bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incremental prognostic value of echocardiography of left ventricular remodeling and diastolic function in STICH trial
Authors: Kim Kyung-Hee , She Lilin , Lee Kerry L. , Dabrowski Rafal , Grayburn Paul A. , Rajda Miroslaw , Prior David L. , Desvigne-Nickens Patrice , Zoghbi William A. , Senni Michele , Stefanelli Guglielmo , Beghi Cesare , Huynh Thao , Velazquez Eric J. , Oh Jae K. , Lin Grace 
Published: May 2020

AbstractAimsWe sought to determine which echocardiographic markers of left ventricular (LV) remodeling and diastolic dysfunction can contribute as incremental and independent prognostic information in addition to current clinical risk markers of ischemic LV systolic dysfunction in the Surgical Treatment for Ischemic Heart Failure (STICH) trial.Methods and resultsThe cohort consisted of 1511 of 2136 patients in STICH for whom baseline transmitral Doppler (E/A ratio) could be measured by an echocardiographic core laboratory blinded to treatment and outcomes, and prognostic value of echocardiographic variables was determined by a Cox regression model. E/A ratio was the most significant predictor of mortality amongst diastolic variables with lowest mortality for E/A closest 0.8, although mortality was consistently low for E/A 0.6 to 1.0. Mortality increased for E/A < 0.6 and > 1.0 up to approximately 2.3, beyond which there was no further increase in risk. Larger LV end-systolic volume index (LVESVI) and E/A < 0.6 and > 1.0 had incremental negative effects on mortality when added to a clinical multivariable model, where creatinine, LVESVI, age, and E/A ratio accounted for 74% of the prognostic information for predicting risk. LVESVI and E/A ratio were stronger predictors of prognosis than New York Heart Association functional class, anemia, diabetes, history of atrial fibrillation, and stroke.ConclusionsEchocardiographic markers of advanced LV remodeling and diastolic dysfunction added incremental prognostic value to current clinical risk markers. LVESVI and E/A ratio outperformed other markers and should be considered as standard in assessing risks in ischemic heart failure. E/A closest to 0.8 was the most optimal filling pattern.
Low doses of Bisphenol S affect post-translational modifications of sperm proteins in male mice
Authors: Řimnáčová Hedvika , Štiavnická Miriam , Moravec Jiří , Chemek Marouane , Kolinko Yaroslav , García-Álvarez Olga , Mouton Peter R. , Trejo Azalia Mariel Carranza , Fenclová Tereza , Eretová Nikola , Hošek Petr , Klein Pavel , Králíčková Milena , Petr Jaroslav , Nevoral Jan 
Published: May 2020

AbstractBackgroundBisphenol S (BPS) is increasingly used as a replacement for bisphenol A in the manufacture of products containing polycarbonates and epoxy resins. However, further studies of BPS exposure are needed for the assessment of health risks to humans. In this study we assessed the potential harmfulness of low-dose BPS on reproduction in male mice.MethodsTo simulate human exposure under experimental conditions, 8-week-old outbred ICR male mice received 8 weeks of drinking water containing a broad range of BPS doses [0.001, 1.0, or 100 μg/kg body weight (bw)/day, BPS1–3] or vehicle control. Mice were sacrificed and testicular tissue taken for histological analysis and protein identification by nano-liquid chromatography/mass spectrometry (MS) and sperm collected for immunodetection of acetylated lysine and phosphorylated tyrosine followed by protein characterisation using matrix-assisted laser desorption ionisation time-of-flight MS (MALDI-TOF MS).ResultsThe results indicate that compared to vehicle, 100 μg/kg/day exposure (BPS3) leads to 1) significant histopathology in testicular tissue; and, 2) higher levels of the histone protein γH2AX, a reliable marker of DNA damage. There were fewer mature spermatozoa in the germ layer in the experimental group treated with 1 μg/kg bw (BPS2). Finally, western blot and MALDI-TOF MS studies showed significant alterations in the sperm acetylome and phosphorylome in mice treated with the lowest exposure (0.001 μg/kg/day; BPS1), although the dose is several times lower than what has been published so far.ConclusionsIn summary, this range of qualitative and quantitative findings in young male mice raise the possibility that very low doses of BPS may impair mammalian reproduction through epigenetic modifications of sperm proteins.
A novel NGS-based microsatellite instability (MSI) status classifier with 9 loci for colorectal cancer patients
Authors: Zheng Kai , Wan Hua , Zhang Jie , Shan Guangyu , Chai Ningning , Li Dongdong , Fang Nan , Liu Lina , Zhang Jingbo , Du Rong , Wu Qixi , Li Xichuan , Zhang Chunze 
Published: May 2020

Abstract
Background
With the recent emergence of immune checkpoint inhibitors, microsatellite instability (MSI) status has become an important biomarker for immune checkpoint blockade therapy. There are growing technical demands for the integration of different genomic alterations profiling including MSI analysis in a single assay for full use of the limited tissues.

Methods
Tumor and paired control samples from 64 patients with primary colorectal cancer were enrolled in this study, including 14 MSI-high (MSI-H) cases and 50 microsatellite stable (MSS) cases determined by MSI-PCR. All the samples were sequenced by a customized NGS panel covering 2.2 MB. A training dataset of 28 samples was used for selection of microsatellite loci and a novel NGS-based MSI status classifier, USCI-msi, was developed. NGS-based MSI status, single nucleotide variant (SNV) and tumor mutation burden (TMB) were detected for all patients. Most of the patients were also independently detected by immunohistochemistry (IHC) staining.

Results
A 9-loci model for detecting microsatellite instability was able to correctly predict MSI status with 100% sensitivity and specificity compared with MSI-PCR, and 84.3% overall concordance with IHC staining. Mutations in cancer driver genes (APC, TP53, and KRAS) were dispersed in MSI-H and MSS cases, while BRAF p.V600E and frameshifts in TCF7L2 gene occurred only in MSI-H cases. Mismatch repair (MMR)-related genes are highly mutated in MSI-H samples.

Conclusion
We established a new NGS-based MSI classifier, USCI-msi, with as few as 9 microsatellite loci for detecting MSI status in CRC cases. This approach possesses 100% sensitivity and specificity, and performed robustly in samples with low tumor purity.
Lipopolysaccharide-induced changes in the neurovascular unit in the preterm fetal sheep brain
Authors: Disdier Clémence , Awa Fares , Chen Xiaodi , Dhillon Simerdeep K. , Galinsky Robert , Davidson Joanne O. , Lear Christopher A. , Bennet Laura , Gunn Alistair J. , Stonestreet Barbara S. 
Published: May 2020

Abstract
Background
Exposure to inflammation during pregnancy can predispose to brain injury in premature infants. In the present study, we investigated the effects of prolonged exposure to inflammation on the cerebrovasculature of preterm fetal sheep.

Methods
Chronically instrumented fetal sheep at 103–104 days of gestation (full term is ~ 147 days) received continuous low-dose lipopolysaccharide (LPS) infusions (100 ng/kg over 24 h, followed by 250 ng/kg/24 h for 96 h plus boluses of 1 μg LPS at 48, 72, and 96 h) or the same volume of normal saline (0.9%, w/v). Ten days after the start of LPS exposure at 113–114 days of gestation, the sheep were killed, and the fetal brain perfused with formalin in situ. Vessel density, pericyte and astrocyte coverage of the blood vessels, and astrogliosis in the cerebral cortex and white matter were determined using immunohistochemistry.

Results
LPS exposure reduced (P < 0.05) microvascular vessel density and pericyte vascular coverage in the cerebral cortex and white matter of preterm fetal sheep, and increased the activation of perivascular astrocytes, but decreased astrocytic vessel coverage in the white matter.

Conclusions
Prolonged exposure to LPS in preterm fetal sheep resulted in decreased vessel density and neurovascular remodeling, suggesting that chronic inflammation adversely affects the neurovascular unit and, therefore, could contribute to long-term impairment of brain development.
Mental health and psychosocial well-being during the COVID-19 pandemic: the invisible elephant in the room
Authors: Otu Akaninyene , Charles Carlo Handy , Yaya Sanni 
Published: May 2020

AbstractThe novel SARS-CoV-2 coronavirus pandemic has emerged as a truly formidable threat to humankind’s existence. In the wake of the massively volatile global situation created by COVID-19, it is vital to recognize that the trauma it causes can affect people in different ways, at the individual and collective levels, resulting in mental health challenges for many. Although mental health problems account for about one-third of the world’s disability among adults, these issues tend to be under-addressed and overlooked in society and are closely associated with deadly disease outbreaks. In large scale outbreaks, the mental health problems experienced are not limited to infected persons but also extend to involve frontline health workers and community members alike. While it is crucial to limit the spread of infections during an outbreak, previous experience suggests that mental and behavioural health interventions should be fully included in public health response strategies.
Long non-coding RNA LINC00520 promotes the proliferation and metastasis of malignant melanoma by inducing the miR-125b-5p/EIF5A2 axis
Authors: Luan Wenkang , Ding Yuting , Yuan Haitao , Ma Shaojun , Ruan Hongru , Wang Jinlong , Lu Feng , Bu Xuefeng 
Published: May 2020

Abstract
Background
Long intergenic non-protein coding RNA 520 (LINC00520), a novel identified lncRNA, has been shown to modulate the malignant phenotype of tumor cells in some malignant tumors. However, the exact role and molecular mechanism of LINC00520 in malignant melanoma has not been studied.

Methods
The expression of LINC00520 in melanoma tissues were detected by using RNA-seq analysis and qRT-PCR. Melanoma cases from the public databases (The Cancer Genome Atlas (TCGA), GEO#GSE15605, GEO#GSE34460 and GEO#GSE24996) were included in this study. CCK-8 assay, EdU assay, transwell and scratch wound assay were used to explore the role of LINC00520 in melanoma cells. Luciferase reporter assays, MS2-RIP, RNA pull-down and RNA-ChIP assay were used to demonstrate the molecular biological mechanism of LINC00520 in melanoma.

Results
We found that LICN00520 was found to be overexpressed in melanoma tissue. High expression of LICN00520 is a risk factor for the prognosis of melanoma patients. LINC00520 promotes the proliferation, invasion and migration of melanoma cells. LICN00520 exerted its oncogenic role by competitive binding miR-125b-5p to promote Eukaryotic initiation factor 5A2 (EIF5A2) expression. We also showed that LICN00520 promotes the growth and metastasis of melanoma in vivo through regulating miR-125b-5p/EIF5A2 axis.

Conclusions
All results elucidated the role and molecular mechanism of LINC00520 in the malignant development of melanoma. LINC00520, a new oncogene in melanoma, maybe serve as a survival biomarkers or therapeutic target for melanoma patients.
Risk of early progression according to circulating ESR1 mutation, CA-15.3 and cfDNA increases under first-line anti-aromatase treatment in metastatic breast cancer
Authors: Clatot Florian , Perdrix Anne , Beaussire Ludivine , Lequesne Justine , Lévy Christelle , Emile George , Bubenheim Michael , Lacaille Sigrid , Calbrix Céline , Augusto Laetitia , Guillemet Cécile , Alexandru Cristina , Fontanilles Maxime , Sefrioui David , Burel Lucie , Guénot Sabine , Richard Doriane , Sarafan-Vasseur Nasrin , Di Fiore Frédéric 
Published: May 2020

Abstract
Background
Endocrine therapy is recommended as a first-line treatment for hormone receptor-positive metastatic breast cancer (HR+MBC) patients. No biomarker has been validated to predict tumor progression in that setting. We aimed to prospectively compare the risk of early progression according to circulating ESR1 mutations, CA-15.3, and circulating cell-free DNA in MBC patients treated with a first-line aromatase inhibitor (AI).

Methods
Patients with MBC treated with a first-line AI were prospectively included. Circulating biomarker assessment was performed every 3 months. The primary objective was to determine the risk of progression or death at the next follow-up visit (after 3 months) in case of circulating ESR1 mutation detection among patients treated with a first-line AI for HR+MBC.

Results
Overall, 103 patients were included, and 70 (68%) had progressive disease (PD). Circulating ESR1 mutations were detected in 22/70 patients with PD and in 0/33 patients without progression (p < 0.001). Among the ESR1-mutated patients, 18/22 had a detectable mutation prior to progression, with a median delay of 110 days from first detection to PD. The detection of circulating ESR1 mutations was associated with a 4.9-fold (95% CI 3.0–8.0) increase in the risk of PD at 3 months. Using a threshold value of 25% or 100%, a CA-15.3 increase was also correlated with progression (p < 0.001 and p = 0.003, respectively). In contrast to ESR1, the CA-15.3 increase occurred concomitantly with PD in most cases, in 27/47 (57%) with a 25% threshold and in 21/25 (84%) with a 100% threshold. Using a threshold value of either 25% or 100%, cfDNA increase was not correlated with progression.

Conclusion
The emergence of circulating ESR1 mutations is associated with a 4.9-fold increase in the risk of early PD during AI treatment in HR+MBC. Our results also highlighted that tracking circulating ESR1 mutations is more relevant than tracking CA-15.3 or cfDNA increase to predict progression in this setting.

Trial registration
ClinicalTrials.gov, NCT02473120. Registered 16 June 2015—retrospectively registered after one inclusion (first inclusion 1 June 2015)
CICERO: a versatile method for detecting complex and diverse driver fusions using cancer RNA sequencing data
Authors: Tian Liqing , Li Yongjin , Edmonson Michael N. , Zhou Xin , Newman Scott , McLeod Clay , Thrasher Andrew , Liu Yu , Tang Bo , Rusch Michael C. , Easton John , Ma Jing , Davis Eric , Trull Austyn , Michael J. Robert , Szlachta Karol , Mullighan Charles , Baker Suzanne J. , Downing James R. , Ellison David W. , Zhang Jinghui 
Published: May 2020

AbstractTo discover driver fusions beyond canonical exon-to-exon chimeric transcripts, we develop CICERO, a local assembly-based algorithm that integrates RNA-seq read support with extensive annotation for candidate ranking. CICERO outperforms commonly used methods, achieving a 95% detection rate for 184 independently validated driver fusions including internal tandem duplications and other non-canonical events in 170 pediatric cancer transcriptomes. Re-analysis of TCGA glioblastoma RNA-seq unveils previously unreported kinase fusions (KLHL7-BRAF) and a 13% prevalence of EGFR C-terminal truncation. Accessible via standard or cloud-based implementation, CICERO enhances driver fusion detection for research and precision oncology. The CICERO source code is available at https://github.com/stjude/Cicero.
Digital ecosystems and their implications for competitive strategy
Authors: Subramaniam Mohan 
Published: May 2020

AbstractThis paper discusses some implications for competitive strategy when business environments are framed as digital ecosystems. Digital ecosystems are ecosystems shaped by interdependencies initiated through data connectivity, galvanized by technologies such as sensors and the Internet of Things (IoT). They are composed of two parts: production and consumption ecosystems. Production ecosystems are founded upon interdependencies associated with value chains. Although their underlying interdependencies are traditional, they gain fresh impetus because of data connectivity. Consumption ecosystems on the other hand are spawned by interdependencies among entities that complement the data generated by product usage. These are largely new interdependencies that did not exist before modern digital technologies enabled connectivity. Taken together, digital ecosystems influence a firm’s strategic landscape. I discuss three implications of digital ecosystems for competitive strategy: (1) the scope of value creation, (2) the scope of competition, and (3) the rise of digital monopoly power. I also discuss the implications of digital ecosystems for organizational design and suggest how studies can assess the processes driving the digitization of ecosystems.
Health Equity, Social Policy, and Promoting Recovery from COVID-19
Authors: Lynch Julia 
Published: May 2020

AbstractThe COVID-19 pandemic has revealed starkly and publicly the close interconnections between social and economic equality, health equity, and population health. To better understand what social policies would best promote population health, economic recovery, and preparedness for future pandemics, one must look both upstream and abroad for inspiration. In this article, the author argues for a suite of near-term and longer-term interventions, including universal health insurance and paid sick leave; upgraded wage insurance policies; tax reform; investments in parental leave, childcare, and education; and upgraded government record systems. Policies that equalize the distribution of the social determinants of health and promote social solidarity also will improve population health and economic performance and allow everyone to confront future pandemics more successfully.
Nucleocytoplasmic shuttling of the glucocorticoid receptor is influenced by tetratricopeptide repeat-containing proteins
Authors: Mazaira Gisela I. , Echeverria Pablo C. , Galigniana Mario D. 
Published: May 2020

ABSTRACT
It has been demonstrated that tetratricopeptide-repeat (TPR) domain proteins regulate the subcellular localization of glucocorticoid receptor (GR). This study analyses the influence of the TPR domain of high molecular weight immunophilins in the retrograde transport and nuclear retention of GR. Overexpression of the TPR peptide prevented efficient nuclear accumulation of the GR by disrupting the formation of complexes with the dynein-associated immunophilin FKBP52 (also known as FKBP4), the adaptor transporter importin-β1 (KPNB1), the nuclear pore-associated glycoprotein Nup62 and nuclear matrix-associated structures. We also show that nuclear import of GR was impaired, whereas GR nuclear export was enhanced. Interestingly, the CRM1 (exportin-1) inhibitor leptomycin-B abolished the effects of TPR peptide overexpression, although the drug did not inhibit GR nuclear export itself. This indicates the existence of a TPR-domain-dependent mechanism for the export of nuclear proteins. The expression balance of those TPR domain proteins bound to the GR–Hsp90 complex may determine the subcellular localization and nucleocytoplasmic properties of the receptor, and thereby its pleiotropic biological properties in different tissues and cell types.
Does contrast-enhanced ultrasound (CEUS) play a better role in diagnosis of breast lesions with calcification? A comparison with MRI
Authors: Pan Jiamin , Tong Wenjuan , Luo Jia , Liang Jinyu , Pan Fushun , Zheng Yanling , Xie Xiaoyan 
Published: May 2020

Objective:
To compare the efficacy of contrast-enhanced ultrasound enabled reclassification of Breast Imaging Reporting and Data System (CEUS-BI-RADS) with MRI in the diagnosis of breast lesions with calcification.

Methods:
A total of 52 breast lesions with calcification from 51 patients were detected by ultrasound as hyperechoic foci and categorized as BI-RADS 3–5. The 51 patients further underwent CEUS scan and MRI. The ultrasound-BI-RADS combined with CEUS 5-point score system redefined the classification of BI-RADS which was called CEUS-BI-RADS. The diagnostic efficacy of three methods was assessed by receiver operating characteristic (ROC) curve analysis. Histopathological assessment used as the gold-standard.

Results:
The sensitivities of Ultrasound-BI-RADS, MRI classification of BI-RADS (MRI-BI-RADS) and CEUS-BI-RADS were 85%, 90% and 95% without significant difference among the three modalities (p &gt; 0.05). The diagnostic specificities of ultrasound-BI-RADS, MRI-BI-RADS and CEUS-BI-RADS were 78.1%, 78.1% and 96.8%, respectively (p &lt; 0.05); and the accuracy were 80.7%, 82.6% and 96.1% for ultrasound-BI-RADS, MRI-BI-RADS and CEUS-BI-RADS, respectively (p &lt; 0.05). The area under ROC (AUROC) in differentiation of breast lesions with calcification was 0.945 for CEUS-BI-RADS, 0.907 for MRI-BI-RADS and 0.853 for ultrasound-BI-RADS, with no significant difference among the three modalities (p &gt; 0.05).

Conclusion:
The CEUS-BI-RADS has a better diagnostic efficiency than MRI-BI-RADS in the differentiation of the breast lesions with calcification.

Advances in knowledge:
•CEUS is a better method in differentiation of breast lesions with calcification.
•CEUS-BI-RADS increases the efficiency of diagnosis compared to MRI.
Parity-based, bias-free optical quantum random number generation with min-entropy estimation
Authors: Coleman Mathew R. , Ingalls Kaylin G. , Kavulich John T. , Kemmerly Sawyer J. , Salinas Nicolas C. , Venegas Ramirez Efrain , Schlosshauer Maximilian 
Published: May 2020

We describe the generation of sequences of random bits from the parity of photon counts produced by polarization measurements on a polarization-entangled state. The resulting sequences are bias free, pass the applicable tests in the NIST battery of statistical randomness tests, and are shown to be Borel normal, without the need for experimental calibration stages or postprocessing of the output. Because the photon counts are produced in the course of a measurement of the violation of the Clauser–Horne–Shimony–Holt inequality, we are able to concurrently verify the nonclassical nature of the photon statistics and estimate a lower bound on the min-entropy of the bit-generating source. The rate of bit production in our experiment is around 13 bits/s.
Time-gated luminescence imaging for background free in vivo tracking of single circulating tumor cells
Authors: Cao Xu , Yao Cuiping , Jiang Shudong , Gunn Jason , Van Namen Austin C. , Bruza Petr , Pogue Brian W. 
Published: May 2020

Fluorescence imaging is severely limited by the background and autofluorescence of tissues for in vivo detection of circulating tumor cells (CTCs). Time-gated luminescence (TGL) imaging, in combination with luminescent probes that possess hundreds of microsecond emission lifetimes, can be used to effectively suppress this background, which has predominantly nanosecond lifetimes. This Letter demonstrates the feasibility of TGL imaging using luminescent probes for the in vivo real time imaging and tracking of single CTCs circulating freely in the blood vessels with higher accuracy given by substantially higher signal-to-noise ratio. The luminescent probe used in this Letter was a commercial

E
u

3
+

chelate (EuC) nanosphere with a super-long lifetime of near 800 µs, which enabled TGL imaging to achieve background-free detection with

∼

5

times higher SNR versus steady state. Phantom and in vivo mouse studies indicated that EuC labeled tumor cells moving in medium or bloodstream at the speed of 1–2 mm/s could be captured in real time.