bluuebunny/crossref_metadata_2025 huggingface dataset:
Parents’ Perception of Family-Centered Music Therapy with Stable Preterm Infants
Authors: Kobus Susann , Diezel Marlis , Huening Britta , Dewan Monia Vanessa , Felderhoff-Mueser Ursula , Bruns Nora
Published: December 2021

Premature birth places considerable demands on preterm infants and their families. Most of these infants are treated on a neonatal intensive care unit immediately after birth, leading to psychosocial stress for parents and making it more difficult to build a stable parent-child bond. We hypothesized that accompaniment with live music therapy by a music therapist supports the parents to get in contact with their child and to promote the parents’ wellbeing. Preterm infants born at less than 32 gestational weeks received creative music therapy twice a week until discharge. At the time of discharge, the parents were asked to complete a Likert-style questionnaire to evaluate the music therapy. Six items related to socio-demographic characteristics, 4 items to observations on the infant and 10 items to personal perception. Of 40 preterm infants receiving music therapy, 32 (80%) parents completed the questionnaires. Thirty (94%) of these parents were able to relax during the music therapy session. Relaxation in their infants was observed by 29 (91%) during and by 28 (88%) after music therapy. Parents perceived music therapy as a positive change and enrichment during their infant’s hospital stay. All parents were thankful for the music therapy they received. Music therapy supports the parents of preterm infants in the first time after birth until discharge from the hospital.
Meta-Analysis of Flipped Learning Effects in Nursing Education
Authors: Park Inhee , Suh Yeonok
Published: December 2021

Background: This study is a meta-analysis confirming the effect size of clinical competence, critical thinking ability, self-directedness, and learning satisfaction, the outcome variables of flipped learning applied to nursing education. Methods: We selected 18 related studies that analyzed data using CMA (Comprehensive Meta-Analysis 2.2). Results: The effect size of the entire study was Hedges’ g = 0.68 (95% CI = 0.43~0.92). The heterogeneity of the overall effect size was I2 = 90.7% (Q = 246.67, p < 0.001); critical thinking ability had an effect size of Hedges’ g = 0.87, learning satisfaction of Hedges’ g = 0.79, clinical competence of Hedges’ g = 0.53, and self-directedness of Hedges’ g = 0.37. The differences were statistically significant. Conclusion: Flipped learning can effectively improve nursing students’ clinical competence, critical thinking ability, self-direction, and learning satisfaction.
Social Distancing, Physical Activity, and COVID-19: Implications for Type 1 Diabetes Mellitus in Brazil
Authors: de Vasconcelos Paulo H. C. , Gomes Daniela L. , Uliana Gabriela C. , Costa e Silva Anselmo de A.
Published: December 2021

A lack of glycemic control and diabetes are risk factors for complications related to COVID-19, and social isolation can hinder adherence to physical activity. Thus, this study sought to assess the impacts of social distancing on the practice of physical activity of individuals with type 1 diabetes mellitus (T1DM). This was a transversal study carried out using an online form to collect sociodemographic, practice of physical activity, and social distancing data. Of the 472 participants, 85.6% reported that they were respecting the steps of social distancing. Social distancing affected the practice of physical activity in adherence to the habit of practicing in frequency, duration, and perception of change in intensity. An association was found between noticing a lot of stress in the home environment and stopping physical activity; lower levels of tolerance to social distancing were associated with less physical activity, and maintaining the habit of practicing physical activity was associated with decreasing the intensity of the practice. Hence, social distancing harmed the practice of physical activity as part of the treatment of individuals with T1DM, both in the habit of practicing and in the characteristics of these practices of physical activity, such as frequency, duration, and intensity.
Eating Healthy: Understanding Added Sugar through Proportional Reasoning
Authors: Basu Debasmita , Nguyen Hong B.
Published: December 2021

Research suggests that integrated STEM activities can best support students in developing their mathematical and scientific understanding. On one hand, while science provides mathematics with real-life authentic problems to investigate, mathematics provides science powerful tools to explore those problems. In line with this call, in this study, we designed an integrated lesson at the cross-section of proportional reasoning and added sugar present in food products to explore how added sugar provides students with a meaningful context to engage in proportional reasoning and how proportional reasoning helps students identify the quantity of added sugar present in different food products and provides students with a platform to initiate a conversation around quality of food products. Developed on the theoretical framework of Realistic Mathematics Education (RME), this lesson was remotely implemented on three middle school students. The result section highlights the design principle of the lesson that provided students with an opportunity to construct an understanding of both the disciplines through a mutual interaction.
A Holistic Approach of Personality Traits in Medical Students: An Integrative Review
Authors: Suciu Nicoleta , Meliț Lorena Elena , Mărginean Cristina Oana
Published: December 2021

Personality is one of the most crucial aspects of human life, since it influences all human behaviours in both personal and social life, and might also trigger important conflicts with a person’s surroundings in the setting of incompatible traits and characteristics. It is true that ‘one must be born’ for a certain medical specialty, but several components of personality might be educated with proper training. Increased levels of Conscientiousness, Agreeableness, and Openness associated with lower levels of Neuroticism might represent the key combination for achieving professional satisfaction in the medical profession. Medical students should receive proper interprofessional education, since effective interprofessional relationships among healthcare providers definitely improve patients’ safety. Empathy contributes to effective patient–physician communication, improving patient trust, compliance, and satisfaction, being positively correlated with Openness, Agreeableness, Conscientiousness and Extraversion. Emotional intelligence—the capacity to respond to one’s own and others’ emotions—was proven to contribute, in a synergistic way with empathy, to increasing empathic ability. Clinical communication skills represent a key component in medical students in order to achieve the best patient care, and they are certainly related and/or influenced by empathy, interprofessional collaboration skills, emotional intelligence and, especially, personality traits. Taking into account the complex interactions mentioned above, the implementation of effective courses based on these concepts in medical students, intending to promote the development of clinical communication skills, represents a real emergency, since it might result in a reduction in medical errors and subsequent related deaths. A thorough understanding of students’ personality is mandatory before designing these courses in order to provide a training tailored to their personality styles.
Rationing of Nursing Care on Example of Selected Health Care Facility
Authors: Tomaszewska Katarzyna , Majchrowicz Bożena , Ratusznik Dorota
Published: December 2021

Contemporary health determinants require nurses to develop new competencies and skills while performing complex tasks in all forms of health care. The problem of rationing of care is present all over the world and usually occurs when available resources are too low to provide adequate care to all patients. The most common reasons for loss of care are shortages of nurses, use of modern treatment methods, increased demand for care by a large number of patients, and greater knowledge of patients about their rights. A questionnaire survey was conducted among 295 nurses employed in hospital wards. The survey was conducted from September to December 2020 using the standardized BERNCA (The Basel Extent of Rationing of Nursing Care) questionnaire to measure the level of rationing of nursing care. The research was hampered by the sanitation regime associated with the SARS CoV-2 pandemic. Nursing care rationing is dependent on seniority and place of work. The mean total BERNCA score of the degree of rationing of nursing care was 2.58 ± 0.96 on a scale of 0 to 4 (where 0 means “no need for it” and 4 means “often”. The median score was 2.69. The higher frequency of rationing nursing care was characteristic of those working on surgical wards. The mean score obtained by them was 2.72 ± 0.86, with the median equal to 2.88. In the case of nurses employed in non-surgical wards, the scores were 2.08 ± 1.07 and 2.28, respectively. Rationing of nursing care is dependent on seniority and work location, with a higher degree of rationing of care occurring in surgical units.
A Comparative Study of Oral Health-Related Quality of Life among Cleft Lip and Palate Patients and Their Families during Orthodontic Treatment
Authors: Francisco Inês , Caramelo Francisco , Fernandes Maria Helena , Vale Francisco
Published: December 2021

(1) Background: It has been recognized that CLP condition may affect oral health-related quality of life (OHRQoL) due to dental anomalies and abnormal craniofacial development. Aim: To assess whether orthodontic treatment affected the levels of OHRQoL in CLP patients and their families. (2) Methods: 226 individuals (111 with cleft and 115 control) and their parents were invited to complete the Oral Health Impact Profile-14 (OHIP-14) and Family Impact Scale (FIS), respectively. The Mann–Whitney test was used for quantitative variables and the Fisher’s exact test for categorical variables. The Spearman Rank Correlation Coefficient was used to correlate the results of the OHIP and FIS questionnaires. (3) Results: No significant difference was found between groups in OHIP-14 but FIS score revealed a significant difference between the two groups evaluated (p < 0.001). Only the social limitation in OHIP score revealed a significant difference (p = 0.001). Regarding FIS score, the most affected dimensions were family activities (p < 0.001), parental emotions (p = 0.001), and family conflict (p = 0.011). (4) Conclusion: Undergoing orthodontic treatment had a similar impact on the overall quality of life in CLP patients and non-cleft patients. Parents of cleft children had a poorer OHRQoL compared to what was perceived by their children and parents of non-cleft children.
Factors Associated with Unfavourable Treatment Outcomes in Patients with Tuberculosis: A 16-Year Cohort Study (2005–2020), Republic of Karakalpakstan, Uzbekistan
Authors: Gadoev Jamshid , Asadov Damin , Harries Anthony D. , Kumar Ajay M. V. , Boeree Martin Johan , Hovhannesyan Araksya , Kuppens Lianne , Yedilbayev Askar , Korotych Oleksandr , Hamraev Atadjan , Kudaybergenov Kallibek , Abdusamatova Barno , Khudanov Bakhtinur , Dara Masoud
Published: December 2021

Tuberculosis (TB) remains a public health burden in the Republic of Karakalpakstan, Uzbekistan. This region-wide retrospective cohort study reports the treatment outcomes of patients registered in the TB electronic register and treated with first-line drugs in the TB Programme of the Republic of Karakalpakstan from 2005–2020 and factors associated with unfavourable outcomes. Among 35,122 registered patients, 24,394 (69%) patients were adults, 2339 (7%) were children, 18,032 (51%) were male and 19,774 (68%) lived in rural areas. Of these patients, 29,130 (83%) had pulmonary TB and 7497 (>22%) had been previously treated. There were 7440 (21%) patients who had unfavourable treatment outcomes. Factors associated with unfavourable treatment outcomes included: increasing age, living in certain parts of the republic, disability, pensioner status, unemployment, being HIV-positive, having pulmonary TB, and receiving category II treatment. Factors associated with death included: being adult and elderly, living in certain parts of the republic, having a disability, pensioner status, being HIV-positive, and receiving category II treatment. Factors associated with failure included: being adolescent, female, having pulmonary TB. Factors associated with loss to follow-up included: being male, disability, pensioner status, unemployment, receiving category II treatment. In summary, there are sub-groups of patients who need special attention in order to decrease unfavourable treatment outcomes.
Reassessing Fitness-to-Drive in Drinker Drivers: The Role of Cognition and Personality
Authors: Tinella Luigi , Caffò Alessandro Oronzo , Lopez Antonella , Nardulli Francesco , Grattagliano Ignazio , Bosco Andrea
Published: December 2021

Drunken driving is among the main challenges for road safety by causing worldwide motor-vehicle crashes with severe injuries and deaths. The reassessment of fitness-to-drive in drivers stopped for drunken driving includes mainly psychological examinations. The present study aimed to investigate the effectiveness and the consistency of selected variables of different psychological driving-related dimensions (i.e., cognitive skills and personality) in discriminating 90 male drinker drivers (DD) from matched non-drinkers controls. The Montreal Cognitive Assessment (MoCA), the Mental Rotation Test (MRT), and the Perspective-Taking Test (PT) were administered to assess overall cognitive functioning, and object- and self-based spatial transformation abilities, respectively. Participants completed a computerized test measuring resilience of attention (DT), reaction times (RT), and perceptual speed (ATAVT). The Personality Psychopathology Five scales (i.e., PSY-5: Aggressiveness-AGGR, Psychoticism-PSYC, Disconstraint-DISC, Negative-Emotionality-NEGE, and Introversion-INTR) the validity scale (L) and the dissimulation index (F-K) were scored from the Minnesota Multiphasic Personality Inventory (MMPI-2). A logistic binomial regression analysis (backward subtraction method) was used to identify discriminant predictors. A prediction analysis (ROC curve method) was performed on the final model. Results showed that the scores obtained in MRT, DT, and the personality measures of PSYC, DISC, NEGE, and INTR significantly discriminated DD from their matched controls with moderate-to-good values of accuracy (0.79), sensitivity (0.80), and specificity (0.79), as well as a good AUC value (0.89). In some cases, the personality dimensions provided—reliable—unexpected results. Low scores of PSYC, NEGE, and INTR were found to predict the membership to the DD group; results are discussed with reference to response management. Personality measures should be assessed with particular attention in a forensic context because they are more prone to be feigned than cognitive ones. Overall, the present study confirmed the relevance of integrating different driving-related psychological dimensions in the evaluation of fitness-to-drive showing the usefulness of standardized tools for the reassessment of drinker drivers.
Mediating Role of Stress at Work in the Relationship of Alexithymia and PTSD among Emergency Call Operators
Authors: Wojciechowska Małgorzata , Jasielska Aleksandra , Ziarko Michał , Sieński Michał , Różewicki Maciej
Published: December 2021

Aim: The main purpose of this research was to investigate the relationship between alexithymia, stress at work, and post-traumatic stress disorder (PTSD) in impact emergency call center operators working in Poland (province of Greater Poland). The risk of exposure to critical life events was also considered. Methods: Data were collected using self-report questionnaires administered after dispatchers’ shifts. The emergency call center operators (N = 66) completed the Impact of Event Scale—Revised, 20-item Toronto Alexithymia Scale, Workplace Perceived Stress Questionnaire, and a questionnaire measuring the frequency and intensity of potentially traumatic events faced by emergency operators (a questionnaire developed by the authors). Results: Twenty of the most frequent events (e.g., child sexual harassment, rape, etc.) were identified. Results indicated that post-traumatic stress positively correlated with (a) work-related stress and (b) one aspect of alexithymia: difficulty expressing feelings. Additionally, work-related stress was identified as a mediator for the relation between alexithymia and the intensity of post-traumatic stress. Conclusions: The results of this study confirm that emergency operators are a high-risk group for the development of PTSD. The study results suggest that performing the work of an emergency dispatcher is not only demanding but also inherently involves participation in potentially traumatic events (as encountered through emergency calls).
Supporting the Sharing of Mental Health Challenges in the Workplace: Findings from Comparative Case Study Research at Two Mental Health Services
Authors: King Alicia Jean , Fortune Tracy Lee , Byrne Louise , Brophy Lisa Mary
Published: December 2021

Personal experience with mental health (MH) challenges has been characterized as a concealable stigma. Identity management literature suggests actively concealing a stigma may negatively impact wellbeing. Reviews of workplace identity management literature have linked safety in revealing a stigma to individual performance, well-being, engagement and teamwork. However, no research to date has articulated the factors that make sharing MH challenges possible. This study employed a comparative case study design to explore the sharing of MH challenges in two Australian MH services. We conducted qualitative analyses of interviews with staff in direct service delivery and supervisory roles, to determine factors supporting safety to share. Workplace factors supporting safety to share MH challenges included: planned and unplanned “check-ins;” mutual sharing and support from colleagues and supervisors; opportunities for individual and team reflection; responses to and management of personal leave and requests for accommodation; and messaging and action from senior organizational leaders supporting the value of workforce diversity. Research involving staff with experience of MH challenges provides valuable insights into how we can better support MH staff across the workforce.
Exploration of the Effect on Genome-Wide DNA Methylation by miR-143 Knock-Out in Mice Liver
Authors: Chen Xingping , Luo Junyi , Liu Jie , Chen Ting , Sun Jiajie , Zhang Yongliang , Xi Qianyun
Published: December 2021

MiR-143 play an important role in hepatocellular carcinoma and liver fibrosis via inhibiting hepatoma cell proliferation. DNA methyltransferase 3 alpha (DNMT3a), as a target of miR-143, regulates the development of primary organic solid tumors through DNA methylation mechanisms. However, the effect of miR-143 on DNA methylation profiles in liver is unclear. In this study, we used Whole-Genome Bisulfite Sequencing (WGBS) to detect the differentially methylated regions (DMRs), and investigated DMR-related genes and their enriched pathways by miR-143. We found that methylated cytosines increased 0.19% in the miR-143 knock-out (KO) liver fed with high-fat diet (HFD), compared with the wild type (WT). Furthermore, compared with the WT group, the CG methylation patterns of the KO group showed lower CG methylation levels in CG islands (CGIs), promoters and hypermethylation in CGI shores, 5′UTRs, exons, introns, 3′UTRs, and repeat regions. A total of 984 DMRs were identified between the WT and KO groups consisting of 559 hypermethylation and 425 hypomethylation DMRs. Furthermore, DMR-related genes were enriched in metabolism pathways such as carbon metabolism (serine hydroxymethyltransferase 2 (Shmt2), acyl-Coenzyme A dehydrogenase medium chain (Acadm)), arginine and proline metabolism (spermine synthase (Sms), proline dehydrogenase (Prodh2)) and purine metabolism (phosphoribosyl pyrophosphate synthetase 2 (Prps2)). In summary, we are the first to report the change in whole-genome methylation levels by miR-143-null through WGBS in mice liver, and provide an experimental basis for clinical diagnosis and treatment in liver diseases, indicating that miR-143 may be a potential therapeutic target and biomarker for liver damage-associated diseases and hepatocellular carcinoma.
A Bioinformatic Workflow for InDel Analysis in the Wheat Multi-Copy α-Gliadin Gene Family Engineered with CRISPR/Cas9
Authors: Guzmán-López María H. , Marín-Sanz Miriam , Sánchez-León Susana , Barro Francisco
Published: December 2021

The α-gliadins of wheat, along with other gluten components, are responsible for bread viscoelastic properties. However, they are also related to human pathologies as celiac disease or non-celiac wheat sensitivity. CRISPR/Cas was successfully used to knockout α-gliadin genes in bread and durum wheat, therefore, obtaining low gluten wheat lines. Nevertheless, the mutation analysis of these genes is complex as they present multiple and high homology copies arranged in tandem in A, B, and D subgenomes. In this work, we present a bioinformatic pipeline based on NGS amplicon sequencing for the analysis of insertions and deletions (InDels) in α-gliadin genes targeted with two single guides RNA (sgRNA). This approach allows the identification of mutated amplicons and the analysis of InDels through comparison to the most similar wild type parental sequence. TMM normalization was performed for inter-sample comparisons; being able to study the abundance of each InDel throughout generations and observe the effects of the segregation of Cas9 coding sequence in different lines. The usefulness of the workflow is relevant to identify possible genomic rearrangements such as large deletions due to Cas9 cleavage activity. This pipeline enables a fast characterization of mutations in multiple samples for a multi-copy gene family.
Cytokinin Perception in Ancient Plants beyond Angiospermae
Authors: Lomin Sergey N. , Savelieva Ekaterina M. , Arkhipov Dmitry V. , Pashkovskiy Pavel P. , Myakushina Yulia A. , Heyl Alexander , Romanov Georgy A.
Published: December 2021

Cytokinins (CKs) control many plant developmental processes and responses to environmental cues. Although the CK signaling is well understood, we are only beginning to decipher its evolution. Here, we investigated the CK perception apparatus in early-divergent plant species such as bryophyte Physcomitrium patens, lycophyte Selaginella moellendorffii, and gymnosperm Picea abies. Of the eight CHASE-domain containing histidine kinases (CHKs) examined, two CHKs, PpCHK3 and PpCHK4, did not bind CKs. All other CHK receptors showed high-affinity CK binding (KD of nM range), with a strong preference for isopentenyladenine over other CK nucleobases in the moss and for trans-zeatin over cis-zeatin in the gymnosperm. The pH dependences of CK binding for these six CHKs showed a wide range, which may indicate different subcellular localization of these receptors at either the plasma- or endoplasmic reticulum membrane. Thus, the properties of the whole CK perception apparatuses in early-divergent lineages were demonstrated. Data show that during land plant evolution there was a diversification of the ligand specificity of various CHKs, in particular, the rise in preference for trans-zeatin over cis-zeatin, which indicates a steadily increasing specialization of receptors to various CKs. Finally, this distinct preference of individual receptors to different CK versions culminated in vascular plants, especially angiosperms.
Influence of Culture Period on Osteoblast Differentiation of Tissue-Engineered Bone Constructed by Apatite-Fiber Scaffolds Using Radial-Flow Bioreactor
Authors: Suzuki Kitaru , Fukasawa Jun , Miura Maiko , Lim Poon Nian , Honda Michiyo , Matsuura Tomokazu , Aizawa Mamoru
Published: December 2021

With the limitation of autografts, the development of alternative treatments for bone diseases to alleviate autograft-related complications is highly demanded. In this study, a tissue-engineered bone was formed by culturing rat bone marrow cells (RBMCs) onto porous apatite-fiber scaffolds (AFSs) with three-dimensional (3D) interconnected pores using a radial-flow bioreactor (RFB). Using the optimized flow rate, the effect of different culturing periods on the development of tissue-engineered bone was investigated. The 3D cell culture using RFB was performed for 0, 1 or 2 weeks in a standard medium followed by 0, 1 or 2 weeks in a differentiation medium. Osteoblast differentiation in the tissue-engineered bone was examined by alkaline phosphatase (ALP) and osteocalcin (OC) assays. Furthermore, the tissue-engineered bone was histologically examined by hematoxylin and eosin and alizarin red S stains. We found that the ALP activity and OC content of calcified cells tended to increase with the culture period, and the differentiation of tissue-engineered bone could be controlled by varying the culture period. In addition, the employment of RFB and AFSs provided a favorable 3D environment for cell growth and differentiation. Overall, these results provide valuable insights into the design of tissue-engineered bone for clinical applications.
Docosahexaenoic Acid Modulates Paracellular Absorption of Testosterone and Claudin-1 Expression in a Tissue-Engineered Skin Model
Authors: Tremblay Andréa , Simard Mélissa , Morin Sophie , Pouliot Roxane
Published: December 2021

Healthy skin moLEdels produced by tissue-engineering often present a suboptimal skin barrier function as compared with normal human skin. Moreover, skin substitutes reconstructed according to the self-assembly method were found to be deficient in polyunsaturated fatty acids (PUFAs). Therefore, in this study, we investigated the effects of a supplementation of the culture media with docosahexaenoic acid (DHA) on the barrier function of skin substitutes. To this end, 10 μM DHA-supplemented skin substitutes were produced (n = 3), analyzed, and compared with controls (substitutes without supplementation). A Franz cell diffusion system, followed by ultra-performance liquid chromatography, was used to perform a skin permeability to testosterone assay. We then used gas chromatography to quantify the PUFAs found in the epidermal phospholipid fraction of the skin substitutes, which showed successful DHA incorporation. The permeability to testosterone was decreased following DHA supplementation and the lipid profile was improved. Differences in the expression of the tight junction (TJ) proteins claudin-1, claudin-4, occludin, and TJ protein-1 were observed, principally a significant increase in claudin-1 expression, which was furthermore confirmed by Western blot analyses. In conclusion, these results confirm that the DHA supplementation of cell culture media modulates different aspects of skin barrier function in vitro and reflects the importance of n-3 PUFAs regarding the lipid metabolism in keratinocytes.
Phase Separation of Intrinsically Disordered Nucleolar Proteins Relate to Localization and Function
Authors: Guillen-Chable Francisco , Bayona Andrea , Rodríguez-Zapata Luis Carlos , Castano Enrique
Published: December 2021

The process of phase separation allows for the establishment and formation of subcompartmentalized structures, thus enabling cells to perform simultaneous processes with precise organization and low energy requirements. Chemical modifications of proteins, RNA, and lipids alter the molecular environment facilitating enzymatic reactions at higher concentrations in particular regions of the cell. In this review, we discuss the nucleolus as an example of the establishment, dynamics, and maintenance of a membraneless organelle with a high level of organization.
A Review of Prostate Organogenesis and a Role for iPSC-Derived Prostate Organoids to Study Prostate Development and Disease
Authors: Buskin Adriana , Singh Parmveer , Lorenz Oliver , Robson Craig , Strand Douglas W. , Heer Rakesh
Published: December 2021

The prostate is vulnerable to two major age-associated diseases, cancer and benign enlargement, which account for significant morbidity and mortality for men across the globe. Prostate cancer is the most common cancer reported in men, with over 1.2 million new cases diagnosed and 350,000 deaths recorded annually worldwide. Benign prostatic hyperplasia (BPH), characterised by the continuous enlargement of the adult prostate, symptomatically afflicts around 50% of men worldwide. A better understanding of the biological processes underpinning these diseases is needed to generate new treatment approaches. Developmental studies of the prostate have shed some light on the processes essential for prostate organogenesis, with many of these up- or downregulated genes expressions also observed in prostate cancer and/or BPH progression. These insights into human disease have been inferred through comparative biological studies relying primarily on rodent models. However, directly observing mechanisms of human prostate development has been more challenging due to limitations in accessing human foetal material. Induced pluripotent stem cells (iPSCs) could provide a suitable alternative as they can mimic embryonic cells, and iPSC-derived prostate organoids present a significant opportunity to study early human prostate developmental processes. In this review, we discuss the current understanding of prostate development and its relevance to prostate-associated diseases. Additionally, we detail the potential of iPSC-derived prostate organoids for studying human prostate development and disease.
Bare Metal Stents on Resveratrol-Coated Balloons in Porcine Coronary and Peripheral Arteries
Authors: Kamann Stefanie , Haase Tobias , Stolzenburg Nicola , Löchel Melanie , Peters-Berg Daniel , Schütt Denise , Schnorr Jörg
Published: December 2021

Balloon angioplasty and stent implantation are standard techniques to reopen stenotic vessels. Often, balloons or stents coated with cytostatic drugs are used to prevent re-occlusion of the arteries. Resveratrol, which is known for its numerous beneficial effects on cardiovascular health, is used as an antioxidant additive on paclitaxel-coated balloon catheters. What is still unclear is whether resveratrol-only balloon coating in combination with a bare metal stent (BMS) also has positive effects on vascular healing. Here, we analyzed neointimal thickening, fibrin deposition, inflammation, vasa vasorum density, and reendothelialization after implantation of BMS via a resveratrol coated balloon approach in a porcine model. In general, resveratrol treatment did not result in significantly altered responses compared to the control group in peripheral arteries. In coronary arteries, an increase in vasa vasorum density became evident three days after resveratrol treatment compared to the control group and abolished up to day 7. Significant effects of the resveratrol treatment on the fibrin score or intima-media area were transient and restricted to either peripheral or coronary arteries. In conclusion, local single-dose resveratrol treatment via a resveratrol-only coated balloon and BMS approach did not lead to adverse systemic or local effects, but also no significant beneficial effects on vascular healing were detected in the current study.
Mechanistic Insights into Potassium-Conferred Drought Stress Tolerance in Cultivated and Tibetan Wild Barley: Differential Osmoregulation, Nutrient Retention, Secondary Metabolism and Antioxidative Defense Capacity
Authors: Sehar Shafaque , Adil Muhammad Faheem , Zeeshan Muhammad , Holford Paul , Cao Fangbin , Wu Feibo , Wang Yizhou
Published: December 2021

Keeping the significance of potassium (K) nutrition in focus, this study explores the genotypic responses of two wild Tibetan barley genotypes (drought tolerant XZ5 and drought sensitive XZ54) and one drought tolerant barley cv. Tadmor, under the exposure of polyethylene glycol-induced drought stress. The results revealed that drought and K deprivation attenuated overall plant growth in all the tested genotypes; however, XZ5 was least affected due to its ability to retain K in its tissues which could be attributed to the smallest reductions of photosynthetic parameters, relative chlorophyll contents and the lowest Na+/K+ ratios in all treatments. Our results also indicate that higher H+/K+-ATPase activity (enhancement of 1.6 and 1.3-fold for shoot; 1.4 and 2.5-fold for root), higher shoot K+ (2 and 2.3-fold) and Ca2+ content (1.5 and 1.7-fold), better maintenance of turgor pressure by osmolyte accumulation and enhanced antioxidative performance to scavenge ROS, ultimately suppress lipid peroxidation (in shoots: 4% and 35%; in roots 4% and 20% less) and bestow higher tolerance to XZ5 against drought stress in comparison with Tadmor and XZ54, respectively. Conclusively, this study adds further evidence to support the concept that Tibetan wild barley genotypes that utilize K efficiently could serve as a valuable genetic resource for the provision of genes for improved K metabolism in addition to those for combating drought stress, thereby enabling the development of elite barley lines better tolerant of abiotic stresses.
Neuroinflammation as a Key Driver of Secondary Neurodegeneration Following Stroke?
Authors: Stuckey Shannon M. , Ong Lin Kooi , Collins-Praino Lyndsey E. , Turner Renée J.
Published: December 2021

Ischaemic stroke involves the rapid onset of focal neurological dysfunction, most commonly due to an arterial blockage in a specific region of the brain. Stroke is a leading cause of death and common cause of disability, with over 17 million people worldwide suffering from a stroke each year. It is now well-documented that neuroinflammation and immune mediators play a key role in acute and long-term neuronal tissue damage and healing, not only in the infarct core but also in distal regions. Importantly, in these distal regions, termed sites of secondary neurodegeneration (SND), spikes in neuroinflammation may be seen sometime after the initial stroke onset, but prior to the presence of the neuronal tissue damage within these regions. However, it is key to acknowledge that, despite the mounting information describing neuroinflammation following ischaemic stroke, the exact mechanisms whereby inflammatory cells and their mediators drive stroke-induced neuroinflammation are still not fully understood. As a result, current anti-inflammatory treatments have failed to show efficacy in clinical trials. In this review we discuss the complexities of post-stroke neuroinflammation, specifically how it affects neuronal tissue and post-stroke outcome acutely, chronically, and in sites of SND. We then discuss current and previously assessed anti-inflammatory therapies, with a particular focus on how failed anti-inflammatories may be repurposed to target SND-associated neuroinflammation.
Atmospheric Pressure Plasma Activation of Hydroxyapatite to Improve Fluoride Incorporation and Modulate Bacterial Biofilm
Authors: Zarif Maria Elena , Yehia Sașa Alexandra , Biță Bogdan , Sătulu Veronica , Vizireanu Sorin , Dinescu Gheorghe , Holban Alina Maria , Marinescu Florica , Andronescu Ecaterina , Grumezescu Alexandru Mihai , Bîrcă Alexandra Cătălina , Farcașiu Alexandru Titus
Published: December 2021

Despite the technological progress of the last decade, dental caries is still the most frequent oral health threat in children and adults alike. Such a condition has multiple triggers and is caused mainly by enamel degradation under the acidic attack of microbial cells, which compose the biofilm of the dental plaque. The biofilm of the dental plaque is a multispecific microbial consortium that periodically develops on mammalian teeth. It can be partially removed through mechanical forces by individual brushing or in specialized oral care facilities. Inhibition of microbial attachment and biofilm formation, as well as methods to strengthen dental enamel to microbial attack, represent the key factors in caries prevention. The purpose of this study was to elaborate a cold plasma-based method in order to modulate microbial attachment and biofilm formation and to improve the retention of fluoride (F−) in an enamel-like hydroxyapatite (HAP) model sample. Our results showed improved F retention in the HAP model, which correlated with an increased antimicrobial and antibiofilm effect. The obtained cold plasma with a dual effect exhibited through biofilm modulation and enamel strengthening through fluoridation is intended for dental application, such as preventing and treating dental caries and enamel deterioration.
TG68, a Novel Thyroid Hormone Receptor-β Agonist for the Treatment of NAFLD
Authors: Caddeo Andrea , Kowalik Marta Anna , Serra Marina , Runfola Massimiliano , Bacci Andrea , Rapposelli Simona , Columbano Amedeo , Perra Andrea
Published: December 2021

Activation of thyroid hormone receptor β (THRβ) has shown beneficial effects on metabolic alterations, including non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effect of TG68, a novel THRβ agonist, on fatty liver accumulation and liver injury in mice fed a high-fat diet (HFD). C57BL/6 mice fed HFD for 17 or 18 weeks, a time when all mice developed massive steatohepatitis, were then given TG68 at a dose of 9.35 or 2.8 mg/kg for 2 or 3 weeks, respectively. As a reference compound, the same treatment was adopted using equimolar doses of MGL-3196, a selective THRβ agonist currently in clinical phase III. The results showed that treatment with TG68 led to a reduction in liver weight, hepatic steatosis, serum transaminases, and circulating triglycerides. qRT-PCR analyses demonstrated activation of THRβ, as confirmed by increased mRNA levels of Deiodinase-1 and Malic enzyme-1, and changes in lipid metabolism, as revealed by increased expression of Acyl-CoA Oxidase-1 and Carnitine palmitoyltransferase-1. The present results showed that this novel THRβ agonist exerts an anti-steatogenic effect coupled with amelioration of liver injury in the absence of extra-hepatic side effects, suggesting that TG68 may represent a useful tool for the treatment of NAFLD.
Using a Cellular System to Directly Assess the Effects of Cosmetic Microemulsion Encapsulated DeoxyArbutin
Authors: Chang Nai-Fang , Tsai Feng-Jie , Zheng Ya-Min , Huang Wei-Hsiang , Lin Chih-Chien
Published: December 2021

DeoxyArbutin (dA) is a tyrosinase inhibitor that has effective skin-lightening activity and has no obvious cytotoxicity toward melanocytes. With the aim of directly evaluating the effects of microemulsions containing dA on cells, we developed oil-in-water (O/W) microemulsions with relatively lower cytotoxicities by using polysorbate-series surfactants. Measurement of the transparent properties and particle size analysis at different storage time periods revealed that the developed microemulsions were stable. Moreover, the developed microemulsions had direct effects on B16-F10 mouse melanoma cells. The anti-melanogenesis activities of dA-containing microemulsions were evidently better than that of the free dA group. The results demonstrated that the developed microemulsion encapsulating dA may allow the use of deoxyArbutin instead of hydroquinone to treat dermal hyperpigmentation disorders in the future.
Viral Transduction of Human Rod Opsin or Channelrhodopsin Variants to Mouse ON Bipolar Cells Does Not Impact Retinal Anatomy or Cause Measurable Death in the Targeted Cells
Authors: Wright Phillip , Rodgers Jessica , Wynne Jonathan , Bishop Paul N. , Lucas Robert J. , Milosavljevic Nina
Published: December 2021

The viral gene delivery of optogenetic actuators to the surviving inner retina has been proposed as a strategy for restoring vision in advanced retinal degeneration. We investigated the safety of ectopic expression of human rod opsin (hRHO), and two channelrhodopsins (enhanced sensitivity CoChR-3M and red-shifted ReaChR) by viral gene delivery in ON bipolar cells of the mouse retina. Adult Grm6Cre mice were bred to be retinally degenerate or non-retinally degenerate (homozygous and heterozygous for the rd1Pde6b mutation, respectively) and intravitreally injected with recombinant adeno-associated virus AAV2/2(quad Y-F) serotype containing a double-floxed inverted transgene comprising one of the opsins of interest under a CMV promoter. None of the opsins investigated caused changes in retinal thickness; induced apoptosis in the retina or in transgene expressing cells; or reduced expression of PKCα (a specific bipolar cell marker). No increase in retinal inflammation at the level of gene expression (IBA1/AIF1) was found within the treated mice compared to controls. The expression of hRHO, CoChR or ReaChR under a strong constitutive promoter in retinal ON bipolar cells following intravitreal delivery via AAV2 does not cause either gross changes in retinal health, or have a measurable impact on the survival of targeted cells.
Bifunctional Inhibitors of Influenza Virus Neuraminidase: Molecular Design of a Sulfonamide Linker
Authors: Evteev Sergei , Nilov Dmitry , Polenova Aleksandra , Švedas Vytas
Published: December 2021

The growing resistance of the influenza virus to widely used competitive neuraminidase inhibitors occupying the active site of the enzyme requires the development of bifunctional compounds that can simultaneously interact with other regulatory sites on the protein surface. When developing such an inhibitor and combining structural fragments that could be located in the sialic acid cavity of the active site and the adjacent 430-cavity, it is necessary to select a suitable linker not only for connecting the fragments, but also to ensure effective interactions with the unique arginine triad Arg118-Arg292-Arg371 of neuraminidase. Using molecular modeling, we have demonstrated the usefulness of the sulfonamide group in the linker design and the potential advantage of this functional group over other isosteric analogues.
Metal-Specificity Divergence between Metallothioneins of Nerita peloronta (Neritimorpha, Gastropoda) Sets the Starting Point for a Novel Chemical MT Classification Proposal
Authors: García-Risco Mario , Calatayud Sara , Pedrini-Martha Veronika , Albalat Ricard , Dallinger Reinhard , Palacios Òscar , Capdevila Mercè
Published: December 2021

Metallothioneins’ (MTs) biological function has been a matter of debate since their discovery. The importance to categorize these cysteine-rich proteins with high coordinating capacity into a specific group led to numerous classification proposals. We proposed a classification based on their metal-binding abilities, gradually sorting them from those with high selectivity towards Zn/Cd to those that are Cu-specific. However, the study of the NpeMT1 and NpeMT2isoforms of Nerita peloronta, has put a new perspective on this classification. N. peloronta has been chosen as a representative mollusk to elucidate the metal-binding abilities of Neritimorpha MTs, an order without any MTs characterized recently. Both isoforms have been recombinantly synthesized in cultures supplemented with ZnII, CdII, or CuII, and the purified metal–MT complexes have been thoroughly characterized by spectroscopic and spectrometric methods, leading to results that confirmed that Neritimorpha share Cd-selective MTs with Caenogastropoda and Heterobranchia, solving a so far unresolved question. NpeMTs show high coordinating preferences towards divalent metal ions, although one of them (NpeMT1) shares features with the so-called genuine Zn-thioneins, while the other (NpeMT2) exhibits a higher preference for Cd. The dissimilarities between the two isoforms let a window open to a new proposal of chemical MT classification.
Identified Three Interferon Induced Proteins as Novel Biomarkers of Human Ischemic Cardiomyopathy
Authors: Chen Cheng , Tian Jiao , He Zhicheng , Xiong Wenyong , He Yingying , Liu Shubai
Published: December 2021

Ischemic cardiomyopathy is the most frequent type of heart disease, and it is a major cause of myocardial infarction (MI) and heart failure (HF), both of which require expensive medical treatment. Precise biomarkers and therapy targets must be developed to enhance improve diagnosis and treatment. In this study, the transcriptional profiles of 313 patients’ left ventricle biopsies were obtained from the PubMed database, and functional genes that were significantly related to ischemic cardiomyopathy were screened using the Weighted Gene Co-Expression Network Analysis and protein–protein interaction (PPI) networks enrichment analysis. The rat myocardial infarction model was developed to validate these findings. Finally, the putative signature genes were blasted through the common Cardiovascular Disease Knowledge Portal to explore if they were associated with cardiovascular disorder. Three interferon stimulated genes (IFIT2, IFIT3 and IFI44L), as well as key pathways, have been identified as potential biomarkers and therapeutic targets for ischemic cardiomyopathy, and their alternations or mutations have been proven to be strongly linked to cardiac disorders. These novel signature genes could be utilized as bio-markers or potential therapeutic objectives in precise clinical diagnosis and treatment of ischemic cardiomyopathy.
Protocadherin-7 Regulates Osteoclast Differentiation through Intracellular SET-Binding Domain-Mediated RhoA and Rac1 Activation
Authors: Kim Hyunsoo , Takegahara Noriko , Choi Yongwon
Published: December 2021

Protocadherin-7 (Pcdh7) is a member of the non-clustered protocadherin δ1 subgroup of the cadherin superfamily. Although the cell-intrinsic role of Pcdh7 in osteoclast differentiation has been demonstrated, the molecular mechanisms of Pcdh7 regulating osteoclast differentiation remain to be determined. Here, we demonstrate that Pcdh7 contributes to osteoclast differentiation by regulating small GTPases, RhoA and Rac1, through its SET oncoprotein binding domain. Pcdh7 is associated with SET along with RhoA and Rac1 during osteoclast differentiation. Pcdh7-deficient (Pcdh7−/−) cells showed abolished RANKL-induced RhoA and Rac1 activation, and impaired osteoclast differentiation. Impaired osteoclast differentiation in Pcdh7−/− cells was restored by retroviral transduction of full-length Pcdh7 but not by a Pcdh7 mutant that lacks SET binding domain. The direct crosslink of the Pcdh7 intracellular region induced the activation of RhoA and Rac1, which was not observed when Pcdh7 lacks the SET binding domain. Additionally, retroviral transduction of the constitutively active form of RhoA and Rac1 completely restored the impaired osteoclast differentiation in Pcdh7−/− cells. Collectively, these results demonstrate that Pcdh7 controls osteoclast differentiation by regulating RhoA and Rac1 activation through the SET binding domain.