bluuebunny/crossref_metadata_2025 huggingface dataset:
Neighborhood Energy Modeling and Monitoring: A Case Study
Authors: Causone Francesco , Scoccia Rossano , Pelle Martina , Colombo Paola , Motta Mario , Ferroni Sibilla
Published: June 2021

Cities and nations worldwide are pledging to energy and carbon neutral objectives that imply a huge contribution from buildings. High-performance targets, either zero energy or zero carbon, are typically difficult to be reached by single buildings, but groups of properly-managed buildings might reach these ambitious goals. For this purpose we need tools and experiences to model, monitor, manage and optimize buildings and their neighborhood-level systems. The paper describes the activities pursued for the deployment of an advanced energy management system for a multi-carrier energy grid of an existing neighborhood in the area of Milan. The activities included: (i) development of a detailed monitoring plan, (ii) deployment of the monitoring plan, (iii) development of a virtual model of the neighborhood and simulation of the energy performance. Comparisons against early-stage energy monitoring data proved promising and the generation system showed high efficiency (EER equal to 5.84), to be further exploited.
Flow Pattern and Resistance Characteristics of Gas–Liquid Two-Phase Flow with Foam under Low Gas–Liquid Flow Rate
Authors: Wang Bin , Hu Jianguo , Chen Weixiong , Cheng Zhongzhao , Gao Fei
Published: June 2021

To reduce the cost of arranging air foam flooding equipment at each wellhead, a method of establishing centralized air foam flooding injection stations is proposed. The flow pattern and resistance characteristics of air foam flooding mixtures in different initial conditions are studied. Experimental results indicate that the probability density function of stratified flow is obtained by comparing stainless steel and transparent pipes. If the gas–liquid ratio is kept constant, then the shape of the probability density function remains unchanged in both stainless steel and transparent tubes. Meanwhile, the flow pattern under the gas–liquid ratio is determined by comparing the image recognition results with the probability density function, and a formula for calculating the resistance and pressure drop of the gas and liquid two-phase flow in the horizontal and upward pipes is established. Compared with the experiments, the error results of the calculation are small. Thus, the proposed equations can be used to predict the flow resistance of real air foam flooding.
Effect of Integrating Metal Wire Mesh with Spray Injection for Liquid Piston Gas Compression
Authors: Ahn Barah , Patil Vikram C. , Ro Paul I.
Published: June 2021

Heat transfer enhancement techniques used in liquid piston gas compression can contribute to improving the efficiency of compressed air energy storage systems by achieving a near-isothermal compression process. This work examines the effectiveness of a simultaneous use of two proven heat transfer enhancement techniques, metal wire mesh inserts and spray injection methods, in liquid piston gas compression. By varying the dimension of the inserts and the pressure of the spray, a comparative study was performed to explore the plausibility of additional improvement. The addition of an insert can help abating the temperature rise when the insert does not take much space or when the spray flowrate is low. At higher pressure, however, the addition of spacious inserts can lead to less efficient temperature abatement. This is because inserts can distract the free-fall of droplets and hinder their speed. In order to analytically account for the compromised cooling effects of droplets, Reynolds number, Nusselt number, and heat transfer coefficients of droplets are estimated under the test conditions. Reynolds number of a free-falling droplet can be more than 1000 times that of a stationary droplet, which results in 3.95 to 4.22 times differences in heat transfer coefficients.
Implementing an Extended Kalman Filter for SoC Estimation of a Li-Ion Battery with Hysteresis: A Step-by-Step Guide
Authors: Rzepka Benedikt , Bischof Simon , Blank Thomas
Published: June 2021

The growing share of renewable energies in power production and the rise of the market share of battery electric vehicles increase the demand for battery technologies. In both fields, a predictable operation requires knowledge of the internal battery state, especially its state of charge (SoC). Since a direct measurement of the SoC is not possible, Kalman filter-based estimation methods are widely used. In this work, a step-by-step guide for the implementation and tuning of an extended Kalman filter (EKF) is presented. The structured approach of this paper reduces efforts compared with empirical filter tuning and can be adapted to various battery models, systems, and cell types. This work can act as a tutorial describing all steps to get a working SoC estimator based on an extended Kalman filter.
Modeling Electric Vehicle Charging Demand with the Effect of Increasing EVSEs: A Discrete Event Simulation-Based Model
Authors: Lopez Neil Stephen , Allana Adrian , Biona Jose Bienvenido Manuel
Published: June 2021

Electric vehicle (EV) use is growing at a steady rate globally. Many countries are planning to ban internal combustion engines by 2030. One of the key issues needed to be addressed before the full-scale deployment of EVs is ensuring energy security. Various studies have developed models to simulate and study hourly electricity demand from EV charging. In this study, we present an improved model based on discrete event simulation, which allows for modeling characteristics of individual EV users, including the availability of electric vehicle supply equipment (EVSE) outside homes and the charging threshold of each EV user. The model is illustrated by simulating 1000 random electric vehicles generated using data from an actual survey. The results agree with previous studies that daily charging demands do not significantly vary. However, the results show a significant shift in charging schedule during weekends. Moreover, the simulation demonstrated that the charging peak demand can be reduced by as much as 11% if EVSEs are made more available outside homes. Interestingly, a behavioral solution, such as requiring users to fully utilize their EV’s battery capacity, is more effective in reducing the peak demand (14–17%). Finally, the study concludes by discussing a few potential implications on electric vehicle charging policy.
Evaluation of PV and CSP Systems to Supply Power in the Zimbabwe Mining Sector
Authors: Maronga Anesu , Nyoni Kumbuso Joshua , Tuohy Paul Gerard , Shane Agabu
Published: June 2021

The drought that occurred in Zimbabwe in 2020 affected the country’s main hydro-power station causing the electricity supply to be less secure and reliable. This challenge resulted in load-shedding, which is not desirable to mining companies that require constant and reliable power for their operations. In that regard, a techno-economic analysis was carried out to assess the potential of integrating concentrated solar power (+thermal storage) and photovoltaics (+battery storage) to supply power at a typical mine in Zimbabwe. Two scenarios were simulated—a base case with no exports to the grid and another case where exports were allowed. The models were evaluated based on the generated renewable energy offsetting the demand from the mine, the energy exported, the grid contribution, the levelised cost of electricity and the net present value. The results show that the addition of a battery storage system to PV improves the percentage of the load offset by the renewable system and the generated energy by the renewable system by almost double. However, the installation cost, required land, LCOE, and simple pay-back also increased by approximately a factor of 2. The addition of a thermal storage system to CSP increased the generated energy, the capacity factor, and the renewable energy contribution by approximately a factor of 2. However, the land required for development and the installation costs also nearly doubled.
Large-Eddy Simulation of Wind Turbine Flows: A New Evaluation of Actuator Disk Models
Authors: Revaz Tristan , Porté-Agel Fernando
Published: June 2021

Large-eddy simulation (LES) with actuator models has become the state-of-the-art numerical tool to study the complex interaction between the atmospheric boundary layer (ABL) and wind turbines. In this paper, a new evaluation of actuator disk models (ADMs) for LES of wind turbine flows is presented. Several details of the implementation of such models are evaluated based on a test case studied experimentally. In contrast to other test cases used in previous similar studies, the present test case consists of a wind turbine immersed in a realistic turbulent boundary-layer flow, for which accurate data for the turbine, the flow, the thrust and the power are available. It is found that the projection of the forces generated by the turbine into the flow solver grid is crucial for rotor predictions, especially for the power, and less important for the wake flow prediction. In this context, the projection of the forces into the flow solver grid should be as accurate as possible, in order to conserve the consistency between the computed axial velocity and the projected axial force. Also, the projection of the force is found to be much more important in the rotor plane directions than in the streamwise direction. It is found that for the case of a wind turbine immersed in a realistic turbulent boundary-layer flow, the potential spurious numerical oscillations originating from sharp force projections are not harmful to the results. By comparing an advanced model which computes the non-uniform distribution of the turbine forces over the rotor with a simple model which assumes uniform effects of the turbine forces, it is found that both can lead to accurate results for the far wake flow and the thrust and power predictions. However, the comparison shows that the advanced model leads to better results for the near wake flow. In addition, it is found that the simple model overestimates the rotor velocity prediction in comparison to the advanced model. These elements are explained by the lack of local feedback between the axial velocity and the axial force in the simple model. By comparing simulations with and without including the effects of the nacelle and tower, it is found that the consideration of the nacelle and tower is relatively important both for the near wake and the power prediction, due to the shadow effects. The grid resolution is not found to be critical once a reasonable resolution is used, i.e., in the order of 10 grid points along each direction across the rotor. The comparison with the experimental data shows that an accurate prediction of the flow, thrust, and power is possible with a very reasonable computational cost. Overall, the results give important guidelines for the implementation of ADMs for LES.
Eco-Trends in Energy Solutions on Cruise Ships
Authors: Kizielewicz Joanna
Published: June 2021

Today the world’s largest cruise ships can take on board more than 6000 passengers and almost 3000 crew members. Managing a significant number of people and all equipment and operations on ships requires the delivery of tens of thousands of kilowatts, which poses a huge challenge for both cruise ship builders and ports supporting these ships as well as for ship owners themselves, as the costs involved represent the largest share in the structure of expenditure in cruise shipping companies. In recent years, various communities and institutions, including the International Maritime Organisation and the European Union, exert pressure on cruise ship owners to use green renewable energy solutions. For these reasons, cruise ship owners are constantly looking for cost-effective and environmentally responsible solutions regarding new energy sources for ships. The aim of this paper is to identify modern solutions applied on cruise ships in the field of energy generation and to indicate benefits for the environment and ship owners in this respect. The following research questions were formulated: (1) What factors force cruise ship owners to introduce modern energy policy solutions? (2) What kind of green energy solutions are currently used on cruise ships? (3) What kind of renewable energy solutions do cruise ship owners use to reduce energy consumption on board cruise ships? The research was conducted by applying a few research methods, i.e., desk research method and exploration method, critical and comparative analysis, and also inductive and deductive reasoning. The results of this research can provide an interesting source of information for cruise ship owners, cruise seaport authorities, and shipyards involved in the construction of new vessels.
Autochthonous Enterococcus durans PFMI565 and Lactococcus lactis subsp. lactis BGBU1–4 in Bio-Control of Listeria monocytogenes in Ultrafiltered Cheese
Authors: Ivanovic Marina , Mirkovic Nemanja , Mirkovic Milica , Miocinovic Jelena , Radulovic Ana , Solevic Knudsen Tatjana , Radulovic Zorica
Published: June 2021

Nowadays, consumers are interested in cheese produced without chemical additives or high-temperature treatments, among which, protective lactic acid bacteria (LAB) cultures could play a major role. In this study, the aims were to isolate, identify and characterize antilisterial LAB from traditionally produced cheese, and utilize suitable LAB in cheese production. Among 200 isolated LAB colonies, isolate PFMI565, with the strongest antilisterial activity, was identified as Enterococcus durans. E. durans PFMI565 was sensitive to clinically important antibiotics (erytromicin, tetracycline, kanamycin, penicillin, vancomycin) and had low acidifying activity in milk. E. durans PFMI565 and the previously isolated bacteriocin producer, Lactococcus lactis subsp. lactis BGBU1–4, were tested for their capability to control Listeria monocytogenes in experimentally contaminated ultrafiltered (UF) cheeses during 35 days of storage at 4 °C. The greatest reductions of L. monocytogenes numbers were achieved in UF cheese made with L. lactis subsp. lactis BGBU1–4 or with the combination of L. lactis subsp. lactis BGBU1–4 and E. durans PFMI565. This study underlines the potential application of E. durans PFMI565 and L. lactis subsp. lactis BGBU1–4 in bio-control of L. monocytogenes in UF cheese.
Efficiency of DNA Mini-Barcoding to Assess Mislabeling in Commercial Fish Products in Italy: An Overview of the Last Decade
Authors: Filonzi Laura , Vaghi Marina , Ardenghi Alessia , Rontani Pietro Maria , Voccia Andrea , Nonnis Marzano Francesco
Published: June 2021

The problem of fish traceability in processed products is still an important issue in food safety. Major attention is nowadays dedicated to consumer health and prevention of possible frauds regulated by national and international laws. For this reason, a technical approach is fundamental in revealing mislabeling at different levels. In particular, the use of genetic markers has been standardized and DNA barcoding is considered the gold-standard strategy to examine and prevent species substitution. Considering the richness of available DNA databases, it is nowadays possible to rapidly reach a reliable taxonomy at the species level. Among different approaches, an innovative method based on DNA mini barcoding has recently been proposed at an international level. Starting from this evidence, we herein illustrate an investigation dealing with the evolution of this topic in Italy over the last decade. The molecular analysis of 71 commercial fish samples based on mini-COI sequencing with two different primer sets reached an amplification success rate of 87.3 and 97.2%. The investigation revealed four major frauds (5.8%) and four minor ones (5.8%). Results highlighted a decrease in incorrect labeling in Italy from 32% to 11.6% over the last decade, although a recurrent involvement of “endangered” species sensu IUCN was still observed.
Influence of the Production System (Intensive vs. Extensive) at Farm Level on Proximate Composition and Volatile Compounds of Portuguese Lamb Meat
Authors: Echegaray Noemí , Domínguez Rubén , Cadavez Vasco A. P. , Bermúdez Roberto , Purriños Laura , Gonzales-Barron Ursula , Hoffman Ettiene , Lorenzo José M.
Published: June 2021

Today’s society demands healthy meat with a special emphasis on integrated animal husbandry combined with the concern for animal welfare. In this sense, the raising of lambs in an extensive system has been one of the most common practices, which results in meats with high nutritional value. However, both the production system and the diet play a fundamental role in the chemical composition of the meat, which has a direct impact on the content of volatile compounds. Thus, the aim of this study was to determine the effect of two production systems (intensive and extensive) on the chemical composition and volatile profile of lamb meat. Twenty-eight lambs of the Bordaleira-de-Entre-Douro-e-Minho (BEDM) sheep breed were raised for meat production under the intensive or extensive system and were fed with concentrate and pasture, respectively. All animals were carried out in the muscle longissimus thoracis et lumborum. Results evidenced that all the composition parameters were affected by the production system. Extensively-reared lambs produced meat with the highest fat and protein contents, while these animals had the lowest percentages of moisture and ash. Similarly, the total content of volatile compounds was affected (p < 0.05) by the production system and were higher in the meat of lambs reared extensively. Furthermore, the content of total acids, alcohols, aldehydes, esters, ethers, furans and sulfur compounds as well as most of the individual compounds were also affected (p < 0.05) by the production system, whereas total hydrocarbons and ketones were not affected (p > 0.05). As a general conclusion, the production system had very high influence not only in proximate composition but also in the volatile compounds.
COVID-19 Vaccination: Status and Willingness to Be Vaccinated among Employees in Health and Welfare Care in Germany
Authors: Kozak Agnessa , Nienhaus Albert
Published: June 2021

Healthcare workers are at particular risk due to their occupational exposure to SARS-CoV-2. Therefore, they belong to the top priority group for vaccination. However, earlier studies show that nursing staff in particular are hesitant to be inoculated. This study presents the current picture with regard to vaccination status, willingness, vaccine preference, and reasons for or against a COVID-19 vaccination among health and welfare workers. An online survey was conducted between 4 March and 10 April 2021 among professional associations and providers of health and social services. Data sets of n = 3401 participants were analyzed. Of these, 62% stated that they had already been vaccinated at least once. A further 22% wanted to be vaccinated, while 6.6% were still hesitant and 9% refused to be vaccinated. Preference was given to predominantly mRNA-based vaccines. Altogether, there was a high vaccination rate and a great willingness to be vaccinated (>80%) across all professional groups and fields of work. Among nursing staff, the total figure was 83.5%. The percentage was highest in geriatric care at 87.5%. Contrary to findings of earlier surveys, vaccination willingness has risen in all professional groups during the course of the vaccination campaign in Germany.
Skeletal Muscle Mass and Higher-Level Functional Capacity in Female Community-Dwelling Older Adults
Authors: Wakayama Shuichi , Fujita Yoshihiko , Fujii Keisuke , Sasaki Takeshi , Yuine Hiroshi , Hotta Kazushi
Published: June 2021

Purpose: In this study, our purpose was to examine the relationship between skeletal muscle mass and higher-level functional capacity in female community-dwelling older adults. Participant(s) and Methods: In this cross-sectional study, we targeted 55 female community-dwelling older adults aged 65 years and above participating in long-term care prevention classes in Ibaraki Prefecture between 2018 and 2020. We excluded individuals with cognitive impairment and those judged as having sarcopenia. The variables of interest included age, height, weight, body mass index, skeletal muscle mass index (SMI), handgrip strength, step count, and family structure. We calculated the SMI by dividing the extremities’ total lean mass by the square of the height (in m), while the number of steps was calculated using the three-axis accelerometer Actigraph GT3X®. We measured skeletal muscle mass via bioelectrical impedance analysis using the InBody270 body composition analyzer and muscular strength as grip strength. Results: We observed significant relationships between skeletal muscle mass and Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) (β = 0.336, p < 0.01) and handgrip strength (β = 0.230). Conclusion: In this study, a relationship between skeletal muscle mass and higher-level functional capacity was demonstrated among elderly female community residents.
Effects of a Web-Based Educational Program Regarding Physical Restraint Reduction in Long-Term Care Settings on Nursing Students: A Cluster Randomized Controlled Trial
Authors: Kong Eun-Hi , Kim Myoungsuk , Kim Seonho
Published: June 2021

Physical restraint is still frequently used in many countries. However, a lack of education hinders physical restraint reduction in long-term care facilities. No study has yet to examine the effects of physical restraint reduction education on nursing students. This study aimed to evaluate the effects of a web-based educational program of physical restraint reduction on nursing students’ knowledge and perceptions. A cluster randomized controlled and single-blind design was used. This study was conducted at four nursing schools in South Korea. A total of 169 undergraduate nursing students completed this study. Using random allocation, two nursing schools (85 students) were allocated as the experimental group and the other two schools (84 students) as the control group. The experimental group received the web-based educational program, and the control group did not receive the educational program. Data were collected immediately before and after the web-based educational program. The experimental group’s knowledge and perceptions significantly improved between pre-test and post-test. The analysis of covariance showed statistically significant differences between groups in knowledge (p < 0.001) and perceptions (p < 0.001) over time, revealing positive effects of the web-based educational program. The web-based educational program regarding physical restraint reduction positively affected nursing students’ knowledge and perceptions. Future studies are required to examine the educational program’s longitudinal effects with more rigorous measurements and research methods.
Suicidal Ideation and Predictors of Psychological Distress during the COVID-19 Pandemic in Eswatini: A Population-Based Household Telephone Survey
Authors: Shongwe Mduduzi Colani , Huang Song-Lih
Published: June 2021

The unpredictability of the COVID-19 pandemic can induce psychological distress in individuals. We investigated perceived stressors, prevalence of psychological distress and suicidal ideation, and predictors of psychological distress among adults during the COVID-19 pandemic in Eswatini. This study was a cross-sectional, population-based household telephone survey of 993 conveniently sampled adults (18+ years) from all the four administrative regions of Eswatini. Data were collected between 9 June and 18 July 2020 during the first wave of the COVID-19 pandemic, when the country was under a partial lockdown. COVID-19-related psychological distress was assessed using the Kessler 6-item Psychological Distress Scale (K6). We performed weighted modified Poisson regression analyses to identify significant predictors of moderate/severe psychological distress (K6 scores: ≥5). The weighted prevalences of moderate (K6 scores: 5–12) and severe psychological distress (K6 scores: ≥13) were 41.7% and 5.4%, respectively. Participants reported several perceived COVID-19-related stressors, including worries and fears of the contagion-specific death, serious need for food and money, and concerns about loss of income or business. The weighted prevalence of suicidal ideation was 1.5%. Statistically significant predictors of increased risk for moderate/severe psychological distress included living in the Hhohho and Manzini regions; feeling not well informed about COVID-19; feeling lonely; having received COVID-19 food or financial relief from the government; feeling burdened by the lockdown; being married; and being youth (18–24 years). The results call for the government to urgently augment the provision of mental health services during the pandemic. Mental health practitioners and programs may use several stressors and risk factors identified in this study to inform interventions and government policies aimed at reducing psychological distress induced by the pandemic.
The Association between a Novel Baby-Friendly Hospital Program and Equitable Support for Breastfeeding in Vietnam
Authors: Joyce Caroline M. , Hou Sherry Shu-Yeu , Ta Binh T. T. , Vu Duong Hoang , Mathisen Roger , Vincent Ilona , Duc Vinh Nguyen , Nandi Arijit
Published: June 2021

Background: Rates of early initiation of breastfeeding are low in Southeast Asia, despite evidence that increased initiation of early breastfeeding would lead to better long-term infant and child health and decrease inequities in long-term health and well-being. In response, a novel performance-based, baby-friendly hospital program designates hospitals that adhere to evidence-based early essential newborn care (EENC) and breastfeeding interventions as Centers of Excellence for Breastfeeding (COE). This study examined whether hospital participation in the program was associated with better breastfeeding outcomes. Methods: Hospitals (n = 28) were invited into the program in December 2018. Hospitals developed an improvement plan for promoting a breastfeeding-friendly environment and meeting the standards of the COE accreditation process and were enrolled on a rolling basis over the course of a year. Post-partum surveys were conducted with parents (n = 9585) from January 2019 through April 2020 to assess their breastfeeding and post-partum experience. Segmented regression models were used to assess how breastfeeding outcomes evolved before and after hospital enrollment in the COE program. Results: Enrollment was associated with a 6 percentage-point (95% CI: 3, 9) increase in the level of early initiation of breastfeeding, which continued to increase in the post-enrollment period, and a 5 percentage-point (95% CI: 2, 9) increase in the level of exclusive breastfeeding during hospital stay. We did not observe evidence that enrollment was immediately associated with receipt of lactation counseling or exclusive breastfeeding at survey time. Conclusion: The prevalence of early and exclusive breastfeeding increased after enrollment in the COE program, suggesting that the program has the potential to improve breastfeeding initiation rates and longer-term child health and well-being. Further research should be conducted to examine whether the program has an impact on the overall duration of breastfeeding.
School Nurses’ Experience of Working in School Health Service during the COVID-19 Pandemic in Sweden
Authors: Martinsson Eva , Garmy Pernilla , Einberg Eva-Lena
Published: June 2021

The COVID-19 pandemic has had a vast influence on Swedish society. Related recommendations and political decisions have greatly affected schools. This study aimed to describe school nurses’ experience working in Sweden during the pandemic in 2020. The study used a qualitative method with an inductive approach. Interviews with 17 school nurses in five focus groups and one individual interview were conducted. Qualitative content analysis was used. The impact of the pandemic on school nurses can be described through three categories: “Changes in working methods in relation to the students/guardians”, “Impact on cooperation with school staff”, and “The school nurse’s prerequisites for major changes.” Overall, school nurses experienced a transition to a digital way of working. Policies and decisions on global and local levels affected the work situations of school nurses as well as the school nurses’ social, cultural, and professional experience. The highest priority for school nurses is students, and school nurses adapted their working methods to give support to students during the changing circumstances. School nurses are both pragmatic and highly creative. Cooperation with other school professions is critical, as is support and guidance during crisis situations.
Developmental Neurotoxicity of Environmentally Relevant Pharmaceuticals and Mixtures Thereof in a Zebrafish Embryo Behavioural Test
Authors: Atzei Alessandro , Jense Ingrid , Zwart Edwin P. , Legradi Jessica , Venhuis Bastiaan J. , van der Ven Leo T.M. , Heusinkveld Harm J. , Hessel Ellen V.S.
Published: June 2021

Humans are exposed daily to complex mixtures of chemical substances via food intake, inhalation, and dermal contact. Developmental neurotoxicity is an understudied area and entails one of the most complex areas in toxicology. Animal studies for developmental neurotoxicity (DNT) are hardly performed in the context of regular hazard studies, as they are costly and time consuming and provide only limited information as to human relevance. There is a need for a combination of in vitro and in silico tests for the assessment of chemically induced DNT in humans. The zebrafish (Danio rerio) embryo (ZFE) provides a powerful model to study DNT because it shows fast neurodevelopment with a large resemblance to the higher vertebrate, including the human system. One of the suitable readouts for DNT testing in the zebrafish is neurobehaviour (stimulus-provoked locomotion) since this provides integrated information on the functionality and status of the entire nervous system of the embryo. In the current study, environmentally relevant pharmaceuticals and their mixtures were investigated using the zebrafish light-dark transition test. Zebrafish embryos were exposed to three neuroactive compounds of concern, carbamazepine (CBZ), fluoxetine (FLX), and venlafaxine (VNX), as well as their main metabolites, carbamazepine 10,11-epoxide (CBZ 10,11E), norfluoxetine (norFLX), and desvenlafaxine (desVNX). All the studied compounds, except CBZ 10,11E, dose-dependently inhibited zebrafish locomotor activity, providing a distinct behavioural phenotype. Mixture experiments with these pharmaceuticals identified that dose addition was confirmed for all the studied binary mixtures (CBZ-FLX, CBZ-VNX, and VNX-FLX), thereby supporting the zebrafish embryo as a model for studying the cumulative effect of chemical mixtures in DNT. This study shows that pharmaceuticals and a mixture thereof affect locomotor activity in zebrafish. The test is directly applicable in environmental risk assessment; however, further studies are required to assess the relevance of these findings for developmental neurotoxicity in humans.
Low-to-Moderate-Intensity Resistance Exercise Is More Effective than High-Intensity at Improving Endothelial Function in Adults: A Systematic Review and Meta-Analysis
Authors: Zhang Yong , Zhang Ya-Jun , Zhang Hong-Wei , Ye Wei-Bing , Korivi Mallikarjuna
Published: June 2021

Aerobic exercise has been confirmed to improve endothelial function (EF). However, the effect of resistance exercise (RE) on EF remains controversial. We conducted this systematic review and meta-analysis on randomized controlled trials (RCTs) to determine the effect of RE and its intensities on EF. We searched Web of Science, PubMed/MEDLINE, Scopus, and Wiley Online Library, and included 15 articles (17 trials) for the synthesis. Overall, RE intervention significantly improved flow-mediated dilatation (FMD) in brachial artery (SMD = 0.76; 95% CI: 0.47, 1.05; p < 0.00001), which represents improved EF. Meta-regression showed that the RE intensity was correlated with changes in FMD (Coef. = −0.274, T = −2.18, p = 0.045). We found both intensities of RE improved FMD, but the effect size for the low- to moderate-intensity (30–70%1RM) was bigger (SMD = 1.02; 95% CI: 0.60, 1.43; p < 0.0001) than for the high-intensity (≥70%1RM; SMD = 0.48; 95% CI: 0.21, 0.74; p = 0.005). We further noticed that RE had a beneficial effect (SMD = 0.61; 95% CI: 0.13, 1.09; p = 0.01) on the brachial artery baseline diameter at rest (BADrest), and the age variable was correlated with the changes in BADrest after RE (Coef. = −0.032, T = −2.33, p = 0.038). Young individuals (<40 years) presented with a bigger effect size for BADrest (SMD = 1.23; 95% CI: 0.30, 2.15; p = 0.009), while middle-aged to elderly (≥40 years) were not responsive to RE (SMD = 0.07; 95% CI: −0.28, 0.42; p = 0.70). Based on our findings, we conclude that RE intervention can improve the EF, and low- to moderate-intensity is more effective than high-intensity.
Adverse Childhood Experiences and Problematic Media Use: Perceptions of Caregivers of High-Risk Youth
Authors: Domoff Sarah E. , Borgen Aubrey L. , Wilke Nicole , Hiles Howard Amanda
Published: June 2021

Youth with a history of adverse childhood experiences (ACEs) are more likely to develop risky health behaviors. With the increase of media use in the general population, it is likely that these high-risk youth are developing maladaptive behaviors associated with media use (i.e., problematic media use). The goals of this article are (1) to describe symptoms of problematic media use in high-risk youth and (2) to determine whether ACEs are related to problematic media use in this population. Data were collected through online questionnaires from 348 parents or legal guardians of children ages 5 to 18 years, the majority of whom had been adopted. Parents and guardians reported on the child’s history of ACEs and completed the Problematic Media Use Measure-Short Form (PMUM-SF). Almost half of the participants reported that their child had a history of four or more ACEs (48.9%). Caregivers of foster or adopted children reported more symptoms of problematic media use than those reporting on their biological children. After adjusting for covariates, the number of ACEs predicted problematic media use above and beyond variance explained by demographic factors or screen time amount. Children with a history of ACEs had higher problematic media use compared to children without ACEs.
Scoping Review: Suicide Specific Intervention Programmes for People Experiencing Homelessness
Authors: Murray Rachael McDonnell , Conroy Eilis , Connolly Michelle , Stokes Diarmuid , Frazer Kate , Kroll Thilo
Published: June 2021

Background: The homeless population are among the most vulnerable groups to experience suicide ideation and behavior. Several studies have shown that people who are homeless experience more significant suicidal ideation and behavior than the general population. However, there is limited information about what suicide interventions exist, to what extent they are grounded in robust research, and which intervention components effectively reduce suicidal ideation and behavior in the homeless community. This research aimed to characterise the current evidence base in the area of suicide prevention for homeless individuals. Methods: A scoping review guided by Arksey and O’Malley’s five-stage framework was conducted and a narrative synthesis was performed. Pubmed, EMBASE, PsychInfo, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Open Grey, and Bielefeld Academic Search Engine were searched up to 8 May 2020. Results: A total of 3209 records were identified through database and grey literature searching. Three studies are included in this review. Key outcomes identify suicide intervention prevention programmes; similarities and differences across interventions, and examples of staff training. A quality review of the studies was completed. Conclusion: A stark gap in the evidence of suicide specific prevention interventions targeted at homeless populations.
Evidence for Non-Cancer-Specific T Cell Exhaustion in the Tcl1 Mouse Model for Chronic Lymphocytic Leukemia
Authors: Parigger Thomas , Gassner Franz Josef , Scherhäufl Christian , Bakar Aryunni Abu , Höpner Jan Philip , Hödlmoser Alexandra , Steiner Markus , Catakovic Kemal , Geisberger Roland , Greil Richard , Zaborsky Nadja
Published: June 2021

The reinvigoration of anti-cancer immunity by immune checkpoint therapies has greatly improved cancer treatment. In chronic lymphocytic leukemia (CLL), patients as well as in the Tcl1 mouse model for CLL, PD1-expressing, exhausted T cells significantly expand alongside CLL development; nevertheless, PD1 inhibition has no clinical benefit. Hence, exhausted T cells are either not activatable by simple PD1 blocking in CLL and/or only an insufficient number of exhausted T cells are CLL-specific. In this study, we examined the latter hypothesis by exploiting the Tcl1 transgenic CLL mouse model in combination with TCR transgene expression specific for a non-cancer antigen. Following CLL tumor development, increased PD1 levels were detected on non-CLL specific T cells that seem dependent on the presence of (tumor-) antigen-specific T cells. Transcriptome analysis confirmed a similar exhaustion phenotype of non-CLL specific and endogenous PD1pos T cells. Our results indicate that in the CLL mouse model, a substantial fraction of non-CLL specific T cells becomes exhausted during disease progression in a bystander effect. These findings have important implications for the general efficacy assessment of immune checkpoint therapies in CLL.
Osteoblast Differentiation and Signaling: Established Concepts and Emerging Topics
Authors: Ponzetti Marco , Rucci Nadia
Published: June 2021

Osteoblasts, the cells that build up our skeleton, are remarkably versatile and important cells that need tight regulation in all the phases of their differentiation to guarantee proper skeletal development and homeostasis. Although we know many of the key pathways involved in osteoblast differentiation and signaling, it is becoming clearer and clearer that this is just the tip of the iceberg, and we are constantly discovering novel concepts in osteoblast physiology. In this review, we discuss well-established pathways of osteoblastic differentiation, i.e., the classical ones committing mesenchymal stromal cells to osteoblast, and then osteocytes as well as recently emerged players. In particular, we discuss micro (mi)RNAs, long non-coding (lnc)RNAs, circular (circ)RNAs, and extracellular vesicles, focusing on the mechanisms through which osteoblasts are regulated by these factors, and conversely, how they use extracellular vesicles to communicate with the surrounding microenvironment.
Targeting Telomere Biology in Acute Lymphoblastic Leukemia
Authors: Karow Axel , Haubitz Monika , Oppliger Leibundgut Elisabeth , Helsen Ingrid , Preising Nicole , Steiner Daniela , Dantonello Tobias M. , Ammann Roland A. , Roessler Jochen , Kartal-Kaess Mutlu , Röth Alexander , Baerlocher Gabriela M.
Published: June 2021

Increased cell proliferation is a hallmark of acute lymphoblastic leukemia (ALL), and genetic alterations driving clonal proliferation have been identified as prognostic factors. To evaluate replicative history and its potential prognostic value, we determined telomere length (TL) in lymphoblasts, B-, and T-lymphocytes, and measured telomerase activity (TA) in leukocytes of patients with ALL. In addition, we evaluated the potential to suppress the in vitro growth of B-ALL cells by the telomerase inhibitor imetelstat. We found a significantly lower TL in lymphoblasts (4.3 kb in pediatric and 2.3 kb in adult patients with ALL) compared to B- and T-lymphocytes (8.0 kb and 8.2 kb in pediatric, and 6.4 kb and 5.5 kb in adult patients with ALL). TA in leukocytes was 3.2 TA/C for pediatric and 0.7 TA/C for adult patients. Notably, patients with high-risk pediatric ALL had a significantly higher TA of 6.6 TA/C compared to non-high-risk patients with 2.2 TA/C. The inhibition of telomerase with imetelstat ex vivo led to significant dose-dependent apoptosis of B-ALL cells. These results suggest that TL reflects clonal expansion and indicate that elevated TA correlates with high-risk pediatric ALL. In addition, telomerase inhibition induces apoptosis of B-ALL cells cultured in vitro. TL and TA might complement established markers for the identification of patients with high-risk ALL. Moreover, TA seems to be an effective therapeutic target; hence, telomerase inhibitors, such as imetelstat, may augment standard ALL treatment.
Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer’s Disease
Authors: Hendrickx Jhana O. , De Moudt Sofie , Calus Elke , Martinet Wim , Guns Pieter-Jan D. F. , Roth Lynn , De Deyn Peter P. , Van Dam Debby , De Meyer Guido R. Y.
Published: June 2021

Increasing epidemiological evidence highlights the association between systemic insulin resistance and Alzheimer’s disease (AD). As insulin resistance can be caused by high-stress hormone levels and since hypercortisolism appears to be an important risk factor of AD, we aimed to investigate the systemic insulin functionality and circulating stress hormone levels in a mutant humanized amyloid precursor protein (APP) overexpressing (hAPP23+/−) AD mouse model. Memory and spatial learning of male hAPP23+/− and C57BL/6 (wild type, WT) mice were assessed by a Morris Water Maze (MWM) test at the age of 4 and 12 months. The systemic metabolism was examined by intraperitoneal glucose and insulin tolerance tests (GTT, ITT). Insulin and corticosterone levels were determined in serum. In the hippocampus, parietal and occipital cortex of hAPP23+/− brains, amyloid-beta (Aβ) deposits were present at 12 months of age. MWM demonstrated a cognitive decline in hAPP23+/− mice at 12 but not at 4 months, evidenced by increasing total path lengths and deteriorating probe trials compared to WT mice. hAPP23+/− animals presented increased serum corticosterone levels compared to WT mice at both 4 and 12 months. hAPP23+/− mice exhibited peripheral insulin resistance compared to WT mice at 4 months, which stabilized at 12 months of age. Serum insulin levels were similar between genotypes at 4 months of age but were significantly higher in hAPP23+/− mice at 12 months of age. Peripheral glucose homeostasis remained unchanged. These results indicate that peripheral insulin resistance combined with elevated circulating stress hormone levels could be potential biomarkers of the pre-symptomatic phase of AD.
Brain Symptoms of Tuberous Sclerosis Complex: Pathogenesis and Treatment
Authors: Mizuguchi Masashi , Ohsawa Maki , Kashii Hirofumi , Sato Atsushi
Published: June 2021

The mammalian target of the rapamycin (mTOR) system plays multiple, important roles in the brain, regulating both morphology, such as cellular size, shape, and position, and function, such as learning, memory, and social interaction. Tuberous sclerosis complex (TSC) is a congenital disorder caused by a defective suppressor of the mTOR system, the TSC1/TSC2 complex. Almost all brain symptoms of TSC are manifestations of an excessive activity of the mTOR system. Many children with TSC are afflicted by intractable epilepsy, intellectual disability, and/or autism. In the brains of infants with TSC, a vicious cycle of epileptic encephalopathy is formed by mTOR hyperactivity, abnormal synaptic structure/function, and excessive epileptic discharges, further worsening epilepsy and intellectual/behavioral disorders. Molecular target therapy with mTOR inhibitors has recently been proved to be efficacious for epilepsy in human TSC patients, and for autism in TSC model mice, indicating the possibility for pharmacological treatment of developmental synaptic disorders.
Six Decades of Research on Human Fetal Gonadal Steroids
Authors: Connan-Perrot Stéphane , Léger Thibaut , Lelandais Pauline , Desdoits-Lethimonier Christèle , David Arthur , Fowler Paul A. , Mazaud-Guittot Séverine
Published: June 2021

Human fetal gonads acquire endocrine steroidogenic capabilities early during their differentiation. Genetic studies show that this endocrine function plays a central role in the sexually dimorphic development of the external genitalia during fetal development. When this endocrine function is dysregulated, congenital malformations and pathologies are the result. In this review, we explain how the current knowledge of steroidogenesis in human fetal gonads has benefited from both the technological advances in steroid measurements and the assembly of detailed knowledge of steroidogenesis machinery and its expression in human fetal gonads. We summarise how the conversion of radiolabelled steroid precursors, antibody-based assays, mass spectrometry, ultrastructural studies, and the in situ labelling of proteins and mRNA have all provided complementary information. In this review, our discussion goes beyond the debate on recommendations concerning the best choice between the different available technologies, and their degrees of reproducibility and sensitivity. The available technologies and techniques can be used for different purposes and, as long as all quality controls are rigorously employed, the question is how to maximise the generation of robust, reproducible data on steroid hormones and their crucial roles in human fetal development and subsequent functions.
Hydrogen Bonds, Topologies, Energy Frameworks and Solubilities of Five Sorafenib Salts
Authors: Phan Chiuyen , Shen Jie , Yu Kaxi , Liu Jiyong , Tang Guping
Published: June 2021

Sorafenib (Sor) is an oral multi-kinase inhibitor, but its water solubility is very low. To improve its solubility, sorafenib hydrochloride hydrate, sorafenib hydrobromide and sorafenib hydrobromide hydrate were prepared in the mixed solvent of the corresponding acid solution, and tetrahydrofuran (THF). The crystal structures of sorafenib hydrochloride trihydrate (Sor·HCl.3H2O), 4-(4-{3-[4-chloro-3-(trifluoro-methyl)phenyl]ureido}phenoxy)-2-(N-methylcarbamoyl) pyridinium hydrochloride trihydrate, C21H17ClF3N4O3+·Cl−.3H2O (I), sorafenib hydrochloride monohydrate (Sor·HCl.H2O), C21H17ClF3N4O3+·Cl−.H2O (II), its solvated form (sorafenib hydrochloride monohydrate monotetrahydrofuran (Sor·HCl.H2O.THF), C21H17ClF3N4O3+·Cl−.H2O.C4H8O (III)), sorafenib hydrobromide (Sor·HBr), 4-(4-{3-[4-chloro-3-(trifluoro-methyl)phenyl]ureido}phenoxy)-2-(N-methylcarbamoyl) pyridinium hydrobromide, C21H17ClF3N4O3+·Br− (IV) and sorafenib hydrobromide monohydrate (Sor·HBr.H2O), C21H17ClF3N4O3+·Br−.H2O (V) were analysed. Their hydrogen bond systems and topologies were investigated. The results showed the distinct roles of water molecules in stabilizing their crystal structures. Moreover, (II) and (V) were isomorphous crystal structures with the same space group P21/n, and similar unit cell dimensions. The predicted morphologies of these forms based on the BFDH model matched well with experimental morphologies. The energy frameworks showed that (I), and (IV) might have better tabletability than (II) and (V). Moreover, the solubility and dissolution rate data exhibited an improvement in the solubility of these salts compared with the free drug.