bluuebunny/crossref_metadata_2025 huggingface dataset:
A Qualitative Exploration of Parental Views When Comparing Individual to Group Sports in Children with Autism Spectrum Disorder—A Pilot Study
Authors: Vella Fondacaro Daniel , Vella Fondacaro Francesca , Camilleri Nigel
Published: June 2022

(1) Background: Physical activity is important for children with autism spectrum disorder. This study aimed to analyse autistic children’s and their parents’ preferences between group and individual physical activity, while exploring potential social barriers that they might encounter. (2) Methods: Retrospective analysis identified 701 new referrals received by the Maltese national child and adolescent mental health service, between 2016 and 2017. Of them, 24 received a sole diagnosis of autism and 10 were chosen via purposive sampling. A semi-structured interview guide was created, including readability testing, translation/back-translation, inter-rater agreements, and focus group testing. Parents were informed, consented, interviewed and thematic analysis carried out. Further quantitative data were tabled accordingly. (3) Results: Only one child met World Health Organisation recommendations for physical activity. More children preferred individual sports while parents described more benefits with group sports. Parents’ perceived benefits with group sports included better socialization, while improved levels of self-esteem and coping with anxiety were highlighted benefits for individual sports. Parents felt misunderstood, burnt out, and described a lack of autism-friendly sports facilities, including geographical disproportionation of adequate facilities on the island. Too much screen time was a major parental concern. (4) Conclusion: Recommendations aim to develop sport therapy systems and well-resourced services in Malta. Staff training is recommended to improve service quality.
Use of Physical Activity and Exercise to Reduce Inflammation in Children and Adolescents with Obesity
Authors: Calcaterra Valeria , Vandoni Matteo , Rossi Virginia , Berardo Clarissa , Grazi Roberta , Cordaro Erika , Tranfaglia Valeria , Carnevale Pellino Vittoria , Cereda Cristina , Zuccotti Gianvincenzo
Published: June 2022

Childhood obesity is a leading public health problem worldwide, as it is increasingly prevalent and therefore responsible for serious obesity-related comorbidities, not only in childhood but also in adulthood. In addition to cardio-metabolic obesity-related disorders, recent evidence suggests that excess adipose tissue in turn is associated with immune cell infiltration, increased adipokine release, and the development of low-grade systemic inflammation obesity. Exercise is considered a non-pharmacological intervention that can delay obesity-related comorbidities, improving cardiovascular fitness and modulating the inflammatory processes. It has been reported that the anti-inflammatory effect of regular exercise may be mediated by a reduction in visceral fat mass, with a subsequent decrease in the release of adipokines from adipose tissue (AT) and/or by the induction of an anti-inflammatory environment. In this narrative review, we discuss the role of AT as an endocrine organ associated with chronic inflammation and its role in obesity-related complications, focusing on the effect of exercise in reducing inflammation in children and adolescents with obesity. Regular physical exercise must be considered as a natural part of a healthy lifestyle, and promoting physical activity starting from childhood is useful to limit the negative effects of obesity on health. The crucial role of the immune system in the development of obesity-induced inflammatory processes and the efficacy of exercise as an anti-inflammatory, non-pharmacological intervention may provide possible targets for the development of new treatments and early preventive strategies.
Raiders of the Olympic Values: Perception of the Development of Women’s Canoeing in Spain for Tokyo 2021
Authors: Guevara-Pérez Juan Carlos , Rojo-Ramos Jorge , Urdaneta-Camacho Rudemarlyn , Vallespín Emilio Martín
Published: June 2022

Although canoeing is one of the oldest sports in the Olympic program, it was not until the Tokyo Olympics in 2021 that women’s canoeing was first included in the competition. This fact has posed a challenge to the initiation and technification systems of countries in order to obtain competitive results, particularly in Spain, as it is one of the sports that contributed the most medals to the Olympic medal tally. The aim of this study was to evaluate the promotion and development of talent in women’s canoeing in Spain for its first-ever Olympic participation. For this purpose, an analytical survey (n = 167) was carried out, the answers to which were contrasted by gender and modality practiced. The results showed a positive evaluation of the current position in flatwater female canoeing regarding talent that is consistent with the competitive results achieved. Additionally, we found that the gender of the respondents influences their perception of the age of sport initiation and the suitability of the progression in the competition systems for the promotion of women’s canoeing in Spain. Therefore, the results of the questionnaire will facilitate a quick diagnosis of critical aspects by sport managers, allowing them to take corrective actions in time for the development of female canoeists and, at the same time, to promote future studies that delve deeper into these topics.
Digital Addiction and Sleep
Authors: Dresp-Langley Birgitta , Hutt Axel
Published: June 2022

In 2020, the World Health Organization formally recognized addiction to digital technology (connected devices) as a worldwide problem, where excessive online activity and internet use lead to inability to manage time, energy, and attention during daytime and produce disturbed sleep patterns or insomnia during nighttime. Recent studies have shown that the problem has increased in magnitude worldwide during the COVID-19 pandemic. The extent to which dysfunctional sleep is a consequence of altered motivation, memory function, mood, diet, and other lifestyle variables or results from excess of blue-light exposure when looking at digital device screens for long hours at day and night is one of many still unresolved questions. This article offers a narrative overview of some of the most recent literature on this topic. The analysis provided offers a conceptual basis for understanding digital addiction as one of the major reasons why people, and adolescents in particular, sleep less and less well in the digital age. It discusses definitions as well as mechanistic model accounts in context. Digital addiction is identified as functionally equivalent to all addictions, characterized by the compulsive, habitual, and uncontrolled use of digital devices and an excessively repeated engagement in a particular online behavior. Once the urge to be online has become uncontrollable, it is always accompanied by severe sleep loss, emotional distress, depression, and memory dysfunction. In extreme cases, it may lead to suicide. The syndrome has been linked to the known chronic effects of all drugs, producing disturbances in cellular and molecular mechanisms of the GABAergic and glutamatergic neurotransmitter systems. Dopamine and serotonin synaptic plasticity, essential for impulse control, memory, and sleep function, are measurably altered. The full spectrum of behavioral symptoms in digital addicts include eating disorders and withdrawal from outdoor and social life. Evidence pointing towards dysfunctional melatonin and vitamin D metabolism in digital addicts should be taken into account for carving out perspectives for treatment. The conclusions offer a holistic account for digital addiction, where sleep deficit is one of the key factors.
Subjective Wellbeing among University Students and Recent Graduates: Evidence from the United Kingdom
Authors: Donald William E. , Jackson Denise
Published: June 2022

This study compares students’ and recent graduates’ perceptions of their subjective wellbeing and offers support mechanisms and resources to enhance wellbeing in higher education. Survey data were collected in September 2021 from 414 UK-based higher education students and recent graduates on their self-perceived subjective wellbeing in March 2020 (before COVID-19 regulations restrictions) and September 2021 (18 months later). Findings showed that subjective wellbeing scores fell for almost three-quarters of university students and recent graduates between March 2020 and September 2021. Interestingly, around one-fifth of participants reported increased subjective wellbeing scores whilst the remaining participants reported no impact. Positive impacts of the pandemic included opportunities for self-improvement with more free time for focusing on health and relationships. Adverse outcomes included feelings of isolation, reduced mental and physical health, difficulties undertaking degree studies and work, travel restrictions, and concerns for labour market competitiveness. The study advances the application of the conservation of resources theory and identifies strategies for higher education institutions to better support and improve their students’ and future graduates’ subjective wellbeing. Strategies include access to counselling, mindfulness, opportunities for participation in hobbies, interaction with peers, flexible work and study options, and guidance on career and finances.
Thyroid Dysfunction and COVID-19: The Emerging Role of Selenium in This Intermingled Relationship
Authors: Gorini Francesca , Sabatino Laura , Coi Alessio , Iervasi Giorgio , Vassalle Cristina
Published: June 2022

COVID-19 represents a worldwide public health emergency, and, beyond the respiratory symptoms characterizing the classic viral disease, growing evidence has highlighted a possible reciprocal relationship between SARS-CoV-2 infection and thyroid dysfunction. The updated data discussed in this review suggests a role of SARS-CoV-2 infection on the thyroid gland, with multiple thyroid pictures described. Conversely, no conclusion can be drawn on the association between pre-existing thyroid disease and increased risk of SARS-CoV-2 infection. In this scenario, selenium (Se), an essential trace element critical for thyroid function and known as an effective agent against viral infections, is emerging as a potential novel therapeutic option for the treatment of COVID-19. Large multicentre cohort studies are required to elucidate the mechanisms underlying thyroid dysfunction during or following recovery from COVID-19, including Se status. Meanwhile, clinical trials should be performed to evaluate whether adequate intake of Se can help address COVID-19 in Se-deficient patients, also avoiding thyroid complications that can contribute to worsening outcomes during infection.
Multishell Diffusion MR Tractography Yields Morphological and Microstructural Information of the Anterior Optic Pathway: A Proof-of-Concept Study in Patients with Leber’s Hereditary Optic Neuropathy
Authors: Manners David Neil , Gramegna Laura Ludovica , La Morgia Chiara , Sighinolfi Giovanni , Fiscone Cristiana , Carbonelli Michele , Romagnoli Martina , Carelli Valerio , Tonon Caterina , Lodi Raffaele
Published: June 2022

Tractography based on multishell diffusion-weighted magnetic resonance imaging (DWI) can be used to estimate the course of myelinated white matter tracts and nerves, yielding valuable information regarding normal anatomy and variability. DWI is sensitive to the local tissue microstructure, so tractography can be used to estimate tissue properties within nerve tracts at a resolution of millimeters. This study aimed to test the applicability of the method using a disease with a well-established pattern of myelinated nerve involvement. Eight patients with LHON and 13 age-matched healthy controls underwent tractography of the anterior optic pathway. Diffusion parameters were compared between groups, and for the patient group correlated with clinical/ophthalmological parameters. Tractography established the course of the anterior optic pathway in both patients and controls. Localized changes in fractional anisotropy were observed, and related to estimates of different tissue compartments within the nerve and tract. The proportion of different compartments correlated with markers of disease severity. The method described allows both anatomical localization and tissue characterization in vivo, permitting both visualization of variation at the individual level and statistical inference at the group level. It provides a valuable adjunct to ex vivo anatomical and histological study of normal variation and disease processes.
Effect of Precipitation Variation on Soil Respiration in Rain-Fed Winter Wheat Systems on the Loess Plateau, China
Authors: Chu Houkun , Ni Hong , Ma Jingyong , Shen Yuying
Published: June 2022

Global climate change has aggravated the hydrological cycle by changing both the amount and distribution of precipitation, and this is especially notable in the semiarid Loess Plateau. How these precipitation variations have affected soil carbon (C) emission by the agroecosystems is still unclear. Here, to evaluate the effects of precipitation variation on soil respiration (Rs), a field experiment (from 2019 to 2020) was conducted with 3 levels of manipulation, including ambient precipitation (CK), 30% decreased precipitation (P−30), and 30% increased precipitation (P+30) in rain-fed winter wheat (Triticum aestivum L.) agroecosystems on the Loess Plateau, China. The results showed that the average Rs in P−30 treatment was significantly higher than those in the CK and P+30 treatments (p < 0.05), and the cumulative CO2 emissions were 406.37, 372.58 and 383.59 g C m−2, respectively. Seasonal responses of Rs to the soil volumetric moisture content (VWC) were affected by the different precipitation treatments. Rs was quadratically correlated with the VWC in the CK and P+30 treatments, and the threshold of the optimal VWC for Rs was approximately 16.06–17.07%. However, Rs was a piecewise linear function of the VWC in the P−30 treatment. The synergism of soil temperature (Ts) and VWC can better explain the variation in soil respiration in the CK and P−30 treatments. However, an increase in precipitation led to the decoupling of the Rs responses to Ts. The temperature sensitivity of respiration (Q10) varied with precipitation variation. Q10 was positive correlated with seasonal Ts in the CK and P+30 treatments, but exhibited a negative polynomial correlation with seasonal Ts in the P−30 treatment. Rs also exhibited diurnal clockwise hysteresis loops with Ts in the three precipitation treatments, and the seasonal dynamics of the diurnal lag time were significantly negatively correlated with the VWC. Our study highlighted that understanding the synergistic and decoupled responses of Rs and Q10 to Ts and VWC and the threshold of the change in response to the VWC under precipitation variation scenarios can benefit the prediction of future C balances in agroecosystems in semiarid regions under climate change.
The Association between mHealth App Use and Healthcare Satisfaction among Clients at Outpatient Clinics: A Cross-Sectional Study in Inner Mongolia, China
Authors: Cao Li , Chongsuvivatwong Virasakdi , McNeil Edward B.
Published: June 2022

Mobile health (mHealth) applications (apps) have been developed in hospital settings to allocate and manage medical care services, which is one of the national strategies to improve health care in China. Little is known about the comprehensive effects of hospital-based mHealth app use on client satisfaction. The aim of this study was to determine the relationship between the full range of mHealth app use and satisfaction domains among clients attending outpatient clinics. A cross-sectional survey was conducted from January to February 2021 in twelve tertiary hospitals in Inner Mongolia. After the construction of the mHealth app use, structural equation modeling was used for data analysis. Of 1889 participants, the standardized coefficients β on environment/convenience, health information, and medical service fees were 0.11 (p < 0.001), 0.06 (p = 0.039), and 0.08 (p = 0.004), respectively. However, app use was not significantly associated with satisfaction of doctor–patient communication (β = 0.05, p = 0.069), short-term outcomes (β = 0.05, p = 0.054), and general satisfaction (β = 0.02, p = 0.429). Clients of the study hospitals were satisfied with the services, but their satisfaction was not much associated with mHealth use. The limitation of the mHealth system should be improved to enhance communication and engagement among clients, doctors, and healthcare givers, as well as to pay more attention to health outcomes and satisfaction of clients.
Relationship between Bone Mineral Density and Dental Caries in Koreans by Sex and Menopausal State
Authors: Lee Yun-Hee , Myong Jun-Pyo
Published: June 2022

We aimed to investigate the relationship between bone mineral density and dental caries in adults of over 19 years of age who were categorized according to their sex and menopausal status. The Korea National Health and Nutrition Examination Survey (KNHANES) dataset was used for the study. Bone mineral density (BMD) and oral health examination data were collected between 2008 and 2011. A total of 17,141 adults of ≥19 years old were eligible for inclusion in the present study. Multiple regression analysis was performed after adjustment for age, household income, educational level, smoking status, and alcohol drinking status for men, and pre- and post-menopausal women. In men, the β-value for the mean decayed, missing, and filled teeth (DMFT) index was 0.98 (95% confidence interval (CI) = 0.71–1.25), and was significantly higher in osteoporotic participants than in participants with normal BMD (p < 0.05). In post-menopausal women, the β-value for the mean DMFT index was 0.86, and was higher in the osteoporotic participants than in the participants with normal BMD (p < 0.05). Men and post-menopausal women with osteoporosis had higher DMFT indexes than those with normal BMD. In addition, there was a correlation between DMFT index and BMD in men and post-menopausal women. Therefore, the prevention of osteoporosis should be implemented alongside proper oral care.
The Role of Motivation Systems, Anxiety, and Low Self-Control in Smartphone Addiction among Smartphone-Based Social Networking Service (SNS) Users
Authors: Kwak Min-Jung , Cho Hyun , Kim Dai-Jin
Published: June 2022

Given that Social Networking Service (SNS) has emerged as the most influential platform, which can lead users to addictive smartphone use, it is necessary to investigate which psychological variables lead smartphone-based SNS users to addictive smartphone use. Still, studies on the relationship between psychological variables and addictive smartphone use among smartphone-based SNS users remain to be explored. Therefore, this study aims to investigate the role of psychological factors on smartphone addiction proneness (SAP). A total of 433 smartphone-based SNS users were collected from 5003 adults in Korea. Data were analyzed with descriptive statistics, Pearson’s correlation coefficients, and path analysis using SPSS 21.0 and AMOS 23.0. The results of a parallel-mediation path analysis demonstrated that Behavioral Inhibition (BIS), Behavioral activation (BAS) drive, anxiety, and low self-control directly influenced SAP, separately. BIS and BAS _drive also had significant indirect effects on SAP through the effect of anxiety. BIS and BAS_fun had significant indirect effects on SAP through the effect of low self-control. The study variables accounted for 38.4 of the total variances of SAP. Thus, when establishing interventions to reduce the users’ addictive smartphone use, these interactive relationships of the variables should be considered.
Oncostatin M Counteracts the Fibrotic Effects of TGF-β1 and IL-4 on Nasal-Polyp-Derived Fibroblasts: A Control of Fibrosis in Chronic Rhinosinusitis with Nasal Polyps?
Authors: Carsuzaa Florent , Béquignon Émilie , Bainaud Matthieu , Jégou Jean-François , Dufour Xavier , Lecron Jean-Claude , Favot Laure
Published: June 2022

Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with inflammation and tissue remodeling including myofibroblasts differentiation and extracellular matrix (ECM) deposition mediated by TGF-β1 and IL-4. Oncostatin M (OSM) is a cytokine involved in fibrotic processes in other cellular subtypes. We investigated the mechanisms of action of OSM in the fibrosis process associated with CRSwNP. The expression of IL-4, OSM and TGF-β1 was assessed by RT-qPCR. Primary human cultures of nasal-polyp-derived fibroblasts were established and stimulated by TGF-β1 and/or IL-4 and/or OSM. The expression of ECM components and αSMA was determined by RT-qPCR and Western blot. TGF-β1-Smad3 signaling was investigated by immunofluorescence. TGF-β1, IL-4 and OSM as well as αSMA were overexpressed in nasal polyps when compared to noninflammatory nasal mucosa. In TGF-β1-stimulated nasal-polyp-derived fibroblasts, ECM genes and αSMA gene and protein were overexpressed, as well as αSMA in IL-4-stimulated fibroblasts. OSM counteracted the profibrotic effect of TGF-β1 on ECM components and αSMA. TGF-β1-induced nuclear translocation of Smad3 was completely reversed by OSM. OSM counteracts the profibrotic effect of IL-4 and also TGF-β1, by inhibiting the nuclear translocation of Smad3. We suggest OSM could be an efficient tool to protect against fibrosis in CRSwNP.
Complex Elucidation of Cells-of-Origin in Pediatric Soft Tissue Sarcoma: From Concepts to Real Life, Hide-and-Seek through Epigenetic and Transcriptional Reprogramming
Authors: Savary Clara , Picard Cécile , Corradini Nadège , Castets Marie
Published: June 2022

Soft tissue sarcoma (STS) comprise a large group of mesenchymal malignant tumors with heterogeneous cellular morphology, proliferative index, genetic lesions and, more importantly, clinical features. Full elucidation of this wide diversity remains a central question to improve their therapeutic management and the identity of cell(s)-of-origin from which these tumors arise is part of this enigma. Cellular reprogramming allows transitions of a mature cell between phenotypes, or identities, and represents one key driver of tumoral heterogeneity. Here, we discuss how cellular reprogramming mediated by driver genes in STS can profoundly reshape the molecular and morphological features of a transformed cell and lead to erroneous interpretation of its cell-of-origin. This review questions the fact that the epigenetic context in which a genetic alteration arises has to be taken into account as a key determinant of STS tumor initiation and progression. Retracing the cancer-initiating cell and its clonal evolution, notably via epigenetic approach, appears as a key lever for understanding the origin of these tumors and improving their clinical management.
Glycan-Lectin Interactions as Novel Immunosuppression Drivers in Glioblastoma
Authors: Pace Angelica , Scirocchi Fabio , Napoletano Chiara , Zizzari Ilaria Grazia , D’Angelo Luca , Santoro Antonio , Nuti Marianna , Rahimi Hassan , Rughetti Aurelia
Published: June 2022

Despite diagnostic and therapeutic improvements, glioblastoma (GB) remains one of the most threatening brain tumor in adults, underlining the urgent need of new therapeutic targets. Lectins are glycan-binding proteins that regulate several biological processes through the recognition of specific sugar motifs. Lectins and their ligands are found on immune cells, endothelial cells and, also, tumor cells, pointing out a strong correlation among immunity, tumor microenvironment and vascularization. In GB, altered glycans and lectins contribute to tumor progression and immune evasion, shaping the tumor-immune landscape promoting immunosuppressive cell subsets, such as myeloid-derived suppressor cells (MDSCs) and M2-macrophages, and affecting immunoeffector populations, such as CD8+ T cells and dendritic cells (DCs). Here, we discuss the latest knowledge on the immune cells, immune related lectin receptors (C-type lectins, Siglecs, galectins) and changes in glycosylation that are involved in immunosuppressive mechanisms in GB, highlighting their interest as possible novel therapeutical targets.
Biochemical, Sensory, and Molecular Evaluation of Flavour and Consumer Acceptability in Australian Papaya (Carica papaya L.) Varieties
Authors: Zhou Ziwei , Bar Ido , Ford Rebecca , Smyth Heather , Kanchana-udomkan Chutchamas
Published: June 2022

Inconsistency in flavour is one of the major challenges to the Australian papaya industry. However, objectively measurable standards of the compound profiles that provide preferable taste and aroma, together with consumer acceptability, have not been set. In this study, three red-flesh papayas (i.e., ‘RB1’, ‘RB4’, and ‘Skybury’) and two yellow-flesh papayas (i.e., ‘1B’ and ‘H13’) were presented to a trained sensory panel and a consumer panel to assess sensory profiles and liking. The papaya samples were also examined for sugar components, total soluble solids, and 14 selected volatile compounds. Additionally, the expression patterns of 10 genes related to sweetness and volatile metabolism were assessed. In general, red papaya varieties had higher sugar content and tasted sweeter than yellow varieties, while yellow varieties had higher concentrations of citrus floral aroma volatiles and higher aroma intensity. Higher concentrations of glucose, linalool oxide, and terpinolene were significantly associated with decreased consumer liking. Significant differences were observed in the expression profiles of all the genes assessed among the selected papaya varieties. Of these, cpGPT2 and cpBGLU31 were positively correlated to glucose production and were expressed significantly higher in ‘1B’ than in ‘RB1’ or ‘Skybury’. These findings will assist in the strategic selective breeding for papaya to better match consumer and, hence, market demand.
Design, Spectroscopy, and Assessment of Cholinesterase Inhibition and Antimicrobial Activities of Novel Coumarin–Thiadiazole Hybrids
Authors: Karcz Dariusz , Starzak Karolina , Ciszkowicz Ewa , Lecka-Szlachta Katarzyna , Kamiński Daniel , Creaven Bernadette , Miłoś Anna , Jenkins Hollie , Ślusarczyk Lidia , Matwijczuk Arkadiusz
Published: June 2022

A novel series of coumarin–thiadiazole hybrids, derived from substituted coumarin-3-carboxylic acids was isolated and fully characterized with the use of a number of spectroscopic techniques and XRD crystallography. Several of the novel compounds showed intensive fluorescence in the visible region, comparable to that of known coumarin-based fluorescence standards. Moreover, the new compounds were tested as potential antineurodegenerative agents via their ability to act as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. Compared to the commercial standards, only a few compounds demonstrated moderate AChE and BuChE activities. Moreover, the novel derivatives were tested for their antimicrobial activity against a panel of pathogenic bacterial and fungal species. Their lack of activity and toxicity across a broad range of biochemical assays, together with the exceptional emission of some hybrid molecules, highlights the possible use of a number of the novel hybrids as potential fluorescence standards or fluorescence imaging agents.
Mechanisms Driving the Emergence of Neuronal Hyperexcitability in Fragile X Syndrome
Authors: Bülow Pernille , Segal Menahem , Bassell Gary J.
Published: June 2022

Hyperexcitability is a shared neurophysiological phenotype across various genetic neurodevelopmental disorders, including Fragile X syndrome (FXS). Several patient symptoms are associated with hyperexcitability, but a puzzling feature is that their onset is often delayed until their second and third year of life. It remains unclear how and why hyperexcitability emerges in neurodevelopmental disorders. FXS is caused by the loss of FMRP, an RNA-binding protein which has many critical roles including protein synthesis-dependent and independent regulation of ion channels and receptors, as well as global regulation of protein synthesis. Here, we discussed recent literature uncovering novel mechanisms that may drive the progressive onset of hyperexcitability in the FXS brain. We discussed in detail how recent publications have highlighted defects in homeostatic plasticity, providing new insight on the FXS brain and suggest pharmacotherapeutic strategies in FXS and other neurodevelopmental disorders.
Cartilage Homeostasis and Osteoarthritis
Authors: Fujii Yuta , Liu Lin , Yagasaki Lisa , Inotsume Maiko , Chiba Tomoki , Asahara Hiroshi
Published: June 2022

Healthy limb joints are important for maintaining health and attaining longevity. Endochondral ossification (the replacement of cartilage with bone, occurring during skeletal development) is essential for bone formation, especially in long-axis bones. In contrast to endochondral ossification, chondrocyte populations in articular cartilage persist and maintain joint tissue into adulthood. Articular cartilage, a connective tissue consisting of chondrocytes and their surrounding extracellular matrices, plays an essential role in the mechanical cushioning of joints in postnatal locomotion. Osteoarthritis (OA) pathology relates to disruptions in the balance between anabolic and catabolic signals, that is, the loss of chondrocyte homeostasis due to aging or overuse of cartilages. The onset of OA increases with age, shortening a person’s healthy life expectancy. Although many people with OA experience pain, the mainstay of treatment is symptomatic therapy, and no fundamental treatment has yet been established. To establish regenerative or preventative therapies for cartilage diseases, further understanding of the mechanisms of cartilage development, morphosis, and homeostasis is required. In this review, we describe the general development of cartilage and OA pathology, followed by a discussion on anabolic and catabolic signals in cartilage homeostasis, mainly microRNAs.
Haploinsufficiency of a Circadian Clock Gene Bmal1 (Arntl or Mop3) Causes Brain-Wide mTOR Hyperactivation and Autism-like Behavioral Phenotypes in Mice
Authors: Singla Rubal , Mishra Abhishek , Lin Hao , Lorsung Ethan , Le Nam , Tin Su , Jin Victor X. , Cao Ruifeng
Published: June 2022

Approximately 50–80% of children with autism spectrum disorders (ASDs) exhibit sleep problems, but the contribution of circadian clock dysfunction to the development of ASDs remains largely unknown. The essential clock gene Bmal1 (Arntl or Mop3) has been associated with human sociability, and its missense mutation is found in ASD. Our recent study found that Bmal1-null mice exhibit a variety of autism-like phenotypes. Here, we further investigated whether an incomplete loss of Bmal1 function could cause significant autism-like behavioral changes in mice. Our results demonstrated that heterozygous Bmal1 deletion (Bmal1+/−) reduced the Bmal1 protein levels by ~50–75%. Reduced Bmal1 expression led to decreased levels of clock proteins, including Per1, Per2, Cry 1, and Clock but increased mTOR activities in the brain. Accordingly, Bmal1+/− mice exhibited aberrant ultrasonic vocalizations during maternal separation, deficits in sociability and social novelty, excessive repetitive behaviors, impairments in motor coordination, as well as increased anxiety-like behavior. The novel object recognition memory remained intact. Together, these results demonstrate that haploinsufficiency of Bmal1 can cause autism-like behavioral changes in mice, akin to those identified in Bmal1-null mice. This study provides further experimental evidence supporting a potential role for disrupted clock gene expression in the development of ASD.
Molecular Markers of Kidney Transplantation Outcome: Current Omics Tools and Future Developments
Authors: Lepoittevin Maryne , Kerforne Thomas , Pellerin Luc , Hauet Thierry , Thuillier Raphael
Published: June 2022

Purpose of review: The emerging field of molecular predictive medicine is aiming to change the traditional medical approach in renal transplantation. Many studies have explored potential biomarker molecules with predictive properties in renal transplantation, issued from omics research. Herein, we review the biomarker molecules of four technologies (i.e., Genomics, Transcriptomics, Proteomics, and Metabolomics) associated with favorable kidney transplant outcomes. Recent findings: Several panels of molecules have been associated with the outcome that the majority of markers are related to inflammation and immune response; although. other molecular ontologies are also represented, such as proteasome, growth, regeneration, and drug metabolism. Throughout this review, we highlight the lack of properly validated statistical demonstration. Indeed, the most preeminent molecular panels either remain at the limited size study stage or are not confirmed during large-scale studies. At the core of this problem, we identify the methodological shortcomings and propose a comprehensive workflow for discovery and validation of molecular biomarkers that aims to improve the relevance of these tools in the future. Summary: Overall, adopting a patient management through omics approach could bring remarkable improvement to transplantation success. An increased effort and investment between scientists, medical biologists, and clinicians seem to be the path toward a proper solution.
Transcriptome Analysis Reveals Crosstalk between the Abscisic Acid and Jasmonic Acid Signaling Pathways in Rice-Mediated Defense against Nilaparvata lugens
Authors: Li Jitong , Chen Lin , Ding Xu , Fan Wenyan , Liu Jinglan
Published: June 2022

The brown planthopper (BPH) impacts both rice yield and quality. The exogenous application of abscisic acid (ABA) and jasmonic acid (JA) has been previously shown to induce rice resistance to BPH; however, the regulation of rice-mediated defense by these plant growth regulators is unclear. We applied exogenous JA and ABA to rice and analyzed molecular responses to BPH infestation. Nine RNA libraries were sequenced, and 6218 differentially expressed genes (DEGs) were generated and annotated. After ABA + BPH and JA + BPH treatments, 3491 and 2727 DEGs, respectively, were identified when compared with the control (BPH alone). GO enrichment and KEGG pathway analysis showed that the expression of several JA pathway genes (OsAOS2, encoding allene oxide synthase; OsOPR, 12-oxo-phytodienoic acid reductase; and OsACOX, acy1-CoA oxidase) were significantly up-regulated after ABA + BPH treatment. Furthermore, exogenous JA increased the expression of genes involved in ABA synthesis. Meanwhile, the expression levels of genes encoding WRKY transcription factors, myelocytomatosis protein 2 (MYC2) and basic leucine zippers (bZIPs) were up-regulated significantly, indicating that ABA and JA might function together to increase the expression of transcription factors during the rice defense response. The DEGs identified in this study provide vital insights into the synergism between ABA and JA and further contribute to the mechanistic basis of rice resistance to BPH.
Targeting PIK3CA Actionable Mutations in the Circulome: A Proof of Concept in Metastatic Breast Cancer
Authors: Cardinali Barbara , De Luca Giuseppa , Tasso Roberta , Coco Simona , Garuti Anna , Buzzatti Giulia , Sciutto Andrea , Arecco Luca , Villa Federico , Carli Franca , Reverberi Daniele , Quarto Rodolfo , Dono Mariella , Del Mastro Lucia
Published: June 2022

The study of circulating cancer-derived components (circulome) is considered the new frontier of liquid biopsy. Despite the recognized role of circulome biomarkers, their comparative molecular profiling is not yet routine. In advanced breast cancer (BC), approximately 40% of hormone-receptor-positive, HER2-negative BC cases harbor druggable PIK3CA mutations suitable for combined alpelisib/fulvestrant treatment. This pilot study investigates PIK3CA mutations in circulating tumor DNA (ctDNA), tumor cells (CTCs), and extracellular vesicles (EVs) with the aim of determining which information on molecular targetable profiling could be recollected in each of them. The in-depth molecular analysis of four BC patients demonstrated, as a proof-of-concept study, that it is possible to retrieve mutational information in the three components. Patient-specific PIK3CA mutations were found in both tissue and ctDNA and in 3/4 cases, as well as in CTCs, in the classical population (large-sized CD45−/EpCAM+/− cells), and/or in the “non-conventional” sub-population (smaller-sized CD44+/EpCAM−/CD45− cells). Consistent mutational profiles of EVs with CTCs suggest that they may have been released by CTCs. This preliminary evidence on the molecular content of the different circulating biomaterials suggests their possible function as a mirror of the intrinsic heterogeneity of BC. Moreover, this study demonstrates, through mutational assessment, the tumor origin of the different CTC sub-populations sustaining the translational value of the circulome for a more comprehensive picture of the disease.
A TIR-NBS-LRR Gene MdTNL1 Regulates Resistance to Glomerella Leaf Spot in Apple
Authors: Lv Lingling , Liu Yingshuang , Bai Suhua , Turakulov Khurshid Sadullaevich , Dong Chaohua , Zhang Yugang
Published: June 2022

Glomerella leaf spot (GLS), caused by the fungus Colletotrichum fructicola, is one of the most devastating apple diseases. Our previous study reported that the GLS resistance locus was defined on the chromosome 15 region. Here, we further found a single-nucleotide polymorphism (SNP) site (SNP7309212) in the GLS resistance that was able to distinguish resistant cultivars (lines) from susceptible ones. On the basis of the SNP site, we cloned a TNL gene from the GLS resistant locus and named it MdTNL1 (NCBI Accession Number: ON402514). This gene contains a toll/interleukin-1 receptor transmembrane domain (TIR), nucleotide-binding sites (NBS), and leucine-rich repeat (LRR) domain. Subcellular location indicated that MdTNL1 was expressed in the nucleus and cell membrane. Ectopic overexpression of MdTNL1 in Nicotiana benthamiana caused cell death. We further demonstrated allelic polymorphisms in MdTNL1. It is noteworthy that NBS and LRR domains of the MdTNL1 protein serve as the repository for generating allelic diversity. Quantitative real-time PCR (qRT-PCR) assay revealed that MdTNL1 was highly expressed in resistant apple cultivar ‘Fuji’ after inoculation with C. fructicola, whereas susceptible cultivar ‘Golden Delicious’ exhibited low expression after inoculation. Over-expression of MdTNL1-1 in susceptible apple fruits and leaves improved disease resistance, while in ‘Orin’ calli, silencing the MdTNL1-1 gene conversely decreased GLS resistance. In conclusion, we identified a GLS associated with SNP7309212 and demonstrated that a TIR-NBS-LRR gene MdTNL1-1 positively regulates GLS resistance in apple.
Analysis of Silver Nanoparticles for the Treatment and Prevention of Nucleopolyhedrovirus Affecting Bombyx mori
Authors: Deng Boyuan , Dong Zhanqi , Wu Qin , Guo Bingyu , Fang Wenxuan , Hu Congwu , Long Jiangqiong , Chen Peng , Lu Cheng , Pan Minhui
Published: June 2022

Bombyx mori nucleopolyhedrovirus (BmNPV) causes major economic losses in sericulture. A number of agents have been employed to treat viral diseases. Silver nanoparticles (AgNPs) have wide applications in biomedical fields due to their unique properties. The anti-BmNPV effect of AgNPs has been evaluated, however, there are insufficient studies concerning its toxicity to other organisms and the environment. We chemically synthesized biocompatible BSA-AgNPs with a diameter range of 2–4 nm and characterized their physical properties. The toxicity of AgNPs towards cells and larvae with different concentrations was examined; the results indicated a biofriendly effect on cells and larvae within specific concentration ranges. The SEM observation of the surface of BmNPV after treatment with AgNPs suggested that AgNPs could destroy the polyhedral structure, and the same result was obtained by Coomassie blue staining. Further assays confirmed the weakened virulence of AgNPs-treated BmNPV toward cells and larvae. AgNPs also could effectively inhibit the replication of BmNPV in infected cells and larvae. In summary, our research provides valuable data for the further development of AgNPs as an antiviral drug for sericulture.
A Novel Homozygous Variant in the COMP Gene Causing a Multiple Epiphyseal Dysplasia 1 with Autosomal Recessive Inheritance
Authors: Markova Tatiana , Murtazina Aysylu , Kenis Vladimir , Melchenko Evgenii , Ampleeva Maria , Nagornova Tatiana , Alieva Aynur , Dadali Elena , Kutsev Sergey
Published: June 2022

Multiple epiphyseal dysplasia type 1 is one of the most common autosomal dominant types of the genetically heterogeneous group of skeletal dysplasias characterized by impaired ossification of the epiphyses of long bones. To date, it is known that the disease is caused by heterozygous variants in the COMP gene and is characterized by a significant variability in the clinical manifestations. We report the first case of a patient with MED 1 caused by novel homozygous single nucleotide variant c.2170dupG (p.Val724Glyfs*20) in the COMP gene identified by whole-exome sequencing. The following segregation analysis in the family found a detected variant in heterozygous state in healthy consanguineous parents of the proband. Clinical and radiological examination revealed the atypical signs of epiphyseal dysplasia including limited range of extension and supination of both forearms, severe bilateral ulnar clubhand, plano-valgus deformity of the feet and generalized muscle weakness with gait disturbances. Among the clinical features, myopathic signs were the most prominent. The radiological and neurophysiological data can be helpful in the differential diagnostics with the congenital myopathies. The novel homozygous variant in the COMP gene that caused multiple epiphyseal dysplasia 1 with autosomal recessive inheritance can contribute to the more detailed description of genotype–phenotype correlations, which will allow research to understand better the role of the C-terminal domain of COMP.
Flying over Eurasia: Geographic Variation of Photoperiodic Control of Nymphal Development and Adult Diapause Induction in Native and Invasive Populations of the Brown Marmorated Stink Bug, Halyomorpha halys (Hemiptera: Heteroptera: Pentatomidae)
Authors: Musolin Dmitry L. , Dolgovskaya Margarita Yu. , Zakharchenko Vilena Ye. , Karpun Natalia N. , Haye Tim , Saulich Aida Kh. , Reznik Sergey Ya.
Published: June 2022

Facultative winter adult diapause in Halyomorpha halys is regulated by a long-day photoperiodic response. Day length also influences nymphal development, which slows down at the critical (near-threshold) day lengths. We compared the photoperiodic responses of one native (Andong, South Korea) and three invasive (Torino, Italy; Basel, Switzerland; and Sochi, Russia) populations in a laboratory common-garden experiment. Nymphs developed and emerging adults were reared at 24 °C in a range of photoperiods with day lengths of 14.0, 14.5, 15.0, 15.5, and 16.0 h. The critical day lengths of the photoperiodic responses of both sexes fell between 14.5 and 15.0 h in the native Korean population and between 15.0 and 15.5 h in three invasive European populations. The differences between the three invasive populations were not significant, despite their distant origins. Moreover, the difference between the Korean and European populations was much smaller than was expected. The microevolution was possibly ‘too slow to keep up’ with the rapid spread of the invader across Eurasia. It is expected that soon the critical day length of the invasive H. halys populations will gradually change to adapt better to local conditions. At present, the critical day length for diapause induction of 15 h 15 min can be used to model the phenology, further spread, and response to climate change for all European populations of the pest.
Complementary Role of Combined Indirect and Direct Cardiac Sympathetic (Hyper)Activity Assessment in Patients with Heart Failure by Spectral Analysis of Heart Rate Variability and Nuclear Imaging: Possible Application in the Evaluation of Exercise Training Effects
Authors: Iellamo Ferdinando , Perrone Marco Alfonso , Cimini Andrea , Caminiti Giuseppe , Chiaravalloti Agostino , Parisi Attilio , Schillaci Orazio
Published: June 2022

In chronic heart failure (CHF), abnormalities in cardiac autonomic control, characterized by sympathetic overactivity, contribute to the progression of the disease and are associated with an unfavorable prognosis. Assessing cardiac autonomic status is clinically important in the management of patients with CHF. To this aim, heart rate variability (HRV) analysis has been extensively used as a non-invasive tool for assessing cardiac autonomic regulation, and has been shown to predict the clinical outcome in patients with CHF. Adrenergic nerve activity has also been estimated using iodine-123 (I-123) metaiodobenzylguanidine (MIBG), a noradrenaline analogue. MIBG is an analogue of norepinephrine sharing the same cellular mechanism of uptake, storage, and release in presynaptic sympathetic neurons. As an innervation tracer, 123I-MIBG allows for the evaluation of cardiac sympathetic neuronal function. Cardiac MIBG imaging has also been reported to predict a poor clinical outcome in CHF. MIBG provides direct information on the function of the presynaptic sympathetic nerve endings, whereas HRV, which depends on postsynaptic signal transduction, reflects the end-organ response of the sinus node. The aim of this brief review is to provide the reader with some basic concepts regarding the spectral analysis of HRV and MIBG, highlighting what is known about their respective roles in detecting cardiac sympathetic hyperactivity in CHF and, in perspective, their possible combined use in assessing non-pharmacological treatments in patients with CHF and reduced ejection fraction, with a particular focus on the effects of exercise training.
Observational Study of the Association between Hyponatremia and Rhabdomyolysis in Patients Presenting to Hospital
Authors: Lim Andy K. H. , Bhonsle Ajinkya , Zhang Karen , Hong Joy , Huang Kuo L. C. , Nim Joseph
Published: June 2022

Hyponatremia may be a risk factor for rhabdomyolysis, but the association is not well defined and may be confounded by other variables. The aims of this study were to determine the prevalence and strength of the association between hyponatremia and rhabdomyolysis and to profile patients with hyponatremia. In a cross-sectional study of 870 adults admitted to hospital with rhabdomyolysis and a median peak creatine kinase of 4064 U/L (interquartile range, 1921–12,002 U/L), glucose-corrected serum sodium levels at presentation showed a U-shape relationship to log peak creatine kinase. The prevalence of mild (130–134 mmol/L), moderate (125–129 mmol/L), and severe (<125 mmol/L) hyponatremia was 9.4%, 2.5%, and 2.1%, respectively. We excluded patients with hypernatremia and used multivariable linear regression for analysis (n = 809). Using normal Na+ (135–145 mmol/L) as the reference category, we estimated that a drop in Na+ moving from one Na+ category to the next was associated with a 25% higher creatine kinase after adjusting for age, alcohol, illicit drugs, diabetes, and psychotic disorders. Multifactorial causes of rhabdomyolysis were more common than single causes. The prevalence of psychotic and alcohol use disorders was higher in the study population compared to the general population, corresponding with greater exposure to psychotropic medications and illicit drugs associated with hyponatremia and rhabdomyolysis. In conclusion, we found an association between hyponatremia and the severity of rhabdomyolysis, even after allowing for confounders.