bluuebunny/crossref_metadata_2025_split huggingface dataset:
External Validation of Generic and Cancer-Specific Risk Stratification Criteria for Predicting 30-Day Mortality in Patients Presenting with Pulmonary Embolism and Active Cancer
Authors: Caranfa Jonathan T , Weeda Erin R , Coleman Craig I , Zeichner Simon B. , Kohn Christine G 
Published: October 2019

Abstract
Introduction: The Hestia criteria has been established as a highly sensitive prognostic tool used by clinicians to identify newly diagnosed pulmonary embolism (PE) patients from the general population at low vs. high risk of early (30 day) mortality. Font et al. applied similar risk stratification criteria in a population restricted to PE patients with cancer. We evaluated the performance of the generic Hestia tool and cancer-specific criteria by Font et al. for predicting 30-day post-PE mortality in patients with active cancer.
Methods: We identified consecutive, adult, objectively confirmed PE patients with active cancer presenting to the emergency department at our institution from 11/2010-1/2014. We calculated the proportion of patients categorized as low-risk by each set of criteria and determined the accuracy of the criteria for predicting 30-day all-cause mortality. Mortality was determined through Social Security Death Index searches.
Results: A total of 124 patients with PE and active cancer (mean age 66.2 years, 46.0% with concurrent deep vein thrombosis, 49.2% with metastatic disease and 46.8%, 16.9% and 10.4% receiving chemotherapy, radiation or both, respectively) were included. Mortality at 30-days occurred in 25 (20.2%) patients. The Hestia tool had a sensitivity of 100% but classified <19% of patients as low-risk; while criteria developed by Font et al. had a sensitivity of 88.0% and classified 41.1% of patients as low-risk (Table). The most common reason patients were classified as high-risk by Hestia but not the criteria from Font et al. was the requirement for oxygen (O2) therapy to maintain an O2 saturation >90% for >24 hours (n=19).
Conclusion: In this external validation study, both the generic Hestia tool and cancer-specific Font et al. risk stratification criteria displayed acceptable sensitivity. Compared to Hestia, the Font et al. criteria classified two times as many patients as low-risk. Larger, prospective studies are needed to confirm our results.

Disclosures
Coleman: Janssen Pharmaceuticals: Consultancy, Research Funding; Bayer Pharmaceuticals AG: Consultancy, Research Funding; Boehringer-Ingelheim Pharmaceuticals, inc.: Consultancy, Research Funding.
Desiderosmia (Craving of Olfaction): A Novel Symptom Associated with Iron Deficiency Anemia
Authors: Hansen Bryar , Ravindran Aishwarya , Bottner Wayne A. , Cole Craig E. , Farnen John P. , Go Ronald S. 
Published: October 2019

Abstract
BACKGROUND:In recent years,we saw four patients with iron deficiency anemia (IDA) in our clinical practices who developed a compulsive craving for certain odors including rubber tires, gasoline, Pine-Sol® (a popular household alcohol ethoxylate-based cleaning agent), and "musty odor of the basement." Such behavior resolved after treatment of IDA, and recurred in a patient whose IDA relapsed. This resembled pica, a craving to eat non-nutritive items, which is commonly associated with IDA. Because we had never heard of or read about this phenomenon, we reviewed the English medical literature and World Wide Web to determine if such experience had been previously reported.
METHODS: We searched the PubMed, Google, and Google Scholar to find publications, reports, presentations, or testimonies of individual in online blogs using a combination of search terms including "nasal, olfactory, smell, craving, iron deficiency, and anemia."
RESULTS: We found no scientific publication, report, or presentation similar to our experience in PubMed and Google Scholar. However, using Google search engine, we found several testimonies of individuals in online blog posts (mostly at babycenter.com and medhelp.org), several of which were pregnancy blogs that reported these peculiar symptoms. Individuals were reporting powerful cravings of olfaction, frequently being overtaken by a desire to smell certain odors. The types of substances for which they craved and their associated medical conditions (when reported) are summarized in the Table.
CONCLUSIONS:These preliminary findings and testimonies give suggestive evidence that a condition, entirely separate from pica, exists in certain patients suffering from IDA or during pregnancy. For this, we propose the name, desiderosmia, derived from the Latin word "desiderare" for desire and the Greek word "osme" for smell. In naming this condition, we hope to inspire further investigation, and hopefully shed some light for patients who suffer from this newly described olfactory symptom.
Table Reports of smell cravings and associated medical conditions found in online blogs Table. Reports of smell cravings and associated medical conditions found in online blogs

Disclosures
No relevant conflicts of interest to declare.
Study of Dense Red Blood Cells in Children with Sickle Cell Disease
Authors: Coulon Basil , Di Liberto Gaetana , Wagner Ballon Orianne , Motterlini Roberto , Decrouy Xavier , Moutereau Stephane , Galacteros Frederic , Pirenne France , Bartolucci Pablo , Pondarré Corinne 
Published: October 2019

Abstract
Many Sickle cell disease (SCD) manifestations begin at an early age and with wide inter-individual variability. High Density Red Blood Cells (DRBCs) are a specific feature of SCD, assessed with phthalate density distribution method. RBCs dehydration causes higher polymerisation of hemoglobin S and sickling, and their percentage is associated to chronic organ damage and hemolysis in adults. The spleen is one of the first altered organs, with considered complete asplenia around the age of five.
We assessed the percentage of DRBCs (%DRBCs) in 50 children followed in the Créteil Paediatric Sickle Cell Referral Centre. Eligible patients had hemoglobin SS or Hemoglobin S-β0 thalassemia, without recent blood transfusion. Endpoints were the %DRBCs, its correlation with hemolytic parameters, with splenic function, with clinical manifestation.
In this first prospective study in pediatric population, %DRBCs was associated with age, with particular low rate before the age of four.
%DRBCs was significantly associated with enhanced haemolysis: higher total bilirubin, higher reticulocytes count, and lower hemoglobin. The results concerning LDH and ASAT were more questionable. A higher %DRBCs was associated with a lower hemoglobin F percentage.
The percentage of Pitted cells, reflecting spleen function, was correlated with %DRBCs in a univariate analysis.
There was no association between %DRBCs and vaso-occlusive symptoms, as expected. No statistical correlation has been found between intracranial velocity and %DRBCs. Among the five patients suffering from chronic complications related to hemolysis (kidney disease, priapism), 4 had high %DRBCs.
Thus, DRBCs appearance seems to be related to the impairment of the spleen function. As in SCD adults, anemia and hemolytic markers are associated with high %DRBCs. Longitudinal analysis, with DRBC measurements before any treatment intensification, in a larger population, will be the key to evaluate the prognostic value of DRBCs for organ damage.

Disclosures
No relevant conflicts of interest to declare.
Pedigree Gene Investigation and Parameters of NK Cell Activity, CD107a Degranulation Amd HLH Related Defective Protein Play Significant Role in the Diagnosis of Primary HLH
Authors: Zhang Jia , Wang Zhao 
Published: October 2019

Abstract
Abstract This study aims to evaluate the significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary HLH and explore their correlation. Twelve Chinese families of primary HLH with mutations in PRF1, UNC13D, LYST, RAB27A, SH2D1A, BIRC4 were recruited and conducted pedigree investigation, including family genetic screening, NK cell activity, CD107a degranulation and expression of HLH related defective protein. Ten patients were identified with homozygous, compound heterozygous, or hemizygous mutations in PRF1, UNC13D, RAB27A, SH2D1A and BIRC4, including one case of homozygous mutation (c.1349C>T:p.T450M) and four cases of compound heterozygous mutations (frameshift deletion c.65delC:p.P22fs and c.G503A:p.S168N; c.1168C>Tp.R390X and c.1349C>T:p.T450M; frameshift mutation c.1090_1091delCT:p.T364fsX93 and c.1349C>T:p.T450M; non-frameshift deletions c.1083_1094del:p.361_365del and c.T172C :p.S58P) in PRF1, one case of homozygous mutation (c.G2588A:p.G863D) and one compound heterozygous (c.C640T:p.R214X and c.G407A:p.C136Y) in UNC13D, one case of homozygous mutation (c.C244T:p.R82C) in RAB27A, and two male cases of hemizygous mutations in SH2D1A(c.32T>G:p.I11S) and BIRC4(c.G592A:p.V198M). Meanwhile, two patients were identified mutations in two or three different gene, including a male with a hemizygous mutation in SH2D1A(c.7G>T:p.A3S) and a heterozygous mutation(c.127C>A: p.L43M) in PRF1, and a female with three hemizygous mutations respectively in UNC13D(c.G680A:p.R227H), LYST(c.A8368C:p.K2790Q) and BIRC4(c.C962G:p.A321G).The primary HLH patients and their family members presented different levels of decreased NK cell activity. Individuals who were found mutations in PRF1, SH2D1A and BIRC4 showed low expression of perforin, SAP and XIAP. And the patients with homozygous and compound heterozygous mutations in UNC13D and RAB27A showed significant reducing of cytotoxic degranulation function and their family members presented normal or different levels of decreased CD107a. The patient with combination defects involving two genes(UNC13D and LYST) in the degranulation pathway showed decreased of CD107a degranulation which implied a digenic inheritance and diagnosed primary HLH. Pedigree genetic screening and rapid detection of immunological parameters play an important role in the diagnosis of primary HLH and demonstrate good consistency.

Disclosures
No relevant conflicts of interest to declare.
Increased Extracellular Nucleosome Levels and Microparticles in Atrial Fibrillation Patients Compared to the Age-Matched Normal Population
Authors: Hoppensteadt Debra , Jabati Sallu , Phan Trung , Liles Jeffrey , Rowe Timothy , Syed Mushabar , Fareed Jawed 
Published: October 2019

Abstract
Introduction : Atrial fibrillation (AF) is currently the most common cardiac arrhythmia encountered in clinical practice and a major cause of morbidity and mortality among adults. It is estimated that atrial fibrillation affects approximately 2.7 million people in the United States. Extracellular plasma nucleosomes (PNs) are complexes of DNA and histones that are released during cell death. Histones have been shown to function as DAMPs when they are translocated from the nucleus to the extracellular space. It is hypothesized that these extracellular nucleosomes contribute to the observed hypercoagulable state and embolic complications in AF.
Methods : The concentration of PNs in 48 plasma samples of atrial fibrillation patients and 38 aged-matched controls were measured using the Cell Death Detection ELISA PLUS assay (Roche Diagnostics, Mannheim, Germany) and functional microparticle levels were measured using an annexin binding method (Hyphen Biomedical, Paris, France).
Results : When comparing the concentration of nucleosomes in plasma, the atrial fibrillation patients (306.1 ± 328.86 μg/mL) had much higher levels than the aged-matched controls (177.9 ± 146.7 μg/mL), (p = 0.0015). Functional microparticles were also markedly elevated in the AF patients (18.6 ± 4.1 nM) in comparison to the aged-matched controls (4.6 ± 3.1 nM), (p=0.001). A significant correlation was observed between the PN's and microparticles, (p < 0.05).
Conclusion : Both the microparticles and PNs were elevated in atrial fibrillation when compared to aged-matched controls, suggesting increased cell death resulting in the generation of these biomarkers. Extracellular nucleosomes function as DAMPs by binding to receptors and triggering the activation of multiple signal pathways which may contribute to the elevation of microparticles. Due to the involvement of inflammation and thrombosis in the pathology of atrial fibrillation, the simultaneously increased circulating nucleosome and microparticle levels in patients with AF implies their role in the pathogenesis of this syndrome.

Disclosures
No relevant conflicts of interest to declare.
Safety and Efficacy of Thrombopoietin Receptor Agonists in Patients with Previously Treated Chronic Immune Thrombocytopenia: A Systematic Review and Meta-Analysis
Authors: Yamada Yuji , Fujii Takeo , Cromwell Caroline , Shapira Ilan 
Published: October 2019

Abstract
Background: The current American Society of Hematology guideline recommends the use of thrombopoietin receptor agonists, eltrombopag or romiplostim as one of the second-line therapies for chronic immune thrombocytopenia (ITP). The efficacy and safety of those drugs have been tested in several clinical trials. However, the safety profile was not consistent throughout trials and is not yet well understood. We herein conducted a meta-analysis of randomized control trials to compare the safety and efficacy of thrombopoietin receptor agonists; eltrombopag and romiplostim versus placebo in patients with previously treated chronic ITP. Our primary outcome was drug-related adverse events greater than CTCAE grade 3.
Methods: We performed a literature search in MEDLINE, EMBASE, Cochrane library, and the American Society of Hematology website up to September, 2015 by two independent authors according to PRISMA guideline. We included only randomized clinical trials comparing eltrombopag or romiplostim versus placebo. Random-effects model was used to estimate pooled odds ratio (OR) with 95% confidence interval (CI).
Results: A total of eight trials involving 834 participants were included in the analysis. There was no significant difference of grade 3 or higher adverse events between placebo and treatment group (OR=1.01, 95% CI=0.57-1.78). Thromboembolism (OR=0.59, 95% CI=0.20-1.73), elevated ALT (OR=0.68, 95% CI=0.26-1.74), headache (OR=1.26, 95% CI=0.90-1.78), nausea (OR=0.82, 95% CI=0.43-1.55), or fatigue (OR=1.13, 95% CI=0.65-1.91) did not show a significant difference between groups, either. Clinical response, which is defined as platelets ≥50,000/μL at least once on treatment was significantly better in treatment group than in placebo group (OR=0.10, 95% CI=0.07-0.15). Bleeding symptoms (WHO Grades 1-4) were significantly more frequent in the placebo group (OR=1.60, 95% CI=1.14-2.24) during treatment.
Conclusions: Although several studies have suggested clinically significant treatment-related adverse events, such as thromboembolism, this meta-analysis showed that thrombopoietin receptor agonists are safe, well-tolerated, and effective in patients with previously treated chronic ITP.

Disclosures
No relevant conflicts of interest to declare.
Identification of Phenotypic Modulation of Angiotensin-(1-7) in Thrombin-Stimulated Human Aortic Endothelial Cells from iTRAQ Quantitative Proteomics
Authors: Peng Ching-Tien , Wu Kang-Hsi 
Published: October 2019

Abstract
Introduction:
The primary effector of renin-angiotensin system (RAS) system is angiotensin II. RAS activation causes many detrimental effects via AT1 receptor. Angiotensin-(1-7)/ angiotensin-converting enzyme 2/Mas axis is a newly identified counter-regulatory pathway against RAS system. Thrombin plays a critical role in coagulation and inflammation processes in vascular endothelium. Although RAS activation is associated with thrombotic complications, it is unknown whether angiotensin-(1-7) can modulate the pleotropic effects of thrombin. In this study, we investigate the proteomic changes of angiotensin-(1-7) effects on thrombin-stimulated human aortic endothelial cells (HAECs).
Materials and methods:
HAECs were pretreated with 10-7M anigotenion-(1-7) for 1 h and stimulated with 2 units/mL thrombin for additional 5 h. Their proteomes were investigated using isobaric tags for the relative and absolute quantification (iTRAQ) and MetaCoreTMsoftware.
Results:
A total of 653, 717 and 801 proteins were identified in triplicated iTRAQ analyses. MetaCoreTM pathway analysis identified that iTRAQ data showed the consistent pathway alterations (70%) in triplicated experiments. The same altered pathways included "Cytoskeleton remodeling_Cytoskeleton remodeling", "Cell adhesion_Integrin-mediated cell adhesion and migration", "Cell adhesion_Chemokines and adhesion" , "Cytoskeleton remodeling _ Regulation of actin cytoskeleton by Rho GTPases", "LRRK2 in neurons in Parkinson's disease", "Cytoskeleton remodeling_Fibronectin-binding integrins in cell motility", "Cytoskeleton remodeling _TGF, WNT and cytoskeletal remodeling" were among the top 10 statistically significant pathways. Additional experiments validated the phenotypes of angiotensin-(1-7) effects in thrombin-stimulated HAECs.
Conclusions:
Several regulatory pathways are altered by angiotensin-(1-7) in thrombin-stimulated HAECs, with cytoskeleton remodeling, cell adhesion and cell migration (motility) as the dominant altered phenotypes.

Disclosures
No relevant conflicts of interest to declare.
Fluorescent Cell Barcoding As New Flow Cytometric Technique for Multiplexed Phenotyping and Signaling Profiling in Hematologic Patients
Authors: Giudice Valentina , Feng Xingmin , Kajigaya Sachiko , Biancotto Angelique , Young Neal S. 
Published: October 2019

Abstract
Fluorescent cell barcoding (FCB) is a high-throughput multiplexing technique, in which samples from one or more donors can be combined, minimizing staining variability, antibody consumption, and decreasing sample volumes needed. In this study, we optimized FCB technique for routine application in immunophenotyping, phosphoFlow, and intracellular cytokine detection. Human peripheral blood mononuclear cells (PBMCs) from healthy controls and patients were used for optimization, and CBD450 and CBD500, Pacific Orange succinimidyl ester, DyLight 350, and DyLight 800 were tested for barcoding 6 to 36 samples. Working concentrations ranging from 0 to 125 µg/mL were tested, and viability dye staining was also optimized to increase data robustness. We first measured fluorescence intensity (MFIs) of six serial dilutions (0, 0.75, 3.25, 12.5, 62.5 and 125 µg/mL) and the difference in intensity separating them. Second, a 3x3 matrix was prepared using three concentrations of two different dyes, and PMBCs were barcoded with nine different combinations of FCB dye concentrations. When gated with the dyes, nine lymphocyte populations were detected. A 4x(3x3) matrix was also designed using three different FCB dyes (CBD450, DyLight 800, and Pacific Orange) at various concentrations to barcode 36 samples simultaneously. Thus, each lymphocyte population was clearly identified. The separation of each population or purity of deconvolution is based on the distance between MFIs and CVs. When we calculated the purity of deconvolution in our experiments, human PBMCs displayed CVs of 10 - 25%. When MFIs were separated by 2-fold increase, barcoded populations could be identified with a good resolution, higher when MFIs were separated by 3- or more fold increase. The use of viability dyes as LIVE/DEAD Fixable Aqua viability dye together with the FCB showed increase of data robustness due to exclusion of dead cells from gating strategy. In combination with viability dye, we successfully performed a six-color phosphoFlow and a simple four-color stainings using the same FCB dye combinations and cytometer voltages, and also combining one healthy control and two different patient samples. Our methods using FCB dye alone and/or in combination with antibody staining should be useful to efficiently perform multiplex drug screening and lymphocyte characterization. FCB minimizes batches and technical variations, and also increases data robustness, thus improving the immune phenotyping of patients.

Disclosures
Young: GSK/Novartis: Research Funding.
Molecular Characterization of Long Non-Coding RNA CASC15 in Leukemogenesis
Authors: Contreras Jorge R. , Fernando Thilini , Tran Tiffany M , Zampini Matteo , Rodriguez-Malave Norma Iris , Palanichamy Jayanth Kumar , Gajeton Jasmine , Ung Nolan , Casero David , Basso Giuseppe , Pigazzi Martina , Rao Dinesh S. 
Published: October 2019

Abstract
High throughput transcriptome sequencing has uncovered a previously uncharacterized layer of gene regulation by long non-coding RNAs (lncRNAs). LncRNAs are characterized by capped, polyadenylated, and spliced transcripts that lack an open reading frame. Despite the similarities in their genetic organization, they play variety of roles at the cellular level, including regulation of transcription and translation, leading to alterations in gene expression. One of these functions is the regulation of expression of chromosomally adjacent genes. Here, we examined the function of the lncRNA CASC15 that was originally discovered as being dysregulated in in ETV6-RUNX1-translocated B-acute lymphoblastic leukemia. Enforced expression of CASC15 in hematopoietic stem and progenitor cells led to a myeloid bias in development with an overall decrease in engraftment and colony formation. Conversely, using a CRISPR-based approach, CASC15 deletion skewed hematopoietic cell progenitors towards a B cell fate. CASC15 was also demonstrated to regulate cellular survival, proliferation, and the expression of its chromosomally adjacent gene, SOX4. Differentially regulated genes following CASC15 knockdown in cell lines were enrichment for predicted transcriptional targets of the Yin and Yang-1 (YY1) transcription factor. To further characterize this, we queried a functional relationship between YY1 and CASC15. Interestingly, we found that YY1 interacts with CASC15, and that CASC15 enhanced YY1-mediated transcription at the SOX4 promoter. Together these studies represent some of the first functional characterizations of lncRNAs in leukemia and highlight the importance of non-coding regulatory mechanisms in malignant hematopoiesis.

Disclosures
No relevant conflicts of interest to declare.