Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypoxia and Stem Cells in Normal and Tumor Development

Neuroblastoma is a childhood malignancy of the sympathetic nervous system and accounts for 15% of all cancer-related deaths in children. To understand the biology behind neuroblastoma, clarify timing of cellular events and expression profiles of proteins preceding neuroblastoma initiation, we need more relevant preclinical models.In the first part of this thesis, we established two preclinical in vitro models of neuroblastoma: patient-derived xenograft (PDX) cells derived from an orthotopic PDX model of high-risk neuroblastoma and chick embryo derived trunk crestospheres. Wedemonstrate that PDX cells can be cultured as spheres in stem cell promoting medium with retained patient tumor characteristics and maintained tumorigenic and metastatic capacity. However, addition of serum to the culture media resulted in loss of theirimmature phenotype and induced neuronal differentiation, while adherent culture on laminin maintained cells in an undifferentiated state. Further, we also isolated and optimized culture conditions for chick embryo derived trunk crestospheres,comprised of both neural crest stem and progenitor cells. We demonstrate that these crestospheres are multipotent, display selfrenewal capacity over several weeks in vitro and can be manipulated via lentiviral transduction.In the second part of this thesis, we first demonstrate that immature mesenchymal-type neuroblastoma cells are resistant to retinoic acid (RA), a differentiating agent used as a component for treatment of high-risk neuroblastoma. We further demonstrate that mesenchymal-type neuroblastoma cells had endogenous synthesis of RA, is dependent on RA for their proliferation and migration and clustered closely with normal peripheral glia stem cells called Schwann cell precursors (SCPs). Together these data indicate that the endogenous dependency on RA in mesenchymal-type neuroblastoma cells might play a role in the acquired resistance towards RA treatment in the clinic. We finally demonstrate that hypoxia-inducible factor (HIF)-2α, a transcription factor involved in cellular adaption to low oxygen levels, is highly expressed at oxygenated conditions both in vitro an in vivo in neuroblastoma, particularly in the cytoplasmic fraction. We further show that treatment with the HIF-2α transcriptional inhibitor PT2385 had no effects on HIF-2 downstream targets, in contrast to HIF-2α protein knockdown, suggesting that HIF-2α possesses additional, non-canonical functions in neuroblastoma. (Less)
Patterns of regional endemism among New Zealand invertebrates

ABSTRACT Biodiversity is unevenly distributed worldwide in terms of both species diversity and species endemism. Although centres of endemism are a conservation priority, both patterns and drivers of endemism are poorly understood in New Zealand. Here we explore whether invertebrate species distribution records in New Zealand represent the complete geographic range of species. We use distribution records of 2,322 invertebrate species to survey variation in range size and regional-endemism among 28 New Zealand regions, and explore the correlates of diversity and regional-endemism. Our data suggest patterns of regional-endemism in New Zealand invertebrates are not artefacts of sampling effort and the majority of species are not widespread. We found that endemism-score (which is a measure that corrects for species diversity) correlates positively with the relative size of the region three million years ago. Five variables (and their interactions) contributed to the relative level of invertebrate species endemism within a region (in a generalised linear model). Level of endemism tends to be lower in regions with greater geographic connectivity. This suggests that high levels of regional-endemism are not simply the product of the accumulation of species over time, but depends on the ability of a region to retain local species.
Systematic position and composition of Merodon nigritarsis and M. avidus groups (Diptera, Syrphidae) with a description of four new hoverflies species

Financial support was provided by the Serbian Ministry of Education, Science and Technological Development (project III43002, OI173002) the Provincial Secretariat for Science and Technological Development (“Evaluation of Ecological Networks in AP Vojvodina as support for nature conservation”) and the Scientific and Technological Research Council of Turkey (TUBITAK, project number: 213O243).
FACTORS AFFECTING APPLYING LEVEL OF BIOSECURITY ACTIVITIES IN BROILER FARMS IN MATROUH GOVERNORATE

he present research work aimed to determine the factors affecting applying level of biosecurity activities in broiler farms in Matrouh Governorate. This research depended on two sources of data secondary and primary data, the research employed surveyed data of 65 broiler farms. The research was based on the descriptive and quantitative analyses by using some economic indicators, general trend equations and analyzing the simple regression. This research identified the level of biosecurity activities already applied by respondents, and the respondents and farm characteristics that influence this level of applicable biosecurity activities. This research developed the measurement of applying a level of biosecurity activities and then used these measures as dependent variables in identifying the factors that affect the level of applying biosecurity activities. The dependent variable was an aggregated biosecurity score, which ranked and aggregated respondents applying biosecurity activities of 36 biosecurity subindicators. The analysis indicated that older, more educated respondents with larger families and respondents with non-poultry sources of income were more likely to apply a better level of biosecurity activities. The farm characteristics that may influence applying level of biosecurity activities were farm area, distance to neighbours’ poultry farm, distance to road and the number, average capacity of farms was also important.
Persistent chromatin states, pervasive transcription, and shared cis-regulatory sequences have shaped the C. elegans genome

Despite highly conserved chromatin states and cis-regulatory elements, studies of metazoan genomes reveal that gene organization and the strategies to control mRNA expression can vary widely among animal species. C. elegans gene regulation is often assumed to be similar to that of other model organisms, yet evidence suggests the existence of distinct molecular mechanisms to pattern the developmental transcriptome, including extensive post-transcriptional RNA control pathways, widespread splice leader (SL) trans-splicing of pre-mRNAs, and the organization of genes into operons. Here, we performed ChIP-seq for histone modifications in highly synchronized embryos cohorts representing three major developmental stages, with the goal of better characterizing whether the dynamic changes in embryonic mRNA expression are accompanied by changes to the chromatin state. We were surprised to find that thousands of promoters are persistently marked by active histone modifications, despite a fundamental restructuring of the transcriptome. We employed global run-on sequencing using a long-read nanopore format to map nascent RNA transcription across embryogenesis, finding that the invariant open chromatin regions are persistently transcribed by Pol II at all stages of embryo development, even though the mature mRNA is not produced. By annotating our nascent RNA sequencing reads into directional transcription units, we find extensive evidence of polycistronic RNA transcription genome-wide, suggesting that nearby genes in C. elegans are linked by shared transcriptional regulatory mechanisms. We present data indicating that the sharing of cis-regulatory sequences has constrained C. elegans gene positioning and likely explains the remarkable retention of syntenic gene pairs over long evolutionary timescales.
Comparative genomics of global optrA-carrying Enterococcus faecalis uncovers common genetic features and a chromosomal hotspot for optrA acquisition

Linezolid-resistant Enterococcus faecalis (LREfs) carrying optrA are increasingly reported globally from multiple sources, but we still lack a comprehensive analysis of human and animal optrA-LREfs strains. We investigated the phylogenetic structure, genetic content [antimicrobial resistance (AMR), virulence, prophages, plasmidome] and optrA-containing platforms of 28 publicly available optrA-positive E. faecalis genomes from different hosts in 7 countries. In the genome-level analysis, in house databases with 57 virulence and 391 plasmid replication genes were tested for the first time. Our analysis showed a diversity of clones and adaptive gene sequences related to a wide range of genera, mainly but not exclusive from Firmicutes. The content in AMR and virulence genes was highly identical in contrast to the diversity of phages and plasmids observed. Epidemiologically unrelated clones (ST476-like and ST21-like) obtained from human clinical and animal hosts in different continents over 5 years (2012-2017) were phylogenetically related (3-122 SNPs difference). They also exhibited identical AMR and virulence profiles, highlighting a global spread of optrA-positive strains with relevant adaptive traits in livestock and that they might originate from an animal reservoir. optrA was located on the chromosome within a Tn6674-like element (n=9) or on medium-size plasmids (30-60 kb; n=14) belonging to main plasmid families (RepA_N/Inc18/Rep_3). In most cases, the immediate gene vicinity of optrA was identical in chromosomal (Tn6674) and plasmid (impB-fexA-optrA) backbones. Tn6674 was always inserted in the same ΔradC integration site and embedded in a 32 kb chromosomal platform common to diverse strains from different origins (patients, healthy humans, and animals) in Europe, Africa, and Asia during 2012-2018. This platform is conserved among hundreds of E. faecalis genomes and we here propose a conserved chromosomal hotspot for optrA integration. The finding of optrA in strains sharing identical adaptive features and genetic backgrounds across different hosts and countries suggest the occurrence of common and independent genetic events occurring in distant regions, and might explain the easy de novo generation of optrA-positive strains. It also anticipates a dramatic increase of optrA carriage and spread with a serious impact in the efficacy of linezolid for the treatment of Gram-positive infections.
“Metabolic contest”, a new way to control carbon source preference

Microorganisms must make the right choice for nutrient consumption to adapt to their changing environment. As a consequence, bacteria and yeasts have developed regulatory mechanisms involving nutrient sensing and signaling, allowing to redirect cell metabolism to maximize the consumption of an energy-efficient carbon source. Here, we report a new mechanism, named “metabolic contest”, for regulating the use of carbon sources without nutrient sensing and signaling. In contrast to most microorganisms, trypanosomes show a glycerol-to-glucose preference that depends on the combination of three conditions: (i) the sequestration of both metabolic pathways in the same subcellular compartment, here in the peroxisomal-like organelles named glycosomes; (ii) the competition for the same substrate, here ATP, with the first enzymatic step of the glycerol and glucose metabolic pathways being both ATP-dependent (glycerol kinase and hexokinase, respectively) and (iii) an unbalanced activity between the competing enzymes, here the glycerol kinase activity being ~80-fold higher than the hexokinase activity.
Diagnostic value of circulating tumor DNA as an effective biomarker in cervical cancer: a meta-analysis

The applications of liquid biopsy have attracted much attention in biomedical research in recent years. Circulating cell-free DNA (cfDNA) in the serum may serve as a unique tumor marker in various types of cancer. Circulating tumor DNA (ctDNA) is a type of serum cfDNA found in patients with cancer and contains abundant information regarding tumor characteristics, highlighting its potential diagnostic value in the clinical setting. However, the diagnostic value of cfDNA as a biomarker in cervical cancer remains unclear. Here, we performed a meta-analysis to evaluate the applications of ctDNA as a biomarker in cervical cancer. A systematic literature search was performed using PubMed, Embase, and WANFANG MED ONLINE databases up to March 18, 2019. All literature was analyzed using Meta Disc 1.4 and STATA 14.0 software. Diagnostic measures of accuracy of ctDNA in cervical cancer were pooled and investigated. Fifteen studies comprising 1109 patients with cervical cancer met our inclusion criteria and were subjected to analysis. The pooled sensitivity and specificity were 0.52 (95% confidence interval [CI], 0.33–0.71) and 0.97 (95% CI, 0.91–0.99), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 16.0 (95% CI, 5.5–46.4) and 0.50 (95% CI, 0.33–0.75), respectively. The diagnostic odds ratio was 32 (95% CI, 10–108), and the area under the summary receiver operating characteristic curve was 0.92 (95% CI, 0.90– 0.94). There was no significant publication bias observed. In the included studies, ctDNA showed clear diagnostic value for diagnosing and monitoring cervical cancer. Our meta-analysis suggested that detection of human papilloma virus ctDNA in patients with cervical cancer could be used as a noninvasive early dynamic biomarker of tumors, with high specificity and moderate sensitivity. Further large-scale prospective studies are required to validate the factors that may influence the accuracy of cervical cancer diagnosis and monitoring.
Eye contact in active and passive viewing: Event-related brain potential evidence from a combined eye tracking and EEG study

Eye contact is a salient social cue which is assumed to influence early brain processes involved in face perception. The N170 component in the event-related potential (ERP) has frequently been reported to be larger to faces with an averted rather than direct gaze towards the observer. In most studies, however, this effect has been investigated in comparatively artificial, passive settings where participants were instructed to fixate their gaze while observing occasional gaze changes in stimulus faces. Yet, it is unclear whether similar mechanisms are in place during naturalistic gaze interactions involving the continuous interplay of directed and averted gaze between the communication partners. To fill this gap, we compared passive viewing of gaze change sequences with an active condition where participants’ own gaze continuously interacted with the gaze of a stimulus face; while recording ERPs and monitoring gaze with eye tracking. In addition, we investigated the relevance of emotional facial expressions for gaze processing. For both passive viewing and active interaction, N170 amplitudes were larger when the gaze of stimulus faces was averted rather than directed at the participants. Furthermore, eye contact decreased P300 amplitudes in both conditions. Emotional facial expression influenced N170 amplitudes but did not elicit an early posterior negativity nor did it interact with gaze direction. We conclude that comparable mechanisms of gaze perception are in place in gaze interaction as compared to passive viewing, encouraging the further study of the eye contact effect in naturalistic settings.
Prevalence of Hypercholesterolemia and Its Related Factors in Middle-aged Taiwanese Adults---A Hospital-based Study

Objectives. Hypercholesterolemia-related chronic diseases such as cardiovascular disease, cerebrovascular disease, and hypertension are major public health concerns in Taiwan. The aim of this study was to explore the prevalence of hypercholesterolemia and its related factors in middle-aged Taiwanese adults. Methods. This was a cross-sectional hospital-based study. We analyzed the health status of adults who voluntarily visited the China Medical College Hospital in Taichung for preventive services - examination, and measurement of fasting blood biochemistry. Of the 2745persons, 39% were men and 61% were women (mean age, 50.2 ±6.9 years). In order to determine the significant related factors of hypercholesterolemia, the t test, the chi-square test and logistic regression analysis were performed. Results. The mean level of total serum cholesterol was5.04 ±0.95mmol/L in men and 5.0. ±0.98 mmol/L in women. The prevalence of hypercholesterolemia was 40.3% in men and 39.6% in women. According to our statistical analysis, hypercholesterolemia increased with age (p ＜0.01). Logistic regression analysis showed that the statistically significant related factors of hypercholesterolemia were age (odds ratio (OR) = 1.03, 95% confidence interval (CI) = l.02-1.04, P＜ 0.000, hypertension (OR = 1.22, 95% C1 = 1.02-1.44, P ＜ 0.05), hypertriglyceridemia (OR = 2.33, 95% CI = 1.94-2.81, P＜ 0.001) and hyperuricemia (OR = 1.38, 95% CI = 1.15-1.67, P＜ 0.001). Conclusions. Hypercholesterolemia is a relatively common problem in middle-aged adults. When older individuals present with hypertension, hypertriglyceridemia or hyperuricemia, it is important to determine total serum cholesterol levels.
An EEG investigation of the trial-by-trial updating of complex knowledge structures

Schemas are higher-level knowledge structures that store an abstraction of multiple previous experiences. They allow us to retain a multitude of information, but without the cost of storing every detail. Schemas are believed to be relatively stable, but occasionally have to be updated to remain useful in the face of changing environmental conditions. Once a schema is consolidated, schema updating has been proposed to be the result of a prediction error (PE) based learning mechanism, similar to the updating of less complex knowledge. However, for schema memory this hypothesis has so far been difficult to test since the tools to track small modifications to abstracted memory schemas have not been sensitive enough. Moreover, existing research on electrophysiological correlates of updating have focused on short-term belief updating tasks. Here I am using EEG and continuous memory measures recorded during the encoding of new schema consistent and inconsistent material to test the behavioural and neural correlates of schema updating. Schema updating was assessed in a memory test 24 hours after encountering inconsistent information, demonstrating the long-term effect of such PE-based learning. I observed a stronger relationship between behavioural PE and schema updating measures for inconsistent compared to consistent material, in line with the idea that more updating is required when a schema changes. Moreover, the P3 EEG signal tracked both the PE at the time of learning, as well as the updating of the memory schema one day later in the inconsistent condition. These results demonstrate that schema updating in the face of inconsistent information is indeed driven by PE-based mechanisms, and that similar neural mechanisms underlie the updating of consolidated long-term schemas and short-term belief structures.
Mental health in family caregivers of patients with heart failure

Background & Aim : Family caregivers of patients with heart failure (HF) deal with a wide range of problems related to caregiving that influence their mental health. The aim of this study was to investigate the mental health status of the family caregivers of patients with HF. Methods & Materials : In this descriptive cross-sectional study, 90 family caregivers of patients with HF, who referred Shahid Rajaei Cardiovascular Center, were selected through convenience sampling method. The data were collected using General Health Questionnaire (GHQ-28) for measuring mental health and were also analyzed by SPSS 16, and then processed using descriptive statistics, independent t-test, one-way ANOVA and Pearson correlation test. Results : The mean score of GHQ-28 was 33.06 ± 14.34 (range: 9–72). The majority of caregivers (74.4%) were suspected cases of mental health disorders. Regarding to instrument subscales, the prevalence of caregivers’ problems were 65.6% in somatic symptoms, 82.2% in anxiety/insomnia, 83.3% in social dysfunction, and 25.6% in depression. The total GHQ-28 score of the caregivers gradually decreased with increasing patient’s age as in the minimum age group of the patients (aged 40 years and lower), the highest mean score of GHQ-28 was observed (P < 0.05). Conclusion : A considerable proportion of family caregivers of patients with HF were suspected cases of mental health disorders. A routine assessment of mental health in this group of caregivers should be considered to identify those at risk. Also, clinical team should design and implement effective programs aimed at improving the mental health, especially in caregiver who provide care for younger patients.
Language Use, Proficiency and Attitudes in Hong Kong

This study builds on the detailed empirical research of the three investigators, who have been collaborating on researching the Hong Kong linguistic situation since the early 1980s. This research utilises social survey methodology to investigate which languages are used within the community. In more technical terms, this has involved carrying out ‘sociolinguistic surveys’ (surveys of languages in society) to investigate which languages are learnt, and which are used, by whom to whom, across a range of settings (or ‘domains’) in Hong Kong society. Previously, three such surveys have been conducted, in 1983, 1993, and 2003. The 1983 sociolinguistic survey used faceto-face interviews with a total of 1240 respondents (Bolton and Luke 1999). This was followed, in 1993 and 2003, by two telephone surveys conducted by the Social Sciences Research Centre of The University of Hong Kong, where a total of 886 respondents were interviewed in the 1993 survey, and 1060 in the 2003 (Bacon-Shone and Bolton 1998, 2008). One broad aim of all three surveys was to describe patterns of language acquisition, language use, and attitudes to language policies in Hong Kong. This study carried out a sociolinguistic survey of Hong Kong in 2014 together with detailed reanalysis of the 2011 census data across the 18 districts and 412 constituency areas, which yields useful and applicable results relating to ethnic/linguistic minorities, multilingualism, multiculturalism, and language planning, of direct interest to public policy in Hong Kong. It also calibrates for the first time, using expert assessment, selfreported claims of proficiency in oral English and Putonghua and written English and simplified Chinese.
Evaluation of postoperative pain in endodontically treated teeth

Introduction: The success of endodontic treatment is directly related to the morphology domain and endodontic infection control. Some factors such as procedural errors (instrumentation, obturation apical deviations and perforations) can cause postoperative pain. Objective: This study aimed to evaluate postoperative pain in endodontically treated teeth at Dentistry Post-graduation Clinic of Meridional School (IMED/CEOM), Passo Fundo/Brazil from January 2010 to June 2013. Material and methods: The study was approved by the Institutional Review Board. After collection, data were analyzed regarding the occurrence of postoperative pain. This research is a quantitative cross-sectional study, whose sample comprised 302 medical records of patients undergoing endodontic treatment from a non-probability sampling. The review of follow-up appointment charts was carried out by the researcher. Results: During the research period and analysis of 302 medical records, 30.80% showed postoperative pain. However, 69.20 % did not feel any pain. Conclusion: It can be concluded that the pain was more frequent when associated with vital pulp, and these data are relevant to the dental clinic.