bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning algorithms for the detection of spurious white blood cell differentials due to erythrocyte lysis resistance
Authors: Bigorra Laura , Larriba Iciar , Gutiérrez-Gallego Ricardo 
Published: April 2019

AimsRed blood cell (RBC) lysis resistance interferes with white blood cell (WBC) count and differential; still, its detection relies on the identification of an abnormal scattergram, and this is not clearly adverted by specific flags in the Beckman-Coulter DXH-800. The aims were to analyse precisely the effect of RBC lysis resistance interference in WBC counts, differentials and cell population data (CPD) and then to design, develop and implement a novel diagnostic machine learning (ML) model to optimise the detection of samples presenting this phenomenon.MethodsWBC counts, differentials and CPD from 232 patients (anaemia or liver disease) were compared with 100 healthy controls (HC) using analysis of variance. The data were analysed after a corrective action, and the analyser differentials were also compared with the digital leucocyte differentials. The ML support vector machine (SVM) algorithm was trained with 70% of the samples (n=233) and the 30% remaining (n=99) were employed exclusively during the validation phase.ResultsWe identified that impedance WBC was not affected by the RBC lysis resistance interference while the DXH-800 differentials overestimated lymphoid subpopulations (17.6%), sometimes even yielding spurious lymphocytosis, and the latter were corrected when sample dilution was performed. The ML-SVM algorithm allowed the classification of the pathological groups when compared with HC with validation accuracies corresponding to 97.98%, 100% and 88.78% for the global, anaemia and liver disease groups, respectively.ConclusionsThe proposed algorithm has an impressive discriminatory potential and its application would be a valuable support system to detect spurious results due to RBC lysis resistance.
Genetic variation of rs7958311 inP2X7Rgene is associated with the susceptibility and disease activity of ankylosing spondylitis
Authors: Pan Zhipeng , Zhang Xu , Ma Yubo , Xu Shengqian , Shuai Zongwen , Pan Faming , Sun Guoping 
Published: April 2019

AbstractObjectivesTo describe association between the genetic variation of inflammation-associated gene, P2X7R, and ankylosing spondylitis (AS) susceptibility.MethodsFour single nucleotide polymorphisms (SNPs) of P2X7R gene were genotyped in 673 patients with AS and 687 healthy controls. Allele and genotype frequencies and different genetic models were performed to calculate ORs and 95% CIs, the demographic and clinical characteristics of patients were recorded. The data analyses were also conducted by sex.ResultsCompared with controls, genetic variation in rs7958311 but not the other three SNPs was statistically significant in female patients (χ2=6.907, p=0.032). Specifically, the P2X7R gene rs7958311 polymorphism A allele showed a protective effect in AS susceptibility (OR=0.704, p=0.049, pFDR=0.061). In addition, female individuals with GA and/or AA genotypes had a lower risk of having AS compared with those with GG genotype (GA vs GG: OR=0.446, p=0.012, pFDR=0.030; AA vs GG: OR=0.440, p=0.039, pFDR=0.061; GA/AA vs GG: OR=0.445, p=0.009, pFDR=0.030). Furthermore, individuals with A allele (ie, GA/AA vs GG) had a higher disease activity, including Bath Ankylosing Spondylitis Disease Activity Index (overall: Z=− 2.630, p=0.014; male: Z=− 2.243, p=0.025), Schober test (overall: Z=− 3.041, p&lt;0.001; male: Z=− 2.243, p=0.025) and chest expansion (overall: Z=− 3.895, p=0.004; male: Z=− 2.403, p=0.016).ConclusionThe allelic variation of rs7958311 SNP in P2X7R gene may have a protective effect on AS susceptibility in females and is associated with disease activity in male patients.
Opportunities to obtain polarization at CEPC
Authors: Nikitin Sergei 
Published: April 2019

The possibility to obtain the transversely polarized electron/positron beams at the [Formula: see text] GeV CEPC collider basing on the radiative self-polarization of particles in the main rings is under consideration. In addition, we consider one of the options for obtaining longitudinal polarization of electrons at CEPC.
Bottom-quark forward–backward asymmetry, dark matter and the LHC
Authors: Liu Da , Liu Jia , Wagner Carlos E. M. , Wang Xiao-Ping 
Published: April 2019

The LEP experiment at CERN provided accurate measurements of the [Formula: see text] neutral gauge boson properties. Although all measurements agree well with the SM predictions, the forward–backward asymmetry of the bottom-quark remains almost [Formula: see text] away from the SM value. We proposed that this anomaly may be explained by the existence of a new [Formula: see text] gauge boson, which couples with opposite charges to the right-handed components of the bottom and charm quarks. Cancellation of gauge anomalies demands the presence of a vector-like singlet charged lepton as well as a neutral Dirac (or Majorana) particle that provides a dark matter candidate. Constraints from precision measurements imply that the mass of the new gauge boson should be around 115 GeV. We discuss the experimental constraints on this scenario, including the existence of a di-jet resonance excess at an invariant mass similar to the mass of this new gauge boson, observed in boosted topologies at the CMS experiment.
Developments in the Space of New MAPK Pathway Inhibitors for BRAF-Mutant Melanoma
Authors: Cohen Justine V. , Sullivan Ryan J. 
Published: April 2019

Abstract
The characterization of the MAPK signaling pathway has led to the development of multiple promising targeted therapy options for a subset of patients with metastatic melanoma. The combination of BRAF and MEK inhibitors represents an FDA-approved standard of care in patients with metastatic and resected BRAF-mutated melanoma. There are currently three FDA-approved BRAF/MEK inhibitor combinations for the treatment of patients with BRAF-mutated melanoma. Although there have been significant advances in the field of targeted therapy, further exploration of new targets within the MAPK pathway will strengthen therapeutic options for patients. Important clinical and translational research focuses on mechanisms of resistance, predictive biomarkers, and challenging patient populations such as those with brain metastases or resected melanoma.
Cellular Plasticity in Cancer
Authors: Yuan Salina , Norgard Robert J. , Stanger Ben Z. 
Published: April 2019

Abstract

During cancer progression, tumor cells undergo molecular and phenotypic changes collectively referred to as cellular plasticity. Such changes result from microenvironmental cues, stochastic genetic and epigenetic alterations, and/or treatment-imposed selective pressures, thereby contributing to tumor heterogeneity and therapy resistance. Epithelial–mesenchymal plasticity is the best-known case of tumor cell plasticity, but recent work has uncovered other examples, often with functional consequences. In this review, we explore the nature and role(s) of these diverse cellular plasticity programs in premalignant progression, tumor evolution, and adaptation to therapy and consider ways in which targeting plasticity could lead to novel anticancer treatments.

Significance:
Changes in cell identity, or cellular plasticity, are common at different stages of tumor progression, and it has become clear that cellular plasticity can be a potent mediator of tumor progression and chemoresistance. Understanding the mechanisms underlying the various forms of cell plasticity may deliver new strategies for targeting the most lethal aspects of cancer: metastasis and resistance to therapy.
Characteristics and Findings of Childhood Urinary Tract Infection in the Last Decade
Authors: Sitthisarunkul Noppasorn , Uthairat Monthida , Dissaneewate Pornsak , McNeil Edward , Vachvanichsanong Prayong 
Published: April 2019

<b><i>Background:</i></b> The strong association between kidney and urinary tract anomalies and childhood urinary tract infection (UTI) often leads to imaging tests being performed. ­<b><i>Objective:</i></b> To describe the epidemiology, characteristics, and imaging findings in Thai children with UTI and compare results between boys and girls. <b><i>Methods:</i></b> We retrospectively reviewed the medical records of children with UTI aged &#x3c; 15 years. Demographic characteristics and findings of investigations are presented. <b><i>Results:</i></b> One hundred seventy-eight boys and 170 girls with 432 UTI episodes were identified. The median (interquartile range) age at presentation was 1.4 (0.6–3.4) years, 1.0 for boys and 2.1 for girls (<i>p</i> &#x3c; 0.001). Renal ultrasound, voiding cystourethrogram and <sup>99m</sup>Tc dimercaptosuccinic acid (DMSA) renal scans were performed in 273, 223 and 113 children, respectively. Overall, 283 children (81.3%) had at least one imaging study done and anomalies of the kidney and urinary tract were detected in 158 (45.4%). Primary vesicoureteral reflux was detected in 73 (32.7%) children. The remaining abnormalities were hydronephrosis (<i>n</i> = 54). DMSA scans detected 54 children with dysplastic or scarred kidneys. <b><i>Conclusions:</i></b> First UTI in a group of Thai children occurred in approximately equal proportion in boys and girls but boys were younger at diagnosis. Kidney and urinary tract anomalies were detected in half of the children.
A Potassium-Competitive Acid Blocker-Based Regimen as Second-Line Therapy Improves Helicobacter pylori Eradication
Authors: Nabeta Haruaki , Shinozaki Satoshi , Abe Yasuhiro , Koyanagi Ryota , Nakamichi Taro , Kobayashi Yasutoshi , Lefor Alan Kawarai , Hirashima Hayato 
Published: April 2019

Background/Aims: Although a potassium-competitive acid blocker (PCAB)-based regimen improves the rate of successful Helicobacter pylori first-line eradication, the efficacy of a PCAB-based regimen as second-line therapy is unclear. The aim of this study is to compare the success of second-line eradication of H. pylori using PCAB and proton pump inhibitor (PPI)-based regimens. Methods: From 2014 to 2017, 624 patients who underwent second-line H. pylori eradication were enrolled. A standard triple regimen for second-line H. pylori eradication includes metronidazole 250 mg, amoxicillin 750 mg, and PPI or PCAB twice daily for 7 days. The success of eradication was compared using intention-to-treat, per-protocol, and propensity-score matching analysis. Results: All patients completed the 7-day course of therapy. Patients using a PCAB-based regimen had a higher rate of eradication than those using a PPI-based regimen in both intention-to-treat (90% [298/330] vs. 85% [250/294], p = 0.045) and per-protocol analyses (96% [298/309] vs. 91% [250/274], p = 0.008). Adverse events occurred in 4 patients. Propensity score matching analysis acquired 274 matched pairs. Patients using a PCAB-based regimen had a higher rate of eradication than those using a PPI-based regimen (96% [264/274] vs. 91% [250/274], p = 0.013). Conclusions: PCAB-based second-line H. pylori eradication is significantly better than PPI-based therapy.
AMINO ACID PROFILE OF PHASEOLUS VULGARIS PODS AND DRY EXTRACT PREPARED OF THEM
Authors: Vronska L. V. , Demyd A. Ye. 
Published: April 2019

The aim of the research was to study the amino acid profile of the phaseolus vulgaris pods and extract prepared of them.
Materials and methods. Five samples of raw material of phaseolus vulgaris pods (erect herbaceous bushes varieties with white seeds) were collected in the Ternopil and Volyn regions, dry extract of phaseolus vulgaris pods was obtained according to previously developed technology. The study of amino acid composition of the raw materials of phaseolus vulgaris pods and extract prepared of them was carried out using a thin-layer chromatography (TLC) and a high-performance liquid chromatography (HPLC).
Results and discussion. The better separation of amino acids in TLC-research of the raw material of phaseolus vulgaris pods was observed in the system of solvents isopropanol - formic acid - water (40: 2: 10). As a result of the study, aspartic and glutamic acids, glycine, valine, tyrosine and leucine were identified.
The amino acid profile of the studied samples of raw material is quite homogeneous in composition: 7 essential amino acids (histidine, threonine, valine, methionine, phenylalanine, isoleucine and leucine) and 8 non-essential amino acids (aspartic and glutamic acids, arginine, serine, glycine, alanine, tyrosine and proline); lysine was found among the bound amino acids in the 4th sample of raw material. Proline predominates in all samples of raw materials among free amino acids. Among the bound amino acids the content of glutamic acid, which is the product of the glutamine hydrolysis, is the highest. The content of glycine, serine and alanine is also high. Among the essential amino acids, leucine, phenylalanine, histidine, threonine, isoleucine, valine were determined in content descending order.
The quantitative determination of amino acids in the extract of phaseolus vulgaris pods proved that the content of proline was the highest (12.47 mg / g); the content of some compounds was also high: aspartic (5.41 mg / g) and glutamic (3.41 mg / g) acids, arginine (5.10 mg / g; both in free and bound forms), glycine (1.02 mg / g) and serine (1.04 mg / g). Among the essential amino acids in the extract, the amount of valine (0.80 mg / g), phenylalanine (0.67 mg / g), threonine (0.66 mg / g), leucine (0.63 mg / g) and isoleucine (0.58 mg / g) was a little different. The total content of amino acids in the extract was 3.2%.
Conclusions. 1. The amino acid profile of five samples of phaseolus vulgaris pods was studied by the HPLC method. It has been established that the composition is quite homogeneous, and the total content varies within 0.7-1.1%.
2. In the dry extract of phaseolus vulgaris pods the content of 5 essential and 7 non-essential amino acids has been determined. The content of free amino acids in the extract is 0.52%; the total content of free and bound amino acids is 3.2%.
3. When studying the stability and establishing the shelf life of the dry extract of phaseolus vulgaris pods, it is necessary to take into account the presence of free amino acids and protein substances.
Rare Missense Variants in
TLN1
Are Associated With Familial and Sporadic Spontaneous Coronary Artery Dissection
Authors: Turley Tamiel N. , Theis Jeanne L. , Sundsbak Rhianna S. , Evans Jared M. , O’Byrne Megan M. , Gulati Rajiv , Tweet Marysia S. , Hayes Sharonne N. , Olson Timothy M. 
Published: April 2019

Background:
Spontaneous coronary artery dissection (SCAD) is an uncommon idiopathic disorder predominantly affecting young, otherwise healthy women. Rare familial cases reveal a genetic predisposition to disease. The aim of this study was to identify a novel susceptibility gene for SCAD.

Methods:
Whole-exome sequencing was performed in a family comprised of 3 affected individuals and filtered to identify rare, predicted deleterious, segregating variants. Immunohistochemical staining was used to evaluate protein expression of the identified candidate gene. The prevalence and spectrum of rare (<0.1%) variants within binding domains was determined by next-generation sequencing or denaturing high-performance liquid chromatography in a sporadic SCAD cohort of 675 unrelated individuals.

Results:

We identified a rare heterozygous missense variant within a highly conserved β-integrin–binding domain of
TLN1
segregating with familial SCAD.
TLN1
encodes talin 1—a large cytoplasmic protein of the integrin adhesion complex that links the actin cytoskeleton and extracellular matrix. Consistent with high mRNA expression in arterial tissues, robust immunohistochemical staining of talin 1 was demonstrated in coronary arteries. Nine additional rare heterozygous missense variants in
TLN1
were identified in 10 sporadic cases. Incomplete penetrance, suggesting genetic or environmental modifiers of this episodic disorder, was evident in the familial case and 5 individuals with sporadic SCAD from whom parental DNA was available.

Conclusions:

Our findings reveal
TLN1
as a disease-associated gene in familial and sporadic SCAD and, together with abnormal vascular phenotypes reported in animal models of talin 1 disruption, implicate impaired structural integrity of the coronary artery cytoskeleton in SCAD susceptibility.
Siponimod (BAF312) Treatment Reduces Brain Infiltration but Not Lesion Volume in Middle-Aged Mice in Experimental Stroke
Authors: Vogelgesang Antje , Domanska Grazyna , Ruhnau Johanna , Dressel Alexander , Kirsch Michael , Schulze Juliane 
Published: April 2019

Background and Purpose—
The contribution of neuroinflammation and, in particular, the infiltration of the brain by lymphocytes is increasingly recognized as a substantial pathophysiological mechanism after stroke. The interaction of lymphocytes with endothelial cells and platelets, termed thromboinflammation, fosters microvascular dysfunction and secondary infarct growth. Siponimod is an S1PR (sphingosine-1-phosphate receptor) modulator, which blocks the egress of lymphocytes from lymphoid organs and has demonstrated beneficial effects in multiple sclerosis treatment. We investigated the effect of treatment with siponimod on stroke outcome in a mouse model of cerebral ischemia.

Methods—
Transient middle cerebral artery occlusion was induced in middle-aged wild-type mice. Animals were either treated with siponimod (3 mg/kg; intraperitoneal) or vehicle for 6 days. Stroke outcome was assessed by magnetic resonance imaging (spleen volume: prestroke, day 3, and day 7; infarct volume: days 1, 3, and 7) and behavioral tests (prestroke, day 2, and day 6). Immune cells of the peripheral blood and brain-infiltrating cells ipsilateral and contralateral were analyzed by VETScan and by flow cytometry.

Results—
Siponimod significantly induced lymphopenia on day 7 after transient middle cerebral artery occlusion and reduced T-lymphocyte accumulation in the central nervous system. No effect was detected for lesion size.

Conclusions—
For siponimod administered at 3 mg/kg in transient middle cerebral artery occlusion mouse model, our findings do not provide preclinical evidence for the use of S1PR1/5 modulators as neuroprotectant in stroke therapy.
Five-Year Risk of Major Ischemic and Hemorrhagic Events After Intracerebral Hemorrhage
Authors: Casolla Barbara , Moulin Solène , Kyheng Maéva , Hénon Hilde , Labreuche Julien , Leys Didier , Bauters Christophe , Cordonnier Charlotte 
Published: April 2019

Background and Purpose—
We aimed to determine incidences and predictors of major vascular events in intracerebral hemorrhage (ICH) survivors.

Methods—
We did a prospective observational cohort study in patients with spontaneous ICH from the Prognosis of Intracerebral Hemorrhage cohort in Lille, France. We studied incidences and predictors of long-term vascular events (cerebral and extracerebral, ischemic and hemorrhagic) in patients alive at 30 days with a prespecified subgroup analysis according to ICH location. We performed multivariable analyses (competing risk analyses, with death during follow-up as a competing event).

Results—
From the 560 patients with spontaneous ICH enrolled between November 2004 and March 2009, we included 310 patients (median age, 70 years). Eighty-two patients presented at least 1 major vascular event leading to an incidence rate of 20.0% (95% CI, 15.7–24.7) at 5 years after ICH. In the overall cohort, ischemic events were more frequent than hemorrhagic events. However, the incidence strikingly differed according to ICH location: deep ICH was associated with future ischemic events (subhazard ratio, 1.85; 95% CI, 1.01–3.40), whereas lobar ICH with hemorrhagic events (subhazard ratio, 2.38; 95% CI, 1.17–4.86). In deep ICH, the incidence of ischemic events at 5 years was 6× higher than the incidence of hemorrhagic events.

Conclusions—
ICH survivors are at high risk of both cerebral and extracerebral vascular events. The ischemic or hemorrhagic risk profile varies according to the index ICH location with a stronger ischemic risk in deep ICH. Secondary prevention, tailored on ICH location, should target not only cerebral recurrences but also extracerebral vascular events.
Subarachnoid and Subdural Hemorrhages in Lobar Intracerebral Hemorrhage Associated With Cerebral Amyloid Angiopathy
Authors: Viguier Alain , Raposo Nicolas , Patsoura Sofia , Calviere Lionel , Albucher Jean François , Ruidavets Jean Bernard , Chollet François , Cognard Christophe , Olivot Jean Marc , Bonneville Fabrice 
Published: April 2019

Background and Purpose—
Identifying underlying cerebral amyloid angiopathy (CAA) in patients with intracerebral hemorrhage (ICH) has important clinical implication. Convexity subarachnoid hemorrhage (cSAH) and subdural hemorrhage (SDH) are computed tomography features of CAA-related ICH. We explored whether cSAH and SDH could be additional magnetic resonance imaging markers of CAA in lobar ICH survivors.

Methods—
We analyzed data from consecutive patients with acute lobar ICH associated with CAA (CAA-ICH) or not attributed to CAA (non–CAA-ICH). Magnetic resonance imaging scans were analyzed for cSAH, SDH, and markers of small vessel disease. The associations of cSAH and SDH with the diagnosis of probable CAA based on the modified Boston criteria were explored using multivariable models.

Results—

We included 165 patients with acute lobar ICH (mean age 70±13 years): 72 patients with CAA-ICH and 93 with non–CAA-ICH. Patients with CAA-ICH had a higher prevalence of cSAH (73.6% versus 39.8%;
P
<0.001) and SDH (37.5% versus 21.5%;
P
=0.02) than non–CAA-ICH. In multivariate logistic regression analysis, the presence of cSAH was independently associated with CAA-ICH (odds ratio, 2.97; 95% CI, 1.26–6.99;
P
=0.013), whereas there was no association between SDH and CAA-ICH.

Conclusions—
Among survivors of acute lobar ICH, the presence of cSAH is associated with the magnetic resonance imaging–based diagnosis of CAA. Further studies should investigate whether cSAH help improve the sensitivity of magnetic resonance imaging for in vivo diagnosis of CAA.
Learning Multilingual Word Embeddings in Latent Metric Space: A Geometric Approach
Authors: Jawanpuria Pratik , Balgovind Arjun , Kunchukuttan Anoop , Mishra Bamdev 
Published: April 2019

Abstract
We propose a novel geometric approach for learning bilingual mappings given monolingual embeddings and a bilingual dictionary. Our approach decouples the source-to-target language transformation into (a) language-specific rotations on the original embeddings to align them in a common, latent space, and (b) a language-independent similarity metric in this common space to better model the similarity between the embeddings. Overall, we pose the bilingual mapping problem as a classification problem on smooth Riemannian manifolds. Empirically, our approach outperforms previous approaches on the bilingual lexicon induction and cross-lingual word similarity tasks.
We next generalize our framework to represent multiple languages in a common latent space. Language-specific rotations for all the languages and a common similarity metric in the latent space are learned jointly from bilingual dictionaries for multiple language pairs. We illustrate the effectiveness of joint learning for multiple languages in an indirect word translation setting.