bluuebunny/crossref_metadata_2025 huggingface dataset:
Provision of Dental Care to Indigenous South Australians and Impacts on Improved General Health: Study Protocol
Authors: Jamieson Lisa , Hedges Joanne , Dodd Zell , Larkins Priscilla , Zbierski Cindy , Nath Sonia , Kapellas Kostas , Ju Xiangqun
Published: February 2023

Background: Indigenous South Australians carry a disproportionate burden of dental diseases, with approximately 80 percent of Indigenous adults having both periodontal disease and dental caries. The chronic inflammatory nature of many dental conditions means there are widespread systemic impacts, particularly on type 2 diabetes, chronic kidney disease and cardiovascular disease. Evidence suggests there are barriers experienced by Indigenous South Australians in accessing timely and culturally safe dental care. This study aims to: (1) elicit the views of Indigenous South Australians regarding their perspectives of what comprises culturally safe dental care; (2) provide such dental care and; (3) assess any changes in both oral and general health using point-of-care testing following receipt of timely, comprehensive and culturally safe dental care. Methods/Design: This mixed-methods study will involve qualitative interviews and an intervention without randomisation. The qualitative component will comprise seeking perspectives of Indigenous South Australians regarding what culturally safe dental care means for them. For the intervention component, participants will take part in oral epidemiological examinations at baseline and 12-month follow-up (after receipt of dental care), which will include collection of saliva, plaque and calculus, as well as completion of a self-report questionnaire. The primary outcome measures—changes in type 2 diabetes (HbA1c), cardiovascular disease (CRP) and chronic kidney disease (ACR)—will be obtained by blood/urine spot from a finger prick/urine collection at baseline and 12-month follow-up via point-of-care testing. Results: Participant recruitment will commence in July 2022. The first results are expected to be submitted for publication one year after recruitment begins. Discussion: The project will have a number of important outcomes, including increased understanding of what culturally safe dental care means for Indigenous South Australians, the delivery of such care, and empirical evidence of how culturally safe dental care leads to better prognosis for chronic diseases linked with poor oral health. This will be important for health services planning, especially in the Aboriginal Community Controlled Health Organisation sector, where the management of dental diseases in a culturally safe manner for better chronic disease outcomes is currently insufficiently understood, planned and budgeted for.
Distribution, Bioaccumulation, and Risks of Pharmaceutical Metabolites and Their Parents: A Case Study in an Yunliang River, Nanjing City
Authors: Yan Zhenhua , Zhou Yixin , Zhang Yan , Zhang Xiadong
Published: February 2023

The occurrence, bioaccumulation, and risks of 11 pairs of pharmaceutical metabolites and their respective parents were investigated in the water, sediment, and fish of an urban river in Nanjing city, China. The results showed that most of the target metabolites and their parents were detected in all water samples, with concentrations ranging from 0.1 ng/L to 72.9 ng/L. In some cases, the concentrations of metabolites in water were significantly higher than their parents, with fold changes reaching up 4.1 in the wet season and 6.6 in the dry season, while in sediment and fish, a lower concentration was observed in most cases. A lowered concentration of detected pharmaceuticals was observed in the dry season when compared to the wet season due to the seasonal variation in pharmaceutical consumption and overflow effluent. The bioaccumulation of pharmaceuticals in different fish tissues were detected with a descending order of overall concentration as gill > brain > muscle > gonad > intestine > liver > blood. In addition, the concentrations of both metabolites and their parents also decreased along the river in two seasons. However, the concentration rates of metabolites and their parents were significantly altered along the river in both water and sediment. The relatively high concentration proportions of the detected pharmaceuticals in water suggested that pharmaceuticals were more likely to apportion in water than in sediment, especially for the metabolites. Meanwhile, the rates of the metabolite/parent pairs between fish and water/sediment were generally lower, indicating the higher excretion capacity of metabolites from fish than their parents. Most of the detected pharmaceuticals had no impact on aquatic organisms. However, the presence of ibuprofen posed a medium risk to fish. Compared to the parents, metabolites showed a relatively low risk value but a high contribution to the total risk. It highlights that metabolites in the aquatic environments cannot be ignored.
Spirituality and Cyberaggression: Mediating and Moderating Effect of Self-Control and School Climate
Authors: Li Shengnan , Nie Yangang
Published: February 2023

Background: Cyberaggression is an essential topic to focus on when it comes to adolescents’ development. We focused on understanding the relationship between spirituality, self-control, school climate, and cyberaggression by examining the mediating and moderating effect of self-control and school climate. Methods: We examined 456 middle school students (M age = 13.45, SD = 1.07), 475 high school students (M age = 16.35, SD = 0.76), and 1117 college students (M age = 20.22, SD = 1.50). Results: Results indicated that the mediating effect of self-control was significant for the college sample on both types of cyberaggression and marginally significant for the high school and middle school sample on reactive cyberaggression. The moderating effect varied across the three samples. School climate moderated the first half of the mediation model for all three samples, the second half for middle school and college student samples on reactive cyberaggression, the direct path for middle school samples on reactive cyberaggression, and the college student sample on both types of cyberaggression. Conclusion: Spirituality has varying degrees of association with cyberaggression through the mediating role of self-control and the moderating role of school climate.
Depression and Anxiety in Old Age during the COVID-19 Pandemic: A Comparative Study of Individuals at Cardiovascular Risk and the General Population
Authors: Gerhards Sina K. , Luppa Melanie , Röhr Susanne , Pabst Alexander , Bauer Alexander , Frankhänel Thomas , Döhring Juliane , Escales Catharina , Zöllinger Isabel Renate , Oey Anke , Brettschneider Christian , Wiese Birgitt , Hoffmann Wolfgang , Gensichen Jochen , König Hans-Helmut , Frese Thomas , Thyrian Jochen René , Kaduszkiewicz Hanna , Riedel-Heller Steffi G.
Published: February 2023

Our study aims to examine the associations of sociodemographic factors, social support, resilience, and perceptions of the COVID-19 pandemic with late-life depression and anxiety symptoms in a cardiovascular risk group and a matched sample from the German general population during the beginning of the pandemic and draw a comparison regarding psychosocial characteristics. Data of n = 1236 participants (aged 64–81 years) were analyzed, with n = 618 participants showing a cardiovascular risk profile, and n = 618 participants from the general population. The cardiovascular risk sample had slightly higher levels of depressive symptoms and felt more threatened by the virus due to pre-existing conditions. In the cardiovascular risk group, social support was associated with less depressive and anxiety symptoms. In the general population, high social support was associated with less depressive symptoms. Experiencing high levels of worries due to COVID-19 was associated with more anxiety in the general population. Resilience was associated with less depressive and anxiety symptoms in both groups. Compared to the general population, the cardiovascular risk group showed slightly higher levels of depressive symptomatology even at the beginning of the pandemic and may be supported by addressing perceived social support and resilience in prevention programs targeting mental health.
Revealing the Impact of COVID-19 on Urban Residential Travel Structure Based on Floating Car Trajectory Data: A Case Study of Nantong, China
Authors: Tao Fei , Wu Junjie , Lin Shuang , Lv Yaqiao , Wang Yu , Zhou Tong
Published: February 2023

The volume of residential travel with different purposes follows relatively stable patterns in a specific period and state; therefore, it can reflect the operating status of urban traffic and even indicate urban vitality. Recent research has focused on changes in the spatiotemporal characteristics of urban mobility affected by the pandemic but has rarely examined the impact of COVID-19 on the travel conditions and psychological needs of residents. To quantitatively assess travel characteristics during COVID-19, this paper proposed a method by which to determine the purpose of residential travel by combining urban functional areas (UFAs) based on machine learning. Then, the residential travel structure, which includes origin–destination (OD) points, residential travel flow, and the proportion of flows for different purposes, was established. Based on taxi trajectory data obtained during the epidemic in Nantong, China, the case study explores changes in travel flow characteristics under the framework of the residential travel structure. Through comparison of the number and spatial distribution of OD points in the residential travel structure, it is found that residential travel hotspots decreased significantly. The ratios of commuting and medical travel increased from 43.8% to 45.7% and 7.1% to 8.1%, respectively. Conversely, the ratios of other travel types all decreased sharply. Moreover, under Maslow’s hierarchy of needs model, further insights into the impacts of COVID-19 on changes in residential psychological needs are discussed in this paper. This work can provide a reference for decision makers to cope with the change in urban traffic during a public health emergency, which is beneficial to the sustainable healthy development of cities.
Quantitative Proteomics of Human Retinal Pigment Epithelium Reveals Key Regulators for the Pathogenesis of Age-Related Macular Degeneration
Authors: Shen Shichen , Kapphahn Rebecca J. , Zhang Ming , Qian Shuo , Montezuma Sandra R. , Shang Peng , Ferrington Deborah A. , Qu Jun
Published: February 2023

Age-related macular degeneration (AMD) is the leading cause of blindness in elderly people, with limited treatment options available for most patients. AMD involves the death of retinal pigment epithelium (RPE) and photoreceptor cells, with mitochondria dysfunction being a critical early event. In the current study, we utilized our unique resource of human donor RPE graded for AMD presence and severity to investigate proteome-wide dysregulation involved in early AMD. Organelle-enriched fractions of RPE were isolated from donors with early AMD (n = 45) and healthy age-matched controls (n = 32) and were analyzed by UHR-IonStar, an integrated proteomics platform enabling reliable and in-depth proteomic quantification in large cohorts. A total of 5941 proteins were quantified with excellent analytical reproducibility, and with further informatics analysis, many biological functions and pathways were found to be significantly dysregulated in donor RPE samples with early AMD. Several of these directly pinpointed changes in mitochondrial functions, e.g., translation, ATP metabolic process, lipid homeostasis, and oxidative stress. These novel findings highlighted the value of our proteomics investigation by allowing a better understanding of the molecular mechanisms underlying early AMD onset and facilitating both treatment development and biomarker discovery.
Overexpression of the Liriodendron tulipifera BOP2 Gene (LtuBOP2) Affects Leaf Margin Development in Transgenic Arabidopsis thaliana
Authors: Zhao Yanqing , Wei Lingmin , Wen Shaoying , Li Huogen
Published: February 2023

BLADE-ON-PETIOLE 2 (BOP2) plays a pivotal role in leaf morphogenesis. Liriodendron tulipifera is a suitable model for exploring the molecular mechanisms underlying leaf serration formation, which are largely unknown. Here, we isolated the full-length LtuBOP2 gene and its promoter from L. tulipifera and characterized its function in leaf morphogenesis through multidimensional approaches. The spatiotemporal expression pattern of LtuBOP2 indicated the high expression of LtuBOP2 in stems and leaf buds. We constructed LtuBOP2 promoter, fused the promoter sequences to the β-glucuronidase (GUS) gene, and then transformed them into Arabidopsis thaliana. Histochemical GUS staining results indicated that GUS activity was higher in petioles and the main vein. LtuBOP2 overexpression in A. thaliana caused moderate serration in the leaf tip, owing to the increased number of abnormal lamina epidermal cells and defective vascular tissue, thus indicating a novel role of BOP2. The ectopic expression of LtuBOP2 in A. thaliana promoted the expression of the lateral organ boundary gene ASYMMETRIC LEAVES2 (AS2) and inhibited JAGGED (JAG) and CUP-SHAPED COTYLEDON2 (CUC2) expression to establish leaf proximal–distal polarity. Moreover, LtuBOP2 participated in leaf serration formation by promoting the antagonistic relationship between KNOX I and hormones during leaf margin development. Our findings revealed the role of LtuBOP2 in the proximal–distal polarity formation and development of leaf margin morphology, providing new insights into the regulatory mechanisms of the leaf formation development of L. tulipifera.
Molecular Mechanism Operating in Animal Models of Neurogenic Detrusor Overactivity: A Systematic Review Focusing on Bladder Dysfunction of Neurogenic Origin
Authors: Ferreira Ana , Nascimento Diogo , Cruz Célia Duarte
Published: February 2023

Neurogenic detrusor overactivity (NDO) is a severe lower urinary tract disorder, characterized by urinary urgency, retention, and incontinence, as a result of a neurologic lesion that results in damage in neuronal pathways controlling micturition. The purpose of this review is to provide a comprehensive framework of the currently used animal models for the investigation of this disorder, focusing on the molecular mechanisms of NDO. An electronic search was performed with PubMed and Scopus for literature describing animal models of NDO used in the last 10 years. The search retrieved 648 articles, of which reviews and non-original articles were excluded. After careful selection, 51 studies were included for analysis. Spinal cord injury (SCI) was the most frequently used model to study NDO, followed by animal models of neurodegenerative disorders, meningomyelocele, and stroke. Rats were the most commonly used animal, particularly females. Most studies evaluated bladder function through urodynamic methods, with awake cystometry being particularly preferred. Several molecular mechanisms have been identified, including changes in inflammatory processes, regulation of cell survival, and neuronal receptors. In the NDO bladder, inflammatory markers, apoptosis-related factors, and ischemia- and fibrosis-related molecules were found to be upregulated. Purinergic, cholinergic, and adrenergic receptors were downregulated, as most neuronal markers. In neuronal tissue, neurotrophic factors, apoptosis-related factors, and ischemia-associated molecules are increased, as well as markers of microglial and astrocytes at lesion sites. Animal models of NDO have been crucial for understanding the pathophysiology of lower urinary tract (LUT) dysfunction. Despite the heterogeneity of animal models for NDO onset, most studies rely on traumatic SCI models rather than other NDO-driven pathologies, which may result in some issues when translating pre-clinical observations to clinical settings other than SCI.
Stimulation of Chondrogenesis in a Developmental Model of Endochondral Bone Formation by Pulsed Electromagnetic Fields
Authors: Littman Jake , Aaron Roy K.
Published: February 2023

Notable characteristics of the skeleton are its responsiveness to physical stimuli and its ability to remodel secondary to changing biophysical environments and thereby fulfill its physiological roles of stability and movement. Bone and cartilage cells have many mechanisms to sense physical cues and activate a variety of genes to synthesize structural molecules to remodel their extracellular matrix and soluble molecules for paracrine signaling. This review describes the response of a developmental model of endochondral bone formation which is translationally relevant to embryogenesis, growth, and repair to an externally applied pulsed electromagnetic field (PEMF). The use of a PEMF allows for the exploration of morphogenesis in the absence of distracting stimuli such as mechanical load and fluid flow. The response of the system is described in terms of the cell differentiation and extracellular matrix synthesis in chondrogenesis. Emphasis is placed upon dosimetry of the applied physical stimulus and some of the mechanisms of tissue response through a developmental process of maturation. PEMFs are used clinically for bone repair and have other potential clinical applications. These features of tissue response and signal dosimetry can be extrapolated to the design of clinically optimal stimulation.
Emerging Effects of Resveratrol Derivatives in Cells Involved in Oral Wound Healing: A Preliminary Study
Authors: D’Amico Emira , Pierfelice Tania Vanessa , Amoroso Rosa , Cacciatore Ivana , D’Arcangelo Camillo , Lepore Stefania , D’Ercole Simonetta , Di Pietro Natalia , Di Rienzo Annalisa , Petrini Morena , Piattelli Adriano , Ricci Alessia , Zara Susi , Di Stefano Antonio , Iezzi Giovanna , De Filippis Barbara
Published: February 2023

Recently, there has been an increasing interest in finding new approaches to manage oral wound healing. Although resveratrol (RSV) exhibited many biological properties, such as antioxidant and anti-inflammatory activities, its use as a drug is limited by unfavorable bioavailability. This study aimed to investigate a series of RSV derivatives (1a–j) with better pharmacokinetic profiles. At first, their cytocompatibility at different concentrations was tested on gingival fibroblasts (HGFs). Among them, derivatives 1d and 1h significantly increased cell viability compared to the reference compound RSV. Thus, 1d and 1h were investigated for cytotoxicity, proliferation, and gene expression in HGFs, endothelial cells (HUVECs), and oral osteoblasts (HOBs), which are the main cells involved in oral wound healing. For HUVECs and HGFs, the morphology was also evaluated, while for HOBs ALP and mineralization were observed. The results showed that both 1d and 1h did not exert negative effects on cell viability, and at a lower concentration (5 µM) both even significantly enhanced the proliferative rate, compared to RSV. The morphology observations pointed out that the density of HUVECs and HGFs was promoted by 1d and 1h (5 µM) and mineralization was promoted in HOBs. Moreover, 1d and 1h (5 µM) induced a higher eNOS mRNA level in HUVECs, higher COL1 mRNA in HGFs, and higher OCN in HOBs, compared to RSV. The appreciable physicochemical properties and good enzymatic and chemical stability of 1d and 1h, along with their promising biological properties, provide the scientific basis for further studies leading to the development of RSV-based agents useful in oral tissue repair.
Natural Polyphenols for Prevention and Treatment of Urinary Tract Infections
Authors: Maisto Maria , Iannuzzo Fortuna , Novellino Ettore , Schiano Elisabetta , Piccolo Vincenzo , Tenore Gian Carlo
Published: February 2023

Urinary tract infections (UTIs) are the second most common type of bacterial infection worldwide. UTIs are gender-specific diseases, with a higher incidence in women. This type of infection could occur in the upper part of the urogenital tract, leading to pyelonephritis and kidney infections, or in the lower part of the urinary tract, leading to less serious pathologies, mainly cystitis and urethritis. The most common etiological agent is uropathogenic E. coli (UPEC), followed by Pseudomonas aeruginosa and Proteus mirabilis. Conventional therapeutic treatment involves the use of antimicrobial agents, but due to the dramatic increase in antimicrobial resistance (AMR), this strategy has partially lost its therapeutic efficacy. For this reason, the search for natural alternatives for UTI treatment represents a current research topic. Therefore, this review summarized the results of in vitro and animal- or human-based in vivo studies aimed to assess the potential therapeutic anti-UTI effects of natural polyphenol-based nutraceuticals and foods. In particular, the main in vitro studies were reported, describing the principal molecular therapeutic targets and the mechanism of action of the different polyphenols studied. Furthermore, the results of the most relevant clinical trials for the treatment of urinary tract health were described. Future research is needed to confirm and validate the potential of polyphenols in the clinical prophylaxis of UTIs.
Ephedra foeminea as a Novel Source of Antimicrobial and Anti-Biofilm Compounds to Fight Multidrug Resistance Phenotype
Authors: Ismail Shurooq , Gaglione Rosa , Masi Marco , Padhi Srichandan , Rai Amit K. , Omar Ghadeer , Cimmino Alessio , Arciello Angela
Published: February 2023

Plants are considered a wealthy resource of novel natural drugs effective in the treatment of multidrug-resistant infections. Here, a bioguided purification of Ephedra foeminea extracts was performed to identify bioactive compounds. The determination of antimicrobial properties was achieved by broth microdilution assays to evaluate minimal inhibitory concentration (MIC) values and by crystal violet staining and confocal laser scanning microscopy analyses (CLSM) to investigate the antibiofilm capacity of the isolated compounds. Assays were performed on a panel of three gram-positive and three gram-negative bacterial strains. Six compounds were isolated from E. foeminea extracts for the first time. They were identified by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) analyses as the well-known monoterpenoid phenols carvacrol and thymol and as four acylated kaempferol glycosides. Among them, the compound kaempferol-3-O-α-L-(2″,4″-di-E-p-coumaroyl)-rhamnopyranoside was found to be endowed with strong antibacterial properties and significant antibiofilm activity against S. aureus bacterial strains. Moreover, molecular docking studies on this compound suggested that the antibacterial activity of the tested ligand against S. aureus strains might be correlated to the inhibition of Sortase A and/or of tyrosyl tRNA synthase. Collectively, the results achieved open interesting perspectives to kaempferol-3-O-α-L-(2″,4″-di-E-p-coumaroyl)-rhamnopyranoside applicability in different fields, such as biomedical applications and biotechnological purposes such as food preservation and active packaging.
Increased Levels of (p)ppGpp Correlate with Virulence and Biofilm Formation, but Not with Growth, in Strains of Uropathogenic Escherichia coli
Authors: Karczewska Monika , Strzelecki Patryk , Bogucka Krystyna , Potrykus Katarzyna , Szalewska-Pałasz Agnieszka , Nowicki Dariusz
Published: February 2023

Urinary tract infections are one of the most frequent bacterial diseases worldwide. UPECs are the most prominent group of bacterial strains among pathogens responsible for prompting such infections. As a group, these extra-intestinal infection-causing bacteria have developed specific features that allow them to sustain and develop in their inhabited niche of the urinary tract. In this study, we examined 118 UPEC isolates to determine their genetic background and antibiotic resistance. Moreover, we investigated correlations of these characteristics with the ability to form biofilm and to induce a general stress response. We showed that this strain collection expressed unique UPEC attributes, with the highest representation of FimH, SitA, Aer, and Sfa factors (100%, 92.5%, 75%, and 70%, respectively). According to CRA (Congo red agar) analysis, the strains particularly predisposed to biofilm formation represented 32.5% of the isolates. Those biofilm forming strains presented a significant ability to accumulate multi-resistance traits. Most notably, these strains presented a puzzling metabolic phenotype—they showed elevated basal levels of (p)ppGpp in the planktonic phase and simultaneously exhibited a shorter generation time when compared to non-biofilm-forming strains. Moreover, our virulence analysis showed these phenotypes to be crucial for the development of severe infections in the Galleria mellonella model.
Structure and Microbiological Activity of 1H-benzo[d]imidazole Derivatives
Authors: Olczak Andrzej , Pawlak Tomasz , Kałużyńska Sylwia , Gobis Katarzyna , Korona-Głowniak Izabela , Suśniak Katarzyna , Zaborowski Marcin , Szczesio Małgorzata
Published: February 2023

Three new crystal structures of 1H-benzo[d]imidazole derivatives were determined. In the structures of these compounds, an identical system of hydrogen bonds, C(4), was observed. Solid-state NMR was applied for testing the quality of the obtained samples. All of these compounds were tested for in vitro antibacterial activity against Gram-positive bacteria and Gram-negative bacteria, as well as antifungal activity, by checking their selectivity. ADME calculations indicate that the compounds can be tested as potential drugs.
ATF5 Attenuates the Secretion of Pro-Inflammatory Cytokines in Activated Microglia
Authors: Zhu Jiebo , Lee Min Joung , An Jong Hun , Oh Eungseok , Chung Woosuk , Heo Jun Young
Published: February 2023

The highly dynamic changes in microglia necessary to achieve a rapid neuroinflammatory response require a supply of energy from mitochondrial respiration, which leads to the accumulation of unfolded mitochondrial proteins. We previously reported that microglial activation is correlated with the mitochondrial unfolded protein response (UPRmt) in a kaolin-induced hydrocephalus model, but we still do not know the extent to which these changes in microglia are involved in cytokine release. Here, we investigated the activation of BV-2 cells and found that treatment with lipopolysaccharide (LPS) for 48 h increased the secretion of pro-inflammatory cytokines. This increase was accompanied by a concurrent decrease in oxygen consumption rate (OCR) and mitochondrial membrane potential (MMP), in association with the up-regulation of the UPRmt. Inhibition of the UPRmt by knockdown of ATF5, a key upstream regulator of the UPRmt, using small-interfering RNA against ATF5 (siATF5) not only increased production of the pro-inflammatory cytokines, interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α), but also decreased MMP. Our results suggest that ATF5-dependent induction of the UPRmt in microglia acts as a protective mechanism during neuroinflammation and may be a potential therapeutic target for reducing neuroinflammation.
Assessment of Inhibition of Biofilm Formation on Non-Thermal Plasma-Treated TiO2 Nanotubes
Authors: Ji Min-Kyung , Lee Seon-Ki , Kim Hee-Seon , Oh Gye-Jeong , Cho Hoonsung , Lim Hyun-Pil
Published: February 2023

Peri-implantitis is an inflammatory disease similar to periodontitis, caused by biofilms formed on the surface of dental implants. This inflammation can spread to bone tissues and result in bone loss. Therefore, it is essential to inhibit the formation of biofilms on the surface of dental implants. Thus, this study examined the inhibition of biofilm formation by treating TiO2 nanotubes with heat and plasma. Commercially pure titanium specimens were anodized to form TiO2 nanotubes. Heat treatment was performed at 400 and 600 °C, and atmospheric pressure plasma was applied using a plasma generator (PGS-200, Expantech, Suwon, Republic of Korea). Contact angles, surface roughness, surface structure, crystal structure, and chemical compositions were measured to analyze the surface properties of the specimens. The inhibition of biofilm formation was assessed using two methods. The results of this study showed that the heat treatment of TiO2 nanotubes at 400 °C inhibited the adhesion of Streptococcus mutans (S. mutans), associated with initial biofilm formation, and that heat treatment of TiO2 nanotubes at 600 °C inhibited the adhesion of Porphyromonas gingivalis (P. gingivalis), which causes peri-implantitis. Applying plasma to the TiO2 nanotubes heat-treated at 600 °C inhibited the adhesion of S. mutans and P. gingivalis.
Current Status of Cell-Based Therapies for Vitiligo
Authors: Domaszewska-Szostek Anna , Polak Agnieszka , Słupecka-Ziemilska Monika , Krzyżanowska Marta , Puzianowska-Kuźnicka Monika
Published: February 2023

Vitiligo is a chronic pigmentary disease with complex etiology, the signs of which are caused by the destruction of melanocytes in the epidermis, leading to the lack of melanin pigment responsible for skin coloration. The treatment of vitiligo, which aims at repigmentation, depends both on the clinical characteristics of the disease as well as on molecular markers that may predict the response to treatment. The aim of this review is to provide an overview of the clinical evidence for vitiligo cell-based therapies taking into account the required procedures and equipment necessary to carry them out as well as their effectiveness in repigmentation, assessed using the percentage of repigmentation of the treated area. This review was conducted by assessing 55 primary clinical studies published in PubMed and ClinicalTrails.gov between 2000 and 2022. This review concludes that the extent of repigmentation, regardless of the treatment method, is highest in stable localized vitiligo patients. Moreover, therapies that combine more than one cell type, such as melanocytes and keratinocytes, or more than one method of treatment, such as the addition of NV-UVB to another treatment, increase the chances of >90% repigmentation. Lastly, this review concludes that various body parts respond differently to all treatments.
Biochemical and Bioinformatic Studies of Mutations of Residues at the Monomer–Monomer Interface of Human Ornithine Aminotransferase Leading to Gyrate Atrophy of Choroid and Retina
Authors: Floriani Fulvio , Borri Voltattorni Carla , Cellini Barbara , Montioli Riccardo
Published: February 2023

Deficit of human ornithine aminotransferase (hOAT), a mitochondrial tetrameric pyridoxal-5′-phosphate (PLP) enzyme, leads to gyrate atrophy of the choroid and retina (GA). Although 70 pathogenic mutations have been identified, only few enzymatic phenotypes are known. Here, we report biochemical and bioinformatic analyses of the G51D, G121D, R154L, Y158S, T181M, and P199Q pathogenic variants involving residues located at the monomer–monomer interface. All mutations cause a shift toward a dimeric structure, and changes in tertiary structure, thermal stability, and PLP microenvironment. The impact on these features is less pronounced for the mutations of Gly51 and Gly121 mapping to the N-terminal segment of the enzyme than those of Arg154, Tyr158, Thr181, and Pro199 belonging to the large domain. These data, together with the predicted ΔΔG values of monomer–monomer binding for the variants, suggest that the proper monomer–monomer interactions seem to be correlated with the thermal stability, the PLP binding site and the tetrameric structure of hOAT. The different impact of these mutations on the catalytic activity was also reported and discussed on the basis of the computational information. Together, these results allow the identification of the molecular defects of these variants, thus extending the knowledge of enzymatic phenotypes of GA patients.
Molecular Markers: A New Paradigm in the Prediction of Sperm Freezability
Authors: Ďuračka Michal , Benko Filip , Tvrdá Eva
Published: February 2023

For decades now, sperm cryopreservation has been a pillar of assisted reproduction in animals as well as humans. Nevertheless, the success of cryopreservation varies across species, seasons, and latitudes and even within the same individual. With the dawn of progressive analytical techniques in the field of genomics, proteomics, and metabolomics, new options for a more accurate semen quality assessment have become available. This review summarizes currently available information on specific molecular characteristics of spermatozoa that could predict their cryotolerance before the freezing process. Understanding the changes in sperm biology as a result of their exposure to low temperatures may contribute to the development and implementation of appropriate measures to assure high post-thaw sperm quality. Furthermore, an early prediction of cryotolerance or cryosensitivity may lead to the establishment of customized protocols interconnecting adequate sperm processing procedures, freezing techniques, and cryosupplements that are most feasible for the individual needs of the ejaculate.
Aggregation of Disordered Proteins Associated with Neurodegeneration
Authors: Tsoi Phoebe S. , Quan My Diem , Ferreon Josephine C. , Ferreon Allan Chris M.
Published: February 2023

Cellular deposition of protein aggregates, one of the hallmarks of neurodegeneration, disrupts cellular functions and leads to neuronal death. Mutations, posttranslational modifications, and truncations are common molecular underpinnings in the formation of aberrant protein conformations that seed aggregation. The major proteins involved in neurodegeneration include amyloid beta (Aβ) and tau in Alzheimer’s disease, α-synuclein in Parkinson’s disease, and TAR DNA-binding protein (TDP-43) in amyotrophic lateral sclerosis (ALS). These proteins are described as intrinsically disordered and possess enhanced ability to partition into biomolecular condensates. In this review, we discuss the role of protein misfolding and aggregation in neurodegenerative diseases, specifically highlighting implications of changes to the primary/secondary (mutations, posttranslational modifications, and truncations) and the quaternary/supramolecular (oligomerization and condensation) structural landscapes for the four aforementioned proteins. Understanding these aggregation mechanisms provides insights into neurodegenerative diseases and their common underlying molecular pathology.
Decreased Vitamin D Levels and Altered Placental Vitamin D Gene Expression at High Altitude: Role of Genetic Ancestry
Authors: Mata-Greenwood Eugenia , Westenburg Hans C. A. , Zamudio Stacy , Illsley Nicholas P. , Zhang Lubo
Published: February 2023

High-altitude hypoxia challenges reproduction; particularly in non-native populations. Although high-altitude residence is associated with vitamin D deficiency, the homeostasis and metabolism of vitamin D in natives and migrants remain unknown. We report that high altitude (3600 m residence) negatively impacted vitamin D levels, with the high-altitude Andeans having the lowest 25-OH-D levels and the high-altitude Europeans having the lowest 1α,25-(OH)2-D levels. There was a significant interaction of genetic ancestry with altitude in the ratio of 1α,25-(OH)2-D to 25-OH-D; with the ratio being significantly lower in Europeans compared to Andeans living at high altitude. Placental gene expression accounted for as much as 50% of circulating vitamin D levels, with CYP2R1 (25-hydroxylase), CYP27B1 (1α-hydroxylase), CYP24A1 (24-hydroxylase), and LRP2 (megalin) as the major determinants of vitamin D levels. High-altitude residents had a greater correlation between circulating vitamin D levels and placental gene expression than low-altitude residents. Placental 7-dehydrocholesterol reductase and vitamin D receptor were upregulated at high altitude in both genetic-ancestry groups, while megalin and 24-hydroxylase were upregulated only in Europeans. Given that vitamin D deficiency and decreased 1α,25-(OH)2-D to 25-OH-D ratios are associated with pregnancy complications, our data support a role for high-altitude-induced vitamin D dysregulation impacting reproductive outcomes, particularly in migrants.
Serious Games and Gamification in Healthcare: A Meta-Review
Authors: Damaševičius Robertas , Maskeliūnas Rytis , Blažauskas Tomas
Published: February 2023

A serious game is a type of game that is designed for a primary purpose other than entertainment. Instead, serious games are intended to achieve specific goals, such as education, training, or health promotion. The goal of serious games is to engage players in a way that is both enjoyable and effective in achieving the intended learning or behavior change outcomes. Recently, several systematic reviews on the development and application of serious games and on the application of gamification techniques have been published, which indicate high activity and ongoing progress in this area of research. Such an extensive body of review papers raises the need to analyze and extract the current state and the prevailing trends of the serious games and gamification (SGG) domain by analyzing and summarizing the systematic review articles. This study presents a systematic meta-review, i.e., a review of the 53 survey papers on the domain of serious games and gamification. The systematic review follows the PRISMA guidelines, while constructive and cross-sectional methods are used to analyze and present the results. Finally, this study identifies the future trends and challenges for the domain. As a result, the meta-review helps the reader to quickly assess the present status of SGG and serves as a reference for finding further information on each technology utilized in SGG. Using the criterion of the citations, the meta-review analysis provides insight into the quantity and academic relevance of the published SGG articles. Moreover, 53 articles published in journals were selected as important surveys in the research field. The study found that serious games and gamification techniques are increasingly being used for a wide range of health conditions and the focus is shifting towards the use of mobile and digital platforms, virtual reality, and machine learning to personalize and adapt interventions. The existing research gaps include the lack of standardization in development and evaluation, insufficient understanding of underlying mechanisms of action, limited understanding of integration into existing healthcare systems, limited understanding of specific game mechanics and design elements for promoting health behaviors, and limited research on scalability, adoption, and long-term effects. These research gaps highlight the need for further research to fully understand the potential and limitations of serious games and gamification for health and how to effectively apply them.
Are Investors Willing to Use Zoom for Entrepreneurs’ Pitch Presentations?
Authors: Kang Jihyun , Van Ouytsel Joris
Published: February 2023

The COVID-19 pandemic led to changes in business communication. As face-to-face communication was no longer possible, many businesses shifted to Zoom because of its ease of use and user-friendly functionality. One unique context in which users were forced to transition to fully online communication was entrepreneurs’ pitch presentations. This study aims to explore whether users intend to continue to use Zoom for these important investment meetings after the pandemic. The study was guided by the Unified Theory of Acceptance and Usage of Technology (UTAUT) model. We surveyed 127 business investors in Korea. The results indicated that performance expectancy and social influence were positively associated with investors’ intentions to use Zoom for entrepreneurs’ pitch presentations in a voluntary setting (i.e., after the pandemic restrictions are fully lifted). Effort expectancy and facilitating conditions were not significantly related to investors’ intentions. The findings help us to better understand the use of video communication within business contexts after the pandemic.
Supramolecular Host–Guest Assemblies of [M6Cl14]2–, M = Mo, W, Clusters with γ-Cyclodextrin for the Development of CLUSPOMs
Authors: Ivanov Anton A. , Abramov Pavel A. , Haouas Mohamed , Molard Yann , Cordier Stéphane , Falaise Clément , Cadot Emmanuel , Shestopalov Michael A.
Published: February 2023

Host–guest assemblies open up opportunities for developing novel functional CLUSPOM multicomponent systems based on transition metal clusters (CLUS), polyoxometalates (POMs) and macrocyclic organic ligands. In water–ethanol solution γ-cyclodextrin (γ-CD) interacts with halide metal clusters [M6Cl14]2– (M = Mo, W) to form sandwich-type structures. The supramolecular association between the clusters and CDs, however, remains weak in solution, and the interactions are not strong enough to prevent the hydrolysis of the inorganic guest. Although analysis of the resulting crystal structures reveals inclusion complexation, 1H NMR experiments in solution show no specific affinity between the two components. The luminescent properties of the host–guest compounds in comparison with the initial cluster complexes are also studied to evaluate the influence of CD.
Testing Scale Models of Hydro-Reactor Profiled Ducts That Create Notable Net Head to Promote Hydroelectric Power from Currents
Authors: dos Santos Costa António J. Arsénio , dos Santos Costa Luís Arsénio
Published: February 2023

In this article, experimental results from the testing of four representative scale models of hydro-reactor profiled channels, which create a net head to promote the extraction of hydroelectric power from currents, are presented. The tested scale models include a narrower intermediate channel section of 300 mm diameter. The different profile models studied include an inlet compression chamber and an outlet depression chamber. A net head is created by the difference in pressure, with the head being higher the narrower channel’s zone than in the kinetic head of the outside stream velocity. Because there were no laboratory premises to test the constructed duct model sizes and to easily change the imposed steady current velocity, the experimental tests were performed by dragging the immersed models, attached to a raft in motion, in a place of steady water (the bay of a port). With this methodology, the same effect was obtained, making it possible to perform the testing for several current velocities (velocity of the raft relative to the steady water). Tests on free-flow to compare the difference in kinetic heads were performed. Furthermore, three loads obstructing different percentages of the channel’s narrower section were inserted to analyze the duct channel obstruction limits. The experimental results are validated by numerical results from finite element analysis.
Development and Validation of Nomograms Predicting the 5- and 8-Year Overall and Cancer-Specific Survival of Bladder Cancer Patients Based on SEER Program
Authors: Wen Peng , Wen Jiao , Huang Xiaolong , Wang Fengze
Published: February 2023

Background: Bladder cancer is often prone to recurrence and metastasis. We sought to construct nomogram models to predict the overall survival (OS) and cancer-specific survival (CSS) of bladder cancer patients. Methods: A reliable random split-sample approach was used to divide patients into two groups: modeling and validation cohorts. Uni-variate and multivariate survival analyses were used to obtain the independent prognostic risk factors based on the modeling cohort. A nomogram was constructed using the R package, “rms”. Harrell’s concordance index (C-index), calibration curves and receiver operating characteristic (ROC) curves were applied to evaluate the discrimination, sensitivity and specificity of the nomograms using the R packages “hmisc”, “rms” and “timeROC”. A decision curve analysis (DCA) was used to evaluate the clinical value of the nomograms via R package “stdca.R”. Results: 10,478 and 10,379 patients were assigned into nomogram modeling and validation cohorts, respectively (split ratio ≈ 1:1). For OS and CSS, the C-index values for internal validation were 0.738 and 0.780, respectively, and the C-index values for external validation were 0.739 and 0.784, respectively. The area under the ROC curve (AUC) values for 5- and 8-year OS and CSS were all greater than 0.7. The calibration curves show that the predicted probability values of 5- and 8-year OS and CSS are close to the actual OS and CSS. The decision curve analysis revealed that the two nomograms have a positive clinical benefit. Conclusion: We successfully constructed two nomograms to forecast OS and CSS for bladder cancer patients. This information can help clinicians conduct prognostic evaluations in an individualized manner and tailor personalized treatment plans.
Anatomic Peculiarities Associated with Axial Elongation of the Myopic Eye
Authors: Jonas Jost B. , Bikbov Mukharram M. , Wang Ya-Xing , Jonas Rahul A. , Panda-Jonas Songhomitra
Published: February 2023

Purpose: To describe anatomical peculiarities associated with axial elongation in the human myopic eye. Methods: Reviewing the results of previous histomorphometrical investigations of enucleated human globes, as well as reviewing findings obtained in population-based studies and hospital-based clinical investigations of myopic patients and non-myopic individuals. Results: Myopic axial elongation is associated with a change from a mostly spherical eye shape to a prolate ellipsoid form. It is combined with choroidal and scleral thinning, most pronounced at the posterior pole and less pronounced in the fundus midperiphery. In the fundus midperiphery, the retina and density of the retinal pigment epithelium (RPE) and photoreceptors decrease with a longer axial length, while in the macular region, retinal thickness, RPE cell density, and choriocapillaris thickness are not related to axial length. With axial elongation, a parapapillary gamma zone develops, leading to an enlargement of the optic disc-fovea distance and a decrease in angle kappa. Axial elongation is also correlated with an increase in the surface and volume of Bruch’s membrane (BM), while BM thickness remains unchanged. Axial elongation causes moderately myopic eyes to show a shift of BM opening to the foveal direction so that the horizontal disc diameter becomes shorter (with a consequent vertical ovalization of the optic disc shape), a temporal gamma zone develops, and the optic nerve exit takes an oblique course. Features of high myopia are an enlargement of the RPE opening (myopic parapapillary beta zone) and BM opening (secondary macrodisc), elongation and thinning of the lamina cribrosa, peripapillary scleral flange (parapapillary delta zone) and peripapillary choroidal border tissue, secondary BM defects in the macular region, myopic maculoschisis, macular neovascularization, and cobblestones in the fundus periphery. Conclusions: These features combined may be explained by a growth in BM in the fundus midperiphery leading to axial elongation.