bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Ref! Could You Help Me?’—Building a Positive Climate by Referees during Floorball Competitions in Youth Sport
Authors: Firek Wiesław , Płoszaj Katarzyna , Gąsior Paweł , Malchrowicz-Mośko Ewa
Published: January 2022

In creating a positive climate in sport for children and youth, the role of adults is of key importance as their behavior and attitudes determine the experiences and multilateral development of young players. Relatively recently, the importance of the referee in creating a supportive sporting environment has begun to be emphasized. This concerns, in particular, team sports in which the referees interact with players many times and influence the course of the game. The aim of the study was to evaluate the quality of the referee–players’ interactions during youth floorball matches in terms of building a positive climate and responsiveness to the players’ needs. Another aim of the study was to examine whether the referee’s qualifications and players’ gender affect the quality of their interactions with the players. The study was conducted among 21 referees officiating matches for girls and boys aged 12–18. Naturalistic and structured observation methods were used in the study. The observation was conducted using a wireless intercom that allows listening to verbal messages directed to the players. Furthermore, the referee’s work was recorded using a camera. The results of the statistical tests did not show any significant differences in the assessment of referees between the groups distinguished in terms of the referees’ license and players’ gender in both examined dimensions. The observations showed that the average rating of building a positive climate by referees during a sporting event measured on a seven-point scale was ‘poor’ (2.81 pts). The referees were assessed significantly higher on the second dimension (responsiveness to the players’ needs), although an overall rating of 3.81 pts means a medium level of interaction quality. The results indicate areas in which referees can improve. They lead to the following conclusions: (i) the contents of training for floorball referees should include problems of pedagogy and developmental psychology; (ii) referees should be equipped with appropriate competencies for building a positive climate during matches and monitoring the players’ needs; (iii) referees appointed to officiate children and youth games should be characterized by appropriate predispositions.
Lifestyle Interventions through Participatory Research: A Mixed-Methods Systematic Review of Alcohol and Other Breast Cancer Behavioural Risk Factors
Authors: Thomas Jessica A. , Miller Emma R. , Ward Paul R.
Published: January 2022

Breast cancer is one of the most frequently diagnosed cancers in women globally. Sex and advancing age represent the dominant risk factors, with strong evidence of alcohol as a modifiable risk factor. The carcinogenic nature of alcohol has been known for over twenty years; however, this has failed to translate into significant behavioural, practice, or policy change. As a result, women have not benefitted from this research and, by extension, have been exposed to unnecessary breast cancer risk. Participatory research presents a solution to research translation in public health through the collaboration of impacted populations with academics in research. This systematic review examines peer-reviewed research studies where participants were involved in the research process and the outcomes related to breast cancer prevention (either alcohol or broader lifestyle modification). Seven of the eight studies reported positive effects, and the collaboration between academic researchers and impacted populations may have supported positive outcomes. Women were receptive and responsive to participatory approaches, and their participation is important to address socially entrenched behaviours such as alcohol consumption. Participatory research presents opportunities for future interventions to improve (or address) modifiable risk factors for breast cancer.
Postural Control in Unipedal Quiet Stance in Young Female Gymnasts and the Effects of Training with Consideration of Transient Behavior of Postural Sway
Authors: Čeklić Urška , Šarabon Nejc , Kozinc Žiga
Published: January 2022

The purpose of this study was twofold: (a) to compare postural control between a group of young female gymnasts (n = 15; age: 11.2 ± 1.9 years) and non-trained peers (n = 15; age: 10.9 ± 2.0 years), and (b) to investigate the effect of an 8-week whole body exercise intervention program on postural control in young female gymnasts. Postural control was assessed by recording center of pressure (CoP) movements during unipedal quiet stance. Velocity and amplitude of CoP movement in anterior-posterior (AP) and medial-lateral (ML) directions were considered. In addition to common trial-averaged CoP outcomes, we also considered the transient behavior of CoP movements, by calculating relative differences between the 1st and 2nd, and the 1st and 3rd 10-s intervals within the whole trial (DIF_21 and DIF_31, respectively). The gymnast group had lower total CoP velocity (Cohen’s d = 0.97) and AP amplitude (Cohen’s d = 0.85), compared to their non-trained peers. The gymnasts also had lower CoP AP amplitude DIF21 (Cohen’s d = 0.73), with almost constant values across all intervals. After the training ML CoP velocity was reduced for 13.12% (Cohen’s d = 0.60), while ML CoP amplitude increased (Cohen’s d = −0.89).
Impact of COVID-19 Pandemic Exacerbation of Depressive Symptoms for Social Frailty from the ORANGE Registry
Authors: Kodama Ayuto , Kume Yu , Lee Sangyoon , Makizako Hyuma , Shimada Hiroyuki , Takahashi Tomoko , Ono Tsuyoshi , Ota Hidetaka
Published: January 2022

Background: Recent longitudinal studies have reported proportion of frailty transition in older individuals during the COVID-19 pandemic. Our study aimed at clarifying the impact of social frailty in community-dwelling older adults during the COVID-19 pandemic and at identifying factors that can predict transition to social frailty. Methods: We performed this study from 2019 (before declaration of the state of emergency over the rising number of COVID-19 cases) to 2020 (after declaration of the emergency). We applied Makizako’s social frail index to our study subjects at the baseline and classified into robust, social prefrailty, and social frailty groups. Multiple logistic regression analysis was performed using robust, social prefrailty, or social frailty status as dependent variable. Results: Analysis by the Kruskal–Wallis test revealed significant differences in the score on the GDS-15 among the robust, social prefrailty, and social frailty groups (p < 0.05). Furthermore, multiple regression analysis identified a significant association between the social frailty status and the score on GDS-15 (odds ratio, 1.57; 95% confidence interval (95% CI), 1.15–2.13; p = 0.001). Conclusion: The increase in the rate of transition of elderly individuals to the social frailty group could have been related to the implementation of the stay-at-home order as part of the countermeasures for COVID-19. Furthermore, the increased prevalence of depressive symptoms associated with the stay-at-home order could also have influenced the increase in the prevalence of social frailty during the COVID-19 pandemic.
Biomechanical Characteristics of the Knee Joint during Gait in Obese versus Normal Subjects
Authors: Al Khatib Fadi , Gouissem Afif , Mbarki Raouf , Adouni Malek
Published: January 2022

Knee osteoarthritis (OA) is a growing source of pain and disability. Obesity is the most important avoidable risk factor underlying knee OA. The processes by which obesity impacts osteoarthritis are of tremendous interest to osteoarthritis researchers and physicians, where the joint mechanical load is one of the pathways generally thought to cause or intensify the disease process. In the current work, we developed a hybrid framework that simultaneously incorporates a detailed finite element model of the knee joint within a musculoskeletal model to compute lower extremity muscle forces and knee joint stresses in normal-weight (N) and obese (OB) subjects during the stance phase gait. This model accounts for the synergy between the active musculature and passive structures. In comparing OB subjects and normal ones, forces significantly increased in all muscle groups at most instances of stance. Mainly, much higher activation was computed with lateral hamstrings and medial gastrocnemius. Cartilage contact average pressure was mostly supported by the medial plateau and increased by 22%, with a larger portion of the load transmitted via menisci. This medial compartment experienced larger relative movement and cartilage stresses in the normal subjects and continued to do so with a higher level in the obese subjects. Finally, the developed bioengineering frame and the examined parameters during this investigation might be useful clinically in evaluating the initiation and propagation of knee OA.
Understanding the Spectrum of Anxiety Responses to Climate Change: A Systematic Review of the Qualitative Literature
Authors: Soutar Catriona , Wand Anne P. F.
Published: January 2022

Background: Knowledge about climate change may produce anxiety, but the concept of climate change anxiety is poorly understood. The primary aim of this study was to systematically review the qualitative literature regarding the scope of anxiety responses to climate change. The secondary aim was to investigate the sociodemographic and geographical factors which influence experiences of climate change anxiety. Methods: A systematic review of empirical qualitative studies was undertaken, examining the scope of climate change anxiety by searching five databases. Studies were critically appraised for quality. Content analysis was used to identify themes. Results: Fifteen studies met the inclusion criteria. The content analysis was organised into two overarching themes. The scope of anxiety included worry about threats to livelihood, worry for future generations, worry about apocalyptic futures, anxiety at the lack of response to climate change, and competing worries. Themes pertaining to responses to climate change anxiety included symptoms of anxiety, feeling helpless and disempowered, and ways of managing climate change anxiety. Relatively few studies were identified, with limited geographical diversity amongst the populations studied. Conclusions: The review furthers understanding of the concept of climate change anxiety and responses to it, highlighting the need for high-quality psychiatric research exploring its clinical significance and potential interventions.
Perception, Reaction, and Future Development of the Influence of COVID-19 on the Hospitality and Tourism Industry in China
Authors: Zhong Lina , Sun Sunny , Law Rob , Li Xiaonan , Yang Liyu
Published: January 2022

The present study examined the perception, reaction (i.e., possible measures), and future development from the perspectives of hotel and tourism practitioners and experts to investigate the influence of coronavirus disease 2019 (i.e., COVID-19) on the hospitality and tourism industry in China. After conducting 58 in-depth interviews among hotel and tourism practitioners and experts, feasible and practical measures were proposed to reduce such influence and predict the future development of China’s hospitality and tourism industry. Findings indicate that the influence of COVID-19 on the industry is perceived mainly through the pandemic’s economic and social effects. Possible measures that can be adopted for the recovery of China’s hospitality and tourism industry include the following aspects: government financial support, employee relationship management and electronic (e)-training, business marketing management, and industry co-operation network. A Perception-Reaction-Predication (PRP) crisis model is also proposed.
Addressing Challenges When Applying GRADE to Public Health Guidelines: A Scoping Review Protocol and Pilot Analysis
Authors: Kantorová Lucia , Friessová Tereza , Slezáková Simona , Langaufová Alena , Kantor Jiří , Munn Zachary , Barker Timothy Hugh , Katikireddi Srinivasa Vittal , Mustafa Reem A. , Žuljević Marija Franka , Lukežić Marina , Klugarová Jitka , Riad Abanoub , Vrbová Tereza , Pokorná Andrea , Búřilová Petra , Búřil Jiří , Kirkovski Aleksandar , Ćaćić Nensi , Delač Ljerka , Tokalić Ružica , Poklepović Peričić Tina , Klugar Miloslav
Published: January 2022

This is a protocol for a scoping review that aims to determine how guideline authors using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach have addressed previously identified challenges related to public health. The Joanna Briggs Institute (JBI) methodology for scoping reviews will be followed. We will search and screen titles of guidelines for all languages published in 2013–2021 in: the GIN library, BIGG database, Epistemonikos GRADE guidelines repository, GRADEpro Database, MAGICapp, NICE and WHO websites. Two reviewers will independently screen full texts of the documents identified. The following information will be extracted: methods used for identifying different stakeholders and incorporating their perspectives; methods for identification and prioritization of non-health outcomes; methods for determining thresholds for decision-making; methods for incorporating and grading evidence from non-randomized studies; methods for addressing concerns with conditional recommendations in public health; methods for reaching consensus; additional methodological concerns; and any modifications made to GRADE. A combination of directed content analysis and descriptive statistics will be used for data analysis, and the findings presented narratively in a tabular and graphical form. In this protocol, we present the pilot results from 13 identified eligible guidelines issued between January and August 2021. We will publish the full review results when they become available.
An Exploratory Study on the Acoustic Musical Properties to Decrease Self-Perceived Anxiety
Authors: Parada-Cabaleiro Emilia , Batliner Anton , Schedl Markus
Published: January 2022

Musical listening is broadly used as an inexpensive and safe method to reduce self-perceived anxiety. This strategy is based on the emotivist assumption claiming that emotions are not only recognised in music but induced by it. Yet, the acoustic properties of musical work capable of reducing anxiety are still under-researched. To fill this gap, we explore whether the acoustic parameters relevant in music emotion recognition are also suitable to identify music with relaxing properties. As an anxiety indicator, the positive statements from the six-item Spielberger State-Trait Anxiety Inventory, a self-reported score from 3 to 12, are taken. A user-study with 50 participants assessing the relaxing potential of four musical pieces was conducted; subsequently, the acoustic parameters were evaluated. Our study shows that when using classical Western music to reduce self-perceived anxiety, tonal music should be considered. In addition, it also indicates that harmonicity is a suitable indicator of relaxing music, while the role of scoring and dynamics in reducing non-pathological listener distress should be further investigated.
Loss of Skeletal Muscle Mass and Intracellular Water as Undesired Outcomes of Weight Reduction in Obese Hyperglycemic Women: A Short-Term Longitudinal Study
Authors: Zalejska-Fiolka Jolanta , Birková Anna , Wielkoszyński Tomasz , Hubková Beáta , Szlachta Beata , Fiolka Rafał , Błaszczyk Urszula , Kuzan Aleksandra , Gamian Andrzej , Mareková Mária , Toborek Michał
Published: January 2022

The current study is focused on the influence of hyperglycemia on weight loss in obese premenopausal women. Specifically, the study evaluated the impact of a six-month individualized low-calorie diet combined with moderate exercise on weight reduction and glucose metabolism in obese women with normoglycemia compared to obese women with moderate hyperglycemia. The results indicated that patients with normoglycemia achieved a successful weight loss, which was connected to a decrease in adipose tissue and reflected by diminished content of visceral fat area (VFA) and percent body fat. In contrast, weight reduction in patients with hyperglycemia was connected not only to the loss of VFA but also to undesired decrease in skeletal muscle mass as well as intracellular and total body water. These unfavorable outcomes were observed despite normalization of glucose metabolism reflected by statistically significant lowering glucose, fructosamine, advanced glycation end-products, and HOMA-IR levels. Overall, the obtained results indicate the importance of the measurement of the carbohydrate profile in obese women and the need for an early introduction of weight reduction strategies before the development of hyperglycemia.
Passability of Chironomid Larvae in Granular Activated Carbon
Authors: Lee Cha Young , Byeon Jinseok , Kim Min Kyung , Lee Tae-gwan , Kim Dong Gun
Published: January 2022

We conducted an experiment to confirm the passability of chironomid larvae (Glyptotendipes tokunagai) in granular activated carbon (GAC) used in water treatment plants. After injecting larvae at different growth stages (first through fourth instars) into circular columns filled with GAC, the number of individuals and their locations within the GAC columns were recorded after 168 h. We found that more than 80% of the injected larvae in the first instar and 3.3% in the second instar passed, whereas none from the third and fourth instars had passed through the column. The second instar larvae were evenly distributed within the column, whereas the third and fourth instar larvae were mostly distributed within 10 cm of the upper layer of the GAC. Our results demonstrate the passability of chironomid larvae in GAC and can be used as basic information for water quality management in water treatment plants.
MRSA Femoral Osteomyelitis from Superinfected Scabies Lesions: A Pediatric Case Report
Authors: Sartorio Marco Ugo Andrea , Munari Alice Marianna , Carlucci Patrizia , Erba Paola , Calcaterra Valeria , Fabiano Valentina
Published: January 2022

Scabies is a skin infestation from the Sarcoptes scabiei. It is considered a public health issue causing concern in developing countries and is considered a “neglected tropical disease” by the World Health Organization (WHO). Scabies skin lesions may cause severe itching and can be the portal of entry for opportunistic and pathogenic bacteria, which can cause serious systemic infections. We report the case of a 3-year-old boy with recurrent scabies infections who presented to the emergency department because of a fever and refusal to walk. Blood tests showed neutrophilic leukocytosis and significantly increased C reactive protein (CRP) and procalcitonin. Upon medical examination, his right thigh was extremely painful upon palpation, knee flexion was lost and he was unable to stand, so magnetic resonance imaging (MRI) was performed. MRI showed osteomyelitis of metaphysis and distal diaphysis of the right femur with associated subperiosteal purulent collection and concomitant pyomyositis and fasciitis of the distal right thigh. Blood cultures were positive for methicillin-resistant Staphylococcus aureus (MRSA). The patient received a long course of intravenous antibiotic therapy and his condition slowly improved. Follow-up femur X-ray showed a mixed pattern of erosion and sclerosis at the meta-diaphyseal region and periosteal reaction at the diaphyseal region. This case highlights the importance of early scabies diagnosis even in Western countries where poverty and household overcrowding are uncommon. Early diagnosis, timely initiation of proper treatment and evidence of clinical resolution are important elements to prevent recurrence of infection and serious systemic superinfections even from multi-drug resistant bacteria. Clinical consequences from unrecognized disease or inadequate eradication are preventable.
Prediction Model for the Risk of HIV Infection among MSM in China: Validation and Stability
Authors: Dong Yinqiao , Liu Shangbin , Xia Danni , Xu Chen , Yu Xiaoyue , Chen Hui , Wang Rongxi , Liu Yujie , Dong Jingwen , Hu Fan , Cai Yong , Wang Ying
Published: January 2022

The impact of psychosocial factors on increasing the risk of HIV infection among men who have sex with men (MSM) has attracted increasing attention. We aimed to develop and validate an integrated prediction model, especially incorporating emerging psychosocial variables, for predicting the risk of HIV infection among MSM. We surveyed and collected sociodemographic, psychosocial, and behavioral information from 547 MSM in China. The participants were split into a training set and a testing set in a 3:1 theoretical ratio. The prediction model was constructed by introducing the important variables selected with the least absolute shrinkage and selection operator (LASSO) regression, applying multivariate logistic regression, and visually assessing the risk of HIV infection through the nomogram. Receiver operating characteristic curves (ROC), Kolmogorov–Smirnov test, calibration plots, Hosmer–Lemeshow test and population stability index (PSI) were performed to test validity and stability of the model. Four of the 15 selected variables—unprotected anal intercourse, multiple sexual partners, involuntary subordination and drug use before sex—were included in the prediction model. The results indicated that the comprehensive prediction model we developed had relatively good predictive performance and stability in identifying MSM at high-risk for HIV infection, thus providing targeted interventions for high-risk MSM.
Diabetes Capabilities for the Healthcare Workforce Identified via a 3-Staged Modified Delphi Technique
Authors: Murfet Giuliana , Ostaszkiewicz Joan , Rasmussen Bodil
Published: January 2022

Consumers access health professionals with varying levels of diabetes-specific knowledge and training, often resulting in conflicting advice. Conflicting health messages lead to consumer disengagement. The study aimed to identify capabilities required by health professionals to deliver diabetes education and care to develop a national consensus capability-based framework to guide their training. A 3-staged modified Delphi technique was used to gain agreement from a purposefully recruited panel of Australian diabetes experts from various disciplines and work settings. The Delphi technique consisted of (Stage I) a semi-structured consultation group and pre-Delphi pilot, (Stage II) a 2-phased online Delphi survey, and (Stage III) a semi-structured focus group and appraisal by health professional regulatory and training organisations. Descriptive statistics and central tendency measures calculated determined quantitative data characteristics and consensus. Content analysis using emergent coding was used for qualitative content. Eighty-four diabetes experts were recruited from nursing and midwifery (n = 60 [71%]), allied health (n = 17 [20%]), and pharmacy (n = 7 [9%]) disciplines. Participant responses identified 7 health professional practice levels requiring differences in diabetes training, 9 capability areas to support care, and 2 to 16 statements attained consensus for each capability—259 in total. Additionally, workforce solutions were identified to expand capacity for diabetes care. The rigorous consultation process led to the design and validation of a Capability Framework for Diabetes Care that addresses workforce enablers identified by the Australian National Diabetes Strategy. It recognises diversity, creating shared understandings of diabetes across health professional disciplines. The findings will inform diabetes policy, practice, education, and research.
Tethered TGF-β1 in a Hyaluronic Acid-Based Bioink for Bioprinting Cartilaginous Tissues
Authors: Hauptstein Julia , Forster Leonard , Nadernezhad Ali , Groll Jürgen , Teßmar Jörg , Blunk Torsten
Published: January 2022

In 3D bioprinting for cartilage regeneration, bioinks that support chondrogenic development are of key importance. Growth factors covalently bound in non-printable hydrogels have been shown to effectively promote chondrogenesis. However, studies that investigate the functionality of tethered growth factors within 3D printable bioinks are still lacking. Therefore, in this study, we established a dual-stage crosslinked hyaluronic acid-based bioink that enabled covalent tethering of transforming growth factor-beta 1 (TGF-β1). Bone marrow-derived mesenchymal stromal cells (MSCs) were cultured over three weeks in vitro, and chondrogenic differentiation of MSCs within bioink constructs with tethered TGF-β1 was markedly enhanced, as compared to constructs with non-covalently incorporated TGF-β1. This was substantiated with regard to early TGF-β1 signaling, chondrogenic gene expression, qualitative and quantitative ECM deposition and distribution, and resulting construct stiffness. Furthermore, it was successfully demonstrated, in a comparative analysis of cast and printed bioinks, that covalently tethered TGF-β1 maintained its functionality after 3D printing. Taken together, the presented ink composition enabled the generation of high-quality cartilaginous tissues without the need for continuous exogenous growth factor supply and, thus, bears great potential for future investigation towards cartilage regeneration. Furthermore, growth factor tethering within bioinks, potentially leading to superior tissue development, may also be explored for other biofabrication applications.
Spectroscopic Characterization of Mitochondrial G-Quadruplexes
Authors: Illodo Sara , Pérez-González Cibrán , Barcia Ramiro , Rodríguez-Prieto Flor , Al-Soufi Wajih , Novo Mercedes
Published: January 2022

Guanine quadruplexes (G4s) are highly polymorphic four-stranded structures formed within guanine-rich DNA and RNA sequences that play a crucial role in biological processes. The recent discovery of the first G4 structures within mitochondrial DNA has led to a small revolution in the field. In particular, the G-rich conserved sequence block II (CSB II) can form different types of G4s that are thought to play a crucial role in replication. In this study, we decipher the most relevant G4 structures that can be formed within CSB II: RNA G4 at the RNA transcript, DNA G4 within the non-transcribed strand and DNA:RNA hybrid between the RNA transcript and the non-transcribed strand. We show that the more abundant, but unexplored, G6AG7 (37%) and G6AG8 (35%) sequences in CSB II yield more stable G4s than the less profuse G5AG7 sequence. Moreover, the existence of a guanine located 1 bp upstream promotes G4 formation. In all cases, parallel G4s are formed, but their topology changes from a less ordered to a highly ordered G4 when adding small amounts of potassium or sodium cations. Circular dichroism was used due to discriminate different conformations and topologies of nucleic acids and was complemented with gel electrophoresis and fluorescence spectroscopy studies.
A High-Methionine Diet for One-Week Induces a High Accumulation of Methionine in the Cerebrospinal Fluid and Confers Bipolar Disorder-like Behavior in Mice
Authors: Ishii Isao , Kamata Shotaro , Ito Saki , Shimonaga Aya , Koizumi Maika , Tsushima Maiko , Miura Asumi , Nagata Tomoko , Tosaka Yuka , Ohtani Haruka , Kamichatani Waka , Akahoshi Noriyuki
Published: January 2022

Methionine (Met) is considered the most toxic amino acid in mammals. Here, we investigated biochemical and behavioral impacts of ad libitum one-week feeding of high-Met diets on mice. Adult male mice were fed the standard rodent diet that contained 0.44% Met (1×) or a diet containing 16 graded Met doses (1.2×–13×). High-Met diets for one-week induced a dose-dependent decrease in body weight and an increase in serum Met levels with a 2.55 mM peak (versus basal 53 µM) on the 12×Met diet. Total homocysteine (Hcy) levels were also upregulated while concentrations of other amino acids were almost maintained in serum. Similarly, levels of Met and Hcy (but not the other amino acids) were highly elevated in the cerebrospinal fluids of mice on the 10×Met diet; the Met levels were much higher than Hcy and the others. In a series of behavioral tests, mice on the 10×Met diet displayed increased anxiety and decreased traveled distances in an open-field test, increased activity to escape from water soaking and tail hanging, and normal learning/memory activity in a Y-maze test, which were reflections of negative/positive symptoms and normal cognitive function, respectively. These results indicate that high-Met ad libitum feeding even for a week can induce bipolar disorder-like disease models in mice.
rs7041 and rs4588 Polymorphisms in Vitamin D Binding Protein Gene (VDBP) and the Risk of Diseases
Authors: Rozmus Dominika , Płomiński Janusz , Augustyn Klaudia , Cieślińska Anna
Published: January 2022

The purpose of the study was to investigate the role of vitamin D binding protein (VDBP, DBP) and its polymorphism in the vitamin D pathway and human health. This narrative review shows the latest literature on the most popular diseases that have previously been linked to VDBP. Vitamin D plays a crucial role in human metabolism, controlling phosphorus and calcium homeostasis. Vitamin D binding protein bonds vitamin D and its metabolites and transports them to target tissues. The most common polymorphisms in the VDBP gene are rs4588 and rs7041, which are located in exon 11 in domain III of the VDBP gene. rs4588 and rs7041 may be correlated with differences not only in vitamin D status in serum but also with vitamin D metabolites. This review supports the role of single nucleotide polymorphisms (SNPs) in the VDBP gene and presents the latest data showing correlations between VDBP variants with important human diseases such as obesity, diabetes mellitus, tuberculosis, chronic obstructive pulmonary disease, and others. In this review, we aim to systematize the knowledge regarding the occurrence of diseases and their relationship with vitamin D deficiencies, which may be caused by polymorphisms in the VDBP gene. Further research is required on the possible influence of SNPs, modifications in the structure of the binding protein, and their influence on the organism. It is also important to mention that most studies do not have a specific time of year to measure accurate vitamin D metabolite levels, which can be misleading in conclusions due to the seasonal nature of vitamin D.
Severe Natural Outbreak of Cryptocaryon irritans in Gilthead Seabream Produces Leukocyte Mobilization and Innate Immunity at the Gill Tissue
Authors: Cervera Laura , González-Fernández Carmen , Arizcun Marta , Cuesta Alberto , Chaves-Pozo Elena
Published: January 2022

The protozoan parasite Cryptocaryon irritans causes marine white spot disease in a wide range of fish hosts, including gilthead seabream, a very sensitive species with great economic importance in the Mediterranean area. Thus, we aimed to evaluate the immunity of gilthead seabream after a severe natural outbreak of C. irritans. Morphological alterations and immune cell appearance in the gills were studied by light microscopy and immunohistochemical staining. The expression of several immune-related genes in the gills and head kidney were studied by qPCR, including inflammatory and immune cell markers, antimicrobial peptides (AMP), and cell-mediated cytotoxicity (CMC) molecules. Serum humoral innate immune activities were also assayed. Fish mortality reached 100% 8 days after the appearance of the C. irritans episode. Gill filaments were engrossed and packed without any space between filaments and included parasites and large numbers of undifferentiated and immune cells, namely acidophilic granulocytes. Our data suggest leukocyte mobilization from the head kidney, while the gills show the up-regulated transcription of inflammatory, AMPs, and CMC-related molecules. Meanwhile, only serum bactericidal activity was increased upon infection. A potent local innate immune response in the gills, probably orchestrated by AMPs and CMC, is triggered by a severe natural outbreak of C. irritans.
NACA and LRP6 Are Part of a Common Genetic Pathway Necessary for Full Anabolic Response to Intermittent PTH
Authors: St-Arnaud René , Pellicelli Martin , Ismail Mahmoud , Arabian Alice , Jafarov Toghrul , Zhou Chengji J.
Published: January 2022

PTH induces phosphorylation of the transcriptional coregulator NACA on serine 99 through Gαs and PKA. This leads to nuclear translocation of NACA and expression of the target gene Lrp6, encoding a coreceptor of the PTH receptor (PTH1R) necessary for full anabolic response to intermittent PTH (iPTH) treatment. We hypothesized that maintaining enough functional PTH1R/LRP6 coreceptor complexes at the plasma membrane through NACA-dependent Lrp6 transcription is important to ensure maximal response to iPTH. To test this model, we generated compound heterozygous mice in which one allele each of Naca and Lrp6 is inactivated in osteoblasts and osteocytes, using a knock-in strain with a Naca99 Ser-to-Ala mutation and an Lrp6 floxed strain (test genotype: Naca99S/A; Lrp6+/fl;OCN-Cre). Four-month-old females were injected with vehicle or 100 μg/kg PTH(1-34) once daily, 5 days a week for 4 weeks. Control mice showed significant increases in vertebral trabecular bone mass and biomechanical properties that were abolished in compound heterozygotes. Lrp6 expression was reduced in compound heterozygotes vs. controls. The iPTH treatment increased Alpl and Col1a1 mRNA levels in the control but not in the test group. These results confirm that NACA and LRP6 form part of a common genetic pathway that is necessary for the full anabolic effect of iPTH.
Inhibitory Effect of Etravirine, a Non-Nucleoside Reverse Transcriptase Inhibitor, via Anterior Gradient Protein 2 Homolog Degradation against Ovarian Cancer Metastasis
Authors: Ly Thanh Truong Giang , Yun Jisoo , Ha Jong-Seong , Kim Yeon-Ju , Jang Woong-Bi , Van Le Thi Hong , Rethineswaran Vinoth Kumar , Choi Jaewoo , Kim Jae-Ho , Min Sang-Hyun , Lee Dong-Hyung , Yang Ju-Seok , Chung Joo-Seop , Kwon Sang-Mo
Published: January 2022

Anterior gradient protein 2 homolog (AGR2), an endoplasmic reticulum protein, is secreted in the tumor microenvironment. AGR2 is a member of the disulfide isomerase family, is highly expressed in multiple cancers, and promotes cancer metastasis. In this study, we found that etravirine, which is a non-nucleoside reverse transcriptase inhibitor, could induce AGR2 degradation via autophagy. Moreover, etravirine diminished proliferation, migration, and invasion in vitro. Moreover, in an orthotopic xenograft mouse model, the combination of etravirine and paclitaxel significantly suppressed cancer progression and metastasis. This drug may be a promising therapeutic agent for the treatment of ovarian cancer.
Cu(II) Binding Increases the Soluble Toxicity of Amyloidogenic Light Chains
Authors: Russo Rosaria , Romeo Margherita , Schulte Tim , Maritan Martina , Oberti Luca , Barzago Maria Monica , Barbiroli Alberto , Pappone Carlo , Anastasia Luigi , Palladini Giovanni , Diomede Luisa , Ricagno Stefano
Published: January 2022

Light chain amyloidosis (AL) is caused by the aberrant overproduction of immunoglobulin light chains (LCs). The resulting abnormally high LC concentrations in blood lead to deposit formation in the heart and other target organs. Organ damage is caused not only by the accumulation of bulky amyloid deposits, but extensive clinical data indicate that circulating soluble LCs also exert cardiotoxic effects. The nematode C. elegans has been validated to recapitulate LC soluble toxicity in vivo, and in such a model a role for copper ions in increasing LC soluble toxicity has been reported. Here, we applied microscale thermophoresis, isothermal calorimetry and thermal melting to demonstrate the specific binding of Cu2+ to the variable domain of amyloidogenic H7 with a sub-micromolar affinity. Histidine residues present in the LC sequence are not involved in the binding, and yet their mutation to Ala reduces the soluble toxicity of H7. Copper ions bind to and destabilize the variable domains and induce a limited stabilization in this domain. In summary, the data reported here, elucidate the biochemical bases of the Cu2+-induced toxicity; moreover, they also show that copper binding is just one of the several biochemical traits contributing to LC soluble in vivo toxicity.
Expression Profile of miRs in Mesial Temporal Lobe Epilepsy: Systematic Review
Authors: Yakovleva Kristina D. , Dmitrenko Diana V. , Panina Iulia S. , Usoltseva Anna A. , Gazenkampf Kirill A. , Konovalenko Olga V. , Kantimirova Elena A. , Novitsky Maxim A. , Nasyrova Regina F. , Shnayder Natalia A.
Published: January 2022

Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy in children and adults. TLE is characterized by variable onset and seizures. Moreover, this form of epilepsy is often resistant to pharmacotherapy. The search for new mechanisms for the development of TLE may provide us with a key to the development of new diagnostic methods and a personalized approach to the treatment. In recent years, the role of non-coding ribonucleic acids (RNA) has been actively studied, among which microRNA (miR) is of the greatest interest. (1) Background: The purpose of the systematic review is to analyze the studies carried out on the role of miRs in the development of mesial TLE (mTLE) and update the existing knowledge about the biomarkers of this disease. (2) Methods: The search for publications was carried out in the databases PubMed, Springer, Web of Science, Clinicalkeys, Scopus, OxfordPress, Cochrane. The search was carried out using keywords and combinations. We analyzed publications for 2016–2021, including original studies in an animal model of TLE and with the participation of patients with TLE, thematic and systemic reviews, and Cochrane reviews. (3) Results: this thematic review showed that miR‒155, miR‒153, miR‒361‒5p, miR‒4668‒5p, miR‒8071, miR‒197‒5p, miR‒145, miR‒181, miR‒199a, miR‒1183, miR‒129‒2‒3p, miR‒143‒3p (upregulation), miR–134, miR‒0067835, and miR‒153 (downregulation) can be considered as biomarkers of mTLE. However, the roles of miR‒146a, miR‒142, miR‒106b, and miR‒223 are questionable and need further study. (4) Conclusion: In the future, it will be possible to consider previously studied miRs, which have high specificity and sensitivity in mTLE, as prognostic biomarkers (predictors) of the risk of developing this disease in patients with potentially epileptogenic structural damage to the mesial regions of the temporal lobe of the brain (congenital disorders of the neuronal migration and neurogenesis, brain injury, neuro-inflammation, tumor, impaired blood supply, neurodegeneration, etc.).
The Role of Mitochondrial DNA Mutations in Cardiovascular Diseases
Authors: Dabravolski Siarhei A. , Khotina Victoria A. , Sukhorukov Vasily N. , Kalmykov Vladislav A. , Mikhaleva Liudmila M. , Orekhov Alexander N.
Published: January 2022

Cardiovascular diseases (CVD) are one of the leading causes of morbidity and mortality worldwide. mtDNA (mitochondrial DNA) mutations are known to participate in the development and progression of some CVD. Moreover, specific types of mitochondria-mediated CVD have been discovered, such as MIEH (maternally inherited essential hypertension) and maternally inherited CHD (coronary heart disease). Maternally inherited mitochondrial CVD is caused by certain mutations in the mtDNA, which encode structural mitochondrial proteins and mitochondrial tRNA. In this review, we focus on recently identified mtDNA mutations associated with CVD (coronary artery disease and hypertension). Additionally, new data suggest the role of mtDNA mutations in Brugada syndrome and ischemic stroke, which before were considered only as a result of mutations in nuclear genes. Moreover, we discuss the molecular mechanisms of mtDNA involvement in the development of the disease.
Orofacial Cleft and Mandibular Prognathism—Human Genetics and Animal Models
Authors: Jaruga Anna , Ksiazkiewicz Jakub , Kuzniarz Krystian , Tylzanowski Przemko
Published: January 2022

Many complex molecular interactions are involved in the process of craniofacial development. Consequently, the network is sensitive to genetic mutations that may result in congenital malformations of varying severity. The most common birth anomalies within the head and neck are orofacial clefts (OFCs) and prognathism. Orofacial clefts are disorders with a range of phenotypes such as the cleft of the lip with or without cleft palate and isolated form of cleft palate with unilateral and bilateral variations. They may occur as an isolated abnormality (nonsyndromic—NSCLP) or coexist with syndromic disorders. Another cause of malformations, prognathism or skeletal class III malocclusion, is characterized by the disproportionate overgrowth of the mandible with or without the hypoplasia of maxilla. Both syndromes may be caused by the presence of environmental factors, but the majority of them are hereditary. Several mutations are linked to those phenotypes. In this review, we summarize the current knowledge regarding the genetics of those phenotypes and describe genotype–phenotype correlations. We then present the animal models used to study these defects.
Paving Therapeutic Avenues for FOXG1 Syndrome: Untangling Genotypes and Phenotypes from a Molecular Perspective
Authors: Akol Ipek , Gather Fabian , Vogel Tanja
Published: January 2022

Development of the central nervous system (CNS) depends on accurate spatiotemporal control of signaling pathways and transcriptional programs. Forkhead Box G1 (FOXG1) is one of the master regulators that play fundamental roles in forebrain development; from the timing of neurogenesis, to the patterning of the cerebral cortex. Mutations in the FOXG1 gene cause a rare neurodevelopmental disorder called FOXG1 syndrome, also known as congenital form of Rett syndrome. Patients presenting with FOXG1 syndrome manifest a spectrum of phenotypes, ranging from severe cognitive dysfunction and microcephaly to social withdrawal and communication deficits, with varying severities. To develop and improve therapeutic interventions, there has been considerable progress towards unravelling the multi-faceted functions of FOXG1 in the neurodevelopment and pathogenesis of FOXG1 syndrome. Moreover, recent advances in genome editing and stem cell technologies, as well as the increased yield of information from high throughput omics, have opened promising and important new avenues in FOXG1 research. In this review, we provide a summary of the clinical features and emerging molecular mechanisms underlying FOXG1 syndrome, and explore disease-modelling approaches in animals and human-based systems, to highlight the prospects of research and possible clinical interventions.
Comparison of Carbonic Anhydrases for CO2 Sequestration
Authors: Steger Franziska , Reich Johanna , Fuchs Werner , Rittmann Simon K.-M. R. , Gübitz Georg M. , Ribitsch Doris , Bochmann Günther
Published: January 2022

Strategies for depleting carbon dioxide (CO2) from flue gases are urgently needed and carbonic anhydrases (CAs) can contribute to solving this problem. They catalyze the hydration of CO2 in aqueous solutions and therefore capture the CO2. However, the harsh conditions due to varying process temperatures are limiting factors for the application of enzymes. The current study aims to examine four recombinantly produced CAs from different organisms, namely CAs from Acetobacterium woodii (AwCA or CynT), Persephonella marina (PmCA), Methanobacterium thermoautotrophicum (MtaCA or Cab) and Sulphurihydrogenibium yellowstonense (SspCA). The highest expression yields and activities were found for AwCA (1814 WAU mg−1 AwCA) and PmCA (1748 WAU mg−1 PmCA). AwCA was highly stable in a mesophilic temperature range, whereas PmCA proved to be exceptionally thermostable. Our results indicate the potential to utilize CAs from anaerobic microorganisms to develop CO2 sequestration applications.
Lipocalin 2 Influences Bone and Muscle Phenotype in the MDX Mouse Model of Duchenne Muscular Dystrophy
Authors: Ponzetti Marco , Ucci Argia , Maurizi Antonio , Giacchi Luca , Teti Anna , Rucci Nadia
Published: January 2022

Lipocalin 2 (Lcn2) is an adipokine involved in bone and energy metabolism. Its serum levels correlate with bone mechanical unloading and inflammation, two conditions representing hallmarks of Duchenne Muscular Dystrophy (DMD). Therefore, we investigated the role of Lcn2 in bone loss induced by muscle failure in the MDX mouse model of DMD. We found increased Lcn2 serum levels in MDX mice at 1, 3, 6, and 12 months of age. Consistently, Lcn2 mRNA was higher in MDX versus WT muscles. Immunohistochemistry showed Lcn2 expression in mononuclear cells between muscle fibres and in muscle fibres, thus confirming the gene expression results. We then ablated Lcn2 in MDX mice, breeding them with Lcn2−/− mice (MDXxLcn2−/−), resulting in a higher percentage of trabecular volume/total tissue volume compared to MDX mice, likely due to reduced bone resorption. Moreover, MDXxLcn2−/− mice presented with higher grip strength, increased intact muscle fibres, and reduced serum creatine kinase levels compared to MDX. Consistently, blocking Lcn2 by treating 2-month-old MDX mice with an anti-Lcn2 monoclonal antibody (Lcn2Ab) increased trabecular volume, while reducing osteoclast surface/bone surface compared to MDX mice treated with irrelevant IgG. Grip force was also increased, and diaphragm fibrosis was reduced by the Lcn2Ab. These results suggest that Lcn2 could be a possible therapeutic target to treat DMD-induced bone loss.
Functional Selectivity of Coumarin Derivates Acting via GPR55 in Neuroinflammation
Authors: Apweiler Matthias , Streyczek Jana , Saliba Soraya Wilke , Collado Juan Antonio , Hurrle Thomas , Gräßle Simone , Muñoz Eduardo , Normann Claus , Hellwig Sabine , Bräse Stefan , Fiebich Bernd L.
Published: January 2022

Anti-neuroinflammatory treatment has gained importance in the search for pharmacological treatments of different neurological and psychiatric diseases, such as depression, schizophrenia, Parkinson’s disease, and Alzheimer’s disease. Clinical studies demonstrate a reduction of the mentioned diseases’ symptoms after the administration of anti-inflammatory drugs. Novel coumarin derivates have been shown to elicit anti-neuroinflammatory effects via G-protein coupled receptor GPR55, with possibly reduced side-effects compared to the known anti-inflammatory drugs. In this study, we, therefore, evaluated the anti-inflammatory capacities of the two novel coumarin-based compounds, KIT C and KIT H, in human neuroblastoma cells and primary murine microglia. Both compounds reduced PGE2-concentrations likely via the inhibition of COX-2 synthesis in SK-N-SH cells but only KIT C decreased PGE2-levels in primary microglia. The examination of other pro- and anti-inflammatory parameters showed varying effects of both compounds. Therefore, the differences in the effects of KIT C and KIT H might be explained by functional selectivity as well as tissue- or cell-dependent expression and signal pathways coupled to GPR55. Understanding the role of chemical residues in functional selectivity and specific cell- and tissue-targeting might open new therapeutic options in pharmacological drug development and might improve the treatment of the mentioned diseases by intervening in an early step of their pathogenesis.