bluuebunny/crossref_metadata_2025 huggingface dataset:
Specters of Mob in David Cronenberg’s Eastern Promises
Authors: Bayer Gerd
Published: November 2021

This article situates David Cronenberg’s film Eastern Promises in the context of post-Cold-War European narratives. It argues that the secret dealings of the Russian mob in London are presented in the film as the uncanny and spectral return of forms of government and business that run counter to the rationale conventionally associated with democratic capitalism and at the same time reveal much about its inherent logic. Cronenberg’s film connects private traumata with the violent reality of globalization, staging one as the ghostly realization of the other.
Hydrogen Gas Improves Seed Germination in Cucumber by Regulating Sugar and Starch Metabolisms
Authors: Huang Panpan , Li Changxia , Liu Huwei , Zhao Zongxi , Liao Weibiao
Published: November 2021

Hydrogen gas (H2), an important gaseous regulator, is involved in various plant growth and development processes. However, there have been few studies on the role of H2 in seed germination. In this study, the role and underlying mechanisms of H2 in enhancing seed germination were investigated in cucumber (Cucumis sativus L.). The results revealed that the germination rate, germ length, germination index, and vitality index of cucumber exhibited a dose-dependent relationship with the increase in concentrations of hydrogen-rich water (HRW, a H2 donor; 0, 1, 10, 25, 50, 75, and 100%), attaining the maximum values with 75% HRW treatment. Treatment with 75% HRW resulted in higher contents of soluble sugar, soluble protein, and starch than the control. Additionally, the activity of α-amylase, β-amylase, and total amylase was significantly improved by 75% HRW treatment compared to the control, reaching the maximum values at 36 h. Moreover, the expression levels of starch-related genes AMY and BMY and sugar-related genes SS4 and SS3 were significantly upregulated by 75% HRW treatment during germination, particularly at 36 h. These results suggest that H2 might promote cucumber seed germination by increasing sugar and starch metabolisms.
RsSOS1 Responding to Salt Stress Might Be Involved in Regulating Salt Tolerance by Maintaining Na+ Homeostasis in Radish (Raphanus sativus L.)
Authors: Zhang Wanting , Li Jingxue , Dong Junhui , Wang Yan , Xu Liang , Li Kexin , Yi Xiaofang , Zhu Yuelin , Liu Liwang
Published: November 2021

Radish is a kind of moderately salt-sensitive vegetable. Salt stress seriously decreases the yield and quality of radish. The plasma membrane Na+/H+ antiporter protein Salt Overly Sensitive 1 (SOS1) plays a crucial role in protecting plant cells against salt stress, but the biological function of the RsSOS1 gene in radish remains to be elucidated. In this study, the RsSOS1 gene was isolated from radish genotype ‘NAU-TR17’, and contains an open reading frame of 3414 bp encoding 1137 amino acids. Phylogenetic analysis showed that RsSOS1 had a high homology with BnSOS1, and clustered together with Arabidopsis plasma membrane Na+/H+ antiporter (AtNHX7). The result of subcellular localization indicated that the RsSOS1 was localized in the plasma membrane. Furthermore, RsSOS1 was strongly induced in roots of radish under 150 mmol/L NaCl treatment, and its expression level in salt-tolerant genotypes was significantly higher than that in salt-sensitive ones. In addition, overexpression of RsSOS1 in Arabidopsis could significantly improve the salt tolerance of transgenic plants. Meanwhile, the transformation of RsSOS1△999 could rescue Na+ efflux function of AXT3 yeast. In summary, the plasma membrane Na+/H+ antiporter RsSOS1 plays a vital role in regulating salt-tolerance of radish by controlling Na+ homeostasis. These results provided useful information for further functional characterization of RsSOS1 and facilitate clarifying the molecular mechanism underlying salt stress response in radish.
Stability of Dry and Liquid Metschnikowia pulcherrima Formulations for Biocontrol Applications against Apple Postharvest Diseases
Authors: Bühlmann Andreas , Kammerecker Sandrine , Müller Laurin , Hilber-Bodmer Maja , Perren Sarah , Freimoser Florian M.
Published: November 2021

The yeast Metschnikowia pulcherrima is frequently isolated from environmental samples and has often been reported to exhibit strong antagonistic activity against plant pathogens. In order to assess the potential of this species for its development into a plant protection product, the survival during formulation and storage were quantified and field efficacy was assessed over a period of five years. Freeze dried and liquid M. pulcherrima formulations (i.e., with skim milk powder (SMP), sucrose, glycerol, xanthan, without additives) were prepared and the number of viable cells was quantified during storage at different temperatures. Field trials against apple postharvest diseases (Neofabreae) were performed with different dry formulations. M. pulcherrima proved exceptionally stable for many months and even years. Five years of field trials with the yeast revealed variable effects, but reduced Neofabreae infections of stored apples were observed in some years. M. pulcherrima applications after prior fungicide treatments repeatedly showed an additive effect as compared to the fungicide treatments alone. In summary, M. pulcherrima exhibited highly advantageous storage properties and encouraging activity against apple postharvest rots. Further studies to identify the factors responsible for antagonistic activity in the field and survival during storage are expected to lay the foundation for the future development of a plant protection product.
Risk Perception, Perception of Collective Efficacy and Sleep Quality in Chinese Adults during COVID-19 Pandemic in Hong Kong: A Cross-Sectional Study
Authors: Lin Shiang-Yi , Chung Kevin Kien Hoa
Published: November 2021

Background: Only a few studies have studied the link between risk perception and sleep in the context of the COVID-19 pandemic. The purpose of our study is to propose and test a theoretical model to understand the relationships between COVID-19 risk appraisals—risk perception and perception of collective coordinated defense (PCCD) in particular—and subjective sleep quality in Chinese adults in Hong Kong during the COVID-19 pandemic. COVID-19-related fear and rumination were examined as potential mediators of the relationships. Methods: Data were collected using a self-report online questionnaire from a convenience sample of 224 Chinese adults during the fourth wave of the COVID-19 pandemic in Hong Kong. Results: Risk perception and PCCD were found to predict poor sleep quality. Mediation analysis showed that both fear and rumination mediated the relationship between risk perception and sleep quality, whereas only fear mediated the relationship between PCCD and sleep quality. The model was an excellent fit to the data and accounted for 44% of the variance in sleep quality in Chinese adults. This study indicated that both perception of high risks of contracting COVID-19 and anticipations of collective disease preventive efforts had adverse effects on subjective sleep quality via increasing COVID-19-related fear. Conclusions: These findings underscore the need for addressing sleep problems induced by psychological consequences of the pandemic. While policy makers often deliver public messaging campaigns that frame disease prevention as a collective goal, developing evidence-based coping strategies to combat COVID-19 adverse impacts on psychological health is equally important.
Cognitive Intervention Using Information and Communication Technology for Older Adults with Mild Cognitive Impairment: A Systematic Review and Meta-Analysis
Authors: Jung Ae-Ri , Kim Dasom , Park Eun-A
Published: November 2021

Background: Outside activities have decreased due to the spread of the COVID-19 since 2019; therefore, the need for education using information and communication technology (ICT) for older adults with mild cognitive impairment (MCI) has increased. This study systematically evaluated the effects of cognitive enhancement interventions using ICT on older adults with MCI. Methods: Six electronic databases (CINAHL, Cochrane CENTRAL, EMBASE, PubMed, RISS, and KISS) were searched for relevant articles published from 25 January to 10 February, 2021. Results: As a result of the systematic literature review, 12 research papers were finally selected as the literature for quality evaluation, and 11 final papers were selected, excluding one in the quality evaluation. From the synthesis in this study, it was found that cognitive intervention using ICT showed a statistically significant positive effect on cognitive function when compared with various control groups (SMD = 0.4547; p < 0.001; 95% CI: 0.1980–0.7113). Conclusions: Through this study, cognitive intervention using ICT showed a small effect size for older adults with mild cognitive impairment, and statistically significant results were found.
Examining the Role of Life Skills in Mediating the Relationship between the Basic Psychological Needs and Subjective Well-Being of Taekwondo Student-Athletes
Authors: Bae Jun-Su , Cho Eun-Hyung , Lim Tae-Hee
Published: November 2021

Various theories in the field of positive youth development (PYD) through sport argue that student athletes’ satisfaction with basic psychological needs, life skills development, and well-being are closely related to each other. This study identified the structural relationship among three basic psychological needs, life skills, and subjective well-being. Korean Taekwondo student athletes (N = 302, Mage = 17.67, range = 17–19) completed a survey evaluating basic psychological needs (autonomy, competence, and relatedness), life skills (teamwork, goal setting, social skills, time management, and leadership), and subjective well-being (life satisfaction, positive/negative affect). Data were analyzed by using descriptive statistics, correlation, and the Structural Equation Model (SEM). The model’s goodness of fit was ϰ2/df = 2.78, TLI = 0.90, CFI = 0.90, RMSEA = 0.077 (95% CI = 0.70, 0.80), and SRMR = 0.085. The three basic psychological needs were positively related to life skills and subjective well-being. In addition, life skills had a mediation effect between the three basic psychological needs and subjective well-being. The interpretation of the results indicated that life skills development and well-being depend on basic psychological needs. Thus, coaches should encourage a PYD climate to satisfy their athletes’ psychological needs.
Evaluating Effectiveness of Outpatient Monitoring in Type 2 Diabetes: The One-Year Experience in an Italian Group of Primary Care
Authors: Lazzarini Francesca , Barbacane Luca , Scoleri Giuseppe , Comoretto Rosanna I. , Cogno Gianni , Disarò Benedetta , Gomirato Luigi , Stocco Francesca , Suppa Alessandro , Toninato Gianluca , Minto Clara , Azzolina Danila , Iliceto Sabino , Gregori Dario
Published: November 2021

Nowadays, chronic disease management is the primary challenge of the healthcare system. From 2015, in the Veneto region (Italy), patients with a diagnosis of type 2 diabetes mellitus (T2DM) have been included in the diagnostic-therapeutic pathway (PDTA) program, and their clinical condition has been continuously monitored. The aim of this retrospective study is to determine the effectiveness of PDTA intervention, alone or in combination with a specialized one, in subjects with diagnosis of T2DM. Clinical and behavioral characteristics were collected at baseline and after 1 year of follow-up. Two subgroups were considered: subjects enrolled in PDTA only and subjects enrolled in both the PDTA program and in the care plan proposed by the specialized medical center (CAD group). Longitudinal analysis showed a relevant positive effect of time on diastolic blood pressure, while CAD enrollment appears to be related to higher levels of glycated hemoglobin. When included together in the same model, interaction between time and CAD covariates results in completely nonsignificant effects. As long-term management of chronic disorders, such as T2DM, is often difficult due to disease characteristics and problems in healthcare organization, monitoring programs, such as PDTA, and specialized care programs, such as CAD, do not show a clinically relevant effect in the first year of follow-up. Therefore, they should be analyzed over a longer period. However, they should also carefully consider the need for adequate tools for data collection and sharing, in addition to the context of application, patient expectations and the need for a long-term educational program.
Gait Ability and Muscle Strength in Institutionalized Older Persons with and without Cognitive Decline and Association with Falls
Authors: Dixe Maria dos Anjos , Madeira Carla , Alves Silvia , Henriques Maria Adriana , Baixinho Cristina Lavareda
Published: November 2021

Falls are a complex problem, given their multifactorial nature, the comorbidities involved, and due to the dependency of older persons living in nursing homes. Risk, fear of falling, falls themselves, and their recurrence are the main factors behind fragility fractures, lack of independence, and increases in pain prevalence, and other comorbidities in older populations. The objectives of the present quantitative and longitudinal study were: (a) to characterize the cognitive state and fall frequency of older persons living in nursing homes; (b) to analyze the relationship between cognitive status and some fall risk factors; and (c) to associate cognitive decline, gait ability, and muscle strength of the examined institutionalized older persons with fall occurrence and recurrence over 12 months. The participants were 204 older persons who lived in Portuguese nursing homes, and data were collected from January 2019 to February 2020 by consulting medical records and applying the following instruments: the Mini-Mental State Examination, Timed Up and Go Test, and Medical Research Council Manual Muscle Testing Scale. Fall prevalence, assessed in two periods, 12 months apart, was similar in both samples (with and without cognitive decline) and close to 42%, and the annual recurrence rate was 38.3%. Older persons with no cognitive decline showed an association between gait speed and occurrence of first fall and recurrent fall (p < 0.05). Muscle strength and use of gait aid devices were not related to falls and their recurrence, regardless of mental state.
Understanding Barriers to the Access to Healthcare and Rehabilitation Services: A Qualitative Study with Mothers or Female Caregivers of Children with a Disability in Indonesia
Authors: Asa Gregorius Abanit , Fauk Nelsensius Klau , Mwanri Lillian , Ward Paul Russell
Published: November 2021

Accessibility to healthcare and rehabilitation services for children with a disability (CWD) is essential to improving their health and wellbeing. However, access to the services, especially in many settings in developing countries with scarcity of resources, is still limited. As part of a qualitative study exploring impacts of caring for CWD on mothers or female caregivers and their coping strategies, this paper describes barriers for access to healthcare and rehabilitation services for CWD in Belu district, Indonesia. One-on-one, in-depth interviews were conducted with 22 mothers or female caregivers of CWD. Participants were recruited using a combination of purposive and snowball sampling techniques. These were supplemented with interviews with two staff of disability rehabilitation centers in Belu to understand any additional barriers. Data analysis was guided by a qualitative data analysis framework. Our analysis identified that lack of affordability of healthcare services (high costs and low financial capacity of mothers) was the key barrier for access to healthcare and rehabilitation services CWD. Religious or faith-based factors, such as being a non-Catholic (Belu is predominantly Catholic), converting from Catholic to other religions, and the belief in children’s disability condition as “God’s will”, were also influencing factors for lack of access to the services. Shortage of staff, distrust in the therapy skills of staff at rehabilitation centers, and unavailability of appropriately trained healthcare professionals were structural or system-related barriers. The findings indicate the need for government-owned and run disability rehabilitation centers (not faith-based), the provision of fully subsidised health insurance to provide free services, and the provision of qualified therapists and healthcare professionals (to build trust) in Belu and other similar settings in Indonesia.
Study on Enhanced Methods for Calculating NH3 Emissions from Fertilizer Application in Agriculture Sector
Authors: Woo Jiyun , Song Saenun , Kang Seongmin , Jeon Eui-Chan
Published: November 2021

Ammonia is a representative PM-2.5 secondary product, and the need for management is emerging as health and living damage caused by fine particulate matter worsens. The main source of ammonia is the agricultural sector, and in Korea, 79% of the total ammonia emissions are emitted from the agricultural sector. Among them, there is high uncertainty about how to calculate emissions from ammonia discharged from fertilizer use, and inventory in the U.S. and Europe is borrowed, so inventory needs to be improved according to the situation in Korea. In this study, the ammonia inventory in the agricultural sector in Korea and abroad was examined, and additional activity data that can be used were reviewed. In addition, in order to improve the emission calculation method, the emission was calculated in three ways by different factors. As a result, it was confirmed that the amount of discharge varies depending on the type of soil use or whether cultivated crops are considered, and the possibility of excessive fertilizer top-dress by farmers was confirmed. In order to calculate the emission at a more detailed level based on this study, basic data such as fertilizer input method and regional distribution of crops should be systematically collected, and related follow-up studies should be conducted.
18-Item Version of the Short Gambling Harm Screen (SGHS-18): Validation of Screen for Assessing Gambling-Related Harm among Finnish Population
Authors: Latvala Tiina , Browne Matthew , Rockloff Matthew , Salonen Anne H.
Published: November 2021

Background and aims: It is common for gambling research to focus on problem and disordered gambling. Less is known about the prevalence of gambling-related harms among people in the general population. This study aimed to develop and validate the 18-item version of the Short Gambling Harms Screen (SGHS-18). Methods: Population-representative web-based and postal surveys were conducted in the three geographical areas of Finland (n = 7186, aged 18 or older). Reliability and internal structure of SGHS-18 was assessed using coefficient omega and via confirmatory factor analysis (CFA). Four measurement models of SGHS-18 were compared: one-factor, six-factor, a second-ordered factor model and a bifactor model (M4). Results: The analysis revealed that only the bifactor model had adequate fit for SGHS-18 (CFI = 0.953, TLI = 0.930, GFI = 0.974, RMSEA = 0.047, SRMR = 0.027). The general factor explained most of the common variance compared to specific factors. Coefficient omega hierarchical value for global gambling harm factor (0.80) was high, which suggested that SGHS-18 assessed the combination of general harm constructs sufficiently. The correlation with the Problem and Pathological Gambling Measures (PPGM) was 0.44, potentially reflecting that gambling harms are closely—although not perfectly—aligned with the mental health issue of problem gambling. SGHS-18 scores were substantially higher for participants who gambled more often, who spent more money or who had gambling problems, demonstrating convergent validity for the screen. Discussion: The SGHS-18 comprehensively measures the domains of gambling harm, while demonstrating desirable properties of internal consistency, and criterion and convergent validity.
Association between Active Transportation and Public Transport with an Objectively Measured Meeting of Moderate-to-Vigorous Physical Activity and Daily Steps Guidelines in Adults by Sex from Eight Latin American Countries
Authors: Herreros-Irarrázabal Diego , Guzmán-Habinger Juan , Mahecha Matsudo Sandra , Kovalskys Irina , Gómez Georgina , Rigotti Attilio , Cortés Lilia Yadira , Yépez García Martha Cecilia , Pareja Rossina G. , Herrera-Cuenca Marianella , Farías-Valenzuela Claudio , Marques Adilson , Leme Ana Carolina B. , Fisberg Mauro , Drenowatz Clemens , Ferrari Gerson
Published: November 2021

This study aimed to examine the associations between active transportation and public transport and the objectively measured meeting of moderate-to-vigorous physical activity (MVPA) and steps per day guidelines in adults by sex from eight Latin American countries. As part of the Latin American Study of Nutrition and Health (ELANS), data were collected from 2524 participants aged 18–65 years. MVPA and steps per day were evaluated using Actigraph GT3X accelerometers. The mode of transportation, its frequency and duration were collected using a self-reported questionnaire. The average time dedicated to active transportation was 12.8 min/day in men (IQR: 2.8–30.0) and 12.9 min/day in women (IQR: 4.3–25.7). A logistic regression analysis was conducted, showing that active transportation (≥10 min) was associated with higher odds of meeting MVPA guidelines (men: OR: 2.01; 95%CI: 1.58–2.54; women: OR: 1.57; 95%CI: 1.25–1.96). These results show a greater association when considering active transportation plus public transport (men: OR: 2.98; 95%CI: 2.31–3.91; women: OR: 1.82; 95%CI: 1.45–2.29). Active transportation plus public transport was positively associated with meeting steps per day guidelines only in men (OR: 1.55; 95%CI: 1.15–2.10). This study supports the suggestion that active transportation plus public transport is significantly associated with meeting the MVPA and daily steps recommendations.
Effectiveness of Peer-Led Wellbeing Interventions in Retirement Living: A Systematic Review
Authors: Barras Lilian , Neuhaus Maike , Cyarto Elizabeth V. , Reid Natasha
Published: November 2021

Retirement living (RL) communities may be an ideal setting in which to utilize peer-leaders to implement or support health and wellbeing interventions. To date, this literature has not been systematically summarized. The purpose of this study was to fill this gap with a particular focus on describing the extent to which interventions addressed each level of the social ecological model of behavior change. This review utilized established frameworks for assessing methodological quality of studies, including the CONSORT guidelines and RoB2 bias assessment for cluster randomized controlled trials. A total of 153 records were identified from database searches, and seven studies met inclusion criteria. Overall, there is emerging evidence that peer-led health and wellbeing programs in RL communities can positively impact both health behavior, such as increased physical activity or nutrition, and health status, such as lower blood pressure. The study quality was modest to very good, but only one study was deemed not to have a high risk of bias. Peers are generally cost-effective, more accessible, and relatable leaders for health interventions that can still produce impactful changes. Future studies are needed to better understand how to sustain promising interventions.
Regulatory Resistance? Narratives and Uses of Evidence around “Black Market” Provision of Gambling during the British Gambling Act Review
Authors: Wardle Heather , Reith Gerda , Dobbie Fiona , Rintoul Angela , Shiffman Jeremy
Published: November 2021

Commercial gambling is increasingly viewed as being part of the unhealthy commodities industries, in which products contribute to preventable ill-health globally. Britain has one of the world’s most liberal gambling markets, meaning that the regulatory changes there have implications for developments elsewhere. A review of the British Gambling Act 2005 is underway. This has generated a range of actions by the industry, including mobilising arguments around the threat of the “black market”. We critically explore industry’s framing of these issues as part of their strategy to resist regulatory change during the Gambling Act review. We used a predefined review protocol to explore industry narratives about the “black market” in media reports published between 8 December 2020 and 26 May 2021. Fifty-five articles were identified and reviewed, and themes were narratively synthesised to examine industry framing of the “black market”. The black market was framed in terms of economic threat and loss, and a direct connection was made between its growth and increased regulation. The articles mainly presented gambling industry perspectives uncritically, citing industry-generated evidence (n = 40). Industry narratives around the “black market” speak to economically and emotionally salient concerns: fear, safety, consumer freedom and economic growth. This dominant framing in political, mainstream and industry media may influence political and public opinion to support the current status quo: “protecting” the existing regulated market rather than “protecting” people. Debates should be reframed to consider all policy options, especially those designed to protect public health.
The Geography of Social Media Data in Urban Areas: Representativeness and Complementarity
Authors: Bernabeu-Bautista Álvaro , Serrano-Estrada Leticia , Perez-Sanchez V. Raul , Martí Pablo
Published: November 2021

This research sheds light on the relationship between the presence of location-based social network (LBSN) data and other economic and demographic variables in the city of Valencia (Spain). For that purpose, a comparison is made between location patterns of geolocated data from various social networks (i.e., Google Places, Foursquare, Twitter, Airbnb and Idealista) and statistical information such as land value, average gross income, and population distribution by age range. The main findings show that there is no direct relationship between land value or age of registered population and the amount of social network data generated in a given area. However, a noteworthy coincidence was observed between Google Places data-clustering patterns, which represent the offer of economic activities, and the spatial concentration of the other LBSNs analyzed, suggesting that data from these sources are mostly generated in areas with a high density of economic activities.
The Protective Role of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia–Reperfusion
Authors: Casili Giovanna , Ardizzone Alessio , Basilotta Rossella , Lanza Marika , Filippone Alessia , Paterniti Irene , Esposito Emanuela , Campolo Michela
Published: November 2021

Ischemia/reperfusion injury (IRI) is a complex pathophysiological process characterized by blood circulation disorder caused by various factors, such as traumatic shock, surgery, organ transplantation, and thrombus. Severe metabolic dysregulation and tissue structure destruction are observed upon restoration of blood flow to the ischemic tissue. The kidney is a highly perfused organ, sensitive to ischemia and reperfusion injury, and the incidence of renal IRI has high morbidity and mortality. Several studies showed that infiltration of inflammatory cells, apoptosis, and angiogenesis are important mechanisms involved in renal IRI. Despite advances in research, effective therapies for renal IRI are lacking. Recently it has been demonstrated the role of KYP2047, a selective inhibitor of prolyl oligopeptidase (POP), in the regulation of inflammation, apoptosis, and angiogenesis. Thus, this research focused on the role of POP in kidney ischemia/reperfusion (KI/R). An in vivo model of KI/R was performed and mice were subjected to KYP2047 treatment (intraperitoneal, 0.5, 1 and 5 mg/kg). Histological analysis, Masson’s trichrome and periodic acid shift (PAS) staining, immunohistochemical and Western blots analysis, real-time PCR (RT-PCR) and ELISA were performed on kidney samples. Moreover, serum creatinine and blood urea nitrogen (BUN) were quantified. POP-inhibition by KYP2047 treatment, only at the doses of 1 and 5 mg/kg, significantly reduced renal injury and collagen amount, regulated inflammation through canonical and non-canonical NF-κB pathway, and restored renal function. Moreover, KYP2047 modulated angiogenesis markers, such as TGF-β and VEGF, also slowing down apoptosis. Interestingly, treatment with KYP2047 modulated PP2A activity. Thus, these findings clarified the role of POP inhibition in AKI, also offering novel therapeutic target for renal injury after KI/R.
Contribution of Dysregulated DNA Methylation to Autoimmunity
Authors: Funes Samanta C. , Fernández-Fierro Ayleen , Rebolledo-Zelada Diego , Mackern-Oberti Juan P. , Kalergis Alexis M.
Published: November 2021

Epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs are known regulators of gene expression and genomic stability in cell growth, development, and differentiation. Because epigenetic mechanisms can regulate several immune system elements, epigenetic alterations have been found in several autoimmune diseases. The purpose of this review is to discuss the epigenetic modifications, mainly DNA methylation, involved in autoimmune diseases in which T cells play a significant role. For example, Rheumatoid Arthritis and Systemic Lupus Erythematosus display differential gene methylation, mostly hypomethylated 5′-C-phosphate-G-3′ (CpG) sites that may associate with disease activity. However, a clear association between DNA methylation, gene expression, and disease pathogenesis must be demonstrated. A better understanding of the impact of epigenetic modifications on the onset of autoimmunity will contribute to the design of novel therapeutic approaches for these diseases.
Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes
Authors: Bomer Nils , Pavez-Giani Mario G. , Deiman Frederik E. , Linders Annet N. , Hoes Martijn F. , Baierl Christiane L.J. , Oberdorf-Maass Silke U. , de Boer Rudolf A. , Silljé Herman H.W. , Berezikov Eugene , Simonides Warner S. , Westenbrink B. Daan , van der Meer Peter
Published: November 2021

Members of the fetal-gene-program may act as regulatory components to impede deleterious events occurring with cardiac remodeling, and constitute potential novel therapeutic heart failure (HF) targets. Mitochondrial energy derangements occur both during early fetal development and in patients with HF. Here we aim to elucidate the role of DIO2, a member of the fetal-gene-program, in pluripotent stem cell (PSC)-derived human cardiomyocytes and on mitochondrial dynamics and energetics, specifically. RNA sequencing and pathway enrichment analysis was performed on mouse cardiac tissue at different time points during development, adult age, and ischemia-induced HF. To determine the function of DIO2 in cardiomyocytes, a stable human hPSC-line with a DIO2 knockdown was made using a short harpin sequence. Firstly, we showed the selenoprotein, type II deiodinase (DIO2): the enzyme responsible for the tissue-specific conversion of inactive (T4) into active thyroid hormone (T3), to be a member of the fetal-gene-program. Secondly, silencing DIO2 resulted in an increased reactive oxygen species, impaired activation of the mitochondrial unfolded protein response, severely impaired mitochondrial respiration and reduced cellular viability. Microscopical 3D reconstruction of the mitochondrial network displayed substantial mitochondrial fragmentation. Summarizing, we identified DIO2 to be a member of the fetal-gene-program and as a key regulator of mitochondrial performance in human cardiomyocytes. Our results suggest a key position of human DIO2 as a regulator of mitochondrial function in human cardiomyocytes.
New Insight into Molecular and Hormonal Connection in Andrology
Authors: Francomano Davide , Sanguigni Valerio , Capogrosso Paolo , Deho Federico , Antonini Gabriele
Published: November 2021

Hormones and cytokines are known to regulate cellular functions in the testes. These biomolecules induce a broad spectrum of effects on various level of spermatogenesis, and among them is the modulation of cell junction restructuring between Sertoli cells and germ cells in the seminiferous epithelium. Cytokines and androgens are closely related, and both correct testicular development and the maintenance of spermatogenesis depend on their function. Cytokines also play a crucial role in the immune testicular system, activating and directing leucocytes across the endothelial barrier to the inflammatory site, as well as in increasing their adhesion to the vascular wall. The purpose of this review is to revise the most recent findings on molecular mechanisms that play a key role in male sexual function, focusing on three specific molecular patterns, namely, cytokines, miRNAs, and endothelial progenitor cells. Numerous reports on the interactions between the immune and endocrine systems can be found in the literature. However, there is not yet a multi-approach review of the literature underlying the role between molecular patterns and testicular and sexual function.
Interplay between Prokineticins and Histone Demethylase KDM6A in a Murine Model of Bortezomib-Induced Neuropathy
Authors: Rullo Laura , Franchi Silvia , Amodeo Giada , Caputi Francesca Felicia , Verduci Benedetta , Losapio Loredana Maria , Sacerdote Paola , Romualdi Patrizia , Candeletti Sanzio
Published: November 2021

Chemotherapy-induced neuropathy (CIN) is a major adverse effect associated with many chemotherapeutics, including bortezomib (BTZ). Several mechanisms are involved in CIN, and recently a role has been proposed for prokineticins (PKs), a chemokine family that induces proinflammatory/pro-algogen mediator release and drives the epigenetic control of genes involved in cellular differentiation. The present study evaluated the relationships between epigenetic mechanisms and PKs in a mice model of BTZ-induced painful neuropathy. To this end, spinal cord alterations of histone demethylase KDM6A, nuclear receptors PPARα/PPARγ, PK2, and pro-inflammatory cytokines IL-6 and IL-1β were assessed in neuropathic mice treated with the PK receptors (PKRs) antagonist PC1. BTZ treatment promoted a precocious upregulation of KDM6A, PPARs, and IL-6, and a delayed increase of PK2 and IL-1β. PC1 counteracted allodynia and prevented the increase of PK2 and of IL-1β in BTZ neuropathic mice. The blockade of PKRs signaling also opposed to KDM6A increase and induced an upregulation of PPAR gene transcription. These data showed the involvement of epigenetic modulatory enzymes in spinal tissue phenomena associated with BTZ painful neuropathy and underline a role of PKs in sustaining the increase of proinflammatory cytokines and in exerting an inhibitory control on the expression of PPARs through the regulation of KDM6A gene expression in the spinal cord.
Functional Selectivity of Dopamine D1 Receptor Signaling: Retrospect and Prospect
Authors: Yang Yang
Published: November 2021

Research progress on dopamine D1 receptors indicates that signaling no longer is limited to G protein-dependent cyclic adenosine monophosphate phosphorylation but also includes G protein-independent β-arrestin-related mitogen-activated protein kinase activation, regulation of ion channels, phospholipase C activation, and possibly more. This review summarizes recent studies revealing the complexity of D1 signaling and its clinical implications, and suggests functional selectivity as a promising strategy for drug discovery to magnify the merit of D1 signaling. Functional selectivity/biased receptor signaling has become a major research front because of its potential to improve therapeutics through precise targeting. Retrospective pharmacological review indicated that many D1 ligands have some degree of mild functional selectivity, and novel compounds with extreme bias at D1 signaling were reported recently. Behavioral and neurophysiological studies inspired new methods to investigate functional selectivity and gave insight into the biased signaling of several drugs. Results from recent clinical trials also supported D1 functional selectivity signaling as a promising strategy for discovery and development of better therapeutics.
Adhesive Antimicrobial Peptides Containing 3,4-Dihydroxy-L-Phenylalanine Residues for Direct One-Step Surface Coating
Authors: Hwang Young Eun , Im Seonghun , Kim Hyun , Sohn Jung-Hoon , Cho Byung-Kwan , Cho Ju Hyun , Sung Bong Hyun , Kim Sun Chang
Published: November 2021

Bacterial colonization and transmission via surfaces increase the risk of infection. In this study, we design and employ novel adhesive antimicrobial peptides to prevent bacterial contamination of surfaces. Repeats of 3,4-dihydroxy-L-phenylalanine (DOPA) were added to the C-terminus of NKC, a potent synthetic antimicrobial peptide, and the adhesiveness and antibacterial properties of the resulting peptides are evaluated. The peptide is successfully immobilized on polystyrene, titanium, and polydimethylsiloxane surfaces within 10 min in a one-step coating process with no prior surface functionalization. The antibacterial effectiveness of the NKC-DOPA5-coated polystyrene, titanium, and polydimethylsiloxane surfaces is confirmed by complete inhibition of the growth of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus within 2 h. The stability of the peptide coated on the substrate surface is maintained for 84 days, as confirmed by its bactericidal activity. Additionally, the NKC-DOPA5-coated polystyrene, titanium, and polydimethylsiloxane surfaces show no cytotoxicity toward the human keratinocyte cell line HaCaT. The antimicrobial properties of the peptide-coated surfaces are confirmed in a subcutaneous implantation animal model. The adhesive antimicrobial peptide developed in this study exhibits potential as an antimicrobial surface-coating agent for efficiently killing a broad spectrum of bacteria on contact.
High-Molecular-Weight Hyaluronic Acid Inhibits IL-1β-Induced Synovial Inflammation and Macrophage Polarization through the GRP78-NF-κB Signaling Pathway
Authors: Lee Chien-Hsing , Chiang Chi-Fu , Kuo Feng-Chih , Su Sheng-Chiang , Huang Chia-Luen , Liu Jhih-Syuan , Lu Chieh-Hua , Hsieh Chang-Hsun , Wang Chih-Chien , Lee Chian-Her , Shen Pei-Hung
Published: November 2021

Recent evidence has suggested that synovial inflammation and macrophage polarization were involved in the pathogenesis of osteoarthritis (OA). Additionally, high-molecular-weight hyaluronic acid (HMW-HA) was often used clinically to treat OA. GRP78, an endoplasmic reticulum (ER) stress chaperone, was suggested to contribute to the hyperplasia of synovial cells in OA. However, it was still unclear whether HMW-HA affected macrophage polarization through GRP78. Therefore, we aimed to identify the effect of HMW-HA in primary synovial cells and macrophage polarization and to investigate the role of GRP78 signaling. We used IL-1β to treat primary synoviocytes to mimic OA, and then treated them with HMW-HA. We also collected conditioned medium (CM) to culture THP-1 macrophages and examine the changes in the phenotype. IL-1β increased the expression of GRP78, NF-κB (p65 phosphorylation), IL-6, and PGE2 in primary synoviocytes, accompanied by an increased macrophage M1/M2 polarization. GRP78 knockdown significantly reversed the expression of IL-1β-induced GRP78-related downstream molecules and macrophage polarization. HMW-HA with GRP78 knockdown had additive effects in an IL-1β culture. Finally, the synovial fluid from OA patients revealed significantly decreased IL-6 and PGE2 levels after the HMW-HA treatment. Our study elucidated a new form of signal transduction for HMW-HA-mediated protection against synovial inflammation and macrophage polarization and highlighted the involvement of the GRP78-NF-κB signaling pathway.
Relevance of BRAF Subcellular Localization and Its Interaction with KRAS and KIT Mutations in Skin Melanoma
Authors: Beleaua Marius-Alexandru , Jung Ioan , Braicu Cornelia , Milutin Doina , Gurzu Simona
Published: November 2021

Although skin melanoma (SKM) represents only one-quarter of newly diagnosed skin malignant tumors, it presents a high mortality rate. Hence, new prognostic and therapeutic tools need to be developed. This study focused on investigating the prognostic value of the subcellular expression of BRAF, KRAS, and KIT in SKM in correlation with their gene-encoding interactions. In silico analysis of the abovementioned gene interactions, along with their mRNA expression, was conducted, and the results were validated at the protein level using immunohistochemical (IHC) stains. For IHC expression, the encoded protein expressions were checked on 96 consecutive SKMs and 30 nevi. The UALCAN database showed no prognostic value for the mRNA expression level of KRAS and BRAF and demonstrated a longer survival for patients with low mRNA expression of KIT in SKMs. IHC examinations of SKMs confirmed the UALCAN data and showed that KIT expression was inversely correlated with ulceration, Breslow index, mitotic rate, and pT stage. KRAS expression was also found to be inversely correlated with ulceration and perineural invasion. When the subcellular expression of BRAF protein was recorded (nuclear vs. cytoplasmatic vs. mixed nucleus + cytoplasm), a direct correlation was emphasized between nuclear positivity and lymphovascular or perineural invasion. The independent prognostic value was demonstrated for mixed expression of the BRAF protein in SKM. BRAF cytoplasmic predominance, in association with KIT’s IHC positivity, was more frequently observed in early-stage nonulcerated SKMs, which displayed a low mitotic rate and a late death event. The present study firstly verified the possible prognostic value of BRAF subcellular localization in SKMs. A low mRNA expression or IHC cytoplasmic positivity for KIT and BRAF might be used as a positive prognostic parameter of SKM. SKM’s BRAF nuclear positivity needs to be evaluated in further studies as a possible indicator of perineural and lymphovascular invasion.
Multi-Run Concrete Autoencoder to Identify Prognostic lncRNAs for 12 Cancers
Authors: Al Mamun Abdullah , Tanvir Raihanul Bari , Sobhan Masrur , Mathee Kalai , Narasimhan Giri , Holt Gregory E. , Mondal Ananda Mohan
Published: November 2021

Background: Long non-coding RNA plays a vital role in changing the expression profiles of various target genes that lead to cancer development. Thus, identifying prognostic lncRNAs related to different cancers might help in developing cancer therapy. Method: To discover the critical lncRNAs that can identify the origin of different cancers, we propose the use of the state-of-the-art deep learning algorithm concrete autoencoder (CAE) in an unsupervised setting, which efficiently identifies a subset of the most informative features. However, CAE does not identify reproducible features in different runs due to its stochastic nature. We thus propose a multi-run CAE (mrCAE) to identify a stable set of features to address this issue. The assumption is that a feature appearing in multiple runs carries more meaningful information about the data under consideration. The genome-wide lncRNA expression profiles of 12 different types of cancers, with a total of 4768 samples available in The Cancer Genome Atlas (TCGA), were analyzed to discover the key lncRNAs. The lncRNAs identified by multiple runs of CAE were added to a final list of key lncRNAs that are capable of identifying 12 different cancers. Results: Our results showed that mrCAE performs better in feature selection than single-run CAE, standard autoencoder (AE), and other state-of-the-art feature selection techniques. This study revealed a set of top-ranking 128 lncRNAs that could identify the origin of 12 different cancers with an accuracy of 95%. Survival analysis showed that 76 of 128 lncRNAs have the prognostic capability to differentiate high- and low-risk groups of patients with different cancers. Conclusion: The proposed mrCAE, which selects actual features, outperformed the AE even though it selects the latent or pseudo-features. By selecting actual features instead of pseudo-features, mrCAE can be valuable for precision medicine. The identified prognostic lncRNAs can be further studied to develop therapies for different cancers.
The Role of Endothelium in COVID-19
Authors: Ionescu Mihaela , Stoian Anca Pantea , Rizzo Manfredi , Serban Dragos , Nuzzo Domenico , Mazilu Laura , Suceveanu Andra Iulia , Dascalu Ana Maria , Parepa Irinel Raluca
Published: November 2021

The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), is causing a global pandemic. The virus primarily affects the upper and lower respiratory tracts and raises the risk of a variety of non-pulmonary consequences, the most severe and possibly fatal of which are cardiovascular problems. Data show that almost one-third of the patients with a moderate or severe form of COVID-19 had preexisting cardiovascular comorbidities such as diabetes mellitus, obesity, hypertension, heart failure, or coronary artery disease. SARS-CoV2 causes hyper inflammation, hypoxia, apoptosis, and a renin–angiotensin system imbalance in a variety of cell types, primarily endothelial cells. Profound endothelial dysfunction associated with COVID-19 can be the cause of impaired organ perfusion that may generate acute myocardial injury, renal failure, and a procoagulant state resulting in thromboembolic events. We discuss the most recent results on the involvement of endothelial dysfunction in the pathogenesis of COVID-19 in patients with cardiometabolic diseases in this review. We also provide insights on treatments that may reduce the severity of this viral infection.
A Novel Heat Shock Transcription Factor (ZmHsf08) Negatively Regulates Salt and Drought Stress Responses in Maize
Authors: Wang Jing , Chen Li , Long Yun , Si Weina , Cheng Beijiu , Jiang Haiyang
Published: November 2021

Heat shock transcription factors (HSFs) play important roles in plant growth, development, and stress responses. However, the function of these transcription factors in abiotic stress responses in maize (Zea mays) remains largely unknown. In this study, we characterized a novel HSF transcription factor gene, ZmHsf08, from maize. ZmHsf08 was highly homologous to SbHsfB1, BdHsfB1, and OsHsfB1, and has no transcriptional activation activity. The expression profiles demonstrated that ZmHsf08 was differentially expressed in various organs of maize and was induced by salt, drought, and abscisic acid (ABA) treatment. Moreover, the overexpression of ZmHsf08 in maize resulted in enhanced sensitivity to salt and drought stresses, displaying lower survival rates, higher reactive oxygen species (ROS) levels, and increased malondialdehyde (MDA) contents compared with wild-type (WT) plants. Furthermore, RT-qPCR analyses revealed that ZmHsf08 negatively regulates a number of stress/ABA-responsive genes under salt and drought stress conditions. Collectively, these results indicate that ZmHsf08 plays a negative role in response to salt and drought stresses in maize.