bluuebunny/crossref_metadata_2025 huggingface dataset:
Anxiety in the Classroom: Only Girls’ Anxiety Is Related to Same-Sex Peers’ Anxiety
Authors: Charbonneau Sandrine , Journault Audrey-Ann , Cernik Rebecca , Longpré Charlotte , Wan Nathalie , Giguère Charles-Édouard , Lupien Sonia
Published: December 2022

Many teens report experiencing anxiety in school, which can negatively impact their well-being. Considering that adolescents tend to adopt the same behaviors as their classmates with whom they spend, on average, 923 h every year, the current exploratory study (1) assessed whether an association exists between a student’s state anxiety score and his/her classmates’ average trait anxiety scores and (2) examined whether this association differed between boys and girls, as well as between elementary school and high school students. During two consecutive school years, 1044 Canadian students (59% girls) from six elementary schools (aged 10–12) and seven high schools (aged 15–17) completed the State-Trait Anxiety Inventory for Children. Multilevel analyses revealed a same-sex peer effect of classmates’ anxiety in girls only (β = 0.40, p < 0.001). This effect was similar for elementary and high school girls (β = 0.07, p = 0.27). Interestingly, no association was found for boys, same-sex peers (β = 0.11, p = 0.25), or opposite-sex peers (β = −0.01, p = 1.00). Our results suggest that factors related to sex may reinforce anxiety in school settings. Future studies should confirm these results and explore the mechanisms involved in this sex-specific difference.
Assessment of 3D-Printed Tooth Containing Simulated Deep Caries Lesions for Practicing Selective Caries Removal: A Pilot Study
Authors: Panpisut Piyaphong , Doungkom Patchayaporn , Padunglappisit Chawal , Romalee Worachate , Suksudaj Nattira
Published: December 2022

A standard model for practicing caries removal skills is needed to support learners in managing deep carious lesions. The aim of the current study was to prepare 3D-printed teeth with added simulated carious layers and a pulpal structure. A first permanent mandibular containing occlusal (Class I) or proximal (Class II) cavities was printed. The teeth were then filled with wax and resin-modified glass ionomer cements mixed with a color modifier to simulate pulp and deep caries, respectively. Undergraduate dental students (n = 61) were asked to remove the caries using the selective caries removal (SCR) technique on the teeth. The students then completed a self-administered questionnaire to rate their caries removal experiences. One instructor then assessed the prepared teeth. Overall, the students provided positive feedback on the use of 3D-printed teeth; 72.1% agreed that the printed teeth provided a realistic model for practicing the SCR technique, 75.4% indicated that the new teeth were the appropriate choice for practicing the SCR technique, and 86.9% agreed that 3D-printed teeth should be used before treating real patients. More than half of the students had satisfactory outcomes in terms of the depth and caries removal aspects of the cavity preparation. These findings suggest that the developed 3D-printed teeth can potentially be adopted to practice caries removals in preclinical dental education.
Spatial and Temporal Pattern of Net Ecosystem Productivity in China and Its Response to Climate Change in the Past 40 Years
Authors: Zhang Cuili , Huang Ni , Wang Li , Song Wanjuan , Zhang Yuelin , Niu Zheng
Published: December 2022

Net ecosystem productivity (NEP), which is considered an important indicator to measure the carbon source/sink size of ecosystems on a regional scale, has been widely studied in recent years. Since China's terrestrial NEP plays an important role in the global carbon cycle, it is of great significance to systematically examine its spatiotemporal pattern and driving factors. Based on China's terrestrial NEP products estimated by a data-driven model from 1981 to 2018, the spatial and temporal pattern of China's terrestrial NEP was analyzed, as well as its response to climate change. The results demonstrate that the NEP in China has shown a pattern of high value in the west and low value in the east over the past 40 years. NEP in China from 1981 to 2018 showed a significantly increasing trend, and the NEP change trend was quite different in two sub-periods (i.e., 1981–1999 and 2000–2018). The temporal and spatial changes of China's terrestrial NEP in the past 40 years were affected by both temperature and precipitation. However, the area affected by precipitation was larger. Our results provide a valuable reference for the carbon sequestration capacity of China's terrestrial ecosystem.
Personality, Anxiety, and Stress in Patients with Small Intestine Bacterial Overgrowth Syndrome. The Polish Preliminary Study
Authors: Kossewska Joanna , Bierlit Karolina , Trajkovski Vladimir
Published: December 2022

Objective: Small intestinal bacterial overgrowth (SIBO) syndrome is associated with depression and anxiety. This study aimed to examine for the first time the correlation between personality traits, situational anxiety, and stress in Polish patients with SIBO. Methodology: This study included 26 patients with SIBO aged 20–35 years and 24 non-SIBO patients aged 20–35 years. The following instruments were used: NEO-FFI Personality Inventory, KPS Sense of Stress Questionnaire, and the anxiety-state subscale from the State-Trait Anxiety Inventory (STAI). Results: Compared to the non-SIBO subgroup, SIBO patients expressed specific patterns of personality traits: higher neuroticism, lower extroversion, and a higher state of anxiety and stress. Unlike the non-SIBO subgroup, stress (total emotional tension, external, and intrapsychic) correlated negatively only with extroversion. Conclusions: Personality is the primary regulator of experience and behavior. The specificity captured in the research is a premise for an in-depth study considering various psychological variables to determine cause-effect relationships.
Effects of Physical Activity and Circadian Rhythm Differences on the Mental Health of College Students in Schools Closed by COVID-19
Authors: Li Huimin , Zhang Yong
Published: December 2022

Purpose: Since the prolonged sequestration management that was implemented in order to achieve lower infection and mortality rates, there has been a surge in depression worldwide. The correlation between the physical activity level and the detection rate of a depressed mood in college students should be of wide concern. A large number of studies have focused on the association between physical activity levels and a negative mood, but circadian rhythm differences seem to be strongly associated with both physical activity levels and mental illness. Therefore, this paper will examine the correlation between physical activity levels, circadian rhythm differences, and mental health levels in college students. METHODS: Data were collected through a web-based cross-sectional survey. In June and December 2022, questionnaires were administered to college students from three universities in Anhui, China. In addition to socio-demographic information, measures included the International Physical Activity Questionnaire-Short Form (IPAQ-SF), Morning and Evening Questionnaire-5 Items (MEQ-5), and Symptom Check List90 (SCL-90) scales. Correlation analysis was used to understand the relationship between physical activity and circadian rhythm differences in the three aspects of college student’s mental health. RESULTS: The analysis of the data led to the conclusion that 28.4% of the 1241 college students in this survey had psychological disorders. The physical activity level of male students was higher than that of female students, but the risk of having depressive tendencies was higher in female students than in male students. There was a significant negative correlation between the physical activity level and scl-90 scores (p < 0.01), which indicates that higher physical activity levels are associated with higher mental health. Circadian rhythm differences and scl-90 scores were significantly positively correlated among college students (p < 0.01), and night-type people had a higher risk of mental illness than intermediate-type and early-morning-type people. CONCLUSIONS: During the period of closed administration due to COVID-19, school college students experienced large and high levels of negative emotional phenomena due to reduced physical activity and public health emergencies. This study showed significant correlations between both physical activity levels and circadian rhythmicity differences and the degree of mental health of college students.
A Method to Measure and Model Acoustic Emissions of Multicopters
Authors: Wunderli Jean Marc , Meister Jonas , Boolakee Oliver , Heutschi Kurt
Published: December 2022

There is a growing interest for commercial applications of Unmanned Aerial Vehicles, but important foundations for an assessment, among others about noise, are missing. This contribution specifically focuses on a method to measure and model the sound radiation of multicopters. The emission prediction is hereby based on measurements using a multiple regression approach. An important finding is that the directivity pattern is widely independent of the rotational speed of the rotors and of the flight procedure. Consequently, the directivity pattern can be determined for a stationary hover flight, which considerably simplifies the measurement procedure. In addition to a rotational speed-dependent sound emission model for hover flight, a multicopter-specific correction term is required to account for forward flight. The validity of this approach is demonstrated based on the field measurements of three different multicopter models.
Human Health Impacts of Residential Radon Exposure: Updated Systematic Review and Meta-Analysis of Case–Control Studies
Authors: Ngoc Le Thi Nhu , Park Duckshin , Lee Young-Chul
Published: December 2022

This study investigated the impact of residential radon exposure on human cancers (i.e., lung cancer and childhood leukemia) through a systematic review and meta-analysis of case–control studies. A total of 9724 articles obtained from electronic databases were assessed; however, only 55 case–control studies were eligible after manually screening and eliminating unnecessary studies. The causal associations were addressed by determining the meta-analysis’s estimated size effects (i.e., ORs/RRs) of the meta-analysis. Residential radon was revealed to significantly increase the incidence of lung cancer and childhood leukemia with pooled ORs of 1.38 [1.19; 1.60] (I2 = 90%; p < 0.00001) and 1.43 [1.19; 1.72] (I2 = 0% and p = 0.51), respectively. In addition, subgroup analyses were performed to reduce the heterogeneity of the initial meta-analyses. The results provided strong evidence that inhaling radon in the indoor environments is closely associated with the development of lung cancer and childhood leukemia in patients living in Europe and areas with high radon levels (≥100 Bq/m3).
Expectations of Patients Recovering from SARS-CoV-2 towards New Forms of Pulmonary Rehabilitation
Authors: Migała Mariusz , Płonka-Syroka Bożena , Rasławska Krystyna , Skolik Beata , Spielvogel Izabela , Piechota Katarzyna , Hołodnik Daria , Hagner-Derengowska Magdalena
Published: December 2022

The purpose of this study was to explore the experiences of patients attending an innovative technology-enhanced pulmonary rehabilitation program of National Health Found Program in Poland. The study included two groups of patients participating in post-COVID-19 stationary rehabilitation. Patients from group I (127 individuals) contracted COVID-19 in 2020, while patients from group II fell ill in 2021 (68 individuals). The study used a self-administered questionnaire. This study was designed as an acceptability study. In the experience related to COVID-19 in both groups of the respondents, the possibility of undertaking inpatient rehabilitation in a hospital ward played an important and positive role. Patients who experienced COVID-19 symptomatically expected that rehabilitation would eliminate the related dysfunctions, such as reduced respiratory efficiency of the lungs, disorders of the nervous system, and cognitive disorders (the so-called brain fog). All respondents who experienced symptomatic COVID-19 positively assessed the rehabilitation program offered. Among the highest-rated rehabilitation, elements were identified: exercise on a cycle ergometer implemented with video stimulation, group fitness exercises, and breathing exercises. Other innovative forms of rehabilitation were positively evaluated by 10% to 25% of patients.
The Happy Home: Ageing, Migration, and Housing in Relation to Older Migrants’ Subjective Wellbeing
Authors: Phlix Micheline , Petermans Ann , Smetcoren An-Sofie , Vanrie Jan
Published: December 2022

(1) Background: With an increasingly diversifying ageing population, it is important to understand what ‘ageing well’ means to older adults with a migration background. Given older adults’ preference to age in place and declining mobility, housing is a significant place in later life. Therefore, this paper explores the influence of housing, migration, and age on older migrants’ subjective wellbeing, with attention to immaterial aspects such as a sense of home as well. (2) Methods: In-depth interviews with older migrants from various ethnicities (N = 22) were conducted. The data collection and analysis were led by an inductive and deductive approach through thematic analysis. (3) Results: The results point to the dynamic nature of age(ing) and the role of migration background in the subjective wellbeing of older migrants. The need for preserving one’s housing situation and environmental mastery in later life is highlighted. Furthermore, the relation and mutual influence of subjective wellbeing and sense of home is uncovered. (4) Conclusions: This study highlights the intersection of age, migration, and housing to the subjective wellbeing and sense of home of older migrants. In addition, influences on older migrants’ subjective wellbeing concern both a material (i.e., housing) and immaterial (i.e., sense of home, age, migration) base.
Development of Machine Learning Model for Prediction of Demolition Waste Generation Rate of Buildings in Redevelopment Areas
Authors: Cha Gi-Wook , Choi Se-Hyu , Hong Won-Hwa , Park Choon-Wook
Published: December 2022

Owing to a rapid increase in waste, waste management has become essential, for which waste generation (WG) information has been effectively utilized. Various studies have recently focused on the development of reliable predictive models by applying artificial intelligence to the construction and prediction of WG information. In this study, research was conducted on the development of machine learning (ML) models for predicting the demolition waste generation rate (DWGR) of buildings in redevelopment areas in South Korea. Various ML algorithms (i.e., artificial neural network (ANN), K-nearest neighbors (KNN), linear regression (LR), random forest (RF), and support vector machine (SVM)) were applied to the development of an optimal predictive model, and the main hyper parameters (HPs) for each algorithm were optimized. The results suggest that ANN-ReLu (coefficient of determination (R2) 0.900, the ratio of percent deviation (RPD) 3.16), SVM-polynomial (R2 0.889, RPD 3.00), and ANN-logistic (R2 0.883, RPD 2.92) are the best ML models for predicting the DWGR. They showed average errors of 7.3%, 7.4%, and 7.5%, respectively, compared to the average observed values, confirming the accurate predictive performance, and in the uncertainty analysis, the d-factor of the models appeared less than 1, showing that the presented models are reliable. Through a comparison with ML algorithms and HPs applied in previous related studies, the results herein also showed that the selection of various ML algorithms and HPs is important in developing optimal ML models for WG management.
Assessment of Nutritional Status and Risk of Malnutrition Using Adapted Standard Tools in Patients with Mental Illness and in Need of Intensive Psychiatric Treatment
Authors: Risch Ladina , Hotzy Florian , Vetter Stefan , Hiller Sascha , Wallimann Kathrin , Seifritz Erich , Mötteli Sonja
Published: December 2022

People with severe mental illness (SMI) are often in poor physical health, resulting in higher mortality and reduced life expectancy compared to the general population. Although eating habits are one of the main predictors of physical health, few studies assess the nutritional status and eating behavior of people with SMI. The aim of this study was to examine the nutritional status and risk of malnutrition in people with SMI who were in need of intensive psychiatric treatment. The cross-sectional study included 65 inpatients and 67 outpatients with psychotic or depressive disorders from the Psychiatric Hospital of the University of Zurich. Patients’ assessments at admission included anthropometric measurements, such as weight and height, and interview data including severity of symptoms and functioning (SCL-K-9, PHQ-D, CGI, m-GAF), personal and medical data, nutrition risk screening tools (adapted NRS, MNA-SF), and laboratory values. The results showed that 32% of the inpatients and 34% of the outpatients were at risk of malnutrition, which was associated with higher levels of psychiatric symptoms and lower levels of functioning. Regardless, the body mass index (BMI) was overweight in both groups (mean BMIinpatients = 25.3, mean BMIoutpatients = 27.9). These results indicate that a substantial proportion of psychiatric patients seems to be at risk of malnutrition, despite most being overweight, and hence they might benefit from nutritional support during their psychiatric treatment. Moreover, nutritional risk screening tools specifically developed for the mental healthcare setting are needed.
Sun-Safe Zones: Investigating Integrated Shading Strategies for Children’s Play Areas in Urban Parks
Authors: Cherian Nikhil C. , Subasinghe Chamila
Published: December 2022

Although Open Space Ratio is a critical control in the Development Approval process, there are no ultraviolet radiation (UVR) protection guidelines for urban parks. This study explores key strategies for shade provision in children’s play areas in urban parks, aiming to promote sun-safe play environments against alarming skin cancer trends. The literature review identified primary issues affecting UVR exposure in public venues, and the research comprises a shade audit of Beaton Park in Dalkeith. The methods involved using virtual park modeling and Shadow Analysis simulations to generate the daily average number of hours in shade for each month. Our recommendations based on this analysis are (a) a minimum canopy cover representing 50% of the entire ground cover; (b) a minimum diameter for a shade (umbrella) of about 2.5 times the diameter of the table; and (c) an ideal umbrella height of 90 cm from the table surface. This research proposes a potential nexus between landscape design and a UVR protection framework for child-friendly Sun-safe Zones (SsZ).
Patient’s Perspective of Telemedicine in Poland—A Two-Year Pandemic Picture
Authors: Sołomacha Sebastian , Sowa Paweł , Kiszkiel Łukasz , Laskowski Piotr Paweł , Alimowski Maciej , Szczerbiński Łukasz , Szpak Andrzej , Moniuszko-Malinowska Anna , Kamiński Karol
Published: December 2022

The outbreak of the COVID-19 pandemic caused the healthcare system to drastically reduce in-person visits and suddenly switch to telemedicine services to provide clinical care to patients. The implementation of teleconsultation in medical facilities was a novelty for most Polish patients. In Poland, the main telehealth services were provided in the form of telephone consultations. The aim of this study is to determine patients’ perceptions of telemedicine in the context of their experiences with the healthcare system during the COVID-19 pandemic. In this study, we presented how the evaluation of telemedicine services from the perspective of patients in Poland changed in the context of the ongoing pandemic. We conducted two surveys (year by year) on a representative quota sample of the Polish population (N = 623). This ensured that our observations took into account the evolution of views on telemedicine over time. We confirmed the well-known relationship that innovations introduced in the healthcare sector require a longer period of adaptation. We also identified significant concerns that limit the positive perception of telemedicine and compared them with experiences described in other countries.
SHAFE Mapping on Social Innovation Ecosystems
Authors: Dantas Carina , Louceiro Juliana , Vieira Joana , van Staalduinen Willeke , Zanutto Oscar , Mackiewicz Karolina
Published: December 2022

There have been several initiatives aiming to promote innovation and support stakeholders to increase investments in relevant societal areas connected to Smart Healthy Age-Friendly Environments—SHAFE. However, their impact usually runs shorter than desirable in the mid- and long-term due to the difficulty to identify, map, and connect stakeholders in the different European and world countries that are willing to work for the practical implementation of social innovation around SHAFE. This mapping and connection can contribute to increase awareness of innovation actors on social innovation concepts and, if well disseminated, may also leverage the creation of alliances and synergies between different stakeholders within ecosystems and between ecosystems. Understanding what relevant practices exist, how they are funded, and how they involve citizens and organisations is also key to ensure that business actors have access to social innovation and entrepreneurial knowledge, which is key for future sustainable societal change. The present study developed and implemented a survey replied by 61 organisations from 28 different countries. The results showed relevant inputs regarding different cultural and societal perceptions, including diverse end-user organisations, and will, thus, facilitate multistakeholder engagement, public awareness, and the overall upscaling of social innovation on SHAFE.
Understanding the Link between Household Food Insecurity and Self-Rated Oral Health in Ghana
Authors: Amoak Daniel , Braimah Joseph Asumah , Agyemang-Duah Williams , Kye Nancy Osei , Anfaara Florence Wullo , Sano Yujiro , Antabe Roger
Published: December 2022

There is increasing scholarly attention on the role of food insecurity on the health of older adults in sub-Saharan Africa, including Ghana. Yet, we know very little about the association between food insecurity and self-rated oral health. To address this void in the literature, this study uses a representative survey of adults aged 60 or older from three regions in Ghana to examine whether respondents who experienced household food insecurity rated their oral health as poor compared to their counterparts who did not. We found that 34% of respondents rated their oral health as poor, while 7%, 21%, and 36% experienced mild, moderate, and severe food insecurity, respectively. Moreover, the results from the logistic regression analysis showed that older adults who experienced mild (OR = 1.66, p < 0.05), moderate (OR = 2.06, p < 0.01), and severe (OR = 2.71, p < 0.01) food insecurity were more likely to self-rate their oral health as poor, compared to those who did not experience any type of food insecurity. Based on these findings, we discuss several implications for policymakers and directions for future research.
Lactate Rewrites the Metabolic Reprogramming of Uveal Melanoma Cells and Induces Quiescence Phenotype
Authors: Longhitano Lucia , Giallongo Sebastiano , Orlando Laura , Broggi Giuseppe , Longo Antonio , Russo Andrea , Caltabiano Rosario , Giallongo Cesarina , Barbagallo Ignazio , Di Rosa Michelino , Giuffrida Rosario , Parenti Rosalba , Li Volti Giovanni , Vicario Nunzio , Tibullo Daniele
Published: December 2022

Uveal melanoma (UM), the most common primary intraocular cancer in adults, is among the tumors with poorer prognosis. Recently, the role of the oncometabolite lactate has become attractive due to its role as hydroxycarboxylic acid receptor 1 (HCAR1) activator, as an epigenetic modulator inducing lysine residues lactylation and, of course, as a glycolysis end-product, bridging the gap between glycolysis and oxidative phosphorylation. The aim of the present study was to dissect in UM cell line (92.1) the role of lactate as either a metabolite or a signaling molecule, using the known modulators of HCAR1 and of lactate transporters. Our results show that lactate (20 mM) resulted in a significant decrease in cell proliferation and migration, acting and switching cell metabolism toward oxidative phosphorylation. These results were coupled with increased euchromatin content and quiescence in UM cells. We further showed, in a clinical setting, that an increase in lactate transporters MCT4 and HCAR1 is associated with a spindle-shape histological type in UM. In conclusion, our results suggest that lactate metabolism may serve as a prognostic marker of UM progression and may be exploited as a potential therapeutic target.
Cold Stress Response Mechanisms in Anther Development
Authors: Huang Borong , Fan Yubo , Cui Lijiao , Li Cheng , Guo Changkui
Published: December 2022

Unlike animals that can escape threats, plants must endure and adapt to biotic and abiotic stresses in their surroundings. One such condition, cold stress, impairs the normal growth and development of plants, in which most phases of reproductive development are particularly susceptible to external low temperature. Exposed to uncomfortably low temperature at the reproductive stage, meiosis, tapetal programmed cell death (PCD), pollen viability, and fertilization are disrupted, resulting in plant sterility. Of them, cold-induced tapetal dysfunction is the main cause of pollen sterility by blocking nutrition supplements for microspore development and altering their timely PCD. Further evidence has indicated that the homeostatic imbalances of hormones, including abscisic acid (ABA) and gibberellic acid (GA), and sugars have occurred in the cold-treated anthers. Among them, cold stress gives rise to the accumulation of ABA and the decrease of active GA in anthers to affect tapetal development and represses the transport of sugar to microspores. Therefore, plants have evolved lots of mechanisms to alleviate the damage of external cold stress to reproductive development by mainly regulating phytohormone levels and sugar metabolism. Herein, we discuss the physiological and metabolic effects of low temperature on male reproductive development and the underlying mechanisms from the perspective of molecular biology. A deep understanding of cold stress response mechanisms in anther development will provide noteworthy references for cold-tolerant crop breeding and crop production under cold stress.
Colourimetric Plate Assays Based on Functionalized Gelatine Hydrogel Useful for Various Screening Purposes in Enzymology
Authors: Labus Karolina , Maniak Halina
Published: December 2022

Hydrogels are intensively investigated biomaterials due to their useful physicochemical and biological properties in bioengineering. In particular, naturally occurring hydrogels are being deployed as carriers for bio-compounds. We used two approaches to develop a plate colourimetric test by immobilising (1) ABTS or (2) laccase from Trametes versicolor in the gelatine-based hydrogel. The first system (1) was applied to detect laccase in aqueous samples. We investigated the detection level of the enzyme between 0.05 and 100 µg/mL and pH ranging between 3 and 9; the stability of ABTS in the solution and the immobilised form, as well as the retention functional property of the hydrogel in 4 °C for 30 days. The test can detect laccase within 20 min in the concentration range of 2.5–100 µg/mL; is effective at pH 3–6; preserves high stability and functionality under storage and can be also successfully applied for testing samples from a microbial culture. The second system with the immobilised laccase (2) was tested in terms of substrate specificity (ABTS, syringaldazine, guaiacol) and inhibitor (NaN3) screening. ABTS appeared the most proper substrate for laccase with detection sensitivity CABTS > 0.5 mg/mL. The NaN3 tested in the range of 0.5–100 µg/mL showed a distinct inhibition effect in 20 min for 0.5 µg/mL and total inhibition for ≥75 µg/mL.
Expanding the Etiology of Oculo–Auriculo–Vertebral Spectrum: A Novel Interstitial Microdeletion at 1p36
Authors: García-Castro Mónica , Martinez-Merino Teresa , Puente Nuria , Riancho José A.
Published: December 2022

The etiology of oculo–auriculo–vertebral spectrum (OAVS) is not well established. About half of patients show a positive family history. The etiology of familiar cases is unclear but appears genetically heterogeneous. This motivated us to report a case of OAVS with microtia, ptosis, facial microsomy, and fusion of vertebral bodies associated with a novel genetic etiology, including a deletion at 1p36.12-13. This case report expands on the genetic etiology of OAVS. Furthermore, it also expands the clinical manifestations of patients with interstitial deletions of the de 1p36.12-13 region.
Emerging Role of MicroRNA-30c in Neurological Disorders
Authors: Kumar Manish , Li Guohong
Published: December 2022

MicroRNAs (miRNAs or miRs) are a class of small non-coding RNAs that negatively regulate the expression of target genes by interacting with 3′ untranslated regions of target mRNAs to induce mRNA degradation and translational repression. The miR-30 family members are involved in the development of many tissues and organs and participate in the pathogenesis of human diseases. As a key member of the miR-30 family, miR-30c has been implicated in neurological disorders such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and stroke. Mechanistically, miR-30c may act as a multi-functional regulator of different pathogenic processes such as autophagy, apoptosis, endoplasmic reticulum stress, inflammation, oxidative stress, thrombosis, and neurovascular function, thereby contributing to different disease states. Here, we review and discuss the biogenesis, gene regulation, and the role and mechanisms of action of miR-30c in several neurological disorders and therapeutic potential in clinics.
Imbalance in Bone Morphogenic Proteins 2 and 7 Is Associated with Renal and Cardiovascular Damage in Chronic Kidney Disease
Authors: Manzano-Lista Francisco Javier , Sanz-Gómez Marta , González-Moreno Daniel , Vega-Martín Elena , Gil-Ortega Marta , Schulz Angela , Rubio Miguel Ángel , Ruiz-Hurtado Gema , Ruilope Luis Miguel , Aránguez Isabel , Kreutz Reinhold , Fernández-Alfonso María S.
Published: December 2022

Arterial stiffness is a major vascular complication of chronic kidney disease (CKD). The development of renal damage, hypertension, and increased pulse wave velocity (PWV) in CKD might be associated with an imbalance in bone morphogenetic proteins (BMP)-2 and BMP-7. Plasma BMP-2 and BMP-7 were determined by ELISA in CKD patients (stages I–III; n = 95) and Munich Wistar Frömter (MWF) rats. Age-matched Wistar rats were used as a control. The expression of BMP-2, BMP-7, and profibrotic and calcification factors was determined in kidney and perivascular adipose tissues (PVAT). BMP-2 was higher in stage III CKD patients compared to control subjects. BMP-7 was lower at any CKD stage compared to controls, with a significant further reduction in stage III patients. A similar imbalance was observed in MWF rats together with the increase in systolic (SBP) and diastolic blood pressure (DBP), or pulse wave velocity (PWV). MWF exhibited elevated urinary albumin excretion (UAE) and renal expression of BMP-2 or kidney damage markers, Kim-1 and Ngal, whereas renal BMP-7 was significantly lower than in Wistar rats. SBP, DBP, PWV, UAE, and plasma creatinine positively correlated with the plasma BMP-2/BMP-7 ratio. Periaortic and mesenteric PVAT from MWF rats showed an increased expression of BMP-2 and profibrotic and calcification markers compared to Wistar rats, together with a reduced BMP-7 expression. BMP-2 and BMP-7 imbalance in plasma, kidney, and PVATs is associated with vascular damage, suggesting a profibrotic/pro-calcifying propensity associated with progressive CKD. Thus, their combined analysis stratified by CKD stages might be of clinical interest to provide information about the degree of renal and vascular damage in CKD.
Insights and Strategies of Melanoma Immunotherapy: Predictive Biomarkers of Response and Resistance and Strategies to Improve Response Rates
Authors: Seyhan Attila A. , Carini Claudio
Published: December 2022

Despite the recent successes and durable responses with immune checkpoint inhibitors (ICI), many cancer patients, including those with melanoma, do not derive long-term benefits from ICI therapies. The lack of predictive biomarkers to stratify patients to targeted treatments has been the driver of primary treatment failure and represents an unmet medical need in melanoma and other cancers. Understanding genomic correlations with response and resistance to ICI will enhance cancer patients’ benefits. Building on insights into interplay with the complex tumor microenvironment (TME), the ultimate goal should be assessing how the tumor ’instructs’ the local immune system to create its privileged niche with a focus on genomic reprogramming within the TME. It is hypothesized that this genomic reprogramming determines the response to ICI. Furthermore, emerging genomic signatures of ICI response, including those related to neoantigens, antigen presentation, DNA repair, and oncogenic pathways, are gaining momentum. In addition, emerging data suggest a role for checkpoint regulators, T cell functionality, chromatin modifiers, and copy-number alterations in mediating the selective response to ICI. As such, efforts to contextualize genomic correlations with response into a more insightful understanding of tumor immune biology will help the development of novel biomarkers and therapeutic strategies to overcome ICI resistance.
Mediterranean Diet and Parkinson’s Disease
Authors: Bisaglia Marco
Published: December 2022

Parkinson’s disease (PD) is an age-related neurodegenerative disorder, diagnosed on the basis of typical motor disturbances, but also characterized by the presence of non-motor symptoms, such as rapid eye movement (REM)-sleep behavior disorders, olfactory impairment, and constipation, which are often prodromal to the onset of the disease. PD is often associated with the presence of oxidative brain injury and chronic neuroinflammation, with infiltration and accumulation of peripheral immune cells that have been found in affected brain regions of PD patients. Recently, the role of the gut-brain axis in the pathogenesis of PD is getting more and more attention, and several pieces of evidence indicate alterations in the gut microbiota of PD-affected patients. Diet exerts a central role in defining the microbiota composition and different dietetic patterns can result in a higher or lower abundance of specific bacteria that, in turn, can affect gut permeability and express anti- or pro-inflammatory metabolites. In the present review, the effects of the Mediterranean diet in modulating both PD onset and its progression will be considered with a special focus on the antioxidant and anti-inflammatory properties of this dietetic regimen as well as on its effects on the microbiota composition.
Research Progress in RNA-Binding Proteins
Authors: Smirnov Alexandre
Published: December 2022

RNA-binding proteins are everywhere and accompany RNA molecules at every stage of their molecular life, from “birth” (transcription) through “growing up” (maturation), “active life” (molecular function) until “death” (turnover) [...]
p53 Family in Resistance to Targeted Therapy of Melanoma
Authors: Vlašić Ignacija , Horvat Anđela , Tadijan Ana , Slade Neda
Published: December 2022

Metastatic melanoma is one of the most aggressive tumors, with frequent mutations affecting components of the MAPK pathway, mainly protein kinase BRAF. Despite promising initial response to BRAF inhibitors, melanoma progresses due to development of resistance. In addition to frequent reactivation of MAPK or activation of PI3K/AKT signaling pathways, recently, the p53 pathway has been shown to contribute to acquired resistance to targeted MAPK inhibitor therapy. Canonical tumor suppressor p53 is inactivated in melanoma by diverse mechanisms. The TP53 gene and two other family members, TP63 and TP73, encode numerous protein isoforms that exhibit diverse functions during tumorigenesis. The p53 family isoforms can be produced by usage of alternative promoters and/or splicing on the C- and N-terminus. Various p53 family isoforms are expressed in melanoma cell lines and tumor samples, and several of them have already shown to have specific functions in melanoma, affecting proliferation, survival, metastatic potential, invasion, migration, and response to therapy. Of special interest are p53 family isoforms with increased expression and direct involvement in acquired resistance to MAPK inhibitors in melanoma cells, implying that modulating their expression or targeting their functional pathways could be a potential therapeutic strategy to overcome resistance to MAPK inhibitors in melanoma.
Skin-Derived ABCB5+ Mesenchymal Stem Cells for High-Medical-Need Inflammatory Diseases: From Discovery to Entering Clinical Routine
Authors: Niebergall-Roth Elke , Frank Natasha Y. , Ganss Christoph , Frank Markus H. , Kluth Mark A.
Published: December 2022

The ATP-binding cassette superfamily member ABCB5 identifies a subset of skin-resident mesenchymal stem cells (MSCs) that exhibit potent immunomodulatory and wound healing-promoting capacities along with superior homing ability. The ABCB5+ MSCs can be easily accessed from discarded skin samples, expanded, and delivered as a highly homogenous medicinal product with standardized potency. A range of preclinical studies has suggested therapeutic efficacy of ABCB5+ MSCs in a variety of currently uncurable skin and non-skin inflammatory diseases, which has been substantiated thus far by distinct clinical trials in chronic skin wounds or recessive dystrophic epidermolysis bullosa. Therefore, skin-derived ABCB5+ MSCs have the potential to provide a breakthrough at the forefront of MSC-based therapies striving to fulfill current unmet medical needs. The most recent milestones in this regard are the approval of a phase III pivotal trial of ABCB5+ MSCs for treatment of recessive dystrophic and junctional epidermolysis bullosa by the US Food and Drug Administration, and national market access of ABCB5+ MSCs (AMESANAR®) for therapy-refractory chronic venous ulcers under the national hospital exemption pathway in Germany.
Bioinformatic Analysis of Na+, K+-ATPase Regulation through Phosphorylation of the Alpha-Subunit N-Terminus
Authors: Blayney Emma-Lucille , Chennath Milna , Cranfield Charles G. , Clarke Ronald J.
Published: December 2022

The Na+, K+-ATPase is an integral membrane protein which uses the energy of ATP hydrolysis to pump Na+ and K+ ions across the plasma membrane of all animal cells. It plays crucial roles in numerous physiological processes, such as cell volume regulation, nutrient reabsorption in the kidneys, nerve impulse transmission, and muscle contraction. Recent data suggest that it is regulated via an electrostatic switch mechanism involving the interaction of its lysine-rich N-terminus with the cytoplasmic surface of its surrounding lipid membrane, which can be modulated through the regulatory phosphorylation of the conserved serine and tyrosine residues on the protein’s N-terminal tail. Prior data indicate that the kinases responsible for phosphorylation belong to the protein kinase C (PKC) and Src kinase families. To provide indications of which particular enzyme of these families might be responsible, we analysed them for evidence of coevolution via the mirror tree method, utilising coevolution as a marker for a functional interaction. The results obtained showed that the most likely kinase isoforms to interact with the Na+, K+-ATPase were the θ and η isoforms of PKC and the Src kinase itself. These theoretical results will guide the direction of future experimental studies.
Plectin Downregulation Inhibits Migration and Suppresses Epithelial Mesenchymal Transformation of Hepatocellular Carcinoma Cells via ERK1/2 Signaling
Authors: Xu Rushuang , He Shan , Ma Di , Liang Rui , Luo Qing , Song Guanbin
Published: December 2022

Plectin, as a cytoskeleton-related protein, is involved in various physiological and pathological processes of many cell types. Studies have found that plectin affects cancer cell invasion and metastasis, but the exact mechanism is not fully understood. In this study, we aim to investigate the role of plectin in the migration of hepatocellular carcinoma (HCC) cells and explore its relevant molecular mechanism. Herein, we found that the expression of plectin in HCC tissue and cells was significantly increased compared with normal liver tissue and cells. After downregulation of plectin, the migration ability of HCC cells was significantly lower than that of the control group. Moreover, the expression of E-cadherin was upregulated and the expression of N-cadherin and vimentin was downregulated, suggesting that plectin downregulation suppresses epithelial mesenchymal transformation (EMT) of HCC cells. Mechanically, we found that plectin downregulation repressed the extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Activation of ERK1/2 recovered the plectin downregulation-inhibited migration and EMT of HCC cells. Taken together, our results demonstrate that downregulation of plectin inhibits HCC cell migration and EMT through ERK1/2 signaling, which provides a novel prognostic biomarker and potential therapeutic target for HCC.
Comparative Study on Epidermal Moisturizing Effects and Hydration Mechanisms of Rice-Derived Glucosylceramides and Ceramides
Authors: Takeda Shogo , Yoneda Akari , Miyasaka Kenchi , Manse Yoshiaki , Morikawa Toshio , Shimoda Hiroshi
Published: December 2022

Ceramide (Cer) plays an important role in skin barrier functions in the stratum corneum (SC). The ingestion of food-derived glucosylceramides (GlcCer) attenuates transepidermal water loss (TEWL). However, the moisturizing effects of single molecules of GlcCer and Cer remain unclear. Therefore, we herein purified 13 GlcCer and 6 Cer, including elasticamide, which has the same structure as human Cer[AP], from rice and compared their epidermal moisturizing effects in a reconstructed human epidermal keratinization model. The results obtained showed that 10 µM of 5 GlcCer[d18:2] with a 4E,8Z sphingadienine and C18 to C26 fatty acids and 10 µg/mL of 3 Cer with C23 or C24 fatty acids significantly reduced TEWL. The moisturizing effects of these GlcCer were dependent on the length of fatty acids. Furthermore, 10 µg/mL of elasticamide increased the SC Cer contents by promoting the expression of GlcCer synthase. Electron microscopic observations revealed that 1 µM of GlcCer[d18:2(4E,8Z)/26:0] increased the number of keratohyalin granules and desmosomes. Immunostaining and Western blotting indicated that 1 µM of GlcCer[d18:2(4E,8Z)/26:0] up-regulated the expression of filaggrin and corneodesmosin, which contribute to epidermal hydration. This comparative study on epidermal moisturization by GlcCer and Cer isolated from rice revealed differences in their hydration mechanisms.
Expanding the Functionality of an Autoinduction Device for Repression of Gene Expression in Bacillus subtilis
Authors: Silva Bruna F. , Corrêa Graciely G. , Zocca Vitória F. B. , Picheli Flavio P. , Lins Milca R. C. R. , Pedrolli Danielle B.
Published: December 2022

Autonomous control of gene expression through engineered quorum-sensing processes is broadly applicable to biosynthetic pathways, including simultaneous control of different genes. It is also a powerful tool for balancing growth and production. We had previously engineered a modular autoinduction device for the control of gene expression in B. subtilis. Now, we expand its functionality to repress gene expression autonomously. The engineered R8 promoter responds to AHL accumulation in the culture medium. In a riboflavin-producing strain, the AHL-Lux complex exerts 5-fold repression on the R8-driven expression of the flavokinase/FAD synthetase gene ribC, resulting in a higher titer of the vitamin. We engineered a strain able to autonomously induce and repress different genes simultaneously, demonstrating the potential of the device for use in metabolic engineering.
A Single Episode of Cortical Spreading Depolarization Increases mRNA Levels of Proinflammatory Cytokines, Calcitonin Gene-Related Peptide and Pannexin-1 Channels in the Cerebral Cortex
Authors: Volobueva Maria N. , Suleymanova Elena M. , Smirnova Maria P. , Bolshakov Alexey P. , Vinogradova Lyudmila V.
Published: December 2022

Cortical spreading depolarization (CSD) is the neuronal correlate of migraine aura and the reliable consequence of acute brain injury. The role of CSD in triggering headaches that follow migraine aura and brain injury remains to be uncertain. We examined whether a single CSD occurring in awake animals modified the expression of proinflammatory cytokines (Il1b, TNF, and Il6) and endogenous mediators of nociception/neuroinflammation-pannexin 1 (Panx1) channel and calcitonin gene-related peptide (CGRP), transforming growth factor beta (TGFb) in the cortex. Unilateral microinjury of the somatosensory cortex triggering a single CSD was produced in awake Wistar rats. Three hours later, tissue samples from the lesioned cortex, intact ipsilesional cortex invaded by CSD, and homologous areas of the contralateral sham-treated cortex were harvested and analyzed using qPCR. Three hours post-injury, intact CSD-exposed cortexes increased TNF, Il1b, Panx1, and CGRP mRNA levels. The strongest upregulation of proinflammatory cytokines was observed at the injury site, while CGRP and Panx1 were upregulated more strongly in the intact cortexes invaded by CSD. A single CSD is sufficient to produce low-grade parenchymal neuroinflammation with simultaneous overexpression of Panx1 and CGRP. The CSD-induced molecular changes may contribute to pathogenic mechanisms of migraine pain and post-injury headache.
Anti-Amnesic Effect of Synbiotic Supplementation Containing Corni fructus and Limosilactobacillus reuteri in DSS-Induced Colitis Mice
Authors: Lee Hyo Lim , Kim Jong Min , Moon Jong Hyun , Kim Min Ji , Jeong Hye Rin , Go Min Ji , Kim Hyun-Jin , Eo Hyun Ji , Lee Uk , Heo Ho Jin
Published: December 2022

This study was conducted to compare the synbiotic activity between Corni fructus (C. fructus) and Limosilactobacillus reuteri (L. reuteri) on dextran sulfate sodium (DSS)-induced colitis and cognitive dysfunction in C57BL/6 mice. C. fructus (as prebiotics, PRE), L. reuteri (as probiotics, PRO), and synbiotics (as a mixture of L. reuteri and C. fructus, SYN) were fed to mice for 3 weeks. Consumption of PRE, PRO, and SYN ameliorated colitis symptoms in body weight, large intestinal length, and serum albumin level. Moreover, SYN showed a synergistic effect on intestinal permeability and intestinal anti-inflammation response. Also, SYN significantly improved cognitive function as a result of measuring the Y-maze and passive avoidance tests in DSS-induced behavioral disorder mice. Especially, SYN also restored memory function by increasing the cholinergic system and reducing tau and amyloid β pathology. In addition, PRE, PRO, and SYN ameliorated dysbiosis by regulating the gut microbiota and the concentration of short-chain fatty acids (SCFAs) in feces. The bioactive compounds of C. fructus were identified with quinic acid, morroniside, loganin, and cornuside, using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS2). In conclusion, synbiotic supplementation alleviated DSS-induced colitis and cognitive dysfunction by modulating gut microbiota, proinflammatory cytokines, and SCFAs production.