bluuebunny/crossref_metadata_2025 huggingface dataset:
Emotions of the Anthropocene across Oceania
Authors: Clissold Rachel , McNamara Karen E. , Westoby Ross
Published: June 2022

As human activities have destabilised life on Earth, a new geological era is upon us. While there is a myriad of challenges that have emerged because of such human-driven planetary changes, one area of investigation that requires ongoing scholarly attention and scientific debate is the emotions of the Anthropocene. The emotional, mental, and psychological burdens induced by rapid and unprecedented change must be understood to better reflect the experiences of people around the globe and to initiate conversations about how emotions may be used for transformative change and effective politics. This paper aims to provide insights into the types of emotions that are emerging in Oceania as the Anthropocene unfolds. To do this, we draw on several data sets: questionnaire results with visitors of Mt Barney Lodge in the World Heritage Gondwana area in Queensland, Australia; another questionnaire with Pacific Island “experts” engaged in climate change, development, and disaster risk management work; interviews with locals living in the Cook Islands; and various spoken, written, and visual art from the Pacific. Bringing these data sets together allows us to explore a diversity of experiences, perspectives, and emotional responses to the Anthropocene from participants across Oceania. We found that acute and slow-onset weather events, experiences of direct loss and change, a perceived lack of agency or control over futures, and a sense of injustice triggered emotions including fear, stress, anxiety, exhaustion, sadness, grief, anger, frustration, helplessness, worry, but also empowerment. These results are critical for the first step of acknowledging and naming the emotions that are emerging in Oceania, such that they can then be worked through, and may be used for transformative change, effective politics, and agency over futures.
The Impact of Meteorology and Emissions on Surface Ozone in Shandong Province, China, during Summer 2014–2019
Authors: Wang Houwen , Gao Yang , Sheng Lifang , Wang Yuhang , Zeng Xinran , Kou Wenbin , Ma Mingchen , Cheng Wenxuan
Published: June 2022

China has been experiencing severe ozone pollution problems in recent years. While a number of studies have focused on the ozone-pollution-prone regions such as the North China Plain, Yangtze River Delta, and Pearl River Delta regions, few studies have investigated the mechanisms modulating the interannual variability of ozone concentrations in Shandong Province, where a large population is located and is often subject to ozone pollution. By utilizing both the reanalysis dataset and regional numerical model (WRF-CMAQ), we delve into the potential governing mechanisms of ozone pollution in Shandong Province—especially over the major port city of Qingdao—during summer 2014–2019. During this period, ozone pollution in Qingdao exceeded the tier II standard of the Chinese National Ambient Air Quality (GB 3095-2012) for 75 days. From the perspective of meteorology, the high-pressure ridge over Baikal Lake and to its northeast, which leads to a relatively low humidity and sufficient sunlight, is the most critical weather system inducing high-ozone events in Qingdao. In terms of emissions, biogenic emissions contribute to ozone enhancement close to 10 ppb in the west and north of Shandong Province. Numerical experiments show that the local impact of biogenic emissions on ozone production in Shandong Province is relatively small, whereas biogenic emissions on the southern flank of Shandong Province enhance ozone production and further transport northeastward, resulting in an increase in ozone concentrations over Shandong Province. For the port city of Qingdao, ship emissions increase ozone concentrations when sea breezes (easterlies) prevail over Qingdao, with the 95th percentile reaching 8.7 ppb. The findings in this study have important implications for future ozone pollution in Shandong Province, as well as the northern and coastal areas in China.
Perceptions of Older People with Cognitive Impairment, Caregivers, and Professionals about ehcoBUTLER (Tablet Health Care Platform): A Qualitative Focus Group Study
Authors: Contreras-Somoza Leslie María , Toribio-Guzmán José Miguel , Sánchez-Gómez María Cruz , Irazoki Eider , Martín-Cilleros María Victoria , Verdugo-Castro Sonia , Parra-Vidales Esther , Perea-Bartolomé María Victoria , Franco-Martín Manuel Ángel
Published: June 2022

EhcoBUTLER is a tablet platform mainly aimed at the elderly with mild cognitive impairment (MCI) to promote their well-being and health. The main objective of this study was to explore the perceptions and feedback level of the ehcoBUTLER potential users and stakeholders to improve its development. Through this exploration, the secondary objective was to contribute to the development of software/apps that promote their integral health. Focus groups were conducted (13 elderly with MCI, 13 with dementia, 12 caregivers, 11 professionals). The content and feedback level were analyzed. Participants liked the appearance of ehcoBUTLER, would like to use it, and were mainly interested in the emotional, healthy lifestyle, cognitive, and ergonomic tools. It is necessary to have prior training, more intuitive/customizable apps, low-price/free, offline/USB content, and add other activities/features. EhcoBUTLER is well-oriented to meet the needs and preferences of potential users. However, improvements in its usability, accessibility, and sustainability are needed. The participants’ perspectives provided a comprehensive view to improve ehcoBUTLER, so that in the future, it can benefit the elderly to be active agents in their health; support caregivers in their role and to have a respite; and professionals to have a multi-intervention platform. The present findings can contribute to the development of tablet software/apps that promote the integral well-being of this population.
Optic Flow Speed and Retinal Stimulation Influence Microsaccades
Authors: Raffi Milena , Trofè Aurelio , Meoni Andrea , Gallelli Luca , Piras Alessandro
Published: June 2022

Microsaccades are linked with extraretinal mechanisms that significantly alter spatial perception before the onset of eye movements. We sought to investigate whether microsaccadic activity is modulated by the speed of radial optic flow stimuli. Experiments were performed in the dark on 19 subjects who stood in front of a screen covering 135 × 107° of the visual field. Subjects were instructed to fixate on a central fixation point while optic flow stimuli were presented in full field, in the foveal, and in the peripheral visual field at different dot speeds (8, 11, 14, 17, and 20°/s). Fixation in the dark was used as a control stimulus. For almost all tested speeds, the stimulation of the peripheral retina evoked the highest microsaccade rate. We also found combined effects of optic flow speed and the stimulated retinal region (foveal, peripheral, and full field) for microsaccade latency. These results show that optic flow speed modulates microsaccadic activity when presented in specific retinal portions, suggesting that eye movement generation is strictly dependent on the stimulated retinal regions.
Impact of School and Peer Connectedness on Adolescent Mental Health and Well-Being Outcomes during the COVID-19 Pandemic: A Longitudinal Panel Survey
Authors: Widnall Emily , Winstone Lizzy , Plackett Ruth , Adams Emma A. , Haworth Claire M. A. , Mars Becky , Kidger Judi
Published: June 2022

School closures and social distancing measures during the pandemic have disrupted young people’s daily routines and social relationships. We explored patterns of change in adolescent mental health and tested the relationship between pre-pandemic levels of school and peer connectedness and changes in mental health and well-being between the first lockdown and the return to school. This is a secondary analysis of a longitudinal 3-wave panel survey. The study sample included 603 students (aged 13–14) in 17 secondary schools across south-west England. Students completed a survey pre-pandemic (October 2019), during lockdown (May 2020) and shortly after returning to school (October 2020). Multilevel models, with random effects, were conducted for anxiety, depression and well-being outcomes with school and peer connectedness as predictor variables. Symptoms of anxiety decreased from pre-pandemic to during the first UK lockdown and increased on the return to school; anxious symptoms decreased the most for students reporting feeling least connected to school pre-pandemic. Students reporting low levels of school and peer connectedness pre-pandemic experienced poorer mental health and well-being at all time points. Low school connectedness pre-pandemic was associated with a greater increase in anxious and depressive symptoms between lockdown and the return to school when compared to students with medium levels of school connectedness. No associations were found with high school connectedness or with low/high peer connectedness. For adolescents with poor school connectedness, the enforced time away from school that the pandemic caused led to reduced anxiety. Going forwards, we need to consider ways in which to promote connection with school as a way of supporting mental health and well-being.
Psychometric Analysis and Contribution to the Evaluation of the Exams-Related Emotions Scale in Primary and Secondary School Students
Authors: Obregón-Cuesta Ana Isabel , Mínguez-Mínguez Luis Alberto , León-del-Barco Benito , Mendo-Lázaro Santiago , Fernández-Solana Jessica , González-Santos Josefa , González-Bernal Jerónimo J.
Published: June 2022

The objective of this research was to perform a construct validity, and a psychometric analysis of the Exams-related Emotions Scale (EES), analyze the differences in their scores regarding gender and academic year in primary and secondary education student, as well as study the relationship between emotions and academic performance. During the construction and analysis of the psychometric characteristics of the scale, an Exploratory Factor Analysis (EFA) and a Confirmatory Factor Analysis (CFA) were performed. To test EES scores based on gender and school year, the T-Student test for independent samples and ANOVA were used, respectively. To verify the relationship between the scores of the different types of emotions and academic performance, the Pearson correlation test was performed. A total of 562 students belonging to the 5th (n = 228) and 6th (n = 186) primary school year and the 1st (n = 134) and 2nd (n = 94) secondary school year participated in the research. Age between 10 and 15 years old (mean = 11.66, standard deviation = 1.206) both males (50.5%) and females (49.5%). The results offered support for the three-factor structure. The analysis of invariance with respect to gender showed that the factor structure was invariant. Boys scored higher on the positive emotions factor and lower scores on anxiety than girls. Regarding school year, negative emotions and anxiety related to exams increase in the secondary courses compared to Primary while for positive emotions it is primary school students who obtain higher scores. The correlation coefficient between negative emotions (as well as anxiety) and school performance is negative whereas the correlation coefficient between positive emotions and academic performance is positive. EES scale is an instrument with scientific rigor and with adequate reliability and validity to be able to know the emotions that primary and secondary school students suffer when they are subjected to evaluation processes in the academic context.
Process Evaluation of “The Hygienic Family” Intervention: A Community-Based Water, Sanitation, and Hygiene Project in Rural Malawi
Authors: Panulo Mindy , Chidziwisano Kondwani , Beattie Tara K. , Tilley Elizabeth , Kambala Christabel , Morse Tracy
Published: June 2022

Process evaluations of environmental health interventions are often under-reported and under-utilized in the development of future programs. The “Hygienic Family” intervention targeted improvements in hygiene behaviors of caregivers with under five-year-old children in rural Malawi. Delivered through a combination of open days, cluster meetings, household visits, and prompts, data were collected from two intervention areas for ten months. A process evaluation framework provided indicators that were measured through intervention implementation and expenditure reports, focus groups discussions, interviews, and household surveys. The collected data assessed the intervention fidelity, dose, reach, acceptability, impact, and cost. Results indicated that all planned hygiene promotion messages were delivered, and study participants were better reached primarily through household visits (78% attended over 75% of the intervention) than cluster meetings (57% attended over 75% of the intervention). However, regression found that the number of household visits or cluster meetings had no discernible effect on the presence of some household hygiene proxy indicators. Intervention implementation cost per household was USD 31.00. The intervention delivery model provided good fidelity, dose, and reach and could be used to strengthen the scope of child health and wellbeing content. The intensive face-to-face method has proven to be effective but would need to be adequately resourced through financial support for community coordinator remuneration.
The Relationships between Physical Activity, Exercise, and Sport on the Immune System
Authors: Forte Pedro , Branquinho Luís , Ferraz Ricardo
Published: June 2022

During their lifetime, human beings are exposed to different microorganisms (i [...]
Lower-Limb Arthropathies and Walking: The Use of 3D Gait Analysis as a Relevant Tool in Clinical Practice
Authors: Fouasson-Chailloux Alban , Menu Pierre , Dauty Marc
Published: June 2022

Arthropathy refers to the notion of joint diseases [...]
Relationship between Step-by-Step Foot Kinematics and Sprint Performance
Authors: Martín-Fuentes Isabel , van den Tillaar Roland
Published: June 2022

Foot stiffness is a modulator of sprint performance. However, studies that analysed foot angular velocities using inertial measuring units (IMU) for different events within the sprint contact time phase are scarce. The aim of this study was to investigate the relationship between angular foot step-by-step kinematics and sprint performance during a 50-metre sprint in experienced male and female sprinters. Foot kinematics were measured using IMU devices integrated with a 3-axis gyroscope and a laser gun. The main findings were that men performed faster sprints (6.11 ± 0.35 s vs. 6.77 ± 0.24 s), but the maximal angular foot kinematics were the same between sexes. Maximal angular velocities increased until strides 6–7, where they stabilized. Time from touchdown to maximal dorsiflexion velocity did not change between strides, whereas time from maximal dorsiflexion velocity to toe off decreased until stride 6. Plantarflexion velocities, especially in toe off, showed the greatest associations with sprint times, whereas maximal dorsiflexion velocity presented no association with sprint times. The time from dorsiflexion velocity to toe off from stride 7 onwards determined the sprint performance and was shorter for faster sprinters. The analysis of these variables provides essential information to athletes and coaches that may help to enhance the quality and efficiency of the sprint cycle by giving detailed information on each single stride of the sprint.
Exploring Cultural Bias in Two Different Motor Competence Test Batteries When Used in African Children
Authors: Smits-Engelsman Bouwien , Verbecque Evi , Denysschen Marisja , Coetzee Dané
Published: June 2022

Both the Movement Assessment Battery for Children second edition (M-ABC-2) and Bruininks-Oseretsky Test of Motor Proficiency second edition short form (BOT-2-SF) are frequently used in research and in the clinical practice to evaluate motor competence in children. Despite its widespread use in research, no studies have reported the results of case identification in African children. Comparing these two motor assessment tools for a different target group is important in order to select the most appropriate clinical and research tool. Methods. A total of 444 children performed MABC-2, 165 children also performed the BOT-2-SF and subsamples were tested on specific subtests of the BOT-2 (Running and Agility, Balance, and Strength). Tests were administered to randomly selected children between 6 and 10 years of age. Results: 36% for the children scored at or below the 16th percentile of the MABC-2, while this was 43%, 27%, and 23% for the component score in Manual Dexterity, Aiming and Catching, and Balance, respectively. Of the children 16% scored at or below the 17th percentile of the BOT-2-SF total score, while this was 3%, 9% and 22% for the subtest scores Running and agility, Balance, and Strength, respectively. A moderate correlation (r = 0.44) was found between total scores of the two tests. No significant correlations were found between the dynamic MABC-2 item (Jumping/Hopping) standard scores and any of the 9 balance items of the BOT-2. Conclusion: Far more children scored in the clinical “at risk” range (<16th percentile) when tested with the MABC-2 than with the BOT-2-SF. Overall, these children seemed not to be limited in motor performance measured by the BOT-2-SF, Running and Agility, and Balance. South African children did show lower levels of strength and explosive power. Children from different cultures will need tests for the specific motor skills that are representative for optimal functioning in their own setting. Thus, adapting reference norms and cut-off values may not be the optimal solution.
Relationship between the COVID-19 Pandemic and the Well-Being of Adolescents and Their Parents in Switzerland
Authors: Berchtold André
Published: June 2022

This study is based on two waves of data collected by the Swiss Household panel, the first one in 2019, before the beginning of the COVID-19 pandemic, and the second one in May–June 2020, just after the end of the partial lockdown that was decided by the Swiss government. We considered “couples” of adolescents (age 14–24, mean = 18.82, 51.96% female) and their parents living together (n = 431). Our main goal was to determine whether the evolution of the well-being among adolescents was similar to the evolution of the well-being among parents. Ten indicators of well-being were measured identically in both waves and for both adolescents and their parents. Results indicate that while almost all indicators of well-being decreased during partial lockdown for both adolescents and their parents, adolescents were more strongly impacted than their parents. Furthermore, the change observed in adolescents was virtually unaffected by the change observed in their parents, and vice versa. This research is a reminder that while different population groups may be affected differently by a sudden and extreme event, it is not only older people who will be most affected. Here, adolescents appear to have been more adversely affected than adults.
Effort–Reward Imbalance among a Sample of Formal US Solid Waste Workers
Authors: Le Aurora B. , Shkembi Abas , Sturgis Anna C. , Tadee Anupon , Gibbs Shawn G. , Neitzel Richard L.
Published: June 2022

Background: Solid waste workers are exposed to a plethora of occupational hazards and may also experience work-related stress. Our study had three specific hypotheses: (1) waste workers experience effort–reward imbalance (ERI) with high self-reported effort but low reward, (2) unionized workers experience greater ERI, and (3) workers with higher income have lower ERI. Methods: Waste workers from three solid waste sites in Michigan participated in this cross-sectional study. We characterized perceived work stress using the short-version ERI questionnaire. Descriptive statistics and linear tests for trend were assessed for each scale. Linear regression models were constructed to examine the relationship between structural factors of work stress and ERI. Gradient-boosted regression trees evaluated which factors of effort or reward best characterize workers’ stress. Results: Among 68 participants, 37% of workers reported high effort and low reward from work (ERI > 1). Constant pressure due to heavy workload was most indicative of ERI among the solid waste workers. Union workers experienced 79% times higher ERI than non-unionized workers, while no significant differences were observed by income, after adjusting for confounders. Conclusions: Organizational-level interventions, such as changes related to workload, consideration of fair compensation, and increased support from supervisors, can decrease work stress.
Exploring Online Payment System Adoption Factors in the Age of COVID-19—Evidence from the Turkish Banking Industry
Authors: Coskun Melih , Saygili Ebru , Karahan Mehmet Oguz
Published: June 2022

Turkey’s e-commerce market is rapidly expanding, and the country is ranked first in the world in monthly mobile purchases. The purpose of this study is to determine the factors that influence the adoption of online payments systems among the customers of a Turkish bank during the COVID-19 pandemic. The research model extends the technology acceptance model (TAM) by further examining the impact of 11 factors on attitude, behavioral intention and actual usage. The results suggest a strong influence of these factors on attitude and behavioral intention. Relative advantage, perceived trust, perceived usefulness, personal innovativeness, perceived integrity, perceived ease of use, health and epidemic effects, income, private sector employment and self-employment all have a positive effect on actual online payment system usage. However, perceived risk and age have a negative impact on the actual online payment system usage.
Corporate Social Responsibility Risk and Firm Performance: A Network Perspective
Authors: Luo Jiaqi , Bi Mingxiao , Jia Dandan
Published: June 2022

This study explored how corporate social responsibility (CSR) risk, social networks, and firm performance interacted in light of resource dependence theory and information asymmetry theory to bridge the literature gap between CSR risk and firm performance under the conditions of China’s network. We used data from Shanghai and Shenzhen A-share listed firms in China from 2010 to 2019 to conduct a social network analysis and random-effects GLS regression analysis. The study revealed the following: (1) CSR risk hurts financial performance, while structural holes and network density attenuate this effect; (2) CSR risk positively impacts capital performance, which is amplified by closeness centrality; (3) CSR risk harms innovation performance, while betweenness centrality and network density mitigate this effect. Despite CSR risk bringing short-term benefits, this effect is not sustained. Generally, CSR risks are more detrimental to firms than beneficial. In this study, we strengthen the basis of the research on CSR risk and firm performance, along with research on social networks, advising firms to avoid CSR risks and utilize their networks to mitigate such risks and achieve a better performance.
A Multi-Scale Residential Areas Matching Method Considering Spatial Neighborhood Features
Authors: Ma Jingzhen , Sun Qun , Zhou Zhao , Wen Bowei , Li Shaomei
Published: June 2022

Residential areas is one of the basic geographical elements on the map and an important content of the map representation. Multi-scale residential areas matching refers to the process of identifying and associating entities with the same name in different data sources, which can be widely used in map compilation, data fusion, change detection and update. A matching method considering spatial neighborhood features is proposed to solve the complex matching problem of multi-scale residential areas. The method uses Delaunay triangulation to divide complex matching entities in different scales into closed domains through spatial neighborhood clusters, which can obtain many-to-many matching candidate feature sets. At the same time, the geometric features and topological features of the residential areas are fully considered, and the Relief-F algorithm is used to determine the weight values of different similarity features. Then the similarity and spatial neighborhood similarity of the polygon residential areas are calculated, after which the final matching results are obtained. The experimental results show that the accuracy rate, recall rate and F value of the matching method are all above 90%, which has a high matching accuracy. It can identify a variety of matching relationships and overcome the influence of certain positional deviations on matching results. The proposed method can not only take account of the spatial neighborhood characteristics of residential areas, but also identify complex matching relationships in multi-scale residential areas accurately with a good matching effect.
Expression of Cellular and Extracellular TERRA, TERC and TERT in Hepatocellular Carcinoma
Authors: Manganelli Michele , Grossi Ilaria , Corsi Jessica , D’Agostino Vito Giuseppe , Jurikova Katarina , Cusanelli Emilio , Molfino Sarah , Portolani Nazario , Salvi Alessandro , De Petro Giuseppina
Published: June 2022

Non-coding RNAs are transcribed from telomeres and the telomeric repeat-containing RNAs (TERRA) are implicated in telomere homeostasis and in cancer. In this study, we aimed to assess in hepatocellular carcinoma (HCC) the cellular and extracellular expression of TERRA, the telomerase RNA subunit (TERC) and the telomerase catalytic subunit (TERT). We determined by qPCR the expression level of TERRA 1_2_10_13q, TERRA 15q, TERRA XpYp, TERC and of TERT mRNA in HCC tissues and in the plasma of HCC patients. Further, we profiled the same transcripts in the HCC cell lines, HA22T/VGH and SKHep1C3, and in the extracellular vesicles (EVs) derived from their secretomes. We found that the expression of TERRA and TERT mRNA was significantly deregulated in HCC, being TERRA downregulated and TERT mRNA upregulated in HCC tissues vs. the peritumoral (PT) ones, and the receiver operating characteristic (ROC) curve analyses revealed a significant ability in discriminating HCC from PT tissue. Further, the determinations of circulating TERRA and TERC showed higher amounts of these transcripts in the plasma of HCC patients vs. controls and ROC analyses gave significant results. The expression characterization of the cultured HCC cells showed their ability to produce and secrete TERRA and TERC into the EVs; the ability to produce TERT mRNA that was not detectable in the EVs; and the ability to respond to sorafenib treatment increasing TERRA expression. Our results highlight that: (i) both cellular and extracellular expressions of TERRA and TERC are dysregulated in HCC as well as the cellular expression of TERT mRNA and (ii) the combined detection of TERRA and TERC in plasma may represent a promising approach for non-invasive diagnostic molecular indicators of HCC.
Epigenetic Regulation in Neurodegeneration Disease
Authors: Bodai László
Published: June 2022

Due to their often age-dependent nature, neurodegenerative diseases impact an increasing portion of modern societies [...]
Transcriptomic and Metabolomic Analysis Unravels the Molecular Regulatory Mechanism of Fatty Acid Biosynthesis in Styrax tonkinensis Seeds under Methyl Jasmonate Treatment
Authors: Chen Chen , Chen Hong , Han Chao , Liu Zemao , Ni Ming , Wu Qikui , Yu Fangyuan
Published: June 2022

As the germ of a highly productive oil tree species, Styrax tonkinensis seeds have great potential to produce biodiesel and they have marvelous fatty acid (FA) composition. In order to explore the molecular regulatory mechanism of FA biosynthesis in S. tonkinensis seeds after methyl jasmonate (MJ) application, transcriptomic and metabolomic techniques were adopted so as to dissect the genes that are related to FA biosynthesis and their expression levels, as well as to discover the major FA concentration and composition. The results revealed that 200 μmol/L of MJ (MJ200) increased the crude fat (CF) mass fraction and generated the greatest impact on CF accumulation at 70 days after flowering. Twenty FAs were identified, among which palmitic acid, oleic acid, linoleic acid and linolenic acid were the major FAs, and the presence of MJ200 affected their concentrations variously. MJ200 could enhance FA accumulation through elevating the activity of enzymes that are related to FA synthesis. The number of differentially expressed genes increased with the seeds’ development in general. Fatty acid biosynthesis, the biosynthesis of unsaturated fatty acid, fatty acid elongation and glycerolipid metabolism were the main lipid metabolism pathways that were found to be involved. The changes in the expression levels of EAR, KAR, accA, accB and SAD2 were consistent with the changes in the CF mass fraction, indicating that they are important genes in the FA biosynthesis of S. tonkinensis seeds and that MJ200 promoted their expression levels. In addition, bZIP (which was screened by weighted correlation network analysis) also created significant impacts on FA biosynthesis. Our research has provided a basis for further studies on FA biosynthesis that is regulated by MJ200 at the molecular level and has helped to clarify the functions of key genes in the FA metabolic pathway in S. tonkinensis seeds.
Critical PDT Theory III: Events at the Molecular and Cellular Level
Authors: Kessel David
Published: June 2022

Photodynamic therapy (PDT) is capable of eradicating neoplastic cells that are accessible to sufficient light and oxygen. There is adequate information now available for assessing conditions where PDT might be the therapy of choice, but limited access to clinical facilities and impediments to regulatory approval of new agents have limited clinical usage. Early reports mainly involved clinical data with few thoughts towards finding death pathways. In 2022, there is a clear understanding of the determinants of successful tumor eradication. While PDT may be the optimal method for many clinical indications, support for this approach has lagged. This report provides a commentary on some elements of recent progress in PDT at the molecular and cellular levels, along with a discussion of some of the limitations in current research efforts.
The Relevance of Physico-Chemical Properties and Protein Corona for Evaluation of Nanoparticles Immunotoxicity—In Vitro Correlation Analysis on THP-1 Macrophages
Authors: Pavlin Mojca , Lojk Jasna , Strojan Klemen , Hafner-Bratkovič Iva , Jerala Roman , Leonardi Adrijana , Križaj Igor , Drnovšek Nataša , Novak Saša , Veranič Peter , Bregar Vladimir Boštjan
Published: June 2022

Alongside physiochemical properties (PCP), it has been suggested that the protein corona of nanoparticles (NPs) plays a crucial role in the response of immune cells to NPs. However, due to the great variety of NPs, target cells, and exposure protocols, there is still no clear relationship between PCP, protein corona composition, and the immunotoxicity of NPs. In this study, we correlated PCP and the protein corona composition of NPs to the THP-1 macrophage response, focusing on selected toxicological endpoints: cell viability, reactive oxygen species (ROS), and cytokine secretion. We analyzed seven commonly used engineered NPs (SiO2, silver, and TiO2) and magnetic NPs. We show that with the exception of silver NPs, all of the tested TiO2 types and SiO2 exhibited moderate toxicities and a transient inflammatory response that was observed as an increase in ROS, IL-8, and/or IL-1β cytokine secretion. We observed a strong correlation between the size of the NPs in media and IL-1β secretion. The induction of IL-1β secretion was completely blunted in NLR family pyrin domain containing 3 (NLRP3) knockout THP-1 cells, indicating activation of the inflammasome. The correlations analysis also implicated the association of specific NP corona proteins with the induction of cytokine secretion. This study provides new insights toward a better understanding of the relationships between PCP, protein corona, and the inflammatory response of macrophages for different engineered NPs, to which we are exposed on a daily basis.
Reaction of N-Acetylcysteine with Cu2+: Appearance of Intermediates with High Free Radical Scavenging Activity: Implications for Anti-/Pro-Oxidant Properties of Thiols
Authors: Valent Ivan , Bednárová Lucie , Schreiber Igor , Bujdák Juraj , Valachová Katarína , Šoltés Ladislav
Published: June 2022

We studied the kinetics of the reaction of N-acetyl-l-cysteine (NAC or RSH) with cupric ions at an equimolar ratio of the reactants in aqueous acid solution (pH 1.4–2) using UV/Vis absorption and circular dichroism (CD) spectroscopies. Cu2+ showed a strong catalytic effect on the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical (ABTSr) consumption and autoxidation of NAC. Difference spectra revealed the formation of intermediates with absorption maxima at 233 and 302 nm (ε302/Cu > 8 × 103 M−1 cm−1) and two positive Cotton effects centered at 284 and 302 nm. These intermediates accumulate during the first, O2-independent, phase of the NAC autoxidation. The autocatalytic production of another chiral intermediate, characterized by two positive Cotton effects at 280 and 333 nm and an intense negative one at 305 nm, was observed in the second reaction phase. The intermediates are rapidly oxidized by added ABTSr; otherwise, they are stable for hours in the reaction solution, undergoing a slow pH- and O2-dependent photosensitive decay. The kinetic and spectral data are consistent with proposed structures of the intermediates as disulfide-bridged dicopper(I) complexes of types cis-/trans-CuI2(RS)2(RSSR) and CuI2(RSSR)2. The electronic transitions observed in the UV/Vis and CD spectra are tentatively attributed to Cu(I) → disulfide charge transfer with an interaction of the transition dipole moments (exciton coupling). The catalytic activity of the intermediates as potential O2 activators via Cu(II) peroxo-complexes is discussed. A mechanism for autocatalytic oxidation of Cu(I)–thiolates promoted by a growing electronically coupled –[CuI2(RSSR)]n– polymer is suggested. The obtained results are in line with other reported observations regarding copper-catalyzed autoxidation of thiols and provide new insight into these complicated, not yet fully understood systems. The proposed hypotheses point to the importance of the Cu(I)–disulfide interaction, which may have a profound impact on biological systems.
Ovulation Enhances Intraperitoneal and Ovarian Seedings of High-Grade Serous Carcinoma Cells Originating from the Fallopian Tube: Confirmation in a Bursa-Free Mouse Xenograft Model
Authors: Hsu Che-Fang , Seenan Vaishnavi , Wang Liang-Yuan , Chu Tang-Yuan
Published: June 2022

Background: Recently, new paradigms for the etiology and origin of ovarian high-grade serous carcinoma (HGSC) have emerged. The carcinogens released during ovulation transform fallopian tube epithelial cells, exfoliating and metastasizing to the peritoneal organs, including the ovaries. Solid in vivo evidence of the paradigms in a mouse model is urgently needed but is hampered by the differing tubo-ovarian structures. In mice, there is a bursa structure surrounding the distal oviduct and ovary. This, on one hand, prevents the direct influence of ovulatory follicular fluid (FF) on the exfoliated tumor cells. On the other hand, it hinders the seeding of exfoliated tumor cells into the ovary. Methods: In this study, we created a bursa-free mouse xenograft model to examine the effect of superovulation on peritoneal and ovarian metastases of transformed human tubal epithelial cells after intraperitoneal injection in NSG mice. Results: The bursa-free mouse model showed a better effect of ovulation on peritoneal metastasis. In this model, superovulation increased the number of transformed human tubal epithelial cell seedlings after intraperitoneal injection. Compared to the bursa-intact state, bursa-free ovaries were more vulnerable to external tumor seeding in either normal ovulation or superovulation state. Conclusions: This study provides the first in vivo evidence that intraperitoneal spreading of tubal HGSC cells is enhanced by ovulation. This study also demonstrated a mouse model for studying ovary-peritoneum interaction in cancer development.
Pathogenic Impact of α-Synuclein Phosphorylation and Its Kinases in α-Synucleinopathies
Authors: Kawahata Ichiro , Finkelstein David I. , Fukunaga Kohji
Published: June 2022

α-Synuclein is a protein with a molecular weight of 14.5 kDa and consists of 140 amino acids encoded by the SNCA gene. Missense mutations and gene duplications in the SNCA gene cause hereditary Parkinson’s disease. Highly phosphorylated and abnormally aggregated α-synuclein is a major component of Lewy bodies found in neuronal cells of patients with sporadic Parkinson’s disease, dementia with Lewy bodies, and glial cytoplasmic inclusion bodies in oligodendrocytes with multiple system atrophy. Aggregated α-synuclein is cytotoxic and plays a central role in the pathogenesis of the above-mentioned synucleinopathies. In a healthy brain, most α-synuclein is unphosphorylated; however, more than 90% of abnormally aggregated α-synuclein in Lewy bodies of patients with Parkinson’s disease is phosphorylated at Ser129, which is presumed to be of pathological significance. Several kinases catalyze Ser129 phosphorylation, but the role of phosphorylation enzymes in disease pathogenesis and their relationship to cellular toxicity from phosphorylation are not fully understood in α-synucleinopathy. Consequently, this review focuses on the pathogenic impact of α-synuclein phosphorylation and its kinases during the neurodegeneration process in α-synucleinopathy.
Blood–Brain Barrier Dysfunction and Astrocyte Senescence as Reciprocal Drivers of Neuropathology in Aging
Authors: Preininger Marcela K. , Kaufer Daniela
Published: June 2022

As the most abundant cell types in the brain, astrocytes form a tissue-wide signaling network that is responsible for maintaining brain homeostasis and regulating various brain activities. Here, we review some of the essential functions that astrocytes perform in supporting neurons, modulating the immune response, and regulating and maintaining the blood–brain barrier (BBB). Given their importance in brain health, it follows that astrocyte dysfunction has detrimental effects. Indeed, dysfunctional astrocytes are implicated in age-related neuropathology and participate in the onset and progression of neurodegenerative diseases. Here, we review two mechanisms by which astrocytes mediate neuropathology in the aging brain. First, age-associated blood–brain barrier dysfunction (BBBD) causes the hyperactivation of TGFβ signaling in astrocytes, which elicits a pro-inflammatory and epileptogenic phenotype. Over time, BBBD-associated astrocyte dysfunction results in hippocampal and cortical neural hyperexcitability and cognitive deficits. Second, senescent astrocytes accumulate in the brain with age and exhibit a decreased functional capacity and the secretion of senescent-associated secretory phenotype (SASP) factors, which contribute to neuroinflammation and neurotoxicity. Both BBBD and senescence progressively increase during aging and are associated with increased risk of neurodegenerative disease, but the relationship between the two has not yet been established. Thus, we discuss the potential relationship between BBBD, TGFβ hyperactivation, and senescence with respect to astrocytes in the context of aging and disease and identify future areas of investigation in the field.
Synaptic Cell Adhesion Molecule 3 (SynCAM3) Deletion Promotes Recovery from Spinal Cord Injury by Limiting Glial Scar Formation
Authors: Song Byeong Gwan , Kwon Su Yeon , Kyung Jae Won , Roh Eun Ji , Choi Hyemin , Lim Chang Su , An Seong Bae , Sohn Seil , Han Inbo
Published: June 2022

Synaptic cell adhesion molecules (SynCAMs) play an important role in the formation and maintenance of synapses and the regulation of synaptic plasticity. SynCAM3 is expressed in the synaptic cleft of the central nervous system (CNS) and is involved in the connection between axons and astrocytes. We hypothesized that SynCAM3 may be related to the astrocytic scar (glial scar, the most important factor of CNS injury treatment) through extracellular matrix (ECM) reconstitution. Thus, we investigated the influence of the selective removal of SynCAM3 on the outcomes of spinal cord injury (SCI). SynCAM3 knock-out (KO) mice were subjected to moderate compression injury of the lower thoracic spinal cord using wild-type (WT) (C57BL/6JJc1) mice as controls. Single-cell RNA sequencing analysis over time, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and immunohistochemistry (IHC) showed reduced scar formation in SynCAM3 KO mice compared to WT mice. SynCAM3 KO mice showed improved functional recovery from SCI by preventing the transformation of reactive astrocytes into scar-forming astrocytes, resulting in improved ECM reconstitution at four weeks after injury. Our findings suggest that SynCAM3 could be a novel therapeutic target for SCI.
Characterisation of LTR-Retrotransposons of Stevia rebaudiana and Their Use for the Analysis of Genetic Variability
Authors: Simoni Samuel , Clemente Clarissa , Usai Gabriele , Vangelisti Alberto , Natali Lucia , Tavarini Silvia , Angelini Luciana G. , Cavallini Andrea , Mascagni Flavia , Giordani Tommaso
Published: June 2022

Stevia rebaudiana is one of the most important crops belonging to the Asteraceae family. Stevia is cultivated all over the world as it represents a valid natural alternative to artificial sweeteners thanks to its leaves, which produce steviol glycosides that have high sweetening power and reduced caloric value. In this work, the stevia genome sequence was used to isolate and characterise full-length long-terminal repeat retrotransposons (LTR-REs), which account for more than half of the genome. The Gypsy retrotransposons were twice as abundant as the Copia ones. A disproportionate abundance of elements belonging to the Chromovirus/Tekay lineage was observed among the Gypsy elements. Only the SIRE and Angela lineages represented significant portions of the genome among the Copia elements. The dynamics with which LTR-REs colonised the stevia genome were also estimated; all isolated full-length elements turned out to be relatively young, with a proliferation peak around 1–2 million years ago. However, a different analysis conducted by comparing sequences encoding retrotranscriptase showed the occurrence of an older period in which there was a lot of LTR-RE proliferation. Finally, a group of isolated full-length elements belonging to the lineage Angela was used to analyse the genetic variability in 25 accessions of S. rebaudiana using the Inter-Retrotransposon Amplified Polymorphism (IRAP) protocol. The obtained fingerprints highlighted a high degree of genetic variability and were used to study the genomic structures of the different accessions. It was hypothesised that there are four ancestral subpopulations at the root of the analysed accessions, which all turned out to be admixed. Overall, these data may be useful for genome sequence annotations and for evaluating genetic variability in this species, which may be useful in stevia breeding.
Recent Progress on the Roles of Regulatory T Cells in IgG4-Related Disease
Authors: Uchida Kazushige
Published: June 2022

IgG4-related disease (RD) is a proposed concept of systemic inflammatory condition from Japanese researchers. Patients with IgG4-RD manifest several immunological and histological characterizations in the organs involved, including elevated levels of serum IgG4 and lympho-plasmacytic infiltration, storiform fibrosis, IgG4-positive plasma cells infiltration, and obstructive phlebitis. Nevertheless, the pathogenesis of IgG4-RD still remains unclear. It has been made clear that several immune cells with regulatory function play a vital part in several diseases. In particular, abnormalities in the function and proportion of regulatory T cells (Tregs) are implicated in several diseases, and their part in IgG4-RD has been investigated. This review offers an overview of the research in IgG4-RD related to Tregs. Herein, the basic information of Tregs, knowledge gained from animal models involving Tregs, and the role of IgG4-RD has been provided. We also included the immunological mechanisms of IgG4-RD based on the data accumulated so far in our hypothesis.
Supervised and Individualized Lifestyle Medicine Therapy of a Patient after Myocardial Infarction—Case Study
Authors: Dvorák Márton , Sztancsik Ilona , Babai László , Tóth Miklós , Ács Pongrác
Published: June 2022

Background: In the rehabilitation of patients with cardiovascular disease (CVD) and after myocardial infarction (MI), lifestyle modifications—exercise and nutritional therapy, smoking cessation, stress management—are essential and have a major, long-term impact on the overall health of patients. Methods: After MI and acute primary care, a lifestyle medicine team (medical doctors, dietitian, exercise physiologist) supervised the therapy of a 40 year-old male patient for 12 months. The program included assessments, regular medical controls, personalized diet, and exercise therapy monitored by a heart rate watch. Results: Gradual and continuous weight loss, major reduction in medication and significant improvement in fitness level, blood glucose level, and cardiac function were measured after the program. Due to these positive changes, the patient’s overall health improved to an even better level than before his MI. Conclusion: The results of this program highlight the benefits and importance of the personalized therapy and the lifestyle medicine team approach in the rehabilitation of CVD patients. Individualized and supervised lifestyle therapy should be part of the primary hospital care of CVD patients lead by medical doctors and supported by other health care providers.
The Race to Replace PDE5i: Recent Advances and Interventions to Treat or Manage Erectile Dysfunction: Evidence from Patent Landscape (2016–2021)
Authors: Islam Mohammed Monirul , Naveen Nimbagal Raghavendra , Anitha Posina , Goudanavar Prakash S. , Rao G. S. N. Koteswara , Fattepur Santosh , Rahman Muhammad Muhitur , Shiroorkar Predeepkumar Narayanappa , Habeebuddin Mohammed , Meravanige Girish , Telsang Mallikarjun , Nagaraja Sreeharsha , Asdaq Syed Mohammed Basheeruddin , Anwer MD. Khalid
Published: June 2022

For a few decades, globally, erectile dysfunction (ED) has become more prominent even in young adults and represents a mounting health concern causing a significant effect on men’s quality of life. There is an expectation that by the end of 2025, the number of ED cases can rise to 322 million. We aimed to comprehensively analyze the scientific output of scholarly articles and studies in the field of ED (2016–2021). Data from scholarly articles were collected using Pubmed, and clinical trials-related information was accessed from the clinical trials website. An extensive patent search was conducted using databases such as USPTO (United States patent and trademark office) and EPO (European patent office), WIPO (World Intellectual Property Organization), etc. Owing to the high market value of ED drugs, considerable interest was attained to grab the opportunities. The race to replace the phosphodiesterase type 5 inhibitor (PDE5 inhibitor-PDE5i) can be identified as evident from the significant number of patents filed and the inventions cleared with clinical trials. Some other intriguing interventions are identified for ED treatment but have yet to gain public acceptance. The current analysis confirms the overall evolution and unexplored corners of research on ED treatment strategies with a current global projection.