bluuebunny/crossref_metadata_2025 huggingface dataset:
Consensus of Julia Sets
Authors: Sun Weihua , Liu Shutang
Published: January 2022

The Julia set is one of the most important sets in fractal theory. The previous studies on Julia sets mainly focused on the properties and graph of a single Julia set. In this paper, activated by the consensus of multi-agent systems, the consensus of Julia sets is introduced. Moreover, two types of the consensus of Julia sets are proposed: one is with a leader and the other is with no leaders. Then, controllers are designed to achieve the consensus of Julia sets. The consensus of Julia sets allows multiple different Julia sets to be coupled. In practical applications, the consensus of Julia sets provides a tool to study the consensus of group behaviors depicted by a Julia set. The simulations illustrate the efficacy of these methods.
Self-Gelling Solid Lipid Nanoparticle Hydrogel Containing Simvastatin as Suitable Wound Dressing: An Investigative Study
Authors: Gupta Bhumika , Sharma Garima , Sharma Pratibha , Sandhu Simarjot Kaur , Kaur Indu Pal
Published: January 2022

Hydrogels, an advanced interactive system, is finding use as wound dressings, however, they exhibit restricted mechanical properties, macroscopic nature, and may not manage high exudate wounds or incorporate lipophilic actives. In this study, we developed a self-gelling solid lipid nanoparticle (SLNs) dressing to incorporate simvastatin (SIM), a lipophilic, potential wound-healing agent, clinically limited due to poor solubility (0.03 mg/mL) and absorption. The study explores unconventional and novel application of SIM. The idea was to incorporate a significant amount of SIM in a soluble form and release it slowly over a prolonged time. Further, a suitable polymeric surfactant was selected that assigned a self-gelling property to SLNs (SLN-hydrogel) so as to be used as a novel wound dressing. SLNs assign porosity, elasticity, and occlusivity to the dressing to keep the wound area moist. It will also provide better tolerance and sensory properties to the hydrogel. SIM loaded SLN-hydrogel was prepared employing an industry amenable high-pressure homogenization technique. The unique hydrogel dressing was characterized for particle size, zeta potential, Fourier transform infra-red spectroscopy, powder X-ray diffraction, differential scanning calorimetry, rheology, and texture. Significant loading of SIM (10% w/w) was achieved in spherical nanoparticule hydrogel (0.3 nm (nanoparticles) to 2 µm (gelled-matrix)) that exhibited good spreadability and mechanical properties and slow release up to 72 h. SLN-hydrogel was safe as per the organization for economic co-operation and development (OECD-404) guidelines, with no signs of irritation. Complete healing of excision wound observed in rats within 11 days was 10 times better than marketed povidone-iodine product. The presented work is novel both in terms of classifying a per se SLN-hydrogel and employing SIM. Further, it was established to be a safe, effective, and industry amenable invention.
ZBED1 Regulates Genes Important for Multiple Biological Processes of the Placenta
Authors: Johansen Simone , Traynor Sofie , Ebstrup Malene Laage , Terp Mikkel Green , Pedersen Christina Bøg , Ditzel Henrik Jørn , Gjerstorff Morten Frier
Published: January 2022

The transcription factor ZBED1 is highly expressed in trophoblast cells, but its functions in the processes of trophoblast and placental biology remain elusive. Here, we characterized the role of ZBED1 in trophoblast cell differentiation using an in vitro BeWo cell model. We demonstrate that ZBED1 is enhanced in its expression early after forskolin-induced differentiation of BeWo cells and regulates many of the genes that are differentially expressed as an effect of forskolin treatment. Specifically, genes encoding markers for the differentiation of cytotrophoblast into syncytiotrophoblast and factors essential for trophoblast cell fusion and invasion were negatively regulated by ZBED1, indicating that ZBED1 might be important for maintaining a steady pool of cytotrophoblast cells. In addition, ZBED1 affected genes involved in the regulation of trophoblast cell survival and apoptosis, in agreement with the observed increase in apoptosis upon knockdown of ZBED1 in forskolin-treated BeWo cells. In addition, genes implicated in the differentiation, recruitment, and function of innate immune cells by the placenta were affected by ZBED1, further suggesting a role for this protein in the regulation of maternal immune tolerance. In conclusion, our study implicates ZBED1 in major biological processes of placental biology.
Trends in Daily Heart Rate Variability Fluctuations Are Associated with Longitudinal Changes in Stress and Somatisation in Police Officers
Authors: de Vries Herman , Kamphuis Wim , van der Schans Cees , Sanderman Robbert , Oldenhuis Hilbrand
Published: January 2022

The emergence of wearable sensors that allow for unobtrusive monitoring of physiological and behavioural patterns introduces new opportunities to study the impact of stress in a real-world context. This study explores to what extent within-subject trends in daily Heart Rate Variability (HRV) and daily HRV fluctuations are associated with longitudinal changes in stress, depression, anxiety, and somatisation. Nine Dutch police officers collected daily nocturnal HRV data using an Oura ring during 15–55 weeks. Participants filled in the Four-Dimensional Symptoms Questionnaire every 5 weeks. A sample of 47 five-week observations was collected and analysed using multiple regression. After controlling for trends in total sleep time, moderate-to-vigorous physical activity and alcohol use, an increasing trend in the seven-day rolling standard deviation of the HRV (HRVsd) was associated with increases in stress and somatisation over 5 weeks. Furthermore, an increasing HRV trend buffered against the association between HRVsd trend and somatisation change, undoing this association when it was combined with increasing HRV. Depression and anxiety could not be related to trends in HRV or HRVsd, which was related to observed floor effects. These results show that monitoring trends in daily HRV via wearables holds promise for automated stress monitoring and providing personalised feedback.
Loneliness, Complaining and Professional Burnout of Medical Personnel of Psychiatric Wards during COVID-19 Pandemic—Cross-Sectional Study
Authors: Karcz Edyta , Zdun-Ryżewska Agata , Zimmermann Agnieszka
Published: January 2022

Background: Professional burnout in the medical community has been present for a long time, also among mental health professionals. The aim of the study was to examine the links between loneliness, complaining and professional burnout among medical personnel in psychiatric care during a pandemic. Loneliness and complaining of the medical staff are not documented in the literature well enough. Methods: Oldenburg Burnout Questionnaire, the Loneliness Scale, the Complaint Questionnaire and author’s questionnaire. The respondents: 265 medical employees—doctors (19.2%), nurses (69.8%), paramedics (4.9%), medical caregivers (5.7%). Results: Loneliness and complaining are significant predictors of exhaustion. The model explains 18% of exhaustion variance. Loneliness, complaining and job seniority are also predictors of disengagement; the model allows to predict 10% of the variance of disengagement. Women are more prone to complain. Complaining significantly correlates with direct support from management. A high rate of loneliness correlates, in a statistically significant way, with worse work organization, less management support, worse atmosphere in the team and with more irresponsible attitudes of colleagues. Conclusions: Loneliness and complaining can be used to predict occupational burnout. Women and people without management support complain more often. Loneliness is connected with bad work organization and bad cooperation in a team.
“The Light at the End of the Tunnel”: Experiences of LGBTQ+ Adults in Portuguese Healthcare
Authors: Pieri Mara , Brilhante Joana
Published: January 2022

This work analyses experiences of LGBTQ+ people accessing healthcare in Portugal. A total of 32 semi-structured interviews were conducted with queer adults (18–59 years old). The thematic analysis and thematic networks brought to light how structural cis-heteronorms are compliant with the maintenance of invisibility regarding sexual and gender diversity. As a consequence, experiences of direct and indirect discrimination show us how crucial it is to have well prepared healthcare providers, capable of embracing diversity and creating safe spaces that allow us to shorten the path between Portugal’s progressive legal frame and the people lived experiences.
An App about Healthy Habits as an Educational Resource during the Pandemic
Authors: Merino-Godoy María de los Ángeles , Moreno-Sánchez Emilia , Gago-Valiente Francisco-Javier , Costa Emília Isabel , Sáez-Padilla Jesús
Published: January 2022

Educational institutions and their agents play a fundamental role in improving people’s health literacy and quality of life. We intend here to describe and justify an educational resource embodied in an application for mobile devices developed through a subsidized project by the Ministry of Health (Government of Andalusia); the purpose of this app is to educate young people in healthy habits. The application was designed to be easily used in both smartphones and tablets with the aim of achieving good physical, psychological and social health. The project comprises several phases and the results we have so far show that, from an early age, health institutions and educational settings must work in partnership, increasing health literacy levels. This cooperative work combined with the use of this innovative approach presents an important potential for change in the lifestyles of younger generations. This type of intervention took on a special role in the pandemic context, allowing for the maintenance of the educational stimulus in a safe context.
Assessment of Pregnant Women’s Satisfaction with Model of Care Initiative: Antenatal Care Service at Primary Health Care in Cluster One in Riyadh, Saudi Arabia
Authors: Alhaqbani Saad M. , Bawazir Amen A.
Published: January 2022

The current study assessed pregnant women’s satisfaction with antenatal care (ANC) services at primary health care centers (PHCs) in Riyadh Cluster One. The study was conducted at 11 PHCs where the ANC initiative has been implemented. A total of 646 pregnant women were enrolled. A questionnaire was completed by participants to measure the level of satisfaction with the provided services, care, and consultation. Subsequently, the data were analyzed to determine the significant differences and conduct regression analysis. The overall satisfaction with initial triage assessment, provided services, consultation, and examination was 93.7%, 87.8%, 71.8%, and 53.9%, respectively. Regarding ANC services, education was the only statistically significant variable that influenced patient satisfaction (p < 0.05). In contrast, satisfaction with the provided care was significantly related to all the variables studied. For consultation, education (p < 0.001) and monthly income (p < 0.05) were the statistically significant role players. In the regression analysis, secondary education was statistically significantly related to the provided services, consultation, and examination. Despite the satisfactory level of ANC at the selected PHCs, higher patient satisfaction could be achieved in the future by improving the consultation and examination practices. Overall satisfaction with the health care workers at PHCs is high. Incorporating implied ameliorations would enhance the quality of services and patient satisfaction.
Physiological Response to Short-Term Heat Stress in the Leaves of Traditional and Modern Plum (Prunus domestica L.) Cultivars
Authors: Viljevac Vuletić Marija , Mihaljević Ines , Tomaš Vesna , Horvat Daniela , Zdunić Zvonimir , Vuković Dominik
Published: January 2022

The aim of this study was to evaluate physiological responses to short-term heat stress in the leaves of traditional (Bistrica) and modern (Toptaste) plum cultivars. In this study, detached plum leaves were incubated at 25 °C (control) and 40 °C (stress). After 1 h of exposure to heat (40 °C), chlorophyll a fluorescence transients were measured, and several biochemical parameters were analyzed. Elevated temperature caused heat stress in both plum cultivars, seen as a decrease in water content (WT), but in the leaves of the cultivar Bistrica, an accumulation of proline and phenols, as well as an accumulation of photosynthetic pigments, suggest the activation of a significant response to unfavorable conditions. Conversely, in the leaves of Toptaste, a significant accumulation of malondialdehyde (MDA) and an activation of guaiacol peroxidase (GPOD), all together with a decreased soluble proteins content, indicate an inadequate response to maintaining homeostasis in the leaf metabolism. The impact of an elevated temperature on photosynthesis was significant in both plum cultivars as reflected in the decrease in performance indexes (PIABS and PItotal) and the maximum quantum yield of PSII (Fv/Fm), with significantly pronounced changes found in Toptaste. Unlike the traditional plum cultivar, Bistrica, in the modern cultivar, Toptaste, short-term heat stress increased the minimal fluorescence (F0) and absorption (ABS/RC), as well as Chl b in total chlorophylls. Additionally, the inactivation of RCs (RC/ABS) suggests that excitation energy was not trapped efficiently in the electron chain transport, which resulted in stronger dissipation (DI0/RC) and the formation of ROSs. Considering all presented results, it can be presumed that the traditional cultivar Bistrica has better tolerance to heat stress than the modern cultivar Toptaste. The cultivar, Bistrica, can be used as a basis in further plum breeding programs, as a source of tolerance for high temperature stress.
Wolfram Syndrome Type 2: A Systematic Review of a Not Easily Identifiable Clinical Spectrum
Authors: Rosanio Francesco Maria , Di Candia Francesca , Occhiati Luisa , Fedi Ludovica , Malvone Francesco Paolo , Foschini Davide Fortunato , Franzese Adriana , Mozzillo Enza
Published: January 2022

Background: Wolfram syndrome (WS) is a rare autosomal recessive disorder that is characterized by the presence of diabetes mellitus, optic atrophy and hearing loss, all of which are crucial elements for the diagnosis. WS is variably associated with diabetes insipidus, neurological disorders, urinary tract anomalies, endocrine dysfunctions and many other systemic manifestations. Since Wolfram and Wagener first described WS in 1938, new phenotypic/genotypic variants of the syndrome have been observed and the clinical picture has been significantly enriched. To date, two main subtypes of WS that associated with two different mutations are known: WS type 1 (WS1), caused by the mutation of the wolframine gene (WS1; 606201), and WS type 2 (WS2), caused by the mutation of the CISD2 gene (WS2; 604928). Methods: A systematic review of the literature was describe the phenotypic characteristics of WS2 in order to highlight the key elements that differentiate it from the classic form. Conclusion: WS2 is the rarest and most recently identified subtype of WS; its clinical picture is partially overlapping with that of WS1, from which it traditionally differs by the absence of diabetes insipidus and the presence of greater bleeding tendency and peptic ulcers.
Dependence of the Distribution and Structure of the White Mulberry (Morus alba) Population in Wrocław on the Intensity of Anthropopressure and Thermal Conditions
Authors: Blitek Katarzyna , Pruchniewicz Daniel , Bąbelewski Przemysław , Czaplicka-Pędzich Marta , Kubus Marcin
Published: January 2022

The selection of species which show the highest possible tolerance to negative habitat conditions, also among plants of foreign origin, is a pressing issue. One of the species we would like to recommend for planting in urban areas is the white mulberry species (Morus alba) due to both its outstanding adaptability and its ecosystem services. There are no reliable studies on the distribution of this species in urbanized areas in Poland, nor sufficient analyses of the methods of its renewal, both deliberate and spontaneous spread through self-seeding. Collecting data on the population of an alien species within individual regions and forecasting potential changes in the population’s size and structure, as well as its possible impacts on other organisms, is one of the basic measures to reduce biological invasions, which is one of the six priority objectives of the European Biodiversity Strategy and an element of the Strategy on Invasive Alien Species. The aim of this study was to determine the size and structure of the white mulberry population in the city of Wrocław and to analyse the relationship between this structure and intensity of anthropopressure and thermal conditions.
Development of 222Rn Emanation Sources with Integrated Quasi 2π Active Monitoring
Authors: Mertes Florian , Röttger Stefan , Röttger Annette
Published: January 2022

In this work, a novel approach for the standardization of low-level 222Rn emanation is presented. The technique is based on the integration of a 222Rn source, directly, with an α-particle detector, which allows the residual 222Rn to be continuously monitored. Preparation of the device entails thermal physical vapor deposition of 226RaCl2 directly onto the surface of a commercially available ion implanted Si-diode detector, resulting in a thin-layer geometry. This enables continuous collection of well resolved α-particle spectra of the nuclei, decaying within the deposited layer, with a detection efficiency of approximately 0.5 in a quasi 2π geometry. The continuously sampled α-particle spectra are used to derive the emanation by statistical inversion. It is possible to achieve this with high temporal resolution due to the small background and the high counting efficiency of the presented technique. The emanation derived in this way exhibits a dependence on the relative humidity of up to 15% in the range from 20% rH to 90% rH. Traceability to the SI is provided by employing defined solid-angle α-particle spectrometry to characterize the counting efficiency of the modified detectors. The presented technique is demonstrated to apply to a range covering the release of at least 1 to 210 222Rn atoms per second, and it results in SI-traceable emanation values with a combined standard uncertainty not exceeding 2%. This provides a pathway for the realization of reference atmospheres covering typical environmental 222Rn levels and thus drastically improves the realization and the dissemination of the derived unit of the activity concentration concerning 222Rn in air.
Challenges of Researchers in Conducting International Study during the Eruption of COVID-19: Student and Mentor Perspectives
Authors: Mobaraka Jenail , Elkazzaz Lian , Rizkalla Niveen
Published: January 2022

Conducting an international research study may bear various challenges; however, during the global COVID-19 crisis, such a study undertakes unpredictable trajectories. This paper explores the challenges experienced by researchers studying Syrian refugees’ physical and mental health and aid workers serving under humanitarian organizations in Lebanon. It includes information about the changes in the study’s goals and design with the emergence and spread of SARS-CoV-2, as necessitated by the circumstances COVID-19 imposed. It focuses on the unique perspectives of the research team of two students and their mentor who faced multiple challenges while involved in the study, and their narratives and subjective experiences that led to new opportunities for growth in the project. The research team specifically engaged in humanistic and existential psychology in order to conduct research in a manner conducive to personal and professional development, productivity and growth. To conclude, the researchers propose recommendations to the academic community on mitigating some of the challenges faced when conducting international research, and suggestions to the humanitarian sector serving vulnerable populations in conflict zones during COVID-19.
The Opportunities and Challenges Associated with the Implementation of Fourth Industrial Revolution Technologies to Manage Health and Safety
Authors: Malomane Reneiloe , Musonda Innocent , Okoro Chioma Sylvia
Published: January 2022

The fourth industrial revolution (4iR) technologies offer an opportunity for the construction industry to improve health and safety (H&S) compliance. Therefore, implementing the technologies is of top priority to improve the endless H&S incidents in construction projects, which lead to poor quality of work, late project delivery, and increased labour injury claims. Central to improving the nature of work and other industrial processes, the 4iR technologies have emerged. Concurrent with this trend is the importance of 4iR technologies in enhancing health and safety performance on construction sites. However, the implementation of 4iR technologies in the construction industry is faced with various challenges. Therefore, this paper reports on a study aimed at examining the challenges associated with implementing 4iR technologies in the construction sector in South Africa towards effective management of H&S. The study followed a systematic literature review, data collection using a questionnaire survey and thereafter, descriptive, and inferential analyses were conducted. The findings revealed that the implementation of 4iR technologies is challenged by a lack of adequate relevant skills, the unavailability of training capacities, expensive technologies, and negative perceptions such as fear of job loss by industry professionals. The findings are essential for the advancement of H&S research and implementation. In addition, the findings are important to industry decision-makers in order to elevate their awareness and promote the use of 4iR technologies to manage construction activities. The study implications include the need for the construction industry to collaborate with higher education institutions to conduct research and include 4iR in the curriculum.
The Influence of Decision Making on Social Inclusion of Persons with Disabilities: A Case Study of Khyber Pakhtunkhwa
Authors: Ahmad Shakeel , Islam Mazhar , Zada Muhammad , Khattak Afraseyab , Ullah Rezwan , Han Heesup , Ariza-Montes Antonio , Araya-Castillo Luis
Published: January 2022

Decision making is an essentially social process adopted by individuals or groups to identify and choose the best choice among several alternatives. Decision-making choices are influenced by the preferences, values, and beliefs of the individuals or groups involved in the decision-making process. This study was conducted to analyze the social inclusion of Persons with Disabilities (PWDs) in the context of their participation in decision making. The study area consisted of 8028 PWDs registered with the government of Pakistan, from which a sample of 488 PWDs was selected through a multistage stratified random sampling technique. These PWDs included physically disabled, blind, crippled, and deaf persons; however, the data were collected from those who were able to be interviewed. Chi-square and Kendall’s Tau-b tests were used to determine the strength, level, and direction of association among variables. At the multivariate level, the study found a spurious relation between social inclusion and participation in decision making when controlling for gender, monthly family income, and level of disability of the PWDs. The results highlighted that participation in decision making improved the social inclusion of male and moderately disabled PWDs more positively. However, participation in decision making was a universal feature explaining the social inclusion of PWDs irrespective of their monthly family income. The logistic regression model explained that the social inclusion of PWDs was more likely to occur when PWDs were married, had high monthly family income (PKR 16,500 and above), belonged to a joint family, and actively participated in decision making. The study recommends that ensuring the participation of PWDs in decision making in family, community, school, and other relevant institutions ultimately enhances their social inclusion.
Rescue Emergencies Due to High-Altitude Illnesses Are Rare in Switzerland
Authors: Gasser Benedikt , Stouder Joel
Published: January 2022

Background: Despite a potential high risk of acute mountain sickness (AMS) in the Swiss Alps, there is a lack of analyses concerning its relevance over longer periods. In consequence, the aim of this study is to analyze the prevalence of AMS in comparison to other causes of mountain emergencies in recent years in Switzerland. Material and Methods: Based on the central registry of mountain emergencies of the Swiss Alpine Club (SAC), all cases in the period between 2009 and 2020 were analyzed for AMS including the most severe forms of high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE). Emergencies were assessed for the severity of the event with a National Advisory Committee for Aeronautics (NACA) score. Results: From a total of 4596 high-altitude mountaineering emergencies identified in the observational period, a total number of 352 cases of illnesses were detected. Detailed analysis revealed 85 cases of AMS, 5 cases of HAPE, and 1 case of HACE. The average altitude was 3845 ± 540 m. Most cases were in the canton of Valais, especially in the Monte Rosa region and the mountains of the Mischabel group (Täschhorn, Dom, Südlenz, Nadelhorn, Hohberghorn). There were only three deaths related to high-altitude illnesses; all the other events could be identified as moderate to severe but not life-threatening. Discussion: An emergency due to AMS that requires rescue is unlikely in the Swiss Alps. This does not imply that AMS is not a concern. However, the facts that the maximal altitude is relatively low and that fast self-descents often seem possible probably minimize the likelihood that mountaineers with symptoms contact emergency services.
768-km Multi-Stage Ultra-Trail Case Study-Muscle Damage, Biochemical Alterations and Strength Loss on Lower Limbs
Authors: Lecina Miguel , Castellar Carlos , Pradas Francisco , López-Laval Isaac
Published: January 2022

A series of case studies aimed to evaluate muscular fatigue in running a 768-km ultra-trail race in 11 days. Four non-professional athletes (four males) were enrolled. Muscle damage blood biomarkers (creatine kinase (CK), lactodeshydrogenase (LDH), aspartate transaminase (AST) and alanine aminotransferase (ALT) and lower limb strength were evaluated by using Bosco jumps test; squat jump (SJ), countermovement jump (CMJ) and Abalakov jump (ABA) were assessed before (pre), after the race (post) and for two and nine days during the recovery period (rec2 and rec9), respectively. Results showed: pre-post SJ = −28%, CMJ = −36% and ABA = −21%. Values returned to basal during rec9: SJ = −1%, CMJ = −2% or even exceeded pre-values ABA = +3%. On the contrary, muscle damage blood biomarkers values increased at post; CK = +888%, LDH = +172%, AST = +167% and ALT = +159% and the values returned gradually to baseline at rec9 except for AST = +226% and ALT = +103% which remained higher. Nonparametric bivariate Spearman’s test showed strong correlations (Rs ≥ 0.8) between some jumps and muscle damage biomarkers at post (SJ-LDH Rs = 0.80, SJ-AST Rs = 0.8, ABA-LD H Rs = 0.80 and ABA-AST Rs = 0.80), at rec2 (SJ-CK Rs = 0.80 and SJ-ALT Rs = 0.80) and even during rec9 (ABA-CK). Similarly, some parameters such as accumulated elevation and training volume showed a strong correlation with LDH values after finishing the ultra-trail race. The alteration induced by completing an ultra-trail event in the muscle affects lower limb strength and may in some circumstances result in serious medical conditions including post- exertional rhabdomyolysis.
Developing a Personalized Integrative Obesity-Coaching Program: A Systems Health Perspective
Authors: Brink Sander M. , Wortelboer Heleen M. , Emmelot Cornelis H. , Visscher Tommy L. S. , van Wietmarschen Herman A.
Published: January 2022

Current obesity management strategies are failing to achieve sustainable and favorable long-term results. We propose a more personalized, dynamic, and systemic perspective on the interactions of key determinants and coaching advice on obesity. The aim of this study was to use a systems view on overweight, complexity science, and a transdisciplinary process to develop a five-year personalized integrative obesity-coaching and research program. Managers, medical specialists, clinical psychologists, dieticians, physical- and psychomotor therapists, and lifestyle coaches aligned their perspectives and objectives with experts in systems thinking and systems biology. A systems health model of obesity was used to identify the causal relations of variables with the most influence on obesity. The model helped to align and design a personalized integrative obesity-coaching program and to identify the key variables to monitor the progress and to adjust the personalized program, depending on the goals and needs of the participant. It was decided to use subtyping of participants by a systems biologist, based on traditional Chinese medicine symptoms, as a novel method to personalize the intervention. The collaborative transdisciplinary approach based upon a systems view on obesity was successful in developing a personalized and adaptive five-year obesity-coaching and research program.
How Perceived Sensory Dimensions of Forest Park Are Associated with Stress Restoration in Beijing?
Authors: An Congying , Liu Jinglan , Liu Qiaohui , Liu Yuqi , Fan Xiaoli , Hu Yishen
Published: January 2022

A growing number of studies suggest that the perceived sensory dimensions (PSDs) of green space are associated with stress restoration offered by restorative environment. However, there is little known about PSDs and stress restoration as well as their relationship to forest park. To fill this gap, an on-site questionnaire survey was conducted in three forest parks in Beijing, as a result of which a total number of 432 completed responses were collected and analyzed. The mean values of PSDs were used to represent PSDs of forest park. Using independent sample t-test and ANOVA, this study analyzed the individual characteristics that affected PSDs and stress restoration. Linear mixed model was used to identify the relationship between PSDs and stress restoration of forest park, which took into account the interactions of stress level and PSDs. The results showed that: (1) the perceived degree of PSDs in forest park from strong to weak was Serene, Space, Nature, Rich in species, Prospect, Refuge, Social and Culture, which varied with visitors’ gender, age, level of stress, visit frequency, activity intensity, visit duration and commuting time; (2) in PSDs, Refuge, Serene, Social and Prospect had significantly positive effects on the stress restoration of forest parks (3) there was no significant difference in the effect of the eight PSDs on the stress restoration between different stress groups; (4) stress restoration was influenced by visitors’ gender, age, visit frequency and visit duration. These findings can offer references for managers to improve the health benefits of forest park for visitors, and can enrich the knowledge about PSDs and stress restoration.
Professionals’ Digital Training for Child Maltreatment Prevention in the COVID-19 Era: A Pan-European Model
Authors: Crocamo Cristina , Bachi Bianca , Cioni Riccardo M. , Schecke Henrike , Nieminen Irja , Zabłocka-Żytka Lidia , Woźniak-Prus Małgorzata , Bartoli Francesco , Riboldi Ilaria , Appleton Jane V. , Bekaert Sarah , Zlatkute Giedre , Jouet Emmanuelle , Viganò Giovanni , Specka Michael , Scherbaum Norbert , Paavilainen Eija , Baldacchino Alexander , Carrà Giuseppe
Published: January 2022

The responsiveness of professionals working with children and families is of key importance for child maltreatment early identification. However, this might be undermined when multifaceted circumstances, such as the COVID-19 pandemic, reduce interdisciplinary educational activities. Thanks to technological developments, digital platforms seem promising in dealing with new challenges for professionals’ training. We examined a digital approach to child maltreatment training through the ERICA project experience (Stopping Child Maltreatment through Pan-European Multiprofessional Training Programme). ERICA has been piloted during the pandemic in seven European centers involving interconnected sectors of professionals working with children and families. The training consisted of interactive modules embedded in a digital learning framework. Different aspects (technology, interaction, and organization) were evaluated and trainers’ feedback on digital features was sought. Technical issues were the main barrier, however, these did not significantly disrupt the training. The trainers perceived reduced interaction between participants, although distinct factors were uncovered as potential favorable mediators. Based on participants’ subjective experiences and perspectives, digital learning frameworks for professionals working with children and families (such as the ERICA model nested in its indispensable adaptation to an e-learning mode) can represent a novel interactive approach to empower trainers and trainees to tackle child maltreatment during critical times such as a pandemic, and as an alternative to more traditional learning frameworks.
Reactive Oxygen Species Production Is Responsible for Antineoplastic Activity of Osmium, Ruthenium, Iridium and Rhodium Half-Sandwich Type Complexes with Bidentate Glycosyl Heterocyclic Ligands in Various Cancer Cell Models
Authors: Kacsir István , Sipos Adrienn , Bényei Attila , Janka Eszter , Buglyó Péter , Somsák László , Bai Péter , Bokor Éva
Published: January 2022

Platinum complexes are used in chemotherapy, primarily as antineoplastic agents. In this study, we assessed the cytotoxic and cytostatic properties of a set of osmium(II), ruthenium(II), iridium(III) and rhodium(III) half-sandwich-type complexes with bidentate monosaccharide ligands. We identified 5 compounds with moderate to negligible acute cytotoxicity but with potent long-term cytostatic activity. These structure-activity relationship studies revealed that: (1) osmium(II) p-cymene complexes were active in all models, while rhodium(III) and iridium(III) Cp* complexes proved largely inactive; (2) the biological effect was influenced by the nature of the central azole ring of the ligands—1,2,3-triazole was the most effective, followed by 1,3,4-oxadiazole, while the isomeric 1,2,4-oxadiazole abolished the cytostatic activity; (3) we found a correlation between the hydrophobic character of the complexes and their cytostatic activity: compounds with O-benzoyl protective groups on the carbohydrate moiety were active, compared to O-deprotected ones. The best compound, an osmium(II) complex, had an IC50 value of 0.70 µM. Furthermore, the steepness of the inhibitory curve of the active complexes suggested cooperative binding; cooperative molecules were better inhibitors than non-cooperative ones. The cytostatic activity of the active complexes was abolished by a lipid-soluble antioxidant, vitamin E, suggesting that oxidative stress plays a major role in the biological activity of the complexes. The complexes were active on ovarian cancer, pancreatic adenocarcinoma, osteosarcoma and Hodgkin’s lymphoma cells, but were inactive on primary, non-transformed human fibroblasts, indicating their applicability as potential anticancer agents.
Activity- and Enrichment-Based Metaproteomics Insights into Active Urease from the Rumen Microbiota of Cattle
Authors: Zhang Xiaoyin , Xiong Zhanbo , Li Ming , Zheng Nan , Zhao Shengguo , Wang Jiaqi
Published: January 2022

Regulation of microbial urease activity plays a crucial role in improving the utilization efficiency of urea and reducing nitrogen emissions to the environment for ruminant animals. Dealing with the diversity of microbial urease and identifying highly active urease as the target is the key for future regulation. However, the identification of active urease in the rumen is currently limited due to large numbers of uncultured microorganisms. In the present study, we describe an activity- and enrichment-based metaproteomic analysis as an approach for the discovery of highly active urease from the rumen microbiota of cattle. We conducted an optimization method of protein extraction and purification to obtain higher urease activity protein. Cryomilling was the best choice among the six applied protein extraction methods (ultrasonication, bead beating, cryomilling, high-pressure press, freeze-thawing, and protein extraction kit) for obtaining protein with high urease activity. The extracted protein by cryomilling was further enriched through gel filtration chromatography to obtain the fraction with the highest urease activity. Then, by using SDS-PAGE, the gel band including urease was excised and analyzed using LC-MS/MS, searching against a metagenome-derived protein database. Finally, we identified six microbial active ureases from 2225 rumen proteins, and the identified ureases were homologous to those of Fibrobacter and Treponema. Moreover, by comparing the 3D protein structures of the identified ureases and known ureases, we found that the residues in the β-turn of flap regions were nonconserved, which might be crucial in influencing the flexibility of flap regions and urease activity. In conclusion, the active urease from rumen microbes was identified by the approach of activity- and enrichment-based metaproteomics, which provides the target for designing a novel efficient urease inhibitor to regulate rumen microbial urease activity.
Immunotherapy for Biliary Tract Cancer in the Era of Precision Medicine: Current Knowledge and Future Perspectives
Authors: Ciardiello Davide , Maiorano Brigida Anna , Parente Paola , Rodriquenz Maria Grazia , Latiano Tiziana Pia , Chiarazzo Cinzia , Pazienza Valerio , Guerrera Luigi Pio , Amoruso Brunella , Normanno Nicola , Martini Giulia , Ciardiello Fortunato , Martinelli Erika , Maiello Evaristo
Published: January 2022

Biliary tract cancers (BTC) represent a heterogeneous and aggressive group of tumors with dismal prognosis. For a long time, BTC has been considered an orphan disease with very limited therapeutic options. In recent years a better understanding of the complex molecular landscape of biology is rapidly changing the therapeutic armamentarium. However, while 40–50% of patients there are molecular drivers susceptible to target therapy, for the remaining population new therapeutic options represent an unsatisfied clinical need. The role of immunotherapy in the continuum of treatment of patients with BTC is still debated. Despite initial signs of antitumor-activity, single-agent immune checkpoint inhibitors (ICIs) demonstrated limited efficacy in an unselected population. Therefore, identifying the best partner to combine ICIs and predictive biomarkers represents a key challenge to optimize the efficacy of immunotherapy. This review provides a critical analysis of completed trials, with an eye on future perspectives and possible biomarkers of response.
Transcriptional Response in a Sepsis Mouse Model Reflects Transcriptional Response in Sepsis Patients
Authors: Rosier Florian , Nuñez Nicolas Fernandez , Torres Magali , Loriod Béatrice , Rihet Pascal , Pradel Lydie C.
Published: January 2022

Mortality due to sepsis remains unacceptably high, especially for septic shock patients. Murine models have been used to better understand pathophysiology mechanisms. However, the mouse model is still under debate. Herein we investigated the transcriptional response of mice injected with lipopolysaccharide (LPS) and compared it to either human cells stimulated in vitro with LPS or to the blood cells of septic patients. We identified a molecular signature composed of 2331 genes with an FDR median of 0%. This molecular signature is highly enriched in regulated genes in peritoneal macrophages stimulated with LPS. There is significant enrichment in several inflammatory signaling pathways, and in disease terms, such as pneumonia, sepsis, systemic inflammatory response syndrome, severe sepsis, an inflammatory disorder, immune suppression, and septic shock. A significant overlap between the genes upregulated in mouse and human cells stimulated with LPS has been demonstrated. Finally, genes upregulated in mouse cells stimulated with LPS are enriched in genes upregulated in human cells stimulated in vitro and in septic patients, who are at high risk of death. Our results support the hypothesis of common molecular and cellular mechanisms between mouse and human sepsis.
Brassinosteroids Mitigate Cadmium Effects in Arabidopsis Root System without Any Cooperation with Nitric Oxide
Authors: Della Rovere Federica , Piacentini Diego , Fattorini Laura , Girardi Nicoletta , Bellanima Dario , Falasca Giuseppina , Altamura Maria Maddalena , Betti Camilla
Published: January 2022

The heavy metal cadmium (Cd) affects root system development and quiescent center (QC)-definition in Arabidopsis root-apices. The brassinosteroids-(BRs)-mediated tolerance to heavy metals has been reported to occur by a modulation of nitric oxide (NO) and root auxin-localization. However, how BRs counteract Cd-action in different root types is unknown. This research aimed to find correlations between BRs and NO in response to Cd in Arabidopsis’s root system, monitoring their effects on QC-definition and auxin localization in root-apices. To this aim, root system developmental changes induced by low levels of 24-epibrassinolide (eBL) or by the BR-biosynthesis inhibitor brassinazole (Brz), combined or not with CdSO4, and/or with the NO-donor nitroprusside (SNP), were investigated using morpho-anatomical and NO-epifluorescence analyses, and monitoring auxin-localization by the DR5::GUS system. Results show that eBL, alone or combined with Cd, enhances lateral (LR) and adventitious (AR) root formation and counteracts QC-disruption and auxin-delocalization caused by Cd in primary root/LR/AR apices. Exogenous NO enhances LR and AR formation in Cd-presence, without synergism with eBL. The NO-signal is positively affected by eBL, but not in Cd-presence, and BR-biosynthesis inhibition does not change the low NO-signal caused by Cd. Collectively, results show that BRs ameliorate Cd-effects on all root types acting independently from NO.
MicroRNAs as Modulators of the Immune Response in T-Cell Acute Lymphoblastic Leukemia
Authors: Del Gaizo Martina , Sergio Ilaria , Lazzari Sara , Cialfi Samantha , Pelullo Maria , Screpanti Isabella , Felli Maria Pia
Published: January 2022

Acute lymphoblastic leukaemia (ALL) is an aggressive haematological tumour driven by the malignant transformation and expansion of B-cell (B-ALL) or T-cell (T-ALL) progenitors. The evolution of T-ALL pathogenesis encompasses different master developmental pathways, including the main role played by Notch in cell fate choices during tissue differentiation. Recently, a growing body of evidence has highlighted epigenetic changes, particularly the altered expression of microRNAs (miRNAs), as a critical molecular mechanism to sustain T-ALL. The immune response is emerging as key factor in the complex multistep process of cancer but the role of miRNAs in anti-leukaemia response remains elusive. In this review we analyse the available literature on miRNAs as tuners of the immune response in T-ALL, focusing on their role in Natural Killer, T, T-regulatory and Myeloid-derived suppressor cells. A better understanding of this molecular crosstalk may provide the basis for the development of potential immunotherapeutic strategies in the leukemia field.
Controlled Release of Epigenetically-Enhanced Extracellular Vesicles from a GelMA/Nanoclay Composite Hydrogel to Promote Bone Repair
Authors: Man Kenny , Barroso Inês A. , Brunet Mathieu Y. , Peacock Ben , Federici Angelica S. , Hoey David A. , Cox Sophie C.
Published: January 2022

Extracellular vesicles (EVs) have garnered growing attention as promising acellular tools for bone repair. Although EVs’ potential for bone regeneration has been shown, issues associated with their therapeutic potency and short half-life in vivo hinders their clinical utility. Epigenetic reprogramming with the histone deacetylase inhibitor Trichostatin A (TSA) has been reported to promote the osteoinductive potency of osteoblast-derived EVs. Gelatin methacryloyl (GelMA) hydrogels functionalised with the synthetic nanoclay laponite (LAP) have been shown to effectively bind, stabilise, and improve the retention of bioactive factors. This study investigated the potential of utilising a GelMA-LAP hydrogel to improve local retention and control delivery of epigenetically enhanced osteoblast-derived EVs as a novel bone repair strategy. LAP was found to elicit a dose-dependent increase in GelMA compressive modulus and shear-thinning properties. Incorporation of the nanoclay was also found to enhance shape fidelity when 3D printed compared to LAP-free gels. Interestingly, GelMA hydrogels containing LAP displayed increased mineralisation capacity (1.41-fold) (p ≤ 0.01) over 14 days. EV release kinetics from these nanocomposite systems were also strongly influenced by LAP concentration with significantly more vesicles being released from GelMA constructs as detected by a CD63 ELISA (p ≤ 0.001). EVs derived from TSA-treated osteoblasts (TSA-EVs) enhanced proliferation (1.09-fold), migration (1.83-fold), histone acetylation (1.32-fold) and mineralisation (1.87-fold) of human bone marrow stromal cells (hBMSCs) when released from the GelMA-LAP hydrogel compared to the untreated EV gels (p ≤ 0.01). Importantly, the TSA-EV functionalised GelMA-LAP hydrogel significantly promoted encapsulated hBMSCs extracellular matrix collagen production (≥1.3-fold) and mineralisation (≥1.78-fold) in a dose-dependent manner compared to untreated EV constructs (p ≤ 0.001). Taken together, these findings demonstrate the potential of combining epigenetically enhanced osteoblast-derived EVs with a nanocomposite photocurable hydrogel to promote the therapeutic efficacy of acellular vesicle approaches for bone regeneration.
Biguanide Pharmaceutical Formulations and the Applications of Bile Acid-Based Nano Delivery in Chronic Medical Conditions
Authors: Jones Melissa , Ionescu Corina Mihaela , Walker Daniel , Wagle Susbin Raj , Kovacevic Bozica , Chester Jacqueline , Foster Thomas , Johnston Edan , Kuthubutheen Jafri , Brown Daniel , Atlas Marcus D. , Mikov Momir , Mooranian Armin , Al-Salami Hani
Published: January 2022

Biguanides, particularly the widely prescribed drug metformin, have been marketed for many decades and have well-established absorption profiles. They are commonly administered via the oral route and, despite variation in oral uptake, remain commonly prescribed for diabetes mellitus, typically type 2. Studies over the last decade have focused on the design and development of advanced oral delivery dosage forms using bio nano technologies and novel drug carrier systems. Such studies have demonstrated significantly enhanced delivery and safety of biguanides using nanocapsules. Enhanced delivery and safety have widened the potential applications of biguanides not only in diabetes but also in other disorders. Hence, this review aimed to explore biguanides’ pharmacokinetics, pharmacodynamics, and pharmaceutical applications in diabetes, as well as in other disorders.