bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface Microanalysis and Sequential Chemical Extraction as Tools for Reliable Environmental Mobility Assessment of Sb and Other Metals
Authors: Álvarez-Quintana Jéssica , Ordóñez Almudena , García-Ordiales Efrén , Álvarez Rodrigo
Published: August 2022

Sequential extraction procedures (SEPs) are widely used in environmental studies to infer the chemical and/or mineralogical forms of pollutants of concern in soils and sediments. Although there is no general agreement among the scientific community, these methods have shown some limitations, especially those with a lack of objectivity in their interpretation. In this work, a soil sampling campaign was carried out in an area affected by an abandoned Sb mine. Samples (0–15 cm) were carefully prepared and analyzed by an SEP. They were also studied by conventional mineralogical methods (optical and electronic microscopy, both scanning and transmission, with a coupled energy dispersive X-ray (EDX) spectrometer). When comparing the results obtained from both techniques, some discrepancies are highlighted, with As, Cu, Pb, Sb and Zn as elements of concern. For Sb, Cu, Pb and As the predominant fraction (excluding the residual one) is that associated with organic matter (from 8.54 for Sb to 18.90% for Cu). The fractions of pollutants linked to Fe and/or Mn oxides are quantitatively important for As, Pb and Zn (6.46%, 12.05% and 7.43%, respectively) and almost negligible for Cu and Sb. On the contrary, analyses carried out by EDX at a grain scale pointed out that no detectable quantities of the elements of concern were present on the surface of the organic particles. Sb and Pb were always detectable in Fe oxides (up to 1.84 and 5.76%, respectively). Regarding the role of the clayey fraction, the only disagreement between the employed SEP and the microanalysis is in relation to As. Arsenic bound to clay minerals was found to be an order of magnitude lower than As associated with Fe oxides (0.56% and 6.46%, respectively); in contrast, EDX microanalyses showed similar As contents in both groups. Given the objectiveness of EDX microanalysis, these differences should be considered inaccuracies in the interpretation of the sequential extraction results.
Does the Element Availability Change in Soils Exposed to Bioplastics and Plastics for Six Months?
Authors: Santini Giorgia , Maisto Giulia , Memoli Valeria , Di Natale Gabriella , Trifuoggi Marco , Santorufo Lucia
Published: August 2022

Plastic sheets are widely used in farming soil to improve the productivity of cultures. Due to their absorption capacity, plastic sheets can alter element and metal content in soils, and in turn affect soil properties. The use of biodegradable films is an attractive eco-sustainable alternative approach to overcome the environmental pollution problems due to the use of plastic films but their impacts on soil are scarcely studied. The aim of the research was to evaluate the impact of conventional plastic and bioplastic sheets on total and available concentrations of elements (Al, Ca, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, and Zn) in soils. The research was performed in mesocosm trials, filled with soil covered by conventional plastic and bioplastic sheets. After six months of exposure, soils were characterized for pH, water content, concentrations of organic and total carbon and total nitrogen, and total and available Al, Ca, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, and Zn element concentrations. The results highlighted that soils covered by bioplastic sheets showed higher total and available concentrations of elements and higher contamination factors, suggesting that bioplastic sheets represented a source of metals or a less-effective sink to these background metals in soils, compared to conventional plastic ones.
Changes in Long-Term Functional Independence in Patients with Moderate and Severe Ischemic Stroke: Comparison of the Responsiveness of the Modified Barthel Index and the Functional Independence Measure
Authors: Lee Eun Young , Sohn Min Kyun , Lee Jong Min , Kim Deog Young , Shin Yong Il , Oh Gyung Jae , Lee Yang Soo , Lee So Young , Song Min Keun , Han Jun Hee , Ahn Jeong Hoon , Lee Young Hoon , Chang Won Hyuk , Choi Soo Mi , Lee Seon Kui , Joo Min Cheol , Kim Yun Hee
Published: August 2022

This study investigated the long-term functional changes in patients with moderate-to-severe ischemic stroke. In addition, we investigated whether there was a difference between the modified Barthel Index (MBI) and Functional Independence Measure (FIM) according to severity. To evaluate the changes in the long-term functional independence of the subjects, six evaluations were conducted over 2 years, and the evaluation was performed using MBI and FIM. A total of 798 participants participated in this study, of which 673 were classified as moderate and 125 as severe. During the first 3 months, the moderate group showed greater recovery than the severe group. The period of significant change in the National Institutes of Health Stroke Scale (NIHSS) score was up to 6 months after onset in the moderate group, and up to 3 months after onset in the severe group. In the severe group, MBI evaluation showed significant changes up to 6 months after onset, whereas FIM showed significant changes up to 18–24 months. Our results showed that functional recovery of patients with ischemic stroke in the 3 months after onset was greater in the moderate group than in the severe group. FIM is more appropriate than MBI for evaluating the functional status of patients with severe stroke.
Children’s Perspectives on Using Serious Games as a Complement to Promoting Their Social–Emotional Skills
Authors: Xavier Ana , Vagos Paula , Palmeira Lara , Menezes Paulo , Patrão Bruno , Pereira Sónia , Rocha Vanessa , Mendes Sofia , Tavares Marta
Published: August 2022

The use of serious games may be an appealing and complementary way to motivate curriculum-based social and emotional learning (SEL); still, investigation into this potential usefulness is scarce. This study aims to address the usefulness of serious games within the program ‘Me and Us of Emotions’. Specifically, we analyzed the differences in children’s satisfaction in sessions that did or did not use serious games as a complement to the intervention, explored the contribution of using serious games to the global satisfaction with the program, and explored children’s qualitative feedback regarding the sessions. The participants were 232 children (122 boys and 110 girls) aged between 8 and 12 years old (M = 9.09, SD = 0.80). The measures were based on the subjective appraisals of the sessions made by the participating children, including quantitative and qualitative assessments of the degree of satisfaction of the participants. The results showed that there were similar levels of satisfaction with the sessions that did or did not use serious games as a complement to the program. However, only satisfaction with the sessions that used serious games (and not satisfaction with the sessions that did not use them) contributed significantly to explaining both the enjoyment of the activities and the interest in the subjects. Satisfaction with serious games was significantly and positively associated with fun, easiness, ability to understand the session, and ability to cope with emotions. Qualitative analysis showed three main themes, namely: positive aspects, negative aspects, and opportunities for improvement of the program. Overall, these results indicate that children’s satisfaction with the ‘Me and Us of Emotions’ program is related to serious games, suggesting the relevance of using this complementary tool more often when intervening with younger generations.
The Effects of Using a Low-Cost and Easily Accessible Exercise Toolkit Incorporated to the Governmental Health Program on Community-Dwelling Older Adults: A Quasi-Experimental Study
Authors: Yang Shih-Hsien , Chang Qi-Xing , Liang Chung-Chao , Chen Jia-Ching
Published: August 2022

The Community Care Station (CCS) service was initiated by the Taiwanese government as a part of its elderly social services programs. This study aimed to investigate the effects of using an inexpensive exercise toolkit, containing a stick, theraband, sandbag and a small ball, led by a physical therapist among community-dwelling older adults participating in CCS. A total of 90 participants (aged 77.0 ± 6.8 years) were recruited and divided into an intervention group (n = 45) and a comparison group (n = 45). The intervention group regularly participated in a health promotion program with the exercise toolkit for approximately 90 min per twice-weekly session for 3 months, and the comparison group maintained their usual CCS activity program. Both groups were assessed before and after the 3-month intervention period. Outcome measures included the Short Physical Performance Battery (SPPB), one-leg stance, functional reach (FR), Timed Up and Go (TUG), and 10 m walk tests; 83 participants completed the study. No significant between-group differences were found at baseline in general characteristics or outcome variables. After 3 months, the intervention group showed the significant group x time interaction effects in SPPB, one-leg stance, FR, TUG and 10 m walk tests compared to the comparison group (p < 0.05).; A structured group-based health promotion program using a low-cost exercise toolkit could be effective in improving the physical performances, balance, and walking ability of community-dwelling older adults receiving CCS program services. Furthermore, the comparison group maintained most of their physical performances, even showing significant progress on FR.
“Seeing and Being Seen” or Just “Seeing” in a Smart Classroom Context When Videoconferencing: A User Experience-Based Qualitative Research on the Use of Cameras
Authors: Petchamé Josep , Iriondo Ignasi , Azanza Garazi
Published: August 2022

This research examines the form in which undergraduates use video cameras during videoconferencing class sessions in a Smart Classroom context and, more specifically, the reasons why a considerable number of students opt to turn off their cameras when videoconferencing during the sessions while others keep them on. The study was carried out in an institution that had previously switched from face-to-face teaching to an Emergency Remote Teaching solution, initially adopted in 2019–2020 to cope with the COVID-19 pandemic restrictions. Findings suggest that using cameras when videoconferencing is associated with increasing and enhancing the interaction between the student and the rest of the class, although not all students agreed with this conclusion. In addition, having the video cameras switched fomented socialization and improved the overall online learning experience for students. However, the surveyed students pointed out diverse negative elements, such as why they had to turn on their personal cameras, privacy concerns, and limitations derived from the available technology infrastructure, in addition to other factors such as distractions, anxiety, and cognitive load. This work discusses how these elements can influence the well-being and the user experience of the students, both positively and negatively.
The Risk for Neonatal Hypoglycemia and Bradycardia after Beta-Blocker Use during Pregnancy or Lactation: A Systematic Review and Meta-Analysis
Authors: de Bruin Rosalie , van Dalen Sarah L. , Franx Shamaya J. , Ramaswamy Viraraghavan V. , Simons Sinno H. P. , Flint Robert B. , van den Bosch Gerbrich E.
Published: August 2022

Beta-blockers are often used during pregnancy to treat cardiovascular diseases. The described neonatal side effects of maternal beta-blocker use are hypoglycemia and bradycardia, but the evidence base for these is yet to be evaluated comprehensively. Hence, this systematic review and meta-analysis was performed to evaluate the potential increased risk for hypoglycemia and bradycardia in neonates exposed to beta-blockers in utero or during lactation. A systematic search of English-language human studies was conducted until 21 April 2021. Both observational studies and randomized controlled trials investigating hypoglycemia and/or bradycardia in neonates following beta-blocker exposure during pregnancy and lactation were included. All articles were screened by two authors independently and eligible studies were included. Pair-wise and proportion-based meta-analysis was conducted and the certainty of evidence (CoE) was performed by standard methodologies. Of the 1.043 screened articles, 55 were included in this systematic review. Our meta-analysis showed a probable risk of hypoglycemia (CoE—Moderate) and possible risk of bradycardia (CoE—Low) in neonates upon fetal beta-blocker exposure. Therefore, we suggest the monitoring of glucose levels in exposed neonates until 24 h after birth. Due to the limited clinical implication, monitoring of the heart rate could be considered for 24 h. We call for future studies to substantiate our findings.
Analysis of Major Factors Affecting the Quality of Life of the Elderly in Korea in Preparation for a Super-Aged Society
Authors: Kim Bo-Ram , Hwang Hyang-Hee
Published: August 2022

In preparation for the expected super-aged society in 2025, this study attempted to prepare basic data that can help design development measures for the welfare of the elderly so that everyone can prepare for a healthy and happy retirement. Accordingly, the major factors affecting the quality of life of the elderly in Korea were verified. To this end, the questionnaire consisted of 22 questions in total, and a mobile survey was conducted between September and October 2021; in total, 250 copies were used for the final analysis, and the following conclusions are derived. The major factors that were found to determine the quality of life of the elderly were age, subjective health status, monthly household income, leisure activities, and health inequality fairness. It was found that the higher the age, the lower the quality of life. Further, the higher the subjective health status, monthly household income, participation in leisure activities, and perceptions of health inequality as fair, the more the quality of life of the elderly was affected. Therefore, policy support such as leisure activity, health programs, and medical welfare services for the elderly and sufficient attention from our society are all required.
Investigating PTG in Cancer Patients: The Role of Time Dimension in the Experience of Personal Growth
Authors: Fioretti Chiara , Vinciarelli Viola , Faggi David , Caligiani Lucia , Tessitore Francesca , Castelnuovo Gianluca , Cozzolino Mauro
Published: August 2022

This study explored the experience of growth related to being a cancer patient by implementing a thematic analysis. An online questionnaire was completed by 69 patients narrating their growth experience related to cancer. Collected narratives were analyzed by running a deductive thematic analysis, starting from the five domains of the Post-Traumatic Growth Inventory (PTGI) and searching for the presence or absence of topics. Descriptive statistics and correlational analysis were performed. The five factors of the PTGI were identified in the narratives. The thematic analysis we performed defined a further theme that we labeled the “time dimension”, which saturated 37.7% of the entire sample. The presences of four sub-themes related to the “time dimension” were also found: “tracing a new temporal rhythm”, “the value of deserved time”, “facing the caducity of life” and “a view on the future”. Each sub-theme significantly correlated with the theme of the “time dimension”. This emergent theme does not correlate in our results with other domains of personal growth in cancer previously described in the scientific literature, emerging as an independent variable not significantly associated with other domains of post-traumatic growth. Our results suggest further investigation in the role of the time dimension in the practical and emotional experience of growth with regard to cancer.
Enhanced Natural Attenuation of Groundwater Cr(VI) Pollution Using Electron Donors: Yeast Extract vs. Polyhydroxybutyrate
Authors: Tumolo Marina , Volpe Angela , Leone Natalia , Cotugno Pietro , De Paola Domenico , Losacco Daniela , Locaputo Vito , de Pinto Maria Concetta , Uricchio Vito Felice , Ancona Valeria
Published: August 2022

Remediation interventions based on the native bacteria’s capability to reduce Cr(VI) represent a valid strategy in terms of economic and environmental sustainability. In this study, a bioremediation test was carried out using viable microcosms set with groundwater and deep soil (4:1), collected from the saturated zone of an industrial site in Southern Italy that was polluted by ~130 µg L−1 of Cr(VI). Conditions simulating the potential natural attenuation were compared to the enhanced natural attenuation induced by supplying yeast extract or polyhydroxybutyrate. Sterile controls were set up to study the possible Cr(VI) abiotic reduction. No pollution attenuation was detected in the unamended viable reactors, whereas yeast extract provided the complete Cr(VI) removal in 7 days, and polyhydroxybutyrate allowed ~70% pollutant removal after 21 days. The incomplete abiotic removal of Cr(VI) was observed in sterile reactors amended with yeast extract, thus suggesting the essential role of native bacteria in Cr(VI) remediation. This was in accordance with the results of Pearson’s coefficient test, which revealed that Cr(VI) removal was positively correlated with microbial proliferation (n = 0.724), and also negatively correlated with pH (n = −0.646), dissolved oxygen (n = −0.828) and nitrate (n = −0.940). The relationships between the Cr(VI) removal and other monitored parameters were investigated by principal component analysis, which explained 76.71% of the total variance.
Estimated Impacts of Alcohol Control Policies on NCD Premature Deaths in Thailand
Authors: Chaiyasong Surasak , Gao Jie , Bundhamcharoen Kanitta
Published: August 2022

Background: This study aimed to assess the impacts of achieving a 10% alcohol reduction target and different alcohol policy interventions on NCD premature deaths during 2010–2025 in Thailand. Methods: The researchers estimated the impacts on three main NCDs: cancers, cardiovascular diseases, and diabetes. These represent two ideal scenarios, which are the target reduction and five intervention scenarios. These intervention scenarios comprise taxation with 50% price increases, a total ban on advertisements, availability restriction by shortening sales times, early psychological intervention, and combined interventions. Consumption data and mortality trends were obtained from available national data. Relative risks and intervention effects were derived from the literature. Results: Achieving a 10% reduction target would lead to 3903–7997 avoidable NCD deaths. Taxation was the most effective intervention, with the highest number of avoidable NCD deaths, followed by early psychological intervention, availability restriction, and an advertisement ban. A combination of these four interventions would reduce 13,286 NCD deaths among men and 4994 NCD deaths among women, accounting for 46.8% of the NCD mortality target. Conclusion: This study suggests using Thailand as an example for low- and middle-income countries to enhance implementation and enforcement of the recommended effective alcohol policies for achieving the global targets.
The Development and Validation of the Comprehensive Assessment of Acceptance and Commitment Therapy Processes (CompACT)—Malay Version
Authors: Musa Nurfarahin , Pang Nicholas Tze Ping , Kamu Assis , Ho Chong Mun , Waters Cerith , Berrett Jennifer , Moghaddam Nima , Wider Walton
Published: August 2022

Objectives: psychological flexibility is a crucial construct highly correlated with psychological wellness. There is a need for a tool to measure psychological flexibility in order to accurately ascertain the effects of treatment. The existing industry standard, the Acceptance and Action Questionnaire-II (AAQ-II), has issues with conflating psychological flexibility with distress; moreover, it does not cover the hexaflexes. The 23-item CompACT was designed to surmount these limitations. Methods: the classical test theory (CTT) and Rasch measurement theory (RMT) were used to check the validity and reliability of the Malay version of the CompACT Scale. Cronbach’s α, McDonald’s Ω, and greatest lower bound were used to measure internal consistency. A Pearson’s correlation test was used to measure test–retest reliability of the Malay versus the original English version. For validity, convergent validity was established by using the Malay AAQ-7 Scale. The dimensionality of the Malay version of the CompACT Scale was explored using exploratory factor analysis. For the RMT, weighted fit statistics (infit) and outlier sensitive fit statistic (outfit) mean square (MnSq) values were used at the item level, while item and person separation reliability values and item and person separation indices were applied at the scale level. Results: the internal consistency measures, including Cronbach α and McDonald’s Ω, passed the suggested cutoff points. Convergent validity with the AAQ-II was 0.693. The quality of the Malay version of the CompACT Scale was also satisfactory, as all item and person reliability values and indices exceeded the suggested cut-off points. Conclusions: the Malay CompACT is a psychometrically sound instrument to assess psychological flexibility in both clinical and research settings.
The Effect of a School-Based Intervention on Children’s Cycling Knowledge, Mode of Commuting and Perceived Barriers: A Randomized Controlled Trial
Authors: Aranda-Balboa María Jesús , Huertas-Delgado Francisco Javier , Gálvez-Fernández Patricia , Saucedo-Araujo Romina , Molina-Soberanes Daniel , Campos-Garzón Pablo , Herrador-Colmenero Manuel , Lara-Sánchez Amador Jesús , Molina-García Javier , Queralt Ana , Crone Diane , Chillón Palma
Published: August 2022

The low rates of active commuting to/from school in Spain, especially by bike, and the wide range of cycling interventions in the literature show that this is a necessary research subject. The aims of this study were: (1) to assess the feasibility of a school-based cycling intervention program for adolescents, (2) to analyse the effectiveness of a school-based cycling intervention program on the rates of cycling and other forms of active commuting to/from school (ACS), and perceived barriers to active commuting in adolescents. A total of 122 adolescents from Granada, Jaén and Valencia (Spain) participated in the study. The cycling intervention group participated in a school-based intervention program to promote cycling to school during Physical Education (PE) sessions in order to analyse the changes in the dependent variables at baseline and follow up of the intervention. Wilcoxon, Signs and McNemar tests were undertaken. The association of the intervention program with commuting behaviour, and perceived barriers to commuting, were analysed by binary logistic regression. There were improvements in knowledge at follow-up and the cycling skill scores were medium-low. The rates of cycling to school and active commuting to/from school did not change, and only the “built environment (walk)” barrier increased in the cycling group at follow-up. School-based interventions may be feasibly effective tools to increase ACS behaviour, but it is necessary to implement a longer period and continue testing further school-based cycling interventions.
Endoglin and MMP14 Contribute to Ewing Sarcoma Spreading by Modulation of Cell–Matrix Interactions
Authors: Puerto-Camacho Pilar , Díaz-Martín Juan , Olmedo-Pelayo Joaquín , Bolado-Carrancio Alfonso , Salguero-Aranda Carmen , Jordán-Pérez Carmen , Esteban-Medina Marina , Álamo-Álvarez Inmaculada , Delgado-Bellido Daniel , Lobo-Selma Laura , Dopazo Joaquín , Sastre Ana , Alonso Javier , Grünewald Thomas G. P. , Bernabeu Carmelo , Byron Adam , Brunton Valerie G. , Amaral Ana Teresa , Álava Enrique De
Published: August 2022

Endoglin (ENG) is a mesenchymal stem cell (MSC) marker typically expressed by active endothelium. This transmembrane glycoprotein is shed by matrix metalloproteinase 14 (MMP14). Our previous work demonstrated potent preclinical activity of first-in-class anti-ENG antibody-drug conjugates as a nascent strategy to eradicate Ewing sarcoma (ES), a devastating rare bone/soft tissue cancer with a putative MSC origin. We also defined a correlation between ENG and MMP14 expression in ES. Herein, we show that ENG expression is significantly associated with a dismal prognosis in a large cohort of ES patients. Moreover, both ENG/MMP14 are frequently expressed in primary ES tumors and metastasis. To deepen in their functional relevance in ES, we conducted transcriptomic and proteomic profiling of in vitro ES models that unveiled a key role of ENG and MMP14 in cell mechano-transduction. Migration and adhesion assays confirmed that loss of ENG disrupts actin filament assembly and filopodia formation, with a concomitant effect on cell spreading. Furthermore, we observed that ENG regulates cell–matrix interaction through activation of focal adhesion signaling and protein kinase C expression. In turn, loss of MMP14 contributed to a more adhesive phenotype of ES cells by modulating the transcriptional extracellular matrix dynamics. Overall, these results suggest that ENG and MMP14 exert a significant role in mediating correct spreading machinery of ES cells, impacting the aggressiveness of the disease.
Dual Mechanism of Action of Curcumin in Experimental Models of Multiple Sclerosis
Authors: ELBini-Dhouib Ines , Manai Maroua , Neili Nour-elhouda , Marzouki Soumaya , Sahraoui Ghada , Ben Achour Warda , Zouaghi Sondes , BenAhmed Melika , Doghri Raoudha , Srairi-Abid Najet
Published: August 2022

Background: Multiple sclerosis (MS) is characterized by a combination of inflammatory and demyelination processes in the spinal cord and brain. Conventional drugs generally target the autoimmune response, without any curative effect. For that reason, there is a great interest in identifying novel agents with anti-inflammatory and myelinating effects, to counter the inflammation and cell death distinctive of the disease. Methods and results: An in vitro assay showed that curcumin (Cur) at 10 µM enhanced the proliferation of C8-D1A cells and modulated the production of Th1/Th2/Th17 cytokines in the cells stimulated by LPS. Furthermore, two in vivo pathophysiological experimental models were used to assess the effect of curcumin (100 mg/kg). The cuprizone model mimics the de/re-myelination aspect in MS, and the experimental autoimmune encephalomyelitis model (EAE) reflects immune-mediated events. We found that Cur alleviated the neurological symptomatology in EAE and modulated the expression of lymphocytes CD3 and CD4 in the spinal cord. Interestingly, Cur restored motor and behavioral deficiencies, as well as myelination, in demyelinated mice, as indicated by the higher index of luxol fast blue (LFB) and the myelin basic protein (MBP) intensity in the corpus callosum. Conclusions: Curcumin is a potential therapeutic agent that can diminish the MS neuroimmune imbalance and demyelination through its anti-inflammatory and antioxidant effects.
Cellular Metabolism and Bioenergetic Function in Human Fibroblasts and Preadipocytes of Type 2 Familial Partial Lipodystrophy
Authors: Algieri Cristina , Bernardini Chiara , Trombetti Fabiana , Schena Elisa , Zannoni Augusta , Forni Monica , Nesci Salvatore
Published: August 2022

LMNA mutation is associated with type-2 familial partial lipodystrophy (FPLD2). The disease causes a disorder characterized by anomalous accumulation of body fat in humans. The dysfunction at the molecular level is triggered by a lamin A/C mutation, impairing the cell metabolism. In human fibroblasts and preadipocytes, a trend for ATP production, mainly supported by mitochondrial oxidative metabolism, is detected. Moreover, primary cell lines with FPLD2 mutation decrease the mitochondrial ATP production if compared with the control, even if no differences are observed in the oxygen consumption rate of bioenergetic parameters (i.e., basal and maximal respiration, spare respiratory capacity, and ATP turnover). Conversely, glycolysis is only inhibited in FPLD2 fibroblast cell lines. We notice that the amount of ATP produced in the fibroblasts is higher than in the preadipocytes, and likewise in the control, with respect to FPLD2, due to a more active oxidative phosphorylation (OXPHOS) and glycolysis. Moreover, the proton leak parameter, which characterizes the transformation of white adipose tissue to brown/beige adipose tissue, is unaffected by FPLD2 mutation. The metabolic profile of fibroblasts and preadipocytes is confirmed by the ability of these cell lines to increase the metabolic potential of both OXPHOS and glycolysis under energy required independently by the FPLD2 mutation.
Diclofenac-Induced Cytotoxicity in Direct and Indirect Co-Culture of HepG2 Cells with Differentiated THP-1 Cells
Authors: Kawase Atsushi , Takashima Ouka , Tanaka Satsuki , Shimada Hiroaki , Iwaki Masahiro
Published: August 2022

Non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (DIC) frequently induce drug-induced liver injury (DILI). It is unclear whether macrophages such as M1 and M2 participate in NSAID-associated DILI; elucidating this relationship could lead to a better understanding of the detailed mechanism of DILI. We co-cultured human hepatoma HepG2 cells with M1 or M2 derived from human monocytic leukemia THP-1 cells to examine the roles of M1 and M2 in DIC-induced cytotoxicity. DIC was added to the direct or indirect co-cultures of HepG2 cells with M1 or M2 (HepG2/M1 or HepG2/M2, respectively) at cell ratios of (1:0, 1:0.1, 1:0.4, and 1:1). In both direct and indirect HepG2/M2 co-cultures (1:0.4), there was lower lactate dehydrogenase release compared with HepG2/M1 co-cultures. Other NSAIDs as well as DIC showed similar protective effects of DIC-induced cytotoxicity. There were only slight differences in mRNA levels of apoptosis- and endoplasmic reticulum stress-associated factors between M1 and M2 after DIC treatment, suggesting that other factors determined the protective effects of M2 on DIC-induced cytotoxicity. Levels of high mobility group box 1 (HMGB1) in the medium and the mRNA expression levels of HMGB1 receptors were different between M1 and M2 after DIC treatment. Increased HMGB1 concentrations and expression of toll-like receptor 2 mRNA in M1 were observed compared with M2 after DIC treatment. In conclusion, these results suggested that the HMGB1/TLR2 signaling axis can be suppressed in M2 but not M1, leading to the different roles of M1 and M2 in NSAID-induced cytotoxicity.
Engineering Hyaluronic Acid for the Development of New Treatment Strategies for Osteoarthritis
Authors: Kim Yu Seon , Guilak Farshid
Published: August 2022

Osteoarthritis (OA) is a degenerative joint disease that is characterized by inflammation of the joints, degradation of cartilage, and the remodeling of other joint tissues. Due to the absence of disease-modifying drugs for OA, current clinical treatment options are often only effective at slowing down disease progression and focus mainly on pain management. The field of tissue engineering has therefore been focusing on developing strategies that could be used not only to alleviate symptoms of OA but also to regenerate the damaged tissue. Hyaluronic acid (HA), an integral component of both the synovial fluid and articular cartilage, has gained widespread usage in developing hydrogels that deliver cells and biomolecules to the OA joint thanks to its biocompatibility and ability to support cell growth and the chondrogenic differentiation of encapsulated stem cells, providing binding sites for growth factors. Tissue-engineering strategies have further attempted to improve the role of HA as an OA therapeutic by developing diverse modified HA delivery platforms for enhanced joint retention and controlled drug release. This review summarizes recent advances in developing HA-based hydrogels for OA treatment and provides additional insights into how HA-based therapeutics could be further improved to maximize their potential as a viable treatment option for OA.
Role of a ZF-HD Transcription Factor in miR157-Mediated Feed-Forward Regulatory Module That Determines Plant Architecture in Arabidopsis
Authors: Lee Young Koung , Kumari Sunita , Olson Andrew , Hauser Felix , Ware Doreen
Published: August 2022

In plants, vegetative and reproductive development are associated with agronomically important traits that contribute to grain yield and biomass. Zinc finger homeodomain (ZF-HD) transcription factors (TFs) constitute a relatively small gene family that has been studied in several model plants, including Arabidopsis thaliana L. and Oryza sativa L. The ZF-HD family members play important roles in plant growth and development, but their contribution to the regulation of plant architecture remains largely unknown due to their functional redundancy. To understand the gene regulatory network controlled by ZF-HD TFs, we analyzed multiple loss-of-function mutants of ZF-HD TFs in Arabidopsis that exhibited morphological abnormalities in branching and flowering architecture. We found that ZF-HD TFs, especially HB34, negatively regulate the expression of miR157 and positively regulate SQUAMOSA PROMOTER BINDING–LIKE 10 (SPL10), a target of miR157. Genome-wide chromatin immunoprecipitation sequencing (ChIP-Seq) analysis revealed that miR157D and SPL10 are direct targets of HB34, creating a feed-forward loop that constitutes a robust miRNA regulatory module. Network motif analysis contains overrepresented coherent type IV feedforward motifs in the amiR zf-HD and hbq mutant background. This finding indicates that miRNA-mediated ZF-HD feedforward modules modify branching and inflorescence architecture in Arabidopsis. Taken together, these findings reveal a guiding role of ZF-HD TFs in the regulatory network module and demonstrate its role in plant architecture in Arabidopsis.
In Vitro Cytotoxicity of D18 and Y6 as Potential Organic Photovoltaic Materials for Retinal Prostheses
Authors: Cetkovic Ana , Bellapianta Alessandro , Irimia-Vladu Mihai , Hofinger Jakob , Yumusak Cigdem , Corna Andrea , Scharber Markus Clark , Zeck Günther , Sariciftci Niyazi Serdar , Bolz Matthias , Salti Ahmad
Published: August 2022

Millions of people worldwide are diagnosed with retinal dystrophies such as retinitis pigmentosa and age-related macular degeneration. A retinal prosthesis using organic photovoltaic (OPV) semiconductors is a promising therapeutic device to restore vision to patients at the late onset of the disease. However, an appropriate cytotoxicity approach has to be employed on the OPV materials before using them as retinal implants. In this study, we followed ISO standards to assess the cytotoxicity of D18, Y6, PFN-Br and PDIN individually, and as mixtures of D18/Y6, D18/Y6/PFN-Br and D18/Y6/PDIN. These materials were proven for their high performance as organic solar cells. Human RPE cells were put in direct and indirect contact with these materials to analyze their cytotoxicity by the MTT assay, apoptosis by flow cytometry, and measurements of cell morphology and proliferation by immunofluorescence. We also assessed electrophysiological recordings on mouse retinal explants via microelectrode arrays (MEAs) coated with D18/Y6. In contrast to PFN-Br and PDIN, all in vitro experiments show no cytotoxicity of D18 and Y6 alone or as a D18/Y6 mixture. We conclude that D18/Y6 is safe to be subsequently investigated as a retinal prosthesis.
Development of Neurogenic Detrusor Overactivity after Thoracic Spinal Cord Injury Is Accompanied by Time-Dependent Changes in Lumbosacral Expression of Axonal Growth Regulators
Authors: Chambel Sílvia Sousa , Ferreira Ana , Oliveira Raquel , Miranda Rafael , Vale Luís , Reguenga Carlos , Schwab Martin E. , Cruz Célia Duarte
Published: August 2022

Thoracic spinal cord injury (SCI) results in urinary dysfunction, which majorly affects the quality of life of SCI patients. Abnormal sprouting of lumbosacral bladder afferents plays a crucial role in this condition. Underlying mechanisms may include changes in expression of regulators of axonal growth, including chondroitin sulphate proteoglycans (CSPGs), myelin-associated inhibitors (MAIs) and repulsive guidance molecules, known to be upregulated at the injury site post SCI. Here, we confirmed lumbosacral upregulation of the growth-associated protein GAP43 in SCI animals with bladder dysfunction, indicating the occurrence of axonal sprouting. Neurocan and Phosphacan (CSPGs), as well as Nogo-A (MAI), at the same spinal segments were upregulated 7 days post injury (dpi) but returned to baseline values 28 dpi. In turn, qPCR analysis of the mRNA levels for receptors of those repulsive molecules in dorsal root ganglia (DRG) neurons showed a time-dependent decrease in receptor expression. In vitro assays with DRG neurons from SCI rats demonstrated that exposure to high levels of NGF downregulated the expression of some, but not all, receptors for those regulators of axonal growth. The present results, therefore, show significant molecular changes at the lumbosacral cord and DRGs after thoracic lesion, likely critically involved in neuroplastic events leading to urinary impairment.
Molecular Mechanisms of Diabetic Kidney Disease
Authors: Rico-Fontalvo Jorge , Aroca Gustavo , Cabrales Jose , Daza-Arnedo Rodrigo , Yánez-Rodríguez Tomas , Martínez-Ávila María Cristina , Uparella-Gulfo Isabella , Raad-Sarabia María
Published: August 2022

The inflammatory component of diabetic kidney disease has become of great interest in recent years, with genetic and epigenetic variants playing a fundamental role in the initiation and progression of the disease. Cells of the innate immune system play a major role in the pathogenesis of diabetic kidney disease, with a lesser contribution from the adaptive immune cells. Other components such as the complement system also play a role, as well as specific cytokines and chemokines. The inflammatory component of diabetic kidney disease is of great interest and is an active research field, with the hope to find potential innovative therapeutic targets.
Angiotensin II Exaggerates SARS-CoV-2 Specific T-Cell Response in Convalescent Individuals following COVID-19
Authors: Almutlaq Moudhi , Mansour Fatmah A. , Alghamdi Jahad , Alhendi Yassen , Alamro Abir Abdullah , Alghamdi Amani Ahmed , Alamri Hassan S. , Alroqi Fayhan , Barhoumi Tlili
Published: August 2022

Dysregulation of renin−angiotensin systems during coronavirus disease 2019 (COVID-19) infection worsens the symptoms and contributes to COVID-19 severity and mortality. This study sought to investigate the effect of exogenous angiotensin II (Ang-II) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cells response in recovered COVID-19 patients. Human peripheral blood mononuclear cells (PBMCs) were treated with Ang II and then stimulated with a SARS-CoV-2 peptide pool. T-cell responses were measured using flow cytometry, while enzyme-linked immunosorbent assay (ELISA) and intracellular cytokine staining (ICS) assays determined functional capability and polarization. Additionally, the relative level of protein phosphorylation was measured using a phosphokinase array. Our results showed that Ang II treatment significantly increased the magnitude of SARS-CoV-2-specific T-cell response in stimulated PBMCs with a SARS-CoV-2 peptide pool. Moreover, the phosphorylation levels of numerous proteins implicated in cardiovascular diseases, inflammation, and viral infection showed significant increases in the presence of Ang II. The mitogenic stimulation of PBMCs after Ang II and SARS-CoV-2 peptide pool stimulation showed functional polarization of T-cells toward Th1/Th17 and Th17 phenotypes, respectively. Meanwhile, ELISA showed increased productions of IL-1β and IL-6 in Ang II-stimulated PBMCs without affecting the IL-10 level. To our knowledge, this study is the first to demonstrate that Ang II exaggerates SARS-CoV-2-specific T-cells response. Therefore, during COVID-19 infection, Ang II may aggravate the inflammatory response and change the immune response toward a more inflammatory profile against SARS-CoV-2 infection.
Effects of Combining Biofactors on Bioenergetic Parameters, Aβ Levels and Survival in Alzheimer Model Organisms
Authors: Babylon Lukas , Schmitt Fabian , Franke Yannik , Hubert Tim , Eckert Gunter P.
Published: August 2022

Increased amyloid beta (Aβ) levels and mitochondrial dysfunction (MD) in the human brain characterize Alzheimer disease (AD). Folic acid, magnesium and vitamin B6 are essential micro-nutrients that may provide neuroprotection. Bioenergetic parameters and amyloid precursor protein (APP) processing products were investigated in vitro in human neuroblastoma SH-SY5Y-APP695 cells, expressing neuronal APP, and in vivo, in the invertebrate Caenorhabditis elegans (CL2006 & GMC101) expressing muscular APP. Model organisms were incubated with either folic acid and magnesium-orotate (ID63) or folic acid, magnesium-orotate and vitamin B6 (ID64) in different concentrations. ID63 and ID64 reduced Aβ, soluble alpha APP (sAPPα), and lactate levels in SH-SY5Y-APP695 cells. The latter might be explained by enhanced expression of lactate dehydrogenase (LDHA). Micronutrient combinations had no effects on mitochondrial parameters in SH-SY5Y-APP695 cells. ID64 showed a significant life-prolonging effect in C. elegans CL2006. Incubation of GMC101 with ID63 significantly lowered Aβ aggregation. Both combinations significantly reduced paralysis and thus improved the phenotype in GMC101. Thus, the combinations of the tested biofactors are effective in pre-clinical models of AD by interfering with Aβ related pathways and glycolysis.
Deubiquitinating Enzyme USP7 Is Required for Self-Renewal and Multipotency of Human Bone Marrow-Derived Mesenchymal Stromal Cells
Authors: Kim You Ji , Park Kwang Hwan , Lee Kyoung-Mi , Chun Yong-Min , Lee Jin Woo
Published: August 2022

Ubiquitin-specific protease 7 (USP7) is highly expressed in a variety of malignant tumors. However, the role of USP7 in regulating self-renewal and differentiation of human bone marrow derived mesenchymal stromal cells (hBMSCs) remains unknown. Herein, we report that USP7 regulates self-renewal of hBMSCs and is required during the early stages of osteogenic, adipogenic, and chondrogenic differentiation of hBMSCs. USP7, a deubiquitinating enzyme (DUB), was found to be downregulated during hBMSC differentiation. Furthermore, USP7 is an upstream regulator of the self-renewal regulating proteins SOX2 and NANOG in hBMSCs. Moreover, we observed that SOX2 and NANOG are poly-ubiquitinated and their expression is downregulated in USP7-deficient hBMSCs. Overall, this study showed that USP7 is required for maintaining self-renewal and multipotency in cultured hBMSCs. Targeting USP7 might be a novel strategy to preserve the self-renewal capacity of hBMSCs intended for stem cell therapy.
FGFR3-TACCs3 Fusions and Their Clinical Relevance in Human Glioblastoma
Authors: Gött Hanna , Uhl Eberhard
Published: August 2022

Oncogenic fusion genes have emerged as successful targets in several malignancies, such as chronic myeloid leukemia and lung cancer. Fusion of the fibroblast growth receptor 3 and the transforming acidic coiled coil containing protein—FGFR3-TACC3 fusion—is prevalent in 3–4% of human glioblastoma. The fusion protein leads to the constitutively activated kinase signaling of FGFR3 and thereby promotes cell proliferation and tumor progression. The subgroup of FGFR3-TACC3 fusion-positive glioblastomas presents with recurrent clinical and histomolecular characteristics, defining a distinctive subtype of IDH-wildtype glioblastoma. This review aims to provide an overview of the available literature on FGFR3-TACC3 fusions in glioblastoma and possible implications for actual clinical practice.
Possible Implications of Bacteriospermia on the Sperm Quality, Oxidative Characteristics, and Seminal Cytokine Network in Normozoospermic Men
Authors: Tvrdá Eva , Lovíšek Daniel , Gálová Eliška , Schwarzová Marianna , Kováčiková Eva , Kunová Simona , Žiarovská Jana , Kačániová Miroslava
Published: August 2022

This study focused on the identification of bacterial profiles of semen in normozoospermic men and their possible involvement in changes to the sperm structural integrity and functional activity. Furthermore, we studied possible fluctuations of selected cytokines, oxidative markers, and antibacterial proteins as a result of bacterial presence in the ejaculate. Sperm motility was assessed with computer-assisted sperm analysis, while sperm apoptosis, necrosis and acrosome integrity were examined with fluorescent methods. Reactive oxygen species (ROS) generation was quantified via luminometry, sperm DNA fragmentation was evaluated using the TUNEL protocol and chromatin-dispersion test, while the JC-1 assay was applied to evaluate the mitochondrial membrane potential. Cytokine levels were quantified with the biochip assay, whilst selected antibacterial proteins were quantified using the ELISA method. The predominant species identified by the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were Staphylococcus hominis, Staphylococcus capitis and Micrococcus luteus. The results revealed that the sperm quality decreased proportionally to the increasing bacterial load and occurrence of conditionally pathogenic bacteria, including Enterococcus faecalis, Staphylococcus aureus and Escherichia coli. Antimicrobial susceptibility tests revealed a substantial resistance of randomly selected bacterial strains to ampicillin, vancomycin, tobramycin, and tetracycline. Furthermore, an increased bacterial quantity in semen was accompanied by elevated levels of pro-inflammatory cytokines, including interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor alpha as well as ROS overproduction and lipid peroxidation of the sperm membranes. Our results suggest that semen quality may be notably affected by the bacterial quantity as well as quality. It seems that bacteriospermia may be associated with inflammatory processes, oxidative stress, sperm structural deterioration, and a subsequent risk for the development of subfertility, even in normozoospermic males.
Structural Evolution of Delta (B.1.617.2) and Omicron (BA.1) Spike Glycoproteins
Authors: Prandi Ingrid Guarnetti , Mavian Carla , Giombini Emanuela , Gruber Cesare E. M. , Pietrucci Daniele , Borocci Stefano , Abid Nabil , Beccari Andrea R. , Talarico Carmine , Chillemi Giovanni
Published: August 2022

The vast amount of epidemiologic and genomic data that were gathered as a global response to the COVID-19 pandemic that was caused by SARS-CoV-2 offer a unique opportunity to shed light on the structural evolution of coronaviruses and in particular on the spike (S) glycoprotein, which mediates virus entry into the host cell by binding to the human ACE2 receptor. Herein, we carry out an investigation into the dynamic properties of the S glycoprotein, focusing on the much more transmissible Delta and Omicron variants. Notwithstanding the great number of mutations that have accumulated, particularly in the Omicron S glycoprotein, our data clearly showed the conservation of some structural and dynamic elements, such as the global motion of the receptor binding domain (RBD). However, our studies also revealed structural and dynamic alterations that were concentrated in the aa 627–635 region, on a small region of the receptor binding motif (aa 483–485), and the so-called “fusion-peptide proximal region”. In particular, these last two S regions are known to be involved in the human receptor ACE2 recognition and membrane fusion. Our structural evidence, therefore, is likely involved in the observed different transmissibility of these S mutants. Finally, we highlighted the role of glycans in the increased RBD flexibility of the monomer in the up conformation of Omicron.