bluuebunny/crossref_metadata_2025 huggingface dataset:
A Cross-Sectional Study of Price and Affordability of Drugs for Rare Diseases in Shandong Province, China
Authors: Mu Yan , Song Kuimeng , Song Yan
Published: October 2022

Objective: The affordability of rare disease drugs has become a social issue that cannot be ignored. This study aims to evaluate the current price and affordability of rare disease drugs in China, with evidence from Shandong province. Methods: Data on prices and affordability of 50 drugs for 22 rare diseases were collected from secondary and tertiary public hospitals in Shandong Province, using an adaptation of the World Health Organization/Health Action International (WHO/HAI) methodology. Prices were measured as Median Price Ratios (MPRs). Affordability was measured as days of daily per capita disposable income required for the cost of one month’s treatment. Results: Out of the 50 rare disease drugs, 11 drugs had MSH reference prices and 34 had PBS reference prices. Median prices of 11 drugs were higher than MSH reference prices (median 1.33), and median prices of 34 drugs were higher that Australian PBS prices (median 1.97). Thirty-six (72.00%) and forty-four (88.00%) drugs were unaffordable for urban and rural residents, respectively. Thirty-four (68.00%) and thirty-eight (76.00%) drugs were unaffordable for urban and rural residents even after reimbursement by the health insurance schemes of China, respectively. Conclusions: The affordability of some rare disease drugs remained poor with their relatively high prices in Shandong Province. Sustainable mechanisms are needed to reduce the price of rare disease drugs and to improve the affordability of rare disease patients.
The Effect of Physical Activity on Sleep Quality among Older Stroke Survivors: Secondary Analysis from a Randomized Controlled Trial
Authors: Marupuru Srujitha , Bell Melanie L. , Grandner Michael A. , Taylor-Piliae Ruth E.
Published: October 2022

Poor sleep quality constitutes one of the most common difficulties faced by stroke survivors. Physical activity has been shown to improve sleep quality among healthy adults. The study objective was to examine the effect of physical activity on sleep outcomes in community-dwelling stroke survivors previously enrolled in a randomized clinical trial (RCT). Secondary analysis of data collected in the RCT was used to examine the effects of physical activity (PA) on sleep outcomes using the Pittsburgh Sleep Quality Index (PSQI), compared to usual care (controls). Unadjusted and adjusted mixed effects models were used to model changes in sleep quality between groups. At baseline, poor sleep quality (PSQI > 5) was reported by about half of the participants (PA group = 48.5%, n = 47/97; controls = 56.3%, n = 27/48). Results from the unadjusted and adjusted models for sleep quality were similar and showed no statistically significant differences between groups (p > 0.05). In the unadjusted model, the difference between groups (change from baseline to 24 weeks) showed that the PA group had better sleep quality than the controls (difference= −1.02 points, 95% CI −2.12, 0.07, p = 0.07). In the model adjusted for age, social support, and marital status, the difference between groups (change from baseline to 24 weeks) showed that the PA group had better sleep quality than the controls (difference= −1.07 points, 95% CI −2.19, 0.05, p = 0.06). PA did not significantly improve sleep quality in older community-dwelling stroke survivors. Further research is needed to confirm or refute these findings.
Biotransformation of 17β-Estradiol through a Denitrifying Sludge
Authors: Camacho-López César , Romo-Gómez Claudia , Otazo-Sánchez Elena María , Acevedo-Sandoval Otilio Arturo , García-Nieto Edelmira , Juárez-Santacruz Libertad
Published: October 2022

17β-estradiol (E2) is the natural estrogen with the most significant potential for endocrine disruption in the biota of aquatic ecosystems at trace concentrations. It is, therefore, essential to study treatments for water polluted with E2 that would guarantee its complete elimination and mineralization. Denitrification is a biological process shown to have the capacity to completely biodegrade drugs, such as ampicillin. This work is aimed to evaluate the biotransformation of 17β-estradiol by employing a denitrifying sludge. The assays performed were: (I) abiotic with 3.5 mg E2-C L−1 and (II) denitrifying with 10 mg CH3COO−-C L−1 as the reference, 10 mg E2-C L−1 as the sole electron donor, and a mixture of (mg L−1) 10 E2-C with 10 CH3COO−-C at C N−1 of 1.1. The E2-C and NO3−-N consumption efficiencies were greater than 99%, and HCO3−-C and N2 production yields were close to 1 in all assays. The denitrifying sludge could biodegrade up to 10 mg E2-C L−1 as the sole electron donor and when mixed with 10 mg CH3COO−-C L−1. No intermediate metabolites were generated from the process.
“No Risk No Fun?”: Determinants of Satisfaction with Life in People Who Engage in Extreme and High-Risk Sports
Authors: Krokosz Daniel , Lipowski Mariusz
Published: October 2022

(1) Background: In this paper, we attempt to identify which personality and motivational variables significantly influence the sense of quality of life of individuals who practice extreme sports (ES) and high-risk sports (HRS). In addition, we examined to what extent these relationships are moderated by the athletes’ gender and experience in a given discipline. (2) Methods: A total of 363 individuals who practice ES or who practice HRS took part in the study. All of the participants were from Poland. Standardized questionnaires were used to measure the investigated personality traits (extraversion, neuroticism, psychoticism), motives, and satisfaction with life, characteristic of the practiced sports. (3) Results: A positive relationship was observed between levels of extroversion and sense of satisfaction with life in the groups of women who engage in HRS (p = 0.045) and men who engage in ES (p = 0.002). The tendency towards addiction was significantly negatively associated with sense of satisfaction with life only in men who engage in ES (p = 0.015). Individuals who engage in ES and HRS did not differ in levels of tendency towards addiction. (4) Conclusions: Individuals who practice ES differ from individuals who practice HRS in terms of personality features, motivations, and the determinants of their sense of satisfaction with life.
Associations between Perception of Help-Seeking Behaviors and Quality of Life among Older People in Rural Communities: A Cross-Sectional Study
Authors: Ohta Ryuichi , Sano Chiaki
Published: October 2022

Older people’s help-seeking behaviors (HSBs) may be limited because of various factors and are essential in improving healthcare in aging societies. This cross-sectional study investigated the association between perception of HSBs, concrete HSBs, quality of life (QOL), and other variables among people over 65 in rural Japan using standardized questionnaires. Participants were divided into high or low health status index score groups based on a median split. Logistic regression was used to assess the association between perception of HSBs and high QOL while controlling for age, sex, living conditions, annual health checks, having chronic diseases, regular clinic visits, smoking, habitual alcohol consumption, education, living conditions, social support, social capital, socioeconomic status (SES), and health literacy. Participants in the high QOL group were younger (p < 0.001), and had fewer chronic diseases and regular clinic visits than those in the low QOL group (p < 0.001). The multivariate logistic regression model revealed that age, chronic diseases, tobacco usage, family consultation, and consulting primary care physicians negatively predicted QOL. High SES, social capital and support, and HSB intention positively predicted QOL. Self-efficacy and intention regarding HSBs should be investigated to improve health among older rural people.
Transfer of Mental Health Services for Medical Students to Cyberspace during the COVID-19 Pandemic: Service Use and Students’ Preferences for Psychological Self-Help Techniques
Authors: Oláh Barnabás , Kuritárné Szabó Ildikó , Kósa Karolina
Published: October 2022

The high risk of mental health problems among medical students has been compounded by the COVID-19 pandemic, which greatly reduced social contact. The mental health support service of the medical school of one Hungarian university was transferred to the online learning management system and was expanded by self-help materials in three domains: Improving study skills, stress management techniques, and reducing stress related to the COVID-19 pandemic. We wanted to understand the preferences of medical students for psychological self-help techniques by investigating the pattern of access to online self-help materials and the characteristics of the users. Access to the online materials between April 2020 and April 2021 among Hungarian and international medical students was analyzed using the logging data of the system. Of all the students who logged in during the examination period (n = 458), 36.6–40.4% viewed materials to improve study skills and 23–29% viewed stress management materials, of which short-duration audio format techniques were preferred. The access rate of content targeting coping with the mental health effects of COVID-19 was 9.5–24%. Support to improve study skills is significantly more preferred than interventions targeting distress-reduction. The pattern of access can be used for the development of interventions that are of most interest to medical students.
Socioeconomic, Ethnocultural, Substance- and Cannabinoid-Related Epidemiology of Down Syndrome USA 1986–2016: Combined Geotemporospatial and Causal Inference Investigation
Authors: Reece Albert , Hulse Gary
Published: October 2022

Background: Down syndrome (DS) is the commonest of the congenital genetic defects whose incidence has been rising in recent years for unknown reasons. This study aims to assess the impact of substance and cannabinoid use on the DS Rate (DSR) and assess their possible causal involvement. Methods: An observational population-based epidemiological study 1986–2016 was performed utilizing geotemporospatial and causal inferential analysis. Participants included all patients diagnosed with DS and reported to state based registries with data obtained from National Birth Defects Prevention Network of Centers for Disease Control. Drug exposure data was from the National Survey of Drug Use and Health (NSDUH) a nationally representative sample interviewing 67,000 participants annually. Drug exposures assessed were: cigarette consumption, alcohol abuse, analgesic/opioid abuse, cocaine use and last month cannabis use. Covariates included ethnicity and median household income from US Census Bureau; maternal age of childbearing from CDC births registries; and cannabinoid concentrations from Drug Enforcement Agency. Results: NSDUH reports 74.1% response rate. Other data was population-wide. DSR was noted to rise over time and with cannabis use and cannabis-use quintile. In the optimal geospatial model lagged to four years terms including Δ9-tetrahydrocannabinol and cannabigerol were significant (from β-est. = 4189.96 (95%C.I. 1924.74, 6455.17), p = 2.9 × 10−4). Ethnicity, income, and maternal age covariates were not significant. DSR in states where cannabis was not illegal was higher than elsewhere (β-est. = 2.160 (1.5, 2.82), R.R. = 1.81 (1.51, 2.16), p = 4.7 × 10−10). In inverse probability-weighted mixed models terms including cannabinoids were significant (from β-estimate = 18.82 (16.82, 20.82), p < 0.0001). 62 E-value estimates ranged to infinity with median values of 303.98 (IQR 2.50, 2.75 × 107) and 95% lower bounds ranged to 1.1 × 1071 with median values of 10.92 (IQR 1.82, 7990). Conclusions. Data show that the association between DSR and substance- and cannabinoid- exposure is robust to multivariable geotemporospatial adjustment, implicate particularly cannabigerol and Δ9-tetrahydrocannabinol, and fulfil quantitative epidemiological criteria for causality. Nevertheless, detailed experimental studies would be required to formally demonstrate causality. Cannabis legalization was associated with elevated DSR’s at both bivariate and multivariable analysis. Findings are consistent with those from Hawaii, Colorado, Canada, Australia and Europe and concordant with several cellular mechanisms. Given that the cannabis industry is presently in a rapid growth-commercialization phase the present findings linking cannabis use with megabase scale genotoxicity suggest unrecognized DS risk factors, are of public health importance and suggest that re-focussing the cannabis debate on multigenerational health concerns is prudent.
When a Pandemic Strikes: Resilience of Swedish Academics in the Face of Coronavirus
Authors: Cetrez Önver Andreas , Zandi Saeid , Ahmadi Fereshteh
Published: October 2022

Background: The COVID-19 pandemic hit the world with severe health consequences, affecting some populations more than others. One understudied population is the academic community. This study, part of a larger project looking at COVID-19 in Sweden and internationally, aims to understand the individual and collective dimensions of resilience among academics in Sweden during the early wave of the pandemic. Method: A quantitative research design was applied for this cross-sectional study. We used simple random sampling, administered through an online survey, on academics at Swedish universities (n = 278, 64% women). We employed the CD-RISC 2 (the Connor–Davidson Resilience Scale) to measure personal/individual resilience, additional items for social/collective resilience, and a meaning-making coping instrument (meaning, control, comfort/spirituality, intimacy/spirituality, life transformation). Results: The results revealed a strong level of personal/individual resilience among men (M = 6.05) and a level just below strong among women (M = 5.90). By age group, those 35–49-year-olds showed strong resilience (M = 6.31). Family was the dominant social/collective resilience factor, followed by friends, nature, work/school, and, lastly, religion/spirituality. There was a positive and significant correlation between self-rated health and personal/individual resilience (r = 0.252, p = 0.001) and positive but weak correlations and negative significant correlations between personal/individual resilience and religious coping methods. Conclusions: During the pandemic, the family took priority in meaning-making, which is an interesting change in a strong individual-oriented society such as Sweden.
Hospitalizations of Ukrainian Migrants and Refugees in Poland in the Time of the Russia-Ukraine Conflict
Authors: Lewtak Katarzyna , Kanecki Krzysztof , Tyszko Piotr , Goryński Paweł , Kosińska Irena , Poznańska Anna , Rząd Michał , Nitsch-Osuch Aneta
Published: October 2022

Background: In the face of a sudden influx of several million migrants and war refugees from Ukraine to other European countries, knowledge about the health of Ukrainian citizens becomes increasingly important. The aim of the study is to identify the main health problems of hospitalized Ukrainian citizens residing in Poland in the period from 2014 to June 2022. Methods: This study is based on hospitalization data of Ukrainian patients in Poland taken from the Nationwide General Hospital Morbidity Study. Results: The study group covered 8591 hospitalization records. We observed two hospitalization peaks, one in patients aged 0–5 and the other one in those aged 20–35. After the official outbreak of the war, 2231 Ukrainian citizens were hospitalized in Poland. At this time, the most often reported principal reasons for the hospitalizations of adult women were diseases related to pregnancy, childbirth and the puerperium, whereas in groups of adult men diseases were related to injury, poisoning and certain other consequences of external causes, and in children and adolescents diseases were infectious and parasitic diseases. Conclusions: Our findings may have implications for healthcare policies and service provision to newly arrived migrants and war refugees in target European countries.
Associations between Greenspaces and Individual Health: A Longitudinal Study in China
Authors: Liao Liping , Du Minzhe
Published: October 2022

Using a longitudinal survey in China, this study identifies the effect of greenspaces on individual health in the aspects of self-rated health, mental health, feeling physical discomfort, and being hospitalized. The normalized difference vegetation index (NDVI) is used to measure the greenery cover of each city, and findings show that higher NDVI leads to the improvement of personal self-rated health status, and it also decreases the probability of being hospitalized, having symptoms of physical discomfort, and being lost in bad mood. The positive health effect of NDVI in the city is much more significant and larger for the middle-aged, the elderly, and the low-educated. The evidence of the three possible channels through which the NDVI of each city shows a positive correlation with individual physical and mental health is found. The increased NDVI in the city encourages residents to foster healthier habits (e.g., decreasing smoking or drinking, increasing sleeping hours), improves air quality and reduces air pollution in each city, and promotes the social cohesion of people, and so the health status of residents is enhanced. This study implies that increasing greenspaces in the city is an effective strategy to improve social welfare and residents’ health.
Oxycodone-Naloxone Combination Hinders Opioid Consumption in Osteoarthritic Chronic Low Back Pain: A Retrospective Study with Two Years of Follow-Up
Authors: Polati Enrico , Nizzero Marta , Rama Jacopo , Martini Alvise , Gottin Leonardo , Donadello Katia , Del Balzo Giovanna , Varrassi Giustino , Marinangeli Franco , Vittori Alessandro , Secchettin Erica , Schweiger Vittorio
Published: October 2022

Chronic low back pain (CLBP) due to osteoarthritis represents a therapeutic challenge worldwide. Opioids are extensively used to treat such pain, but the development of tolerance, i.e., less susceptibility to the effects of the opioid, which can result in a need for higher doses to achieve the same analgesic effect, may limit their use. Animal models suggest that ultra-low doses of opioid antagonists combined with opioid agonists can decrease or block the development of opioid tolerance. In this retrospective study, we tested this hypothesis in humans. In 2019, 53 patients suffering from CLBP were treated with either Oxycodone and Naloxone Prolonged Release (27 patients, OXN patients) or Oxycodone Controlled Release (26 patients, OXY patients). The follow-up period lasted 2 years, during which 10 patients discontinued the treatment, 5 out of each group. The remaining 43 patients reached and maintained the targeted pain relief, but at 18 and 24 months, the OXY patients showed a significantly higher oxycodone consumption than OXN patients to reach the same level of pain relief. No cases of respiratory depression or opioid abuse were reported. There were no significant differences in the incidence of adverse effects between the two treatments, except for constipation, more common in OXY patients. From our results, we can affirm that a long-term opioid treatment with oxycodone-naloxone combination, when compared with oxycodone only, may significantly hinder the development of opioid tolerance. We were also able to confirm, in our cohort, the well known positive effect of naloxone in terms of opioid-induced bowel dysfunction incidence reduction.
Factors Affecting the Career Continuation of Newly Graduated and Reinstated Dental Hygienists Who Participated in a Technical Training Program in Japan
Authors: Noritake Kanako , Oshima Katsuo , Fukuda Hideki , Tano Rumi , Oshiro Akiko , Nitta Hiroshi , Miura Hiroko
Published: October 2022

This study aimed to identify (1) what newly graduated dental hygienists and reinstated dental hygienists consider important for preventing early turnover in their own professions and for encouraging them to continue in the profession more generally and (2) relevant factors among hygienists intending to continue working in the field. An anonymous, self-administered questionnaire survey was distributed to 215 Japanese dental hygienists who participated in the technical training programs (response rate: 72.6%). Of them, 143 participants were classified into two groups: newly graduated (NGDH, n = 32) and those reinstated to work (RDH, n = 111). Follow-up for lack of skills was most often selected as important for preventing early turnover among both groups and follow-up for lack of knowledge was significantly selected in the RDH group (p < 0.001). Regarding factors important for career continuation, NGDHs significantly selected gaining job satisfaction, whereas RDHs significantly selected working support. Relevant factors contributing to participants’ intentions to continue in the profession were job satisfaction (NGDH, OR = 8.37; RDH, OR = 8.83), career outlook (RDH, OR = 3.11), and job turnover experience because of marriage and parenting (RDH, OR = 2.70), thereby suggesting the importance of raising awareness regarding career progression and job-related rewards among dental hygienists, their educators, and the government through ongoing career education.
What Is the Value of a Global Health Research School for PhD Students?
Authors: Darj Elisabeth , Hoem Irene Bisasso , Dvergsdal Elin Yli
Published: October 2022

The aim of the study was to investigate previous PhD students’ views on the Norwegian Research School of Global Health and its activities. Of the research schools for PhD students, few focus on global health and even fewer have evaluated the students’ perspectives of the schools. In this study, a questionnaire including quantitative and qualitative questions were sent to alumni PhD students. Demographic status was investigated, along with the alumni’s views on activities offered at the research school, suggestions for improvement, views on his or her social life as a student and as a member of the school. A total of 60 alumni were contacted by email and invited to participate in an anonymous online survey. The response rate was 65%; 90% were in employment and a few were seeking employment. All research school activities were evaluated as useful. Content analysis of qualitative questions generated three categories of the alumni’s reflections on their involvement in the research school: valued activities, challenges, and future. The alumni expressed a wish for continued contact with the school. The findings indicated that a research school for PhD students with similar interests should be continued; although modifications should be considered, based on the specific challenges revealed in the evaluation.
Cognitive Benefits of Physical Exercise, Physical–Cognitive Training, and Technology-Based Intervention in Obese Individuals with and without Postmenopausal Condition: A Narrative Review
Authors: Keawtep Puntarik , Wichayanrat Wanachaporn , Boripuntakul Sirinun , Chattipakorn Siriporn C. , Sungkarat Somporn
Published: October 2022

Obesity and estrogen deprivation have been identified as significant risk factors for cognitive impairment. Thus, postmenopausal conditions when paired with obesity may amplify the risks of developing dementia. Physical exercise has been recommended as a primary treatment for preventing obesity-related comorbidities and alleviating menopausal symptoms. This narrative review aimed to summarize the effects of exercise on cognition in obese individuals with and without menopausal condition, along with potential physiological mechanisms linking these interventions to cognitive improvement. Research evidence has demonstrated that exercise benefits not only physical but also cognitive and brain health. Among various types of exercise, recent studies have suggested that combined physical–cognitive exercise may exert larger gains in cognitive benefits than physical or cognitive exercise alone. Despite the scarcity of studies investigating the effects of physical and combined physical–cognitive exercise in obese individuals, especially those with menopausal condition, existing evidence has shown promising findings. Applying these exercises through technology-based interventions may be a viable approach to increase accessibility and adherence to the intervention. More evidence from randomized clinical trials with large samples and rigorous methodology is required. Further, investigations of biochemical and physiological outcomes along with behavioral changes will provide insight into underlying mechanisms linking these interventions to cognitive improvement.
An e-Problem-Based Learning Program for Infection Control in Nursing Homes: A Quasi-Experimental Study
Authors: Choi Young-Rim , Lee Ye-Na , Kim Dayeong , Park Won Hee , Kwon Dai Young , Chang Sung Ok
Published: October 2022

Infection is a significant factor adversely affecting the health of nursing home (NH) residents, potentially even leading to death. Therefore, educating NH staff to think critically is necessary to prevent and control infection. In this study, we developed an electronic problem-based learning (e-PBL) program using the Network-Based Instructional System Design model to enhance South Korean NH staff’s critical thinking competencies; subsequently, its effectiveness was evaluated. This study utilized a quasi-experimental nonequivalent pretest–post-test design. The participants (n = 54) were randomly allocated into an experimental group (n = 28) and a control group (n = 26). The results indicate that the e-PBL program significantly improved the critical thinking disposition in the experimental group compared with in the control group.
Simultaneous Detection of SARS-CoV-2 and Influenza Virus in Wastewater of Two Cities in Southeastern Germany, January to May 2022
Authors: Dumke Roger , Geissler Michael , Skupin Annett , Helm Björn , Mayer Robin , Schubert Sara , Oertel Reinhard , Renner Bertold , Dalpke Alexander H.
Published: October 2022

Dependent on the excretion pattern, wastewater monitoring of viruses can be a valuable approach to characterizing their circulation in the human population. Using polyethylene glycol precipitation and reverse transcription-quantitative PCR, the occurrence of RNA of SARS-CoV-2 and influenza viruses A/B in the raw wastewater of two treatment plants in Germany between January and May 2022 was investigated. Due to the relatively high incidence in both exposal areas (plant 1 and plant 2), SARS-CoV-2-specific RNA was determined in all 273 composite samples analyzed (concentration of E gene: 1.3 × 104 to 3.2 × 106 gc/L). Despite a nation-wide low number of confirmed infections, influenza virus A was demonstrated in 5.2% (concentration: 9.8 × 102 to 8.4 × 104 gc/L; plant 1) and in 41.6% (3.6 × 103 to 3.0 × 105 gc/L; plant 2) of samples. Influenza virus B was detected in 36.0% (7.2 × 102 to 8.5 × 106 gc/L; plant 1) and 57.7% (9.6 × 103 to 2.1 × 107 gc/L; plant 2) of wastewater samples. The results of the study demonstrate the frequent detection of two primary respiratory viruses in wastewater and offer the possibility to track the epidemiology of influenza by wastewater-based monitoring.
Heterotrophic Bioleaching of Vanadium from Low-Grade Stone Coal by Aerobic Microbial Consortium
Authors: Zhang Han , Shi Jiaxin , Chen Cuibai , Yang Meng , Lu Jianping , Zhang Baogang
Published: October 2022

Bioleaching is a viable method that assists in increasing the vanadium output in an economical and environmentally friendly manner. Most bioleaching is conducted by pure cultures under autotrophic conditions, which frequently require strong acidity and produce acid wastewater. However, little is known about heterotrophic bioleaching of vanadium by mixed culture. This study investigated the bioleaching of vanadium from low-grade stone coal by heterotrophic microbial consortium. According to the results, vanadium was efficiently extracted by the employed culture, with the vanadium recovery percentage in the biosystem being 7.24 times greater than that in the control group without inoculum. The average vanadium leaching concentration reached 680.7 μg/L in the first three cycles. The kinetic equation indicated that the main leaching process of vanadium was modulated by a diffusion process. Scanning electron microscopy revealed traces of bacterial erosion with fluffy structures on the surface of the treated stone coal. X-ray photoelectron spectroscopy confirmed the reduction of the vanadium content in the stone coal after leaching. Analysis of high-throughput 16S rRNA gene sequencing revealed that the metal-oxidizing bacteria, Acidovorax and Delftia, and the heterotrophic-metal-resistant Pseudomonas, were significantly enriched in the bioleaching system. Our findings advance the understanding of bioleaching by aerobic heterotrophic microbial consortium and offer a promising technique for vanadium extraction from low-grade stone coals.
The Role of Family Health in Mediating the Association between Smartphone Use and Health Risk Behaviors among Chinese Adolescent Students: A National Cross-Sectional Study
Authors: Gong Fangmin , Lei Zhaowen , Gong Zhuliu , Min Hewei , Ge Pu , Guo Yi , Ming Wai-Kit , Sun Xinying , Wu Yibo
Published: October 2022

The direct impact of smartphones on health risk behaviors of adolescent students has been verified. However, the mediating mechanisms that underly this relationship remain largely unknown. Therefore, the aim of the study is to explore the role of family health in mediating the relationship between the frequency of smartphone use and adolescent students’ health risk behaviors. A questionnaire was used to collect cross-sectional data from 693 adolescent students aged 12–18 in China and a structural equation model was analyzed. Among the nine health risk behaviors, the most frequent health risk behaviors in Chinese adolescent students were non-compliance walking behaviors (M=Mean; SD = Standard deviation) (M ± SD) (2.78 ± 1.747), eating unhygienic food (M ± SD) (2.23 ± 1.299), being subjected to physical violence (M ± SD) (2.19 ± 0.645), and leaving home (M ± SD) (2.13 ± 0.557). The SEM results showed that the adolescent students’ smartphone use had a positive impact on delaying the age of first alcohol consumption (β = 0.167, CI:0.067 0.287) and a negative impact on the non-compliance walking behaviors (β = 0.176, CI:0.011 0.266). Family health plays an indirect-only mediated role (the proportions of indirect-only mediated roles are 11.2%, 12.4%, and 11.5%) in the relationship between smartphone use and adolescent students’ partial health risk behaviors: (CI: −0.042 −0.002), (CI: −0.049 −0.005), and (CI: −0.043 −0.002). These findings provided a theoretical and practical basis for better interventions in adolescent health risk behaviors.
Virtual Drug Repositioning as a Tool to Identify Natural Small Molecules That Synergize with Lumacaftor in F508del-CFTR Binding and Rescuing
Authors: Fossa Paola , Uggeri Matteo , Orro Alessandro , Urbinati Chiara , Rondina Alessandro , Milanesi Maria , Pedemonte Nicoletta , Pesce Emanuela , Padoan Rita , Ford Robert C. , Meng Xin , Rusnati Marco , D’Ursi Pasqualina
Published: October 2022

Cystic fibrosis is a hereditary disease mainly caused by the deletion of the Phe 508 (F508del) of the cystic fibrosis transmembrane conductance regulator (CFTR) protein that is thus withheld in the endoplasmic reticulum and rapidly degraded by the ubiquitin/proteasome system. Cystic fibrosis remains a potentially fatal disease, but it has become treatable as a chronic condition due to some CFTR-rescuing drugs that, when used in combination, increase in their therapeutic effect due to a synergic action. Also, dietary supplementation of natural compounds in combination with approved drugs could represent a promising strategy to further alleviate cystic fibrosis symptoms. On these bases, we screened by in silico drug repositioning 846 small synthetic or natural compounds from the AIFA database to evaluate their capacity to interact with the highly druggable lumacaftor binding site of F508del-CFTR. Among the identified hits, nicotinamide (NAM) was predicted to accommodate into the lumacaftor binding region of F508del-CFTR without competing against the drug but rather stabilizing its binding. The effective capacity of NAM to bind F508del-CFTR in a lumacaftor-uncompetitive manner was then validated experimentally by surface plasmon resonance analysis. Finally, the capacity of NAM to synergize with lumacaftor increasing its CFTR-rescuing activity was demonstrated in cell-based assays. This study suggests the possible identification of natural small molecules devoid of side effects and endowed with the capacity to synergize with drugs currently employed for the treatment of cystic fibrosis, which hopefully will increase the therapeutic efficacy with lower doses.
The OmpR-like Transcription Factor as a Negative Regulator of hrpR/S in Pseudomonas syringae pv. actinidiae
Authors: Zhao Fu , Zhi Taihui , Hu Renjian , Fan Rong , Long Youhua , Tian Fenghua , Zhao Zhibo
Published: October 2022

Bacterial canker of kiwifruit is a devastating disease caused by Pseudomonas syringae pv. actinidiae (Psa). The type III secretion system (T3SS), which translocates effectors into plant cells to subvert plant immunity and promote extracellular bacterial growth, is required for Psa virulence. Despite that the “HrpR/S-HrpL” cascade that sophisticatedly regulates the expression of T3SS and effectors has been well documented, the transcriptional regulators of hrpR/S remain to be determined. In this study, the OmpR-like transcription factor, previously identified by DNA pull-down assay, was found to be involved in the regulation of hrpR/S genes, and its regulatory mechanisms and other functions in Psa were explored through techniques including gene knockout and overexpression, ChIP-seq, and RNA-seq. The OmpR-like transcription factor had binding sites in the promoter region of the hrpR/S, and the transcriptional level of the hrpR/S increased after the deletion of OmpR-like and decreased upon its overexpression in an OmpR-like deletion background. Additionally, OmpR-like overexpression reduced the strain’s capacity to form biofilms and lipopolysaccharides, led to its slow growth in King’s B medium, and reduced its swimming ability, although there was no significant effect on its pathogenicity against kiwifruit hosts. Our results indicated that OmpR-like directly and negatively regulates the transcription of hrpR/S and may be involved in the regulation of multiple biological processes in Psa. Our results provide a basis for further understanding the transcriptional regulation mechanism of hrpR/S in Psa.
Application of the Mutant Libraries for Candida albicans Functional Genomics
Authors: Wang Ruina , Liu Jiacun , Liu Yu , Lv Quanzhen , Yan Lan
Published: October 2022

Candida albicans is a typical opportunistic pathogen in humans that causes serious health risks in clinical fungal infections. The construction of mutant libraries has made remarkable developments in the study of C. albicans molecular and cellular biology with the ongoing advancements of gene editing, which include the application of CRISPR-Cas9 and novel high-efficient transposon. Large-scale genetic screens and genome-wide functional analysis accelerated the investigation of new genetic regulatory mechanisms associated with the pathogenicity and resistance to environmental stress in C. albicans. More importantly, sensitivity screening based on C. albicans mutant libraries is critical for the target identification of novel antifungal compounds, which leads to the discovery of Sec7p, Tfp1p, Gwt1p, Gln4p, and Erg11p. This review summarizes the main types of C. albicans mutant libraries and interprets their applications in morphogenesis, biofilm formation, fungus–host interactions, antifungal drug resistance, and target identification.
Papaya Leaf Extracts as Potential Dengue Treatment: An In-Silico Study
Authors: Madushanka Ayesh , Verma Niraj , Freindorf Marek , Kraka Elfi
Published: October 2022

Dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) cause serious public health problems, with nearly 390 million people affected and 20,000 deaths per year in tropical and subtropical countries. Despite numerous attempts, no antiviral drug or vaccine is currently available to combat the manifestation. The challenge of discovering an efficient vaccine is enhanced by the surplus presence of efficient vectors and drug resistance from the virus. For centuries, papaya (Carica papaya) extracts have been traditionally used to treat DF, DHF, and DSS. In the present study, we systematically investigated seven compounds isolated from papaya leaf extract with regard to their potential as inhibitors for non-structural (NS) proteins, NS3 and NS5, which play a crucial role in viral RNA replication. The computational tools applied stretched across classical molecular docking, molecular dynamics (MD) simulations and SwissADME used to calculate binding affinities; binding free energies; Absorption, Distribution, Metabolism, and Excretion (ADME); and drug-likeness properties, thus, identifying Kaempferol, Chlorogenic acid, and Quercetin as potential candidates, with Kaempferol and Quercetin scoring best. Therefore, for the Kaempferol and Quercetin complexes, hybrid quantum mechanical/molecular mechanical (QM/MM) geometry and frequency calculations were performed, followed by the local mode analysis developed in our group to quantify Kaempferol-NS and Quercetin-NS hydrogen bonding. Given the non-toxic nature and the wide availability of the Kaempferol and Quercetin papaya extract in almost all of the susceptible regions, and our results showing high NS3 and NS5 binding affinities and energies, strong hydrogen bonding with both NS3 and NS5, and excellent ADME properties, we suggest Kaempferol and Quercetin as a strong NS3 and NS5 inhibitor to be further investigated in vitro.
Assessment of Brain-Derived Neurotrophic Factor (BDNF) Concentration in Children with Idiopathic Nephrotic Syndrome
Authors: Badeński Andrzej , Badeńska Marta , Świętochowska Elżbieta , Didyk Agnieszka , Morawiec-Knysak Aurelia , Szczepańska Maria
Published: October 2022

Idiopathic nephrotic syndrome (INS) is a chronic disease affecting children in early childhood. It is characterized by proteinuria, hypoalbuminemia, edema and hyperlipidemia. To date, the diagnosis is usually established at an advanced stage of proteinuria. Therefore, new methods of early INS detection are desired. This study was designed to assess brain-derived neurotrophic factor (BDNF) as a potential marker in the early diagnosis of INS. The study group included patients with a diagnosis of idiopathic nephrotic syndrome (n = 30) hospitalized in Clinical Hospital No. 1 in Zabrze, from December 2019 to December 2021. Our study shows that serum BDNF concentration decreased and urine BDNF concentration increased in a group of patients with INS, compared with healthy controls. Such outcomes might be related to loss of the BDNF contribution in podocyte structure maintenance. Moreover, we anticipate the role of BDNF in urine protein concentration increase, which could be used as a direct predictor of urine protein fluctuations in clinical practice. Moreover, the ROC curve has also shown that serum BDNF and urine BDNF levels might be useful as an INS marker.
Coenzyme Q10 Attenuates Human Platelet Aggregation Induced by SARS-CoV-2 Spike Protein via Reducing Oxidative Stress In Vitro
Authors: Wang Ruijie , Chen Yiting , Tian Zezhong , Zhu Meiyan , Zhang Bingying , Du Sijin , Li Yanzhang , Liu Zhihao , Hou Shanshan , Yang Yan
Published: October 2022

Platelet hyperreactivity and oxidative stress are the important causes of thrombotic disorders in patients with COVID-19. Oxidative stress, induced by the excessive generation of reactive oxygen species (ROS), could increase platelet function and the risk of thrombus formation. Coenzyme Q10 (CoQ10), exhibits strong antioxidative activity and anti-platelet effect. However, the effects and mechanisms of CoQ10 on attenuating platelet aggregation induced by spike protein have never been studied. This study aims to investigate whether the SARS-CoV-2 spike protein potentiates human platelet function via ROS signaling and the protective effect of CoQ10 in vitro. Using a series of platelet function assays, we found that spike protein potentiated platelet aggregation and oxidative stress, such as ROS level, mitochondrial membrane potential depolarization, and lipid damage level (MDA and 8-iso-PGF2α) in vitro. Furthermore, CoQ10 attenuated platelet aggregation induced by spike protein. As an anti-platelet mechanism, we showed that CoQ10 significantly decreased the excess production of ROS induced by spike protein. Our findings show that the protective effect of CoQ10 on spike protein-potentiated platelet aggregation is probably associated with its strong antioxidative ability.
cd1 Mutation in Drosophila Affects Phenoxazinone Synthase Catalytic Site and Impairs Long-Term Memory
Authors: Zhuravlev Aleksandr V. , Ivanova Polina N. , Makaveeva Ksenia A. , Zakharov Gennadii A. , Nikitina Ekaterina A. , Savvateeva-Popova Elena V.
Published: October 2022

Being involved in development of Huntington’s, Parkinson’s and Alzheimer’s diseases, kynurenine pathway (KP) of tryptophan metabolism plays a significant role in modulation of neuropathology. Accumulation of a prooxidant 3-hydroxykynurenine (3-HOK) leads to oxidative stress and neuronal cell apoptosis. Drosophila mutant cardinal (cd1) with 3-HOK excess shows age-dependent neurodegeneration and short-term memory impairments, thereby presenting a model for senile dementia. Although cd gene for phenoxazinone synthase (PHS) catalyzing 3-HOK dimerization has been presumed to harbor the cd1 mutation, its molecular nature remained obscure. Using next generation sequencing, we have shown that the cd gene in cd1 carries a long deletion leading to PHS active site destruction. Contrary to the wild type Canton-S (CS), cd1 males showed defective long-term memory (LTM) in conditioned courtship suppression paradigm (CCSP) at days 5–29 after eclosion. The number of dopaminergic neurons (DAN) regulating fly locomotor activity showed an age-dependent tendency to decrease in cd1 relative to CS. Thus, in accordance with the concept “from the gene to behavior” proclaimed by S. Benzer, we have shown that the aberrant PHS sequence in cd1 provokes drastic LTM impairments and DAN alterations.
Quantitative Analysis of Collective Migration by Single-Cell Tracking Aimed at Understanding Cancer Metastasis
Authors: Xin Zhuohan , Deguchi Keiko , Suye Shin-ichiro , Fujita Satoshi
Published: October 2022

Metastasis is a major complication of cancer treatments. Studies of the migratory behavior of cells are needed to investigate and control metastasis. Metastasis is based on the epithelial–mesenchymal transition, in which epithelial cells acquire mesenchymal properties and the ability to leave the population to invade other regions of the body. In collective migration, highly migratory “leader” cells are found at the front of the cell population, as well as cells that “follow” these leader cells. However, the interactions between these cells are not well understood. We examined the migration properties of leader–follower cells during collective migration at the single-cell level. Different mixed ratios of “leader” and “follower” cell populations were compared. Collective migration was quantitatively analyzed from two perspectives: cell migration within the colony and migration of the entire colony. Analysis of the effect of the cell mixing ratio on migration behavior showed that a small number of highly migratory cells enhanced some of the migratory properties of other cells. The results provide useful insights into the cellular interactions in collective cell migration of cancer cell invasion.
Chronic Nodular Prurigo: An Update on the Pathogenesis and Treatment
Authors: Wong Lai-San , Yen Yu-Ta
Published: October 2022

Chronic nodular prurigo (CNPG) is a recalcitrant chronic itchy disorder that affects the quality of life. It can be triggered by multiple etiologies, such as atopic dermatitis, diabetes, and chronic renal diseases. The mechanisms of CNPG are complicated and involved the interaction of the cutaneous, immune, and nervous systems. Diverse immune cells, including eosinophils, neutrophils, T cells, macrophages, and mast cells infiltrated the lesional skin of CNPG, which initiated the inflammatory cytokines and pruritogens release. In addition, the interaction between the immune cells and activated peripheral sensory nerve fibers by neurotransmitters caused neuroinflammation in the skin and intractable itch. This itch-scratch vicious cycle of CNPG results in disease exacerbation. CNPG is difficult to treat with traditional therapies. Recently, great advances have been made in the pathophysiology of both inflammation and pruritus transmission in CNPG. In this review, we summarize the updated mechanisms and novel therapies for CNPG.
Emerging Roles of RNA-Binding Proteins in Inner Ear Hair Cell Development and Regeneration
Authors: Shi De-Li , Cheng Xiao-Ning , Saquet Audrey , Grifone Raphaëlle
Published: October 2022

RNA-binding proteins (RBPs) regulate gene expression at the post-transcriptional level. They play major roles in the tissue- and stage-specific expression of protein isoforms as well as in the maintenance of protein homeostasis. The inner ear is a bi-functional organ, with the cochlea and the vestibular system required for hearing and for maintaining balance, respectively. It is relatively well documented that transcription factors and signaling pathways are critically involved in the formation of inner ear structures and in the development of hair cells. Accumulating evidence highlights emerging functions of RBPs in the post-transcriptional regulation of inner ear development and hair cell function. Importantly, mutations of splicing factors of the RBP family and defective alternative splicing, which result in inappropriate expression of protein isoforms, lead to deafness in both animal models and humans. Because RBPs are critical regulators of cell proliferation and differentiation, they present the potential to promote hair cell regeneration following noise- or ototoxin-induced damage through mitotic and non-mitotic mechanisms. Therefore, deciphering RBP-regulated events during inner ear development and hair cell regeneration can help define therapeutic strategies for treatment of hearing loss. In this review, we outline our evolving understanding of the implications of RBPs in hair cell formation and hearing disease with the aim of promoting future research in this field.