tbuckley/cabot-search huggingface dataset:
High-affinity peptide ligand LXY30 for targeting α3β1 integrin in non-small cell lung cancer
Authors: Wenwu Xiao, Weijie Ma, Sixi Wei, Qianping Li, Ruiwu Liu, Randy P. Carney, Kevin Yang, Joyce Lee, Alan Nyugen, Ken Y. Yoneda, Kit S. Lam, Tianhong Li
Journal: Journal of Hematology & Oncology (2019)

α3β1 integrin is a promising cancer biomarker and drug target. We previously identified a 9-amino-acid cyclic peptide LXY30 for detecting α3β1 integrin on the surface of live tumor cells. This study was undertaken to characterize LXY30 in the detection, cellular function, imaging, and targeted delivery of in vitro and in vivo non-small cell lung cancer (NSCLC) models. The whole-cell binding assay was performed by incubating NSCLC cells, extracellular vesicles (EVs), and peripheral blood mononuclear cells (PBMCs) with TentaGel resin beads coated with LXY30. In this study, we defined the nanosize EVs as exosomes, which were characterized by flow cytometry, transmission electron microscopy, dynamic light scattering, and Western blots. The function of LXY30 was determined by modulating the epidermal growth factor receptor (EGFR) signaling pathway by growth inhibition and Western blots. For in vivo biodistribution, mice bearing subcutaneous and intracranial NSCLC xenograft tumors were administrated intraveneously with LXY30-biotin/streptavidin-Cy5.5 complex and then analyzed for in vivo and ex vivo optical imaging and histopathology. We showed that LXY30 specifically and sensitively detected α3β1 integrin-expressing NSCLC cells and tumor-derived exosomes. Tumor DNA isolated from LXY30-enriched plasma exosomes might be used to detect driver oncogenic mutations in patients with metastatic NSCLC. LXY30 only enriches tumor cells but not neutrophils, macrophages, or monocytes in the malignant pleural effusion of NSCLC patients for detecting genomic alterations by next-generation sequencing. LXY30 detected increased α3β1 integrin expression on the EGFR-mutant NSCLC cells with acquired resistance to erlotinib compared to parental erlotinib-sensitive EGFR-mutant NSCLC cells. We further showed that LXY30 modulated the EGFR signaling pathway independently from another peptide ligand LXW64 targeting αvβ3 integrin in erlotinib-resistant, EGFR-mutant H1975 cells. Analysis of The Cancer Genome Atlas (TCGA) revealed high α3 integrin expression was associated with poor prognosis in lung squamous cell carcinoma. LXY30-biotin/streptavidin-Cy5.5 complex had higher uptakes in the subcutaneous and intracranial xenografts of various α3β1 integrin-expressing lung adenocarcinoma and patient-derived lung squamous cell carcinoma xenografts while sparing the surrounding normal tissues. LXY30 is a promising peptide for the cancer diagnosis and in vivo targeted delivery of imaging agents and cancer drugs in NSCLC, independent of histology and tumor genotype.
Brain-wide Organization of Neuronal Activity and Convergent Sensorimotor Transformations in Larval Zebrafish
Authors: Xiuye Chen, Yu Mu, Yu Hu, Aaron T. Kuan, Maxim Nikitchenko, Owen Randlett, Alex B. Chen, Jeffery P. Gavornik, Haim Sompolinsky, Florian Engert, Misha B. Ahrens
Journal: Neuron (2018)
PB1735 POSTDIAGNOSIS SMOKING WITH RISK OF ALL‐CAUSE AND CANCER MORTALITY AMONG LEUKEMIA SURVIVORS: A PROSPECTIVE COHORT STUDY
Authors: H. Tao
Journal: HemaSphere (2019)

Background: Smoking is associated with higher leukemia risk, but smoking and risk of all‐cause and cancer mortality among leukemia survivors is unclear. Aims: To evaluate more thoroughly the risk of all‐cause and cancer mortality between cigarette smoking and leukemia Methods: We identified 316 subjects who were diagnosed with leukemia from National Health Interview Survey participants≥18 years of age from 13 cross‐sectional waves conducted during 1997 to 2009 (linked to mortality data in 2015) at baseline. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of all‐cause and cancer mortality caused by smoking exposure. Results: After a median follow‐up of 13 years, 141 (50%) were alive and 141 (50%) died due to all‐cause mortality during the follow‐up. Of all the patients who died, 70 (50%) died due to cancer and 20 (14%) died due to cardiovascular disease (CVD). Compared to never smokers, former smoking could increase the risk of cancer mortality (HR, 1.95; 95%CI, 1.04‐3.68), especially for those who quit smoking recently (HR, 2.59; 95%CI, 1.17‐5.74). For cancer mortality, dose relationship was obvious among former smokers who had quit more recently than for those who had quit earlier with a “U” shaped curve (P trend &lt; 0.05). Current smokers who smoke less than 10 cigarettes per day had higher risk of cancer mortality (HR, 3.72; 95%CI, 1.01‐13.73) than never smoking when patients with a history of CVD were excluded. Summary/Conclusion: This study adds to the existing evidence that cigarette smoking is associated with higher cancer mortality among leukemia patients, especially for former smokers. image
Vascular Positron Emission Tomography and Restenosis in Symptomatic Peripheral Arterial Disease
Authors: Mohammed M. Chowdhury, Jason M. Tarkin, Mazen S. Albaghdadi, Nicholas R. Evans, Elizabeth P.V. Le, Thomas B. Berrett, Umar Sadat, Francis R. Joshi, Elizabeth A. Warburton, John R. Buscombe, Paul D. Hayes, Marc R. Dweck, David E. Newby, James H.F. Rudd, Patrick A. Coughlin
Journal: JACC. Cardiovascular imaging (2019)

This study determined whether in vivo positron emission tomography (PET) of arterial inflammation (18F-fluorodeoxyglucose [18F-FDG]) or microcalcification (18F-sodium fluoride [18F-NaF]) could predict restenosis following PTA. Restenosis following lower limb percutaneous transluminal angioplasty (PTA) is common, unpredictable, and challenging to treat. Currently, it is impossible to predict which patient will suffer from restenosis following angioplasty. In this prospective observational cohort study, 50 patients with symptomatic peripheral arterial disease underwent 18F-FDG and 18F-NaF PET/computed tomography (CT) imaging of the superficial femoral artery before and 6 weeks after angioplasty. The primary outcome was arterial restenosis at 12 months. Forty subjects completed the study protocol with 14 patients (35%) reaching the primary outcome of restenosis. The baseline activities of femoral arterial inflammation (18F-FDG tissue-to-background ratio [TBR] 2.43 [interquartile range (IQR): 2.29 to 2.61] vs. 1.63 [IQR: 1.52 to 1.78]; p < 0.001) and microcalcification (18F-NaF TBR 2.61 [IQR: 2.50 to 2.77] vs. 1.69 [IQR: 1.54 to 1.77]; p < 0.001) were higher in patients who developed restenosis. The predictive value of both 18F-FDG (cut-off TBRmax value of 1.98) and 18F-NaF (cut-off TBRmax value of 2.11) uptake demonstrated excellent discrimination in predicting 1-year restenosis (Kaplan Meier estimator, log-rank p < 0.001). Baseline and persistent femoral arterial inflammation and micro-calcification are associated with restenosis following lower limb PTA. For the first time, we describe a method of identifying complex metabolically active plaques and patients at risk of restenosis that has the potential to select patients for intervention and to serve as a biomarker to test novel interventions to prevent restenosis.
The Amount of Nitrogen Used for Photosynthesis Modulates Molecular Evolution in Plants
Authors: Steven Kelly
Journal: Molecular Biology and Evolution (2018)

Genome and transcript sequences are composed of long strings of nucleotide monomers (A, C, G, and T/U) that require different quantities of nitrogen atoms for biosynthesis. Here, it is shown that the strength of selection acting on transcript nitrogen content is influenced by the amount of nitrogen plants require to conduct photosynthesis. Specifically, plants that require more nitrogen to conduct photosynthesis experience stronger selection on transcript sequences to use synonymous codons that cost less nitrogen to biosynthesize. It is further shown that the strength of selection acting on transcript nitrogen cost constrains molecular sequence evolution such that genes experiencing stronger selection evolve at a slower rate. Together these findings reveal that the plant molecular clock is set by photosynthetic efficiency, and provide a mechanistic explanation for changes in plant speciation rates that occur concomitant with improvements in photosynthetic efficiency and changes in the environment such as light, temperature, and atmospheric CO2 concentration.
PS1199 SCREENING FOR HEREDITARY SPHEROCYTOSIS IN DAILY PRACTICE: WHICH IS THE BEST ALGORITHM USING ERYTHROCYTE AND RETICULOCYTE PARAMETERS?
Authors: A.‐S. Adam, B. Gulbis, F. Cotton
Journal: HemaSphere (2019)

Background: Hereditary spherocytosis (HS) is the most common inherited chronic haemolytic anemia in Northern Europe. Its prevalence is estimated to 1 in every 2000 births. The actual guidelines for the screening and diagnosis of HS are based on clinical and family histories, physical examination and laboratory findings. Additional parameters based on complete blood count (CBC) and reticulocyte parameters have been developed on haematology analyzers leading to many publications about their effectiveness as HS screening tool. Aims: We evaluated and compared the effectiveness of four published algorithms for the screening of HS using two haematology analyzers i.e. the UniCel DxH800 (DxH; Beckman‐Coulter, Miami, FL) and the XN‐9000 (XN; Sysmex, Kobe, Japan) and determined which algorithm could be the most suitable in our daily clinical practice. Methods: A total of 96 EDTA samples obtained for HS screening were analyzed prospectively on both haematology analyzers and a CBC with extended reticulocyte parameters were collected. These included 12 confirmed HS patients and 84 non‐HS patients. The diagnosis of HS was based on clinical and family histories, cryohaemolysis test, eosin‐5’‐maleimide (EMA) dye binding test, ektacytometry and identification of the defective protein. The specific reticulocyte parameters used on the DxH800 were mean reticulocyte volume (MRV), immature reticulocyte fraction (IRF) and mean sphered cell volume (MSCV), and on the XN‐9000 were hypohaemoglobinized erythrocytes (Hypo‐He), microcytic erythrocytes (MicroR) and IRF. For each algorithm, we established sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV). Results: The results are reported in Table 1 . The only algorithm that provided a sensitivity of 100% was the algorithm published by Lazarova et al. in 2014 using the DxH800. The three algorithms published based on the Sysmex parameters showed much lower performances than the one based on the DxH800 parameters i.e. out of the 96 patients with HS, between 2 to 6 patients were screened as negative for HS. Three of the published algorithms were evaluated on a previous XE model i.e. XE‐5000, mode of HS diagnosis is not always comparable as well as the amount of patients involved in the different studies. Table 1: Performance characteristics of the different algorithms (original stated performance characteristics) tested prospectively on 12 HS and 84 non‐HS patients. Summary/Conclusion: To screen for HS in the daily practice, the extended reticulocyte parameters provided by the Sysmex analyzers seem promising but the clinical cut‐offs on the XN‐9000 should be reevaluated on a larger number of patients. image
PS1515 PREMEDICATION WITH MONTELUKAST AND RUPATADINE DECREASES INFUSION TIME, RATE AND SEVERITY OF REACTIONS AND OVERALL COST OF RITUXIMAB ADMINISTRATION
Authors: R. Kotchetkov, J. McLean, L. Gerard, D. Nay, S. Hopkins
Journal: HemaSphere (2019)

Background: Rituximab is associated with frequent infusion reactions, which carry significant burden to both patients and health care practitioners. Standard pre‐medications (SP) do not prevent reactions sufficiently. Montelukast (M) and Rupatadine (R) are used for treatment of urticarial, allergic rhinitis, and may impact Rituximab infusion Aims: We assessed impact of addition of R, M and their combination (R+M) on Rituximab infusion/rate, rate/severity of reactions and administration cost Methods: Adult patients with lymphoproliferative disorders treated at our cancer center between Jan 2018 to Jan 2019 were evaluated with Rituximab‐containing regiments. Since the majority of reactions occur during the first infusion, our study was limited to the initial Rituximab treatment. Patients received either SP with diphenhydramine/acetaminophen and additional R, M or R+M combination. Comparative analysis of infusion time/rate, severity of infusion reactions, number of rescue medications and cost of Rituximab infusions among groups was performed using one‐way ANOVA with Tukey post‐hoc or chi‐square. The study was approved by our institutional ethics board Results: Patients received either: 1) standard premedications (SP); 2) SP + Rupatadine (R) 10 mg; 3) SP + Montelukast (M) 10 mg; or 4) both (SP+R+M). Patient characteristics and therapy are shown in Table 1. Compared to SP, the R, M and R+M groups had greater improvement in Rituximab delivery. Mean infusion time was 305 [range 235–441] min. in SP, 254 [105–390] in M, 265 [193–350] in R and 238 [196–342] in R+M groups, (p = 0.0001). Infusion reactions occurred in 92% in SP vs. 38, 45, 31% in M, R and R+M groups (p = 0.0001). Median reaction grade was 2 in SP, 1 (M), 0 (R and R+M). Median number of rescue medications was 3 [0–10] in SP vs 0 [0–7] in M, R and R+M groups. Cost of rescue medications (US$) was 41 [0–63] (SP), 11 [0–50] (M), 17 [0–63] (R), 7 [0–58] (R+M) groups (p &lt; 0.0001). Mean nursing cost (US$) per patient infusion was calculated as 269 [207–388] in SP vs 222 [92–343] (M), 233 [170–308] (R), 209 [174–301] (R+M) group. RCHOP, Rituximab/Cyclophosphamide/Doxorubicin/ Oncovin/Prednisone; BR, Bendamustine/Rituximab; FCR, Fludarabine/Cyclophosphamide/Rituximab image Summary/Conclusion: Addition of R, M and particularly R+M combination significantly improved Rituximab delivery, decreased the rate and severity of infusion reactions, and lowered the cost of Rituximab administration
FRI0282 STATINS REDUCE RELAPSE RATE IN TAKAYASU ARTERITIS
Authors: Oh Chan Kwon, Wook Jang Seo, Ji Seon Oh, Min-Chan Park, Seokchan Hong, Chang-Keun Lee, Bin Yoo, Yong-Gil Kim
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Takayasu arteritis (TAK) is a chronic inflammatory disease, mainly affecting aorta and its major branches. Despite treatment with glucocorticoid and adjunctive immunosuppressive agent, relapse is common. Considering the high relapse rate, it is important to identify additional medications that may help sustain remission. Statins, as having anti-inflammatory and immunomodulartory effects, may be one such possibility. <h3>Objectives:</h3> To investigate the effect of statins on relapse of Takayasu arteritis (TAK), which frequently occurs after achievement of remission. <h3>Methods:</h3> We conducted a retrospective study on TAK patients with active disease, diagnosed between 2012 and 2017. Relapse was defined as recurrence of active disease after achieving remission. Demographic and clinical parameters of patients who experienced relapse were compared to those who did not. To identify factors associated with relapse, multivariate Cox regression analysis with stepwise backward elimination was performed. Inverse probability of treatment weighting (IPTW)-adjusted analysis was used to evaluate the influence of statins on relapse. <h3>Results:</h3> Of the total 74 TAK patients, 40 (54.1%) patients received statins, whereas 34 (45.9%) patients did not. Relapse was observed in 36 (48.6%) patients of the total 74 TAK patients. Compared with patients who did not experience relapse, patients who experienced relapse were younger (44.5±13.5 years vs 34.1±12.6 years, p=0.001), had lower prevalence of hypertension (63.2% vs 38.9%, p=0.037), more commonly had carotidynia (7.9% vs 27.8%, p=0.025), had higher LDL-cholesterol (84.8±18.8 mg/dl vs 100.5±26.1 mg/dl, p=0.010), and were less commonly taking statins (71.1% vs 36.1%, p=0.003). These variables were included in multivariate Cox regression analysis. The use of statins was significantly associated with lower risk of relapse (adjusted hazard ratio 0.260, 95% confidence interval 0.120–0.563, p=0.001). Furthermore, IPTW-adjusted analysis confirmed that statin use was associated with a lower risk of relapse (IPTW-adjusted hazard ratio 0.153, 95% confidence interval 0.038–0.616, p=0.008). <h3>Conclusion:</h3> In TAK, statins can be beneficial in reducing relapse rate after achieving remission. Covariates: age (continuous), hypertension (yes/no), carotidynia (yes/no), LDL-cholesterol (continuous), and statin use (yes/no) <h3>Disclosure of Interests:</h3> None declared
AB1043 CLINICAL OUTCOMES OF ANTI-NUCLEAR ANTIBODY POSITIVENESS IN THE 0-18 AGE GROUP: SINGLE-CENTER REAL-WORLD EXPERIENCE
Authors: Nihal Sahin, Aysenur Pac Kisaarslan, Sumeyra Ozdemir Cicek, Neslihan Günay, AyŞe Seda Pinarbasi, Sibel Yel, İsmail Dursun, Muammer Hakan Poyrazoglu, Hüseyin KılıÇ, Ruhan DüŞünsel
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Anti-nuclear antibody (ANA) assay is important in the diagnosis of autoimmune diseases. However, it has a poor positive predictive value and is detected positive in 10% of general population. In this study, the children that ANA assay was performed in a tertiary pediatric clinic, was evaluated and was aimed to investigate the clinical outcomes in positives. <h3>Objectives</h3> In this study, the children that ANA assay was performed in a tertiary pediatric clinic, was evaluated and was aimed to investigate the clinical outcomes in positives. <h3>Methods</h3> 0-18 age group patients that ANA assay was requested in the various clinics of Erciyes University were included. The patients with positive ANA assay and access to hospital records were retrospectively examined. Patients with and without autoimmune disease were identified as group 1 and group 2, respectively. <h3>Results</h3> The number of patients who required ANA assay in pediatric clinics was 3812. There was a positive ANA assay in 1010 of these patients. The medical records of 909 patients were reached. There were 345 (38%) patients in group 1 and 564 (62%) in group 2. In group 1, female gender was higher compared to group 2 (p &lt;0.05). Musculoskeletal, hematologic, enterohepatic, and ocular findings as initial findings were significantly high in group 1 (p &lt;0.05). Pediatric Rheumatology, general pediatrics and pediatric neurology are the three clinics which the assay was requested most common. The patients who were examined in pediatric rheumatology, pediatric hematology-oncology, pediatric gastroenterology departments had a higher incidence of autoimmune disease (p &lt;0.05). In patients with autoimmune disease, ≥1/1000 ANA titer and homogenous staining were frequent (p &lt;0.05). <h3>Conclusion</h3> In our center, which is a tertiary health center, the autoimmune disease was not detected in most of the patients whose ANA assay was positive. The proportion of patients with autoimmune disease was low in most of the commonly requested departments. The ANA assay should be requested after the patient's clinical findings are evaluated in detail. <h3>References</h3> [1] Abeles AM, Abeles M. The clinical utility of a positive antinuclear antibody test result. Am J Med. 2013 Apr;126(4):342-8. doi: 10.1016/j.amjmed.2012.09.014. <h3>Disclosure of Interests</h3> None declared
Long-Term Results and Cost-Effectiveness of the Flagida-Lite Regimen in Elderly Patients with Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Authors: Almudena Cabero Martínez, Arancha Bermudez, Lucrecia Yañez, Andrés Insunza, Mercedes Araujo Colorado, Cristina Fernandez Martinez, Virginia Martinez Callejo, Teresa Bernal Del Castillo, Miriam Sánchez Escamilla, Mónica López Duarte, German Pérez Vázquez, Carmen Montes, Eulogio Conde, Maria Luisa Gutiérrez, Sara García Ávila, Mara Celis, Carlos Richard
Journal: Blood (2017)
PB2141 FEATURES OF THE DIRECT ANTIGLOBULIN TEST IN PATIENTS WITH MULTIPLE MYELOMA
Authors: E. Poponina, E. Butina, A. Yovdiy, G. Zaitseva, E. Vaneeva, I. Paramonov
Journal: HemaSphere (2019)

Background: The direct antiglobulin test (DAT) is used to detect autoantibodies that are fixed on the surface of red blood cells. A differentiated DAT allows to estimate the amount of absorbed immunoglobulins, describe their class and subclass, and detect the components of the complement on the membrane of red blood cells. This information helps to predict the risk of hemolysis and suggest the cause of anemia in a particular patient. Aims: To study the frequency and features of positive DAT in patients with multiple myeloma (MM). Methods The results of differentiated DAT were analyzed in 80 patients first hospitalized at the Institute clinic in 2018–2019 with the diagnosis MM. DAT was performed by gel method using anti‐IgG/C3d, DC‐Screening I and DAT IgG1/IgG3 cards (BioRad, USA). The frequency of positive DAT in patients was compared with the same in 200 healthy residents of the region–donors of blood components. Results: All blood donors were DAT‐negative. Autoantibodies to red blood cells were detected in 27.5% (22) of patients with MM (p &lt; 0.05). The intensity of the reaction (+) was observed in 50.0% (11) of patients with positive DAT, (++)–in 50.0% (11). DAT (++ + ), (++ + +) was not revealed. In the 100% of cases immunoglobulins G subclasses 2,4 were fixed on the surface of red blood cells, associated with a low risk of immune hemolysis. None of the patients was positive due to immunoglobulins classes A, M and complement components, which could contribute to the development of hemolytic complications. No clinical and laboratory signs of hemolysis were observed in the patients with positive DAT. Positive DAT was more frequently found in the group of patients with MM older than 60 years (48.0%), whereas in the group of patients younger than 60 years it was 18.2% (p &lt;0.05). When observing patients with MM with positive DAT, it was noted that in one third of patients receiving chemotherapy, the result of DAT becomes negative within 5 months. Autoantibodies can interact with test and donors red blood cells, being detected in an indirect antiglobulin test (IAT). Positive IAT was in 9.1% of patients with positive DAT and in 3.4% ‐ with negative. These patients had difficulties in donor's selection due to non‐specific agglutination. Summary/Conclusion: Even though positive DAT is often found in patients with MM, not in every case it should be regarded as a sign of autoimmune hemolysis. To correctly assess the risk of hemolysis, physicians should analyze other laboratory and clinical data. Positive DAT may be correlated with the difficulties of selection of the donor for such patient.