bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissociation, Cognitive Reflection and Health Literacy Have a Modest Effect on Belief in Conspiracy Theories about COVID-19
Authors: Pisl Vojtech , Volavka Jan , Chvojkova Edita , Cechova Katerina , Kavalirova Gabriela , Vevera Jan
Published: May 2021

Understanding the predictors of belief in COVID-related conspiracy theories and willingness to get vaccinated against COVID-19 may aid the resolution of current and future pandemics. We investigate how psychological and cognitive characteristics influence general conspiracy mentality and COVID-related conspiracy theories. A cross-sectional study was conducted based on data from an online survey of a sample of Czech university students (n = 866) collected in January 2021, using multivariate linear regression and mediation analysis. Sixteen percent of respondents believed that COVID-19 is a hoax, and 17% believed that COVID-19 was intentionally created by humans. Seven percent of the variance of the hoax theory and 10% of the variance of the creation theory was explained by (in descending order of relevance) low cognitive reflection, low digital health literacy, high experience with dissociation and, to some extent, high bullshit receptivity. Belief in COVID-related conspiracy theories depended less on psychological and cognitive variables compared to conspiracy mentality (16% of the variance explained). The effect of digital health literacy on belief in COVID-related theories was moderated by cognitive reflection. Belief in conspiracy theories related to COVID-19 was influenced by experience with dissociation, cognitive reflection, digital health literacy and bullshit receptivity.
Attitudinal Acceptance of Intimate Partner Violence and Mental Health Outcomes for Female Survivors in Sub-Saharan Africa
Authors: Ibala Reine-Marcelle , Seff Ilana , Stark Lindsay
Published: May 2021

While current literature evidences a strong association between gender-based violence exposure and adverse mental health outcomes, few studies have explored how attitudinal acceptance of intimate partner violence (IPV) might impact this relationship. This analysis employed data from 13–24-year-old females as part of the Violence Against Children Surveys in Nigeria, Uganda, and Malawi. Mental health status, defined by the Kessler Screening Scale for Psychological Distress, and suicide ideation served as outcome measures. Predictors of interest included lifetime experiences of IPV and attitudinal acceptance of IPV. Country-stratified logistic and ordinary least squares regressions were used to predict outcomes and included interactions between violence exposure and attitudinal acceptance of IPV. Violence exposure was associated with increased symptoms of mental distress and increased suicide ideation in all countries. Among those who experienced IPV, exhibiting attitudinal acceptance of IPV was associated with improved mental health in Nigeria and Malawi. IPV tolerance conferred lower odds of suicide ideation following IPV exposure in Nigeria. The findings suggest that programs aiming to reduce attitudinal acceptance of IPV must consider how these changes may interact with women’s exposure to IPV.
Does Online Community Participation Contribute to Medication Adherence? An Empirical Study of Patients with Chronic Diseases
Authors: Wu Jyh-Jeng , Chen Yueh-Mei , Talley Paul C. , Kuo Kuang-Ming
Published: May 2021

Effectively improving the medication adherence of patients is crucial. Past studies focused on treatment-related factors, but little attention has been paid to factors concerning human beliefs such as trust or self-efficacy. The purpose of this study is to explore the following aspects of patients with chronic diseases: (1) The relationship between emotional support, informational support, self-efficacy, and trust; (2) the relationship between self-efficacy, trust, and medication adherence; and, (3) whether chronic patients’ participation in different types of online communities brings about significant statistical differences in the relationships between the abovementioned variables. A questionnaire survey was conducted in this study, with 452 valid questionnaires collected from chronic patients previously participating in online community activities. Partial Least Squares-Structural Equation Modeling analysis showed that emotional support and informational support positively predict self-efficacy and trust, respectively, and consequently, self-efficacy and trust positively predict medication adherence. In addition, three relationships including the influence of emotional support on trust, the influence of trust on medication adherence, and the influence of self-efficacy on medication adherence, the types of online communities result in significant statistical differences. Based on the findings, this research suggests healthcare professionals can enhance patients’ self-efficacy in self-care by providing necessary health information via face-to-face or online communities, and assuring patients of demonstrable support. As such, patients’ levels of trust in healthcare professionals can be established, which in turn improves their medication adherence.
Effects of Substituting Types of Physical Activity on Body Fat Mass and Work Efficiency among Workers
Authors: Ma Jiameng , Ma Dongmei , Kim Junghoon , Wang Qiang , Kim Hyunshik
Published: May 2021

Low levels of physical activity (PA) not only increase healt h risks but also affect employee productivity. Although daily activity is interdependent with work productivity and personal health, few studies have examined how substituting physical activities would affect health and work efficiency. The present study aimed to investigate how substituting sedentary behaviors (SB) with increased PA and increasing the intensity of low-level activities during waking times affects the body fat mass and work efficiency of employees. Data were collected from 224 Japanese employees. SB, light physical activity (LPA), moderate physical activity (MPA), and vigorous physical activity (VPA) were measured using a tri-axial accelerometer, and body fat mass and work efficiency were also assessed. Analyses of the effects of substituting behaviors were based on the methods used in the isotemporal substitution model. Body fat mass decreased after substituting behaviors for 30 min per day: from SB to VPA (β = −4.800, 95% CI = −7.500; −2.100), from LPA to VPA (β = −4.680, 95% CI = −7.350; −1.980), and from MPA to VPA (β = −4.920, 95% CI = −7.680; −2.190). For work efficiency and physical activities, a higher work efficiency score was observed when substituting SB with LPA (β = 0.120, 95% CI = 0.030; 0.240), and a lower work efficiency score was observed when substituting LPA with VPA (β = −0.660, 95% CI = −1.350; −0.030). These results should help achieve greater results in promoting health and increasing work productivity by properly distributing and practicing daily physical activities during work hours.
Lessons from Disability Counting in Ecuador, with a Contribution from Primary Health Care
Authors: Debrouwere Inge , Álvarez Vera Pedro Celestino , Pavón Benítez Ximena del Carmen , Rosero Arboleda Celia Katherine , Prinzie Peter , Lebeer Jo
Published: May 2021

Disability data are essential for policy. Yet, the predominant use of disability prevalence for service planning reflects dichotomous counting, increasingly less compatible with current disability thinking. Difficulties relate to variations in rates, the lack of matching with needs, and the use of prevalence to compare disability situations. From the perspective of Primary Health Care (PHC), we explore methods for disability counting regarding the usefulness of prevalences in identifying persons with disabilities and meeting their needs with local service implementation. First, we analyze the methods and results of six national cross-sectional studies in Ecuador. Then, we present a case about an exploratory needs-driven method for disability counting in a local PHC setting. The analysis of variations in rates focuses the attention on reasons for and risks of a priori exclusion of persons with disabilities from services. Longitudinal disability counting as a collateral result of meeting needs in the PHC setting yields local disability data worthy of further exploration. Thinking about disability counting from a PHC scope in a developing country prompted reflection on the comparison of prevalences to evaluate disability situations. Findings invite further exploration of the needs-driven counting method, its contributions to planning local services, and complementarity with cross-sectional disability counting.
One Year of the COVID-19 Pandemic in Galicia: A Global View of Age-Group Statistics during Three Waves
Authors: Area Iván , Lorenzo Henrique , Marcos Pedro J. , Nieto Juan J.
Published: May 2021

In this work we look at the past in order to analyze four key variables after one year of the COVID-19 pandemic in Galicia (NW Spain): new infected, hospital admissions, intensive care unit admissions and deceased. The analysis is presented by age group, comparing at each stage the percentage of the corresponding group with its representation in the society. The time period analyzed covers 1 March 2020 to 1 April 2021, and includes the influence of the B.1.1.7 lineage of COVID-19 which in April 2021 was behind 90% of new cases in Galicia. It is numerically shown how the pandemic affects the age groups 80+, 70+ and 60+, and therefore we give information about how the vaccination process could be scheduled and hints at why the pandemic had different effects in different territories.
Impact of the COVID-19 Pandemic on Life Space Extent and Apathy: A Comparison of Competitive Japanese Swimmers with and without Disabilities
Authors: Kaneda Kazuki , Maeda Noriaki , Suzuki Yuta , Fukui Kazuki , Urabe Yukio
Published: May 2021

Changes in the daily lives and mental health of people with disabilities due to the coronavirus disease (COVID-19) pandemic have not been reported. The Japanese government closed public facilities, including swimming pools, during the first wave of COVID-19, and many competitive swimmers lost their places of activities. This study aimed to investigate the impact of the COVID-19 pandemic on life space and apathy among swimmers and investigated differences in the impact on swimmers with and without disabilities. A total of 39 competitive swimmers participated in this study, including 11 male and nine female swimmers with disabilities (swimmers with disabilities = para-swimmers), and e11 male and eight female swimmers without disabilities. Baseline and follow-up web-based questionnaire surveys were conducted, and changes in life space and apathy scale (AS) were assessed. Female para-swimmers showed significantly lower apathy than female able-bodied subjects (para, during; 16.0 ± 1.9; after, 12.8 ± 3.2; non-disabled; during, 10.5 ± 4.4; after, 10.6 ± 4.8; p < 0.05). Female swimmers with disabilities may be more likely to experience worsening mental health due to changes in their lifestyle.
Association of Child Mental Health with Child and Family Characteristics in Rural China: A Cross-Sectional Analysis
Authors: Wang Huan , Abbey Cody , She Xinshu , Rozelle Scott , Ma Xiaochen
Published: May 2021

Assessing the mental health problems encountered by school children and understanding the contributing factors are crucial to inform strategies aimed at improving mental health in low-resource contexts. However, few studies have investigated the mental health problems among disadvantaged children in poorer countries. This study examines the prevalence of mental health problems in rural China and their association with child and family characteristics. The study uses survey data from 9696 children in 120 rural primary schools and measures child mental health using the Strengths and Difficulties Questionnaire (SDQ). Overall, 17.9% of the sample children were found to be in the abnormal range of the SDQ total difficulties scores. The mean score was 12.93 (SD = 4.94). Abnormal scores were associated with child and family characteristics, including older child age (Odds Ratio, OR = 0.704, 95% CI: 0.611, 0.810; p < 0.001), gender (OR = 1.235, 95% CI: 1.112, 1.371; p < 0.001), and academic performance (OR = 0.421, 95% CI: 0.369, 0.480; p < 0.001). Reading time was found to be protective for mental health. Risk factors include excessive screen time (OR = 1.685, 95% CI: 1.409, 2.016; p < 0.001) and being bullied (OR = 3.695, 95% CI: 3.301, 4.136; p < 0.001). Our study suggests that future mental health illness prevention programs in rural China should consider targeting different aspects of children’s social contexts.
Mechanism of Stability and Transport of Chitosan-Stabilized Nano Zero-Valent Iron in Saturated Porous Media
Authors: Huang Dan , Ren Zhongyu , Li Xiaoyu , Jing Qi
Published: May 2021

Chitosan-stabilized nano zero-valent iron (CTS-nZVI) prepared by the liquid-phase reduction method has been shown to achieve a good dispersion effect. However, there has been little analysis on the mechanism affecting its stability and transport in saturated porous media. In this paper, settling experiments were conducted to study the stabilization of CTS-nZVI. The transport of CTS-nZVI in saturated porous media at different influencing factors was studied by sand column experiments. The stability mechanism of CTS-nZVI was analyzed from the point of view of colloidal stability by settling experiments and a zeta potential test. The theoretical model of colloidal filtration was applied for the calculation of transport coefficients on the basis of the column experiments data. Considering attachment–detachment effects, a particle transport model was built using HYDRUS-1D software to analyze the transport and spatial distribution of CTS-nZVI in a sand column.
Nature’s Role in Outdoor Therapies: An Umbrella Review
Authors: Harper Nevin J. , Fernee Carina R. , Gabrielsen Leiv E.
Published: May 2021

Objective: To report on the role of nature in outdoor therapies through review and summary of existing systematic and meta-analytic reviews in an effort to articulate a theoretical framework for practice. Materials and methods: An umbrella review was conducted following systematic protocols PRISMA guidelines. Results: Fourteen studies met the inclusion criteria and represented five self-identified approaches: nature-based therapies, forest therapy, horticultural therapy, wilderness therapy, and adventure therapy. Clear and comprehensive descriptions of theory, program structure, and activity details with causal links to outcomes were mostly absent. Conclusions: A rigorous and determined program of research is required in order to explicit in-depth theories of change in outdoor therapies. Conversely, or maybe concurrently, a holistic theory of integrated relatedness may be developed as a parallel expression of support for nature in therapy while the explanatory science catches up.
Assessing Factors Associated with TB Awareness in Nepal: A National and Subnational Study
Authors: Iwaki Yoko , Rauniyar Santosh Kumar , Nomura Shuhei , Huang Michael C.
Published: May 2021

Tuberculosis (TB) has still remained a serious global health threat in low- and middle-income countries in recent years. As of 2021, Nepal is one of the high TB burden countries, with an increasing prevalence of cases. This study evaluates factors associated with TB awareness in Nepal. This study uses data from the Nepal Demographic and Health Survey, a cross-sectional survey carried out from June 2016 to January 2017. Multilevel logistic regression is performed to examine the association of demographic and socioeconomic factors with TB awareness. Our findings show a high level of TB awareness in all seven provinces of Nepal. Province 5 has the highest level of awareness (98.1%) among all provinces, followed by provinces 3 and 4, while province 6 has the lowest awareness level (93.2%) compared to others. Socioeconomic factors such as wealth, education and owning a mobile phone are significantly associated with TB awareness. Socioeconomic determinants are influential factors associated with TB awareness in Nepal. The wide variation in the proportion of awareness at a regional level emphasizes the importance of formulating tailored strategies to increase TB awareness. For instance, the use of mobile phones could be an effective strategy to promote TB awareness at a regional level. This study provides valuable evidence to support further research on the contribution of information and communication technology (ICT) usage to improving TB awareness in Nepal.
Movement-Specific Reinvestment in Older People Explains Past Falls and Predicts Future Error-Prone Movements
Authors: Musculus Lisa , Kinrade Noel , Laborde Sylvain , Gleißert Melina , Streich Miriam , Lobinger Babett Helen
Published: May 2021

The tendency to think about or consciously control automated movements (i.e., movement-specific reinvestment) is a crucial factor associated with falling in the elderly. We tested whether elderly people’s movement-specific reinvestment depended on their past falling history and whether it can predict future error-prone movements. In a longitudinal pre-post design, we assessed n = 21 elderly people’s (Mage = 84.38 years, SD = 5.68) falling history, movement-specific reinvestment (i.e., Movement-Specific Reinvestment Scale), and physical functioning (i.e., Short-Physical-Performance Battery). Following a baseline assessment, participants reported their movement behavior in a daily diary for 2 months, after which we assessed their movement-specific reinvestment and physical functioning again (longitudinal, pre-post design). Results revealed, first, that participants’ movement self-consciousness score was fairly stable, while their conscious-motor-processing score was less stable. Second, conscious motor processing was higher in participants who had fallen as opposed to those who had not fallen in the past. Third, conscious motor processing predicted error-prone future movement behavior reported in the daily diary. For identifying individuals who are more prone to fall, caregivers, rehabilitation staff, or doctors could apply the Movement-Specific Reinvestment Scale to screen elderly people’s psychomotor behavior. Based on conscious motor processing, monitoring cognitions could be tailored in theory-based, individual interventions involving both cognitive and motor training.
A Review of Prolonged Post-COVID-19 Symptoms and Their Implications on Dental Management
Authors: Chakraborty Trishnika , Jamal Rizwana Fathima , Battineni Gopi , Teja Kavalipurapu Venkata , Marto Carlos Miguel , Spagnuolo Gianrico
Published: May 2021

The available data regarding the short and long-term consequences of COVID-19 is still insufficient. This narrative review aims to provide information on the prolonged COVID-19 symptoms in recovered patients and their implications during dental management. Additionally, this manuscript highlights the oral manifestations of COVID-19 and its management. A systematic search was conducted in PubMed, Embase, Cochrane Library and Web of Science databases, WHO and CDC websites, and grey literature was searched through Google Scholar. Clinical articles (clinical trials, case-reports, cohort, and cross-sectional studies) were included, reporting prolonged post-COVID-19 symptoms. Although COVID-19 is an infectious disease primarily affecting the lungs, its multi-organ involvement is responsible for several prolonged symptoms, including oral implications. In recovered patients with prolonged COVID-19 symptoms, considerations for providing dental treatment has to be made as they can present with assortment of symptoms. These prolonged post-COVID-19 symptoms can affect the delivery of the required dental treatment. Hence, the recommendations proposed in this narrative review can be a useful starting point to aid dental teams providing adequate care for such recovered patients.
Effects of Mini-Basketball Training Program on Social Communication Impairment and Executive Control Network in Preschool Children with Autism Spectrum Disorder
Authors: Yang Sixin , Liu Zhimei , Xiong Xuan , Cai Kelong , Zhu Lina , Dong Xiaoxiao , Wang Jingui , Zhu Hao , Shi Yifan , Chen Aiguo
Published: May 2021

This study evaluated the effect of a 12-week mini-basketball training program (MBTP) on social communication (SC) and the executive control network (ECN) in preschool children with autism spectrum disorders (ASD). We finally assigned 30 preschool children with ASD to an experiment group (n = 15, 12 males, 3 females) or a control group (n = 15, 13 males, 2 females). The experiment group participated in a 12-week MBTP (40-min sessions per day, 5 days a week), while the control group only received the institutional routine behavioral rehabilitation intervention. The SC of preschool children with ASD was measured using the Social Responsiveness Scale, Second Edition (SRS-2), whereas functional connectivity (FC) of the ECN was assessed using resting-state functional magnetic resonance imaging (rs-fMRI) at pre-and post-test. Our results showed that SC exhibited significant improvement in the intervention group, especially in SRS-2 total score, social cognition, and social communication. We found significantly enhanced functional connectivity between the right cerebellum and left inferior frontal gyrus in the experimental group, while functional connectivity between the left middle temporal gyrus and right cerebellum were decreased in the control group. Furthermore, there were no significant correlations between the change in SC scores and FC of the ECN. Altogether, this study provides valuable insights that a 12-week MBTP improves SC and functional connectivity of the ECN in preschool children with ASD. We further inferred that neural mechanisms might be associated with changing the ECN of preschool ASD children caused by the 12-week MBTP.
Influence of Socioeconomic Status on SARS-CoV-2 Infection in Spanish Pregnant Women. The MOACC-19 Cohort
Authors: Llorca Javier , Lechosa-Muñiz Carolina , Lasarte-Oria Lorena , Cuesta-González Rocío , López-Hoyos Marcos , Gortázar Pilar , Gómez-Acebo Inés , Dierssen-Sotos Trinidad , Cabero-Pérez María J. , The MOACC-19 Group
Published: May 2021

Little is known on socio-economic factors associated with SARS-CoV-2 infection in pregnant women. Here, we analyze the relationship between educational, occupational, and housing variables with SARS-CoV-2 infection in a cohort of 988 pregnant women in Spain. Pregnant women were recruited at the University Hospital Marques de Valdecilla, Santander, Spain, among those delivering from 23 March 2020 onwards or consulting for their 12th week of pregnancy from 26 May 2020 onwards. Information on occupational variables and housing characteristics was self-reported. Pregnant women were tested for a current or past infection of SARS-CoV-2 using both PCR and antibodies detection (ELISA). Logistic regression models were used to analyze factors associated with SARS-CoV-2 infection, adjusting for age and country of origin. Infection by SARS-CoV-2 was not associated with educational level or occupational variables, except for where the pregnant woman was a healthcare worker (odds ratio (OR) = 2.87, 95% confidence interval (CI): 0.84–9.79). Housing with four or more rooms (OR = 2.07, 95% CI: 0.96–4.47), four or more people in the household (OR = 1.91, 95% CI: 0.89–4.14), lack of heating (OR = 2.81, 95% CI: 1.24–6.34) and less than 23 square meters per person (OR = 3.97, 95% CI: 1.43–11.1) were the housing characteristics associated with SARS-CoV-2 infection. Housing characteristics, but not occupational or educational variables, were associated with SARS-CoV-2 infection. Guidelines on the prevention of COVID-19 should reinforce household measures to prevent pregnant women from becoming infected by their relatives.
Comparison of Physical Activity Levels in Youths before and during a Pandemic Lockdown
Authors: Bronikowska Małgorzata , Krzysztoszek Jana , Łopatka Marlena , Ludwiczak Mateusz , Pluta Beata
Published: May 2021

This study aimed to compare physical activity (PA) levels before and during a pandemic lockdown among adolescent Polish youths in relation to meeting the World Health Organization’s (WHO) recommendations of moderate-to-vigorous physical activity (MVPA) and identify potential environmental factors that may affect these levels. An online survey tool that included validated measures of adolescents’ MVPA and socio-environmental, potential confounders was administered to youths (e.g., lack of classmates, motivation, possibility of choosing any physical exercise time, possibility of choosing your own exercises, home environment). The analytic sample comprised 127 adolescents aged 15.4 ± 0.5 years on average (52% girls and 48% boys). The results highlight that among adolescents who did not meet the WHO MVPA recommendations before the lockdown, 13.4% had an increased frequency of PA (from 2.9 to 5.4 day/week) (p = 0.01) during the lockdown. In the group who did meet these recommendations before the lockdown, 50% significantly decreased their level of MVPA below the WHO’s recommendations (p = 0.01). Self-rated health for PA showed a significantly strong correlation with MVPA in the group of students who met the WHO recommendations before the pandemic (r = 0.76; p < 0.05) but failed to maintain that recommendation during the COVID-19 restriction. The results suggest a negative impact of the pandemic on PA undertaken by youths. Based on these results we see the need for increased action by both Physical Education (PE) teachers and parents to motivate and support youngsters in taking up systematic PA consciously.
The Effectiveness of an Annual Nationally Delivered Workplace Step Count Challenge on Changing Step Counts: Findings from Four Years of Delivery
Authors: Niven Ailsa , Ryde Gemma Cathrine , Wilkinson Guy , Greenwood Carl , Gorely Trish
Published: May 2021

Paths for All’s 8-week online Workplace Step Count Challenge (SCC) is a flagship program of Scotland’s National Walking Strategy. The aim of this study was to examine changes in step counts throughout the duration of the SCC, across four years of delivery. Participants were those who registered for the 2015–2018 SCCs, and reported demographic data at registration. Participants self-reported their device-measured step count for each day of the SCC. Following data screening, mean daily steps for each week were calculated. Linear mixed models (R nlme procedure), controlling for the within subject nature of the step count measure, were used to explore changes in steps over time. Gender and age group (<45 years; ≥45 years) were entered into a subsequent model. Separate models were created for each year of the SCC and for all years combined. Participants (n = 10,183) were predominantly women (76.8%), aged <45 (54.6%) and ≥45 years. In general, steps increased each week compared to week 1 (p < 0.001), with a significant increase evident at all but seven of 28 data points. Across the four years of SCC, the increase in steps at week 8 compared to week 1 ranged from 506 to 1223 steps per day, making a substantial contribution to the recommended physical activity levels for health. There was no consistent age or gender effect. The findings provide support for the continued investment in such workplace interventions.
Entrepreneurship and Resilience in Spanish Sports Clubs: A Cluster Analysis
Authors: Escamilla-Fajardo Paloma , Parra-Camacho David , Núñez-Pomar Juan Manuel
Published: May 2021

Entrepreneurial orientation can be an effective response by sports clubs to manage a recession, such as the COVID-19 crisis. Therefore, its study can be fundamental to understand different ways of managing a recession. This study analyzes the entrepreneurial orientation of Spanish non-profit sports clubs to identify different groups and their profiles. The sample is composed of 145 Spanish non-profit sports clubs. Different validated scales have been used to analyze entrepreneurial orientation, business model adaptation, service quality, and economic and social performance (performance in social impact and performance in social causes). Entrepreneurial orientation is the variable used to differentiate the groups. This is made up of three dimensions: innovation, risk-taking, and proactivity. According to the results obtained, there are three groups of sports clubs according to their entrepreneurial orientation: non-entrepreneurs (n = 11), moderate entrepreneurs (n = 85), and strong entrepreneurs (n = 45). There are substantial differences between the three groups according to the adaptation of the business model, the perceived impact of COVID-19, and the returns analyzed. Strong entrepreneurs have considerably higher levels of business model adaptation, economic performance, social performance, and perceived service quality than non-entrepreneurs. Theoretical and practical implications have been drawn that can bring new information to the sports and organizational sector. For example, the diagnosis of the different profiles according to the level of entrepreneurship can be useful to propose strategies to improve performance. In this way, it can help to evaluate the return on the investment made by sponsors or governments in the organization.
Empagliflozin Inhibits IL-1β-Mediated Inflammatory Response in Human Proximal Tubular Cells
Authors: Pirklbauer Markus , Sallaberger Sebastian , Staudinger Petra , Corazza Ulrike , Leierer Johannes , Mayer Gert , Schramek Herbert
Published: May 2021

SGLT2 inhibitor-related nephroprotection is—at least partially—mediated by anti-inflammatory drug effects, as previously demonstrated in diabetic animal and human studies, as well as hyperglycemic cell culture models. We recently presented first evidence for anti-inflammatory potential of empagliflozin (Empa) under normoglycemic conditions in human proximal tubular cells (HPTC) by demonstrating Empa-mediated inhibition of IL-1β-induced MCP-1/CCL2 and ET-1 expression on the mRNA and protein level. We now add corroborating evidence on a genome-wide level by demonstrating that Empa attenuates the expression of several inflammatory response genes in IL-1β-induced (10 ng/mL) normoglycemic HPTCs. Using microarray-hybridization analysis, 19 inflammatory response genes out of >30.000 human genes presented a consistent expression pattern, that is, inhibition of IL-1β (10 ng/mL)-stimulated gene expression by Empa (500 nM), in both HK-2 and RPTEC/TERT1 cells. Pathway enrichment analysis demonstrated statistically significant clustering of annotated pathways (enrichment score 3.64). Our transcriptomic approach reveals novel genes such as CXCL8/IL8, LOX, NOV, PTX3, and SGK1 that might be causally involved in glycemia-independent nephroprotection by SGLT2i.
Hybrid Cyclobutane/Proline-Containing Peptidomimetics: The Conformational Constraint Influences Their Cell-Penetration Ability
Authors: Illa Ona , Ospina Jimena , Sánchez-Aparicio José-Emilio , Pulido Ximena , Abengozar María Ángeles , Gaztelumendi Nerea , Carbajo Daniel , Nogués Carme , Rivas Luis , Maréchal Jean-Didier , Royo Miriam , Ortuño Rosa M.
Published: May 2021

A new family of hybrid β,γ-peptidomimetics consisting of a repetitive unit formed by a chiral cyclobutane-containing trans-β-amino acid plus a Nα-functionalized trans-γ-amino-l-proline joined in alternation were synthesized and evaluated as cell penetrating peptides (CPP). They lack toxicity on the human tumoral cell line HeLa, with an almost negligible cell uptake. The dodecapeptide showed a substantial microbicidal activity on Leishmania parasites at 50 µM but with a modest intracellular accumulation. Their previously published γ,γ-homologues, with a cyclobutane γ-amino acid, showed a well-defined secondary structure with an average inter-guanidinium distance of 8–10 Å, a higher leishmanicidal activity as well as a significant intracellular accumulation. The presence of a very rigid cyclobutane β-amino acid in the peptide backbone precludes the acquisition of a defined conformation suitable for their cell uptake ability. Our results unveiled the preorganized charge-display as a relevant parameter, additional to the separation among the charged groups as previously described. The data herein reinforce the relevance of these descriptors in the design of CPPs with improved properties.
The Role of Mitochondria in Carcinogenesis
Authors: Kozakiewicz Paulina , Grzybowska-Szatkowska Ludmiła , Ciesielka Marzanna , Rzymowska Jolanta
Published: May 2021

The mitochondria are essential for normal cell functioning. Changes in mitochondrial DNA (mtDNA) may affect the occurrence of some chronic diseases and cancer. This process is complex and not entirely understood. The assignment to a particular mitochondrial haplogroup may be a factor that either contributes to cancer development or reduces its likelihood. Mutations in mtDNA occurring via an increase in reactive oxygen species may favour the occurrence of further changes both in mitochondrial and nuclear DNA. Mitochondrial DNA mutations in postmitotic cells are not inherited, but may play a role both in initiation and progression of cancer. One of the first discovered polymorphisms associated with cancer was in the gene NADH-ubiquinone oxidoreductase chain 3 (mt-ND3) and it was typical of haplogroup N. In prostate cancer, these mutations and polymorphisms involve a gene encoding subunit I of respiratory complex IV cytochrome c oxidase subunit 1 gene (COI). At present, a growing number of studies also address the impact of mtDNA polymorphisms on prognosis in cancer patients. Some of the mitochondrial DNA polymorphisms occur in both chronic disease and cancer, for instance polymorphism G5913A characteristic of prostate cancer and hypertension.
Sensitive High-Throughput Assays for Tumour Burden Reveal the Response of a Drosophila melanogaster Model of Colorectal Cancer to Standard Chemotherapies
Authors: Adams Jamie , Casali Andreu , Campbell Kyra
Published: May 2021

Drosophila melanogaster (Drosophila) models of cancer are emerging as powerful tools to investigate the basic mechanisms underlying tumour progression and identify novel therapeutics. Rapid and inexpensive, it is possible to carry out genetic and drug screens at a far larger scale than in vertebrate organisms. Such whole-organism-based drug screens permits assessment of drug absorption and toxicity, reducing the possibility of false positives. Activating mutations in the Wnt and Ras signalling pathways are common in many epithelial cancers, and when driven in the adult Drosophila midgut, it induces aggressive intestinal tumour-like outgrowths that recapitulate many aspects of human colorectal cancer (CRC). Here we have taken a Drosophila CRC model in which tumourous cells are marked with both GFP and luciferase reporter genes, and developed novel high-throughput assays for quantifying tumour burden. Leveraging these assays, we find that the Drosophila CRC model responds rapidly to treatment with standard CRC-drugs, opening the door to future rapid genetic and drug screens.
Impaired Wound Healing, Fibrosis, and Cancer: The Paradigm of Recessive Dystrophic Epidermolysis Bullosa
Authors: Tartaglia Grace , Cao Qingqing , Padron Zachary M. , South Andrew P.
Published: May 2021

Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a devastating skin blistering disease caused by mutations in the gene encoding type VII collagen (C7), leading to epidermal fragility, trauma-induced blistering, and long term, hard-to-heal wounds. Fibrosis develops rapidly in RDEB skin and contributes to both chronic wounds, which emerge after cycles of repetitive wound and scar formation, and squamous cell carcinoma—the single biggest cause of death in this patient group. The molecular pathways disrupted in a broad spectrum of fibrotic disease are also disrupted in RDEB, and squamous cell carcinomas arising in RDEB are thus far molecularly indistinct from other sub-types of aggressive squamous cell carcinoma (SCC). Collectively these data demonstrate RDEB is a model for understanding the molecular basis of both fibrosis and rapidly developing aggressive cancer. A number of studies have shown that RDEB pathogenesis is driven by a radical change in extracellular matrix (ECM) composition and increased transforming growth factor-beta (TGFβ) signaling that is a direct result of C7 loss-of-function in dermal fibroblasts. However, the exact mechanism of how C7 loss results in extensive fibrosis is unclear, particularly how TGFβ signaling is activated and then sustained through complex networks of cell-cell interaction not limited to the traditional fibrotic protagonist, the dermal fibroblast. Continued study of this rare disease will likely yield paradigms relevant to more common pathologies.
Special Issue: “Unraveling the Involvement of Adipose Tissue in Breast Cancer Progression”
Authors: Triulzi Tiziana
Published: May 2021

White adipose tissue (WAT) is a heterogeneous tissue that is composed of adipocytes and several non-adipocyte cell populations, including adipose progenitors, fibroblasts, endothelial and infiltrating immune cells [...]
PARP Power: A Structural Perspective on PARP1, PARP2, and PARP3 in DNA Damage Repair and Nucleosome Remodelling
Authors: van Beek Lotte , McClay Éilís , Patel Saleha , Schimpl Marianne , Spagnolo Laura , Maia de Oliveira Taiana
Published: May 2021

Poly (ADP-ribose) polymerases (PARP) 1-3 are well-known multi-domain enzymes, catalysing the covalent modification of proteins, DNA, and themselves. They attach mono- or poly-ADP-ribose to targets using NAD+ as a substrate. Poly-ADP-ribosylation (PARylation) is central to the important functions of PARP enzymes in the DNA damage response and nucleosome remodelling. Activation of PARP happens through DNA binding via zinc fingers and/or the WGR domain. Modulation of their activity using PARP inhibitors occupying the NAD+ binding site has proven successful in cancer therapies. For decades, studies set out to elucidate their full-length molecular structure and activation mechanism. In the last five years, significant advances have progressed the structural and functional understanding of PARP1-3, such as understanding allosteric activation via inter-domain contacts, how PARP senses damaged DNA in the crowded nucleus, and the complementary role of histone PARylation factor 1 in modulating the active site of PARP. Here, we review these advances together with the versatility of PARP domains involved in DNA binding, the targets and shape of PARylation and the role of PARPs in nucleosome remodelling.
Resistance to Targeted Therapy and RASSF1A Loss in Melanoma: What Are We Missing?
Authors: McKenna Stephanie , García-Gutiérrez Lucía
Published: May 2021

Melanoma is one of the most aggressive forms of skin cancer and is therapeutically challenging, considering its high mutation rate. Following the development of therapies to target BRAF, the most frequently found mutation in melanoma, promising therapeutic responses were observed. While mono- and combination therapies to target the MAPK cascade did induce a therapeutic response in BRAF-mutated melanomas, the development of resistance to MAPK-targeted therapies remains a challenge for a high proportion of patients. Resistance mechanisms are varied and can be categorised as intrinsic, acquired, and adaptive. RASSF1A is a tumour suppressor that plays an integral role in the maintenance of cellular homeostasis as a central signalling hub. RASSF1A tumour suppressor activity is commonly lost in melanoma, mainly by aberrant promoter hypermethylation. RASSF1A loss could be associated with several mechanisms of resistance to MAPK inhibition considering that most of the signalling pathways that RASSF1A controls are found to be altered targeted therapy resistant melanomas. Herein, we discuss resistance mechanisms in detail and the potential role for RASSF1A reactivation to re-sensitise BRAF mutant melanomas to therapy.
Genetic Relationship of Fall Armyworm (Spodoptera frugiperda) Populations That Invaded Africa and Asia
Authors: Acharya Rajendra , Akintola Ashraf Akintayo , Malekera Matabaro Joseph , Kamulegeya Patrick , Nyakunga Keneth Benedictor , Mutimbu Munyaradzi Kennedy , Shrestha Yam Kumar , Hemayet Jahan S. M. , Hoat Trinh Xuan , Dao Hang Thi , Park Jeong-Hoon , Kim Iksoo , Nam Moon , Lee Sung-Jin , Kim Sang-Mok , Hwang Hwal-Su , Lee Kyeong-Yeoll
Published: May 2021

The fall armyworm, Spodoptera frugiperda, is an important agricultural pest native to tropical and subtropical regions of the Western Hemisphere, and has invaded Africa and further spread into most countries of Asia within two years. Here, we analyzed the genetic variation of invaded populations by comparing the nucleotide sequences of two genes: the nuclear Z-chromosome linked gene triose phosphate isomerase (Tpi) and the mitochondrial gene cytochrome oxidase subunit I (COI) of 27 specimens collected in Africa (DR Congo, Tanzania, Uganda, and Zimbabwe) and Asia (Bangladesh, Korea, Nepal, and Vietnam). The results revealed that 25 specimens were from a heterogeneous hybrid (Tpi-corn strain and COI-rice strain; Tpi-C/COI-R) of the corn strain male and rice strain female, but two specimens were from a homogenous corn strain (Tpi-corn strain and COI-corn strain; Tpi-C/COI-C). The further analysis of the fourth exon and the fourth intron sequences of the Tpi gene identified at least four subgroups of the corn strain. These four genetic subgroups were identified in Africa and Asia, suggesting no significant genetic change due to the rapid migration within two years. Our study provides essential information for understanding the genetic diversity of fall armyworm in new habitats.
Venous Thromboembolic Disease in Chronic Inflammatory Lung Diseases: Knowns and Unknowns
Authors: Keramidas George , Gourgoulianis Konstantinos I. , Kotsiou Ourania S.
Published: May 2021

Persistent inflammation within the respiratory tract underlies the pathogenesis of numerous chronic pulmonary diseases. There is evidence supporting that chronic lung diseases are associated with a higher risk of venous thromboembolism (VTE). However, the relationship between lung diseases and/or lung function with VTE is unclear. Understanding the role of chronic lung inflammation as a predisposing factor for VTE may help determine the optimal management and aid in the development of future preventative strategies. We aimed to provide an overview of the relationship between the most common chronic inflammatory lung diseases and VTE. Asthma, chronic obstructive pulmonary disease, interstitial lung diseases, or tuberculosis increase the VTE risk, especially pulmonary embolism (PE), compared to the general population. However, high suspicion is needed to diagnose a thrombotic event early as the clinical presentation inevitably overlaps with respiratory disorders. PE risk increases with disease severity and exacerbations. Hence, hospitalized patients should be considered for thromboprophylaxis administration. Conversely, all VTE patients should be asked for lung comorbidities before determining anticoagulant therapy duration, as those patients are at increased risk of recurrent PE episodes rather than DVT. Further research is needed to understand the underlying pathophysiology of in-situ thrombosis in those patients.
Movement Disorders in Children with a Mitochondrial Disease: A Cross-Sectional Survey from the Nationwide Italian Collaborative Network of Mitochondrial Diseases
Authors: Ticci Chiara , Orsucci Daniele , Ardissone Anna , Bello Luca , Bertini Enrico , Bonato Irene , Bruno Claudio , Carelli Valerio , Diodato Daria , Doccini Stefano , Donati Maria Alice , Dosi Claudia , Filosto Massimiliano , Fiorillo Chiara , La Morgia Chiara , Lamperti Costanza , Marchet Silvia , Martinelli Diego , Minetti Carlo , Moggio Maurizio , Mongini Tiziana Enrica , Montano Vincenzo , Moroni Isabella , Musumeci Olimpia , Pancheri Elia , Pegoraro Elena , Primiano Guido , Procopio Elena , Rubegni Anna , Scalise Roberta , Sciacco Monica , Servidei Serenella , Siciliano Gabriele , Simoncini Costanza , Tolomeo Deborah , Tonin Paola , Toscano Antonio , Tubili Flavia , Mancuso Michelangelo , Battini Roberta , Santorelli Filippo Maria
Published: May 2021

Movement disorders are increasingly being recognized as a manifestation of childhood-onset mitochondrial diseases (MDs). However, the spectrum and characteristics of these conditions have not been studied in detail in the context of a well-defined cohort of patients. We retrospectively explored a cohort of individuals with childhood-onset MDs querying the Nationwide Italian Collaborative Network of Mitochondrial Diseases database. Using a customized online questionnaire, we attempted to collect data from the subgroup of patients with movement disorders. Complete information was available for 102 patients. Movement disorder was the presenting feature of MD in 45 individuals, with a mean age at onset of 11 years. Ataxia was the most common movement disorder at onset, followed by dystonia, tremor, hypokinetic disorders, chorea, and myoclonus. During the disease course, most patients (67.7%) encountered a worsening of their movement disorder. Basal ganglia involvement, cerebral white matter changes, and cerebellar atrophy were the most commonly associated neuroradiological patterns. Forty-one patients harbored point mutations in the mitochondrial DNA, 10 carried mitochondrial DNA rearrangements, and 41 cases presented mutations in nuclear-DNA-encoded genes, the latter being associated with an earlier onset and a higher impairment in activities of daily living. Among our patients, 32 individuals received pharmacological treatment; clonazepam and oral baclofen were the most commonly used drugs, whereas levodopa and intrathecal baclofen administration were the most effective. A better delineation of the movement disorders phenotypes starting in childhood may improve our diagnostic workup in MDs, fine tuning management, and treatment of affected patients.
The Role of Novel Agents in Treating CLL-Associated Autoimmune Hemolytic Anemia
Authors: Noto Alessandro , Cassin Ramona , Mattiello Veronica , Reda Gianluigi
Published: May 2021

Autoimmune cytopenias (AICs) have been reported as a common complication in chronic lymphocytic leukemia (CLL) with autoimmune hemolytic anemia (AIHA), accounting for most cases. According to iwCLL guidelines, AICs poorly responsive to corticosteroids are considered indication for CLL-directed treatment. Chemo-immunotherapy has classically been employed, with variable results, and little data are available on novel agents, the current backbone of CLL therapy. The use of idelalisib in the setting of AICs is controversial and recent recommendations suggest avoiding idelalisib in this setting. Ibrutinib, through ITK-driven Th1 polarization of cell-mediated immune response, is known to produce an immunological rebalancing in CLL, which stands as a fascinating rationale for its use to treat autoimmunity. Although treatment-emergent AIHA has rarely been reported, ibrutinib has shown rapid and durable responses when used to treat AIHA arising in CLL. There is poor evidence regarding the role of BCL-2 inhibitors in CLL-associated AICs and the use of venetoclax in such cases is debated. Furthermore, their frequent use in combination with anti-CD20 agents might represent a confounding factor in evaluating their efficacy. In conclusions, because of their ability to mitigate an immunological dysregulation that is (at least partly) responsible for autoimmunity in CLL, to date BTK-inhibitors stand out as the most suitable choice when treatment of autoimmune cytopenias is required.