Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence and Intra-Family Phylogenetic Divergence of Burkholderiaceae-Related Endobacteria Associated with Species of Mortierella

Endofungal bacteria are widespread within the phylum Mucoromycota, and these include Burkholderiaceae-related endobacteria (BRE). However, the prevalence of BRE in Mortierellomycotinan fungi and their phylogenetic divergence remain unclear. Therefore, we examined the prevalence of BRE in diverse species of Mortierella. We surveyed 238 isolates of Mortierella spp. mainly obtained in Japan that were phylogenetically classified into 59 species. BRE were found in 53 isolates consisting of 22 species of Mortierella. Among them, 20 species of Mortierella were newly reported as the fungal hosts of BRE. BRE in a Glomeribacter-Mycoavidus clade in the family Burkholderiaceae were separated phylogenetically into three groups. These groups consisted of a group containing Mycoavidus cysteinexigens, which is known to be associated with M. elongata, and two other newly distinguishable groups. Our results demonstrated that BRE were harbored by many species of Mortierella and those that associated with isolates of Mortierella spp. were more phylogenetically divergent than previously reported.
Therapeutic trends in pancreatic ductal adenocarcinoma (PDAC)

ABSTRACT Introduction: Prognosis remains dismal for pancreatic ductal adenocarcinoma (PDAC). Genomics and proteomics have depicted heterogeneity in PDAC. Collectively, this information could be useful in improving diagnosis, prognosis, modalities of therapy, treatment responses, deciphering drug resistance and new drug development. Areas covered: We describe major advances in the cellular and molecular subtypes based on next-generation sequencing and their predictive and prognostic value in PDAC patients. We review aberrant genes involving in defined cellular processes in PDAC. Finally, the current state of drug development with novel investigational agents targeting cell fate, cell survival, genomic instability, tumor-stroma, and immune checkpoints are discussed. Expert opinion: Molecular techniques have revealed distinct driver mutations in PDAC. Common genes and cellular processes are dysregulated in the pathogenesis of PDAC. These cellular processes categorized by aberrant pathways include control cell fate, genome maintenance, and cell survival. Dysregulation of the tumor microenvironment promotes an intense fibrosis and immune suppression that play a major role in drug resistance. New information on tumor biology has led to the development of targeted/stromal therapies, immunotherapies or combinations with current chemotherapy in PDAC. New drug development targeting multiple hallmarks of PDAC we hope will positively impact the quality and survival of PDAC patients.
Intellectual, adaptive and behavioural characteristics in four patients with 18p deletion syndrome

BACKGROUND The association of behavioural phenotype assessment with cytogenomic characterisation may provide a better comprehension of genotype-phenotype correlations in syndromes caused by chromosomal abnormalities, such as 18p deletion syndrome. METHOD We report on four Brazilian patients with 18p deletion syndrome characterised by cytogenomic techniques and detailed neuropsychological evaluation. Intellectual, adaptive and behavioural characteristics were assessed through the Wechsler's Scales, the Vineland-II Scale and the Child Behaviour Checklist, respectively. Socio-economic measures including main caretaker educational level and family income as defined by Brazilian criteria for social class classification were also collected to evaluate a possible contribution of environmental factors in neurocognitive variability. RESULTS Two out of four patients showed intellectual disability (IQ < 70). Wechsler's scale results suggest that in our sample, interpretation of social situations based on observation of non-verbal behaviour constitute a cognitive strength while judgement of social rules and language skills associated with word knowledge and verbal fluency may be a cognitive weakness. Concerning adaptive behaviour, motor and socialisation domains showed to better develop than communication and daily living skills on the Vineland-II Scale. Only one patient presented internalising behavioural problems based on the Child Behaviour Checklist. Our results also suggested that socio-economic status may contribute to overall patient development. CONCLUSION Our results suggest that some 18p deletion syndrome patients may present average intellectual performance and that the segment deletion size and some families' socio-economic conditions may influence cognitive development.
Correlates of Residual Limb Pain: From Residual Limb Length and Usage to Metabolites and Activity in Secondary Somatosensory Cortex

Most recent studies attribute residual limb pain to peripheral pathological changes of the stump. However, in this paper, we focus on its associations with the residual limb length, usage, as well as the metabolic and functional alterations of the brain. The secondary somatosensory cortex (S2), one important area involved in pain intensity discrimination, was selected as the region of interest. Twenty-two upper-limb amputees were recruited and divided into two groups, i.e., amputees with residual limb pain (9/22) and without residual limb pain (13/22). The residual limb length, usage, as well as the metabolite concentration, resting-state activity and BOLD responses to the tactile stimulation in the contralateral S2, were compared between the two groups and correlated with the pain intensity. The amputees with residual limb pain showed significantly shorter length and less usage of the residual limb than the amputees without residual limb pain, and the pain intensity was significantly negatively correlated with the residual limb length and usage. In addition, the pain intensity was significantly correlated with the tNAA/tCr ratio, resting-state fALFF in the slow-4 band, and BOLD response to the tactile stimulation in the contralateral S2, although there were no significant group differences. Regression analysis suggested that residual limb pain is associated with shorter residual limb length and less residual limb usage.
Large-scale analysis reveals a novel risk score to predict overall survival in hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) is a major cause of cancer mortality and an increasing incidence worldwide; however, there are very few effective diagnostic approaches and prognostic biomarkers. Materials and methods One hundred forty-nine pairs of HCC samples from Gene Expression Omnibus (GEO) were obtained to screen differentially expressed genes (DEGs) between HCC and normal samples. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene ontology enrichment analyses, and protein–protein interaction network were used. Cox proportional hazards regression analysis was used to identify significant prognostic DEGs, with which a gene expression signature prognostic prediction model was identified in The Cancer Genome Atlas (TCGA) project discovery cohort. The robustness of this panel was assessed in the GSE14520 cohort. We verified details of the gene expression level of the key molecules through TCGA, GEO, and qPCR and used immunohistochemistry for substantiation in HCC tissues. The methylation states of these genes were also explored. Results Ninety-eight genes, consisting of 13 upregulated and 85 downregulated genes, were screened out in three datasets. KEGG and Gene ontology analysis for the DEGs revealed important biological features of each subtype. Protein–protein interaction network analysis was constructed, consisting of 64 nodes and 115 edges. A subset of four genes (SPINK1, TXNRD1, LCAT, and PZP) that formed a prognostic gene expression signature was established from TCGA and validated in GSE14520. Next, the expression details of the four genes were validated with TCGA, GEO, and clinical samples. The expression panels of the four genes were closely related to methylation states. Conclusion This study identified a novel four-gene signature biomarker for predicting the prognosis of HCC. The biomarkers may also reveal molecular mechanisms underlying development of the disease and provide new insights into interventional strategies.
The gap between women’s needs when diagnosed with asymptomatic osteoporosis and what is provided by the healthcare system: A qualitative study

Objectives Women diagnosed with asymptomatic osteoporosis need better support to understand the implications of the condition and how to practice self-management in their daily lives. In contrast, physicians report that asymptomatic osteoporosis is not a serious chronic condition and do not pay much attention to the condition compared to other chronic conditions. Therefore, the aim of this study was to investigate the gap between women’s needs, when diagnosed with asymptomatic osteoporosis, and what is provided by the healthcare system. Methods A secondary analysis of semi-structured interviews with 17 women newly diagnosed with asymptomatic osteoporosis was conducted and combined with semi-structured interviews with six physicians. Giorgi’s descriptive phenomenological method was used in the analysis. Results Two overall themes were identified: different perceptions of asymptomatic osteoporosis and discrepancies in the osteoporosis consultation. Habermas was used as a theoretical approach to discuss the findings. Discussion We discuss that physicians pay too much attention to the objective world and highlight that there is a need for better inclusion of women’s subjective and social worlds, to enable mutual understanding and communicative action in the osteoporosis consultation. This would lead to treatment decisions based on women’s needs and support women in their self-management of osteoporosis.
Structural adaptions of phytoplankton assemblages along two contrasting reservoirs

Differences in limnological and hydrological conditions between storage and run-of-river reservoirs caused variations in phytoplankton assemblages along the two types of reservoirs. Instead of exploring variations in phytoplankton assemblages along one type of reservoir, this study identified similarities and differences in phytoplankton assemblages along two types of reservoirs. Phytoplankton assemblages from Xiaowan (storage reservoir) and Manwan (run-of-river reservoir) reservoirs in the Lancang River, China were used as case study. Taxonomic approach and functional group method were used to compare phytoplankton assemblages at sampling sites located in impounded areas of reservoirs, free-flowing areas directly below reservoirs, and free-flowing intermediate areas between the two contrasting reservoirs. With the reduction of reservoir disturbance, phytoplankton assemblages in free-flowing intermediate areas between reservoirs will recover to rich and diverse. Because of the inoculation and dispersion of phytoplankton from the upstream reservoir, dominant functional groups at the sampling sites located in impounded areas of reservoirs and free-flowing areas directly below reservoirs were mainly represented by groups that prefer long water residence times. The functional group TB (Nitzschia lorenziana) and W2 (Strombomonas ensifera) could be used as useful indicators to determine hydrological conditions due to their strong sensitivity to water residence times. Results of the linear redundancy analysis demonstrated that phytoplankton assemblages were mainly affected by DO and flow. These results should aid river managers in acquiring better insight into the effect of cascade reservoirs on the biomass and structure of phytoplankton in the aquatic ecosystem.
Relationship between unilateral posterior crossbite and mandibular asymmetry during late adolescence.

THE AIM OF THE STUDY Was to evaluate the relationship of mandibular condylar and ramal symmetry with unilateral posterior crossbite during late adolescence. MATERIAL AND METHOD 120 pre-orthodontic patients of the Lithuanian University of Health Sciences Department of Orthodontics were included in the study. The main inclusion criteria of the study group were the following: permanent dentition, age 15 to 18 years, unilateral crossbite. Panoramic radiographs database were analyzed, the following parameters were evaluated: mandibular condylar and ramal height, and asymmetry index according to Habets' technique. Statistical data analysis was performed using SPSS 22.0 statistical software. RESULTS In the study group the mandibular condylar height, ramal height, and ramal plus condylar height on the crossbite side were statistically significantly lower than those on the noncrossbite side. Comparing the asymmetry indices between the study and the control groups, it was found all indices were statistically significantly higher in the group with unilateral posterior crossbite than those in the control group, p<0.001. CONCLUSION Relationship between unilateral posterior crossbite and mandibular asymmetry during late adolescent was found, in subjects with unilateral posterior crossbite statistically significantly reduced mandibular condylar height and mandibular ramal height on the crossbite side was detected, they demonstrated a higher mandibular condylar and mandibular ramal asymmetry index, compared to the control group subjects, p<0.001.
Nomenclature of cutaneous vasculitides – German translation of the dermatologic addendum to the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides

The nomenclature system agreed upon by the Chapel Hill Consensus Conference (CHCC) with respect to the terminology and precise definition of the various types of vasculitis has gained widespread interdisciplinary and international acceptance. As the revised version from 2012 (CHCC 2012) does not address the special features of vasculitis of the skin, it has recently been supplemented with an addendum containing the nomenclature of cutaneous vasculitides (D‐CHCC).
WFSBP guidelines on how to grade treatment evidence for clinical guideline development

Abstract Objective and methods: This paper reviews sources of data typically used in guideline development, available grading systems, their pros and cons, and the methods for evaluating risks of bias in publications, and proposes a revised method for grading evidence and recommendations for use in development of clinical treatment guidelines. Results: The new World Federation of Societies of Biological Psychiatry (WFSBP) grading system allows guideline developers to follow a multi-step approach of defining levels of evidence, applying criteria for grading (define the acceptability) and the grading of recommendations. Conclusions: Further, these updated WFSBP recommendations for rating evidence and treatment recommendations provide a grading system that takes into account potential biases in sources of evidence in arriving at final ratings that are likely more clinically meaningful and pragmatic and thus should be used for the development of future treatment guidelines.
AFF3-DNA methylation interplay in maintaining the mono-allelic expression pattern of XIST in terminally differentiated cells

Abstract X chromosome inactivation and genomic imprinting are two classic epigenetic regulatory processes that cause mono-allelic gene expression. In female mammals, mono-allelic expression of the long non-coding RNA gene X-inactive specific transcript (XIST) is essential for initiation of X chromosome inactivation upon differentiation. We have previously demonstrated that the central factor of super elongation complex-like 3 (SEC-L3), AFF3, is enriched at gamete differentially methylated regions (DMRs) of the imprinted loci and regulates the imprinted gene expression. Here, we found that AFF3 can also bind to the DMR downstream of the XIST promoter. Knockdown of AFF3 leads to de-repression of the inactive allele of XIST in terminally differentiated cells. In addition, the binding of AFF3 to the XIST DMR relies on DNA methylation and also regulates DNA methylation level at DMR region. However, the KAP1-H3K9 methylation machineries, which regulate the imprinted loci, might not play major roles in maintaining the mono-allelic expression pattern of XIST in these cells. Thus, our results suggest that the differential mechanisms involved in the XIST DMR and gDMR regulation, which both require AFF3 and DNA methylation.
Syntaxin-1/TI-VAMP SNAREs interact with Trk receptors and are required for neurotrophin-dependent outgrowth

SNARE proteins are essential components of the machinery that regulates vesicle trafficking and exocytosis. Their role is critical for the membrane-fusion processes that occur during neurotransmitter release. However, research in the last decade has also unraveled the relevance of these proteins in membrane expansion and cytoskeletal rearrangements during developmental processes such as neuronal migration and growth cone extension and attraction. Neurotrophins are neurotrophic factors that are required for many cellular functions throughout the brain, including neurite outgrowth and guidance, synaptic formation, and plasticity. Here we show that neurotrophin Trk receptors form a specific protein complex with the t-SNARE protein Syntaxin 1, both in vivo and in vitro. We also demonstrate that blockade of Syntaxin 1 abolishes neurotrophin-dependent growth of axons in neuronal cultures and decreases exocytotic events at the tip of axonal growth cones. 25-kDa soluble N-ethylmaleimide-sensitive factor attachment protein and Vesicle-associated membrane protein 2 do not participate in the formation of this SNARE complex, while tetanus neurotoxin-insensitive vesicle-associated membrane protein interacts with Trk receptors; knockdown of this (v) SNARE impairs Trk-dependent outgrowth. Taken together, our results support the notion that an atypical SNARE complex comprising Syntaxin 1 and tetanus neurotoxin-insensitive vesicle-associated membrane protein is required for axonal neurotrophin function.
miR-190a-5p participates in the regulation of hypoxia-induced pulmonary hypertension by targeting KLF15 and can serve as a biomarker of diagnosis and prognosis in chronic obstructive pulmonary disease complicated with pulmonary hypertension

Purpose miR-190a-5p expression alters dynamically in response to hypoxia. However, the role of miR-190a-5p expression in hypoxia-induced pulmonary hypertension (PH) remains unclear. We sought to correlate the miR-190a-5p expression levels with the severity, diagnosis, and prognosis of PH in relation to chronic obstructive pulmonary disease (COPD-PH). Additionally, we evaluated the effect of miR-190a-5p through in vitro experiments on human pulmonary endothelial cells (HPECs) that were exposed to hypoxia and in vivo experiments using an animal model of hypoxia-induced PH. Methods Circulating miR-190a-5p levels were measured from 73 patients with PH and 32 healthy controls through quantitative real-time PCR. The levels of miR-190a-5p and the expression of Krüppel-like factor 15 (KLF15) were analyzed in HPECs that were exposed to hypoxia, and the effects of antagomir-190a-5p in mice with chronic hypoxia-induced PH were tested. Target gene analysis was performed by Western blot and luciferase assay. Results The miR-190a-5p level was significantly higher in patients with COPD-PH than in the healthy controls. Higher miR-190a-5p levels were associated with a greater severity of COPD-PH. In vitro experiments on HPECs showed that exposure to hypoxia increased the miR-190a-5p levels significantly. KLF15 was validated as a target of miR-190a-5p. Transfection with miR-190a-5p mimicked inhibition of KLF15 expression in HPECs. In the mouse model of PH, antagomir-190a-5p reduced right ventricular systolic pressure and enhanced the KLF15 expression levels in lung tissue. Conclusion miR-190a-5p regulates hypoxia-induced PH by targeting KLF15. The circulating levels of miR-190a-5p correlate with the severity of COPD-PH, thereby confirming the diagnostic and prognostic value of this parameter in COPD-PH.
Neuroprotective Effects of a Traditional Multi-Herbal Medicine Kyung-Ok-Ko in an Animal Model of Parkinson's Disease: Inhibition of MAPKs and NF-κB Pathways and Activation of Keap1-Nrf2 Pathway

Kyung-Ok-Ko (KOK), a traditional multi-herbal medicine, has been widely used in Oriental medicine as a restorative that can enforce vitality of whole organs and as a medicine that can treat age-related symptoms including lack of vigor and weakened immunity. However, the beneficial effect of KOK on neurological diseases such as Parkinson's diseases (PD) is largely unknown. Thus, the objective of this study was to examine the protective effect of KOK on neurotoxicity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Pre-treatment with KOK at 1 or 2 g/kg/day (p.o.) showed significant mitigating effects on neurological dysfunction (motor and welfare) based on pole, rotarod, and nest building tests. It also showed effects on survival rate. These positive effects of KOK were related to inhibition of loss of tyrosine hydroxylase–positive neurons, reduction of MitoSOX activity, increased apoptotic cells, microglia activation, and upregulation of inflammatory factors [interleukin (IL)-1β, IL-6, cyclooxygenase-2, and inducible nitric oxide], and reduced blood-brain barrier (BBB) disruption in the substantia nigra pars compacta (SNpc) and/or striatum after MPTP intoxication. Interestingly, these effects of KOK against MPTP neurotoxicity were associated with inhibition of phosphorylation of mitogen-activated protein kinases and nuclear factor-kappa B signaling pathways along with up-regulation of nuclear factor erythroid 2-related factor 2 pathways in SNpc and/or striatum. Collectively, our findings suggest that KOK might be able to mitigate neurotoxicity in MPTP-induced mouse model of PD via multi-effects, including anti-neuronal and anti-BBB disruption activities through its anti-inflammatory and anti-oxidative activities. Therefore, KOK might have potential for preventing and/or treating PD.
PrimeLife Policy Language

The sudden popularity of social networks and web 2.0 applications changed radically the Internet landscape and the users’ behavior. Today’s young people are the first generation with the ability to distribute information quickly, cheaply and to large groups of people. The amount of personal and private information published and stored in the servers becomes so huge that the traditional concepts of privacy were radically affected. To appease such concerns, enterprises and service providers publish privacy statements that promise fair information practices. Written in natural language or formalized using languages like P3P [1], EPAL [2], XACML [3] etc. they are only promises but not necessarily enforced by technical measures. These problems are amplified if personal data is used not only by the enterprise that collected the data, but also by secondary users such as partner organizations, or government agencies. These flows of data are complex. Threats to data privacy can come from inside (accidental disclosure, insider curiosity and subornation) as well as from the outside (uncontrolled secondary usage) of each organization. Putting customer information online further increases the risk of exposing private and sensitive information to outsiders. In this paper we propose a new policy language handling access control and data usage at the same time. In the context of the European ICT PrimeLife1 we propose an extension of the eXtensible access control markup language (XACML 3.0) offering one of the most popular standardized policy language. This extension suggests a new obligation handling mechanism taking into account temporal constraints, pre-obligations, conditional obligations, and repeating obligations together with a down-stream usage authorization system defining the access control rules under which personal information collected by an entity can be forwarded to a third party. Moreover, our language is based on the concept of trusted credentials.