bluuebunny/crossref_metadata_2025 huggingface dataset:
“Not Alone in Loneliness”: A Qualitative Evaluation of a Program Promoting Social Capital among Lonely Older People in Primary Health Care
Authors: Coll-Planas Laura , Rodríguez-Arjona Dolors , Pons-Vigués Mariona , Nyqvist Fredrica , Puig Teresa , Monteserín Rosa
Published: May 2021

The weekly group-based program “Paths: from loneliness to participation” was conducted face-to-face over 15 sessions by nurses, social workers and volunteers in primary care in Catalonia (Spain) to alleviate loneliness among older people by promoting peer support and participation in community assets. We aimed at exploring participants’ experiences of loneliness and participation prior to the program and its perceived benefits. The qualitative design was descriptive-interpretative. Data were collected through three focus groups and 41 interviews applying a semistructured topic guide involving 26 older participants, six professionals and nine volunteers. Participant-observation of all sessions involved the 38 older people who started the program. A thematic content analysis was applied. Older persons with diverse profiles of loneliness and participation explained different degrees of decrease in loneliness, an increase in participation in local community assets, companionship, peer support and friendship, and an empowerment process. Successful cases reported improvements in mental wellbeing and recovering the sense that life was worth living. Loneliness persisted among some widowed participants and vulnerabilities hampered some benefits. Participants, professionals and volunteers reported different degrees of success in older people to alleviate loneliness by enhancing social relationships and activities through complex processes interrelated with health and socioeconomic factors.
Reply to Brzozek et al. Comment on “Choi et al. Cellular Phone Use and Risk of Tumors: Systematic Review and Meta-Analysis. Int. J. Environ. Res. Public Health 2020, 17, 8079”
Authors: Moskowitz Joel M. , Myung Seung-Kwon , Choi Yoon-Jung , Hong Yun-Chul
Published: May 2021

We appreciate Christopher Brzozek and his colleagues’ interest [...]
Analysis of the Relationship between the Psychological Well-Being, Emotional Intelligence, Willpower, and Job-Efficacy of Clinical Nurses: A Structural Model Application
Authors: Lee Jin-Hwa , Sim In-Ok
Published: May 2021

The aim of this study to discover the relationship between psychological well-being, emotional intelligence, willpower, and job-efficacy. The data were collected from 26 May to 30 May 2020 by distributing a questionnaire to 317 clinical nurses with six months of experience in a general hospital located in Seoul. Three hundred copies were collected and used for final data analysis. The results of the study verified that the direct factors of psychological well-being, emotional intelligence, and willpower affect the job-efficacy of clinical nurses and confirmed that emotional intelligence is a mediating factor between psychological well-being and job-efficacy. This study is meaningful in that it proves the necessity of establishing various curriculums focusing on these factors so that nursing students can best perform their duties as professional nurses. In particular, it is suggested that an educational program and curriculum be established that can strengthen the psychological well-being and enhance the emotional intelligence of nursing students. It is expected that such training will equip professional clinical nurses to effectively handle future work in their stress-filled field.
Searching for New Model of Digital Informatics for Human–Computer Interaction: Testing the Institution-Based Technology Acceptance Model (ITAM)
Authors: Kang Youngcheoul , Choi Nakbum , Kim Seoyong
Published: May 2021

The fourth industrial revolution has produced new information technology (IT) that is widely used in the healthcare industry. Although the nature of the institution affects IT adoption, the Technology Acceptance Model (TAM), a dominant theory, has dismissed its role and influence. Our research investigates how institutions influence the adoption of new IT by using the Institution-based Technology Acceptance Model (ITAM). We conducted an empirical test by using survey data collected from 300 employees in the public sector. Structural equation modeling was applied to test the proposed hypotheses. The results showed the total effect of institutions on the intention to use new IT is positive and significant. Second, IT adoption is not only affected by external institutions but also by type of institution; the external institution takes a greater role in inducing perceived usefulness, perceived ease of use, and intention to use than does the internal. Third, perceived ease of use and perceived usefulness play mediating roles between institution and IT adoption. Fourth, an alternative expanded model to which more individual and organizational factors were added confirmed the results of the base model. We concluded that institutions have a strong impact on the level of intention for IT use through perceived ease of use and perceived usefulness.
Sleep Duration Is Closely Associated with Suicidal Ideation and Suicide Attempt in Korean Adults: A Nationwide Cross-Sectional Study
Authors: Ko Yujin , Moon Jieun , Han Sangsoo
Published: May 2021

Introduction: Suicidal ideation and suicide attempts are major risk factors for suicidal death, and sleep problems are associated with an increased risk for mental disorders. We investigated the relationship between sleep duration and suicidal ideation and suicide attempts in a representative sample of the Korean general population from a nationwide survey. Methods: We analyzed data collected from the Korea National Health and Nutrition Examination Survey VI and VII (2013–2018). Suicidal ideation was identified via self-report, and we accessed suicide attempt history. Sleep duration was divided into three categories: short sleep duration (SSD) (≤5 h), normal sleep duration (NSD) (>5 and <9 h), and long sleep duration (LSD) (≥9 h). Sampling weights were applied to obtain estimates for the general Korean population. Results: Overall, 4015 (12.0%), 25,609 (76.5%), and 3857 (11.5%) participants were in the SSD, NSD, and LSD groups, respectively. Among these groups, 7.2%, 2.8%, and 3.3% reported suicidal ideation; while 1.2%, 0.4%, and 0.7% reported a history of suicide attempts. Multiple regression analyses revealed that SSD was significantly more strongly associated with suicidal ideation (adjusted odds ratio (AOR) 1.46, p < 0.001) and attempts (AOR 2.05, p = 0.003) than NSD. No association was found between LSD and suicidal ideation/attempts. Conclusion: Sleep duration is significantly associated with suicidal behavior, and SSD was particularly closely related with an increased risk for suicidal ideation and suicide attempt. Clinicians should carefully consider sleep duration in suicidal patients.
Classification and Prediction on the Effects of Nutritional Intake on Overweight/Obesity, Dyslipidemia, Hypertension and Type 2 Diabetes Mellitus Using Deep Learning Model: 4–7th Korea National Health and Nutrition Examination Survey
Authors: Kim Hyerim , Lim Dong Hoon , Kim Yoona
Published: May 2021

Few studies have been conducted to classify and predict the influence of nutritional intake on overweight/obesity, dyslipidemia, hypertension and type 2 diabetes mellitus (T2DM) based on deep learning such as deep neural network (DNN). The present study aims to classify and predict associations between nutritional intake and risk of overweight/obesity, dyslipidemia, hypertension and T2DM by developing a DNN model, and to compare a DNN model with the most popular machine learning models such as logistic regression and decision tree. Subjects aged from 40 to 69 years in the 4–7th (from 2007 through 2018) Korea National Health and Nutrition Examination Survey (KNHANES) were included. Diagnostic criteria of dyslipidemia (n = 10,731), hypertension (n = 10,991), T2DM (n = 3889) and overweight/obesity (n = 10,980) were set as dependent variables. Nutritional intakes were set as independent variables. A DNN model comprising one input layer with 7 nodes, three hidden layers with 30 nodes, 12 nodes, 8 nodes in each layer and one output layer with one node were implemented in Python programming language using Keras with tensorflow backend. In DNN, binary cross-entropy loss function for binary classification was used with Adam optimizer. For avoiding overfitting, dropout was applied to each hidden layer. Structural equation modelling (SEM) was also performed to simultaneously estimate multivariate causal association between nutritional intake and overweight/obesity, dyslipidemia, hypertension and T2DM. The DNN model showed the higher prediction accuracy with 0.58654 for dyslipidemia, 0.79958 for hypertension, 0.80896 for T2DM and 0.62496 for overweight/obesity compared with two other machine leaning models with five-folds cross-validation. Prediction accuracy for dyslipidemia, hypertension, T2DM and overweight/obesity were 0.58448, 0.79929, 0.80818 and 0.62486, respectively, when analyzed by a logistic regression, also were 0.52148, 0.66773, 0.71587 and 0.54026, respectively, when analyzed by a decision tree. This study observed a DNN model with three hidden layers with 30 nodes, 12 nodes, 8 nodes in each layer had better prediction accuracy than two conventional machine learning models of a logistic regression and decision tree.
Exposure to Organophosphate and Neonicotinoid Insecticides and Its Association with Steroid Hormones among Male Reproductive-Age Farmworkers in Northern Thailand
Authors: Suwannarin Neeranuch , Prapamontol Tippawan , Isobe Tomohiko , Nishihama Yukiko , Hashimoto Yuki , Mangklabruks Ampica , Pantasri Tawiwan , Chantara Somporn , Naksen Warangkana , Nakayama Shoji F.
Published: May 2021

Several studies indicated organophosphate (OP) and neonicotinoid (NEO) insecticides are endocrine disruptors; however, data are scarce. This cross-sectional study recruited 143 male farmworkers aged 18–40 years in Fang district, Chiang Mai province, northern Thailand. OP exposure was assessed by measuring urinary dialkylphosphate (DAPs) using a gas-chromatography flame photometric detector. Urinary NEOs, their metabolites (NEO/m) and serum steroid hormones were measured using liquid chromatography–tandem mass spectrometry. Characteristics of participants were determined by face-to-face interviews. DAPs and five NEO/m were detected in more than 60% of samples. The concentration of diethylphosphate was highest among DAP metabolites (geometric mean concentration (GM: 23.9 ng/mL) and the concentration of imidacloprid (IMI) was highest among NEO/m (GM: 17.4 ng/mL). Linear regression models showed that the IMI level was positively associated with testosterone, dehydrocorticosterone (DHC) and dehydroepiandrosterone (DHEA) levels. Imidacloprid-olefin and DHEA levels were positively associated. Thiamethoxam (THX) were inversely associated with DHC and deoxycorticosterone levels. Clothianidin (CLO), THX and N-desmethyl-acetamiprid levels were positively associated with the androstenedione level. CLO and THX levels were inversely associated with the cortisone level. In conclusion, the association between NEO insecticides exposure and adrenal androgens, glucocorticoids and mineralocorticoids, suggest potential steroidogenesis activities. Our findings warrant further investigation.
Utilisation of a Suite of Screening Tools to Determine Adverse Healthcare Outcomes in an Older Frail Population Admitted to a Community Virtual Ward
Authors: Lewis Clare , O’Caoimh Rónán , Patton Declan , O’Connor Tom , Moore Zena , Nugent Linda E.
Published: May 2021

Risk stratification to assess healthcare outcomes among older people is challenging due to the interplay of multiple syndromes and conditions. Different short risk-screening tools can assist but the most useful instruments to predict responses and outcomes following interventions are unknown. We examined the relationship between a suite of screening tools and risk of adverse outcomes (pre-determined clinical ‘decline’ i.e., becoming ‘unstable’ or ‘deteriorating’ at 60–90 days, and institutionalisation, hospitalisation and death at 120 days), among community dwellers (n = 88) after admission to a single-centre, Irish, Community Virtual Ward (CVW). The mean age of patients was 82.8 (±6.4) years. Most were severely frail, with mean Clinical Frailty Scale (CFS) scores of 6.8 ± 1.33. Several instruments were useful in predicting ‘decline’ and other healthcare outcomes. After adjustment for age and gender, higher frailty levels, odds ratio (OR) 3.29, (p = 0.002), impaired cognition (Mini Mental State Examination; OR 4.23, p < 0.001), lower mobility (modified FIM) (OR 3.08, p < 0.001) and reduced functional level (Barthel Index; OR 6.39, p < 0.001) were significantly associated with clinical ‘decline’ at 90 days. Prolonged (>30 s) TUG times (OR 1.27, p = 0.023) and higher CFS scores (OR 2.29, p = 0.045) were associated with institutionalisation. Only TUG scores were associated with hospitalisation and only CFS, MMSE and Barthel scores at baseline were associated with mortality. Utilisation of a multidimensional suite of risk-screening tools across a range of domains measuring frailty, mobility and cognition can help predict clinical ‘decline’ for an already frail older population. Their association with other outcomes was less useful. A better understanding of the utility of these instruments in vulnerable populations will provide a framework to inform the impact of interventions and assist in decision-making and anticipatory care planning for older patients in CVW models.
The Burnout Syndrome among Women Working in the Retail Network in Associations with Psychosocial Work Environment Factors
Authors: Kalinienė Gintarė , Lukšienė Dalia , Ustinavičienė Rūta , Škėmienė Lina , Januškevičius Vidmantas
Published: May 2021

The burnout syndrome is a significant occupational health problem in various employees’ populations. The aim of this study was to evaluate burnout level among retail network workers and its associations with psychosocial work environment. The cross-sectional epidemiological study was conducted on workers of one Lithuanian retail network (n = 254), where all respondents were women. In order to assess their occupational stress and burnout, two instruments were used: HSE management standards work-related stress indicator tool and Copenhagen burnout inventory (CBI). The statistical analysis showed high prevalence of burnout—the frequency of personal, work-related and client-related burnout was 53.5%, 66.5% and 55.5% respectively. The Spearman’s correlation analysis revealed that job demands, control manager’s support, coworkers’ support and relationships significantly associated with all burnout subscales. The multivariable logistic regression analysis was performed to determine the independent associations between HSE indicators and burnout subscales. The multivariate logistic regression model revealed that job demands and manager’s support were significant factors for all burnout dimensions. In conclusion, in order to reduce occupational burnout among employees working in retail companies, it would be useful for occupational interventions to focus on workload reduction and optimization, and for the human resources management strategy to focus on maintaining this.
The Differences in Clinical Presentation, Management, and Prognosis of Laboratory-Confirmed COVID-19 between Pregnant and Non-Pregnant Women: A Systematic Review and Meta-Analysis
Authors: Khan Durray Shahwar A. , Pirzada Areeba N. , Ali Anna , Salam Rehana A. , Das Jai K. , Lassi Zohra S.
Published: May 2021

Background: The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people across the globe. Previous coronavirus outbreaks led to worsened symptoms amongst pregnant women, suggesting that pregnant women are at greater risk. Objectives: Our aim is to investigate the differences in clinical presentation, management, and prognosis of COVID-19 infection in pregnant and non-pregnant women. Methods: We ran a search on electronic databases and analysis of the relevant articles was done using Revie Manager 5.4. Results: The review consists of nine studies comprising 591,058 women (28,797 pregnant and 562,261 non-pregnant), with most of the data derived from two large studies. The risk of experiencing fever (RR: 0.74; 95% CI: 0.64–0.85), headache (RR: 0.77; 95% CI: 0.74–0.79), myalgia (RR: 0.92; 95% CI: 0.89–0.95), diarrhea (RR: 0.40, 95% CI: 0.39–0.43), chest tightness (RR: 0.86; 95% CI: 0.77–0.95), and expectoration (RR: 0.45; 95% CI: 0.21–0.97) were greater amongst non-pregnant COVID-19-infected women. Pregnant women with COVID-19 were less likely to be obese (RR: 0.68; 95% CI: 0.63–0.73) or have a smoking history (RR: 0.32; 95% CI: 0.26–0.39). COVID-19-infected non-pregnant women had a higher frequency of comorbidity such as chronic cardiac disease (RR: 0.58; 95% CI: 0.44–0.77), renal disease (RR: 0.45; 95% CI: 0.29–0.71), and malignancy (RR: 0.82; 95% CI: 0.68–0.98), compared to COVID-19-infected pregnant women. The risk of ICU admission (RR: 2.26; 95% CI: 1.68–3.05) and requirement of invasive mechanical ventilation (RR: 2.68; 95% CI: 2.07–3.47) were significantly higher amongst pregnant women. Conclusions: Although the frequency of risk factors and the risk of experiencing clinical symptoms of COVID-19 were higher among non-pregnant women, COVID-19-infected pregnant women had a higher requirement of ICU admission and invasive mechanical ventilation compared to non-pregnant COVID-19-infected women. More well-conducted studies from varying contexts are needed to draw conclusions. Prospero registration: CRD42020204638.
Strength and Power Characteristics in National Amateur Rugby Players
Authors: Alonso-Aubin Diego Alexandre , Picón-Martínez Moisés , Chulvi-Medrano Iván
Published: May 2021

Rugby players need muscular strength and power to meet the demands of the sport; therefore, a proper assessment of the performance in rugby players should include both variables. The purpose of this study was to examine the strength and power characteristics (SPC) during the squat (SQ) and bench press (BP) in national amateur rugby players and to analyze gender- and position-related differences. A total of 47 players (30 males and 17 females; age: 25.56 ± 1.14 and 23.16 ± 1.38 years, respectively) participated in the study. The one repetition-maximum (1-RM) and SPC in SQ and BP were obtained using a Smith Machine. Then, subjects performed one set of five repetitions on the SQ and BP against six relative loads (30–40–50–60–70–80% 1-RM) using a linear transducer. Differences between genders were found in 1-RM for maximal power, kilograms lifted at maximal power, maximal power, maximal strength and maximal speed in BP (p < 0.00) and 1-RM, kilograms lifted at maximal power, maximal power, maximal strength and maximal speed in SQ (p < 0.00). Comparisons between variables in SQ and BP present a significant relationship (p < 0.01) in SQ and BP 1-RM with kilograms lifted at maximal power (r = 0.86 and r = 0.84), maximal strength (r = 0.53 and r = 0.92) and maximal power (r = 0.76 and r = 0.93). This study confirms the importance of the SPC assessment for training prescription in rugby amateur players.
Noise Disturbance and Potential Hearing Loss Due to Exposure of Dental Equipment in Flemish Dentists
Authors: Dierickx Michael , Verschraegen Suzanne , Wierinck Els , Willems Guy , van Wieringen Astrid
Published: May 2021

Long-term exposure to occupational noise is often associated with noise-induced hearing loss (NIHL) among dentists. This study aims to investigate potential hearing loss (HL) and self-reported annoyance as a result of exposure to noise produced by contemporary dental equipment. Methods: Three cohorts participated: 53 dentists with more than 5 years of service, 47 dentists with at most 5 years of service, and 53 pharmacists as controls, age and gender-matched to the first group. After the exclusion of one person, the hearing of 304 ears was screened with the Flemish version of the digit triplet in noise test (DTT). If screening failed, otoscopy and pure tone audiometry (PTA) were performed for both ears. Furthermore, general information, knowledge, exposure, annoyance, general health, and preventive measures were assessed with a custom-made questionnaire. Results: NIHL did not occur significantly more often with dentists than with controls. However, dentists revealed a significantly higher annoyance (related to the noise from their equipment) and reported more complaints than the pharmacists. All three groups indicated lack of knowledge on hearing care. Conclusions: While noise levels in contemporary dentistry are not harmful and do not induce NIHL, the sounds emitted by the devices are disturbing and affect mental health. This study calls for increased awareness of the consequences of sound exposure and stresses the need to monitor and protect the hearing of dentists regularly.
Transmembrane TNF and Its Receptors TNFR1 and TNFR2 in Mycobacterial Infections
Authors: Ruiz Andy , Palacios Yadira , Garcia Irene , Chavez-Galan Leslie
Published: May 2021

Tumor necrosis factor (TNF) is one of the main cytokines regulating a pro-inflammatory environment. It has been related to several cell functions, for instance, phagocytosis, apoptosis, proliferation, mitochondrial dynamic. Moreover, during mycobacterial infections, TNF plays an essential role to maintain granuloma formation. Several effector mechanisms have been implicated according to the interactions of the two active forms, soluble TNF (solTNF) and transmembrane TNF (tmTNF), with their receptors TNFR1 and TNFR2. We review the impact of these interactions in the context of mycobacterial infections. TNF is tightly regulated by binding to receptors, however, during mycobacterial infections, upstream activation signalling pathways may be influenced by key regulatory factors either at the membrane or cytosol level. Detailing the structure and activation pathways used by TNF and its receptors, such as its interaction with solTNF/TNFRs versus tmTNF/TNFRs, may bring a better understanding of the molecular mechanisms involved in activation pathways which can be helpful for the development of new therapies aimed at being more efficient against mycobacterial infections.
Effect of Pig-Adipose-Derived Stem Cells’ Conditioned Media on Skin Wound-Healing Characteristics In Vitro
Authors: Wiśniewska Joanna , Słyszewska Magda , Stałanowska Karolina , Walendzik Katarzyna , Kopcewicz Marta , Machcińska Sylwia , Gawrońska-Kozak Barbara
Published: May 2021

The primary mechanism by which adipose-derived stem cells (ASCs) exert their reparative or regenerative potential relies predominantly on paracrine action. Secretory abilities of ASCs have been found to be amplified by hypoxia pre-conditioning. This study investigates the impact of hypoxia (1% O2) on the secretome composition of pig ASCs (pASCs) and explores the effect of pASCs’ conditioned media (CM) on skin cell functions in vitro and the expression of markers attributed to wound healing. Exposure of pASCs to hypoxia increased levels of vascular endothelial growth factor (VEGF) in CM-Hyp compared to CM collected from the cells cultured in normoxia (CM-Nor). CM-Hyp promoted the migratory ability of pig keratinocytes (pKERs) and delayed migration of pig dermal fibroblasts (pDFs). Exposure of pKERs to either CM-Nor or CM-Hyp decreased the levels of pro-fibrotic indicators WNT10A and WNT11. Furthermore, CM-Hyp enhanced the expression of KRT14, the marker of the basal epidermis layer. In contrast, CM-Nor showed a stronger effect on pDFs manifested by increases in TGFB1, COL1A1, COL3A1, and FN1 mRNA expression. The formation of three-dimensional endothelial cell networks was improved in the presence of CM-Hyp. Overall, our results demonstrate that the paracrine activity of pASCs affects skin cells, and this property might be used to modulate wound healing.
Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives
Authors: Zhang Zuo-Peng , Zhong Ye , Han Zhen-Bin , Zhou Lin , Su Hua-Sheng , Wang Jian , Liu Yang , Cheng Mao-Sheng
Published: May 2021

A series of saccharide-modified thiadiazole sulfonamide derivatives has been designed and synthesized by the “tail approach” and evaluated for inhibitory activity against carbonic anhydrases II, IX, and XII. Most of the compounds showed high topological polar surface area (TPSA) values and excellent enzyme inhibitory activity. The impacts of some compounds on the viability of HT-29, MDA-MB-231, and MG-63 human cancer cell lines were examined under both normoxic and hypoxic conditions, and they showed certain inhibitory effects on cell viability. Moreover, it was found that the series of compounds had the ability to raise the pH of the tumor cell microenvironment. All the results proved that saccharide-modified thiadiazole sulfonamides have important research prospects for the development of CA IX inhibitors.
The Meiosis-Specific Crs1 Cyclin Is Required for Efficient S-Phase Progression and Stable Nuclear Architecture
Authors: Bustamante-Jaramillo Luisa F. , Ramos Celia , Martín-Castellanos Cristina
Published: May 2021

Cyclins and CDKs (Cyclin Dependent Kinases) are key players in the biology of eukaryotic cells, representing hubs for the orchestration of physiological conditions with cell cycle progression. Furthermore, as in the case of meiosis, cyclins and CDKs have acquired novel functions unrelated to this primal role in driving the division cycle. Meiosis is a specialized developmental program that ensures proper propagation of the genetic information to the next generation by the production of gametes with accurate chromosome content, and meiosis-specific cyclins are widespread in evolution. We have explored the diversification of CDK functions studying the meiosis-specific Crs1 cyclin in fission yeast. In addition to the reported role in DSB (Double Strand Break) formation, this cyclin is required for meiotic S-phase progression, a canonical role, and to maintain the architecture of the meiotic chromosomes. Crs1 localizes at the SPB (Spindle Pole Body) and is required to stabilize the cluster of telomeres at this location (bouquet configuration), as well as for normal SPB motion. In addition, Crs1 exhibits CDK(Cdc2)-dependent kinase activity in a biphasic manner during meiosis, in contrast to a single wave of protein expression, suggesting a post-translational control of its activity. Thus, Crs1 displays multiple functions, acting both in cell cycle progression and in several key meiosis-specific events.
Extracellular Vesicles as Potential Therapeutics for Inflammatory Diseases
Authors: Hwang Hee Sook , Kim Hyosuk , Han Geonhee , Lee Jong Won , Kim Kwangmeyung , Kwon Ick Chan , Yang Yoosoo , Kim Sun Hwa
Published: May 2021

Extracellular vesicles (EV) deliver cargoes such as nucleic acids, proteins, and lipids between cells and serve as an intercellular communicator. As it is revealed that most of the functions associated to EVs are closely related to the immune response, the important role of EVs in inflammatory diseases is emerging. EVs can be functionalized through EV surface engineering and endow targeting moiety that allows for the target specificity for therapeutic applications in inflammatory diseases. Moreover, engineered EVs are considered as promising nanoparticles to develop personalized therapeutic carriers. In this review, we highlight the role of EVs in various inflammatory diseases, the application of EV as anti-inflammatory therapeutics, and the current state of the art in EV engineering techniques.
Prognostic Role of Tumoral PD-L1 and IDO1 Expression, and Intratumoral CD8+ and FoxP3+ Lymphocyte Infiltrates in 132 Primary Cutaneous Merkel Cell Carcinomas
Authors: Donizy Piotr , Wu Cheng-Lin , Kopczynski Janusz , Pieniazek Malgorzata , Biecek Przemyslaw , Ryś Janusz , Hoang Mai P.
Published: May 2021

The association of immune markers and clinicopathologic features and patient outcome has not been extensively studied in Merkel cell carcinoma (MCC). We correlated tumoral PD-L1 and IDO1 expression, and intratumoral CD8+ and FoxP3+ lymphocytes count with clinicopathologic variables, Merkel cell polyomavirus (MCPyV) status, and patient outcomes in a series of 132 MCC. By univariate analyses, tumoral PD-L1 expression >1% and combined tumoral PD-L1 >1% and high intratumoral FoxP3+ lymphocyte count correlated with improved overall survival (OS) (p = 0.016, 0.0072), MCC-specific survival (MSS) (p = 0.019, 0.017), and progression-free survival (PFS) (p = 0.043, 0.004, respectively). High intratumoral CD8+ and FoxP3+ lymphocyte count correlated with longer MSS (p = 0.036) and improved PFS (p = 0.047), respectively. Ulceration correlated with worse OS and worse MSS. Age, male gender, and higher stage (3 and 4) significantly correlated with worse survival. MCPyV positivity correlated with immune response. By multivariate analyses, only ulceration and age remained as independent predictors of worse OS; gender and stage remained for shorter PFS. Tumoral PD-L1 expression and increased density of intratumoral CD8+ lymphocytes and FoxP+ lymphocytes may represent favorable prognosticators in a subset of MCCs. Tumoral PD-L1 expression correlated with intratumoral CD8+ and FoxP3+ lymphocytes, which is supportive of an adaptive immune response.
Gene Therapy for Mucopolysaccharidosis Type II—A Review of the Current Possibilities
Authors: Zapolnik Paweł , Pyrkosz Antoni
Published: May 2021

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder based on a mutation in the IDS gene that encodes iduronate 2-sulphatase. As a result, there is an accumulation of glycosaminoglycans—heparan sulphate and dermatan sulphate—in almost all body tissues, which leads to their dysfunction. Currently, the primary treatment is enzyme replacement therapy, which improves the course of the disease by reducing somatic symptoms, including hepatomegaly and splenomegaly. The enzyme, however, does not cross the blood–brain barrier, and no improvement in the function of the central nervous system has been observed in patients with the severe form of the disease. An alternative method of treatment that solves typical problems of enzyme replacement therapy is gene therapy, i.e., delivery of the correct gene to target cells through an appropriate vector. Much progress has been made in applying gene therapy for MPS II, from cellular models to human clinical trials. In this article, we briefly present the history and basics of gene therapy and discuss the current state of knowledge about the methods of this therapy in mucopolysaccharidosis type II.
The Crossroads between Host Copper Metabolism and Influenza Infection
Authors: Puchkova Ludmila V. , Kiseleva Irina V. , Polishchuk Elena V. , Broggini Massimo , Ilyechova Ekaterina Yu.
Published: May 2021

Three main approaches are used to combat severe viral respiratory infections. The first is preemptive vaccination that blocks infection. Weakened or dead viral particles, as well as genetic constructs carrying viral proteins or information about them, are used as an antigen. However, the viral genome is very evolutionary labile and changes continuously. Second, chemical agents are used during infection and inhibit the function of a number of viral proteins. However, these drugs lose their effectiveness because the virus can rapidly acquire resistance to them. The third is the search for points in the host metabolism the effect on which would suppress the replication of the virus but would not have a significant effect on the metabolism of the host. Here, we consider the possibility of using the copper metabolic system as a target to reduce the severity of influenza infection. This is facilitated by the fact that, in mammals, copper status can be rapidly reduced by silver nanoparticles and restored after their cancellation.
Expression of Cholinergic Markers and Characterization of Splice Variants during Ontogenesis of Rat Dorsal Root Ganglia Neurons
Authors: Corsetti Veronica , Perrone-Capano Carla , Salazar Intriago Michael Sebastian , Botticelli Elisabetta , Poiana Giancarlo , Augusti-Tocco Gabriella , Biagioni Stefano , Tata Ada Maria
Published: May 2021

Dorsal root ganglia (DRG) neurons synthesize acetylcholine (ACh), in addition to their peptidergic nature. They also release ACh and are cholinoceptive, as they express cholinergic receptors. During gangliogenesis, ACh plays an important role in neuronal differentiation, modulating neuritic outgrowth and neurospecific gene expression. Starting from these data, we studied the expression of choline acetyltransferase (ChAT) and vesicular ACh transporter (VAChT) expression in rat DRG neurons. ChAT and VAChT genes are arranged in a “cholinergic locus”, and several splice variants have been described. Using selective primers, we characterized splice variants of these cholinergic markers, demonstrating that rat DRGs express R1, R2, M, and N variants for ChAT and V1, V2, R1, and R2 splice variants for VAChT. Moreover, by RT-PCR analysis, we observed a progressive decrease in ChAT and VAChT transcripts from the late embryonic developmental stage (E18) to postnatal P2 and P15 and in the adult DRG. Interestingly, Western blot analyses and activity assays demonstrated that ChAT levels significantly increased during DRG ontogenesis. The modulated expression of different ChAT and VAChT splice variants during development suggests a possible differential regulation of cholinergic marker expression in sensory neurons and confirms multiple roles for ACh in DRG neurons, both in the embryo stage and postnatally.
Achievements in Thermosensitive Gelling Systems for Rectal Administration
Authors: Bialik Maria , Kuras Marzena , Sobczak Marcin , Oledzka Ewa
Published: May 2021

Rectal drug delivery is an effective alternative to oral and parenteral treatments. This route allows for both local and systemic drug therapy. Traditional rectal dosage formulations have historically been used for localised treatments, including laxatives, hemorrhoid therapy and antipyretics. However, this form of drug dosage often feels alien and uncomfortable to a patient, encouraging refusal. The limitations of conventional solid suppositories can be overcome by creating a thermosensitive liquid suppository. Unfortunately, there are currently only a few studies describing their use in therapy. However, recent trends indicate an increase in the development of this modern therapeutic system. This review introduces a novel rectal drug delivery system with the goal of summarising recent developments in thermosensitive liquid suppositories for analgesic, anticancer, antiemetic, antihypertensive, psychiatric, antiallergic, anaesthetic, antimalarial drugs and insulin. The report also presents the impact of various types of components and their concentration on the properties of this rectal dosage form. Further research into such formulations is certainly needed in order to meet the high demand for modern, efficient rectal gelling systems. Continued research and development in this field would undoubtedly further reveal the hidden potential of rectal drug delivery systems.
An Overview on Dietary Polyphenols and Their Biopharmaceutical Classification System (BCS)
Authors: Truzzi Francesca , Tibaldi Camilla , Zhang Yanxin , Dinelli Giovanni , D′Amen Eros
Published: May 2021

Polyphenols are natural organic compounds produced by plants, acting as antioxidants by reacting with ROS. These compounds are widely consumed in daily diet and many studies report several benefits to human health thanks to their bioavailability in humans. However, the digestion process of phenolic compounds is still not completely clear. Moreover, bioavailability is dependent on the metabolic phase of these compounds. The LogP value can be managed as a simplified measure of the lipophilicity of a substance ingested within the human body, which affects resultant absorption. The biopharmaceutical classification system (BCS), a method used to classify drugs intended for gastrointestinal absorption, correlates the solubility and permeability of the drug with both the rate and extent of oral absorption. BCS may be helpful to measure the bioactive constituents of foods, such as polyphenols, in order to understand their nutraceutical potential. There are many literature studies that focus on permeability, absorption, and bioavailability of polyphenols and their resultant metabolic byproducts, but there is still confusion about their respective LogP values and BCS classification. This review will provide an overview of the information regarding 10 dietarypolyphenols (ferulic acid, chlorogenic acid, rutin, quercetin, apigenin, cirsimaritin, daidzein, resveratrol, ellagic acid, and curcumin) and their association with the BCS classification.
AR-V7 in Metastatic Prostate Cancer: A Strategy beyond Redemption
Authors: Sobhani Navid , Neeli Praveen Kumar , D’Angelo Alberto , Pittacolo Matteo , Sirico Marianna , Galli Ilaria Camilla , Roviello Giandomenico , Nesi Gabriella
Published: May 2021

Metastatic prostate cancer is the most common cancer in males and the fifth cause of cancer mortality worldwide. Despite the major progress in this field, leading to the approval of novel anti-androgens, the prognosis is still poor. A significant number of patients acquire an androgen receptor splice variant 7 (AR-V7), which is constitutively activated and lacks the ligand-binding domain (LBD) while maintaining the nuclear localization signal and DNA-binding domain (DBD). This conformational change, even in the absence of the ligand, allows its retention within the nucleus, where it acts as a transcription factor repressing crucial tumor suppressor genes. AR-V7 is an important oncogenic driver and plays a role as an early diagnostic and prognostic marker, as well as a therapeutic target for antagonists such as niclosamide and TAS3681. Anti-AR-V7 drugs have shown promise in recent clinical investigations on this subset of patients. This mini-review focuses on the relevance of AR-V7 in the clinical manifestations of castration-resistant prostate cancer (CRPC) and summarizes redemptive therapeutic strategies.
The Emerging Roles of JNK Signaling in Drosophila Stem Cell Homeostasis
Authors: Herrera Salvador C. , Bach Erika A.
Published: May 2021

The Jun N-terminal kinase (JNK) pathway is an evolutionary conserved kinase cascade best known for its roles during stress-induced apoptosis and tumor progression. Recent findings, however, have identified new roles for this pleiotropic pathway in stem cells during regenerative responses and in cellular plasticity. Here, we provide an overview of recent findings about the new roles of JNK signaling in stem cell biology using two well-established Drosophila models: the testis and the intestine. We highlight the pathway’s roles in processes such as proliferation, death, self-renewal and reprogramming, and discuss the known parallels between flies and mammals.
Simulating Peptide Monolayer Formation: GnRH-I on Silica
Authors: Pujol-Navarro Neret , Kubiak-Ossowska Karina , Ferro Valerie , Mulheran Paul
Published: May 2021

Molecular dynamics (MD) simulations can provide a detailed view of molecule behaviour at an atomic level, which can be useful when attempting to interpret experiments or design new systems. The decapeptide gonadotrophin-releasing hormone I (GnRH-I) is known to control fertility in mammals for both sexes. It was previously shown that inoculation with silica nanoparticles (SiNPs) coated with GnRH-I makes an effective anti-fertility vaccine due to how the peptide adsorbs to the nanoparticle and is presented to the immune system. In this paper, we develop and employ a protocol to simulate the development of a GnRH-I peptide adlayer by allowing peptides to diffuse and adsorb in a staged series of trajectories. The peptides start the simulation in an immobile state in solution above the model silica surface, and are then released sequentially. This facile approach allows the adlayer to develop in a natural manner and appears to be quite versatile. We find that the GnRH-I adlayer tends to be sparse, with electrostatics dominating the interactions. The peptides are collapsed to the surface and are seemingly free to interact with additional solutes, supporting the interpretations of the GNRH-I/SiNP vaccine system.
Neuroprotection: Rescue from Neuronal Death in the Brain
Authors: Lee Bae Hwan
Published: May 2021

The brain plays important roles in mental processing and in controlling other bodily organs [...]
Comparative Analysis of Mitochondrial Genome Features among Four Clonostachys Species and Insight into Their Systematic Positions in the Order Hypocreales
Authors: Zhao Zhiyuan , Zhu Kongfu , Tang Dexiang , Wang Yuanbing , Wang Yao , Zhang Guodong , Geng Yupeng , Yu Hong
Published: May 2021

The mycoparasite fungi of Clonostachys have contributed to the biological control of plant fungal disease and nematodes. The Clonostachys fungi strains were isolated from Ophiocordyceps highlandensis, Ophiocordycepsnigrolla and soil, which identified as Clonostachyscompactiuscula, Clonostachysrogersoniana, Clonostachyssolani and Clonostachys sp. To explore the evolutionary relationship between the mentioned species, the mitochondrial genomes of four Clonostachys species were sequenced and assembled. The four mitogenomes consisted of complete circular DNA molecules, with the total sizes ranging from 27,410 bp to 42,075 bp. The GC contents, GC skews and AT skews of the mitogenomes varied considerably. Mitogenomic synteny analysis indicated that these mitogenomes underwent gene rearrangements. Among the 15 protein-coding genes within the mitogenomes, the nad4L gene exhibited the least genetic distance, demonstrating a high degree of conservation. The selection pressure analysis of these 15 PCGs were all below 1, indicating that PCGs were subject to purifying selection. Based on protein-coding gene calculation of the significantly supported topologies, the four Clonostachys species were divided into a group in the phylogenetic tree. The results supplemented the database of mitogenomes in Hypocreales order, which might be a useful research tool to conduct a phylogenetic analysis of Clonostachys. Additionally, the suitable molecular marker was significant to study phylogenetic relationships in the Bionectriaceae family.
Epithelial–Mesenchymal Transition (EMT) Induced by TGF-β in Hepatocellular Carcinoma Cells Reprograms Lipid Metabolism
Authors: Soukupova Jitka , Malfettone Andrea , Bertran Esther , Hernández-Alvarez María Isabel , Peñuelas-Haro Irene , Dituri Francesco , Giannelli Gianluigi , Zorzano Antonio , Fabregat Isabel
Published: May 2021

(1) Background: The transforming growth factor (TGF)-β plays a dual role in liver carcinogenesis. At early stages, it inhibits cell growth and induces apoptosis. However, TGF-β expression is high in advanced stages of hepatocellular carcinoma (HCC) and cells become resistant to TGF-β induced suppressor effects, responding to this cytokine undergoing epithelial–mesenchymal transition (EMT), which contributes to cell migration and invasion. Metabolic reprogramming has been established as a key hallmark of cancer. However, to consider metabolism as a therapeutic target in HCC, it is necessary to obtain a better understanding of how reprogramming occurs, which are the factors that regulate it, and how to identify the situation in a patient. Accordingly, in this work we aimed to analyze whether a process of full EMT induced by TGF-β in HCC cells induces metabolic reprogramming. (2) Methods: In vitro analysis in HCC cell lines, metabolomics and transcriptomics. (3) Results: Our findings indicate a differential metabolic switch in response to TGF-β when the HCC cells undergo a full EMT, which would favor lipolysis, increased transport and utilization of free fatty acids (FFA), decreased aerobic glycolysis and an increase in mitochondrial oxidative metabolism. (4) Conclusions: EMT induced by TGF-β in HCC cells reprograms lipid metabolism to facilitate the utilization of FFA and the entry of acetyl-CoA into the TCA cycle, to sustain the elevated requirements of energy linked to this process.
Deep Learning-Based Advances in Protein Structure Prediction
Authors: Pakhrin Subash C. , Shrestha Bikash , Adhikari Badri , KC Dukka B.
Published: May 2021

Obtaining an accurate description of protein structure is a fundamental step toward understanding the underpinning of biology. Although recent advances in experimental approaches have greatly enhanced our capabilities to experimentally determine protein structures, the gap between the number of protein sequences and known protein structures is ever increasing. Computational protein structure prediction is one of the ways to fill this gap. Recently, the protein structure prediction field has witnessed a lot of advances due to Deep Learning (DL)-based approaches as evidenced by the success of AlphaFold2 in the most recent Critical Assessment of protein Structure Prediction (CASP14). In this article, we highlight important milestones and progresses in the field of protein structure prediction due to DL-based methods as observed in CASP experiments. We describe advances in various steps of protein structure prediction pipeline viz. protein contact map prediction, protein distogram prediction, protein real-valued distance prediction, and Quality Assessment/refinement. We also highlight some end-to-end DL-based approaches for protein structure prediction approaches. Additionally, as there have been some recent DL-based advances in protein structure determination using Cryo-Electron (Cryo-EM) microscopy based, we also highlight some of the important progress in the field. Finally, we provide an outlook and possible future research directions for DL-based approaches in the protein structure prediction arena.
DyP-Type Peroxidases: Recent Advances and Perspectives
Authors: Sugano Yasushi , Yoshida Toru
Published: May 2021

In this review, we chart the major milestones in the research progress on the DyP-type peroxidase family over the past decade. Though mainly distributed among bacteria and fungi, this family actually exhibits more widespread diversity. Advanced tertiary structural analyses have revealed common and different features among members of this family. Notably, the catalytic cycle for the peroxidase activity of DyP-type peroxidases appears to be different from that of other ubiquitous heme peroxidases. DyP-type peroxidases have also been reported to possess activities in addition to peroxidase function, including hydrolase or oxidase activity. They also show various cellular distributions, functioning not only inside cells but also outside of cells. Some are also cargo proteins of encapsulin. Unique, noteworthy functions include a key role in life-cycle switching in Streptomyces and the operation of an iron transport system in Staphylococcus aureus, Bacillus subtilis and Escherichia coli. We also present several probable physiological roles of DyP-type peroxidases that reflect the widespread distribution and function of these enzymes. Lignin degradation is the most common function attributed to DyP-type peroxidases, but their activity is not high compared with that of standard lignin-degrading enzymes. From an environmental standpoint, degradation of natural antifungal anthraquinone compounds is a specific focus of DyP-type peroxidase research. Considered in its totality, the DyP-type peroxidase family offers a rich source of diverse and attractive materials for research scientists.