bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Cardiovascular Risk Factors on Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Performance in Cognitively Healthy Older Adults
Authors: De Vito Alyssa N , Bernstein John P K , Weitzner Daniel , Calamia Matthew , Keller Jeffrey N 
Published: July 2019

Abstract

Objective
The current study investigated the differential impact cardiovascular risk factors (CVRFs) on Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) performance in a large, cognitively healthy, older adult sample across 4 years.

Method
Participants were 486 individuals recruited through a longitudinal aging research study in the southeastern United States. Participants were 69.3% female, an average of 69.96 years old (SD = 6.58), 16.32 years of education (SD = 2.27), and Mini-Mental Status Exam score of 29.12 (SD = 1.16). Participants completed the RBANS at baseline and yearly thereafter, as well as the Uniform Data Set demographic and health questionnaires and the Geriatric Depression Scale.

Results
Multilevel modeling was conducted using standardized RBANS index scores. Overall, across indices, performance generally improved across time consistent with practice effects from repeated testing. Some CVRFs were associated with worse performance over time. For example, individuals with hypertension performed more poorly on immediate memory over time (t = −2.06, p &lt; .05). Other CVRFs (e.g., BMI) were not associated with baseline performance or performance over time. (p &gt; .05).

Conclusions
CVRFs differentially affect RBANS performance over time. These results extend previous cross-sectional findings regarding the impact of different cardiovascular health risks to a large, cognitively healthy, longitudinal sample.
Noise-cancelling repeat finder: uncovering tandem repeats in error-prone long-read sequencing data
Authors: Harris Robert S , Cechova Monika , Makova Kateryna D 
Published: July 2019

AbstractSummaryTandem DNA repeats can be sequenced with long-read technologies, but cannot be accurately deciphered due to the lack of computational tools taking high error rates of these technologies into account. Here we introduce Noise-Cancelling Repeat Finder (NCRF) to uncover putative tandem repeats of specified motifs in noisy long reads produced by Pacific Biosciences and Oxford Nanopore sequencers. Using simulations, we validated the use of NCRF to locate tandem repeats with motifs of various lengths and demonstrated its superior performance as compared to two alternative tools. Using real human whole-genome sequencing data, NCRF identified long arrays of the (AATGG)n repeat involved in heat shock stress response.Availability and implementationNCRF is implemented in C, supported by several python scripts, and is available in bioconda and at https://github.com/makovalab-psu/NoiseCancellingRepeatFinder.Supplementary informationSupplementary data are available at Bioinformatics online.
Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs
Authors: Raimondi Lavinia , De Luca Angela , Gallo Alessia , Costa Viviana , Russelli Giovanna , Cuscino Nicola , Manno Mauro , Raccosta Samuele , Carina Valeria , Bellavia Daniele , Conigliaro Alice , Alessandro Riccardo , Fini Milena , Conaldi Pier Giulio , Giavaresi Gianluca 
Published: July 2019

AbstractBone microenvironment provides growth and survival signals essential for osteosarcoma (OS) initiation and progression. OS cells regulate communications inside tumor microenvironment through different ways and, among all, tumor-derived exosomes support cancer progression and metastasis. To define the contribution of OS-derived exosomes inside the microenvironment, we investigated the effects induced in bone remodeling mechanism and tumor angiogenesis. We demonstrated that exosomes promoted osteoclasts differentiation and bone resorption activity. Furthermore, exosomes potentiated tube formation of endothelial cells and increased angiogenic markers expression. We therefore investigated the micro RNA (miRNA) cargo from exosomes and their parental cells by performing small RNA sequencing through NGS Illumina platform. Hierarchical clustering highlighted a unique molecular profile of exosomal miRNA; bioinformatic analysis by DIANA-mirPath revealed that miRNAs identified take part in various biological processes and carcinogenesis. Among these miRNAs, some were already known for their involvement in the tumor microenvironment establishment, as miR-148a and miR-21-5p. Enforced expression of miR-148a and miR-21-5p in Raw264.7 and hTert immortalized umbilical vein endothelial cells recapitulated the effects induced by exosomes. Overall, our study highlighted the importance of OS exosomes in tumor microenvironment also by a specific packaging of miRNAs.
Unique Features of Subcortical Circuits in a Macaque Model of Congenital Blindness
Authors: Magrou Loïc , Barone Pascal , Markov Nikola T , Scheeren Gwylan , Killackey Herbert P , Giroud Pascale , Berland Michel , Knoblauch Kenneth , Dehay Colette , Kennedy Henry 
Published: July 2019

Abstract
There is an extensive modification of the functional organization of the brain in the congenital blind human, although there is little understanding of the structural underpinnings of these changes. The visual system of macaque has been extensively characterized both anatomically and functionally. We have taken advantage of this to examine the influence of congenital blindness in a macaque model of developmental anophthalmia. Developmental anophthalmia in macaque effectively removes the normal influence of the thalamus on cortical development leading to an induced “hybrid cortex (HC)” combining features of primary visual and extrastriate cortex. Here we show that retrograde tracers injected in early visual areas, including HC, reveal a drastic reduction of cortical projections of the reduced lateral geniculate nucleus. In addition, there is an important expansion of projections from the pulvinar complex to the HC, compared to the controls. These findings show that the functional consequences of congenital blindness need to be considered in terms of both modifications of the interareal cortical network and the ascending visual pathways.
Efficacy of catheter ablation for paroxysmal atrial fibrillation in patients with atrial septal defect: a comparison with transcatheter closure alone
Authors: Nakagawa Koji , Akagi Teiji , Nagase Satoshi , Takaya Yoichi , Kijima Yasufumi , Toh Norihisa , Watanabe Atsuyuki , Nishii Nobuhiro , Nakamura Kazufumi , Morita Hiroshi , Kusano Kengo , Ito Hiroshi 
Published: July 2019

Abstract

Aims
There is no valid treatment strategy for addressing paroxysmal atrial fibrillation (AF) in patients with unclosed atrial septal defect (ASD). We aimed to assess the efficacy of catheter ablation (CA) compared with transcatheter ASD closure alone for treating pre-existing paroxysmal AF in patients with ASD.

Methods and results
Among 908 patients who underwent transcatheter ASD closure, we evaluated 50 consecutive patients (63 ± 12 years) with paroxysmal AF. We compared the AF outcomes of these patients after transcatheter ASD closure between those with and without CA prior to ASD closure. Thirty (60%) patients underwent CA. During the follow-up period after ASD closure (mean: 49 ± 23 months), recurrence of AF was observed in 6/30 (20%) patients with upfront CA and 12/20 (60%) patients with ASD closure alone. Kaplan–Meier analysis showed that the AF-free survival rate was significantly higher for patients with CA than for those with ASD closure alone (79% vs. 37% at 5 years, P = 0.002). Upfront CA and previous heart failure hospitalization were associated with recurrence of AF after ASD closure [hazard ratio (HR) 0.18, 95% confidence interval (CI) 0.06–0.53; P = 0.002 and HR 4.64, 95% CI 1.60–13.49; P = 0.005, respectively].

Conclusion
In ASD patient with paroxysmal AF, transcatheter ASD closure alone demonstrated high AF recurrence rate after ASD closure. On the other hand, upfront CA prior to ASD closure substantially suppressed AF recurrence over the long term. A combination of CA and transcatheter ASD closure may be a feasible treatment strategy for paroxysmal AF in patients with ASD.
Integrated specialized atrial fibrillation clinics reduce all-cause mortality: post hoc analysis of a randomized clinical trial
Authors: Hendriks Jeroen M L , Tieleman Robert G , Vrijhoef Hubertus J M , Wijtvliet Petra , Gallagher Celine , Prins Martin H , Sanders Prashanthan , Crijns Harry J G M 
Published: July 2019

Abstract

Aims
An integrated chronic care programme in terms of a specialized outpatient clinic for patients with atrial fibrillation (AF), has demonstrated improved clinical outcomes. The aim of this study is to assess all-cause mortality in patients in whom AF management was delivered through a specialized outpatient clinic offering an integrated chronic care programme.

Methods and results
Post hoc analysis of a Prospective Randomized Open Blinded Endpoint Clinical trial to assess all-cause mortality in AF patients. The study included 712 patients with newly diagnosed AF, who were referred for AF management to the outpatient service of a University hospital. In the specialized outpatient clinic (AF-Clinic), comprehensive, multidisciplinary, and patient-centred AF care was provided, i.e. nurse-driven, physician supervised AF treatment guided by software based on the latest guidelines. The control group received usual care by a cardiologist in the regular outpatient setting.
After a mean follow-up of 22 months, all-cause mortality amounted 3.7% (13 patients) in the AF-Clinic arm and 8.1% (29 patients) in usual care [hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.23–0.85; P = 0.014]. This included cardiovascular mortality in 4 AF-Clinic patients (1.1%) and 14 patients (3.9%) in usual care (HR 0.28; 95% CI 0.09–0.85; P = 0.025). Further, 9 patients (2.5%) died in the AF-Clinic arm due to a non-cardiovascular reason and 15 patients (4.2%) in the usual care arm (HR 0.59; 95% CI 0.26–1.34; P = 0.206).

Conclusion
An integrated specialized AF-Clinic reduces all-cause mortality compared with usual care. These findings provide compelling evidence that an integrated approach should be widely implemented in AF management.
A reduced stochastic model of core surface dynamics based on geodynamo simulations
Authors: Gillet N , Huder L , Aubert J 
Published: July 2019

SUMMARYWe make use of recent geodynamo simulations to propose a reduced stochastic model of the dynamics at the surface of Earth’s core. On decadal and longer periods, this model replicates the most energetic eigen directions of the geodynamo computation. Towards shorter timescales, it proposes a compensation for weaknesses of these simulations. This model furthermore accounts for the signature, in the geomagnetic secular variation, of errors of representativeness associated with unresolved processes. We incorporate the reduced stochastic model into a geomagnetic data assimilation algorithm—an augmented state ensemble Kalman filter—and apply it to re-analyse magnetic field changes over the period 1880–2015. Errors of representativeness appear to be responsible for an important fraction of the observed changes in the secular variation, as it is the case in the dynamo simulation.Recovered core surface motions are primarily symmetric with respect to the equator. We observe the persistence of the eccentric westward gyre over the whole studied era and vortices that partly follow isocontours of the radial magnetic field at the core surface. Our flow models provide a good fit to decadal changes in the length-of-day and predict its interannual variations over the period 1940–2005. The largest core flow acceleration patterns are found in an equatorial belt below 10° in latitude and are associated with non-axisymmetric features. No systematic longitudinal drift of acceleration patterns is found, even over the past decades where satellite data are available. The acceleration of the high-latitude westward jet in the Pacific hemisphere is, during the satellite era, a factor 5 smaller than previously reported and its structure shows some evidence for equatorial asymmetry. The era of continuous satellite records provides enhanced contrast on the rapid core flow variations. The proposed assimilation algorithm offers the prospect of evaluating Earth-likeness of geodynamo simulations.
LMO2 gene deletions significantly worsen the prognosis of Wilms’ tumor development in patients with WAGR syndrome
Authors: Marakhonov Andrey V , Vasilyeva Tatyana A , Voskresenskaya Anna A , Sukhanova Natella V , Kadyshev Vitaly V , Kutsev Sergey I , Zinchenko Rena A 
Published: July 2019

AbstractWAGR syndrome (OMIM #194072) is a rare genetic disorder that consists of development of Wilms’ tumor (nephroblastoma), aniridia, genitourinary anomalies and intellectual disability (mental retardation). It is associated with WAGR-region deletions in the 11p13 chromosome region. Our previous study of congenital aniridia patients revealed a noticeable number of aniridia patients with WAGR-region deletions but without Wilms’ tumor in their medical history. We assessed the involvement of other neighboring genes from affected chromosome regions in the patients with and without Wilms’ tumor. Reliable confidence was obtained for the LMO2 gene, which is significantly more often deleted in patients with nephroblastoma. Thus, our study presents genetic evidence that the development of Wilms tumors in WAGR syndrome patients should be attributed to the deletion of WT1 and LMO2 rather than WT1 only.
Reproduction, DNA methylation and biological age
Authors: Kresovich Jacob K , Harmon Quaker E , Xu Zongli , Nichols Hazel B , Sandler Dale P , Taylor Jack A 
Published: July 2019

Abstract

STUDY QUESTION
Are reproductive characteristics associated with genome-wide DNA methylation and epigenetic age?

SUMMARY ANSWER
Our data suggest that increasing parity is associated with differences in blood DNA methylation and small increases in epigenetic age.

WHAT IS KNOWN ALREADY
A study of 397 young Filipino women (ages 20–22) observed increasing epigenetic age with an increasing number of pregnancies.

STUDY DESIGN, SIZE, DURATION
We used data from 2356 non-Hispanic white women (ages 35–74) enrolled in the Sister Study cohort.

PARTICIPANTS/MATERIALS, SETTING, METHODS
Data on reproductive history were ascertained via questionnaire. Of the 2356 women, 1897 (81%) reported at least one live birth. Among parous women, 487 (26%) women reported ever experiencing a pregnancy complication. Three epigenetic clocks (i.e. Hannum, Horvath and Levine) and genome-wide methylation were measured in DNA from whole blood using Illumina’s HumanMethylation450 BeadChip. We estimated association β-values and 95% CIs using linear regression.

MAIN RESULTS AND THE ROLE OF CHANCE
All three epigenetic clocks showed weak associations between number of births and epigenetic age (per live birth; Hannum: β = 0.16, 95% CI = 0.02, 0.29, P = 0.03; Horvath: β = 0.12, 95% CI = −0.04, 0.27, P = 0.14; Levine: β = 0.27, 95% CI = 0.08, 0.45, P = 0.01); however, additional adjustment for current BMI attenuated the associations. Among parous women, a history of abnormal glucose tolerance during pregnancy was associated with increased epigenetic age by the Hannum clock (β = 0.96; 95% CI = 0.10, 1.81; P = 0.03) and Levine clocks (β = 1.69; 95% CI = 0.54, 2.84; P &lt; 0.01). In epigenome-wide analysis, increasing parity was associated with methylation differences at 17 CpG sites (Bonferroni corrected P≤ 1.0 × 10-7).

LIMITATIONS, REASONS FOR CAUTION
We relied on retrospective recall to ascertain reproductive history and pregnancy complications.

WIDER IMPLICATIONS OF THE FINDINGS
Our findings suggest that parity is associated with small increases in epigenetic age and with DNA methylation at multiple sites in the genome.

STUDY FUNDING/COMPETING INTEREST(S)
This research was supported by the Intramural Research program of the NIH, National Institute of Environmental Health Sciences (Z01-ES049033, Z01-ES049032 and Z01-ES044055). None of the authors have a conflict of interest.

TRIAL REGISTRATION NUMBER
Not applicable.
Patents and corporate credit risk
Authors: Frey Carl Benedikt , Neuhäusler Peter , Blind Knut 
Published: July 2019

AbstractA vast literature documents a positive relationship between patents and companies stock market performance. Nevertheless, evidence on the influence of patents on companies’ debt capacity remains sparse. In this article, we examine the relationship between companies’ patent portfolios and their credit rating, providing relevant, albeit indirect, evidence on patents as a debt funding mechanism. Using a panel dataset on 155 U.S. firms, we find a positive relationship between companies’ credit rating and the size of their patent portfolio. Our indicators for valuable patents, however, provide a mixed picture. While there is a positive link between the average family size of a company’s patent portfolio and its credit ratings, we surprisingly find a significant negative relationship between patent forward citations and companies ratings. We hypothesize that this finding is the result of citations being associated with patent lawsuits, potentially incurring substantial losses on creditors.
Klebsiella pneumoniae and Klebsiella quasipneumoniae define the population structure of blaKPC-2Klebsiella: a 5 year retrospective genomic study in Singapore
Authors: Octavia Sophie , Kalisvar Marimuthu , Venkatachalam Indumathi , Ng Oon Tek , Xu Weizhen , Sridatta Prakki Sai Rama , Ong Yi Fa , Wang Liang De , Chua Amanda , Cheng Bernadette , Lin Raymond T P , Teo Jeanette W P 
Published: July 2019

Abstract

Objectives
To describe the population structure, molecular epidemiology and genetic context of blaKPC-2-bearing Klebsiella pneumoniae.

Methods
Isolates (n = 157) were retrospective, phenotypically carbapenem-resistant blaKPC-positive K. pneumoniae, collected from public hospitals. WGS was performed on the Illumina platform. Phylogenomic analysis, screening of resistance and virulence genes, and comparison of the genetic environment of blaKPC were carried out.

Results
Based on core-tree phylogeny, 67.5% of the isolates were K. pneumoniae and the remainder comprised Klebsiella quasipneumoniae. No Klebsiella variicola strains were observed. Only a single K. pneumoniae carbapenemase (KPC) variant type, blaKPC-2, was seen. MLSTs were diverse and did not comprise the ‘traditional’ KPC clonal group (CG) 258. blaKPC-2 was associated with a non-Tn4401 element (NTE) in &gt;99% of genomes. Screening for four key virulence loci: yersiniabactin (ybt), aerobactin (iuc), salmochelin (iro) and colibactin (clb) as well as ICEKp (virulence-associated integrative conjugative element of K. pneumoniae), revealed the lack of virulence factors and ICEKp within K. quasipneumoniae. Amongst the K. pneumoniae, there were 32 ybt+ isolates (32/106, 30.2%) and, of these, 8 isolates were also clb+ (7.5%). K. pneumoniae serotypes K1 and K2, the majority of capsular serotype seen in patients with invasive liver abscess syndrome, were detected at 4.5% (7/157).

Conclusions
Results suggest that dissemination of blaKPC-2 is driven by NTEKPC in non-ST258 isolates. The detection of blaKPC-2K. pneumoniae serotypes K1/K2 carrying virulence factors, albeit in low numbers, reflects the worrisome convergence of carbapenem resistance and hypervirulence in K. pneumoniae.
Phase III study of tri-modality combination therapy with induction docetaxel plus cisplatin and 5-fluorouracil versus definitive chemoradiotherapy for locally advanced unresectable squamous-cell carcinoma of the thoracic esophagus (JCOG1510: TRIANgLE)
Authors: Terada Mitsumi , Hara Hiroki , Daiko Hiroyuki , Mizusawa Junki , Kadota Tomohiro , Hori Keisuke , Ogawa Hirofumi , Ogata Takashi , Sakanaka Katsuyuki , Sakamoto Takeshi , Kato Ken , Kitagawa Yuko 
Published: July 2019

Abstract
A randomized phase III trial commenced in Japan in February 2018. Definitive chemoradiotherapy (CRT) with cisplatin plus 5-fluorouracil is the current standard treatment for locally advanced unresectable esophageal carcinoma. The purpose of this study is to confirm the superiority of induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (DCF) followed by conversion surgery or definitive CRT over definitive CRT alone for overall survival (OS) in patients with locally advanced unresectable squamous-cell carcinoma of thoracic esophagus. A total of 230 patients will be accrued from 47 Japanese institutions over 4.5 years. The primary endpoint is OS, and the secondary endpoints are progression-free survival, complete response rate of CRT, response rate of DCF, adverse events of DCF and CRT, late adverse events and surgical complications. This trial has been registered at the Japan Registry of Clinical Trials as jRCTs031180181.
TRIM65 E3 ligase targets VCAM-1 degradation to limit LPS-induced lung inflammation
Authors: Li Yong , Huang Xuan , Guo Fang , Lei Tianhua , Li Shitao , Monaghan-Nichols Paula , Jiang Zhisheng , Xin Hong-Bo , Fu Mingui 
Published: July 2019

AbstractAlthough the adhesion molecules-mediated leukocyte adherence and infiltration into tissues is an important step of inflammation, the post-translational regulation of these proteins on the endothelial cells is poorly understood. Here, we report that TRIM65, an ubiquitin E3 ligase of tripartite protein family, selectively targets vascular cell adhesion molecule 1 (VCAM-1) and promotes its ubiquitination and degradation, by which it critically controls the duration and magnitude of sepsis-induced pulmonary inflammation. TRIM65 is constitutively expressed in human vascular endothelial cells. During TNFα-induced endothelial activation, the protein levels of TRIM65 and VCAM-1 are inversely correlated. Expression of wild-type TRIM65, but not expression of a TRIM65 mutant that lacks E3 ubiquitin ligase function in endothelial cells, promotes VCAM-1 ubiquitination and degradation, whereas small interference RNA-mediated knockdown of TRIM65 attenuates VCAM-1 protein degradation. Further experiments show that TRIM65 directly interacts with VCAM-1 protein and directs its polyubiquitination, by which TRIM65 controls monocyte adherence and infiltration into tissues during inflammation. Importantly, TRIM65-deficient mice are more sensitive to lipopolysaccharide-induced death, due to sustained and severe pulmonary inflammation. Taken together, our studies suggest that TRIM65-mediated degradation of VCAM-1 represents a potential mechanism that controls the duration and magnitude of inflammation.