bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital Elevation Models of Rockfalls and Landslides: A Review and Meta-Analysis
Authors: Kakavas Maria P. , Nikolakopoulos Konstantinos G.
Published: June 2021

The scope of this paper is to summarize previous research pertaining to the use of digital elevation models (DEMs) and digital terrain models (DTMs) in the study of rockfalls and landslides. Research from 1983 to 2020 was surveyed in order to understand how the spatial resolution of DEMs and DTMs affects landslide detection, validation, and mapping. Another major question examined was the relationship between the DEM resolution and the extent of the rockfall or landslide event. It emerged from the study that, for landslides, the majority of researchers used DEMs with a spatial resolution of between 10 m and 30 m, while for rockfalls, they used DEMs with a spatial resolution of between 5 m and 20 m. We concluded that DEMs with a very high resolution (less than 5 m) are suitable for local-scale occurrences, while medium-resolution (from 20 m to 30 m) DEMs are suitable for regional-scale events. High resolution is associated with high accuracy and detailed structural characteristics, while medium accuracy better illustrates the topographic features. A low pixel size (more than 90 m) is not recommended for this type of research. Susceptibility maps, inventory maps, hazard risk zones, and vulnerability assessments are some of the main tools used in landslide/rockfall investigations, and topographic indexes, methods, models, and software optimize the reliability of the results. All of these parameters are closely related to DEMs and DTMs as the cell size affects the credibility of the final outcome.
Smaller Cortisol Awakening Responses Are Associated with Greater Visual Dependence in Postural Control
Authors: Smyth Nina , Milani Monica , Thorn Lisa , Flynn Maria , Golding John F. , Evans Phil , Clow Angela
Published: June 2021

There are known links between the hypothalamic–pituitary–adrenal (HPA) axis and systems responsible for regulating posture. Our aim was to explore directly, for the first time, whether an aspect of circadian HPA axis activity (the cortisol awakening response: CAR) was associated with greater visual dependency in postural control. For measurement of the CAR, electronically monitored saliva samples were collected by participants following morning awakening in their home environment. On the afternoons of the same days, postural sway was measured in the laboratory by exposing participants to static (control) and moving visual stimuli whilst standing still and upright on a force platform. Visual dependence was assessed as the increase in postural sway (path length) during exposure to the moving compared with the static condition. The 44 measurement days were derived from four days for each of eleven healthy participants (mean ± SD age: 51.18 ± 3.3 years). As expected, postural sway was greater when exposed to moving versus static cues. Mixed regression modelling showed that participants with smaller four day average CARs had greater deterioration in postural sway when presented with moving stimuli. These data are the first to document associations between the CAR and visual dependency in postural sway.
Impacts of the COVID-19 Pandemic on the Bereaved: A Study of Bereaved Weibo Users
Authors: Han Nuo , Chen Gewei , Li Sijia , Huang Feng , Wang Xiaoyang , Ren Xiaopeng , Zhu Tingshao
Published: June 2021

The global COVID-19 pandemic may significantly affect the experiences of death and bereavement. This study aimed to learn from recent outbreaks of infectious diseases and further understand their impacts on bereavement. We obtained psychological status scores for 32 individuals bereaved due to COVID-19 and 127 individuals bereaved due to non-COVID-19 causes using the online ecological recognition (OER) approach. Next, a sentiment analysis and independent sample t-test were performed to examine the differences between these two groups. The results indicated that the individuals bereaved due to COVID-19 were more insecure and more preoccupied with the grief of the moment than those bereaved due to non-COVID-19 reasons, while the latter group had higher depression scores than the former group. This study can guide policy-makers and clinical practitioners to provide more targeted and sustainable post-bereavement support for both bereaved groups during the COVID-19 period.
Effects of Long Working Hours and Night Work on Subjective Well-Being Depending on Work Creativity and Task Variety, and Occupation: The Role of Working-Time Mismatch, Variability, Shift Work, and Autonomy
Authors: Shin Min-Gwan , Kim Yoon-Ji , Kim Tae-Kyoung , Kang Dongmug
Published: June 2021

This study explored the effects of long working hours (LW) and night work (NW) on subjective well-being and the modifying effects of work creativity and task variety (WCTV) and occupation. In addition, we examined the influence of working time-related variables including working-time mismatch, variability, shift work, and autonomy on the effects of LW and NW. This study used data from the 5th Korean Working Conditions Survey on 50,205 workers. LW and NW were defined as 52–60 h (L1) or >60 h (L2) per week, and 1–10 days (N1) or >10 days (N2) of night work per month. Multiple logistic regression was used to examine the effects of LW and NW and the modifying influences of WCTV and occupation. Differences in ORs of LW and NW caused by working time-related variables were investigated, to determine effect sizes and directions. A high level of WCTV alleviated the risks of LW and NW. White-collar workers were more vulnerable to the risk associated with NW. Regarding working-time related variables, working-time mismatch and variability increased the risks of LW and NW, respectively, while shift work alleviated the risks of NW. In countries where flexible work systems are not well utilized, working-time autonomy might not be associated with the risk of LW or NW. This study showed that it is necessary to comprehensively consider the occupation and task characteristics of individual workers performing LW or NW. Further studies of the modifying effects of working time-related variables on LW and NW are needed.
Influence of Epilepsy on the Quality of Life of Patients with Brain Tumors
Authors: Krajewski Stanisław , Wójcik Magdalena , Harat Marek , Furtak Jacek
Published: June 2021

Epilepsy is a common consequence of brain tumors, occurring in 35 to 75% of cases. Here we evaluated the influence of epilepsy on the quality of life (QoL) of patients with malignant brain tumors (primary and metastatic) and assessed which areas of function are most affected by epilepsy and brain tumors. Sixty patients undergoing brain tumor surgery at the Neurosurgery Clinic of the 10th Military Research Hospital, Bydgoszcz, Poland (30 with epilepsy and 30 without epilepsy) were studied. Relationships between categorical variables were determined with Pearson’s chi-squared test, while continuous data were analyzed with the Mann-Whitney U-test. A p value < 0.05 was considered statistically significant. A multiple regression model was used for multivariate analysis of QoL. Patients with epilepsy more frequently reported memory disorders as a problem in their daily life. There were trends towards greater impairments in social, professional, and family life, sports and recreational activities, and daily physical activities in brain tumor patients with epilepsy rather than those without epilepsy. Higher frequency and generalized seizures significantly and adversely influenced the ability of patients to leave home and drive vehicles, but a proportion of patients with frequent, generalized seizures continued to drive regardless. Patients with generalized seizures considered the adverse effects of taking medicines as significantly disruptive. Memory disorders significantly affect the QoL of patients with epilepsy, and the importance of stopping driving must be emphasized by all healthcare professionals.
On the Reciprocal Relationship between Quantitative and Qualitative Job Insecurity and Outcomes. Testing a Cross-Lagged Longitudinal Mediation Model
Authors: Nawrocka Sonia , De Witte Hans , Brondino Margherita , Pasini Margherita
Published: June 2021

Prior cross-sectional research indicates that the negative effects of quantitative job insecurity (i.e., threat to job loss) on employees’ wellbeing are fully mediated by qualitative job insecurity (i.e., threat to job characteristics). In the current longitudinal study, we replicated and further extended this view to include a direct effect of qualitative job insecurity on quantitative job insecurity. We explored these reciprocal relations in the context of their concurrent effects on work related outcomes by means of dual-mediation modelling. We identified a wide range of the outcomes, classified as: job strains (i.e., exhaustion, emotional and cognitive impairment), psychological coping reactions (i.e., job satisfaction, work engagement, turnover intention), and behavioral coping reactions (i.e., in-role and extra role performance, counterproductive behavior). We employed a three-wave panel design and surveyed 2003 Flemish employees. The results showed that the dual-mediation model had the best fit to the data. However, whereas qualitative job insecurity predicted an increase in quantitative job insecurity and the outcome variables six months later, quantitative job insecurity did not affect qualitative job insecurity or the outcomes over time. The study demonstrates the importance of qualitative job insecurity not only as a severe work stressor but also as an antecedent of quantitative job insecurity. Herewith, we stress the need for further research on the causal relations between both dimensions of job insecurity.
Revisiting the Effects of High-Speed Railway Transfers in the Early COVID-19 Cross-Province Transmission in Mainland China
Authors: Chan Chun-Hsiang , Wen Tzai-Hung
Published: June 2021

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic that was reported at the end of 2019 in Wuhan, China, and was rapidly disseminated to all provinces in around one month. The study aims to assess the changes in intercity railway passenger transport on the early spatial transmission of COVID-19 in mainland China. Examining the role of railway transport properties in disease transmission could help quantify the spatial spillover effects of large-scale travel restriction interventions. This study used daily high-speed railway schedule data to compare the differences in city-level network properties (destination arrival and transfer service) before and after the Wuhan city lockdown in the early stages of the spatial transmission of COVID-19 in mainland China. Bayesian multivariate regression was used to examine the association between structural changes in the railway origin-destination network and the incidence of COVID-19 cases. Our results show that the provinces with rising transfer activities after the Wuhan city lockdown had more confirmed COVID-19 cases, but changes in destination arrival did not have significant effects. The regions with increasing transfer activities were located in provinces neighboring Hubei in the widthwise and longitudinal directions. These results indicate that transfer activities enhance interpersonal transmission probability and could be a crucial risk factor for increasing epidemic severity after the Wuhan city lockdown. The destinations of railway passengers might not be affected by the Wuhan city lockdown, but their itinerary routes could be changed due to the replacement of an important transfer hub (Wuhan city) in the Chinese railway transportation network. As a result, transfer services in the high-speed rail network could explain why the provinces surrounded by Hubei had a higher number of confirmed COVID-19 cases than other provinces.
Evaluation of Neighborhood Socio-Economic Status, as Measured by the Delphi Method, on Dengue Fever Distribution in Jeddah City, Saudi Arabia
Authors: Alkhaldy Ibrahim , Barnett Pauline
Published: June 2021

Dengue fever, a mosquito-transmitted viral disease, is present in many neighborhoods in Jeddah City, Saudi Arabia. One factor likely to affect its distribution is the socio-economic status of local neighborhoods; however, the absence of socio-economic census data in Saudi Arabia has precluded detailed investigation. This study aims to develop a proxy measure of socio-economic status in Jeddah City in order to assess its relationship with the occurrence of dengue fever. The Delphi method was used to assess the socio-economic status (high, medium or low) of local neighborhoods in Jeddah City. A Geographic Information System (GIS) was applied to understand the distribution of dengue fever according to the socio-economic status of Jeddah City neighborhoods. Low-socio-economic status neighborhoods in south Jeddah City, with poor environmental conditions and high levels of poverty and population density, reported most cases of dengue fever. Nevertheless, dengue continues to increase in high socio-economic status neighborhoods in the northern part of the city, possibly due to ideal breeding conditions caused by the presence of standing water associated with high levels of construction. Moreover, the low-socioeconomic-status neighborhoods had the highest average number of cases, being 3.95 times that of high-status neighborhoods for the period 2006–2009. The Delphi approach can produce a useful and robust measure of socio-economic status for use in the analysis of patterns of dengue fever. Results suggest that there are nuances in the relationship between socio-economic status and dengue that indicate that higher status areas are also at risk. A useful additional tool for researchers in Saudi Arabia would be the development of census data or other systematic measures that allow socio-economic status to be included in spatial analyses of dengue fever and other diseases.
Association between Blood Mercury Levels and Non-Alcoholic Fatty Liver Disease in Non-Obese Populations: The Korean National Environmental Health Survey (KoNEHS) 2012–2014
Authors: Yang Yun-Jung , Yang Eun-Jung , Park Kyongjin , Oh Subin , Kim Taehyen , Hong Yeon-Pyo
Published: June 2021

Mercury is widely distributed in the environment, and a plausible association between mercury exposure and hepatic damage has been reported. Non-alcoholic fatty liver disease (NAFLD), which comprises a spectrum of liver diseases, has recently been recognized in non-obese subjects. However, there have been no studies on the relationship between internal mercury levels and NAFLD in non-obese individuals. Therefore, we investigated the association between blood mercury levels and NAFLD in non-obese subjects. Cross-sectional data (n = 5919) were obtained from the Korean National Environmental Health Survey (2012–2014). NAFLD was defined using the hepatic steatosis index (HSI). Blood mercury levels were log-transformed and divided into quartiles based on a weighted sample distribution. The association between blood mercury levels and NAFLD was analyzed using a multivariate logistic analysis after body mass index stratification. The geometric mean of blood mercury in the overweight group was significantly higher than that of the non-obese group (p < 0.001). The weighted frequencies of patients with NAFLD based on the HSI were 3.0–7.2% for the non-obese subjects and 52.3–63.2% for the overweight subjects. In the multivariate analysis, blood mercury levels were positively associated with NAFLD for both the overweight and non-obese groups (all p for trend < 0.001). Increased blood mercury levels are closely associated with NAFLD. In particular, mercury could be a risk factor for NAFLD in the non-obese population.
Self-Rated Oral Health and Associated Factors among an Adult Population in Rural India—An Epidemiological Study
Authors: Bhat Meghashyam , Bhat Sreevidya , Roberts-Thomson Kaye Frances , Do Loc Giang
Published: June 2021

Background: To determine the perception of oral health status and its associated factors among adults living in rural areas in Karnataka state, India. Methods: A cross-sectional study was conducted among adults in the age group of 35–54 years old residing in villages in a southern state in India. The main outcome measure was poor self-rated oral health (SROH) among adults in rural India. Results: About 873 adults participated in the study. The prevalence of poor SROH was 15.2%. Adults of age 40–44 years, females, those in lower socioeconomic conditions, and those with high caries experience (DMFT ≥ 4) and periodontal disease were associated with poor SROH. Those who had visited a dentist in the previous one year were 1.9 times more likely to report poor oral health. Conclusions: Nearly 15% of rural people reported poor oral health. Socioeconomic conditions, sex, age, smoking, and dental visiting were associated with poor SROH. People’s perception of poor oral health was associated with severe periodontitis and DMFT ≥ 4. A dose–response relationship was observed between experience with dental caries and poor SROH.
The Assessment of Attitudes of Medical Doctors towards Psychiatric Patients—A Cross-Sectional Online Survey in Poland
Authors: Babicki Mateusz , Kotowicz Kamila , Mastalerz-Migas Agnieszka
Published: June 2021

(1) Introduction: Stigmatization is a multi-level process leading to depreciation of particular social groups. It is particularly visible among people suffering from mental illnesses. Patient stigmatization is a serious problem in psychiatric care; thus, a reliable assessment of its level is important in the context of effective medical interventions. The aim of this paper is to assess the level of stigmatization of psychiatric patients among doctors. (2) Methods: An online, quantitative, CAWI (Computer Assisted Web Interview) study was conducted in the form of an anonymous, voluntary survey addressed to doctors working in Poland. The questionnaire questions included a socio-geographic assessment and questions assessing the level of stigmatization. A standardized psychometric tool, the MICA-4 Scale for doctors, was also used. The results obtained were compared with the evaluation of the existing reports on stigmatization among Polish society. (3) Results: 501 doctors of various specialties and at various stages of career participated in the study. Most of the respondents were women (75%). The average score of MICA-4 obtained by the respondents was 40.26 (minimum 17; maximum 67; SD 8.93). The women’s score was lower than the men’s (p = 0.034). (4) Conclusions: Stigmatization of psychiatric patients is a common phenomenon among doctors. The type of performed work and career stage has an impact on the perception of psychiatric patients. Specialists scored highest in the MICA-4 Scale, similarly to physicians of surgical fields. Due to the prevalence of the phenomenon of stigmatization, especially among people who are meant to provide patients with help, there is an urgent need to implement anti-stigma programs.
Childhood Circumstances and Mental Health in Old Age: A Life Course Survey in China
Authors: Zhu Huoyun , Liao Mengting
Published: June 2021

Current evidence and research of the life course approach on the association between life experiences and health in old age are fragmentary. This paper empirically examines the “long arm” effect of the childhood circumstances on mental health in later life using a large longitudinal dataset (CHARLS) conducted in 2014 and 2015. We operationalize the childhood circumstances as family economic conditions, community environment, and peer network to include the meaningful content and understand their interaction. The SEM results indicate that effects of those factors contributing to older people’s mental health are unequal and vary among age groups and genders. Of those, peer network in childhood determines to a large extent the mental health through the whole life course, while economic conditions and community environment are weakly associated with mental health. Furthermore, we find a distinct interaction mechanism linking those variables. The peer network completely mediates the effect of the community environment on the mental health of older adults and has a partial mediating effect on the economic conditions. Those findings suggest that social policies aimed at promoting older people’s mental health in the context of the active ageing and health ageing strategy should go beyond the old age stage and target social conditions early in childhood.
Multi-Substance Use Behaviors: Prevalence and Correlates of Alcohol, Tobacco and Other Drug (ATOD) Use among University Students in Finland
Authors: El Ansari Walid , Salam Abdul
Published: June 2021

Virtually no studies appraised the co-use of alcohol, tobacco, and other drug (ATOD) among Finn undergraduates. We assessed the associations between sociodemographic, health, academic, policy, and lifestyle characteristics (independent variables); and individual, multiple and increasing ATOD use (dependent variables) using regression analyses. Data were collected by online questionnaire at the University of Turku, Finland (1177 students). Roughly 22% of the sample smoked, 21% ever used illicit drug/s, 41% were high frequency drinkers, and 31.4%, 16.3%, and 6.7% reported 1, 2, or 3 ATOD behaviors respectively. Individual ATOD use was significantly positively associated with the use of the other two substances [adjusted odds ratio (Adj OR range 1.893–3.311)]. Multiple ATOD use was negatively associated with being single (p = 0.021) or agreeing with total smoking or alcohol ban policy on campus (p < 0.0001 for each); but positively associated with not living with parents (p = 0.004). Increasing ATOD behaviors were significantly less likely among those agreeing with total smoking or alcohol ban policy on campus (p range 0.024 to <0.0001). Demographics significant to either individual, multiple, or increasing ATOD use included males, being single, not living with their parents during semesters, and to some extent, religiosity. Age, depressive symptoms, perceived stress, self-rated health, health awareness, income sufficiency, and academic variables were not associated with individual, multiple, or increasing ATOD use. Education and prevention efforts need to reinforce abstinence from ATOD, highlight their harmful outcomes, and target risk groups highlighted above. University strategies should be part of the wider country-wide successful ATOD control policies.
Three-Dimensional Measurement and Three-Dimensional Printing of Giant Coastal Rocks
Authors: Gao Zhiyi , Doi Akio , Sakakibara Kenji , Hosokawa Tomonaru , Harata Masahiro
Published: June 2021

In recent years, the use of three-dimensional (3D) measurement and printing technologies has become an effective means of analyzing and reproducing both physical and natural objects, regardless of size. However, in some complex environments, such as coastal environments, it is difficult to obtain the required data by conventional measurement methods. In this paper, we describe our efforts to archive and digitally reproduce a giant coastal rock formation known as Sanouiwa, a famous site off the coast of Miyako City, Iwate Prefecture, Japan. We used two different 3D measurement techniques. The first involved taking pictures using a drone-mounted camera, and the second involved the use of global navigation satellite system data. The point cloud data generated from the high-resolution camera images were integrated using 3D shape reconstruction software, and 3D digital models were created for use in tourism promotion and environmental protection awareness initiatives. Finally, we fabricated the 3D digital models of the rocks with 3D printers for use as museum exhibitions, school curriculum materials, and related applications.
Emojis as Contextual Indicants in Location-Based Social Media Posts
Authors: Hauthal Eva , Dunkel Alexander , Burghardt Dirk
Published: June 2021

The presented study aims to investigate the relationship between the use of emojis in location-based social media and the location of the corresponding post in terms of perceived objects and conducted activities connected to this place. The basis for this is not a purely frequency-based assessment, but a specifically introduced measure called typicality. To evaluate the typicality measure and examine the assumption that emojis are contextual indicants, a dataset of worldwide geotagged posts from Instagram relating to sunset and sunrise events is used, converted to a privacy-aware version based on a Hyperloglog approach. Results suggest that emojis can often provide more nuanced information about user activities and the surrounding environment than is possible with hashtags. Thus, emojis may be suitable for identifying less obvious characteristics and the sense of a place. Emojis are already explored in research, but mainly for sentiment analysis, for semantic studies or as part of emoji prediction. In contrast, this work provides novel insights into the user’s spatial or activity context by applying the typicality measure and therefore considers emojis contextual indicants.
Analyzing Olfactory Neuron Precursors Non-Invasively Isolated through NADH FLIM as a Potential Tool to Study Oxidative Stress in Alzheimer’s Disease
Authors: Gómez-Virgilio Laura , Luarte Alejandro , Ponce Daniela P. , Bruna Bárbara A. , Behrens María I.
Published: June 2021

Among all the proposed pathogenic mechanisms to understand the etiology of Alzheimer’s disease (AD), increased oxidative stress seems to be a robust and early disease feature where many of those hypotheses converge. However, despite the significant lines of evidence accumulated, an effective diagnosis and treatment of AD are not yet available. This limitation might be partially explained by the use of cellular and animal models that recapitulate partial aspects of the disease and do not account for the particular biology of patients. As such, cultures of patient-derived cells of peripheral origin may provide a convenient solution for this problem. Peripheral cells of neuronal lineage such as olfactory neuronal precursors (ONPs) can be easily cultured through non-invasive isolation, reproducing AD-related oxidative stress. Interestingly, the autofluorescence of key metabolic cofactors such as reduced nicotinamide adenine dinucleotide (NADH) can be highly correlated with the oxidative state and antioxidant capacity of cells in a non-destructive and label-free manner. In particular, imaging NADH through fluorescence lifetime imaging microscopy (FLIM) has greatly improved the sensitivity in detecting oxidative shifts with minimal intervention to cell physiology. Here, we discuss the translational potential of analyzing patient-derived ONPs non-invasively isolated through NADH FLIM to reveal AD-related oxidative stress. We believe this approach may potentially accelerate the discovery of effective antioxidant therapies and contribute to early diagnosis and personalized monitoring of this devastating disease.
Autophagy: A Friend or Foe in Allergic Asthma?
Authors: Theofani Efthymia , Xanthou Georgina
Published: June 2021

Autophagy is a major self-degradative process through which cytoplasmic material, including damaged organelles and proteins, are delivered and degraded in the lysosome. Autophagy represents a dynamic recycling system that produces new building blocks and energy, essential for cellular renovation, physiology, and homeostasis. Principal autophagy triggers include starvation, pathogens, and stress. Autophagy plays also a pivotal role in immune response regulation, including immune cell differentiation, antigen presentation and the generation of T effector responses, the development of protective immunity against pathogens, and the coordination of immunometabolic signals. A plethora of studies propose that both impaired and overactive autophagic processes contribute to the pathogenesis of human disorders, including infections, cancer, atherosclerosis, autoimmune and neurodegenerative diseases. Autophagy has been also implicated in the development and progression of allergen-driven airway inflammation and remodeling. Here, we provide an overview of recent studies pertinent to the biology of autophagy and molecular pathways controlling its activation, we discuss autophagy-mediated beneficial and detrimental effects in animal models of allergic diseases and illuminate new advances on the role of autophagy in the pathogenesis of human asthma. We conclude contemplating the potential of targeting autophagy as a novel therapeutic approach for the management of allergic responses and linked asthmatic disease.
Behavioral and Neuronal Effects of Inhaled Bromine Gas: Oxidative Brain Stem Damage
Authors: Shakil Shazia , Masjoan Juncos Juan Xavier , Mariappan Nithya , Zafar Iram , Amudhan Apoorva , Amudhan Archita , Aishah Duha , Siddiqui Simmone , Manzoor Shajer , Santana Cristina M. , Rumbeiha Wilson K. , Salim Samina , Ahmad Aftab , Ahmad Shama
Published: June 2021

The risk of accidental bromine (Br2) exposure to the public has increased due to its enhanced industrial use. Inhaled Br2 damages the lungs and the heart; however, adverse effects on the brain are unknown. In this study, we examined the neurological effects of inhaled Br2 in Sprague Dawley rats. Rats were exposed to Br2 (600 ppm for 45 min) and transferred to room air and cage behavior, and levels of glial fibrillary acidic protein (GFAP) in plasma were examined at various time intervals. Bromine exposure resulted in abnormal cage behavior such as head hitting, biting and aggression, hypervigilance, and hyperactivity. An increase in plasma GFAP and brain 4-hydroxynonenal (4-HNE) content also was observed in the exposed animals. Acute and delayed sympathetic nervous system activation was also evaluated by assessing the expression of catecholamine biosynthesizing enzymes, tryptophan hydroxylase (TrpH1 and TrpH2), and tyrosine hydroxylase (TyrH), along with an assessment of catecholamines and their metabolites. TyrH was found to be increased in a time-dependent manner. TrpH1 and TrpH2 were significantly decreased upon Br2 exposure in the brainstem. The neurotransmitter content evaluation indicated an increase in 5-HT and dopamine at early timepoints after exposure; however, other metabolites were not significantly altered. Taken together, our results predict brain damage and autonomic dysfunction upon Br2 exposure.
Evaluation of Oxford Nanopore MinION RNA-Seq Performance for Human Primary Cells
Authors: Massaiu Ilaria , Songia Paola , Chiesa Mattia , Valerio Vincenza , Moschetta Donato , Alfieri Valentina , Myasoedova Veronika A. , Schmid Michael , Cassetta Luca , Colombo Gualtiero I. , D’Alessandra Yuri , Poggio Paolo
Published: June 2021

Transcript sequencing is a crucial tool for gaining a deep understanding of biological processes in diagnostic and clinical medicine. Given their potential to study novel complex eukaryotic transcriptomes, long-read sequencing technologies are able to overcome some limitations of short-read RNA-Seq approaches. Oxford Nanopore Technologies (ONT) offers the ability to generate long-read sequencing data in real time via portable protein nanopore USB devices. This work aimed to provide the user with the number of reads that should be sequenced, through the ONT MinION platform, to reach the desired accuracy level for a human cell RNA study. We sequenced three cDNA libraries prepared from poly-adenosine RNA of human primary cardiac fibroblasts. Since the runs were comparable, they were combined in a total dataset of 48 million reads. Synthetic datasets with different sizes were generated starting from the total and analyzed in terms of the number of identified genes and their expression levels. As expected, an improved sensitivity was obtained, increasing the sequencing depth, particularly for the non-coding genes. The reliability of expression levels was assayed by (i) comparison with PCR quantifications of selected genes and (ii) by the implementation of a user-friendly multiplexing method in a single run.
From the (Epi)Genome to Metabolism and Vice Versa; Examples from Hematologic Malignancy
Authors: Karagianni Panagiota , Giannouli Stavroula , Voulgarelis Michael
Published: June 2021

Hematologic malignancies comprise a heterogeneous group of neoplasms arising from hematopoietic cells or their precursors and most commonly presenting as leukemias, lymphomas, and myelomas. Genetic analyses have uncovered recurrent mutations which initiate or accumulate in the course of malignant transformation, as they provide selective growth advantage to the cell. These include mutations in genes encoding transcription factors and epigenetic regulators of metabolic genes, as well as genes encoding key metabolic enzymes. The resulting alterations contribute to the extensive metabolic reprogramming characterizing the transformed cell, supporting its increased biosynthetic needs and allowing it to withstand the metabolic stress that arises as a consequence of increased metabolic rates and changes in its microenvironment. Interestingly, this cross-talk is bidirectional, as metabolites also signal back to the nucleus and, via their widespread effects on modulating epigenetic modifications, shape the chromatin landscape and the transcriptional programs of the cell. In this article, we provide an overview of the main metabolic changes and relevant genetic alterations that characterize malignant hematopoiesis and discuss how, in turn, metabolites regulate epigenetic events during this process. The aim is to illustrate the intricate interrelationship between the genome (and epigenome) and metabolism and its relevance to hematologic malignancy.
Proteome Profiling of PMJ2-R and Primary Peritoneal Macrophages
Authors: Rusanov Alexander L. , Kozhin Peter M. , Tikhonova Olga V. , Zgoda Victor G. , Loginov Dmitry S. , Chlastáková Adéla , Selinger Martin , Sterba Jan , Grubhoffer Libor , Luzgina Nataliya G.
Published: June 2021

In vitro models are often used for studying macrophage functions, including the process of phagocytosis. The application of primary macrophages has limitations associated with the individual characteristics of animals, which can lead to insufficient standardization and higher variability of the obtained results. Immortalized cell lines do not have these disadvantages, but their responses to various signals can differ from those of the living organism. In the present study, a comparative proteomic analysis of immortalized PMJ2-R cell line and primary peritoneal macrophages isolated from C57BL/6 mice was performed. A total of 4005 proteins were identified, of which 797 were quantified. Obtained results indicate significant differences in the abundances of many proteins, including essential proteins associated with the process of phagocytosis, such as Elmo1, Gsn, Hspa8, Itgb1, Ncf2, Rac2, Rack1, Sirpa, Sod1, C3, and Msr1. These findings indicate that outcomes of studies utilizing PMJ2-R cells as a model of peritoneal macrophages should be carefully validated. All MS data are deposited in ProteomeXchange with the identifier PXD022133.
Impaired Morphogenesis and Function of Rat Adrenal Zona Glomerulosa by Developmental Low-Dose Exposure to DDT Is Associated with Altered Oct4 Expression
Authors: Yaglova Nataliya V. , Obernikhin Sergey S. , Tsomartova Dibakhan A. , Nazimova Svetlana V. , Yaglov Valentin V. , Tsomartova Elina S. , Chereshneva Elizaveta V. , Ivanova Marina Y. , Lomanovskaya Tatiana A.
Published: June 2021

Dichlorodiphenyltrichloroethane (DDT) is a persistent organic pollutant and one of the most widespread endocrine disrupting chemicals. The impact of low-dose exposure to DDT on the morphogenesis of the adrenal gland is still poorly understood. The development and function of zona glomerulosa in rats has been found to be associated with changes in the expression of the transcription factor Oct4 (Octamer 4), which is the most important player in cell pluripotency. The aim of the study was to investigate the morphogenesis and function of rat adrenal zona glomerulosa in rats exposed to low doses of DDT during prenatal and postnatal development and to determine the possible role of Oct4 in DDT-mediated structural and functional changes. The DDT-exposed rats demonstrated slower development and lower functional activity of the zona glomerulosa during the pubertal period associated with higher expression of Oct4. Further, accelerated growth and restoration of hormone production was associated with, firstly, a decrease in Oct4 expressing cells and secondly, the loss of the inverse relationship between basal aldosterone levels and the number of Oct4 expressing cells. Thus, the transcriptional factor Oct4 exhibited an altered pattern of expression in the DDT-exposed rats during postnatal development. The results of the study uncover a novel putative mechanism by which low doses of DDT disrupt the development of adrenal zona glomerulosa.
Preclinical Development of FA5, a Novel AMP-Activated Protein Kinase (AMPK) Activator as an Innovative Drug for the Management of Bowel Inflammation
Authors: Antonioli Luca , Pellegrini Carolina , Fornai Matteo , Benvenuti Laura , D’Antongiovanni Vanessa , Colucci Rocchina , Bertani Lorenzo , Di Salvo Clelia , Semeghini Giorgia , La Motta Concettina , Giusti Laura , Zallocco Lorenzo , Ronci Maurizio , Quattrini Luca , Angelucci Francesco , Coviello Vito , Oh Won-Keun , Ha Quy Thi Kim , Németh Zoltan H. , Haskó Gyorgy , Blandizzi Corrado
Published: June 2021

Acadesine (ACA), a pharmacological activator of AMP-activated protein kinase (AMPK), showed a promising beneficial effect in a mouse model of colitis, indicating this drug as an alternative tool to manage IBDs. However, ACA displays some pharmacodynamic limitations precluding its therapeutical applications. Our study was aimed at evaluating the in vitro and in vivo effects of FA-5 (a novel direct AMPK activator synthesized in our laboratories) in an experimental model of colitis in rats. A set of experiments evaluated the ability of FA5 to activate AMPK and to compare the efficacy of FA5 with ACA in an experimental model of colitis. The effects of FA-5, ACA, or dexamethasone were tested in rats with 2,4-dinitrobenzenesulfonic acid (DNBS)-induced colitis to assess systemic and tissue inflammatory parameters. In in vitro experiments, FA5 induced phosphorylation, and thus the activation, of AMPK, contextually to the activation of SIRT-1. In vivo, FA5 counteracted the increase in spleen weight, improved the colon length, ameliorated macroscopic damage score, and reduced TNF and MDA tissue levels in DNBS-treated rats. Of note, FA-5 displayed an increased anti-inflammatory efficacy as compared with ACA. The novel AMPK activator FA-5 displays an improved anti-inflammatory efficacy representing a promising pharmacological tool against bowel inflammation.
Diet-Regulating Microbiota and Host Immune System in Liver Disease
Authors: Eom Jung A , Kwon Goo Hyun , Kim Na Yeon , Park Eun Ju , Won Sung Min , Jeong Jin Ju , Raja Ganesan , Gupta Haripriya , Asmelash Gebru Yoseph , Sharma Satyapriya , Choi Ye Rin , Kim Hyeong Seop , Yoon Sang Jun , Hyun Ji Ye , Jeong Min Kyo , Park Hee Jin , Min Byeong Hyun , Choi Mi Ran , Kim Dong Joon , Suk Ki Tae
Published: June 2021

The gut microbiota has been known to modulate the immune responses in chronic liver diseases. Recent evidence suggests that effects of dietary foods on health care and human diseases are related to both the immune reaction and the microbiome. The gut-microbiome and intestinal immune system play a central role in the control of bacterial translocation-induced liver disease. Dysbiosis, small intestinal bacterial overgrowth, translocation, endotoxemia, and the direct effects of metabolites are the main events in the gut-liver axis, and immune responses act on every pathways of chronic liver disease. Microbiome-derived metabolites or bacteria themselves regulate immune cell functions such as recognition or activation of receptors, the control of gene expression by epigenetic change, activation of immune cells, and the integration of cellular metabolism. Here, we reviewed recent reports about the immunologic role of gut microbiotas in liver disease, highlighting the role of diet in chronic liver disease.
Reorganization of Thalamic Inputs to Lesioned Cortex Following Experimental Traumatic Brain Injury
Authors: Ndode-Ekane Xavier Ekolle , Puigferrat Pérez Maria del Mar , Di Sapia Rossella , Lapinlampi Niina , Pitkänen Asla
Published: June 2021

Traumatic brain injury (TBI) disrupts thalamic and cortical integrity. The effect of post-injury reorganization and plasticity in thalamocortical pathways on the functional outcome remains unclear. We evaluated whether TBI causes structural changes in the thalamocortical axonal projection terminals in the primary somatosensory cortex (S1) that lead to hyperexcitability. TBI was induced in adult male Sprague Dawley rats with lateral fluid-percussion injury. A virus carrying the fluorescent-tagged opsin channel rhodopsin 2 transgene was injected into the ventroposterior thalamus. We then traced the thalamocortical pathways and analyzed the reorganization of their axonal terminals in S1. Next, we optogenetically stimulated the thalamocortical relays from the ventral posterior lateral and medial nuclei to assess the post-TBI functionality of the pathway. Immunohistochemical analysis revealed that TBI did not alter the spatial distribution or lamina-specific targeting of projection terminals in S1. TBI reduced the axon terminal density in the motor cortex by 44% and in S1 by 30%. A nematic tensor-based analysis revealed that in control rats, the axon terminals in layer V were orientated perpendicular to the pial surface (60.3°). In TBI rats their orientation was more parallel to the pial surface (5.43°, difference between the groups p < 0.05). Moreover, the level of anisotropy of the axon terminals was high in controls (0.063) compared with TBI rats (0.045, p < 0.05). Optical stimulation of the sensory thalamus increased alpha activity in electroencephalography by 312% in controls (p > 0.05) and 237% (p > 0.05) in TBI rats compared with the baseline. However, only TBI rats showed increased beta activity (33%) with harmonics at 5 Hz. Our findings indicate that TBI induces reorganization of thalamocortical axonal terminals in the perilesional cortex, which alters responses to thalamic stimulation.
Engineered Microvessel for Cell Culture in Simulated Microgravity
Authors: ElGindi Mei , Ibrahim Ibrahim Hamed , Sapudom Jiranuwat , Garcia-Sabate Anna , Teo Jeremy C.M.
Published: June 2021

As the number of manned space flights increase, studies on the effects of microgravity on the human body are becoming more important. Due to the high expense and complexity of sending samples into space, simulated microgravity platforms have become a popular way to study these effects on earth. In addition, simulated microgravity has recently drawn the attention of regenerative medicine by increasing cell differentiation capability. These platforms come with many advantages as well as limitations. A main limitation for usage of these platforms is the lack of high-throughput capability due to the use of large cell culture vessels. Therefore, there is a requirement for microvessels for microgravity platforms that limit waste and increase throughput. In this work, a microvessel for commercial cell culture plates was designed. Four 3D printable (polycarbonate (PC), polylactic acid (PLA) and resin) and castable (polydimethylsiloxane (PDMS)) materials were assessed for biocompatibility with adherent and suspension cell types. PDMS was found to be the most suitable material for microvessel fabrication, long-term cell viability and proliferation. It also allows for efficient gas exchange, has no effect on cell culture media pH and does not induce hypoxic conditions. Overall, the designed microvessel can be used on simulated microgravity platforms as a method for long-term high-throughput biomedical studies.
Transcriptome-Wide Identification and Quantification of Caffeoylquinic Acid Biosynthesis Pathway and Prediction of Its Putative BAHDs Gene Complex in A. spathulifolius
Authors: Claude Sivagami-Jean , Park Sunmi , Park Seon-Joo
Published: June 2021

The phenylpropanoid pathway is a major secondary metabolite pathway that helps plants overcome biotic and abiotic stress and produces various byproducts that promote human health. Its byproduct caffeoylquinic acid is a soluble phenolic compound present in many angiosperms. Hydroxycinnamate-CoA shikimate/quinate transferase is a significant enzyme that plays a role in accumulating CQA biosynthesis. This study analyzed transcriptome-wide identification of the phenylpropanoid to caffeoylquinic acid biosynthesis candidate genes in A. spathulifolius flowers and leaves. Transcriptomic analyses of the flowers and leaves showed a differential expression of the PPP and CQA biosynthesis regulated unigenes. An analysis of PPP-captive unigenes revealed a major duplication in the following genes: PAL, 120 unigenes in leaves and 76 in flowers; C3′H, 169 unigenes in leaves and 140 in flowers; 4CL, 41 unigenes in leaves and 27 in flowers; and C4H, 12 unigenes in leaves and 4 in flowers. The phylogenetic analysis revealed 82 BAHDs superfamily members in leaves and 72 in flowers, among which five unigenes encode for HQT and three for HCT. The three HQT are common to both leaves and flowers, whereas the two HQT were specialized for leaves. The pattern of HQT synthesis was upregulated in flowers, whereas HCT was expressed strongly in the leaves of A. spathulifolius. Overall, 4CL, C4H, and HQT are expressed strongly in flowers and CAA and HCT show more expression in leaves. As a result, the quantification of HQT and HCT indicates that CQA biosynthesis is more abundant in the flowers and synthesis of caffeic acid in the leaves of A. spathulifolius.
Integrin-Functionalised Giant Unilamellar Vesicles via Gel-Assisted Formation: Good Practices and Pitfalls
Authors: Souissi Mariem , Pernier Julien , Rossier Olivier , Giannone Gregory , Le Clainche Christophe , Helfer Emmanuèle , Sengupta Kheya
Published: June 2021

Giant unilamellar vesicles (GUV) are powerful tools to explore physics and biochemistry of the cell membrane in controlled conditions. For example, GUVs were extensively used to probe cell adhesion, but often using non-physiological linkers, due to the difficulty of incorporating transmembrane adhesion proteins into model membranes. Here we describe a new protocol for making GUVs incorporating the transmembrane protein integrin using gel-assisted swelling. We report an optimised protocol, enumerating the pitfalls encountered and precautions to be taken to maintain the robustness of the protocol. We characterise intermediate steps of small proteoliposome formation and the final formed GUVs. We show that the integrin molecules are successfully incorporated and are functional.