bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Internalized Stigma on LGBT Parenting and the Importance of Health Care Structures: A Qualitative Study
Authors: Alday-Mondaca Carolina , Lay-Lisboa Siu
Published: May 2021

Research on LGBTIQ+ families has focused on the effects of being in a diverse family on the development of children. We seek to show the experience of parenthood from the perspective of LGBTIQ+ people, considering its particularities and the role that health care services play as a potential support network. We used the biographical method through open-ended interviews, participants were LGBT people, and key informants from Chile, Colombia, and Mexico were selected based on a sociostructural sampling. We found that internalized stigma impacts LGBTIQ+ parenting in five ways: the impossibility of thinking of oneself as a parent, fear of violating children’s rights, fear of passing on the stigma, fear of introducing their LGBTIQ+ partner, and the greater discrimination that trans and intersex people suffer. We identified gaps in health care perceptions: the need to guarantee universal access to health care, the need to include a gender perspective and inclusive treatment by health personnel, mental health programs with a community approach, access to assisted fertilization programs, and the generation of collaborative alliances between health services, civil society organizations, and the LGBTIQ+ community. We conclude that the health system is a crucial space from which to enable guarantees for the exercise of rights and overcome internalized stigma.
Comparison of Physical Activity and Sedentary Behaviour between Schoolchildren with Cystic Fibrosis and Healthy Controls: A Gender Analysis
Authors: Valencia-Peris Alexandra , Lizandra Jorge , Moya-Mata Irene , Gómez-Gonzalvo Fernando , Castillo-Corullón Silvia , Escribano Amparo
Published: May 2021

The purpose of this study was to examine differences in sports participation and the levels of physical activity (PA) and sedentary behaviour (SB) between schoolchildren with cystic fibrosis (CF) and a healthy control group (CG) taking into account the gender variable. PA and SB were measured with an accelerometer for 7 consecutive days in 44 children (24 girls; 11.0 (3.2) years) with CF and 45 age-, sex-, and socioeconomic status-matched controls (24 girls; 11.1 (3.0) years). CF patients and CG did not differ in moderate-to-vigorous PA (54 (31) vs. 59 (27) min/day respectively) or in SB (558 (106) vs. 553 (92) min/day respectively). There were no differences in meeting the PA guidelines between both groups (CF: 36.4% vs. CG: 42.4%). Gender analysis revealed that boys were more active and met more PA guidelines than girls regardless of the group (CF or CG), girls with CF being the least active group (only 16.7% met PA guidelines). A possible compensatory effect was found between SB and PA only in the CF sample, as for each minute/day spent in SB the odds of meeting PA guidelines decreased by 34%. These findings suggest that promoting a reduction in SB is as important as promoting PA in the CF population, especially in girls. Health caregivers, coaches, teachers, or parents could offer appealing supervised and unsupervised physical activities, foster the adoption of active lifestyles, or incorporate PA into daily routines to improve the health of CF schoolchildren.
Assessing Biocompatibility of Face Mask Materials during COVID-19 Pandemic by a Rapid Multi-Assays Strategy
Authors: Petrachi Tiziana , Ganzerli Francesco , Cuoghi Aurora , Ferrari Alberto , Resca Elisa , Bergamini Valentina , Accorsi Luca , Burini Francesco , Pasini Davide , Arnaud Gaelle Françoise , Piccini Mattia , Aldrovandi Laura , Mari Giorgio , Tomasi Aldo , Rovati Luigi , Dominici Massimo , Veronesi Elena
Published: May 2021

During the coronavirus disease 2019 (COVID-19) pandemic, scientific authorities strongly suggested the use of face masks (FMs). FM materials (FMMs) have to satisfy the medical device biocompatibility requirements as indicated in the technical standard EN ISO 10993-1:2018. The biologic evaluation must be confirmed by in vivo tests to verify cytotoxicity, sensitisation, and skin irritation. Some of these tests require an extensive period of time for their execution, which is incompatible with an emergency situation. In this study, we propose to verify the safety of FMMs combining the assessment of 3-[4,5-dimethylthiazolyl-2]-2,5-diphenyltetrazolium bromide (MTT) with quantification of nitric oxide (NO) and interleukin-6 (IL-6), as predictive markers of skin sensitisation or irritation based on human primary fibroblasts. Two hundred and forty-two FMMs were collected and classified according to spectrometer IR in polypropylene, paper, cotton, polyester, polyethylene terephthalate, 3-dimensional printing, and viscose. Of all FMMs tested, 50.8% passed all the assays, 48% failed at least one, and only 1.2% failed all. By a low cost, rapid and highly sensitive multi assays strategy tested on human skin fibroblasts against a large variety of FMMs, we propose a strategy to promptly evaluate biocompatibility in wearable materials.
The More Fertile, the More Creative: Changes in Women’s Creative Potential across the Ovulatory Cycle
Authors: Galasinska Katarzyna , Szymkow Aleksandra
Published: May 2021

Creative thinking is a defining human feature. It provides novel solutions and as such undoubtedly has contributed to our survival. However, according to signaling theory, creativity could also have evolved through sexual selection as a potential fitness indicator. In our study, we tested one implication of this theory. Specifically, we hypothesized that if creativity can serve as a signal of women’s fitness, then we should observe an increase in creative thinking in the fertile phase of the ovulatory cycle compared to other non-fertile phases. In our study (N = 751), we tested creative potential throughout the ovulatory cycle. We found a positive correlation between the probability of conception and both creative originality and flexibility. Importantly, we also tested the mediating role of arousal in the relationship between the probability of conception and creative thinking. The results of our study are discussed in terms of signaling theory, through which women advertise their fitness with their creativity.
Prevalence and Outcomes of Major Psychiatric Disorders Preceding Index Surgery for Degenerative Thoracic/Lumbar Spine Disease
Authors: Huang Yu-Chi , Chang Chih-Hui , Lin Chih-Lung , Wang Liang-Jen , Hsu Chih-Wei , Su Yu-Feng , Lo Yi-Ching , Hung Chi-Fa , Hsieh Yun-Yu , Chen Cheng-Sheng
Published: May 2021

The relationship between preexisting major psychiatric disorders and outcomes of spine surgery for degenerative thoracic/lumbar disease remains unclear. A 5% subset of inpatients was randomly selected from the Taiwan National Health Insurance Research Database. A total of 10,109 inpatients aged 18 years or over with degenerative thoracic/lumbar disease and underwent spine surgery met inclusion criteria. Major psychiatric disorders diagnosed by psychiatrists preceding index surgery, including anxiety disorder, depression disorder, bipolar disorder, schizophrenia and dementia, were identified. The prevalence of psychiatric disorders, and their differential risks on in-hospital and post-discharge outcomes were examined. 10.4% had major psychiatric disorders, of which depression (6.6%) and anxiety (4.9%) were most common. Logistic regression revealed increased risks of ventilator use in depression (OR = 1.62, 95% CI = 1.04–2.54, p < 0.05), extended hospitalization length in bipolar (OR = 1.77, 95% CI = 1.08–2.89, p < 0.05), and higher rehabilitation utilization in depression (OR = 1.25, 95% CI = 1.06–1.47, p < 0.01) and bipolar (OR = 1.69, 95% CI = 1.04–2.76, p < 0.05). Those patients with anxiety had a decreased risk of longer hospitalization duration (OR = 0.77, 95% CI = 0.60–0.98, p < 0.05), while those with dementia and schizophrenia had no change in risks. Preoperative recognition of major psychiatric disorders for risk and treatment assessment is suggested as people with preexisting depression or bipolar disorder have worse outcomes after spine surgery.
Activity Patterns and Functioning. A Contextual–Functional Approach to Pain Catastrophizing in Women with Fibromyalgia
Authors: Peñacoba Cecilia , Pastor-Mira Maria Ángeles , Suso-Ribera Carlos , Catalá Patricia , Nardi-Rodríguez Ainara , López-Roig Sofía
Published: May 2021

Background: The psychological flexibility model states that activity patterns are not deemed to be intrinsically functional or dysfunctional; it is considered that underlying factors, such as personal goals and contextual factors, are what will determine their effects on disability. Pain catastrophizing has frequently been associated with several important pain-related outcomes. Despite its recent conceptualization within affective–motivational approaches, its moderating role between activity patterns and dysfunction has not been analyzed. Methods: This study analyzes the moderating role of pain catastrophizing and its dimensions (Pain Catastrophizing Scale) between activity patterns (Activity Patterns Scale) and disease impact (Fibromyalgia Impact Questionnaire—Revised) in 491 women with fibromyalgia. Results: Activity avoidance (p < 0.001), excessive persistence (p < 0.001) and pacing (p < 0.01) patterns were positively associated with fibromyalgia impact. Helplessness shows a moderating role between pain avoidance (B = 0.100, t =2.30, p = 0.021, [0.01, 0.18]), excessive persistence (B = −0.09, t = −2.24, p = 0.02, [−0.18, −0.01]), pain persistence (B = −0.10, t = −2.04, p = 0.04, [−0.19, −0.004]) and functioning. Conclusion: Helplessness (within pain catastrophizing) is a relevant variable within psychological flexibility models applied to activity patterns. Specifically, pain avoidance is especially dysfunctional in patients with high helplessness. To improve excessive persistence and pain persistence, it is necessary to reduce helplessness before regulating activity patterns.
Competition Nutrition Practices of Elite Male Professional Rugby Union Players
Authors: Posthumus Logan , Fairbairn Kirsty , Darry Katrina , Driller Matthew , Winwood Paul , Gill Nicholas
Published: May 2021

Thirty-four elite male professional rugby union players from the New Zealand Super Rugby championship completed dietary intakes via the Snap-N-Send method during a seven-day competition week. Mean seven-day absolute energy intake was significantly higher for forwards (4606 ± 719 kcal·day−1) compared to backs (3761 ± 618 kcal·day−1; p < 0.01; d = 1.26). Forwards demonstrated significantly higher mean seven-day absolute macronutrient intakes compared to backs (p < 0.03; d = 0.86–1.58), but no significant differences were observed for mean seven-day relative carbohydrate (3.5 ± 0.8 vs. 3.7 ± 0.7 g·kg·day−1), protein (2.5 ± 0.4 vs. 2.4 ± 0.5 g·kg·day−1), and fat (1.8 ± 0.4 vs. 1.8 ± 0.5 g·kg·day−1) intakes. Both forwards and backs reported their highest energy (5223 ± 864 vs. 4694 ± 784 kcal·day−1) and carbohydrate (4.4 ± 1.2 vs. 5.1 ± 1.0 g·kg·day−1) intakes on game day, with ≈62% of total calories being consumed prior to kick-off. Mean pre-game meal composition for all players was 1.4 ± 0.5 g·kg−1 carbohydrate, 0.8 ± 0.2 g·kg−1 protein, and 0.5 ± 0.2 g·kg−1 fat. Players fell short of daily sports nutrition guidelines for carbohydrate and appeared to “eat to intensity” by increasing or decreasing energy and carbohydrate intake based on the training load. Despite recommendations and continued education, many rugby players select what would be considered a “lower” carbohydrate intake. Although these intakes appear adequate to be a professional RU player, further research is required to determine optimal dietary intakes.
Factors Influencing Preparedness for Bioterrorism among Koreans
Authors: Kim Yujeong , Lee Eunmi
Published: May 2021

Bioterrorism is destructive enough to cause a societal collapse, and preparation for bioterrorism is imperative. This study aims to identify the factors influencing preparedness for bioterrorism among Koreans. A total of 1050 subjects were included in the study, which were allocated according to region and age in proportion to population. An online survey was used to examine the following factors: participants’ general characteristics; cognitive factors including perceived probability, perceived seriousness, perceived personal impact, perceived coping efficacy, and perceived resilience; social–contextual factors including perceived governmental preparedness and perceived front-line preparedness; affective responses including affective response to terrorism and anxiety; and bioterrorism preparedness. The factors influencing the level of preparedness for bioterrorism included age, marital status, experience of bioterrorism education, perceived personal impact, perceived coping efficacy, perceived resilience, and perceived front-line preparedness. The factors that most significantly affected the level of preparedness for bioterrorism were perceived coping efficacy and perceived front-line preparedness, with an R2 of 41.4%. Relevant education and public relations programs should be strengthened to help citizens minimize their exposure and known to inform relevant institutions in the event of suspected bioterrorism, and front-line responders should cultivate their ability to respond to bioterrorism quickly and accurately.
A Spatial Approach for Modeling Amphibian Road-Kills: Comparison of Regression Techniques
Authors: Sousa-Guedes Diana , Franch Marc , Sillero Neftalí
Published: May 2021

Road networks are the main source of mortality for many species. Amphibians, which are in global decline, are the most road-killed fauna group, due to their activity patterns and preferred habitats. Many different methodologies have been applied in modeling the relationship between environment and road-kills events, such as logistic regression. Here, we compared the performance of five regression techniques to relate amphibians’ road-kill frequency to environmental variables. For this, we surveyed three country roads in northern Portugal in search of road-killed amphibians. To explain the presence of road-kills, we selected a set of environmental variables important for the presence of amphibians and the occurrence of road-kills. We compared the performances of five modeling techniques: (i) generalized linear models, (ii) generalized additive models, (iii) random forest, (iv) boosted regression trees, and (v) geographically weighted regression. The boosted regression trees and geographically weighted regression techniques performed the best, with a percentage of deviance explained between 61.8% and 76.6% and between 55.3% and 66.7%, respectively. Moreover, the geographically weighted regression showed a great advantage over the other techniques, as it allows mapping local parameter coefficients as well as local model performance (pseudo-R2). The results suggest that geographically weighted regression is a useful tool for road-kill modeling, as well as to better visualize and map the spatial variability of the models.
Spatiotemporal Patterns of Human Mobility and Its Association with Land Use Types during COVID-19 in New York City
Authors: Jiang Yuqin , Huang Xiao , Li Zhenlong
Published: May 2021

The novel coronavirus disease (COVID-19) pandemic has impacted every facet of society. One of the non-pharmacological measures to contain the COVID-19 infection is social distancing. Federal, state, and local governments have placed multiple executive orders for human mobility reduction to slow down the spread of COVID-19. This paper uses geotagged tweets data to reveal the spatiotemporal human mobility patterns during this COVID-19 pandemic in New York City. With New York City open data, human mobility pattern changes were detected by different categories of land use, including residential, parks, transportation facilities, and workplaces. This study further compares human mobility patterns by land use types based on an open social media platform (Twitter) and the human mobility patterns revealed by Google Community Mobility Report cell phone location, indicating that in some applications, open-access social media data can generate similar results to private data. The results of this study can be further used for human mobility analysis and the battle against COVID-19.
Simulation of Land-Use Changes Using the Partitioned ANN-CA Model and Considering the Influence of Land-Use Change Frequency
Authors: Xu Quanli , Wang Qing , Liu Jing , Liang Hong
Published: May 2021

Land-use change is a typical geographic evolutionary process characterized by spatial heterogeneity. As such, the driving factors, conversion rules, and rate of change vary for different regions around the world. However, most cellular automata (CA) models use the same transition rules for all cells in the model space when simulating land-use change. Thus, spatial heterogeneity change is ignored in the model, which means that these models are prone to over- or under simulation, resulting in a large deviation from reality. An effective means of accounting for the influence of spatial heterogeneity on the quality of the CA model is to establish a partitioned model based on cellular space partitioning. This study established a partitioned, dual-constrained CA model using the area-weighted frequency of land-use change (AWFLUC) to capture its spatial heterogeneity. This model was used to simulate the land-use evolution of the Dianchi Lake watershed. First, the CA space was divided into subzones using a dual-constrained spatial clustering method. Second, an artificial neural network (ANN) was used to automatically acquire conversion rules to construct an ANN-CA model of land-use change. Finally, land-use changes were simulated using the ANN-CA model based on data from 2006 to 2016, and model reliability was validated. The experimental results showed that compared with the non-partitioned CA model, the partitioned counterpart was able to improve the accuracy of land-use change simulation significantly. Furthermore, AWFLUC is an important indicator of the spatial heterogeneity of land-use change. The shapes of the division spaces were more similar to reality and the simulation accuracy was higher when AWFLUC was considered as a land-use change characteristic.
A Quantitative Analysis of Factors Influencing Organic Matter Concentration in the Topsoil of Black Soil in Northeast China Based on Spatial Heterogeneous Patterns
Authors: Du Zhenbo , Gao Bingbo , Ou Cong , Du Zhenrong , Yang Jianyu , Batsaikhan Bayartungalag , Dorjgotov Battogtokh , Yun Wenju , Zhu Dehai
Published: May 2021

Black soil is fertile, abundant with organic matter (OM) and is exceptional for farming. The black soil zone in northeast China is the third-largest black soil zone globally and produces a quarter of China’s commodity grain. However, the soil organic matter (SOM) in this zone is declining, and the quality of cultivated land is falling off rapidly due to overexploitation and unsustainable management practices. To help develop an integrated protection strategy for black soil, this study aimed to identify the primary factors contributing to SOM degradation. The geographic detector, which can detect both linear and nonlinear relationships and the interactions based on spatial heterogeneous patterns, was used to quantitatively analyze the natural and anthropogenic factors affecting SOM concentration in northeast China. In descending order, the nine factors affecting SOM are temperature, gross domestic product (GDP), elevation, population, soil type, precipitation, soil erosion, land use, and geomorphology. The influence of all factors is significant, and the interaction of any two factors enhances their impact. The SOM concentration decreases with increased temperature, population, soil erosion, elevation and terrain undulation. SOM rises with increased precipitation, initially decreases with increasing GDP but then increases, and varies by soil type and land use. Conclusions about detailed impacts are presented in this paper. For example, wind erosion has a more significant effect than water erosion, and irrigated land has a lower SOM content than dry land. Based on the study results, protection measures, including conservation tillage, farmland shelterbelts, cross-slope ridges, terraces, and rainfed farming are recommended. The conversion of high-quality farmland to non-farm uses should be prohibited.
Coupling Historical Maps and LiDAR Data to Identify Man-Made Landforms in Urban Areas
Authors: Terrone Martino , Piana Pietro , Paliaga Guido , D’Orazi Marco , Faccini Francesco
Published: May 2021

In recent years, there has been growing interest in urban geomorphology both for its applications in terms of landscape planning, and its historical, cultural, and scientific interest. Due to recent urban growth, the identification of landforms in cities is difficult, particularly in Mediterranean and central European cities, characterized by more than 1000 years of urban stratification. By comparing and overlapping 19th-century cartography and modern topography from remote sensing data, this research aims to assess the morphological evolution of the city of Genoa (Liguria, NW Italy). The analysis focuses on a highly detailed 1:2’000 scale map produced by Eng. Ignazio Porro in the mid-19th century. The methodology, developed in QGIS, was applied on five case studies of both hillside and valley floor areas of the city of Genoa. Through map overlay and digitalization of elevation data and contour lines, it was possible to identify with great accuracy the most significant morphological transformations that have occurred in the city since the mid-19th century. In addition, the results were validated by direct observation and by drills data of the regional database. The results allowed the identification and quantification of the main anthropic landforms. The paper suggests that the same methodology can be applied to other historical urban contexts characterized by urban and architectural stratification.
Sexual Dimorphism of Corticosteroid Signaling during Kidney Development
Authors: Laulhé Margaux , Dumeige Laurence , Vu Thi An , Hani Imene , Pussard Eric , Lombès Marc , Viengchareun Say , Martinerie Laetitia
Published: May 2021

Sexual dimorphism involves differences between biological sexes that go beyond sexual characteristics. In mammals, differences between sexes have been demonstrated regarding various biological processes, including blood pressure and predisposition to develop hypertension early in adulthood, which may rely on early events during development and in the neonatal period. Recent studies suggest that corticosteroid signaling pathways (comprising glucocorticoid and mineralocorticoid signaling pathways) have distinct tissue-specific expression and regulation during this specific temporal window in a sex-dependent manner, most notably in the kidney. This review outlines the evidence for a gender differential expression and activation of renal corticosteroid signaling pathways in the mammalian fetus and neonate, from mouse to human, that may favor mineralocorticoid signaling in females and glucocorticoid signaling in males. Determining the effects of such differences may shed light on short term and long term pathophysiological consequences, markedly for males.
Genome-Wide Analysis of nsLTP Gene Family and Identification of SiLTPs Contributing to High Oil Accumulation in Sesame (Sesamum indicum L.)
Authors: Song Shengnan , You Jun , Shi Lisong , Sheng Chen , Zhou Wangyi , Dossou Senouwa Segla Koffi , Dossa Komivi , Wang Linhai , Zhang Xiurong
Published: May 2021

The biosynthesis and storage of lipids in oil crop seeds involve many gene families, such as nonspecific lipid-transfer proteins (nsLTPs). nsLTPs are cysteine-rich small basic proteins essential for plant development and survival. However, in sesame, information related to nsLTPs was limited. Thus, the objectives of this study were to identify the Sesamum indicum nsLTPs (SiLTPs) and reveal their potential role in oil accumulation in sesame seeds. Genome-wide analysis revealed 52 SiLTPs, nonrandomly distributed on 10 chromosomes in the sesame variety Zhongzhi 13. Following recent classification methods, the SiLTPs were divided into nine types, among which types I and XI were the dominants. We found that the SiLTPs could interact with several transcription factors, including APETALA2 (AP2), DNA binding with one finger (Dof), etc. Transcriptome analysis showed a tissue-specific expression of some SiLTP genes. By integrating the SiLTPs expression profiles and the weighted gene co-expression network analysis (WGCNA) results of two contrasting oil content sesame varieties, we identified SiLTPI.23 and SiLTPI.28 as the candidate genes for high oil content in sesame seeds. The presumed functions of the candidate gene were validated through overexpression of SiLTPI.23 in Arabidopsis thaliana. These findings expand our knowledge on nsLTPs in sesame and provide resources for functional studies and genetic improvement of oil content in sesame seeds.
NRF2 DLG Domain Mutations Identified in Japanese Liver Cancer Patients Affect the Transcriptional Activity in HCC Cell Lines
Authors: Haque Effi , Śmiech Magdalena , Łuczyńska Kamila , Bouchard Marie France , Viger Robert , Kono Hidetoshi , Pierzchała Mariusz , Taniguchi Hiroaki
Published: May 2021

Geographically, East Asia had the highest liver cancer burden in 2017. Besides this, liver cancer-related deaths were high in Japan, accounting for 3.90% of total deaths. The development of liver cancer is influenced by several factors, and genetic alteration is one of the critical factors among them. Therefore, the detailed mechanism driving the oncogenic transformation of liver cells needs to be elucidated. Recently, many researchers have focused on investigating the liver cancer genome and identified somatic mutations (MTs) of several transcription factors. In this line, next-generation sequencing of the cancer genome identified that oxidative stress-related transcription factor NRF2 (NFE2L2) is mutated in different cancers, including hepatocellular carcinoma (HCC). Here, we demonstrated that NRF2 DLG motif mutations (NRF2 D29A and L30F), found in Japanese liver cancer patients, upregulate the transcriptional activity of NRF2 in HCC cell lines. Moreover, the transcriptional activity of NRF2 mutations is not suppressed by KEAP1, presumably because NRF2 MTs disturb proper NRF2-KEAP1 binding and block KEAP1-mediated degradation of NRF2. Additionally, we showed that both MTs upregulate the transcriptional activity of NRF2 on the MMP9 promoter in Hepa1-6 and Huh7 cells, suggesting that MT derived gain-of-function of NRF2 may be important for liver tumor progression. We also found that ectopic overexpression of oncogenic BRAF WT and V600E increases the transcriptional activity of NRF2 WT on both the 3xARE reporter and MMP9 promoter. Interestingly, NRF2 D29A and L30F MTs with oncogenic BRAF V600E MT synergistically upregulate the transcription activity of NRF2 on the 3xARE reporter and MMP9 promoter in Hepa1-6 and Huh7 cells. In summary, our findings suggest that MTs in NRF2 have pathogenic effects, and that NRF2 MTs together with oncogenic BRAF V600E MT synergistically cause more aberrant transcriptional activity. The high activity of NRF2 MTs in HCC with BRAF MT warrants further exploration of the potential diagnostic, prognostic, and therapeutic utility of this pathway in HCC.
Optogenetic Approaches for the Spatiotemporal Control of Signal Transduction Pathways
Authors: Kramer Markus M. , Lataster Levin , Weber Wilfried , Radziwill Gerald
Published: May 2021

Biological signals are sensed by their respective receptors and are transduced and processed by a sophisticated intracellular signaling network leading to a signal-specific cellular response. Thereby, the response to the signal depends on the strength, the frequency, and the duration of the stimulus as well as on the subcellular signal progression. Optogenetic tools are based on genetically encoded light-sensing proteins facilitating the precise spatiotemporal control of signal transduction pathways and cell fate decisions in the absence of natural ligands. In this review, we provide an overview of optogenetic approaches connecting light-regulated protein-protein interaction or caging/uncaging events with steering the function of signaling proteins. We briefly discuss the most common optogenetic switches and their mode of action. The main part deals with the engineering and application of optogenetic tools for the control of transmembrane receptors including receptor tyrosine kinases, the T cell receptor and integrins, and their effector proteins. We also address the hallmarks of optogenetics, the spatial and temporal control of signaling events.
Allogenic Use of Human Placenta-Derived Stromal Cells as a Highly Active Subtype of Mesenchymal Stromal Cells for Cell-Based Therapies
Authors: Gorodetsky Raphael , Aicher Wilhelm K.
Published: May 2021

The application of mesenchymal stromal cells (MSCs) from different sources, including bone marrow (BM, bmMSCs), adipose tissue (atMSCs), and human term placenta (hPSCs) has been proposed for various clinical purposes. Accumulated evidence suggests that the activity of the different MSCs is indirect and associated with paracrine release of pro-regenerative and anti-inflammatory factors. A major limitation of bmMSCs-based treatment for autologous application is the limited yield of cells harvested from BM and the invasiveness of the procedure. Similar effects of autologous and allogeneic MSCs isolated from various other tissues were reported. The easily available fresh human placenta seems to represent a preferred source for harvesting abundant numbers of human hPSCs for allogenic use. Cells derived from the neonate tissues of the placenta (f-hPSC) can undergo extended expansion with a low risk of senescence. The low expression of HLA class I and II on f-hPSCs reduces the risk of rejection in allogeneic or xenogeneic applications in normal immunocompetent hosts. The main advantage of hPSCs-based therapies seems to lie in the secretion of a wide range of pro-regenerative and anti-inflammatory factors. This renders hPSCs as a very competent cell for therapy in humans or animal models. This review summarizes the therapeutic potential of allogeneic applications of f-hPSCs, with reference to their indirect pro-regenerative and anti-inflammatory effects and discusses clinical feasibility studies.
Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats
Authors: Chun Kyung-Ju , Lee Chang-Ho , Kim Kyung-Woon , Lee So-Min , Kim So-Young
Published: May 2021

Megalin has been proposed as an endocytic receptor for aminoglycosides as well as estrogen and androgen. We aimed to investigate the otoprotective effects of antiandrogens (flutamide, FM) on kanamycin (KM)-induced hearing loss in rats. Rats were divided into four groups. The KM group was administered KM (20 mg/kg/day) for 5 days, while the FM group received FM (15 mg/kg/day) for 10 days. In the KM + FM group, KM and FM (15 mg/kg/day) were simultaneously injected for 5 days and then FM was injected for 5 days. Auditory brainstem responses were measured. Western blotting and/or quantitative reverse transcriptase-polymerase chain reaction were performed for megalin, cytochrome P450 1A1 (Cyp1a1), Cyp1b1, metallothionein 1A (MT1A), MT2A, tumor necrosis factor (TNF)-α, caspase 3, and cleaved caspase 3. The FM + KM group showed attenuated auditory thresholds when compared with the KM group at 4, 8, 16, and 32 kHz (all p < 0.05). The KM + FM group showed lower megalin and Cyp1b1 levels than the KM group (all p < 0.05). The KM + FM group revealed lower MT1A, TNFα, and caspase 3 protein levels, compared with those in the KM group (all p < 0.05). Androgen receptor inhibition protects against cochlear injuries in KM-induced hearing loss rats by attenuating megalin expression, revealing anti-inflammatory and anti-apoptotic effects.
Reviewing Evidence for the Relationship of EEG Abnormalities and RTT Phenotype Paralleled by Insights from Animal Studies
Authors: Smirnov Kirill , Stroganova Tatiana , Molholm Sophie , Sysoeva Olga
Published: May 2021

Rett syndrome (RTT) is a rare neurodevelopmental disorder that is usually caused by mutations of the MECP2 gene. Patients with RTT suffer from severe deficits in motor, perceptual and cognitive domains. Electroencephalogram (EEG) has provided useful information to clinicians and scientists, from the very first descriptions of RTT, and yet no reliable neurophysiological biomarkers related to the pathophysiology of the disorder or symptom severity have been identified to date. To identify consistently observed and potentially informative EEG characteristics of RTT pathophysiology, and ascertain areas most worthy of further systematic investigation, here we review the literature for EEG abnormalities reported in patients with RTT and in its disease models. While pointing to some promising potential EEG biomarkers of RTT, our review identify areas of need to realize the potential of EEG including (1) quantitative investigation of promising clinical-EEG observations in RTT, e.g., shift of mu rhythm frequency and EEG during sleep; (2) closer alignment of approaches between patients with RTT and its animal models to strengthen the translational significance of the work (e.g., EEG measurements and behavioral states); (3) establishment of large-scale consortium research, to provide adequate Ns to investigate age and genotype effects.
A Novel DUF569 Gene Is a Positive Regulator of the Drought Stress Response in Arabidopsis
Authors: Nabi Rizwana Begum Syed , Tayade Rupesh , Hussain Adil , Adhikari Arjun , Lee In-Jung , Loake Gary J. , Yun Byung-Wook
Published: May 2021

In the last two decades, global environmental change has increased abiotic stress on plants and severely affected crops. For example, drought stress is a serious abiotic stress that rapidly and substantially alters the morphological, physiological, and molecular responses of plants. In Arabidopsis, several drought-responsive genes have been identified; however, the underlying molecular mechanism of drought tolerance in plants remains largely unclear. Here, we report that the “domain of unknown function” novel gene DUF569 (AT1G69890) positively regulates drought stress in Arabidopsis. The Arabidopsis loss-of-function mutant atduf569 showed significant sensitivity to drought stress, i.e., severe wilting at the rosette-leaf stage after water was withheld for 3 days. Importantly, the mutant plant did not recover after rewatering, unlike wild-type (WT) plants. In addition, atduf569 plants showed significantly lower abscisic acid accumulation under optimal and drought-stress conditions, as well as significantly higher electrolyte leakage when compared with WT Col-0 plants. Spectrophotometric analyses also indicated a significantly lower accumulation of polyphenols, flavonoids, carotenoids, and chlorophylls in atduf569 mutant plants. Overall, our results suggest that novel DUF569 is a positive regulator of the response to drought in Arabidopsis.
MicroRNA Profiles of Maternal and Neonatal Endothelial Progenitor Cells in Preeclampsia
Authors: Brodowski Lars , Schröder-Heurich Bianca , von Hardenberg Sandra , Richter Katja , von Kaisenberg Constantin S. , Dittrich-Breiholz Oliver , Meyer Nadia , Dörk Thilo , von Versen-Höynck Frauke
Published: May 2021

Preeclampsia is associated with an increased cardiovascular morbidity of mother and offspring, thus contributing to a substantial burden in women and children’s health. It has been proven that endothelial progenitor cell (EPC) numbers and functional characteristics are impaired in cardiovascular disease and preeclampsia, although causative factors for the latter have remained elusive. MicroRNA (miRNA) modifications are a potential mechanism through which exposure to an altered environment translates into the development of chronic disease. In this study, we examined whether development of preeclampsia corresponds to alterations of miRNAs in maternal- and cord-blood-derived EPC. To test this end, we analyzed maternal and neonatal miRNAs via RNA sequencing from endothelial cells of preeclamptic and healthy controls in different cell culture passages. We were able to demonstrate differentially represented miRNAs in all groups. Hsa-miR-1270 showed significantly different levels in cord blood EPC from preeclampsia versus control and was negatively correlated with mRNA levels of its predicted targets ANGPTL7 and TFRC. Transfection with an hsa-miR-1270 inhibitor decreased the tube formation capacity and chemotactic motility but did not change proliferation in vitro. Target predictions and gene set enrichment analyses identified alternative splicing as a significantly enriched pathway for hsa-miR-1270. The top miRNAs in three other groups were predicted to target transcriptional and developmental pathways. Here, we showed for the first time significantly different levels of miRNAs and differently represented mRNA levels of predicted target genes in EPC derived from preeclampsia. Understanding the effects of preeclampsia on the epigenetic mechanisms of EPC will be crucial and may provide initial insights for further evaluation of the benefits of therapies targeting this cell population.
Lack of WWC2 Protein Leads to Aberrant Angiogenesis in Postnatal Mice
Authors: Brücher Viktoria Constanze , Egbring Charlotte , Plagemann Tanja , Nedvetsky Pavel I. , Höffken Verena , Pavenstädt Hermann , Eter Nicole , Kremerskothen Joachim , Heiduschka Peter
Published: May 2021

The WWC protein family is an upstream regulator of the Hippo signalling pathway that is involved in many cellular processes. We examined the effect of an endothelium-specific WWC1 and/or WWC2 knock-out on ocular angiogenesis. Knock-outs were induced in C57BL/6 mice at the age of one day (P1) and evaluated at P6 (postnatal mice) or induced at the age of five weeks and evaluated at three months of age (adult mice). We analysed morphology of retinal vasculature in retinal flat mounts. In addition, in vivo imaging and functional testing by electroretinography were performed in adult mice. Adult WWC1/2 double knock-out mice differed neither functionally nor morphologically from the control group. In contrast, the retinas of the postnatal WWC knock-out mice showed a hyperproliferative phenotype with significantly enlarged areas of sprouting angiogenesis and a higher number of tip cells. The branching and end points in the peripheral plexus were significantly increased compared to the control group. The deletion of the WWC2 gene was decisive for these effects; while knocking out WWC1 showed no significant differences. The results hint strongly that WWC2 is an essential regulator of ocular angiogenesis in mice. As an activator of the Hippo signalling pathway, it prevents excessive proliferation during physiological angiogenesis. In adult animals, WWC proteins do not seem to be important for the maintenance of the mature vascular plexus.
The Intention and Influence Factors of Nurses’ Participation in Telenursing
Authors: Chang Mei-Ying , Kuo Fang-Li , Lin Ting-Ru , Li Chin-Ching , Lee Tso-Ying
Published: May 2021

This study aimed to identify factors that significantly affect the behavioral intention of nursing staff to practice telenursing, applying the decomposed theory of planned behavior (DTPB) as the research framework. This cross-sectional survey study collected data from a valid sample of 203 responses from nurses from a regional hospital in Taipei City, Taiwan. The results of data analysis showed that nursing staff’s attitude, subjective norms, and perceived behavioral control toward telenursing correlated positively with behavioral intention to participate in telenursing. Decomposing the main concepts identified two significant predictive determinants that influence nurses’ behavioral intentions: (a) facilitating conditions (β = 0.394, t = 5.817, p = 0.000 < 0.001) and (b) supervisor influence (β= 0.232, t = 3.431, p = 0.001 < 0.01), which together explain 28.6% of the variance for behavioral intention. The results of this study indicated that support and encouragement from nursing supervisors are important factors affecting nurses’ intention to practice telenursing. Education and training, health policies advocacy and the provision of adequate facilitating technologies and recourses are important factors for improving intention to practice telenursing.
Geographic Monitoring of Insecticide Resistance Mutations in Native and Invasive Populations of the Fall Armyworm
Authors: Yainna Sudeeptha , Nègre Nicolas , Silvie Pierre J. , Brévault Thierry , Tay Wee Tek , Gordon Karl , dAlençon Emmanuelle , Walsh Thomas , Nam Kiwoong
Published: May 2021

Field evolved resistance to insecticides is one of the main challenges in pest control. The fall armyworm (FAW) is a lepidopteran pest species causing severe crop losses, especially corn. While native to the Americas, the presence of FAW was confirmed in West Africa in 2016. Since then, the FAW has been detected in over 70 countries covering sub-Saharan Africa, the Middle East, North Africa, South Asia, Southeast Asia, and Oceania. In this study, we tested whether this invasion was accompanied by the spread of resistance mutations from native to invasive areas. We observed that mutations causing Bt resistance at ABCC2 genes were observed only in native populations where the mutations were initially reported. Invasive populations were found to have higher gene numbers of cytochrome P450 genes than native populations and a higher proportion of multiple resistance mutations at acetylcholinesterase genes, supporting strong selective pressure for resistance against synthetic insecticides. This result explains the susceptibility to Bt insecticides and resistance to various synthetic insecticides in Chinese populations. These results highlight the necessity of regular and standardized monitoring of insecticide resistance in invasive populations using both genomic approaches and bioassay experiments.
Clinical Performance of Implant Crown Retained Removable Partial Dentures for Mandibular Edentulism—A Retrospective Study
Authors: Yoo Soo-Yeon , Kim Seong-Kyun , Heo Seong-Joo , Koak Jai-Young , Jeon Hye-Rin
Published: May 2021

The studies on implant-crown-retained removable partial dentures (IC-RPDs) for edentulism are scarce. The purpose of this study was to evaluate survival rates and marginal bone loss (MBL) of IC-RPDs compared to implant overdentures (IODs) in mandibular edentulism. Variables that influenced survival and marginal bone loss (MBL) of implants in both treatment modalities were analyzed and the functional/esthetic satisfaction of patients as well as prosthetic complications were also observed. Eighteen IC-RPDs with a total of 60 implant-supported survey crowns and 24 IODs with a total 94 implants retained with magnet attachments were observed. After a median observation period of 46.6 months (up to 149 months), we observed 98.3% implant survival rates for IC-RPDs and 92.5% for IODs. Kaplan–Meier survival curves based on the treatment modality showed that, at 96 months, cumulative survival rates were 98.3% in IC-RPD and 83.1% in IOD. For implant survival rates, no statistical differences were observed according to age, sex, opposing dentition, or implant positions (p = 0.515, 0.666, 0.201, 0.749, respectively). The implant MBL measurements for IC-RPD and IOD groups at the final recall check were 0.93 ± 1.22 mm and 2.12 ± 2.09 mm, respectively. Additionally, there were no significant differences between groups (p = 0.554). The implants with peri-implantitis at year 1 showed significantly higher MBL at final check-up (p < 0.001). The MBL of implants showed significant differences based on age (p = 0.008) and opposing dentition (p = 0.003). No significant differences of implant MBL were observed for the position of placed implants (p = 0.621) or sex (p = 0.666). Patient-reported outcome measures (PROMs) on functional and esthetic satisfaction were significantly improved after IC-RPD or IOD treatment (p < 0.001). The most frequent prosthetic complication of IC-RPD was clasp loosening, while for IOD group, it was attachment dislodgement. Within the limitations of this retrospective study, we concluded that IC-RPDs could be considered as a viable treatment option for edentulous patients who need few fixed abutments for satisfaction.
Analysis of Frailty in Geriatric Patients as a Prognostic Factor in Endovascular Treated Patients with Large Vessel Occlusion Strokes
Authors: Schnieder Marlena , Bähr Mathias , Kirsch Mareike , Maier Ilko , Behme Daniel , Riedel Christian Heiner , Psychogios Marios-Nikos , Brehm Alex , Liman Jan , von Arnim Christine A. F.
Published: May 2021

Frailty is associated with an increased risk of adverse health-care outcomes in elderly patients. The Hospital Frailty Risk Score (HFRS) has been developed and proven to be capable of identifying patients which are at high risk of adverse outcomes. We aimed to investigate whether frail patients also face adverse outcomes after experiencing an endovascular treated large vessel occlusion stroke (LVOS). In this retrospective observational cohort study, we analyzed patients ≥ 65 years that were admitted during 2015–2019 with LVOS and endovascular treatment. Primary outcomes were mortality and the modified Rankin Scale (mRS) after three months. Regression models were used to determine the impact of frailty. A total of 318 patients were included in the cohort. The median HFRS was 1.6 (IQR 4.8). A total of 238 (75.1%) patients fulfilled the criteria for a low-frailty risk with a HFRS < 5.72 (22.7%) for moderate-frailty risk with an HFRS from 5–15 and 7 (2.2%) patients for a high-frailty risk. Multivariate regression analyses revealed that the HFRS was associated with an increased mortality after 90 days (CI (95%) 1.001 to 1.236; OR 1.112) and a worse mRS (CI (95%) 1.004 to 1.270; OR 1.129). We identified frailty as an impact factor on functional outcome and mortality in patients undergoing thrombectomy in LVOS.
Machine Learning Models to Predict 30-Day Mortality in Mechanically Ventilated Patients
Authors: Kim Jong Ho , Kwon Young Suk , Baek Moon Seong
Published: May 2021

Previous scoring models, such as the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score, do not adequately predict the mortality of patients receiving mechanical ventilation in the intensive care unit. Therefore, this study aimed to apply machine learning algorithms to improve the prediction accuracy for 30-day mortality of mechanically ventilated patients. The data of 16,940 mechanically ventilated patients were divided into the training-validation (83%, n = 13,988) and test (17%, n = 2952) sets. Machine learning algorithms including balanced random forest, light gradient boosting machine, extreme gradient boost, multilayer perceptron, and logistic regression were used. We compared the area under the receiver operating characteristic curves (AUCs) of machine learning algorithms with those of the APACHE II and ProVent score results. The extreme gradient boost model showed the highest AUC (0.79 (0.77–0.80)) for the 30-day mortality prediction, followed by the balanced random forest model (0.78 (0.76–0.80)). The AUCs of these machine learning models as achieved by APACHE II and ProVent scores were higher than 0.67 (0.65–0.69), and 0.69 (0.67–0.71)), respectively. The most important variables in developing each machine learning model were APACHE II score, Charlson comorbidity index, and norepinephrine. The machine learning models have a higher AUC than conventional scoring systems, and can thus better predict the 30-day mortality of mechanically ventilated patients.