bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Fruit and Vegetable Consumption and Depression Symptoms in Young People and Adults Aged 15–45: A Systematic Review of Cohort Studies
Authors: Dharmayani Putu Novi Arfirsta , Juergens Melissa , Allman-Farinelli Margaret , Mihrshahi Seema
Published: January 2021

Higher consumption of fruit and vegetables has been associated with a lower risk of various chronic diseases including coronary heart disease, obesity, and certain cancers. Recently, fruit and vegetable intake has also been linked with mental health, including depression; however, this area is largely unexplored studies in young people and adults. This systematic review aimed to evaluate the association between fruit and vegetable intake and depressive symptoms in young people and adults aged 15–45. The review used a predefined protocol registered with International Prospective Register of Systematic Reviews (PROSPERO) database (ID no: CRD42018091642). The systematic review focused on peer-reviewed cohort studies published from 1 January 2000 to 31 August 2020 using searches of six electronic databases. The exposure was fruit and vegetable consumption analysed both separately and/or together, and the outcome was depression or depressive symptoms. Data from eligible studies were extracted according to predefined criteria and the studies were appraised using the Newcastle–Ottawa Scale (NOS) for cohort studies to evaluate for study quality and risk of bias. A total of 12 studies from seven countries were deemed eligible and included in the qualitative synthesis, one study was categorised as “very good” quality, nine studies were “good” quality, and two studies were “moderate” quality by the quality assessment based on the total score for the NOS. The majority of cohort studies support the evidence that fruit consumption is associated with decreased risk of developing depression. However, the inconsistent results were observed when the effects of vegetable consumption were analysed independently, and the effects of fruit and vegetables combined were analysed. Despite this, the evidence seems to be building that a possible association exists, and this may have implications for addressing the burden of mental illness in young people and adults aged 15–45 years. More well-designed prospective cohort studies are needed to provide more robust evidence on the relationship between fruit and vegetable intake and depression.
Association between Childhood Maltreatment History and Premenstrual Syndrome
Authors: Ito Kanako , Doi Satomi , Isumi Aya , Fujiwara Takeo
Published: January 2021

Childhood maltreatment history has known relationships with various mental and physical diseases; however, little is known about its association with premenstrual syndrome (PMS). In this study, we investigated the association between childhood maltreatment history and PMS among young women in Japan. In a Japanese city, we approached 3815 women aged 10–60 years who visited a gynecology clinic and one general practice clinic. A questionnaire on childhood maltreatment history and PMS was administered to them. We observed that women with histories of childhood maltreatment demonstrated a significantly increased risk of PMS compared with those without such histories (odds ratio: 1.47, 95% confidence interval: 1.20–1.81). Particularly, women with childhood physical or emotional abuse demonstrated a stronger association with PMS, whereas other forms of childhood maltreatment (emotional neglect, witnessing of intimate-partner violence, or sexual abuse) were not associated with PMS. Our results illustrate that childhood maltreatment may be a risk factor for PMS.
Detection of Leptospira interrogans DNA in Urine of a Captive Ocelot (Leopardus pardalis)
Authors: Paz Lucas N. , Hamond Camila , Pinna Melissa H.
Published: January 2021

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As the Pandemic Progresses, How Does Willingness to Vaccinate against COVID-19 Evolve?
Authors: Alley Stephanie J. , Stanton Robert , Browne Matthew , To Quyen G. , Khalesi Saman , Williams Susan L. , Thwaite Tanya L. , Fenning Andrew S. , Vandelanotte Corneel
Published: January 2021

Controversy around the safety and efficacy of COVID-19 vaccines may lead to low vaccination rates. Survey data were collected in April and August 2020 from a total of 2343 Australian adults. A quarter (n = 575, 24%) completed both surveys. A generalized linear mixed model analysis was conducted to determine whether willingness to vaccinate changed in the repeated sample, and a multinominal logistic regression was conducted in all participants to determine whether willingness to vaccinate was associated with demographics, chronic disease, or media use. Willingness to vaccinate slightly decreased between April (87%) and August (85%) but this was not significant. Willingness to vaccinate was lower in people with a certificate or diploma (79%) compared to those with a Bachelor degree (87%), p < 0.01 and lower in infrequent users of traditional media (78%) compared to frequent users of traditional media (89%), p < 0.001. Women were more likely to be unsure if they would be willing to vaccinate (10%) compared to men (7%), p < 0.01. There were no associations between willingness to vaccinate and age, chronic disease, or social media use. Promotion of a COVID-19 vaccine should consider targeting women, and people with a certificate or diploma, via non-traditional media channels.
Satisfaction with Life, Emotions, and Identity Processes in Polish First-Time Mothers and Fathers and Their Child’s Age
Authors: Liberska Hanna , Deja Monika
Published: January 2021

The experiences of women regarding conception, the birth of the first child, and care of an infant in the perinatal period have long attracted the attention of researchers, but the knowledge about the experiences of men entering the role of fathers for the first time is still insufficient. The aim of the research was to identify the level of satisfaction with life, emotions and identity formation of first-time parents depending on the gender and age of the child. Seventy-five pairs of Polish first-time parents participated in the study. The research used the SUPIN scale (Polish adaptation of Positive and Negative Affect Schedule), the Satisfaction with Life Scale (SWLS), the Dimension of Identity Development Scale (DIDS), and a questionnaire prepared by the authors. On the basis of the conducted research, it can be concluded that there is a similarity of satisfaction with life, experienced emotions, and identity processes of first-time mothers and fathers, as well as the importance of the child’s age for the specificity of developmental changes in women and men. Understanding development changes which include identity, emotional functioning, and life satisfaction of first-time parents can provide bases for creating supporting programs in the case that problems in undertaking the role of a parent emerge.
Sun Exposure during Water Sports: Do Elite Athletes Adequately Protect Their Skin against Skin Cancer?
Authors: De Castro-Maqueda Guillermo , Gutierrez-Manzanedo Jose V. , Lagares-Franco Carolina , de Troya-Martin Magdalena
Published: January 2021

Excessive sun exposure is the main avoidable cause of skin cancer. Outdoor sports performed without adequate photoprotection are risky practices in this respect. This study examines whether elite athletes in water sports (specifically surfing, windsurfing, and sailing) take appropriate measures to protect their skin from the sun, and whether there are differences in this respect according to age, gender, or sports discipline. This study is based on a questionnaire-based health survey. World championship competitors completed a self-administered questionnaire on their sun protection and exposure habits, as well as sunburns during the last sports season. In total, 246 participants, with an age range of 16–30 years, completed the questionnaire. Of these, 49.6% used inadequate sun protection. Those who protected their skin appropriately tended to be older than those who did not (average age = 23.28 and 20.69 years, respectively; p = 0.000). There were no significant differences in sun protection habits between male and female athletes. The rate of sunburn was very high (76.7%). A high proportion (22.5%) of participants never used sunscreen. Elite athletes in water sports are at real risk of skin lesions from overexposure to the sun, associated with inadequate photoprotection practices. Campaigns to raise awareness and to promote the early detection of skin cancer should target these risk groups.
Influence on Forgiveness, Character Strengths and Satisfaction with Life of a Short Mindfulness Intervention via a Spanish Smartphone Application
Authors: Pizarro-Ruiz Juan Pablo , Ordóñez-Camblor Nuria , Del-Líbano Mario , Escolar-LLamazares María-Camino
Published: January 2021

Mindfulness-based interventions (MBI) are a recognized effective psychological practice characterized by attention control, awareness, acceptance, non-reactivity, and non-judgmental thinking obtained through the practice of meditation. They have been shown to be useful in reducing stress and enhancing well-being in different contexts. In this research, the effectiveness of an MBI was evaluated on variables that can promote successful job performance such as mindfulness trait, positive and negative affect, forgiveness, personality strengths and satisfaction with life. The intervention was carried out through a smartphone application called “Aire Fresco” (Fresh Air) during 14 days in the middle of the quarantine produced by the Covid-19 pandemic. The study sample was composed of 164 Spanish people who were distributed in two groups: control group and experimental group, which were evaluated before and after the intervention. The MANCOVA performed showed an overall positive effect of the intervention on the variables evaluated. The different ANCOVAs carried out showed that the intervention was beneficial in increasing mindfulness trait, reducing negative affect or increasing life satisfaction, among others. Our study is, as far as we know, the first to demonstrate the effectiveness of a brief intervention in mindfulness conducted using a smartphone application in Spanish.
Nursing Students’ Satisfaction: A Comparison between Medium- and High-Fidelity Simulation Training
Authors: Alconero-Camarero Ana Rosa , Sarabia-Cobo Carmen María , Catalán-Piris María José , González-Gómez Silvia , González-López José Rafael
Published: January 2021

Training based on clinical simulation is an effective method of teaching in nursing. Nevertheless, there is no clear evidence about if it is better to use high- or medium-fidelity simulation. The aim is to analyse if students are more satisfied when their clinical simulation practices are based on high-fidelity simulation (HFS) or medium-fidelity simulation (MFS). Students´ satisfaction was assessed using the Satisfaction Scale Questionnaire with High-Fidelity Clinical Simulation. The sample is composed of 393 students from two Spanish Universities. Satisfaction with simulation in nursing students is significantly greater in MFS than HFS. Simulation is beneficial for learning in all its forms, but for the acquisition of basic skills, and at a lower cost, MFS proves to be effective. However, high-fidelity is not always better than medium-fidelity as this depends on the student’s level of knowledge and clinical experience.
Effects of Untreated Drinking Water at Three Indigenous Yaqui Towns in Mexico: Insights from a Murine Model
Authors: Navarro-Espinoza Sofia , Angulo-Molina Aracely , Meza-Figueroa Diana , López-Cervantes Guillermo , Meza-Montenegro Mercedes , Armienta Aurora , Soto-Puebla Diego , Silva-Campa Erika , Burgara-Estrella Alexel , Álvarez-Bajo Osiris , Pedroza-Montero Martín
Published: January 2021

Background: Reports in a northwestern Mexico state linked arsenic (As) in drinking water to DNA damage in people from indigenous communities. However, this correlation remains under discussion due to unknown variables related to nutrition, customs, and the potential presence of other metal(oid)s. Methods: To determine this association, we sampled water from three Yaqui towns (Cócorit, Vícam, and Pótam), and analyzed the metals by ICP-OES. We exposed four separate groups, with five male CD-1 mice each, to provide further insight into the potential effects of untreated drinking water. Results: The maximum concentrations of each metal(oid) in µg·L−1 were Sr(819) > Zn(135) > As(75) > Ba(57) > Mo(56) > Cu(17) > Al(14) > Mn(12) > Se(19). Histological studies revealed brain cells with angulation, satellitosis, and reactive gliosis with significant statistical correlation with Mn and As. Furthermore, the liver cells presented hepatocellular degeneration. Despite the early response, there is no occurrence of both statistical and significative changes in hematological parameters. Conclusions: The obtained results provide experimental insights to understand the potential effects of untreated water with low As and Mn contents in murine models. This fact is noteworthy because of the development of histological changes on both the brain and liver at subchronic exposure.
Association of Social Frailty with Physical Health, Cognitive Function, Psychological Health, and Life Satisfaction in Community-Dwelling Older Koreans
Authors: Ko Hana , Jung SuJung
Published: January 2021

Social frailty affects various aspects of health in community-dwelling older adults. This study aimed to identify the prevalence of social frailty and the significance of its association with South Korean older adults’ health status and life satisfaction. This study involved a secondary data analysis of the 2017 National Survey of Older Koreans. From the 10,299 respondents of the survey, 10,081 were selected with no exclusion criteria. Multiple regression analyses were conducted to identify the factors related to life satisfaction. Compared with the robust and social prefrailty groups, the social frailty group had higher nutritional risk (χ² = 312.161, p = 0.000), depressive symptoms (χ² = 977.587, p = 0.000), cognitive dysfunction (χ² = 25.051, p = 0.000), and lower life satisfaction (F = 1050.272, p = 0.000). The results of multiple linear regression, adjusted for sociodemographic and health-related characteristics, indicated that social frailty had the strongest negative association with life satisfaction (β = −0.267, p = 0.000). However, cognitive function was significantly positively associated with life satisfaction (β = 0.062, p = 0.000). Social frailty was significantly correlated with physical, psychological, and mental health as well as life satisfaction in community-dwelling older South Koreans. Therefore, accounting for the social aspect of functioning is an essential part of a multidimensional approach to improving health and life satisfaction in communities.
Bioremediation of Petroleum Hydrocarbons Using Acinetobacter sp. SCYY-5 Isolated from Contaminated Oil Sludge: Strategy and Effectiveness Study
Authors: Cai Yiyun , Wang Runkai , Rao Pinhua , Wu Baichun , Yan Lili , Hu Lijiang , Park Sangsook , Ryu Moonhee , Zhou Xiaoya
Published: January 2021

Biodegradation has been considered as an ideal technique for total petroleum hydrocarbon (TPH) contamination, but its efficiency is limited by its application in the field. Herein, an original TPH-degrading strain, SCYY-5, was isolated from contaminated oil sludge and identified as Acinetobacter sp. by 16S rDNA sequence analysis. The biological function of the isolate was investigated by heavy metal tolerance, carbon, and nitrogen source and degradation tests. To enhance its biodegradation efficiency, the response surface methodology (RSM) based on a function model was adopted to investigate and optimize the strategy of microbial and environmental variables for TPH removal. Furthermore, the performance of the system increased to 79.94% with the further addition of extra nutrients, suggesting that the RSM and added nutrients increased the activity of bacteria to meet the needs of the co-metabolism matrix during growth or degradation. These results verified that it is feasible to adopt the optimal strategy of combining bioremediation with RSM to improve the biodegradation efficiency, for contaminated oil sludge.
Determinants of Residents’ Approach–Avoidance Responses to the Personal Carbon Trading Scheme: An Empirical Analysis of Urban Residents in Eastern China
Authors: Guo Daoyan , Chen Hong , Long Ruyin , Zou Shaohui
Published: January 2021

The personal carbon trading (PCT) scheme is a policy instrument for reducing downstream carbon emissions and creating a green lifestyle, and a bottleneck hampering its implementation is the behavioral willingness of residents. Due to a pre-existing stimulus-response association, the willingness of residents can be intuitively reflected by their approach–avoidance responses. This study theoretically analyzed the mechanisms for influencing residents’ approach–avoidance responses towards the personal carbon trading scheme based on open-ended interviews, and empirically examined the mechanisms by developing rating scales and conducting questionnaire surveys on urban residents in eastern China. Findings showed that residents’ approach–avoidance responses could be negatively affected by their preference for comfort, whereas they were positively impacted by their ecological values, sense of social responsibility, cognition of the behaviors for carbon emission reduction, and cognition of personal carbon trading. In terms of subjective norms, the culture of environmentalism had a positive effect on residents’ responses to PCT scheme, while the culture of consumerism caused a negative impact on their responses. Furthermore, the perceived behavioral controls of residents partially mediated the relationships between their psychological characteristics and approach–avoidance responses. Finally, primary and pivotal suggestions were proposed for nudging Chinese urban residents towards approaching the personal carbon trading scheme, which provide theoretical support and practical guidance for its implementation.
No Interaction Effect between Interleukin-6 Polymorphisms and Acid Ash Diet with Bone Resorption Marker in Postmenopausal Women
Authors: Lim Sook Yee , Chan Yoke Mun , Ramachandran Vasudevan , Shariff Zalilah Mohd , Chin Yit Siew , Arumugam Manohar
Published: January 2021

Background: Evidence is growing that a high-acid diet might accelerate the rate of bone loss, and gene polymorphisms such as Interleukin 6 (IL6) -174G/C and -572G/C are related to bone deterioration. However, no study of the interaction between diet and IL6 polymorphisms has been conducted among Asians. Thus, the objective of this study was to determine whether IL6 gene polymorphisms modified the association between dietary acidity and the rate of bone resorption. Methods: This cross-sectional study recruited 203 postmenopausal women (age ranged from 51 to 85 years old) in community settings. The dietary intakes of the participants were assessed using a validated interviewer-administered semi-quantitative food frequency questionnaire (FFQ), while dietary acid load (DAL) was estimated using net endogenous acid production (NEAP). Agena® MassARRAY genotyping analysis and serum collagen type 1 cross-linked C-telopeptide (CTX1) were used to identify the IL6 genotype and as a bone resorption marker, respectively. The interactions between diet and single-nucleotide polymorphisms (SNPs) were assessed using linear regressions. Results: A total of 203 healthy postmenopausal women aged between 51 and 85 years participated in this study. The mean BMI of the participants was 24.3 kg/m2. In IL6 -174 G/C, all the participants carried the GG genotype, while the C allele was absent. Approximately 40% of the participants had a high dietary acid load. Dietary acid load (B = 0.15, p = 0.031) and the IL6 -572 CC genotype group (B = 0.14, p = 0.044) were positively associated with a higher bone resorption. However, there was no moderating effect of the IL6 genetic polymorphism on the relationship between and acid ash diet and bone resorption markers among the postmenopausal women (p = 0.79). Conclusion: High consumption of an acid ash diet and the IL6 -572 C allele seem to attribute to high bone resorption among postmenopausal women. However, our finding does not support the interaction effect of dietary acidity and IL6 (-174G/C and -572G/C) polymorphisms on the rate of bone resorption. Taken together, these results have given scientific research other candidate genes to focus on which may interact with DAL on bone resorption, to enhance planning for preventing or delaying the onset of osteoporosis among postmenopausal women.
Pilot Study to Develop and Test Palliative Care Quality Indicators for Nursing Homes
Authors: Dupont Charlèss , De Schreye Robrecht , Cohen Joachim , De Ridder Mark , Van den Block Lieve , Deliens Luc , Leemans Kathleen
Published: January 2021

An increasingly frail population in nursing homes accentuates the need for high quality care at the end of life and better access to palliative care in this context. Implementation of palliative care and its outcomes can be monitored by using quality indicators. Therefore, we developed a quality indicator set for palliative care in nursing homes and a tailored measurement procedure while using a mixed-methods design. We developed the instrument in three phases: (1) literature search, (2) interviews with experts, and (3) indicator and measurement selection by expert consensus (RAND/UCLA). Second, we pilot tested and evaluated the instrument in nine nursing homes in Flanders, Belgium. After identifying 26 indicators in the literature and expert interviews, 19 of them were selected through expert consensus. Setting-specific themes were advance care planning, autonomy, and communication with family. The quantitative and qualitative analyses showed that the indicators were measurable, had good preliminary face validity and discriminative power, and were considered to be useful in terms of quality monitoring according to the caregivers. The quality indicators can be used in a large implementation study and process evaluation in order to achieve continuous monitoring of the access to palliative care for all of the residents in nursing homes.
A Case Study on Curling Stone and Sweeping Effect According to Sweeping Conditions
Authors: Kim Tae-Whan , Lee Sang-Cheol , Kil Se-Kee , Choi Sang-Hyup , Song Yong-Gwan
Published: January 2021

The purpose of this study was to use the same ice temperature and air temperature as the Pyeongchang Curling Stadium by using an Ice Chamber. Then, launch the stone at the same speed, and move according to the sweeping conditions (perpendicular to the axis of motion, along the axis of motion) of male and female elite curlers. The aim is to provide sports science information required for curling athletes by analyzing the distance of the stone, the change in the speed of a moved stone, the change in broom acceleration, and athletes’ muscle activity. The results of experiments conducted on four male and four elite female curlers are as follows. Under gender, the stone’s movement distance was long after the sweeping of male athletes, and the speed of the stone was not different according to the conditions. The broom’s acceleration did not show a difference in both the sweeping condition and the athlete’s gender condition, and the muscle activity did not show a significant difference in both the sweeping condition and the gender condition. In summary, it is thought that male athletes moved the stone farther by raising the ice surface temperature by vertical load than female athletes. Also, there was no statistically significant difference in muscle activity results, but it was found that there was a specific pattern of muscle activity in the pushing and pulling motions during the sweeping of male and female athletes. It is expected to be used as primary data.
Toothpastes with Enzymes Support Gum Health and Reduce Plaque Formation
Authors: Paqué Pune N. , Schmidlin Patrick R. , Wiedemeier Daniel B. , Wegehaupt Florian J. , Burrer Phoebe D. , Körner Philipp , Deari Shengjile , Sciotti Michel-Angelo , Attin Thomas
Published: January 2021

Enzymes in toothpastes can support host immune responses, and thus maintain oral health. This study aimed to investigate gingival health and the plaque-reducing effects of enzyme-containing toothpastes. A laboratory study tested the antimicrobial potential of different enzyme-containing toothpaste formulations. Two promising formulations (enzyme-containing toothpastes with glucose oxidase and D-glucose with (C+) and without Citrox (C−) Citrox) were investigated in a clinical crossover trial (two slurries: sodium lauryl sulfate-containing (SLS), a toothpaste without SLS (reference), and water). Subjects (n = 20) abstained from toothbrushing for four days and rinsed with a toothpaste slurry. Bleeding on probing (BOP) and plaque indices (PI) were measured. A mixed linear model was used to statistically compare the slurries with respect to BOP and PI change. The in vitro bacterial growth-inhibiting evaluation showed the best results for SLS, followed by C+ and C−. The change in BOP and PI exhibited statistically significant differences to water rinsing (BOP; PI changes in % points (difference of the baseline and post-rinse values: water = 8.8%; 90.0%; C+ = −1.4%; 80.4%; SLS = 1.5%; 72.1%; reference = 0.8%; 77.5%; C− = −1.8%; 75.1%). All slurries exhibited anti-gingivitis and anti-plaque effects, resulting in a prophylactic benefit for limited-access regions during brushing.
Comparison of Ensemble Machine Learning Methods for Soil Erosion Pin Measurements
Authors: Nguyen Kieu Anh , Chen Walter , Lin Bor-Shiun , Seeboonruang Uma
Published: January 2021

Although machine learning has been extensively used in various fields, it has only recently been applied to soil erosion pin modeling. To improve upon previous methods of quantifying soil erosion based on erosion pin measurements, this study explored the possible application of ensemble machine learning algorithms to the Shihmen Reservoir watershed in northern Taiwan. Three categories of ensemble methods were considered in this study: (a) Bagging, (b) boosting, and (c) stacking. The bagging method in this study refers to bagged multivariate adaptive regression splines (bagged MARS) and random forest (RF), and the boosting method includes Cubist and gradient boosting machine (GBM). Finally, the stacking method is an ensemble method that uses a meta-model to combine the predictions of base models. This study used RF and GBM as the meta-models, decision tree, linear regression, artificial neural network, and support vector machine as the base models. The dataset used in this study was sampled using stratified random sampling to achieve a 70/30 split for the training and test data, and the process was repeated three times. The performance of six ensemble methods in three categories was analyzed based on the average of three attempts. It was found that GBM performed the best among the ensemble models with the lowest root-mean-square error (RMSE = 1.72 mm/year), the highest Nash-Sutcliffe efficiency (NSE = 0.54), and the highest index of agreement (d = 0.81). This result was confirmed by the spatial comparison of the absolute differences (errors) between model predictions and observations using GBM and RF in the study area. In summary, the results show that as a group, the bagging method and the boosting method performed equally well, and the stacking method was third for the erosion pin dataset considered in this study.
From Spaceflight to Mars g-Levels: Adaptive Response of A. Thaliana Seedlings in a Reduced Gravity Environment Is Enhanced by Red-Light Photostimulation
Authors: Villacampa Alicia , Ciska Malgorzata , Manzano Aránzazu , Vandenbrink Joshua P. , Kiss John Z. , Herranz Raúl , Medina F. Javier
Published: January 2021

The response of plants to the spaceflight environment and microgravity is still not well understood, although research has increased in this area. Even less is known about plants’ response to partial or reduced gravity levels. In the absence of the directional cues provided by the gravity vector, the plant is especially perceptive to other cues such as light. Here, we investigate the response of Arabidopsis thaliana 6-day-old seedlings to microgravity and the Mars partial gravity level during spaceflight, as well as the effects of red-light photostimulation by determining meristematic cell growth and proliferation. These experiments involve microscopic techniques together with transcriptomic studies. We demonstrate that microgravity and partial gravity trigger differential responses. The microgravity environment activates hormonal routes responsible for proliferation/growth and upregulates plastid/mitochondrial-encoded transcripts, even in the dark. In contrast, the Mars gravity level inhibits these routes and activates responses to stress factors to restore cell growth parameters only when red photostimulation is provided. This response is accompanied by upregulation of numerous transcription factors such as the environmental acclimation-related WRKY-domain family. In the long term, these discoveries can be applied in the design of bioregenerative life support systems and space farming.
Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms
Authors: Schmit Megan , Bielinsky Anja-Katrin
Published: January 2021

Deoxyribonucleic acid (DNA) replication can be divided into three major steps: initiation, elongation and termination. Each time a human cell divides, these steps must be reiteratively carried out. Disruption of DNA replication can lead to genomic instability, with the accumulation of point mutations or larger chromosomal anomalies such as rearrangements. While cancer is the most common class of disease associated with genomic instability, several congenital diseases with dysfunctional DNA replication give rise to similar DNA alterations. In this review, we discuss all congenital diseases that arise from pathogenic variants in essential replication genes across the spectrum of aberrant replisome assembly, origin activation and DNA synthesis. For each of these conditions, we describe their clinical phenotypes as well as molecular studies aimed at determining the functional mechanisms of disease, including the assessment of genomic stability. By comparing and contrasting these diseases, we hope to illuminate how the disruption of DNA replication at distinct steps affects human health in a surprisingly cell-type-specific manner.
Metabolomic and Transcriptomic Profiling Provide Novel Insights into Fruit Ripening and Ripening Disorder Caused by 1-MCP Treatments in Papaya
Authors: Zheng Senlin , Hao Yanwei , Fan Silin , Cai Jiahui , Chen Weixin , Li Xueping , Zhu Xiaoyang
Published: January 2021

Treatment with 1-methylcyclopropylene (1-MCP) is an effective technique to preserve fruits, but inappropriate treatment with 1-MCP causes a ripening disorder (rubbery texture) in papaya fruit. In this study, a combined metabolomic and transcriptomic analysis was conducted to reveal the possible mechanism of the ripening disorder caused by unsuitable 1-MCP in papaya. A total of 203 differential accumulated metabolites (DAMs) were identified in the metabolome analysis. Only 24 DAMs were identified in the control (CK) vs. the 1-MCP 2 h group, and they were primarily flavonoids. Ninety and 89 DAMs were identified in the CK vs. 1-MCP 16 h and 1-MCP 2 h vs. 1-MCP 16 h groups, respectively, indicating that long-term 1-MCP treatment severely altered the metabolites during fruit ripening. 1-MCP 16 h treatment severely reduced the number of metabolites, which primarily consisted of flavonoids, lipids, phenolic acids, alkaloids, and organic acids. An integrated analysis of RNA-Seq and metabolomics showed that various energy metabolites for the tricarboxylic acid cycle were reduced by long-term treatment with 1-MCP, and the glycolic acid cycle was the most significantly affected, as well as the phenylpropane pathway. These results provide valuable information for fruit quality control and new insight into the ripening disorder caused by unsuitable treatment with 1-MCP in papaya.
Functional Inactivation of Drosophila GCK Orthologs Causes Genomic Instability and Oxidative Stress in a Fly Model of MODY-2
Authors: Mascolo Elisa , Liguori Francesco , Stufera Mecarelli Lorenzo , Amoroso Noemi , Merigliano Chiara , Amadio Susanna , Volonté Cinzia , Contestabile Roberto , Tramonti Angela , Vernì Fiammetta
Published: January 2021

Maturity-onset diabetes of the young (MODY) type 2 is caused by heterozygous inactivating mutations in the gene encoding glucokinase (GCK), a pivotal enzyme for glucose homeostasis. In the pancreas GCK regulates insulin secretion, while in the liver it promotes glucose utilization and storage. We showed that silencing the DrosophilaGCK orthologs Hex-A and Hex-C results in a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin producing cells (IPCs) whereas Hex-C is specifically expressed in the fat body. We showed that Hex-A is essential for insulin secretion and it is required for Hex-C expression. Reduced levels of either Hex-A or Hex-C resulted in chromosome aberrations (CABs), together with an increased production of advanced glycation end-products (AGEs) and reactive oxygen species (ROS). This result suggests that CABs, in GCK depleted cells, are likely due to hyperglycemia, which produces oxidative stress through AGE metabolism. In agreement with this hypothesis, treating GCK-depleted larvae with the antioxidant vitamin B6 rescued CABs, whereas the treatment with a B6 inhibitor enhanced genomic instability. Although MODY-2 rarely produces complications, our data revealed the possibility that MODY-2 impacts genome integrity.
Assessment of the Efficacy and Clinical Utility of Different Circulating Tumor Cell (CTC) Detection Assays in Patients with Chemotherapy-Naïve Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
Authors: Papadaki Maria A. , Messaritakis Ippokratis , Fiste Oraianthi , Souglakos John , Politaki Eleni , Kotsakis Athanasios , Georgoulias Vassilis , Mavroudis Dimitrios , Agelaki Sofia
Published: January 2021

We herein investigated the detection frequency and clinical relevance of circulating tumor cells (CTCs) in chemotherapy-naïve stage IIIB/IV non-small cell lung cancer (NSCLC), by using the CellSearch and real-time CEACAM5mRNA assays. Blood samples from 43 patients were obtained at different time points during first-line chemotherapy. CellSearch revealed the detection of ≥1 CTCs in 41.9%, 40.9%, and 16.7% of patients at baseline, post-1st, and post-2nd treatment cycle, respectively, and of ≥5 CTCs in 11.6%, 9.1%, and 5.6%, respectively. CEACAM5mRNA+ CTCs were detected in 29.3% and 16% of patients pre- and post-treatment, respectively. The positivity concordance between the two assays was 2.2%. CTC-detection by CellSearch (≥5 CTCs: p = 0.004), CEACAM5mRNA (p = 0.010), or by any assay (p = 0.000) was associated with disease progression. Reduced survival was demonstrated for patients harboring ≥5 CTCs (progression-free survival; PFS: p = 0.000; overall survival; OS: p = 0.009), CEACAM5mRNA+ CTCs (PFS: p = 0.043; OS: p = 0.039), and CTCs by any assay (PFS: p = 0.005; OS: p = 0.006, respectively). CTC-detection by any assay independently predicted for increased risk of relapse (hazard ratio; HR: 3.496; p = 0.001) and death (HR: 2.866; p = 0.008). CellSearch-positivity either pre-, post-1st, or post-2nd cycle, was predictive for shorter PFS (p = 0.036) compared to negativity in all time points. Persistent CEACAM5mRNA-positivity pre- and post-treatment was associated with reduced PFS (p = 0.036) and OS (p = 0.026). In conclusion, CTC detection and monitoring using the CellSearch and CEACAM5mRNA assays provides valuable and complementary clinical information for chemo-naïve advanced or metastatic NSCLC.
Apolipoprotein CIII Is an Important Piece in the Type-1 Diabetes Jigsaw Puzzle
Authors: Valladolid-Acebes Ismael , Berggren Per-Olof , Juntti-Berggren Lisa
Published: January 2021

It is well known that type-2 diabetes mellitus (T2D) is increasing worldwide, but also the autoimmune form, type-1 diabetes (T1D), is affecting more people. The latest estimation from the International Diabetes Federation (IDF) is that 1.1 million children and adolescents below 20 years of age have T1D. At present, we have no primary, secondary or tertiary prevention or treatment available, although many efforts testing different strategies have been made. This review is based on the findings that apolipoprotein CIII (apoCIII) is increased in T1D and that in vitro studies revealed that healthy β-cells exposed to apoCIII became apoptotic, together with the observation that humans with higher levels of the apolipoprotein, due to mutations in the gene, are more susceptible to developing T1D. We have summarized what is known about apoCIII in relation to inflammation and autoimmunity in in vitro and in vivo studies of T1D. The aim is to highlight the need for exploring this field as we still are only seeing the top of the iceberg.
Prediction of Protein–ATP Binding Residues Based on Ensemble of Deep Convolutional Neural Networks and LightGBM Algorithm
Authors: Song Jiazhi , Liu Guixia , Jiang Jingqing , Zhang Ping , Liang Yanchun
Published: January 2021

Accurately identifying protein–ATP binding residues is important for protein function annotation and drug design. Previous studies have used classic machine-learning algorithms like support vector machine (SVM) and random forest to predict protein–ATP binding residues; however, as new machine-learning techniques are being developed, the prediction performance could be further improved. In this paper, an ensemble predictor that combines deep convolutional neural network and LightGBM with ensemble learning algorithm is proposed. Three subclassifiers have been developed, including a multi-incepResNet-based predictor, a multi-Xception-based predictor, and a LightGBM predictor. The final prediction result is the combination of outputs from three subclassifiers with optimized weight distribution. We examined the performance of our proposed predictor using two datasets: a classic ATP-binding benchmark dataset and a newly proposed ATP-binding dataset. Our predictor achieved area under the curve (AUC) values of 0.925 and 0.902 and Matthews Correlation Coefficient (MCC) values of 0.639 and 0.642, respectively, which are both better than other state-of-art prediction methods.
Pathological ATX3 Expression Induces Cell Perturbations in E. coli as Revealed by Biochemical and Biophysical Investigations
Authors: Ami Diletta , Sciandrone Barbara , Mereghetti Paolo , Falvo Jacopo , Catelani Tiziano , Visentin Cristina , Tortora Paolo , Ventura Salvador , Natalello Antonino , Regonesi Maria Elena
Published: January 2021

Amyloid aggregation of human ataxin-3 (ATX3) is responsible for spinocerebellar ataxia type 3, which belongs to the class of polyglutamine neurodegenerative disorders. It is widely accepted that the formation of toxic oligomeric species is primarily involved in the onset of the disease. For this reason, to understand the mechanisms underlying toxicity, we expressed both a physiological (ATX3-Q24) and a pathological ATX3 variant (ATX3-Q55) in a simplified cellular model, Escherichia coli. It has been observed that ATX3-Q55 expression induces a higher reduction of the cell growth compared to ATX3-Q24, due to the bacteriostatic effect of the toxic oligomeric species. Furthermore, the Fourier transform infrared microspectroscopy investigation, supported by multivariate analysis, made it possible to monitor protein aggregation and the induced cell perturbations in intact cells. In particular, it has been found that the toxic oligomeric species associated with the expression of ATX3-Q55 are responsible for the main spectral changes, ascribable mainly to the cell envelope modifications. A structural alteration of the membrane detected through electron microscopy analysis in the strain expressing the pathological form supports the spectroscopic results.
An In Vivo Study of a Rat Fluid-Percussion-Induced Traumatic Brain Injury Model with [11C]PBR28 and [18F]flumazenil PET Imaging
Authors: Ghosh Krishna Kanta , Padmanabhan Parasuraman , Yang Chang-Tong , Wang Zhimin , Palanivel Mathangi , Ng Kian Chye , Lu Jia , Carlstedt-Duke Jan , Halldin Christer , Gulyás Balázs
Published: January 2021

Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron emission tomography (PET) have made it possible to map certain features of TBI-induced cellular and molecular changes equally in humans and animals. The PET imaging technique is an apt supplement to nanotheranostic-based treatment alternatives that are emerging to tackle TBI. The present study aims to investigate whether the two radioligands, [11C]PBR28 and [18F]flumazenil, are able to accurately quantify in vivo molecular-cellular changes in a rodent TBI-model for two different biochemical targets of the processes. In addition, it serves to observe any palpable variations associated with primary and secondary injury sites, and in the affected versus the contralateral hemispheres. As [11C]PBR28 is a radioligand of the 18 kD translocator protein, the up-regulation of which is coupled to the level of neuroinflammation in the brain, and [18F]flumazenil is a radioligand for GABAA-benzodiazepine receptors, whose level mirrors interneuronal activity and eventually cell death, the use of the two radioligands may reveal two critical features of TBI. An up-regulation in the [11C]PBR28 uptake triggered by the LFP in the injured (right) hemisphere was noted on day 14, while the uptake of [18F]flumazenil was down-regulated on day 14. When comparing the left (contralateral) and right (LFPI) hemispheres, the differences between the two in neuroinflammation were obvious. Our results demonstrate a potential way to measure the molecular alterations in a rodent-based TBI model using PET imaging with [11C]PBR28 and [18F]flumazenil. These radioligands are promising options that can be eventually used in exploring the complex in vivo pharmacokinetics and delivery mechanisms of nanoparticles in TBI treatment.
Exosomes: A Key Piece in Asthmatic Inflammation
Authors: Cañas José A. , Rodrigo-Muñoz José M. , Gil-Martínez Marta , Sastre Beatriz , del Pozo Victoria
Published: January 2021

Asthma is a chronic disease of the airways that has an important inflammatory component. Multiple cells are implicated in asthma pathogenesis (lymphocytes, eosinophils, mast cells, basophils, neutrophils), releasing a wide variety of cytokines. These cells can exert their inflammatory functions throughout extracellular vesicles (EVs), which are small vesicles released by donor cells into the extracellular microenvironment that can be taken up by recipient cells. Depending on their size, EVs can be classified as microvesicles, exosomes, or apoptotic bodies. EVs are heterogeneous spherical structures secreted by almost all cell types. One of their main functions is to act as transporters of a wide range of molecules, such as proteins, lipids, and microRNAs (miRNAs), which are single-stranded RNAs of approximately 22 nucleotides in length. Therefore, exosomes could influence several physiological and pathological processes, including those involved in asthma. They can be detected in multiple cell types and biofluids, providing a wealth of information about the processes that take account in a pathological scenario. This review thus summarizes the most recent insights concerning the role of exosomes from different sources (several cell populations and biofluids) in one of the most prevalent respiratory diseases, asthma.
The Functions of the Demethylase JMJD3 in Cancer
Authors: Sanchez Anna , Houfaf Khoufaf Fatma Zohra , Idrissou Mouhamed , Penault-Llorca Frédérique , Bignon Yves-Jean , Guy Laurent , Bernard-Gallon Dominique
Published: January 2021

Cancer is a major cause of death worldwide. Epigenetic changes in response to external (diet, sports activities, etc.) and internal events are increasingly implicated in tumor initiation and progression. In this review, we focused on post-translational changes in histones and, more particularly, the tri methylation of lysine from histone 3 (H3K27me3) mark, a repressive epigenetic mark often under- or overexpressed in a wide range of cancers. Two actors regulate H3K27 methylation: Jumonji Domain-Containing Protein 3 demethylase (JMJD3) and Enhancer of zeste homolog 2 (EZH2) methyltransferase. A number of studies have highlighted the deregulation of these actors, which is why this scientific review will focus on the role of JMJD3 and, consequently, H3K27me3 in cancer development. Data on JMJD3’s involvement in cancer are classified by cancer type: nervous system, prostate, blood, colorectal, breast, lung, liver, ovarian, and gastric cancers.
Characteristics and Therapeutic Potential of Human Amnion-Derived Stem Cells
Authors: Liu Quan-Wen , Huang Qi-Ming , Wu Han-You , Zuo Guo-Si-Lang , Gu Hao-Cheng , Deng Ke-Yu , Xin Hong-Bo
Published: January 2021

Stem cells including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells (ASCs) are able to repair/replace damaged or degenerative tissues and improve functional recovery in experimental model and clinical trials. However, there are still many limitations and unresolved problems regarding stem cell therapy in terms of ethical barriers, immune rejection, tumorigenicity, and cell sources. By reviewing recent literatures and our related works, human amnion-derived stem cells (hADSCs) including human amniotic mesenchymal stem cells (hAMSCs) and human amniotic epithelial stem cells (hAESCs) have shown considerable advantages over other stem cells. In this review, we first described the biological characteristics and advantages of hADSCs, especially for their high pluripotency and immunomodulatory effects. Then, we summarized the therapeutic applications and recent progresses of hADSCs in treating various diseases for preclinical research and clinical trials. In addition, the possible mechanisms and the challenges of hADSCs applications have been also discussed. Finally, we highlighted the properties of hADSCs as a promising source of stem cells for cell therapy and regenerative medicine and pointed out the perspectives for the directions of hADSCs applications clinically.