bluuebunny/crossref_metadata_2025 huggingface dataset:
Update on the Phenotypic and Genotypic Spectrum of KIF11-Related Retinopathy
Authors: Wang You , Zhang Zhaotian , Huang Li , Sun Limei , Li Songshan , Zhang Ting , Ding Xiaoyan
Published: April 2022

Background: This study aimed to report the frequency of KIF11-mutations in a large familial exudative vitreoretinopathy (FEVR) population, extend the clinical spectrum of KIF11-associated retinopathy and compare KIF11-associated retinopathy to FEVR with mutations in other genes. Methods: Genetic data collected from 696 FEVR families were reviewed. The ocular phenotypes in patients with KIF11 mutations were analyzed and compared with those of FEVR patients with mutations in other genes (FZD4, TSPAN12, LRP5, NDP and JAG1). Results: In a cohort of 696 FEVR families, disease-causing KIF11 mutations were identified in 3.6% of families (25/696). Among 25 KIF11 mutations, 80% (20/25) carried variants of loss of function and 48% (12/25) of variants were de novo. The phenotypes were variable. Compared with FEVR with disease-causing mutations in other genes, chorioretinal dysplasia was observed in 44.2% (31/70) of eyes with KIF11-associated retinopathy and in only 1.3% (1/70) of eyes with FEVR with mutations in other genes (p < 0.01). Increase and straightening of peripheral vessels (ISPV) was observed in 17.1% (12/70) of eyes with KIF11-associated retinopathy, and in 50% (39/78) of eyes with FEVR with mutations in other genes (p < 0.01). Conclusions: The frequency of the KIF11 mutation in FEVR was 3.6% in our database. The manifestation of KIF11-associated retinopathy was variable and different from the phenotype in FEVR caused by other genes. Chorioretinal dysplasia, instead of retinal folds, was the dominant phenotype in KIF11-associated retinopathy. ISPV was rare in KIF11-associated retinopathy. Moreover, our study revealed that most pathogenic KIF11 mutations were de novo.
Physical Activity and Its Diurnal Fluctuations Vary by Non-Motor Symptoms in Patients with Parkinson’s Disease: An Exploratory Study
Authors: Nagaki Koichi , Fujioka Shinsuke , Sasai Hiroyuki , Yamaguchi Yumiko , Tsuboi Yoshio
Published: April 2022

Background: This exploratory study investigated the association between non-motor symptoms (NMS) and both physical activity and diurnal activity patterns in patients with Parkinson’s disease (PwPD). Methods: Participants included PwPD with modified Hoehn and Yahr stages 1–3. The presence of NMS was assessed with Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part I. Physical activity was measured using a waist-mounted triaxial accelerometer. Logistic regression analyses evaluated associations between NMS and physical activity; furthermore, diurnal fluctuation in physical activity due to NMS was examined by ANCOVA. Results: Forty-five PwPD were included in the study. Among the domains of NMS, pain and other sensations (OR, 8.36; 95% CI, 1.59–43.94) and fatigue (OR, 14.26; 95% CI, 1.85–109.90) were associated with low daily step count (<4200 steps/day). Analysis by time of day showed no characteristic variability in physical activity but had constant effect sizes for pain and other sensations (p = 0.20, ES = 0.36) and fatigue (p = 0.08, ES = 0.38). Conclusion: Our exploratory study suggested that PwPD with pain and other sensations and fatigue recorded lower step counts than their asymptomatic counterparts. Therefore, PwPD with pain and fatigue may need more support in promoting physical activity.
Public Health Financing and Responses to COVID-19: Lessons from South Korea
Authors: Park Hyeki , Sim Boram , Zhao Bo , Nam Eun Woo
Published: April 2022

Health financing strategies contribute significantly to containing the outbreak of the Coronavirus disease 2019 (COVID-19). This study aims to reassess Korea’s financing strategies in response to COVID-19 in 2020, to ascertain its effects and sustainability. The Joint External Evaluation tool was adopted to analyze the data collected from government reports, official statistics, and other sources. Findings show that Korea could maintain a low incidence and fatality rate compared with other countries, at low costs. It was a result of rapidly procured healthcare resources based on laws and policies established after the 2015 epidemic, and the National Health Insurance. However, to achieve long-term sustainability, it is important to enhance the financial stability of the national health insurance and increase the proportion of the public sector in healthcare resources.
Effect of Genotype and Harvest Date on Fruit Quality, Bioactive Compounds, and Antioxidant Capacity of Strawberry
Authors: Zhang Yunting , Yang Min , Hou Guoyan , Zhang Yong , Chen Qing , Lin Yuanxiu , Li Mengyao , Wang Yan , He Wen , Wang Xiaorong , Tang Haoru , Luo Ya
Published: April 2022

Fruit quality is strongly affected by genotype and harvest date. In this study, parameters regarding fruit quality, bioactive compounds, and antioxidant capacity of different strawberry cultivars at three harvesting dates were quantified to elucidate the influence of genotype and harvest date on strawberry quality. The results showed that harvest date was the major contributor to appearance color, TSS, TA, and TSS/TA ratio of strawberries, while genotype mainly affected firmness, anthocyanin content, and antioxidant capacity. Moreover, the interaction of genotype and harvest date had a primary influence on the content of ascorbic acid. The content of total phenolics and amino acids received the similar influence caused by genotype and harvest date. However, the interaction of genotype and harvest date significantly affected total phenolic content as well. These findings give a better understanding of the influence of the genotype and harvest date on strawberry, which might contribute to breed cultivars with more attractive fruits in terms of quality acceptance and nutritional value.
Consumer Cognition and Management Perspective on Express Packaging Pollution
Authors: Wu Sisi , Gong Xuan , Wang Yunfei , Cao Jian
Published: April 2022

Consumer awareness of environmental protection is getting stronger. However, with the development of the logistics industry, the environmental pollution caused by express packaging has become increasingly severe. Therefore, it is of great importance to know consumer cognition and willingness about how to reduce the express packaging pollution. In this study, through the analysis of 561 questionnaires, we analyze the impact of consumer evaluation of recyclable express packaging and green express packaging on responsibility awareness of government, logistics enterprises, and e-commerce corporates, and analyze whether there is a positive correlation between consumer evaluation and reducing environmental pressure. We find that consumers are willing to use recyclable express packaging and green express packaging, especially the latter. Moreover, the government is supposed to play a central role in solving environmental pollution problems caused by express packaging. It is recommended that the government proposes some corresponding solutions, such as introducing a packaging tax policy, setting up an environmental fund, and developing environment-friendly packaging materials. Meanwhile, consumers expect logistics enterprises and e-commerce companies to cooperate with the government actively and switch to using environment-friendly express packaging in a timely manner.
“Did You Bring It Home with You?” A Qualitative Investigation of the Impacts of the COVID-19 Pandemic on Victorian Frontline Healthcare Workers and Their Families
Authors: Sheen Jade , Clancy Elizabeth M. , Considine Julie , Dwyer Alison , Tchernegovski Phillip , Aridas Anna , Lee Brian En Chyi , Reupert Andrea , Boyd Leanne
Published: April 2022

Concerns regarding the physical and mental health impacts of frontline healthcare roles during the COVID-19 pandemic have been well documented, but the impacts on family functioning remain unclear. This study provides a unique contribution to the literature by considering the impacts of the COVID-19 pandemic on frontline healthcare workers and their families. Thirty-nine frontline healthcare workers from Victoria, Australia, who were parents to at least one child under 18 were interviewed. Data were analysed using reflexive thematic analysis. Five superordinate and 14 subordinate themes were identified. Themes included more family time during lockdowns, but at a cost; changes in family responsibilities and routines; managing increased demands; healthcare workers hypervigilance and fear of bringing COVID-19 home to their family members; ways in which families worked to “get through it”. While efforts have been made by many healthcare organisations to support their workers during this challenging time, the changes in family functioning observed by participants suggest that more could be done for this vulnerable cohort, particularly with respect to family support.
Efficacy of Mobile Health Applications to Improve Physical Activity and Sedentary Behavior: A Systematic Review and Meta-Analysis for Physically Inactive Individuals
Authors: Zhang Meng , Wang Wei , Li Mingye , Sheng Haomin , Zhai Yifei
Published: April 2022

Physical inactivity and sedentary behavior (SB) have attracted growing attention globally since they relate to noninfectious chronic diseases (NCDs) and could further result in the loss of life. This systematic literature review aimed to identify existing evidence on the efficacy of mobile health (mHealth) technology in inducing physical activity and reducing sedentary behavior for physically inactive people. Studies were included if they used a smartphone app in an intervention to improve physical activity and/or sedentary behavior for physically inactive individuals. Interventions could be stand-alone interventions or multi-component interventions, including an app as one of several intervention components. A total of nine studies were included, and all were randomized controlled trials. Two studies involved interventions delivered solely via a mobile application (stand-alone intervention) and seven studies involved interventions that used apps and other intervention strategies (multi-component intervention). Methodological quality was assessed, and the overall quality of the studies was ensured. The pooled data favored intervention in improving physical activity and reducing sedentary behavior. This review provided evidence that mobile health intervention improved physical activity and reduced sedentary behavior among inactive individuals. More beneficial effects can be guaranteed when interventions include multiple components. Further studies that maintain the effectiveness of such interventions are required to maximize user engagement and intervention efficacy.
Reference Ranges of Selenium in Plasma and Whole Blood for Child-Bearing-Aged Women in China
Authors: Cao Yang , Zhang Huidi , Yang Jingxin , Man Qingqing , Song Pengkun , Mao Deqian , Lu Jiaxi , Yang Lichen
Published: April 2022

Selenium (Se) is a “dual-surface” element. Both Se-deficiency and Se-overload have bad effects on humans. The amount of Se in the blood is a good indicator of Se intake, and there are considerable differences in the reference ranges among different regions and populations. The purpose of this study was to establish the age-specific reference interval of blood Se in healthy child-bearing-aged women in China. A total of 187 healthy women aged 18–45 years old were enrolled with strict inclusion criteria from the China Adult Chronic Disease and Nutrition Surveillance (2015 CACDNS) database to establish the reference interval of Se. Plasma and whole-blood Se were detected by inductively coupled plasma mass spectrometry (ICP-MS). The reference range (RR) estimated as P2.5–P97.5 percentiles (geometric mean) was 73.81–140.75 (100.94) μg/L and P2.5–P97.5 percentiles (median) 81.06–164.75 (121.05) μg/L for plasma and whole-blood Se, respectively. The proposed RR of plasma Se in this study was used to evaluate the Se nutritional status of a representative sample of 1950 women of child-bearing age who were randomly selected from 2015 CACDNS. The proportion of Se level lower than P2.5 cut-off value was 24.05%, and there were 5.08% child-bearing-aged women with plasma Se higher than the upper limit of RR. Women in the western and rural areas tend to have lower Se levels.
Exploring the Workplace Bullying of Indonesian Caregivers and Its Influencing Factors in Taiwan
Authors: Lu Yun-Ping , Lee Bih-O , Liu Chih-Kuang , Chueh Ke-Hsin
Published: April 2022

Background: Bullying can pose a risk to the health and safety of humans, including the risk of damage to the emotional, psychosocial, mental, or physical health of employees in the workplace. In this study, we aimed to understand the personal characteristics, mental health, sleep quality, and workplace bullying status of Indonesian caregivers and explore the influencing factors of workplace bullying among them. Methods: This cross-sectional study was based on a structured questionnaire in Indonesian, which was designed to collect the data of essential personal characteristics, workplace bullying, sleep quality, and mental health using the Indonesian versions of the Negative Acts Questionnaire–Revised (NAQ-R), Pittsburgh Sleep Quality Index (PSQI), and the Brief Symptoms Rating Scale (BSRS-5). Results: A total of 60.9% of Indonesian caregivers never experienced workplace bullying in Taiwan. A multiple regression analysis revealed that being a household caregiver (β = 0.14, p = 0.021), sleep quality (β = 0.18, p = 0.031), and mental health (β = 0.44, p < 0.001) were significantly correlated with the overall workplace bullying scores of the respondents and revealed that these three variables explained 45% of the variance. Conclusions: Taiwan Indonesian caregivers have a similar workplace bullying rate to Indonesian employees in the workplace. This study indicated the relationships among the workplace bullying of foreign caregivers and demonstrated that being a household caregiver, sleep quality, and mental health were closely related.
Involvement of Non-Parental Caregivers in Obesity Prevention Interventions among 0–3-Year-Old Children: A Scoping Review
Authors: Ramirez Andrea , Tovar Alison , Garcia Gretel , Nieri Tanya , Hernandez Stephanie , Sastre Myrna , Cheney Ann M.
Published: April 2022

Introduction: We examined the scope of literature including non-parental caregiver involvement in child obesity prevention interventions. Methods: We conducted a scoping review following the Arksey and O’Malley framework, including only studies reporting the effect of an intervention on growth, weight, or early childhood obesity risk among children ages 0 to three years, published between 2000 and 2021. Interventions that did not include non-parental caregivers (adults regularly involved in childcare other than parents) were excluded. Results: Of the 14 studies that met the inclusion criteria, all were published between 2013 and 2020, and most interventions (n = 9) were implemented in the United States. Eight of the 14 interventions purposefully included other non-parental caregivers: five included both parents and non-parental caregivers, and the remaining three included only non-parental caregivers. Most interventions (n = 9) showed no significant impact on anthropometric outcomes. All interventions found improvements in at least one behavioral outcome (e.g., food groups intake (n = 5), parental feeding practices (n = 3), and screen time (n = 2)). This review can inform future interventions that plan to involve non-parental caregivers, which may be beneficial in shaping early health behaviors and preventing obesity early in life.
Biomechanical Risks Associated with Foot and Ankle Injuries in Ballet Dancers: A Systematic Review
Authors: Li Fengfeng , Adrien Ntwali , He Yuhuan
Published: April 2022

Professional ballet dancers can be classified as dance artists and sports performers. This systematic review aims to consider the biomechanical risk factors for foot and ankle injuries in ballet dancers, as this could potentially reduce the impact that ‘cost of injury’ may have on ballet companies. An additional outcome was to examine the effects of injury on the career of ballet dancers. This study searched articles in four electronic databases for information in peer-reviewed journals. The included articles examined the relationships between biomechanical factors and the relationship between ballet shoes and foot performance. There were 9 articles included in this review. Among these articles, two focused on the peak force of the foot using two types of pointe shoes, three focused on overuse injuries of the ballet dancer’s foot, one article focused on the loading of the foot of a dancer, and three articles focused on the function and biomechanics of the foot in dancers. This review also found that the pointe shoe condition was the most important factor contributing to a foot injury; overuse injury related to high-intensity training and affected both the ankle and the foot; and metatarsophalangeal joint injury related to the function and structure of the foot. Finally, strengthening the lower extremity muscle is also a recommendation to improve muscle coordination and reduce injuries.
Diverging Trends and Expanding Educational Gaps in Smoking in China
Authors: Jin Lei , Tao Lin , Lao Xiangqian
Published: April 2022

Introduction: The male smoking rate in China declined moderately through the 1990s and early 2000s, but the decline has since stagnated. It is unclear why the decline stalled and whether it stalled uniformly across all social strata. Theories that view socioeconomic status as a fundamental cause of health predict that socioeconomic gaps in smoking may widen, but theories emphasizing the cultural context of health behavior cast doubt on the prediction. We investigated changes in the socioeconomic gaps in smoking during recent decades in China. Methods: We applied growth-curve models to examine inter- and intra-cohort changes in socioeconomic gaps in male smoking in China using data from a national longitudinal survey spanning 25 years. Results: We found diverging trends in smoking in men with different education levels among the post-1980 cohorts; for high-education men, smoking participation consistently declined, but for low-education men, the decline stopped and possibly reversed. The stagnation in the decline in overall smoking rate since 2010 was mostly due to the stalling of the decline of smoking among low-education men in the most recent cohorts. The diverging trends were a continuation of a general trend in expanding educational gaps in smoking that emerged in the cohorts born after 1960. Our analysis also identified widening educational gaps over age within each cohort. Conclusion: We identified a long-term widening in educational gaps in smoking in China. An effective way to reduce smoking, social inequality in smoking and possibly health disparities in China is to target the smoking behavior of vulnerable groups.
Current Situation of Palytoxins and Cyclic Imines in Asia-Pacific Countries: Causative Phytoplankton Species and Seafood Poisoning
Authors: Kim Young-Sang , An Hyun-Joo , Kim Jaeseong , Jeon You-Jin
Published: April 2022

Among marine biotoxins, palytoxins (PlTXs) and cyclic imines (CIs), including spirolides, pinnatoxins, pteriatoxins, and gymnodimines, are not managed in many countries, such as the USA, European nations, and South Korea, because there are not enough poisoning cases or data for the limits on these biotoxins. In this article, we review unregulated marine biotoxins (e.g., PlTXs and CIs), their toxicity, causative phytoplankton species, and toxin extraction and detection protocols. Due to global warming, the habitat of the causative phytoplankton has expanded to the Asia-Pacific region. When ingested by humans, shellfish that accumulated toxins can cause various symptoms (muscle pain or diarrhea) and even death. There are no systematic reports on the occurrence of these toxins; however, it is important to continuously monitor causative phytoplankton and poisoning of accumulating shellfish by PlTXs and CI toxins because of the high risk of toxicity in human consumers.
Feasibility of the Remote Physical Activity Follow-Up Intervention after the Face-to-Face Program for Healthy Middle-Aged Adults: A Randomized Trial Using ICT and Mobile Technology
Authors: Yamatsu Koji , Narazaki Kenji
Published: April 2022

Although the effectiveness of face-to-face and remote intervention for increasing and maintaining physical activity (PA) have been compared, the effect of combining the two forms of intervention is unknown. The purpose of this study was to examine the feasibility of the remote PA follow-up intervention after the face-to-face PA program on changing PA behaviors and some health outcomes in healthy middle-aged adults. As a secondary analysis, we also attempted a preliminary analysis of the difference in the number of behavior change interviews in the remote PA follow-up intervention. After the face-to-face intervention, 30 healthy subjects were randomly divided into four behavior change coaching interviews (BCI4 group) or three BCI (BCI3 group). The results of this study showed that body weight, body fat mass, and waist circumference were significantly reduced after face-to-face intervention, and were further reduced after remote PA follow-up intervention. However, the difference in the number of BCI affected only body fat mass. The remote PA follow-up intervention may have potential to maintain the effects of face-to-face intervention. In the future, it is necessary to refine the research design and conduct a full-scale intervention study.
Work-Life Stress during the Coronavirus Pandemic among Latina Farmworkers in a Rural California Region
Authors: Keeney Annie J. , Quandt Amy , Flores Daniela , Flores Luis
Published: April 2022

Objectives: To examine the type and severity of stressors experienced among Latina farmworkers during the COVID-19 pandemic. Methods: A survey containing the Migrant Farmworker Stress Inventory was administered to 77 female-identifying Latina farmworkers working in a US–Mexico border region. A sub-sample of five participants participated in key-informant interviews. Data collection occurred in Summer 2021. Results: Nearly 40% of Latina farmworkers reported high stress levels indicative of clinical mental health risks. Health and safety concerns and experienced stressors identified included visible substance abuse and poor bathroom conditions at the field site, language barriers, and balancing work and home life demands. Conclusions: Latina farmworkers have unique health and safety needs, and COVID-19 has contributed to the experienced stressors. Understanding the familial and working environment sources of stress specific to female agriculture workers is imperative to implementing culturally and gender-responsive strategies to better support the health and safety of farming populations in future pandemics.
Gender Differences in the Factors Associated with Alcohol Binge Drinking: A Population-Based Analysis in a Latin American Country
Authors: Hernández-Vásquez Akram , Chacón-Torrico Horacio , Vargas-Fernández Rodrigo , Grendas Leandro Nicolás , Bendezu-Quispe Guido
Published: April 2022

Alcohol consumption is a public health problem in Peru, fostered by traditional practices, where promoting social interaction in celebrations, facilitating field work as a source of energy and warmth, and achieving objectives in certain labor negotiations, play an important role. However, research on the risk factors of binge drinking according to gender is limited. The study aim was to determine the factors associated with binge drinking in the Peruvian adult population by gender. An analytical study of secondary data from the 2018 Peruvian Demographic and Family Health Survey was conducted. The dependent variable was binge drinking in the last 30 days. Adjusted prevalence ratios (aPR) were estimated for the association between sociodemographic and health-related variables with binge drinking. A total of 32,020 adults were included. Binge drinking was found in 22.4%. Men (32.6%; 95% confidence interval [CI]: 31.4–33.8) presented a higher consumption pattern compared to women (12.8%; 95% CI: 12.0–13.6). For both genders, differences were found in binge drinking according to sociodemographic characteristics (age and wealth quintile was associated in both genders while the educational level was associated only for men, and ethnic self-identification and marital status for women) and health- characteristics related (health insurance, smoking in the last 30 days, overweight and obesity were associated in both genders). Several factors are associated with binge drinking according to gender in the Peruvian population, including age and education level among men, as well as marital status and ethnic self-identification among women.
Effect of the COVID-19 Confinement Period on Selected Neuromuscular Performance Indicators in Young Male Soccer Players: Can the Maturation Process Counter the Negative Effect of Detraining?
Authors: Asimakidis Nikolaos D. , Vasileiou Stylianos S. , Dalamitros Athanasios A. , Nikolaidis Pantelis T. , Manou Vasiliki
Published: April 2022

The COVID-19 outbreak has led to an unprecedented long-term cessation in athletes’ training routines. This study examined the effect of a 32-week detraining period, caused by the COVID-19 pandemic lockdown, on selected neuromuscular performance indicators in 29 young male soccer players, assessed close to their adolescent growth spurt (age = 13.0 ± 0.8 years). Change of direction ability of both lower limbs (COD), linear sprint times (10 and 20 m), and vertical jump height (CMJ) was evaluated twice, once before the first national lockdown, and one week after the return to training activities. Paired-sample t-tests detected significant improvements in all three testing variables (COD: 2.82 ± 0.23 vs. 2.66 ± 0.22 s, p ≤ 0.005, 0.001, effect size [ES] = 0.91 to 1.05 for the right and left limb, respectively; 10 m: 2.12 ± 0.16 vs. 1.96 ± 0.15 s, p ≤ 0.001, effect size [ES] = 1.67, 20 m: 3.56 ± 0.3 vs. 3.42 ± 0.27 s, p ≤ 0.001, effect size [ES] = 1.02 and CMJ: 23.3 ± 7.5 vs. 24.5 ± 7.6 cm, p = 0.033, ES = 0.42). These results indicate that maturation-related adaptations can lead to enhanced change of direction, linear sprint, and vertical jump performance, even in the absence of exposure to any level of exercise. Soccer coaches and practitioners working with youth athletes should consider the stage of maturation when planning and implementing training programs aiming to enhance neuromuscular performance.
Quantitative Relations between Topological Similarity Degree and Map Scale Change of Contour Clusters in Multi-Scale Map Spaces
Authors: Wang Rong , Yan Haowen , Lu Xiaomin
Published: April 2022

Quantitative relations between topological similarity degree and map scale change of multi-scale contour clusters are vital to the automation of map generalization. However, no method has been proposed to calculate the relations. This paper aims at filling the gap by proposing a new approach. It firstly constructed a directed contour tree by pre-processing of unclosed contours, and then developed a quantitative expression of topological relations of contour cluster based on directed contour tree. After this, it employed 108 groups of multi-scale contour clusters with different geomorphological types to explore the changing regularity of topological indices with map scale. Last, it used 416 points to calculate the quantitative relations between topological similarity degree and map scale change by curve fitting method. The results show that the quantitative expression of multi-scale topological indexes is closely related to the contour interval change, and power function is the best fit among the candidate functions.
Landslide Susceptibility Assessment Considering Spatial Agglomeration and Dispersion Characteristics: A Case Study of Bijie City in Guizhou Province, China
Authors: Yao Kezhen , Yang Saini , Wu Shengnan , Tong Bin
Published: April 2022

Landslide susceptibility assessment serves as a critical scientific reference for geohazard control, land use, and sustainable development planning. The existing research has not fully considered the potential impact of the spatial agglomeration and dispersion of landslides on assessments. This issue may cause a systematic evaluation bias when the field investigation data are insufficient, which is common due to limited human resources. Accordingly, this paper proposes two novel strategies, including a clustering algorithm and a preprocessing method, for these two ignored features to strengthen assessments, especially in high-susceptibility regions. Multiple machine learning models are compared in a case study of the city of Bijie (Guizhou Province, China). Then we generate the optimal susceptibility map and conduct two experiments to test the validity of the proposed methods. The primary conclusions of this study are as follows: (1) random forest (RF) was superior to other algorithms in the recognition of high-susceptibility areas and the portrayal of local spatial features; (2) the susceptibility map incorporating spatial feature messages showed a noticeable improvement over the spatial distribution and gradual change of susceptibility, as well as the accurate delineation of critical hazardous areas and the interpretation of historical hazards; and (3) the spatial distribution feature had a significant positive effect on modeling, as the accuracy increased by 5% and 10% after including the spatial agglomeration and dispersion consideration in the RF model, respectively. The benefit of the agglomeration is concentrated in high-susceptibility areas, and our work provides insight to improve the assessment accuracy in these areas, which is critical to risk assessment and prevention activities.
Therapeutic Approaches of Ryanodine Receptor-Associated Heart Diseases
Authors: Szentandrássy Norbert , Magyar Zsuzsanna É. , Hevesi Judit , Bányász Tamás , Nánási Péter P. , Almássy János
Published: April 2022

Cardiac diseases are the leading causes of death, with a growing number of cases worldwide, posing a challenge for both healthcare and research. Therefore, the most relevant aim of cardiac research is to unravel the molecular pathomechanisms and identify new therapeutic targets. Cardiac ryanodine receptor (RyR2), the Ca2+ release channel of the sarcoplasmic reticulum, is believed to be a good therapeutic target in a group of certain heart diseases, collectively called cardiac ryanopathies. Ryanopathies are associated with the impaired function of the RyR, leading to heart diseases such as congestive heart failure (CHF), catecholaminergic polymorphic ventricular tachycardia (CPVT), arrhythmogenic right ventricular dysplasia type 2 (ARVD2), and calcium release deficiency syndrome (CRDS). The aim of the current review is to provide a short insight into the pathological mechanisms of ryanopathies and discuss the pharmacological approaches targeting RyR2.
Inhibition of KIF23 Alleviates IPAH by Targeting Pyroptosis and Proliferation of PASMCs
Authors: Wu Zeang , Zhou Guangyuan , Wang Haixia , Yao Ping
Published: April 2022

Idiopathic pulmonary arterial hypertension (IPAH) is a progressive vascular disease with high mortality and heritability. Pyroptosis is a novel form of programmed cell death, and it is closely associated with IPAH. However, the roles of pyroptosis-related genes (PRGs) in IPAH are still largely unknown. In this study, we identified KIF23 as the most relevant gene for IPAH and pyroptosis, and its expression was significantly increased in pulmonary arterial smooth muscle cells (PASMCs) of IPAH. Besides, the pyroptosis level of PASMCs was also considerably upregulated in IPAH. Knockdown of KIF23 in PASMCs could significantly suppress the PASMCs’ pyroptosis and proliferation and then alleviate the increase in pulmonary arterial pressure, right ventricular hypertrophy, and pulmonary vascular resistance in IPAH. KIF23 regulated the expression of Caspase3, NLRP3, and HMGB1, and they were all involved in the PI3K/AKT and MAPK pathways, indicating that PI3K/AKT and MAPK pathways might participate in regulating PASMCs pyroptosis by KIF23. In conclusion, our study suggests that KIF23 may be a new therapeutic target for IPAH, which can alleviate the symptoms of IPAH by inhibiting the pyroptosis and proliferation of PASMCs.
Editorial of Special Issue “The Self-Assembly and Design of Polyfunctional Nanosystems 2.0”
Authors: Kashapov Ruslan , Zakharova Lucia
Published: April 2022

The intention of this Special Issue, entitled “The Self-Assembly and Design of Polyfunctional Nanosystems 2 [...]
Identification of Novel Natural Product Inhibitors against Matrix Metalloproteinase 9 Using Quantum Mechanical Fragment Molecular Orbital-Based Virtual Screening Methods
Authors: Lim Hocheol , Hong Hansol , Hwang Seonik , Kim Song Ja , Seo Sung Yum , No Kyoung Tai
Published: April 2022

Matrix metalloproteinases (MMPs) are calcium-dependent zinc-containing endopeptidases involved in multiple cellular processes. Among the MMP isoforms, MMP-9 regulates cancer invasion, rheumatoid arthritis, and osteoarthritis by degrading extracellular matrix proteins present in the tumor microenvironment and cartilage and promoting angiogenesis. Here, we identified two potent natural product inhibitors of the non-catalytic hemopexin domain of MMP-9 using a novel quantum mechanical fragment molecular orbital (FMO)-based virtual screening workflow. The workflow integrates qualitative pharmacophore modeling, quantitative binding affinity prediction, and a raw material search of natural product inhibitors with the BMDMS-NP library. In binding affinity prediction, we made a scoring function with the FMO method and applied the function to two protein targets (acetylcholinesterase and fibroblast growth factor 1 receptor) from DUD-E benchmark sets. In the two targets, the FMO method outperformed the Glide docking score and MM/PBSA methods. By applying this workflow to MMP-9, we proposed two potent natural product inhibitors (laetanine 9 and genkwanin 10) that interact with hotspot residues of the hemopexin domain of MMP-9. Laetanine 9 and genkwanin 10 bind to MMP-9 with a dissociation constant (KD) of 21.6 and 0.614 μM, respectively. Overall, we present laetanine 9 and genkwanin 10 for MMP-9 and demonstrate that the novel FMO-based workflow with a quantum mechanical approach is promising to discover potent natural product inhibitors of MMP-9, satisfying the pharmacophore model and good binding affinity.
Linear and Circular Long Non-Coding RNAs in Acute Lymphoblastic Leukemia: From Pathogenesis to Classification and Treatment
Authors: Maimaitiyiming Yasen , Ye Linyan , Yang Tao , Yu Wenjuan , Naranmandura Hua
Published: April 2022

The coding regions account for only a small part of the human genome, and the remaining vast majority of the regions generate large amounts of non-coding RNAs. Although non-coding RNAs do not code for any protein, they are suggested to work as either tumor suppressers or oncogenes through modulating the expression of genes and functions of proteins at transcriptional, posttranscriptional and post-translational levels. Acute Lymphoblastic Leukemia (ALL) originates from malignant transformed B/T-precursor-stage lymphoid progenitors in the bone marrow (BM). The pathogenesis of ALL is closely associated with aberrant genetic alterations that block lymphoid differentiation and drive abnormal cell proliferation as well as survival. While treatment of pediatric ALL represents a major success story in chemotherapy-based elimination of a malignancy, adult ALL remains a devastating disease with relatively poor prognosis. Thus, novel aspects in the pathogenesis and progression of ALL, especially in the adult population, need to be further explored. Accumulating evidence indicated that genetic changes alone are rarely sufficient for development of ALL. Recent advances in cytogenic and sequencing technologies revealed epigenetic alterations including that of non-coding RNAs as cooperating events in ALL etiology and progression. While the role of micro RNAs in ALL has been extensively reviewed, less attention, relatively, has been paid to other non-coding RNAs. Herein, we review the involvement of linear and circular long non-coding RNAs in the etiology, maintenance, and progression of ALL, highlighting the contribution of these non-coding RNAs in ALL classification and diagnosis, risk stratification as well as treatment.
A Non-Hazardous Deparaffinization Protocol Enables Quantitative Proteomics of Core Needle Biopsy-Sized Formalin-Fixed and Paraffin-Embedded (FFPE) Tissue Specimens
Authors: Mitsa Georgia , Guo Qianyu , Goncalves Christophe , Preston Samuel E. J. , Lacasse Vincent , Aguilar-Mahecha Adriana , Benlimame Naciba , Basik Mark , Spatz Alan , Batist Gerald , Miller Wilson H. , del Rincon Sonia V. , Zahedi René P. , Borchers Christoph H.
Published: April 2022

Most human tumor tissues that are obtained for pathology and diagnostic purposes are formalin-fixed and paraffin-embedded (FFPE). To perform quantitative proteomics of FFPE samples, paraffin has to be removed and formalin-induced crosslinks have to be reversed prior to proteolytic digestion. A central component of almost all deparaffinization protocols is xylene, a toxic and highly flammable solvent that has been reported to negatively affect protein extraction and quantitative proteome analysis. Here, we present a ‘green’ xylene-free protocol for accelerated sample preparation of FFPE tissues based on paraffin-removal with hot water. Combined with tissue homogenization using disposable micropestles and a modified protein aggregation capture (PAC) digestion protocol, our workflow enables streamlined and reproducible quantitative proteomic profiling of FFPE tissue. Label-free quantitation of FFPE cores from human ductal breast carcinoma in situ (DCIS) xenografts with a volume of only 0.79 mm3 showed a high correlation between replicates (r2 = 0.992) with a median %CV of 16.9%. Importantly, this small volume is already compatible with tissue micro array (TMA) cores and core needle biopsies, while our results and its ease-of-use indicate that further downsizing is feasible. Finally, our FFPE workflow does not require costly equipment and can be established in every standard clinical laboratory.
HPR1 Is Required for High Light Intensity Induced Photorespiration in Arabidopsis thaliana
Authors: Wang Zi , Wang Yetao , Wang Yukun , Li Haotian , Wen Zhiting , Hou Xin
Published: April 2022

High light intensity as one of the stresses could lead to generation of large amounts of reactive oxygen species (ROS) in plants, resulting in severe plant growth retardation. The photorespiration metabolism plays an important role in producing and removing a variety of ROS, maintaining the dynamic balance of the redox reaction, and preventing photoinhibition. Arabidopsis hydroxypyruvate reductase 1 (HPR1) is a primary metabolic enzyme in the photorespiration cycle. However, the role of HPR1 in plants response to high light is not clear. Here, we found that the expression of HPR1 could be induced by high light intensity. The growth and photosynthetic capacity of hpr1 mutants are seriously affected under high light intensity. The absence of HPR1 suppresses the rates of photorepair of Photosystem II (PSII), aggravates the production of ROS, and accelerates photorespiration rates. Moreover, the activity of ROS scavenging enzymes in the hpr1 mutants is significantly higher. These results indicate that HPR1 is involved in plant response to high light intensity and is essential for maintaining the dynamic balance of ROS and photorespiration.
Comment on Tremmel et al. In Vitro Metabolism of Six C-Glycosidic Flavonoids from Passiflora incarnata L. Int. J. Mol. Sci. 2021, 22, 6566
Authors: Beszterda Monika , Frański Rafał
Published: April 2022

In recent years, growing attention has been paid to the chemical composition of aerial parts extracts and the bioavailability of active compounds from different species of Passiflora genus [...]
Thrombin Preconditioning Improves the Therapeutic Efficacy of Mesenchymal Stem Cells in Severe Intraventricular Hemorrhage Induced Neonatal Rats
Authors: Jung So Yeon , Kim Young Eun , Park Won Soon , Ahn So Yoon , Sung Dong Kyung , Sung Se In , Joo Kyeung Min , Kim Seong Gi , Chang Yun Sil
Published: April 2022

Severe intraventricular hemorrhage (IVH) remains a major cause of high mortality and morbidity in extremely preterm infants. Mesenchymal stem cell (MSC) transplantation is a possible therapeutic option, and development of therapeutics with enhanced efficacy is necessary. This study investigated whether thrombin preconditioning improves the therapeutic efficacy of human Wharton’s jelly-derived MSC transplantation for severe neonatal IVH, using a rat model. Severe neonatal IVH was induced by injecting 150 μL blood into each lateral ventricle on postnatal day (P) 4 in Sprague-Dawley rats. After 2 days (P6), naïve MSCs or thrombin-preconditioned MSCs (1 × 105/10 μL) were transplanted intraventricularly. After behavioral tests, brain tissues and cerebrospinal fluid of P35 rats were obtained for histological and biochemical analyses, respectively. Thrombin-preconditioned MSC transplantation significantly reduced IVH-induced ventricular dilatation on in vivo magnetic resonance imaging, which was coincident with attenuations of reactive gliosis, cell death, and the number of activated microglia and levels of inflammatory cytokines after IVH induction, compared to naïve MSC transplantation. In the behavioral tests, the sensorimotor and memory functions significantly improved after transplantation of thrombin-preconditioned MSCs, compared to naïve MSCs. Overall, thrombin preconditioning significantly improves the therapeutic potential and more effectively attenuates brain injury, including progressive ventricular dilatation, gliosis, cell death, inflammation, and neurobehavioral functional impairment, in newborn rats with induced severe IVH than does naïve MSC transplantation.
Small RNAs beyond Model Organisms: Have We Only Scratched the Surface?
Authors: Boutet Emilie , Djerroud Samia , Perreault Jonathan
Published: April 2022

Small RNAs (sRNAs) are essential regulators in the adaptation of bacteria to environmental changes and act by binding targeted mRNAs through base complementarity. Approximately 550 distinct families of sRNAs have been identified since their initial characterization in the 1980s, accelerated by the emergence of RNA-sequencing. Small RNAs are found in a wide range of bacterial phyla, but they are more prominent in highly researched model organisms compared to the rest of the sequenced bacteria. Indeed, Escherichia coli and Salmonella enterica contain the highest number of sRNAs, with 98 and 118, respectively, with Enterobacteriaceae encoding 145 distinct sRNAs, while other bacteria families have only seven sRNAs on average. Although the past years brought major advances in research on sRNAs, we have perhaps only scratched the surface, even more so considering RNA annotations trail behind gene annotations. A distinctive trend can be observed for genes, whereby their number increases with genome size, but this is not observable for RNAs, although they would be expected to follow the same trend. In this perspective, we aimed at establishing a more accurate representation of the occurrence of sRNAs in bacteria, emphasizing the potential for novel sRNA discoveries.
E2F1 Expression and Apoptosis Initiation in Crayfish and Rat Peripheral Neurons and Glial Cells after Axonal Injury
Authors: Dzreyan Valentina , Eid Moez , Rodkin Stanislav , Pitinova Maria , Demyanenko Svetlana
Published: April 2022

Neurotrauma is among the main causes of human disability and mortality. The transcription factor E2F1 is one of the key proteins that determine the fate of cells. The involvement of E2F1 in the regulation of survival and death of peripheral nerve cells after axotomy has not been previously studied. We, for the first time, studied axotomy-induced changes in the expression and localization of E2F1 following axonal injury in rats and crayfish. Immunoblotting and immunofluorescence microscopy were used for the analysis of the expression and intracellular localization of E2F1 and its changes after axotomy. To evaluate whether this transcription factor promotes cell apoptosis, we examined the effect of pharmacological inhibition of E2F activity in axotomized rat models. In this work, axotomy caused increased expression of E2F1 as early as 4 h and even 1 h after axotomy of mechanoreceptor neurons and ganglia of crayfish ventral nerve cord (VNC), as well as rat dorsal root ganglia (DRG). The level of E2F1 expression increased both in the cytoplasm and the nuclei of neurons. Pharmacological inhibition of E2F demonstrated a pronounced neuroprotective activity against axotomized DRGs. E2F1 and downstream targets could be considered promising molecular targets for the development of potential neuroprotective agents.
CRISPR-Based Genome Editing: Advancements and Opportunities for Rice Improvement
Authors: Zegeye Workie Anley , Tsegaw Mesfin , Zhang Yingxin , Cao Liyong
Published: April 2022

To increase the potentiality of crop production for future food security, new technologies for plant breeding are required, including genome editing technology—being one of the most promising. Genome editing with the CRISPR/Cas system has attracted researchers in the last decade as a safer and easier tool for genome editing in a variety of living organisms including rice. Genome editing has transformed agriculture by reducing biotic and abiotic stresses and increasing yield. Recently, genome editing technologies have been developed quickly in order to avoid the challenges that genetically modified crops face. Developing transgenic-free edited plants without introducing foreign DNA has received regulatory approval in a number of countries. Several ongoing efforts from various countries are rapidly expanding to adopt the innovations. This review covers the mechanisms of CRISPR/Cas9, comparisons of CRISPR/Cas9 with other gene-editing technologies—including newly emerged Cas variants—and focuses on CRISPR/Cas9-targeted genes for rice crop improvement. We have further highlighted CRISPR/Cas9 vector construction model design and different bioinformatics tools for target site selection.
Transcriptomic Data Meta-Analysis Sheds Light on High Light Response in Arabidopsis thaliana L.
Authors: Bobrovskikh Aleksandr V. , Zubairova Ulyana S. , Bondar Eugeniya I. , Lavrekha Viktoriya V. , Doroshkov Alexey V.
Published: April 2022

The availability and intensity of sunlight are among the major factors of growth, development and metabolism in plants. However, excessive illumination disrupts the electronic balance of photosystems and leads to the accumulation of reactive oxygen species in chloroplasts, further mediating several regulatory mechanisms at the subcellular, genetic, and molecular levels. We carried out a comprehensive bioinformatic analysis that aimed to identify genetic systems and candidate transcription factors involved in the response to high light stress in Arabidopsis thaliana L. using resources GEO NCBI, string-db, ShinyGO, STREME, and Tomtom, as well as programs metaRE, CisCross, and Cytoscape. Through the meta-analysis of five transcriptomic experiments, we selected a set of 1151 differentially expressed genes, including 453 genes that compose the gene network. Ten significantly enriched regulatory motifs for TFs families ZF-HD, HB, C2H2, NAC, BZR, and ARID were found in the promoter regions of differentially expressed genes. In addition, we predicted families of transcription factors associated with the duration of exposure (RAV, HSF), intensity of high light treatment (MYB, REM), and the direction of gene expression change (HSF, S1Fa-like). We predicted genetic components systems involved in a high light response and their expression changes, potential transcriptional regulators, and associated processes.
Microgravity and Space Medicine 2.0
Authors: Grimm Daniela
Published: April 2022

This Special Issue (SI), “Microgravity and Space Medicine 2 [...]