bluuebunny/crossref_metadata_2025_split huggingface dataset:
EPIGENE: genome-wide transcription unit annotation using a multivariate probabilistic model of histone modifications
Authors: Sahu Anshupa , Li Na , Dunkel Ilona , Chung Ho-Ryun 
Published: April 2020

AbstractBackgroundUnderstanding the transcriptome is critical for explaining the functional as well as regulatory roles of genomic regions. Current methods for the identification of transcription units (TUs) use RNA-seq that, however, require large quantities of mRNA rendering the identification of inherently unstable TUs, e.g. miRNA precursors, difficult. This problem can be alleviated by chromatin-based approaches due to a correlation between histone modifications and transcription.ResultsHere, we introduce EPIGENE, a novel chromatin segmentation method for the identification of active TUs using transcription-associated histone modifications. Unlike the existing chromatin segmentation approaches, EPIGENE uses a constrained, semi-supervised multivariate hidden Markov model (HMM) that models the observed combination of histone modifications using a product of independent Bernoulli random variables, to identify active TUs. Our results show that EPIGENE can identify genome-wide TUs in an unbiased manner. EPIGENE-predicted TUs show an enrichment of RNA Polymerase II at the transcription start site and in gene body indicating that they are indeed transcribed. Comprehensive validation using existing annotations revealed that 93% of EPIGENE TUs can be explained by existing gene annotations and 5% of EPIGENE TUs in HepG2 can be explained by microRNA annotations. EPIGENE outperformed the existing RNA-seq-based approaches in TU prediction precision across human cell lines. Finally, we identified 232 novel TUs in K562 and 43 novel cell-specific TUs all of which were supported by RNA Polymerase II ChIP-seq and Nascent RNA-seq data.ConclusionWe demonstrate the applicability of EPIGENE to identify genome-wide active TUs and to provide valuable information about unannotated TUs. EPIGENE is an open-source method and is freely available at:https://github.com/imbbLab/EPIGENE.
Associated factors of poor treatment outcomes in patients with giant cell arteritis: clinical implication of large vessel lesions
Authors:   Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis (JPVAS), Sugihara Takahiko , Hasegawa Hitoshi , Uchida Haruhito A. , Yoshifuji Hajime , Watanabe Yoshiko , Amiya Eisuke , Maejima Yasuhiro , Konishi Masanori , Murakawa Yohko , Ogawa Noriyoshi , Furuta Shunsuke , Katsumata Yasuhiro , Komagata Yoshinori , Naniwa Taio , Okazaki Takahiro , Tanaka Yoshiya , Takeuchi Tsutomu , Nakaoka Yoshikazu , Arimura Yoshihiro , Harigai Masayoshi , Isobe Mitsuaki 
Published: April 2020

Abstract
Background
Relapses frequently occur in giant cell arteritis (GCA), and long-term glucocorticoid therapy is required. The identification of associated factors with poor treatment outcomes is important to decide the treatment algorithm of GCA.

Methods
We enrolled 139 newly diagnosed GCA patients treated with glucocorticoids between 2007 and 2014 in a retrospective, multi-center registry. Patients were diagnosed with temporal artery biopsy, 1990 American College of Rheumatology classification criteria, or large vessel lesions (LVLs) detected by imaging based on the modified classification criteria. Poor treatment outcomes (non-achievement of clinical remission by week 24 or relapse during 52 weeks) were evaluated. Clinical remission was defined as the absence of clinical signs and symptoms in cranial and large vessel areas, polymyalgia rheumatica (PMR), and elevation of C-reactive protein (CRP) levels. A patient was determined to have a relapse if he/she had either one of the signs and symptoms that newly appeared or worsened after achieving clinical remission. Re-elevation of CRP without clinical manifestations was considered as a relapse if other causes such as infection were excluded and the treatment was intensified. Associated factors with poor treatment outcomes were analyzed by using the Cox proportional hazard model.

Results
Cranial lesions, PMR, and LVLs were detected in 77.7%, 41.7%, and 52.5% of the enrolled patients, respectively. Treatment outcomes were evaluated in 119 newly diagnosed patients who were observed for 24 weeks or longer. The mean initial dose of prednisolone was 0.76 mg/kg/day, and 29.4% received any concomitant immunosuppressive drugs at baseline. Overall, 41 (34.5%) of the 119 patients had poor treatment outcomes; 13 did not achieve clinical remission by week 24, and 28 had a relapse after achieving clinical remission. Cumulative rates of the events of poor treatment outcomes in patients with and without LVLs were 47.5% and 17.7%, respectively. A multivariable model showed the presence of LVLs at baseline was significantly associated with poor treatment outcomes (adjusted hazard ratio [HR] 3.54, 95% CI 1.52–8.24, p = 0.003). Cranial lesions and PMR did not increase the risk of poor treatment outcomes.

Conclusion
The initial treatment intensity in the treatment algorithm of GCA could be determined based upon the presence or absence of LVLs detected by imaging at baseline.
Proof-of-concept trial of the combination of lactitol with Bifidobacterium bifidum and Lactobacillus acidophilus for the eradication of intestinal OXA-48-producing Enterobacteriaceae
Authors: Ramos-Ramos Juan Carlos , Lázaro-Perona Fernando , Arribas José Ramón , García-Rodríguez Julio , Mingorance Jesús , Ruiz-Carrascoso Guillermo , Borobia Alberto M. , Paño-Pardo José Ramón , Herruzo Rafael , Arnalich Francisco 
Published: April 2020

Abstract
Background
The major reservoir of carbapenemase-producing Enterobacteriaceae (CPE) is the gastrointestinal tract of colonized patients. Colonization is silent and may last for months, but the risk of infection by CPE in colonized patients is significant.

Methods
Eight long-term intestinal carriers of OXA-48-producing Enterobacteriaceae (OXA-PE) were treated during 3 weeks with daily oral lactitol (Emportal®), Bifidobacterium bifidum and Lactobacillus acidophilus (Infloran®). Weekly stool samples were collected during the treatment period and 6 weeks later. The presence of OXA-PE was investigated by microbiological cultures and qPCR.

Results
At the end of treatment (EoT, secondary endpoint 1), four of the subjects had negative OXA-PE cultures. Three weeks later (secondary endpoint 2), six subjects were negative. Six weeks after the EoT (primary endpoint), three subjects had negative OXA-PE cultures. The relative intestinal load of OXA-PE decreased in all the patients during treatment.

Conclusions
The combination of prebiotics and probiotics was well tolerated. A rapid reduction on the OXA-PE intestinal loads was observed. At the EoT, decolonization was achieved in three patients.
Clinical Trials Registration: NCT02307383. EudraCT Number: 2014-000449-65.
Differential CpG DNA methylation in peripheral naïve CD4+ T-cells in early rheumatoid arthritis patients
Authors: Pitaksalee R. , Burska A. N. , Ajaib S. , Rogers J. , Parmar R. , Mydlova K. , Xie X. , Droop A. , Nijjar J. S. , Chambers P. , Emery P. , Hodgett R. , McInnes I. B. , Ponchel F. 
Published: April 2020

AbstractBackgroundThe genetic risk associated with rheumatoid arthritis (RA) includes genes regulating DNA methylation, one of the hallmarks of epigenetic re-programing, as well as many T-cell genes, with a strong MHC association, pointing to immunogenetic mechanisms as disease triggers leading to chronicity. The aim of our study was to explore DNA methylation in early, drug-naïve RA patients, towards a better understanding of early events in pathogenesis.ResultMonocytes, naïve and memory CD4+T-cells were sorted from 6 healthy controls and 10 RA patients. DNA methylation was assessed using a genome-wide Illumina 450K CpG promoter array. Differential methylation was confirmed using bisulfite sequencing for a specific gene promoter, ELISA for several cytokines and flow cytometry for cell surface markers. Differentially methylated (DM) CpGs were observed in 1047 genes in naïve CD4+T-cells, 913 in memory cells and was minimal in monocytes with only 177 genes. Naive CD4+T-cells were further investigated as presenting differential methylation in the promoter of > 500 genes associated with several disease-relevant pathways, including many cytokines and their receptors. We confirmed hypomethylation of a region of the TNF-alpha gene in early RA and differential expression of 3 cytokines (IL21, IL34 and RANKL). Using a bioinformatics package (DMRcate) and an in-house analysis based on differences in β values, we established lists of DM genes between health and RA. Publicly available gene expression data were interrogated to confirm differential expression of over 70 DM genes. The lists of DM genes were further investigated based on a functional relationship database analysis, which pointed to an IL6/JAK1/STAT3 node, related to TNF-signalling and engagement in Th17 cell differentiation amongst many pathways. Five DM genes for cell surface markers (CD4, IL6R, IL2RA/CD25, CD62L, CXCR4) were investigated towards identifying subpopulations of CD4+T-cells undergoing these modifications and pointed to a subset of naïve T-cells, with high levels of CD4, IL2R, and CXCR4, but reduction and loss of IL6R and CD62L, respectively.ConclusionOur data provided novel conceptual advances in the understanding of early RA pathogenesis, with implications for early treatment and prevention.
Ocular microvascular changes in patients with sepsis: a prospective observational study
Authors: Simkiene Jurate , Pranskuniene Zivile , Vitkauskiene Astra , Pilvinis Vidas , Boerma E. Christiaan , Pranskunas Andrius 
Published: April 2020

Abstract
Background
The aim of the study was to detect differences in the conjunctival microcirculation between septic patients and healthy subjects and to evaluate the course of conjunctival and retinal microvasculature in survivors and non-survivors over a 24-h period of time.

Methods
This single-center prospective observational study was performed in mixed ICU in a tertiary teaching hospital. We included patients with sepsis or septic shock within the first 24 h after ICU admission. Conjunctival imaging, using an IDF video microscope, and retinal imaging, using portable digital fundus camera, as well as systemic hemodynamic measurements, were performed at three time points: at baseline, 6 h and 24 h. Baseline conjunctival microcirculatory parameters were compared with healthy controls.

Results
A total of 48 patients were included in the final assessment and analysis. Median APACHE II and SOFA scores were 16[12–21] and 10[7–12], respectively. Forty-four (92%) patients were in septic shock, 48 (100%) required mechanical ventilation. 19 (40%) patients were discharged alive from the intensive care unit. We found significant reductions in all microcirculatory parameters in the conjunctiva when comparing septic and healthy subjects. In addition, we observed a significant lower microvascular flow index (MFI) of small conjunctival vessels during all three time points in non-survivors compared with survivors. However, retinal arteriolar vessels were not different between survivors and non-survivors.

Conclusions
Conjunctival microvascular blood flow was altered in septic patients. In the 24-h observation period conjunctival small vessels had a significantly higher MFI, but no difference in retinal arteriolar diameter in survivors in comparison with non-survivors.
Trial registration NCT04214743, https://www.clinicaltrials.gov. Date of registration: 31 December 2019 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04214743
Investigation of suitability of marbles to standards with inequality expressions and statistical approach using some physical and mechanical properties
Authors: Ozer Ozge , Yalcin Fusun , Tarinc Orhan Kemal , Yalcin Mustafa Gurhan 
Published: April 2020

AbstractMarble, one of the metamorphic rock formation products, forms by undergoing different physical and chemical processes. The marble samples are tested under laboratory conditions to understand these processes. This study aims to find whether the Akcay region marble (Antalya) is compatible with national and international standards using some physical and mechanical properties. For this purpose, samples were subjected to some laboratory tests (real density, apparent density, total porosity, open porosity, breaking load, compressive strength, flexural strength, rupture energy). A number of statistical findings, linear equations, inequalities, and spatial distribution maps were obtained from the physical and mechanical data found at the end of the laboratory tests. The variables which were found to be statistically significantly correlated according to the results of the correlation analysis were analyzed using regression analysis; then their distributions were explained using linear equations. The spatial distribution maps of the variables reveal the part corresponding to the symbol color ranging between the light green and yellow and covering almost 70% of the area is compliant with both TurkStat and ASTM standards and this is proved using the inequalities.
Assessment of a virtual reality temporal bone surgical simulator: A national face and content validity study
Authors: Compton Evan C. , Agrawal Sumit K. , Ladak Hanif M. , Chan Sonny , Hoy Monica , Nakoneshny Steven C. , Siegel Lauren , Dort Joseph C. , Lui Justin T. 
Published: April 2020

Background Trainees in Otolaryngology–Head and Neck Surgery must gain proficiency in a variety of challenging temporal bone surgical techniques. Traditional teaching has relied on the use of cadavers; however, this method is resource-intensive and does not allow for repeated practice. Virtual reality surgical training is a growing field that is increasingly being adopted in Otolaryngology. CardinalSim is a virtual reality temporal bone surgical simulator that offers a high-quality, inexpensive adjunct to traditional teaching methods. The objective of this study was to establish the face and content validity of CardinalSim through a national study. Methods Otolaryngologists and resident trainees from across Canada were recruited to evaluate CardinalSim. Ethics approval and informed consent was obtained. A face and content validity questionnaire with questions categorized into 13 domains was distributed to participants following simulator use. Descriptive statistics were used to describe questionnaire results, and either Chi-square or Fishers exact tests were used to compare responses between junior residents, senior residents, and practising surgeons. Results Sixty-two participants from thirteen different Otolaryngology–Head and Neck Surgery programs were included in the study (32 practicing surgeons; 30 resident trainees). Face validity was achieved for 5 out of 7 domains, while content validity was achieved for 5 out of 6 domains. Significant differences between groups ( p-value of < 0.05) were found for one face validity domain (realistic ergonomics, p = 0.002) and two content validity domains (teaching drilling technique, p = 0.011 and overall teaching utility, p = 0.006). The assessment scores, global rating scores, and overall attitudes towards CardinalSim, were universally positive. Open-ended questions identified limitations of the simulator. Conclusion CardinalSim met acceptable criteria for face and content validity. This temporal bone virtual reality surgical simulation platform may enhance surgical training and be suitable for patient-specific surgical rehearsal for practicing Otolaryngologists.
Bridging the gap between low-frequency and very-low-frequency earthquakes
Authors: Masuda Koki , Ide Satoshi , Ohta Kazuaki , Matsuzawa Takanori 
Published: April 2020

AbstractSlow earthquakes that are observed in the > 1 Hz frequency band are called tectonic tremor or low-frequency earthquakes (LFEs) and those in the 0.01–0.10 Hz band are called very-low-frequency earthquakes (VLFEs). These two phenomena are separated by large microseismic noise at 0.1–1.0 Hz. However, recent observations of the signal in this microseismic frequency band accompanying LFEs and VLFEs in the shallow part of the Nankai subduction zone suggest that LFEs and VLFEs are parts of the same broadband phenomenon, “broadband slow earthquakes”. Here, we report the observation of slow earthquake signals in the microseismic frequency band in the western Shikoku region of the Nankai subduction zone, Japan, by stacking many seismograms relative to the timing of the high-frequency LFE signals. We relocate LFE events detected by the Japan Meteorological Agency, use these LFE waveforms to construct synthetic templates, perform a matched-filter event detection analysis using these templates, stack the seismograms recorded by broadband high-sensitivity accelerometers relative to the timing of the detections, and compare the amplitude of the stacked waveforms at different frequency bands. The stacked waveforms have a continuous signal in the 0.015625 Hz (64 s) to 8 Hz frequency band, and support the idea that LFEs are just a small part of the broadband slow earthquake spectrum, which extends to the VLFE frequency band. Furthermore, the frequency dependency of the maximum amplitudes in this study is similar to that of slow earthquakes in the Cascadia subduction zone, and this is also explained by a Brownian slow earthquake model. However, the frequency dependency is inconsistent with the omega-square model, which is a model for ordinary earthquakes.
Primary myeloid cell proteomics and transcriptomics: importance of β-tubulin isotypes for osteoclast function
Authors: Guérit David , Marie Pauline , Morel Anne , Maurin Justine , Verollet Christel , Raynaud-Messina Brigitte , Urbach Serge , Blangy Anne 
Published: April 2020

ABSTRACT
Among hematopoietic cells, osteoclasts (OCs) and immature dendritic cells (DCs) are closely related myeloid cells with distinct functions: OCs participate skeleton maintenance while DCs sample the environment for foreign antigens. Such specificities rely on profound modifications of gene and protein expression during OC and DC differentiation. We provide global proteomic and transcriptomic analyses of primary mouse OCs and DCs, based on original stable isotope labeling with amino acids in cell culture (SILAC) and RNAseq data. We established specific signatures for OCs and DCs, including genes and proteins of unknown functions. In particular, we showed that OCs and DCs have the same α- and β-tubulin isotype repertoire but that OCs express much more of the β tubulin isotype Tubb6 (also known as TBB6). In both mouse and human OCs, we demonstrate that elevated expression of Tubb6 in OCs is necessary for correct podosomes organization and thus for the structure of the sealing zone, which sustains the bone resorption apparatus. Hence, lowering Tubb6 expression hinders OC resorption activity. Overall, we highlight here potential new regulators of OC and DC biology, and illustrate the functional importance of the tubulin isotype repertoire in the biology of differentiated cells.
Adoption and uptake of the lateral flow urine LAM test in countries with high tuberculosis and HIV/AIDS burden: current landscape and barriers
Authors: Singhroy Diane N. , MacLean Emily , Kohli Mikashmi , Lessem Erica , Branigan David , England Kathleen , Suleiman Khairunisa , Drain Paul K. , Ruhwald Morten , Schumacher Samuel , Denkinger Claudia M. , Waning Brenda , Van Gemert Wayne , Pai Madhukar 
Published: April 2020

Background: Since 2015, the World Health Organization (WHO) has recommended a commercially available lateral-flow urine LAM test (Alere-LAM) to assist in the diagnosis of tuberculosis (TB) in severely ill people living with HIV (PLHIV). The test can rapidly detect TB in severely ill PLHIV and can identify PLHIV most at-risk of death, leading to mortality reductions. However, its uptake in countries with high burdens of TB and HIV has been slow. To assess the current use landscape and identify barriers to the adoption of Alere-LAM, we conducted a questionnaire-based study in 31 high TB and HIV/AIDS burden countries. Methods: Between November 2018 and December 2019, we collected responses to a semi-structured questionnaire that had been emailed to staff and affiliates of National TB Programs or HIV/AIDS Programs, Ministries of Health, and TB or HIV institutes of 31 high TB/HIV burden countries. Questions concerned country policies, adoption, and current use of Alere-LAM testing, as well as testing algorithms and barriers preventing Alere-LAM uptake. Results: We received questionnaire responses from 24 out of 31 (77%) high TB/HIV burden countries. Of these 24 countries, 11 (46%) had adopted Alere-LAM policies, with only five (21%) countries currently using Alere-LAM testing. Testing algorithms were generally aligned with WHO recommendations. Fifteen countries (63%) said they were planning to implement Alere-LAM testing in the near future. The most commonly cited constraint to adoption and implementation was budget limitations. Additional barriers to Alere-LAM implementation included lack of country-specific data and piloting, administrative hurdles such as regulatory agency approval, lack of coordination between National TB and HIV programs, and small perceived patient population. Conclusion: Responses to our questionnaire demonstrate the persistent gap between country-level policy and real-world use of Alere-LAM, as well as specific barriers that must be addressed to scale-up testing in PLHIV.
Measuring the topological charge of terahertz vortex beams with a focal hyperbolic lens
Authors: Yang Yongqiang , Niu Liting , Yang Zhengang , Liu Jinsong 
Published: April 2020

An efficient method is proposed to measure the topological charge (TC) of terahertz (THz) vortex beams with a focal hyperbolic (FH) lens at 0.1 THz. The FH lens is designed and fabricated by 3D printing. The diffraction fringes acquired in the focal plane of the FH lens can judge the number and sign of the TC. Furthermore, after the horizontal or vertical measurement curve is recorded by rotating the FH lens to a suitable angle, the TC value can then be simply and effectively identified. The TC value of the experiment measurement reaches 5. The experiment results are in excellent accord with the simulation.
Biometric Aesthetics
Authors: Heynen Robert 
Published: April 2020

Abstract
This article examines contemporary biometric science against the backdrop of its development in nineteenth century eugenic and biostatistical practices, most notably the composite photography of Francis Galton. Focusing on automated face recognition, the article argues that contemorary biometric science is inextricable from its aesthetic investments, which in turn shape the ways in which faces and bodies are differentiated in identification systems. Based on a close reading of biometric engineering texts and projects, this aesthetico-scientific approach offers new ways of conceptualizing how biometrics constitutes rather than merely reflects bodies, and encodes racist, misogynist, and other social logics into the conception and design of technologies themselves. These are not biases that can be corrected, as ostensibly progressive biometric projects like IBM’s Diversity in Faces initiative suggest, but rather are inextricable from the biometric desire to render faces and bodies as transparent and machine-readable.
Digiti Sonus and Eyes
Authors: Han Yoon Chung 
Published: April 2020

Abstract
This paper discusses design process and motivations of two interactive biometric data artworks (Digiti Sonus and Eyes). Narratives and artistic explorations using two forms of biometric data, from fingerprints and the iris, are discussed based on insights from various fields such as genetics, visual feature analysis, user interface design and data visualization and sonification. Digiti Sonus and Eyes extracted the unique visual features of each type of biometric data and transformed the data into musical sound with multimodal interactions so that the result was real time experimental sound. Various aspects of the two artworks are compared in this paper.