients. The content of macronutrients in mushrooms was also determined. Chemical analyses were performed using the generally accepted test methods. The study showed that in NW Poland, B. edulis grew on the acidic soils of Arenosols, and I. badia and L. scabrum grew on Podzols. The uptake of K, Mg and Ca by the tested mushrooms was positively, and P and Na negatively correlated with the content of these elements in the soil. The acidity of the soil affected the uptake of K and Mg by mushrooms. There was no effect of the amount of organic matter in the soil noticed on the content of macronutrients (except sodium) in mushrooms. Among the studied macronutrients, none of the mushrooms accumulated Ca, while P and K were generally accumulated in the highest amounts, regardless of the species. Each of the other elements was usually accumulated at a similar level in the fruiting bodies of the species we studied. The exception was I. badia, which accumulated higher amounts of Mg compared to B. edulis and L. scabrum. Mushrooms can enrich the diet with some macronutrients, especially in P and K.
Combination of Coagulation–Flocculation–Decantation and Ozonation Processes for Winery Wastewater Treatment
Authors: Jorge Nuno , Teixeira Ana R. , Matos Carlos C. , Lucas Marco S. , Peres José A.
Published: August 2021

This research assessed a novel treatment process of winery wastewater, through the application of a chemical-based process aiming to decrease the high organic carbon content, which represents a difficulty for wastewater treatment plants and a public health problem. Firstly, a coagulation–flocculation–decantation process (CFD process) was optimized by a simplex lattice design. Afterwards, the efficiency of a UV-C/ferrous iron/ozone system was assessed for organic carbon removal in winery wastewater. This system was applied alone and in combination with the CFD process (as a pre- and post-treatment). The coagulation–flocculation–decantation process, with a mixture of 0.48 g/L potassium caseinate and 0.52 g/L bentonite at pH 4.0, achieved 98.3, 97.6, and 87.8% removals of turbidity, total suspended solids, and total polyphenols, respectively. For the ozonation process, the required pH and ferrous iron concentration (Fe2+) were crucial variables in treatment optimization. With the application of the best operational conditions (pH = 4.0, [Fe2+] = 1.0 mM), the UV-C/ferrous iron/ozone system achieved 63.2% total organic carbon (TOC) removal and an energy consumption of 1843 kWh∙m−3∙order−1. The combination of CFD and ozonation processes increased the TOC removal to 66.1 and 65.5%, respectively, for the ozone/ferrous iron/UV-C/CFD and CFD/ozone/ferrous iron/UV-C systems. In addition, the germination index of several seeds was assessed and excellent values (>80%) were observed, which revealed the reduction in phytotoxicity. In conclusion, the combination of CFD and UV-C/ferrous iron/ozone processes is efficient for WW treatment.
Sleep Quality in Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI)
Authors: Lorenzoni Giulia , Azzolina Danila , Fraccaro Chiara , Zoccarato Caterina , Minto Clara , Iliceto Sabino , Gregori Dario , Tarantini Giuseppe
Published: August 2021

The present study aimed to analyze sleep quality and quality of Life (QoL) in patients undergoing Transcatheter Aortic Valve Implantation (TAVI). It was conducted at the Interventional Cardiology Unit of the Department of Cardiac, Thoracic, Vascular Sciences and Public Health of the University of Padova on 27 adult patients who underwent TAVI via the transfemoral approach. Patients completed two validated instruments, i.e., the Pittsburgh Sleep Quality Index (PSQI) and the EuroQoL (EQ-5D-5L), on the day of discharge and one month after the hospital discharge. Twenty-seven patients were enrolled with a severe aortic stenosis diagnosis, treated with transfemoral TAVI procedure. The study population included seventeen poor sleepers and ten good sleepers with a median age of 81.92 years overall. The global PSQI evaluation revealed a small significant improvement at follow-up (p-value 0.007). Small positive changes were detected in the Self-care and Usual activity domains of the EQ-5D-5L and the EQ-VAS. No correlation was detected between EQ-5D-5L and sleep quality. The present study confirms the importance of sleep quality monitoring in patients who undergo TAVI procedure for aortic stenosis treatment.
Spatiotemporal Dynamic Analysis of A-Level Scenic Spots in Guizhou Province, China
Authors: Qiu Yuanhong , Yin Jian , Zhang Ting , Du Yiming , Zhang Bin
Published: August 2021

A-level scenic spots are a unique evaluation form of tourist attractions in China, which have an important impact on regional tourism development. Guizhou is a key tourist province in China. In recent years, the number of A-level scenic spots in Guizhou Province has been increasing, and the regional tourist economy has improved rapidly. The spatial distribution evolution characteristics and influencing factors of A-level scenic spots in Guizhou Province from 2005 to 2019 were measured using spatial data analysis methods, trend analysis methods, and geographical detector methods. The results elaborated that the number of A-level scenic spots in all counties of Guizhou Province increased, while in the south it developed slowly. From 2005 to 2019, the spatial distribution in A-level scenic spots were characterized by spatial agglomeration. The spatial distribution equilibrium degree of scenic spots in nine cities in Guizhou Province was gradually developed to reach the “relatively average” level. By 2019, the kernel density distribution of A-level scenic spots had formed the “two-axis, multi-core” layout. One axis was located in the north central part of Guizhou Province, and the other axis ran across the central part. The multi-core areas were mainly located in Nanming District, Yunyan District, Honghuagang District, and Xixiu District. From 2005 to 2007, the standard deviation ellipses of the scenic spots distribution changed greatly in direction and size. After 2007, the long-axis direction of the ellipses gradually formed a southwest to northeast direction. We chose elevation, population density, river density, road network density, tourism income, and GDP as factors, to discuss the spatiotemporal evolution of the scenic spots’ distribution with coupling and attribution analysis. It was found that the river, population distribution, road network density, and the A-level scenic spots’ distribution had a relatively high coupling phenomenon. Highway network density and tourist income have a higher influence on A-level tourist resorts distribution. Finally, on account of the spatiotemporal pattern characteristics of A-level scenic spots in Guizhou Province and the detection results of influencing factors, we put forward suggestions to strengthen the development of scenic spots in southern Guizhou Province and upgrade the development model of “point-axis network surface” to the current “two-axis multi-core” pattern of tourism development. This study can explain the current situation of the spatial development of tourist attractions in Guizhou Province, formulate a regulation mechanism of tourism development, and provide a reference for decision-making to boost the high-quality development of the tourist industry.
Molecular Iodine/Cyclophosphamide Synergism on Chemoresistant Neuroblastoma Models
Authors: Álvarez-León Winniberg , Mendieta Irasema , Delgado-González Evangelina , Anguiano Brenda , Aceves Carmen
Published: August 2021

Neuroblastoma (Nb), the most common extracranial tumor in children, exhibited remarkable phenotypic diversity and heterogeneous clinical behavior. Tumors with MYCN overexpression have a worse prognosis. MYCN promotes tumor progression by inducing cell proliferation, de-differentiation, and dysregulated mitochondrial metabolism. Cyclophosphamide (CFF) at minimum effective oral doses (metronomic therapy) exerts beneficial actions on chemoresistant cancers. Molecular iodine (I2) in coadministration with all-trans retinoic acid synergizes apoptosis and cell differentiation in Nb cells. This work analyzes the impact of I2 and CFF on the viability (culture) and tumor progression (xenografts) of Nb chemoresistant SK-N-BE(2) cells. Results showed that both molecules induce dose-response antiproliferative effects, and I2 increases the sensibility of Nb cells to CFF, triggering PPARγ expression and acting as a mitocan in mitochondrial metabolism. In vivo oral I2/metronomic CFF treatments showed significant inhibition in xenograft growth, decreasing proliferation (Survivin) and activating apoptosis signaling (P53, Bax/Bcl-2). In addition, I2 decreased the expression of master markers of malignancy (MYCN, TrkB), vasculature remodeling, and increased differentiation signaling (PPARγ and TrkA). Furthermore, I2 supplementation prevented loss of body weight and hemorrhagic cystitis secondary to CFF in nude mice. These results allow us to propose the I2 supplement in metronomic CFF treatments to increase the effectiveness of chemotherapy and reduce side effects.
Multiomic Approaches to Uncover the Complexities of Dystrophin-Associated Cardiomyopathy
Authors: Gowran Aoife , Brioschi Maura , Rovina Davide , Chiesa Mattia , Piacentini Luca , Mallia Sara , Banfi Cristina , Pompilio Giulio , Santoro Rosaria
Published: August 2021

Despite major progress in treating skeletal muscle disease associated with dystrophinopathies, cardiomyopathy is emerging as a major cause of death in people carrying dystrophin gene mutations that remain without a targeted cure even with new treatment directions and advances in modelling abilities. The reasons for the stunted progress in ameliorating dystrophin-associated cardiomyopathy (DAC) can be explained by the difficulties in detecting pathophysiological mechanisms which can also be efficiently targeted within the heart in the widest patient population. New perspectives are clearly required to effectively address the unanswered questions concerning the identification of authentic and effectual readouts of DAC occurrence and severity. A potential way forward to achieve further therapy breakthroughs lies in combining multiomic analysis with advanced preclinical precision models. This review presents the fundamental discoveries made using relevant models of DAC and how omics approaches have been incorporated to date.
Anti-Inflammatory Effects of Endogenously Released Adenosine in Synovial Cells of Osteoarthritis and Rheumatoid Arthritis Patients
Authors: Sohn Rebecca , Junker Marius , Meurer Andrea , Zaucke Frank , Straub Rainer H. , Jenei-Lanzl Zsuzsa
Published: August 2021

Exogenous adenosine and its metabolite inosine exert anti-inflammatory effects in synoviocytes of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. We analyzed whether these cells are able to synthesize adenosine/inosine and which adenosine receptors (ARs) contribute to anti-inflammatory effects. The functionality of synthesizing enzymes and ARs was tested using agonists/antagonists. Both OA and RA cells expressed CD39 (converts ATP to AMP), CD73 (converts AMP to adenosine), ADA (converts adenosine to inosine), ENT1/2 (adenosine transporters), all AR subtypes (A1, A2A, A2B and A3) and synthesized predominantly adenosine. The CD73 inhibitor AMPCP significantly increased IL-6 and decreased IL-10 in both cell types, while TNF only increased in RA cells. The ADA inhibitor DAA significantly reduced IL-6 and induced IL-10 in both OA and RA cells. The A2AAR agonist CGS 21680 significantly inhibited IL-6 and induced TNF and IL-10 only in RA, while the A2BAR agonist BAY 60-6583 had the same effect in both OA and RA. Taken together, OA and RA synoviocytes express the complete enzymatic machinery to synthesize adenosine/inosine; however, mainly adenosine is responsible for the anti- (IL-6 and IL-10) or pro-inflammatory (TNF) effects mediated by A2A- and A2BAR. Stimulating CD39/CD73 with simultaneous ADA blockage in addition to TNF inhibition might represent a promising therapeutic strategy.
Altered Differentiation of Tendon-Derived Stem Cells in Diabetic Conditions Mediated by Macrophage Migration Inhibitory Factor
Authors: Kim Du-Hwan , Noh Sun-Up , Chae Seoung-Wan , Kim Sang-Jun , Lee Yong-Taek
Published: August 2021

The purpose of our study was to evaluate the role of macrophage migration inhibitory factor (MIF) in the differentiation of tendon-derived stem cells (TdSCs) under hyperglycemic conditions. In the in vivo experiment, rats were classified into diabetic (DM) and non-DM groups depending on the intraperitoneal streptozotocin (STZ) or saline injection. Twelve-week after STZ injection, the supraspinatus tendon was harvested and prepared for histological evaluation and real-time reverse transcription polymerase chain reaction for osteochondrogenic (aggrecan, BMP-2, and Sox9) and tenogenic (Egr1, Mkx, scleraxis, type 1 collagen, and Tnmd) markers. For the in vitro experiment, TdSCs were isolated from healthy rat Achilles tendons. Cultured TdSCs were treated with methylglyoxal and recombinant MIF or MIF gene knockdown to determine the effect of hyperglycemic conditions and MIF on the differentiation function of TdSCs. These conditions were classified into four groups: hyperglycemic-control group, hyperglycemic-recombinant-MIF group, hyperglycemic-knockdown-MIF group, and normal-control group. The mRNA expression of osteochondrogenic and tenogenic markers was compared among the groups. In the in vivo experiment, the mRNA expression of all osteochondrogenic and tenogenic differentiation markers in the DM group was significantly higher and lower than that in the non-DM group, respectively. Similarly, in the in vitro experiments, the expression of all osteochondrogenic and tenogenic differentiation markers was significantly upregulated and downregulated, respectively, in the hyperglycemic-control group compared to that in the normal-control group. The hyperglycemic-knockdown-MIF group demonstrated significantly decreased expression of all osteochondrogenic differentiation markers and increased expression of only some tenogenic differentiation markers compared with the hyperglycemic-control group. In contrast, the hyperglycemic-recombinant-MIF group showed significantly increased expression of all osteochondrogenic differentiation markers, but no significant difference in any tenogenic marker level, compared to the hyperglycemic-control group. These results suggest that tendon homeostasis could be affected by hyperglycemic conditions, and MIF appears to alter the differentiation of TdSCs via enhancement of the osteochondrogenic differentiation in hyperglycemic conditions. These are preliminary findings, and must be confirmed in a further study.
Characterization of Lipids in Saliva, Tears and Minor Salivary Glands of Sjögren’s Syndrome Patients Using an HPLC/MS-Based Approach
Authors: Fineide Fredrik , Chen Xiangjun , Bjellaas Thomas , Vitelli Valeria , Utheim Tor Paaske , Jensen Janicke Liaaen , Galtung Hilde Kanli
Published: August 2021

The diagnostic work-up of primary Sjögren’s syndrome (pSS) includes quantifying saliva and tear production, evaluation of autoantibodies in serum and histopathological analysis of minor salivary glands. Thus, the potential for further utilizing these fluids and tissues in the quest to find better diagnostic and therapeutic tools should be fully explored. Ten samples of saliva and tears from female patients diagnosed with pSS and ten samples of saliva and tears from healthy females were included for lipidomic analysis of tears and whole saliva using high-performance liquid chromatography coupled to time-of-flight mass spectrometry. In addition, lipidomic analysis was performed on minor salivary gland biopsies from three pSS and three non-SS females. We found significant differences in the lipidomic profiles of saliva and tears in pSS patients compared to healthy controls. Moreover, there were differences in individual lipid species in stimulated saliva that were comparable to those of glandular biopsies, representing an intriguing avenue for further research. We believe a comprehensive elucidation of the changes in lipid composition in saliva, tears and minor salivary glands in pSS patients may be the key to detecting pSS-related dry mouth and dry eyes at an early stage. The identified differences may illuminate the path towards future innovative diagnostic methodologies and treatment modalities for alleviating pSS-related sicca symptoms.
The Arabidopsis HY2 Gene Acts as a Positive Regulator of NaCl Signaling during Seed Germination
Authors: Piao Mingxin , Zou Jinpeng , Li Zhifang , Zhang Junchuan , Yang Liang , Yao Nan , Li Yuhong , Li Yaxing , Tang Haohao , Zhang Li , Yang Deguang , Yang Zhenming , Du Xinglin , Zuo Zecheng
Published: August 2021

Phytochromobilin (PΦB) participates in the regulation of plant growth and development as an important synthetase of photoreceptor phytochromes (phy). In addition, Arabidopsis long hypocotyl 2 (HY2) appropriately works as a key PΦB synthetase. However, whether HY2 takes part in the plant stress response signal network remains unknown. Here, we described the function of HY2 in NaCl signaling. The hy2 mutant was NaCl-insensitive, whereas HY2-overexpressing lines showed NaCl-hypersensitive phenotypes during seed germination. The exogenous NaCl induced the transcription and the protein level of HY2, which positively mediated the expression of downstream stress-related genes of RD29A, RD29B, and DREB2A. Further quantitative proteomics showed the patterns of 7391 proteins under salt stress. HY2 was then found to specifically mediate 215 differentially regulated proteins (DRPs), which, according to GO enrichment analysis, were mainly involved in ion homeostasis, flavonoid biosynthetic and metabolic pathways, hormone response (SA, JA, ABA, ethylene), the reactive oxygen species (ROS) metabolic pathway, photosynthesis, and detoxification pathways to respond to salt stress. More importantly, ANNAT1–ANNAT2–ANNAT3–ANNAT4 and GSTU19–GSTF10–RPL5A–RPL5B–AT2G32060, two protein interaction networks specifically regulated by HY2, jointly participated in the salt stress response. These results direct the pathway of HY2 participating in salt stress, and provide new insights for the plant to resist salt stress.
Investigation of Bemethyl Biotransformation Pathways by Combination of LC–MS/HRMS and In Silico Methods
Authors: Belinskaia Daria A. , Savelieva Elena I. , Karakashev Georgy V. , Orlova Olga I. , Leninskii Mikhail A. , Khlebnikova Nataliia S. , Shestakova Natalia N. , Kiskina Alexandra R.
Published: August 2021

Bemethyl is an actoprotector, an antihypoxant, and a moderate psychostimulant. Even though the therapeutic effectiveness of bemethyl is well documented, there is a gap in knowledge regarding its metabolic products and their quantitative and qualitative characteristics. Since 2018, bemethyl is included to the Monitoring Program of the World Anti-Doping Agency, which highlights the challenge of identifying its urinary metabolites. The objective of the study was to investigate the biotransformation pathways of bemethyl using a combination of liquid chromatography-high-resolution mass spectrometry and in silico studies. Metabolites were analyzed in a 24 h rat urine collected after oral administration of bemethyl at a single dose of 330 mg/kg. The urine samples were prepared for analysis by a procedure developed in the present work and analyzed by high performance liquid chromatography–tandem mass spectrometry. For the first time, nine metabolites of bemethyl with six molecular formulas were identified in rat urine. The most abundant metabolite was a benzimidazole–acetylcysteine conjugate; this biotransformation pathway is associated with the detoxification of xenobiotics. The BioTransformer and GLORY computational tools were used to predict bemethyl metabolites in silico. The molecular docking of bemethyl and its derivatives to the binding site of glutathione S-transferase has revealed the mechanism of bemethyl conjugation with glutathione. The findings will help to understand the pharmacokinetics and pharmacodynamics of actoprotectors and to improve antihypoxant and adaptogenic therapy.
Signaling Pathways and Downstream Effectors of Host Innate Immunity in Plants
Authors: Kumar Jitendra , Ramlal Ayyagari , Kumar Kamal , Rani Anita , Mishra Vachaspati
Published: August 2021

Phytopathogens, such as biotrophs, hemibiotrophs and necrotrophs, pose serious stress on the development of their host plants, compromising their yields. Plants are in constant interaction with such phytopathogens and hence are vulnerable to their attack. In order to counter these attacks, plants need to develop immunity against them. Consequently, plants have developed strategies of recognizing and countering pathogenesis through pattern-triggered immunity (PTI) and effector-triggered immunity (ETI). Pathogen perception and surveillance is mediated through receptor proteins that trigger signal transduction, initiated in the cytoplasm or at the plasma membrane (PM) surfaces. Plant hosts possess microbe-associated molecular patterns (P/MAMPs), which trigger a complex set of mechanisms through the pattern recognition receptors (PRRs) and resistance (R) genes. These interactions lead to the stimulation of cytoplasmic kinases by many phosphorylating proteins that may also be transcription factors. Furthermore, phytohormones, such as salicylic acid, jasmonic acid and ethylene, are also effective in triggering defense responses. Closure of stomata, limiting the transfer of nutrients through apoplast and symplastic movements, production of antimicrobial compounds, programmed cell death (PCD) are some of the primary defense-related mechanisms. The current article highlights the molecular processes involved in plant innate immunity (PII) and discusses the most recent and plausible scientific interventions that could be useful in augmenting PII.
Doxorubicin Paradoxically Ameliorates Tumor-Induced Inflammation in Young Mice
Authors: Abdelgawad Ibrahim Y. , Grant Marianne K. O. , Popescu Flavia E. , Largaespada David A. , Zordoky Beshay N.
Published: August 2021

Doxorubicin (DOX) is one of the most widely used chemo-therapeutic agents in pediatric oncology. DOX elicits an inflammatory response in multiple organs, which contributes to DOX-induced adverse effects. Cancer itself causes inflammation leading to multiple pathologic conditions. The current study investigated the inflammatory response to DOX and tumors using an EL4-lymphoma, immunocompetent, juvenile mouse model. Four-week old male C57BL/6N mice were injected subcutaneously with EL4 lymphoma cells (5 × 104 cells/mouse) in the flank region, while tumor-free mice were injected with vehicle. Three days following tumor implantation, both tumor-free and tumor-bearing mice were injected intraperitoneally with either DOX (4 mg/kg/week) or saline for 3 weeks. One week after the last DOX injection, the mice were euthanized and the hearts, livers, kidneys, and serum were harvested. Gene expression and serum concentration of inflammatory markers were quantified using real-time PCR and ELISA, respectively. DOX treatment significantly suppressed tumor growth in tumor-bearing mice and caused significant cardiac atrophy in tumor-free and tumor-bearing mice. EL4 tumors elicited a strong inflammatory response in the heart, liver, and kidney. Strikingly, DOX treatment ameliorated tumor-induced inflammation paradoxical to the effect of DOX in tumor-free mice, demonstrating a widely divergent effect of DOX treatment in tumor-free versus tumor-bearing mice.
Candidate Genes and Proteomic Biomarkers of Serum and Urine in Medication-Overuse Headache
Authors: Shnayder Natalia A. , Sharavii Victoria B. , Petrova Marina M. , Moskaleva Polina V. , Pozhilenkova Elena A. , Kaskaeva Darya S. , Tutynina Olga. V. , Popova Tatiana E. , Garganeeva Natalia P. , Nasyrova Regina F.
Published: August 2021

Chronic headache is a topical problem of neurology, psychiatry and general practice. The medication-overuse headache (MOH) is one of the leading pathologies in the structure of chronic headache. However, early diagnosis of the MOH is challenging. We analyzed potential proteomic biomarkers of serum and urine in patients with MOH. Methods: We searched PubMed, Springer, Scopus, Web of Science, ClinicalKey, and Google Scholar databases for English publications over the past 10 years using keywords and their combinations. Results: We found and analyzed seven studies that met the search criteria for the purpose of the review, including 24 serum proteomic biomarkers and 25 urine proteomic biomarkers of MOH. Moreover, the candidate genes and locus of the studied serum (vitamin D-binding protein, lipocalin-type prostaglandin D2 synthase, apolipoprotein E, etc.) and urine proteomic biomarkers (uromodulin, alpha-1-microglobulin, zinc-alpha-2-glycoprotein, etc.) of MOH are presented in this review. Conclusions: The serum and urine proteomic biomarkers of MOH can potentially help with the identification of patients with MOH development. Due to the relevance of the problem, the authors believe that further investigation of the MOH proteomic biomarkers in different ethnic and racial groups of patients with primary headache is necessary. In addition, it is important to investigate whether medications of different drug classes influence the levels of serum and urine proteomic biomarkers.
The Importance of Digging into the Genetics of SMN Genes in the Therapeutic Scenario of Spinal Muscular Atrophy
Authors: Costa-Roger Mar , Blasco-Pérez Laura , Cuscó Ivon , Tizzano Eduardo F.
Published: August 2021

After 26 years of discovery of the determinant survival motor neuron 1 and the modifier survival motor neuron 2 genes (SMN1 and SMN2, respectively), three SMN-dependent specific therapies are already approved by FDA and EMA and, as a consequence, worldwide SMA patients are currently under clinical investigation and treatment. Bi-allelic pathogenic variants (mostly deletions) in SMN1 should be detected in SMA patients to confirm the disease. Determination of SMN2 copy number has been historically employed to correlate with the phenotype, predict disease evolution, stratify patients for clinical trials and to define those eligible for treatment. In view that discordant genotype-phenotype correlations are present in SMA, besides technical issues with detection of SMN2 copy number, we have hypothesized that copy number determination is only the tip of the iceberg and that more deepen studies of variants, sequencing and structures of the SMN2 genes are necessary for a better understanding of the disease as well as to investigate possible influences in treatment responses. Here, we highlight the importance of a comprehensive approach of SMN1 and SMN2 genetics with the perspective to apply for better prediction of SMA in positive neonatal screening cases and early diagnosis to start treatments.