bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting cardiovascular inflammation: next steps in clinical translation
Authors: Lawler Patrick R , Bhatt Deepak L , Godoy Lucas C , Lüscher Thomas F , Bonow Robert O , Verma Subodh , Ridker Paul M 
Published: February 2020

AbstractSystemic vascular inflammation plays multiple maladaptive roles which contribute to the progression and destabilization of atherosclerotic cardiovascular disease (ASCVD). These roles include: (i) driving atheroprogression in the clinically stable phase of disease; (ii) inciting atheroma destabilization and precipitating acute coronary syndromes (ACS); and (iii) responding to cardiomyocyte necrosis in myocardial infarction (MI). Despite an evolving understanding of these biologic processes, successful clinical translation into effective therapies has proven challenging. Realizing the promise of targeting inflammation in the prevention and treatment of ASCVD will likely require more individualized approaches, as the degree of inflammation differs among cardiovascular patients. A large body of evidence has accumulated supporting the use of high-sensitivity C-reactive protein (hsCRP) as a clinical measure of inflammation. Appreciating the mechanistic diversity of ACS triggers and the kinetics of hsCRP in MI may resolve purported inconsistencies from prior observational studies. Future clinical trial designs incorporating hsCRP may hold promise to enable individualized approaches. The aim of this Clinical Review is to summarize the current understanding of how inflammation contributes to ASCVD progression, destabilization, and adverse clinical outcomes. We offer forward-looking perspective on what next steps may enable successful clinical translation into effective therapeutic approaches—enabling targeting the right patients with the right therapy at the right time—on the road to more individualized ASCVD care.
Acute and chronic musculoskeletal pain situations among the working population and their pain education needs: an exploratory study
Authors: Tang Shuk Kwan , Tse Mimi Mun Yee , Leung Sau Fong , Fotis Theofanis 
Published: February 2020

Abstract

Background
Pain affects a person’s physical and psychological well-being, work performance and productivity. Working population bear their pain and continue to work which may contribute to the worsening of their pain condition. However, their pain situation was not well-examined.

Objective
The aim of the study was to explore the prevalence of acute and chronic pain in the working population in Hong Kong, understand their pain management strategies and determine their preferences with regard to the use of electronic pain management materials.

Methods
This was an exploratory online survey. The participants’ pain history, their preferences in methods of pain management, the source of the pain management education that they had received, sources and preferences in relation to the use of the Internet for pain education, and the participants’ demographic characteristics were collected.

Results
A total of 210 participants joined the study, 67% of whom were experiencing pain. Of the group in pain, 71.6% were in chronic pain that has persisted for 3 months or more. Pain intensities ranged from 2.82 to 3.82 on a 10-point numeric scale. Of the participants, 85.7% reported not receiving adequate pain management education, and 91.4% of those agreed pain services were inadequate. Websites and health care professionals were the sources from which they obtained their pain management education.

Conclusions
The high prevalence of pain in the working population requires special attention. Health care professionals should be proactive and an online pain management programme can be a solution to address the critical problem of pain in the working population.
TET2-mediated Cdkn2A DNA hydroxymethylation in midbrain dopaminergic neuron injury of Parkinson’s disease
Authors: Wu Ting-Ting , Liu Te , Li Xuan , Chen Ya-Jing , Chen Tian-Jiao , Zhu Xiao-Ying , Chen Jiu-Lin , Li Qing , Liu Ye , Feng Ya , Wu Yun-Cheng 
Published: February 2020

Abstract
It has been reported that abnormal epigenetic modification is associated with the occurrence of Parkinson’s disease (PD). Here, we found that a ten-eleven translocation 2 (TET2), a staff of the DNA hydroxylases family, was increased in dopaminergic neurons in vitro and in vivo. Genome-wide mapping of DNA 5-hydroxymethylcytosine (5-hmC)-sequencing has revealed an aberrant epigenome 5-hmC landscape in 1-methyl-4-phenylpyridinium iodide (MPP+)-induced SH-SY5Y cells. The TET family of DNA hydroxylases could reverse DNA methylation by oxidization of 5-methylcytosine (5-mC) to 5-hmC. However, the relationship between modification of DNA hydroxymethylation and the pathogenesis of PD is not clear. According to the results of 5-hmC-sequencing studies, 5-hmC was associated with gene-rich regions in the genomes related to cell cycle, especially gene-cyclin-dependent kinase inhibitor 2A (Cdkn2A). Downregulation of TET2 expression could significantly rescue MPP+-stimulated SH-SY5Y cell damage and cell cycle arrest. Meanwhile, knockdown of Tet2 expression in the substantia nigra pars compacta of MPTP-induced PD mice resulted in attenuated MPTP-induced motor deficits and dopaminergic neuronal injury via p16 suppression. In this study, we demonstrated a critical function of TET2 in PD development via the CDKN2A activity-dependent epigenetic pathway, suggesting a potential new strategy for epigenetic therapy.
Extra-anatomical bypass to treat aortic endograft infection after thoracic endovascular aortic repair
Authors: Tang Yangfeng , Han Lin , Fan Xinli , Zhang Boyao , Zhang Jiajun , Xue Qin , Xu Zhiyun 
Published: February 2020

Abstract
This study aimed to report the case of 7 consecutive patients who underwent surgical treatment for aortic endograft infection after thoracic endovascular aortic repair (TEVAR). The management included the reconstruction of aorta using extra-anatomic prosthetic graft bypass (between the ascending aorta and the abdominal aorta), removal of the infected endograft with debridement of the infected tissue and sac drainage, followed by prolonged antibiotic therapy. This brief communication highlights that the reconstruction of aorta using extra-anatomic prosthetic graft bypass during surgical treatment for aortic endograft infection after TEVAR was reliable and effective.
Negative controls to detect uncontrolled confounding in observational studies of mammographic screening comparing participants and non-participants
Authors: Lousdal Mette Lise , Lash Timothy L , Flanders W Dana , Brookhart M Alan , Kristiansen Ivar Sønbø , Kalager Mette , Støvring Henrik 
Published: February 2020

Abstract

Background
When comparing mammography-screening participants and non-participants, estimates of reduction in breast-cancer mortality may be biased by poor baseline comparability. We used negative controls to detect uncontrolled confounding.

Methods
We designed a closed cohort of Danish women invited to a mammography-screening programme at age 50–52 years in Copenhagen or Funen from 1991 through 2001. We included women with a normal screening result in their first-invitation round. Based on their second-invitation round, women were divided into participants and non-participants and followed until death, emigration or 31 December 2014, whichever came first. We estimated hazard ratios (HRs) of death from breast cancer, causes other than breast cancer and external causes. We added dental-care participation as an exposure to test for an independent association with breast-cancer mortality. We adjusted for civil status, parity, age at first birth, educational attainment, income and hormone use.

Results
Screening participants had a lower hazard of breast-cancer death [HR 0.47, 95% confidence interval (CI) 0.32, 0.69] compared with non-participants. Participants also had a lower hazard of death from other causes (HR 0.43, 95% CI 0.39, 0.46) and external causes (HR 0.35, 95% CI 0.23, 0.54). Reductions persisted after covariate adjustment. Dental-care participants had a lower hazard of breast-cancer death (HR 0.75, 95% CI 0.56, 1.01), irrespective of screening participation.

Conclusions
Negative-control associations indicated residual uncontrolled confounding when comparing breast-cancer mortality among screening participants and non-participants.
A multicentre outbreak of ST45 MRSA containing deletions in the spa gene in New South Wales, Australia
Authors: Beukers Alicia G , Newton Peter , Hudson Bernard , Ross Kimberly , Gottlieb Thomas , O’Sullivan Matthew , Daley Denise A , Pang Stanley , Coombs Geoffrey W , van Hal Sebastiaan J 
Published: February 2020

Abstract

Background
Early identification of MRSA by diagnostic medical microbiology laboratories enables improved antimicrobial choice and outcomes. The Cepheid Xpert® MRSA/SA BC test rapidly identifies Staphylococcus aureus bloodstream infections through spa gene detection and methicillin resistance via mecA gene detection. Recent emergence of S. aureus with deletions in the spa gene has resulted in false-negative results for this test, leading to misidentification of infections with this organism, particularly MRSA ST45.

Objectives
To investigate the emergence and prevalence of ST45 MRSA in New South Wales (NSW), Australia.

Methods
WGS read data from six NSW hospitals were collected for 131 ST45 MRSA isolates and analysed.

Results
Of the 131 ST45 MRSA investigated, 88.5% (116/131) contained a deletion in the spa gene that appeared to have arisen once in approximately 2010 followed by clonal expansion. Given the successful establishment of this ‘spa-deletion’ MRSA clone, the Cepheid Xpert® MRSA/SA BC test became unreliable for confirming S. aureus bacteraemia in NSW. Subsequently, the algorithm used by this test has been updated and evaluated to take into account the presence of S. aureus with either a spa deletion or SCCmec target variations.

Conclusions
This study highlighted the applied use of WGS for assessing diagnostic assays and informing necessary changes to ensure the viability of the Cepheid Xpert® MRSA/SA BC test in the context of the new ‘spa-deletion’ MRSA clone. It demonstrated how continued surveillance through WGS can reveal evolutionary events that may impact diagnostic assays, allowing corrective modifications to be made in real time.
An urban labor market with frictional housing markets: theory and an application to the Paris urban area
Authors: Chapelle Guillaume , Wasmer Etienne , Bono Pierre-Henri 
Published: February 2020

AbstractWe build a tractable model of frictional labor markets and segmented housing markets to study welfare effects of regulations, including spatial misallocation and deviation from competitive pricing of rents. The model is summarized by a labor demand curve depending on rents and wages, a wage curve reflecting labor market tightness and rents, and finally a rent curve reflecting employment. In this economy, the rent gradient in the flexible rent sector is higher than in a purely competitive housing market. This leads to spatial misallocation due to some employees commuting too much and some non-employed living inefficiently close to jobs. In turn, reducing generalized commuting costs reduces the rent gradient in the flexible rent sector and the cost of spatial misallocation of workers. The reduction in market rents is maximal when labor markets are less frictional and housing markets are more frictional, and welfare gains are larger when both are more efficient.
Conditional Survival, Cause-Specific Mortality, and Risk Factors of Late Mortality After Allogeneic Hematopoietic Cell Transplantation
Authors: Wong F Lennie , Teh Jennifer Berano , Atencio Liezl , Stiller Tracey , Kim Heeyoung , Chanson Dayana , Forman Stephen J , Nakamura Ryotaro , Armenian Saro H 
Published: February 2020

Abstract

Background
Long-term mortality after hematopoietic cell transplantation (HCT) is conventionally calculated from the time of HCT, ignoring temporal changes in survivors’ mortality risks. Conditional survival rates, accounting for time already survived, are relevant for optimal delivery of survivorship care but have not been widely quantified. We estimated conditional survival by elapsed survival time in allogeneic HCT patients and examined cause-specific mortality.

Methods
We calculated conditional survival rates and standardized mortality ratio for overall and cause-specific mortality in 4485 patients who underwent HCT for malignant hematologic diseases at a large transplant center during 1976–2014. Statistical tests were two-sided.

Results
The 5-year survival rate from HCT was 48.6%. After surviving 1, 2, 5, 10, and 15 years, the subsequent 5-year survival rates were 71.2%, 78.7%, 87.4%, 93.5%, and 86.2%, respectively. The standardized mortality ratio was 30.3 (95% confidence interval [CI] = 29.2 to 35.5). Although the standardized mortality ratio declined in longer surviving patients, it was still elevated by 3.6-fold in survivors of 15 years or more (95% CI = 3.0 to 4.1). Primary disease accounted for 50% of deaths in the overall cohort and only 10% in 15-year survivors; the leading causes of nondisease-related mortality were subsequent malignancy (26.1%) and cardiopulmonary diseases (20.2%). We also identified the risk factors for nondisease-related mortality in 1- and 5-year survivors.

Conclusion
Survival probability improves the longer patients survive after HCT. However, HCT recipients surviving 15 years or more remain at elevated mortality risk, largely because of health conditions other than their primary disease. Our study findings help inform preventive and interventional strategies to improve long-term outcomes after allogeneic HCT.
‘We can’t integrate in Europe. We will pay a high price if we go there’: Culture, Time and Migration Aspirations for Syrian Refugees in Istanbul
Authors: Rottmann Susan , Kaya Ayhan 
Published: February 2020

Abstract
In popular media, it is often assumed that Syrian refugees wish to reach Europe by any means necessary but, during field research in 2018, we found that many Syrians hoped to remain in Istanbul, despite their tenuous legal and social situation. The article examines how migrants established cultural intimacy and strong community social networks over time, and became increasingly sceptical about the life they imagined they would have in Europe. Addressing research on migration aspirations, we show that migration decisions are strongly affected by experiences in a transit country. Most research on aspirations stresses economic drivers and rational choices, but here we highlight the importance of emotions, the qualitative feeling of acceptance and safety, temporal effects and the growing feeling of being home over time. Prior research with Turkey’s Syrians has pointed to the significance of culture and social networks for creating a sense of being at home. This research explores these issues in more detail to show how culture, religion and gender are interlinked in migrant imaginings, how social networks evolve and how Europe is imagined.
Molecular and physiological characterization of the monosaccharide transporters gene family in Medicago truncatula
Authors: Komaitis Fotios , Kalliampakou Katerina , Botou Maria , Nikolaidis Marios , Kalloniati Chrysanthi , Skliros Dimitrios , Du Baoguo , Rennenberg Heinz , Amoutzias Grigoris D , Frillingos Stathis , Flemetakis Emmanouil 
Published: February 2020

AbstractMonosaccharide transporters (MSTs) represent key components of the carbon transport and partitioning mechanisms in plants, mediating the cell-to-cell and long-distance distribution of a wide variety of monosaccharides. In this study, we performed a thorough structural, molecular, and physiological characterization of the monosaccharide transporter gene family in the model legume Medicago truncatula. The complete set of MST family members was identified with a novel bioinformatic approach. Prolonged darkness was used as a test condition to identify the relevant transcriptomic and metabolic responses combining MST transcript profiling and metabolomic analysis. Our results suggest that MSTs play a pivotal role in the efficient partitioning and utilization of sugars, and possibly in the mechanisms of carbon remobilization in nodules upon photosynthate-limiting conditions, as nodules are forced to acquire a new role as a source of both C and N.
Magnitude to luminance conversions and visual brightness of the night sky
Authors: Bará Salvador , Aubé Martin , Barentine John , Zamorano Jaime 
Published: February 2020

ABSTRACT
The visual brightness of the night sky is not a single-valued function of its brightness in other photometric bands, because the transformations between photometric systems depend on the spectral power distribution of the skyglow. We analyse the transformation between the night sky brightness in the Johnson–Cousins V band (mV, measured in magnitudes per square arcsecond, mpsas) and its visual luminance (L, in SI units cd m−2) for observers with photopic and scotopic adaptation, in terms of the spectral power distribution of the incident light. We calculate the zero-point luminances for a set of skyglow spectra recorded at different places in the world, including strongly light-polluted locations and sites with nearly pristine natural dark skies. The photopic skyglow luminance corresponding to mV=0.00 mpsas is found to vary in the range 1.11–1.34 × 105 cd m−2 if mV is reported in the absolute (AB) magnitude scale, and in the range 1.18–1.43 × 105 cd m−2 if a Vega scale for mV is used instead. The photopic luminance for mV=22.0 mpsas is correspondingly comprised between 176 and 213 μcd m−2 (AB), or 187 and 227 μcd m−2 (Vega). These constants tend to decrease for increasing correlated colour temperature (CCT). The photopic zero-point luminances are generally higher than the ones expected for blackbody radiation of comparable CCT. The scotopic-to-photopic luminance (S/P) ratio for our spectral data set varies from 0.8 to 2.5. Under scotopic adaptation the dependence of the zero-point luminances with the CCT, and their values relative to blackbody radiation, is reversed with respect to photopic ones.
Trafficking of siRNA precursors by the dsRBD protein Blanks in Drosophila
Authors: Nitschko Volker , Kunzelmann Stefan , Fröhlich Thomas , Arnold Georg J , Förstemann Klaus 
Published: February 2020

Abstract
RNA interference targets aberrant transcripts with cognate small interfering RNAs, which derive from double-stranded RNA precursors. Several functional screens have identified Drosophila blanks/lump (CG10630) as a facilitator of RNAi, yet its molecular function has remained unknown. The protein carries two dsRNA binding domains (dsRBD) and blanks mutant males have a spermatogenesis defect. We demonstrate that blanks selectively boosts RNAi triggered by dsRNA of nuclear origin. Blanks binds dsRNA via its second dsRBD in vitro, shuttles between nucleus and cytoplasm and the abundance of siRNAs arising at many sites of convergent transcription is reduced in blanks mutants. Since features of nascent RNAs - such as introns and transcription beyond the polyA site – contribute to the small RNA pool, we propose that Blanks binds dsRNA formed by cognate nascent RNAs in the nucleus and fosters its export to the cytoplasm for dicing. We refer to the resulting small RNAs as blanks exported siRNAs (bepsiRNAs). While bepsiRNAs were fully dependent on RNA binding to the second dsRBD of blanks in transgenic flies, male fertility was not. This is consistent with a previous report that linked fertility to the first dsRBD of Blanks. The role of blanks in spermatogenesis appears thus unrelated to its role in dsRNA export.
HDAC3 functions as a positive regulator in Notch signal transduction
Authors: Ferrante Francesca , Giaimo Benedetto Daniele , Bartkuhn Marek , Zimmermann Tobias , Close Viola , Mertens Daniel , Nist Andrea , Stiewe Thorsten , Meier-Soelch Johanna , Kracht Michael , Just Steffen , Klöble Patricia , Oswald Franz , Borggrefe Tilman 
Published: February 2020

AbstractAberrant Notch signaling plays a pivotal role in T-cell acute lymphoblastic leukemia (T-ALL) and chronic lymphocytic leukemia (CLL). Amplitude and duration of the Notch response is controlled by ubiquitin-dependent proteasomal degradation of the Notch1 intracellular domain (NICD1), a hallmark of the leukemogenic process. Here, we show that HDAC3 controls NICD1 acetylation levels directly affecting NICD1 protein stability. Either genetic loss-of-function of HDAC3 or nanomolar concentrations of HDAC inhibitor apicidin lead to downregulation of Notch target genes accompanied by a local reduction of histone acetylation. Importantly, an HDAC3-insensitive NICD1 mutant is more stable but biologically less active. Collectively, these data show a new HDAC3- and acetylation-dependent mechanism that may be exploited to treat Notch1-dependent leukemias.
Looping of upstream cis-regulatory elements is required for CFTR expression in human airway epithelial cells
Authors: NandyMazumdar Monali , Yin Shiyi , Paranjapye Alekh , Kerschner Jenny L , Swahn Hannah , Ge Alex , Leir Shih-Hsing , Harris Ann 
Published: February 2020

Abstract
The CFTR gene lies within an invariant topologically associated domain (TAD) demarcated by CTCF and cohesin, but shows cell-type specific control mechanisms utilizing different cis-regulatory elements (CRE) within the TAD. Within the respiratory epithelium, more than one cell type expresses CFTR and the molecular mechanisms controlling its transcription are likely divergent between them. Here, we determine how two extragenic CREs that are prominent in epithelial cells in the lung, regulate expression of the gene. We showed earlier that these CREs, located at −44 and −35 kb upstream of the promoter, have strong cell-type-selective enhancer function. They are also responsive to inflammatory mediators and to oxidative stress, consistent with a key role in CF lung disease. Here, we use CRISPR/Cas9 technology to remove these CREs from the endogenous locus in human bronchial epithelial cells. Loss of either site extinguished CFTR expression and abolished long-range interactions between these sites and the gene promoter, suggesting non-redundant enhancers. The deletions also greatly reduced promoter interactions with the 5′ TAD boundary. We show substantial recruitment of RNAPII to the −35 kb element and identify CEBPβ as a key activator of airway expression of CFTR, likely through occupancy at this CRE and the gene promoter.