bluuebunny/crossref_metadata_2025 huggingface dataset:
Validity and Reliability of a COVID-19 Stigma Scale Using Exploratory and Confirmatory Factor Analysis in a Sample of Egyptian Physicians: E16-COVID19-S
Authors: Mostafa Aya , Mostafa Nayera S. , Ismail Nashwa
Published: May 2021

Introduction: To date, a universal validated and specific tool for assessing coronavirus disease 2019 (COVID-19) stigma among healthcare workers is lacking. We adapted a SARS stigma scale that was developed using the Berger HIV scale for use as a COVID-19 stigma scale and evaluated its psychometric properties among Egyptian physicians. Methods: We administered the 17-item SARS stigma scale in an anonymous online questionnaire among 509 Egyptian physicians recruited via convenience sampling during a cross-sectional study in June 2020. Exploratory factor analysis was performed on half of the sample. Confirmatory factor analysis of the resulting model was done using structural equation modeling on the other half. Scale reliability was examined using Cronbach’s alpha for internal consistency. Convergent construct validity was assessed using regression models to examine the association between the adapted COVID-19 stigma scale and relevant factors. Results: Exploratory factor analysis yielded 16 items (E16-COVID19-S) that supported a three-factor structure: personalized stigma (8 items); concerns of disclosure and public attitudes (5 items); and negative experiences (3 items). Cronbach’s α was 0.909 for the total scale and 0.907, 0.663, and 0.789 for the three subscales. E16-COVID19-S was confirmed to have good model fit (comparative fit index = 0.964; root mean squared error of approximation = 0.056). E16-COVID19-S was independently associated with physicians’ younger age, lower qualification, working in an isolation hospital, and self-stigma, whether the scale was treated as categorical or continuous. Conclusions: E16-COVID19-S exhibited good internal consistency and construct validity among this sample of Egyptian physicians. These adequate psychometric properties make the E16-COVID19-S scale appropriate for use by researchers and practitioners.
Age and Sex-Related Differences in the Tongue Pressure Generated during Maximum Isometric and Swallowing Tasks by Healthy Chinese Adults
Authors: Lin Wen-Yu , Chen Yu-Mei , Wu Kuen-Ming , Chen Pei-Kai , Hwu Yueh-Juen
Published: May 2021

The aims of this prospective observational study were to investigate age, sex, and factors related to the tongue pressure generated. A correlational research design was used. A total of 150 Chinese people who had a normal swallowing condition were enrolled by convenience sampling. Pressure was measured for each participant during maximum isometric press tasks, as well as for saliva and water swallows (5 mL) at the anterior and posterior tongue. The results illustrated that age has an impact on anterior tongue pressure (r = −0.22), posterior tongue pressure (r = −0.26); however, it does not have an impact on the swallowing pressure (SP) of the tongue. Sex differences were noted; males demonstrated a greater strength of the anterior tongue. There was a significant correlation between BMI and the maximum isometric pressure of the anterior tongue (MIPant). The pressures between anterior and posterior tongue were not significantly different in the maximum isometric or swallowing tasks. There were significant differences among the maximum isometric pressure (MIP), saliva swallowing pressure, and water swallowing pressure. The MIP generated was greater than the pressure in the swallowing tasks for the younger groups of both sexes. The study supplement the exploration of age-and-sex related differences and the interaction of sex and age in tongue pressure.
Musculoskeletal Pain in Gymnasts: A Retrospective Analysis on a Cohort of Professional Athletes
Authors: Farì Giacomo , Fischetti Francesco , Zonno Alessandra , Marra Francesco , Maglie Alessia , Bianchi Francesco Paolo , Messina Giuseppe , Ranieri Maurizio , Megna Marisa
Published: May 2021

Gymnastics athletes are exposed to a high risk of injury, but also of developing musculoskeletal pain. These data are still little investigated in the available scientific literature. An online survey was distributed to 79 professional athletes who practiced artistic and rhythmic gymnastics. The survey collected demographic and anthropometric data, information about the sport practice, the training sessions, the prevalence of musculoskeletal pain gymnastics-related, and lifestyle habits. Musculoskeletal pain had a high prevalence, involving 65 of 79 athletes (82.3%). A significant correlation was found between musculoskeletal pain and the duration of sports practice, both for general pain (p = 0.041) and for specific districts: right wrist pain (p = 0.031), left wrist pain (p = 0.028), right shoulder (p = 0.039), left hip (p = 0.031), right thigh (p = 0.031), and left knee (p = 0.005). Another statistical association was found between right wrist pain and BMI (p = 0.001), and hip pain and BMI (p = 0.030). Hours spent in a sitting position were also correlated with the incidence of pain (p = 0.045). Wrist pain and right shoulder pain had a statistically significant association with the age of the athletes (right wrist pain: p = 0.038; left wrist pain: p = 0.004; right shoulder pain: p = 0.035). The more the gymnasts practice this sport, the more likely they are to develop musculoskeletal pain. Increased age and a higher BMI, as well as daily prolonged sitting position, seem to be potential risk factors for the onset of musculoskeletal pain. Future studies could plan training strategies aimed at preventing musculoskeletal pain associated with gymnastics, in order to promote its further spread.
Prevalence of High HDL Cholesterol and Its Associated Factors Among Tunisian Women of Childbearing Age: A Cross-Sectional Study
Authors: Ben Cherifa Fatma , El Ati Jalila , Doggui Radhouene , El Ati-Hellal Myriam , Traissac Pierre
Published: May 2021

The protective role of high high-density lipoprotein cholesterol (HDL-C) against cardiovascular risk has been questioned recently. Due to the increasing trend of cardiovascular diseases (CVD) in Tunisia, this study aimed to determine the prevalence of high HDL-C and its associated factors in Tunisian women of childbearing age. A cross-sectional survey was conducted among a subsample of 1689 women, aged 20 to 49 years, in the Great Tunis region. Data on socio-demographic and lifestyle factors were collected by a questionnaire. Overall adiposity was assessed by body mass index (BMI). All biological variables were assayed in blood samples coated with anticoagulant ethylene diamine tetra acetic acid (EDTA) by enzymatic methods. Stata software (2015) was used for data management and statistical analysis. High HDL-C values were recorded in 26.6% of selected women. After adjustment for all socio-demographic and lifestyle factors, age, hypertension, and smoking were negatively associated with high HDL-C levels, while family history of cancer was positively associated with high HDL-C in women. An additional investigation on the relationship between high HDL-C and cancer risk should be performed due to controversial results.
The Use of Diagnosis-Related Group-Based Reimbursement in the Czech Hospital Care System
Authors: Kotherová Zuzana , Caithamlová Martina , Nemec Juraj , Dolejšová Kateřina
Published: May 2021

(1) Background: Diagnosis-Related Groups (DRG), one possibility of a hospital payment system, are currently used in most European countries. Introduced to the Czech system in the 1990s, the DRGs are currently used mainly for care reporting and partly for reimbursement. According to most experts, the use of DRG remain controversial. The goal of this paper was to study the effects of the current Czech DRG system on hospitals financing and, on this basis, to propose possible changes to the reimbursement mechanism in the Czech Republic. (2) Methods: Qualitative research methods were used for evaluating DRG mechanisms of application in three selected healthcare establishments in the CR in the period of 2012–2018. (3) Results: Our study shows that the current implementation of the DRG system is set up in a way that is very similar to traditional flat rates and is unlikely to yield major positive effects of the DRG mechanism, such as predictability of payments for hospitalisation cases, care quality and efficiency and transparent financing. (4) Conclusions: Based on our results, deep systemic change of the reimbursement mechanism in the Czech Republic is necessary. We propose five partial measures leading to the cultivation of the Czech DRG.
Special Issue on the Effects of Prenatal Smoking/Nicotine Exposure on the Child’s Health
Authors: Ekblad Mikael O. , Blanc Julie , Berlin Ivan
Published: May 2021

Smoking increases the risk of negative pregnancy and perinatal outcomes and may have negative effects on a child’s short and long-term health [...]
The Physio-Psychological Effect of Forest Therapy Programs on Juvenile Probationers
Authors: Jeon Jin Young , Kim In Ok , Yeon Poung-sik , Shin Won Sop
Published: May 2021

The study aimed to investigate the psychological and physiological effects of forest therapy programs on adolescents under probation. Fifty probationary teenagers from the Ministry of Gyeonggi Justice Compliance Support Center participated in the study. The study explored the effectiveness of a nonrandomized control group pretest–posttest design forest therapy program. The forest therapy program was conducted for two days and one night for the experimental groups (N = 33), who participated in the forest therapy program, and the control group (N = 17), who received two days of attendance center orders program in the lecture room of the Ministry of Gyeonggi Justice Compliance Support Center. As a result, adolescents under probation who participated in forest therapy programs had a beneficial effect on psychological well-being (K-WBMMS) and HRV’s HF (high frequency) and LF/HF (A ratio of Low Frequency to High Frequency) compared to those who received the general attendance center orders program. These results support that forest therapy programs play a positive role in the psychological and physiological effects of probationary adolescents and can affect the diversity of rehabilitation programs for probationary adolescents.
Effects of Vertical Lifting Distance on Upper-Body Muscle Fatigue
Authors: Fang Nianli , Zhang Chang , Lv Jian
Published: May 2021

Manual material handling (MMH) is commonly demanded in the manufacturing industry. Occupational muscle fatigue of the arm, shoulder, and back, which arise from MMH tasks, can cause work absences and low efficiency. The available literature presents the lack of the fatigue comparison between targeted muscles, on the same part or on different parts. The main aim of the present study was to evaluate and compare the fatigue of upper-body muscles during repetitive bending tasks, an experiment involving 12 male subjects has been conducted to simulate material handling during furniture board drilling. The vertical lifting distance was chosen to be the single independent variable, and the three levels were 0, 250, and 500 mm. Surface electromyography (sEMG) was used to measure the muscle fatigue of the biceps brachii, upper trapezius, and multifidus, while the sEMG parameters, including the normalized electromyographic amplitude (Normalized EA) and mean power frequency (MPF), of the target muscles were analyzed. The experimental results reveal that during the manual handling tasks, the biceps brachii was the most relaxed muscle, contributing the least muscle tension, while the multifidus was the most easily fatigued muscle. Furthermore, the EMG MPF fatigue threshold (MPFFT) of multifidus muscle tension was tested to estimate its maximum workload in the long-term muscle contraction. In conclusion, bending angle should be maintained to a small range or bending should even be avoided during material-handling tasks.
Sociopolitical Approach to the Launch History of the KBO League: Application of Complex System Paradigm
Authors: Bing Won-Chul
Published: May 2021

The Korean Baseball Organization (KBO) League is a sports culture that Koreans love and enjoy most. However, the launch of the KBO League is related to political issues in Korea. The purpose of this study is to explain the launch history of the KBO league through a sociopolitical approach. The history of the KBO league was explained by applying a complex paradigm that explains sociocultural phenomena from a new perspective. This study used historical analysis, a qualitative study approach. Literature related to Korean professional baseball, complex system theory, sports, and politics were reviewed. This study introduces the characteristics and theory of the complex system paradigm and analyzes the history of the KBO League based on this theory. The edge of chaos, bifurcation point, positive feedback, emergence of the theory of complex system are used as elements of an overall theoretical framework to analyze the history and development of the KBO league. The study results are explained in four frameworks. First, the KBO was launched on the edge of chaos, or in the midst of social chaos provoked by Chun Doo-Hwan, who seized power through a military coup. Second, the Chun Doo-Hwan regime launched the professional baseball league to divert the public’s attention from politics to sports and provided support to construct baseball fields as venues for the national pastime. The Chun Doo-Hwan regime’s appeasement policy became a bifurcation point, which promoted the launch of the professional baseball league. Third, from the viewpoint of the complex system paradigm, the launch of the Korean baseball league was enabled by the positive feedback of the Korea professional baseball promotion committee, established in 1975 under the initiative of Korean American businessman Hong Yoon-Hee. Fourth, the Korean professional baseball league led to the emergence of the consumption culture of professional sports, and it became a national leisure and a crucial part of Korea’s sports culture. In terms of sociopolitical, the KBO League started in the dark of Korean society, but it is becoming a vitality for Korean sports culture and health.
How Loneliness Worked on Suicidal Ideation among Chinese Nursing Home Residents: Roles of Depressive Symptoms and Resilience
Authors: Yang Yang , Wang Rui , Zhang Dan , Zhao Xia , Su Yonggang
Published: May 2021

Suicide in later life is becoming severe under rapid population aging, especially for nursing home residents. Loneliness, an increasingly represented issue among nursing home residents, is found to be a risk factor for depressive symptoms. Both loneliness and depressive symptoms may contribute to the development of suicidal ideation. According to the Protective Factor Model, resilience can act as a moderating role interacting with risk factors to buffer the negative effects on the outcome. The present study aimed to assess the mediating role of depressive symptoms and the moderating effect of resilience on the risk factors of suicidal ideation to attenuate the adverse contribution among nursing home residents. A total of 538 nursing home residents participated in this cross-sectional study, and their suicidal ideation, resilience, loneliness, and depressive symptoms were measured. The mediating effect and moderated mediation model were tested using the Macro Process of SPSS 21.0. Statistics showed that 19.7% of participants had suicidal ideation. The mediating model (H1: B = 0.477, p < 0.001; H2: B = 0.325, p < 0.001; H3: B = 0.308, p < 0.001) and the moderating effect of resilience interacting loneliness (H4: B = −0.133, p < 0.001; H6: B = −0.109, p < 0.001) and depressive symptoms (H5: B = −0.077, p < 0.001) were statistically significant. The findings indicated the protective effect of resilience in alleviating the negative influence of risk factors for suicidal ideation, suggesting that positive psychological interventions for resilience building might be effective in suicide prevention among nursing home residents.
Workplace Health in Kentucky: A Statewide Comparison
Authors: Macy Gretchen , Basham Jacqueline , Watkins Cecilia , Golla Vijay
Published: May 2021

The objectives of this study were to assess the state of Kentucky’s workplace health promotion and occupational safety and health programs, to ensure the ability to comprehend any possible trends over the past six years in the state’s progress in offering workplace health promotion and health protection programs, to compare the results of this survey with the 2013 Kentucky state-wide assessment, and to identify gaps in Kentucky’s workplace health promotion and occupational safety and health based on Total Worker Health® (TWH) concepts. Using Qualtrics research software, the Workplace Health in America assessment was sent to companies located in Kentucky and having 10 or more employees. Participants were identified using Dun and Bradstreet’s Hoover’s database. The results showed that, as with the 2013 survey, larger workplaces significantly were more likely to offer workplace health promotion programs than smaller companies (X2 = 24.30; p < 0.001). However, more companies (78%) reported offering programs compared to the 2013 assessment (49%). Given the results of the current study as compared to the statewide assessment conducted in 2013, Kentucky’s WHP is moving in a positive direction; yet, there is still much to be done. There remains a strong need to provide cost-effective and accessible resources for all elements of TWH to small workplaces.
Treadmill and Running Speed Effects on Acceleration Impacts: Curved Non-Motorized Treadmill vs. Conventional Motorized Treadmill
Authors: Encarnación-Martínez Alberto , Catalá-Vilaplana Ignacio , Berenguer-Vidal Rafael , Sanchis-Sanchis Roberto , Ochoa-Puig Borja , Pérez-Soriano Pedro
Published: May 2021

An increase in the popularity of running can be seen over the last decades, with a large number of injuries on it. Most of the running injuries are related to impact accelerations and are due to overuse. In order to reduce the risk of injury or to improve performance and health new treadmill designs have been created, as it can be the curved non-motorized treadmill. The aim of this study was to analyse impact accelerations, spatio-temporal parameters and perceptual differences while running on curved non-motorized treadmill (cNMT) compared to motorized treadmill (MT) at different speeds. Therefore, 27 recreational runners completed two tests consisting of 10 min warm-up and three bouts of 8 min running at 2.77 m/s, 3.33 m/s and self-selected speed on cNMT and MT, previously randomised. Although the surface did not influence spatio-temporal parameters, a reduction in impact accelerations, head acceleration rate (mean effect size [ES] = 0.86), tibia peak (mean ES = 0.45) and tibia magnitude (mean ES = 0.55), was observed while running on cNMT in comparison with running on MT. Moreover, higher heart rate (HR) (mean ES = 0.51) and rating of perceived effort (RPE) (mean ES = 0.34) were found while running on cNMT. These findings demonstrated that higher intensity training and lower impact accelerations are experimented on cNMT, what can be used by trainers and athletes while planning training sessions.
Social Comparison and Stress Appraisal in Women with Chronic Illness
Authors: Terol Cantero M. Carmen , Bernabé Miguel , Martín-Aragón Maite , Vázquez Carolina , Buunk Abraham P.
Published: May 2021

(1) Background: The present study examined how social comparison orientation, stress appraisal and different social comparison strategies interact in women facing chronic illness. (2) Methods: Assessments were conducted by a trained professional in face-to face semistructured interviews (n = 179 women with chronic illness). Main outcome measures included social comparison scales and a stress appraisal questionnaire. The mediation model, by a bootstrapping procedure, was used to analyze the interaction among variables. (3) Results: Regarding the relationships among variables studied, they were related to each other except for a downward contrast, which allowed us to propose our hypothetical mediation model. Results showed that stress appraisal fully mediates between social comparison orientation and social comparison strategies except for the upward identification strategy. (4) Conclusions: Our results suggest that uncertainty, feelings of threat and low control over one’s illness or, in general, stress appraisal, had an important mediating effects over social comparison processes in patients with chronic illnesses. Therefore, by understanding the stress appraisal process, and the variables that might modify it, we could improve the use of social comparison as a favorable coping strategy.
Fecundability and Sterility by Age: Estimates Using Time to Pregnancy Data of Japanese Couples Trying to Conceive Their First Child with and without Fertility Treatment
Authors: Konishi Shoko , Kariya Fumiko , Hamasaki Kisuke , Takayasu Lena , Ohtsuki Hisashi
Published: May 2021

Fecundability, the probability of conception in a month or in a menstrual cycle, varies across and within age groups for both women and men. Fertility treatment has become common in a number of countries including Japan, but its impact on the age pattern of fecundability is unknown. By utilizing the previously collected data on time to pregnancy (TTP) of Japanese couples trying to conceive their first child, the present study aimed to estimate fecundability and sterility by women’s age and to assess how the estimates may differ by including or excluding assisted conceptions. Duration between discontinuing contraception and conception (including both natural and assisted) resulted in a live birth was called TTP-all, and the duration ending with natural conception was called TTP-natural. TTP-natural was censored when a participant received fertility consultation or treatment. A zero-inflated beta distribution model was used to estimate a proportion of sterile (zero probability of conception) and a distribution of fecundability for each age group. Parameters of the distribution were estimated using the maximum likelihood method. When TTP-all and TTP-natural were used, the sterile proportion of the whole sample was, respectively, 2% and 14%, and the median (interquartile range) of fecundability was, respectively, 0.10 (0.04, 0.19) and 0.11 (0.05, 0.19). The median (interquartile range) of fecundability was 0.18 (0.10, 0.29) for women aged 24 years or younger and 0.05 (0.02, 0.13) for 35–39 years old when TTP-all was used, and the estimates were quite similar with those based on TTP-natural: it was 0.18 (0.10, 0.29) for women aged 24 years or younger and 0.06 (0.00, 0.15) for 35–39 years old. Exclusion of assisted conceptions resulted in larger proportions of sterility, but it had little impact on median or interquartile ranges of fecundability estimates. Fecundability is overall lower at higher ages, while interquartile ranges are overlapping, suggesting that inter-individual variability of fecundability within an age group is as large as the variability across age groups.
Effects of Tele-Rehabilitation Compared with Home-Based in-Person Rehabilitation for Older Adult’s Function after Hip Fracture
Authors: Ortiz-Piña Mariana , Molina-Garcia Pablo , Femia Pedro , Ashe Maureen C. , Martín-Martín Lydia , Salazar-Graván Susana , Salas-Fariña Zeus , Prieto-Moreno Rafael , Castellote-Caballero Yolanda , Estevez-Lopez Fernando , Ariza-Vega Patrocinio
Published: May 2021

This study aimed to examine the effect of a multidisciplinary tele-rehabilitation program on functional recovery of older adults with hip fracture compared with home-based in-person rehabilitation. In this single-blinded, non-randomized clinical trial, we included older with hip fracture. The tele-rehabilitation group received a 12-week tele-rehabilitation program (supervised by their family caregivers). The control group received the usual postoperative rehabilitation provided by the Andalusian health system (Spain). The primary outcome was the patient-reported functional status assessed with the Functional Independence Measure. We also measured performance-based functional recovery using the Timed Up and Go Test and Short Physical Performance Battery. We performed both a per-protocol (62 participants; 28 tele-rehabilitation and 34 control groups) and an intention-to-treat analysis (71 participants; 35 tele-rehabilitation and 36 control groups). Participants who used the tele-rehabilitation program had higher Functional Independence Measure scores (high effect size: 0.98 Cohen’s d; p < 0.001) and better performance in the Timed Up and Go Test (medium effect size: 0.63 Cohen’s d; p = 0.025) compared with the control group. Differences between groups post-intervention were not statistically significant in the Short Physical Performance Battery. The tele-rehabilitation intervention proposed in this study is a valuable treatment option in the recovery process for older adults with hip fracture. ClinicalTrials.gov Identifier: NCT02968589.
The Health Impacts of Hazardous Chemical Exposures among Child Labourers in Low- and Middle-Income Countries
Authors: Scott Natasha B. , Pocock Nicola S.
Published: May 2021

Of 218 million working children worldwide, many are suspected to be exposed to hazardous chemicals. This review aims to synthesize reported evidence over the last two decades on chemical exposure and adverse health consequences in children labourers in low- and middle-income Countries (LMIC). Included studies investigated health outcomes related to chemical exposures among child labourers aged 5–18 in LMIC. Twenty-three papers were selected for review, focusing on pesticides (n = 5), solvents (n = 3), metals (n = 13) and persistent organic pollutants (POPs) (n = 2). Adverse health effects identified among child labourers included abnormal biomarkers, for example elevated blood and urine chemical concentrations, neurobehavioural deficits and neurological symptoms, mental health issues, oxidative stress and DNA damage, poor growth, asthma, and hypothyroidism. Workplace exposure to chemicals has pernicious health effects on child labourers. Large research gaps exist, in particular for long-term health impacts through chronic conditions and diseases with long latencies. A sizeable disease burden in later life is likely to be directly attributable to chemicals exposures. We urge national and international agencies concerned with child labour and occupational health, to prioritize research and interventions aiming to reduce noxious chemical exposures in workplaces where children are likely to be present.
A GIS Assessment of the Suitability of Tilapia and Clarias Pond Farming in Tanzania
Authors: Berg Håkan , Mulokozi Deogratias , Udikas Lars
Published: May 2021

Aquaculture production in Tanzania has increased in recent years, responding to an increased demand for fish, but the scale and productivity of smallholder aquaculture remains below the level needed to support significant sector growth in Tanzania. This study assesses, through geospatial analyses, the suitability for freshwater pond farming of Oreochromis niloticus and Clarias gariepinus in Tanzania, by assessing the geographical distribution of seven criteria (water availability, water temperature, soil texture, terrain slope, availability of farm inputs, potential farm-gate sales, and access to local markets) identified as important for fish pond farming. The criteria were developed and standardized from 15 sub-criteria, which were classified into a four-level suitability scale based on physical scores. The individual weights of the different criteria in the overall GIS suitability assessment were determined through a multi-criteria evaluation. The final results were validated and compared through field observations, interviews with 89 rural and 11 urban aquaculture farmers, and a questionnaire survey with 16 regional fisheries officers. Our results indicate that there is a good potential for aquaculture in Tanzania. Almost 60% of Tanzania is assessed as being suitable and 40% as moderately suitable for small-scale subsistence pond farming, which is the dominating fish farming practice currently. The corresponding figures for medium-scale commercial farming, which many regions expect to be the dominating farming method within ten-years, were 52% and 47% respectively. The availability of water was the most limiting factor for fish pond farming, which was confirmed by both farmers and regional fisheries officers, and assessed as being “suitable” in only 28% of the country. The availability of farm-gate sales and local markets were “moderate suitable” to “suitable” and were seen as a constraint for commercial farms in rural areas. The availability of farm inputs (agriculture waste and manure) was overall good (26% very suitable and 32% suitable), but high-quality fish feed was seen as a constraint to aquaculture development, both by farmers and regional fisheries officers. Soil, terrain, and water temperature conditions were assessed as good, especially at low altitudes and in regions close to the sea and south of Lake Victoria.
X-ray Crystallographic Structure of α-Helical Peptide Stabilized by Hydrocarbon Stapling at i,i + 1 Positions
Authors: Makura Yui , Ueda Atsushi , Kato Takuma , Iyoshi Akihiro , Higuchi Mei , Doi Mitsunobu , Tanaka Masakazu
Published: May 2021

Hydrocarbon stapling is a useful tool for stabilizing the secondary structure of peptides. Among several methods, hydrocarbon stapling at i,i + 1 positions was not extensively studied, and their secondary structures are not clarified. In this study, we investigate i,i + 1 hydrocarbon stapling between cis-4-allyloxy-l-proline and various olefin-tethered amino acids. Depending on the ring size of the stapled side chains and structure of the olefin-tethered amino acids, E- or Z-selectivities were observed during the ring-closing metathesis reaction (E/Z was up to 8.5:1 for 17–14-membered rings and up to 1:20 for 13-membered rings). We performed X-ray crystallographic analysis of hydrocarbon stapled peptide at i,i + 1 positions. The X-ray crystallographic structure suggested that the i,i + 1 staple stabilizes the peptide secondary structure to the right-handed α-helix. These findings are especially important for short oligopeptides because the employed stapling method uses two minimal amino acid residues adjacent to each other.
A Negative Energy Balance Is Associated with Metabolic Dysfunctions in the Hypothalamus of a Humanized Preclinical Model of Alzheimer’s Disease, the 5XFAD Mouse
Authors: López-Gambero Antonio J. , Rosell-Valle Cristina , Medina-Vera Dina , Navarro Juan Antonio , Vargas Antonio , Rivera Patricia , Sanjuan Carlos , Rodríguez de Fonseca Fernando , Suárez Juan
Published: May 2021

Increasing evidence links metabolic disorders with neurodegenerative processes including Alzheimer’s disease (AD). Late AD is associated with amyloid (Aβ) plaque accumulation, neuroinflammation, and central insulin resistance. Here, a humanized AD model, the 5xFAD mouse model, was used to further explore food intake, energy expenditure, neuroinflammation, and neuroendocrine signaling in the hypothalamus. Experiments were performed on 6-month-old male and female full transgenic (Tg5xFAD/5xFAD), heterozygous (Tg5xFAD/-), and non-transgenic (Non-Tg) littermates. Although histological analysis showed absence of Aβ plaques in the hypothalamus of 5xFAD mice, this brain region displayed increased protein levels of GFAP and IBA1 in both Tg5xFAD/- and Tg5xFAD/5xFAD mice and increased expression of IL-1β in Tg5xFAD/5xFAD mice, suggesting neuroinflammation. This condition was accompanied by decreased body weight, food intake, and energy expenditure in both Tg5xFAD/- and Tg5xFAD/5xFAD mice. Negative energy balance was associated with altered circulating levels of insulin, GLP-1, GIP, ghrelin, and resistin; decreased insulin and leptin hypothalamic signaling; dysregulation in main metabolic sensors (phosphorylated IRS1, STAT5, AMPK, mTOR, ERK2); and neuropeptides controlling energy balance (NPY, AgRP, orexin, MCH). These results suggest that glial activation and metabolic dysfunctions in the hypothalamus of a mouse model of AD likely result in negative energy balance, which may contribute to AD pathogenesis development.
Extracellular Vesicles from Plants: Current Knowledge and Open Questions
Authors: Urzì Ornella , Raimondo Stefania , Alessandro Riccardo
Published: May 2021

The scientific interest in the beneficial properties of natural substances has been recognized for decades, as well as the growing attention in extracellular vesicles (EVs) released by different organisms, in particular from animal cells. However, there is increasing interest in the isolation and biological and functional characterization of these lipoproteic structures in the plant kingdom. Similar to animal vesicles, these plant-derived extracellular vesicles (PDEVs) exhibit a complex content of small RNAs, proteins, lipids, and other metabolites. This sophisticated composition enables PDEVs to be therapeutically attractive. In this review, we report and discuss current knowledge on PDEVs in terms of isolation, characterization of their content, biological properties, and potential use as drug delivery systems. In conclusion, we outline controversial issues on which the scientific community shall focus the attention shortly.
RABL6A Regulates Schwann Cell Senescence in an RB1-Dependent Manner
Authors: Kohlmeyer Jordan L. , Kaemmer Courtney A. , Umesalma Shaikamjad , Gourronc Francoise A. , Klingelhutz Aloysius J. , Quelle Dawn E.
Published: May 2021

Schwann cells are normally quiescent, myelinating glia cells of the peripheral nervous system. Their aberrant proliferation and transformation underlie the development of benign tumors (neurofibromas) as well as deadly malignant peripheral nerve sheath tumors (MPNSTs). We discovered a new driver of MPNSTs, an oncogenic GTPase named RABL6A, that functions in part by inhibiting the RB1 tumor suppressor. RB1 is a key mediator of cellular senescence, a permanent withdrawal from the cell cycle that protects against cell immortalization and transformation. Based on the RABL6A-RB1 link in MPNSTs, we explored the hypothesis that RABL6A promotes Schwann cell proliferation and abrogates their senescence by inhibiting RB1. Using sequentially passaged normal human Schwann cells (NHSCs), we found that the induction of replicative senescence was associated with reduced expression of endogenous RABL6A. Silencing RABL6A in low passage NHSCs caused premature stress-induced senescence, which was largely rescued by co-depletion of RB1. Consistent with those findings, Rabl6-deficient MEFs displayed impaired proliferation and accelerated senescence compared to wildtype MEFs. These results demonstrate that RABL6A is required for maintenance of proper Schwann cell proliferation and imply that aberrantly high RABL6A expression may facilitate malignant transformation.
Regulatory Noncoding and Predicted Pathogenic Coding Variants of CCR5 Predispose to Severe COVID-19
Authors: Cantalupo Sueva , Lasorsa Vito Alessandro , Russo Roberta , Andolfo Immacolata , D’Alterio Giuseppe , Rosato Barbara Eleni , Frisso Giulia , Abete Pasquale , Cassese Gian Marco , Servillo Giuseppe , Gentile Ivan , Piscopo Carmelo , Della Monica Matteo , Fiorentino Giuseppe , Russo Giuseppe , Cerino Pellegrino , Buonerba Carlo , Pierri Biancamaria , Zollo Massimo , Iolascon Achille , Capasso Mario
Published: May 2021

Genome-wide association studies (GWAS) found locus 3p21.31 associated with severe COVID-19. CCR5 resides at the same locus and, given its known biological role in other infection diseases, we investigated if common noncoding and rare coding variants, affecting CCR5, can predispose to severe COVID-19. We combined single nucleotide polymorphisms (SNPs) that met the suggestive significance level (P ≤ 1 × 10−5) at the 3p21.31 locus in public GWAS datasets (6406 COVID-19 hospitalized patients and 902,088 controls) with gene expression data from 208 lung tissues, Hi-C, and Chip-seq data. Through whole exome sequencing (WES), we explored rare coding variants in 147 severe COVID-19 patients. We identified three SNPs (rs9845542, rs12639314, and rs35951367) associated with severe COVID-19 whose risk alleles correlated with low CCR5 expression in lung tissues. The rs35951367 resided in a CTFC binding site that interacts with CCR5 gene in lung tissues and was confirmed to be associated with severe COVID-19 in two independent datasets. We also identified a rare coding variant (rs34418657) associated with the risk of developing severe COVID-19. Our results suggest a biological role of CCR5 in the progression of COVID-19 as common and rare genetic variants can increase the risk of developing severe COVID-19 by affecting the functions of CCR5.
Discoidin Domain Receptor 2 Mediates Lysophosphatidic Acid-Induced Ovarian Cancer Aggressiveness
Authors: Jeong Bo Young , Cho Kyung Hwa , Yoon Se-Hee , Park Chang Gyo , Park Hwan-Woo , Lee Hoi Young
Published: May 2021

Lysophosphatidic acid (LPA), a bioactive lipid produced extracellularly by autotaxin (ATX), has been known to induce various pathophysiological events, including cancer cell invasion and metastasis. Discoidin domain receptor 2 (DDR2) expression is upregulated in ovarian cancer tissues, and is closely associated with poor clinical outcomes in ovarian cancer patients. In the present study, we determined a critical role and signaling cascade for the expression of DDR2 in LPA-induced ovarian cancer cell invasion. We also found ectopic expression of ATX or stimulation of ovarian cancer cells with LPA-induced DDR2 expression. However, the silencing of DDR2 expression significantly inhibited ATX- and LPA-induced ovarian cancer cell invasion. In addition, treatment of the cells with pharmacological inhibitors of phosphoinositide 3-kinase (PI3K), Akt, and mTOR abrogated LPA-induced DDR2 expression. Moreover, we observed that HIF-1α, located downstream of the mTOR, is implicated in LPA-induced DDR2 expression and ovarian cancer cell invasion. Finally, we provide evidence that LPA-induced HIF-1α expression mediates Twist1 expression to upregulate DDR2 expression. Collectively, the present study demonstrates that ATX, and thereby LPA, induces DDR2 expression through the activation of the PI3K/Akt/mTOR/HIF-1α/Twist1 signaling axes, aggravating ovarian cancer cell invasion.
Nonalcoholic Fatty Liver Disease (NAFLD). Mitochondria as Players and Targets of Therapies?
Authors: Di Ciaula Agostino , Passarella Salvatore , Shanmugam Harshitha , Noviello Marica , Bonfrate Leonilde , Wang David Q.-H. , Portincasa Piero
Published: May 2021

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and represents the hepatic expression of several metabolic abnormalities of high epidemiologic relevance. Fat accumulation in the hepatocytes results in cellular fragility and risk of progression toward necroinflammation, i.e., nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and eventually hepatocellular carcinoma. Several pathways contribute to fat accumulation and damage in the liver and can also involve the mitochondria, whose functional integrity is essential to maintain liver bioenergetics. In NAFLD/NASH, both structural and functional mitochondrial abnormalities occur and can involve mitochondrial electron transport chain, decreased mitochondrial β-oxidation of free fatty acids, excessive generation of reactive oxygen species, and lipid peroxidation. NASH is a major target of therapy, but there is no established single or combined treatment so far. Notably, translational and clinical studies point to mitochondria as future therapeutic targets in NAFLD since the prevention of mitochondrial damage could improve liver bioenergetics.
Carbon Dots-Mediated Fluorescent Scaffolds: Recent Trends in Image-Guided Tissue Engineering Applications
Authors: Vedhanayagam Mohan , Raja Iruthayapandi Selestin , Molkenova Anara , Atabaev Timur Sh. , Sreeram Kalarical Janardhanan , Han Dong-Wook
Published: May 2021

Regeneration of damaged tissues or organs is one of the significant challenges in tissue engineering and regenerative medicine. Many researchers have fabricated various scaffolds to accelerate the tissue regeneration process. However, most of the scaffolds are limited in clinical trials due to scaffold inconsistency, non-biodegradability, and lack of non-invasive techniques to monitor tissue regeneration after implantation. Recently, carbon dots (CDs) mediated fluorescent scaffolds are widely explored for the application of image-guided tissue engineering due to their controlled architecture, light-emitting ability, higher chemical and photostability, excellent biocompatibility, and biodegradability. In this review, we provide an overview of the recent advancement of CDs in terms of their different synthesis methods, tunable physicochemical, mechanical, and optical properties, and their application in tissue engineering. Finally, this review concludes the further research directions that can be explored to apply CDs in tissue engineering.
Programmed Death-Ligand 1 as a Regulator of Tumor Progression and Metastasis
Authors: Vathiotis Ioannis A. , Gomatou Georgia , Stravopodis Dimitrios J. , Syrigos Nikolaos
Published: May 2021

Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint has long been implicated in modeling antitumor immunity; PD-1/PD-L1 axis inhibitors exert their antitumor effects by relieving PD-L1-mediated suppression on tumor-infiltrating T lymphocytes. However, recent studies have unveiled a distinct, tumor-intrinsic, potential role for PD-L1. In this review, we focus on tumor-intrinsic PD-L1 signaling and delve into preclinical evidence linking PD-L1 protein expression with features of epithelial-to-mesenchymal transition program, cancer stemness and known oncogenic pathways. We further summarize data from studies supporting the prognostic significance of PD-L1 in different tumor types. We show that PD-L1 may indeed have oncogenic potential and act as a regulator of tumor progression and metastasis.
KRAS and EGFR Mutations Differentially Alter ABC Drug Transporter Expression in Cisplatin-Resistant Non-Small Cell Lung Cancer
Authors: Jaromi Luca , Csongei Veronika , Vesel Monika , Abdelwahab ElHusseiny Mohamed Mahmud , Soltani Amina , Torok Zsofia , Smuk Gabor , Sarosi Veronika , Pongracz Judit Erzsebet
Published: May 2021

Lung carcinoma is still the most common malignancy worldwide. One of the major subtypes of non-small cell lung cancer (NSCLC) is adenocarcinoma (AC). As driver mutations and hence therapies differ in AC subtypes, we theorized that the expression and function of ABC drug transporters important in multidrug resistance (MDR) would correlate with characteristic driver mutations KRAS or EGFR. Cisplatin resistance (CR) was generated in A549 (KRAS) and PC9 (EGFR) cell lines and gene expression was tested. In three-dimensional (3D) multicellular aggregate cultures, both ABCB1 and ABCG2 transporters, as well as the WNT microenvironment, were investigated. ABCB1 and ABCG2 gene expression levels were different in primary AC samples and correlated with specific driver mutations. The drug transporter expression pattern of parental A549 and PC9, as well as A549-CR and PC9-CR, cell lines differed. Increased mRNA levels of ABCB1 and ABCG2 were detected in A549-CR cells, compared to parental A549, while the trend observed in the case of PC9 cells was different. Dominant alterations were observed in LEF1, RHOU and DACT1 genes of the WNT signalling pathway in a mutation-dependent manner. The study confirmed that, in lung AC-s, KRAS and EGFR driver mutations differentially affect both drug transporter expression and the cisplatin-induced WNT signalling microenvironment.
The Study on Molecular Profile Changes of Pathogens via Zinc Nanocomposites Immobilization Approach
Authors: Rogowska Agnieszka , Railean-Plugaru Viorica , Pomastowski Paweł , Walczak-Skierska Justyna , Król-Górniak Anna , Gołębiowski Adrian , Buszewski Bogusław
Published: May 2021

The most critical group of all includes multidrug resistant bacteria that pose a particular threat in hospitals, as they can cause severe and often deadly infections. Modern medicine still faces the difficult task of developing new agents for the effective control of bacterial-based diseases. The targeted administration of nanoparticles can enhance the efficiency of conventional pharmaceutical agents. However, the interpretation of interfaces’ interactions between nanoparticles and biological systems still remains a challenge for researchers. In fact, the current research presents a strategy for using ZnO NPs immobilization with ampicillin and tetracycline. Firstly, the study provides the mechanism of the ampicillin and tetracycline binding on the surface of ZnO NPs. Secondly, it examines the effect of non-immobilized ZnO NPs, immobilized with ampicillin (ZnONPs/AMP) and tetracycline (ZnONPs/TET), on the cells’ metabolism and morphology, based on the protein and lipid profiles. A sorption kinetics study showed that the antibiotics binding on the surface of ZnONPs depend on their structure. The efficiency of the process was definitely higher in the case of ampicillin. In addition, flow cytometry results showed that immobilized nanoparticles present a different mechanism of action. Moreover, according to the MALDI approach, the antibacterial activity mechanism of the investigated ZnO complexes is mainly based on the destruction of cell membrane integrity by lipids and proteins, which is necessary for proper cell function. Additionally, it was noticed that some of the identified changes indicate the activation of defense mechanisms by cells, leading to a decrease in the permeability of a cell’s external barriers or the synthesis of repair proteins.
Human Genomics and the Biocultural Origin of Music
Authors: Beccacece Livia , Abondio Paolo , Cilli Elisabetta , Restani Donatella , Luiselli Donata
Published: May 2021

Music is an exclusive feature of humankind. It can be considered as a form of universal communication, only partly comparable to the vocalizations of songbirds. Many trends of research in this field try to address music origins, as well as the genetic bases of musicality. On one hand, several hypotheses have been made on the evolution of music and its role, but there is still debate, and comparative studies suggest a gradual evolution of some abilities underlying musicality in primates. On the other hand, genome-wide studies highlight several genes associated with musical aptitude, confirming a genetic basis for different musical skills which humans show. Moreover, some genes associated with musicality are involved also in singing and song learning in songbirds, suggesting a likely evolutionary convergence between humans and songbirds. This comprehensive review aims at presenting the concept of music as a sociocultural manifestation within the current debate about its biocultural origin and evolutionary function, in the context of the most recent discoveries related to the cross-species genetics of musical production and perception.