Miracle-dz/UniFAR-FTUs huggingface dataset:
miR-202 Diminishes TGFβ Receptors and Attenuates TGFβ1-Induced EMT in Pancreatic Cancer

Previous studies in our laboratory identified that 3-deazaneplanocin A (DZNep), a carbocyclic adenosine analog and histone methyl transferase inhibitor, suppresses TGFβ-induced epithelial-to-mesenchymal (EMT) characteristics. In addition, DZNep epigenetically reprograms miRNAs to regulate endogenous TGFβ1 levels via miR-663/4787-mediated RNA interference (Mol Cancer Res. 2016 Sep 13. pii: molcanres.0083.2016) (1). Although DZNep also attenuates exogenous TGFβ-induced EMT response, the mechanism of this inhibition was unclear. Here, DZNep induced miR-202-5p to target both TGFβ receptors, TGFBR1 and TGFBR2, for RNA interference and thereby contributes to the suppression of exogenous TGFβ-induced EMT in pancreatic cancer cells. Lentiviral overexpression of miR-202 significantly reduced the protein levels of both TGFβ receptors and suppressed TGFβ signaling and EMT phenotypic characteristics of cultured parenchymal pancreatic cancer cells. Consistently, transfection of anti-miRNAs against miR-202-5p resulted in increased TGFBR1 and TGFBR2 protein expressions and induced EMT characteristics in these cells. In stellate pancreatic cells, miR-202 overexpression slowed growth as well as reduced stromal extracellular membrane matrix protein expression. In orthotopic pancreatic cancer mouse models, both immunodeficient and immunocompetent, miR-202 reduced tumor burden and metastasis. Together, these findings demonstrate an alternative mechanism of DZNep in suppressing TGFβ signaling at the receptor level and uncover the EMT-suppressing role of miR-202 in pancreatic cancer. Implications: These findings support the possibility of combining small molecule–based (e.g., DZNep analogs) or large molecule–based (e.g., miRNAs) epigenetic modifiers with conventional nucleoside analogs (e.g., gemcitabine, capecitabine) to improve the antimetastatic potential of current pancreatic cancer therapy. Mol Cancer Res; 15(8); 1029–39. ©2017 AACR.
In Vitro Differentiation of Mature Myofibers for Live Imaging

Skeletal muscles are composed of myofibers, the biggest cells in the mammalian body and one of the few syncytia. How the complex and evolutionarily conserved structures that compose it are assembled remains under investigation. Their size and physiological features often constrain manipulation and imaging applications. The culture of immortalized cell lines is widely used, but it can only replicate the early steps of differentiation. Here, we describe a protocol that enables easy genetic manipulation of myofibers originating from primary mouse myoblasts. After one week of differentiation, the myofibers display contractility, aligned sarcomeres and triads, as well as peripheral nuclei. The entire differentiation process can be followed by live imaging or immunofluorescence. This system combines the advantages of the existing ex vivo and in vitro protocols. The possibility of easy and efficient transfection as well as the ease of access to all differentiation stages broadens the potential applications. Myofibers can subsequently be used not only to address relevant developmental and cell biology questions, but also to reproduce muscle disease phenotypes for clinical applications.
Relative evolutionary rate inference in HyPhy with LEISR

We introduce LEISR (Likehood Estimation of Individual Site Rates, pronounced “laser”), a tool to infer relative evolutionary rates from protein and nucleotide data, implemented in HyPhy. LEISR is based on the popular Rate4Site (Pupko et al., 2002) approach for inferring relative site-wise evolutionary rates, primarily from protein data. We extend the original method for more general use in several key ways: i) We increase the support for nucleotide data with additional models, ii) We allow for datasets of arbitrary size, iii) We support analysis of site-partitioned datasets to correct for the presence of recombination breakpoints, and iv) We implemented LEISR as MPI-enabled to support rapid, high-throughput analysis. LEISR is available in HyPhy starting with version 2.3. 8.
CHARACTERIZATION OF THE MEDIUM-DENSITY FIBERBOARD OBTAINED THROUGH ACID DIGESTION TO PRODUCE BIO-OIL AND CARBON BLACK

Solid wastes from furniture industries require proper disposal and may have potential to be used in other production chains. The aim of the current study is to assess the use of medium density fiberboard (MDF) to produce bio-oil and carbon black with low emission of toxic elements. A full factorial design was used to assess 27 bio-oil preparation procedures based on the acid digestion of MDF shavings. The influence of three concentrated acid types (HNO 3 , H 2 SO 4 and HCl) at three different temperatures (25, 75 and 150 ° C) and digestion times (30, 60 and 90min) was assessed. The contents of Al, Ba, Cd, Cr, Cu, Ni and Pb were determined through ICP OES. The Al and Ba contents oscillated between 442.2 ± 235.9 mg kg -1 and 17.9 ± 8.6 mg kg -1 , respectively. The Cd, Cr, Ni and Pb contents were below the detection limit set by the technique. The tests showed that the studied material has the potential to be used as bio-oil and carbon black with low emission of metallic elements; Thus, it was considered a potential alternative source of biomass-generated energy and, in parallel, it provides the furniture sector with an additional waste management option
Ethnic inequalities in periodontal disease among British adults.

AIM To explore ethnic inequalities in periodontal disease among British adults, and the role of socioeconomic position (SEP) in those inequalities. METHODS We analysed data on 1925 adults aged 16-65 years, from the East London Oral Health Inequality (ELOHI) Study, which included a random sample of adults living in an ethnically diverse and socially deprived area. Participants completed a questionnaire and were clinically examined for the number of teeth with periodontal pocket depth (PPD)≥4 mm and loss of attachment (LOA)≥4 mm. Ethnic inequalities in periodontal measures were assessed in negative binomial regression models before and after adjustment for demographic (gender and age groups) and SEP indicators (education and socioeconomic classification). RESULTS Compared to White British, Pakistani, Indian, Bangladeshi and Asian Others had more teeth with PPD≥4 mm whereas White East European, Black African and Bangladeshi had more teeth with LOA≥4 mm, after adjustments for demographic and SEP measures. The association of ethnicity with periodontal disease was moderated by education, but not by socioeconomic classification. Stratified analysis showed that ethnic disparities in the two periodontal measures were limited to more educated groups. CONCLUSION This study showed considerable ethnic disparities in periodontal disease between and within the major ethnic categories.
When can two unlabeled networks be aligned under partial overlap?

Network alignment refers to the problem of matching the vertex sets of two unlabeled graphs, which can be viewed as a generalization of the classic graph isomorphism problem. Network alignment has applications in several fields, including social network analysis, privacy, pattern recognition, computer vision, and computational biology. A number of heuristic algorithms have been proposed in these fields. Recent progress in the analysis of network alignment over stochastic models sheds light on the interplay between network parameters and matchability. In this paper, we consider the alignment problem when the two networks overlap only partially, i.e., there exist vertices in one network that have no counterpart in the other. We define a random bigraph model that generates two correlated graphs G1,2; it is parameterized by the expected node overlap t2 and by the expected edge overlap s2. We define a cost function for structural mismatch under a particular alignment, and we identify a threshold for perfect matchability: if the average node degrees of G1,2 grow as ω(s-2t-1 log(n)), then minimization of the proposed cost function results in an alignment which (i) is over exactly the set of shared nodes between G1 and G2, and (ii) agrees with the true matching between these shared nodes. Our result shows that network alignment is fundamentally robust to partial edge and node overlaps.
Assessment of depression in epilepsy: the utility of common and disease-specific self-report depression measures

Abstract Objectives: Depression is common in epilepsy, with rates ranging from 20 to 55% in most samples and reports as high as 70% in patients with intractable epilepsy. However, some contend that depression may be over- and/or under-reported and treated in this population. This may be due to the use of common self-report depression measures that fail to take into account the overlap of disease and depressive symptoms and also the host of side effects associated with antiepileptic medication, which may also be construed as depression. Methods: The present study examined the utility of common self-report depression measures and those designed specifically for the medically ill, including a proposed new measure, to determine which may be more appropriate for use among people with epilepsy. Results: We found that common self-report depression measures are useful for screening depression in epilepsy, particularly with a raised cutoff for one, with sensitivities ranging from . 91 to . 96. A measure designed for the medically ill obtained the greatest specificity of . 91, suggesting its use as a diagnostic tool with a slightly raised cutoff. The positive likelihood ratio of this latter measure was 8.76 with an overall classification accuracy of 88%. Conclusions: Assessment of depression in epilepsy can be improved when utilizing self-report measures that better differentiate disease symptoms from neurovegetative symptoms of depression (e.g. fatigue, sleep disturbance). This was demonstrated in the present study. Clinical implications are discussed.
The Myosin5‐mediated actomyosin motility system is required for Verticillium pathogenesis of cotton

The vascular wilt fungus Verticillium dahliae is one of the most destructive pathogens of cotton (Gossypium hirsutum) and many other economically important dicot plants. Fungal pathogens require Myosin-mediated actomyosin motility system for colonization of their host plants; however, the mechanisms underlying this process have not been fully characterized for V. dahliae. Here, in a knock-out experiment, we characterized the role of VdMyo5, a member of the Myosin V family, before and during infection of cotton and Arabidopsis thaliana. The VdMyo5 deletion mutant (ΔVdmyo5) fungi showed obvious defects in the development of conidia and the polarized elongation of vegetative hyphae, but no inhibition of host root penetration. Overall, the ΔVdmyo5 fungi exhibited dramatically reduced virulence in cotton and Arabidopsis, with almost no colonization in sections of host vascular tissue. We found labelled Myosin5-GFP to be specifically enriched at the hyphal tip, co-localized with FM4-64 labelled Spitzenkörper, which is the vesicle supply centre in filamentous fungi. Comparative secretome analysis revealed that proteins associated with cell wall modification and degradation of reactive oxygen species were significantly altered in mutant strains. Our results indicate that Myosin5 is required for vegetative growth and full virulence, possibly by regulating vesicle transport. The findings provide important insight into the cellular mechanisms of Verticillium pathogenesis.
Establishment of a Disease-Specific Graded Prognostic Assessment for Hepatocellular Carcinoma Patients with Spinal Metastasis

Background/Aims Hepatocellular carcinoma (HCC) patients with spinal metastasis (SM) show heterogeneous lengths of survival. In this study, we develop and propose a graded prognostic assessment for HCC patients with SM (HCC-SM GPA). Methods We previously reported the outcomes of 192 HCC patients with SM who received radiotherapy from April 1992 to February 2012. Prognostic factors that significantly affected survival in that study were used to establish the HCC-SM GPA. Validation was performed using an independent cohort of 63 patients recruited from September 2011 to March 2016. Results We developed the HCC-SM GPA using the following factors: Eastern Cooperative Oncology Group performance status (0–2, 0 point; 3–4, 1 point), controlled primary HCC (yes, 0 point; no, 2 points), and extrahepatic metastases other than bone (no, 0 point; yes, 1 point). Patients were stratified into low (GPA=0), intermediate (GPA=1 to 2), and high risk (GPA=3 to 4). When applied to the validation cohort, the HCC-SM GPA determined median survival durations of 13.6, 4.8, and 2.6 months and 1-year overall survival rates of 58.3%, 17.8%, and 7.3% for the low-, intermediate-, and high-risk patient groups, respectively (p<0.001). Conclusions Our newly proposed HCC-SM GPA successfully predicted survival outcomes.
Sleep Problems as Consequence, Contributor, and Comorbidity: Introduction to the Special Issue on Sleep, Published in Coordination With Special Issues in Clinical Practice in Pediatric Psychology and Journal of Developmental and Behavioral Pediatrics.

Despite long-standing public and scientific interest in the phenomenon of sleep, the current decade has shown tremendous growth in our understanding of the sleep of children who have medical or developmental conditions. To accommodate, promote, and guide that growth, Journal of Pediatric Psychology, Clinical Practice in Pediatric Psychology, and Journal of Developmental and Behavioral Pediatrics have published coordinated special issues, encompassing >30 relevant articles. This article introduces the special issue in Journal of Pediatric Psychology, highlighting papers that illustrate how sleep problems are not only commonly comorbid with childhood medical and developmental conditions; they are also likely caused by and contribute to these conditions. In doing so, these coordinated special issues guide clinical care and reveal opportunities for future research.
Validation of Sleep-Tracking Technology Compared with Polysomnography in Adolescents.

STUDY OBJECTIVES To evaluate the accuracy in measuring nighttime sleep of a fitness tracker (Jawbone UP) compared to polysomnography (PSG). DESIGN Jawbone UP and PSG data were simultaneously collected from adolescents during an overnight laboratory recording. Agreements between Jawbone UP and PSG sleep outcomes were analyzed using paired t tests and Bland-Altman plots. Multiple regressions were used to investigate which PSG sleep measures predicted Jawbone UP "Sound sleep" and "Light sleep. " SETTING SRI International Human Sleep Laboratory. PARTICIPANTS Sixty-five healthy adolescents (28 females, mean age ± standard deviation [SD]: 15.8 ± 2.5 y). INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Outcomes showed good agreements between Jawbone UP and PSG for total sleep time (mean differences ± SD: -10.0 ± 20.5 min), sleep efficiency (mean differences ± SD: -1.9 ± 4.2 %), and wake after sleep onset (WASO) (mean differences ± SD: 10.6 ± 14.7 min). Overall, Jawbone UP overestimated PSG total sleep time and sleep efficiency and underestimated WASO but differences were small and, on average, did not exceed clinically meaningful cutoffs of > 30 min for total sleep time and > 5% for sleep efficiency. Multiple regression models showed that Jawbone UP "Sound sleep" measure was predicted by PSG time in N2 (β = 0.25), time in rapid eye movement (β = 0.29), and arousal index (β = -0.34). Jawbone UP "Light sleep" measure was predicted by PSG time in N2 (β = 0.48), time in N3 (β = 0.49), arousal index (β = 0.38) and awakening index (β = 0.28). Jawbone UP showed a progression from slight overestimation to underestimation of total sleep time and sleep efficiency with advancing age. All relationships were similar in boys and girls. CONCLUSIONS Jawbone UP shows good agreement with polysomnography in measures of total sleep time and wake after sleep onset in adolescent boys and girls. Further validation is needed in other age groups and clinical populations before advocating use of these inexpensive and easy-to-use devices in clinical sleep medicine and research.
A Better Model for Job Redundancy: Decoupling Server Slowdown and Job Size

Recent computer systems research has proposed using redundant requests to reduce latency. The idea is to replicate a request so that it joins the queue at multiple servers. The request is considered complete as soon as any one of its copies completes. Redundancy allows us to overcome server-side variability–the fact that a server might be temporarily slow due to factors such as background load, network interrupts, and garbage collection to reduce response time. In the past few years, queueing theorists have begun to study redundancy, first via approximations, and, more recently, via exact analysis. Unfortunately, for analytical tractability, most existing theoretical analysis has assumed an Independent Runtimes (IR) model, wherein the replicas of a job each experience independent runtimes (service times) at different servers. The IR model is unrealistic and has led to theoretical results that can be at odds with computer systems implementation results. This paper introduces a much more realistic model of redundancy. Our model decouples the inherent job size (<inline-formula> <tex-math notation="LaTeX">$X$ </tex-math></inline-formula>) from the server-side slowdown (<inline-formula> <tex-math notation="LaTeX">$S$ </tex-math></inline-formula>), where we track both <inline-formula> <tex-math notation="LaTeX">$S$ </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">$X$ </tex-math></inline-formula> for each job. Analysis within the <inline-formula> <tex-math notation="LaTeX">$S\&X$ </tex-math></inline-formula> model is, of course, much more difficult. Nevertheless, we design a dispatching policy, Redundant-to-Idle-Queue, which is both analytically tractable within the <inline-formula> <tex-math notation="LaTeX">$S\&X$ </tex-math></inline-formula> model and has provably excellent performance.
[Direct effect of contemporary health education programmes on the knowledge about hand hygiene and technique of hand washing in primary school age children].

INTRODUCTION AND AIM In the case of primary school children in Budapest (n = 165), data on their social status and their previous knowledge on hand hygiene were elicited with the help of pre-knowledge questionnaires issued by students of higher education. The aim of the research was introducing a novel pedagogical procedure - application and optimization of peer education in the development of proper hand hygiene among primary school students. METHOD The knowledge-based survey was conducted after four (n = 85) and eight hours of teaching (n = 36). In addition, the effectiveness of hand washing was tested immediately before (n = 166) and after the four (n = 74) and eight hours of teaching (n = 35) with Semmelweis Scanner after rubbing the hand with fluorescent cream. RESULTS Prior knowledge of hand hygiene significantly increased after the four-hour and eight-hour trainings. In the case of smaller children, the effect of the eight-hour training was more pronounced. Similar results were obtained with regards to the changes in the number of areas missed while rubbing the surface of the hand as a result of the teaching. CONCLUSION Sociological surveys on hand hygiene knowledge and direct physical measurements indicate that training with appropriate pedagogical procedures is effective and contributes to the environmentally conscious hygiene culture of children aged 6 to 10. Orv Hetil. 2018; 159(12): 485-490.
PreSERVE-AMI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intracoronary Administration of Autologous CD34+ Cells in Patients With Left Ventricular Dysfunction Post STEMI.

RATIONALE Despite direct immediate intervention and therapy, ST-segment-elevation myocardial infarction (STEMI) victims remain at risk for infarct expansion, heart failure, reinfarction, repeat revascularization, and death. OBJECTIVE To evaluate the safety and bioactivity of autologous CD34+ cell (CLBS10) intracoronary infusion in patients with left ventricular dysfunction post STEMI. METHODS AND RESULTS Patients who underwent successful stenting for STEMI and had left ventricular dysfunction (ejection fraction≤48%) ≥4 days poststent were eligible for enrollment. Subjects (N=161) underwent mini bone marrow harvest and were randomized 1:1 to receive (1) autologous CD34+ cells (minimum 10 mol/L±20% cells; N=78) or (2) diluent alone (N=83), via intracoronary infusion. The primary safety end point was adverse events, serious adverse events, and major adverse cardiac event. The primary efficacy end point was change in resting myocardial perfusion over 6 months. No differences in myocardial perfusion or adverse events were observed between the control and treatment groups, although increased perfusion was observed within each group from baseline to 6 months (P<0.001). In secondary analyses, when adjusted for time of ischemia, a consistently favorable cell dose-dependent effect was observed in the change in left ventricular ejection fraction and infarct size, and the duration of time subjects was alive and out of hospital (P=0.05). At 1 year, 3.6% (N=3) and 0% deaths were observed in the control and treatment group, respectively. CONCLUSIONS This PreSERVE-AMI (Phase 2, randomized, double-blind, placebo-controlled trial) represents the largest study of cell-based therapy for STEMI completed in the United States and provides evidence supporting safety and potential efficacy in patients with left ventricular dysfunction post STEMI who are at risk for death and major morbidity. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials. gov. Unique identifier: NCT01495364.
Disruption of Rab8a and Rab11a causes formation of basolateral microvilli in neonatal enteropathy

ABSTRACT Misplaced formation of microvilli to basolateral domains and intracellular inclusions in enterocytes are pathognomonic features in congenital enteropathy associated with mutation of the apical plasma membrane receptor syntaxin 3 (STX3). Although the demonstrated binding of Myo5b to the Rab8a and Rab11a small GTPases in vitro implicates cytoskeleton-dependent membrane sorting, the mechanisms underlying the microvillar location defect remain unclear. By selective or combinatory disruption of Rab8a and Rab11a membrane traffic in vivo, we demonstrate that transport of distinct cargo to the apical brush border rely on either individual or both Rab regulators, whereas certain basolateral cargos are redundantly transported by both factors. Enterocyte-specific Rab8a and Rab11a double-knockout mouse neonates showed immediate postnatal lethality and more severe enteropathy than single knockouts, with extensive formation of microvilli along basolateral surfaces. Notably, following an inducible Rab11a deletion from neonatal enterocytes, basolateral microvilli were induced within 3 days. These data identify a potentially important and distinct mechanism for a characteristic microvillus defect exhibited by enterocytes of patients with neonatal enteropathy. Summary: Loss of Rab8a and Rab11a trafficking results in severe microvillus atrophy and extensive formation of basolateral microvilli in mice with neonatal enteropathy.