tbuckley/cabot-search huggingface dataset:
PB1955 REAL LIFE DATA OF NILOTINIB IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA RESISTANT OR INTOLERANT TO IMATINIB
Authors: A.T. Tuğlular, T. Elibol, T. Memiş, B. Aldağ, Ö. Dedeoğlu, T. Ercan, Y. İpek, F. Arıkan, A.F. Yılmaz, I. Kaygusuz Atagündüz, T. Toptaş
Journal: HemaSphere (2019)

Background: Nilotinib is an effective treatment option for patient's refractory or intolerant to imatinib and can be given as 2nd or 3rd line treatment in Turkey. Aims: In this retrospective study, we aim to demonstrate the frequency of side effects in patients on Nilotinib. Methods: We analyzed 253 patients with chronic myeloid leukemia (CML) followed by Marmara University Hematology Department. 53 of these patients (%20.9) were on Nilotinib in a period of their treatment. Clinical characteristics of the patients are given in table 1. Results: Median duration of patients on imatinib before switching to 2ndline TKI were 19 months (1‐96). Reasons for changing therapy were primary imatinib resistance in 13 patients (%24.5), loss of response in 31 patients (%58.4), drug intolerance in 8 patients (%15.1). In one patient cause of treatment change could not be found. Nilotinib was used as 2nd line TKI in 37 of patients (%69.8) and was used after Dasatinib as 3rd line TKI in 16 of patients (%30.2). Median dasatinib treatment duration before switching to nilotinib was 14 months. Reasons for switching to nilotinib therapy were primary resistance in 3 patients (%18.7), loss of response in 4 patients (%25) and drug intolerance in 8 patients (%50). Nilotinib dosage were 800 mg, median duration of treatment on Nilotinib was 28 months (1‐120). 31 patients (%58.5) are still on Nilotinib. Reasons for discontinuation were primary Nilotinib resistance in 3 patients (%5.6), loss of response in 6 patients (%11.3) and drug intolerance in 8 patients (%15.1). Five patients were lost to follow up. Adverse events were seen on 21 patients (%39.6) and 9 of these (%17) were serious adverse events (SAE). SAE were ischemic cerebrovascular disease in 1 patient, myocardial infarct (MI) in 3 patients, acute pancreatitis in 2 patients, treatment‐resistant nausea‐vomiting in 1 patient, treatment‐resistant rash in 1 patient and grade IV thrombocytopenia in 1 patient. Treatment duration of Nilotinib in patients with MI were 24, 45 and 50 months. Cardiovascular risk factors were not observed in 2 of 3 patients who had MI; other patient had diabetes and hypertension. Treatment duration of Nilotinib in patients with pancreatitis were 1 and 25 months. Summary/Conclusion: In conclusion, Nilotinib is a highly effective treatment for patients who are refractory or intolerant to imatinib or dasatinib. Patients should be followed carefully in terms of side effects such as MI, arterial occlusive diseases and pancreatitis. image
Loter: A Software Package to Infer Local Ancestry for a Wide Range of Species
Authors: Thomas Dias-Alves, Julien Mairal, Michael G B Blum
Journal: Molecular Biology and Evolution (2018)

Admixture between populations provides opportunity to study biological adaptation and phenotypic variation. Admixture studies rely on local ancestry inference for admixed individuals, which consists of computing at each locus the number of copies that originate from ancestral source populations. Existing software packages for local ancestry inference are tuned to provide accurate results on human data and recent admixture events. Here, we introduce Loter, an open-source software package that does not require any biological parameter besides haplotype data in order to make local ancestry inference available for a wide range of species. Using simulations, we compare the performance of Loter to HAPMIX, LAMP-LD, and RFMix. HAPMIX is the only software severely impacted by imperfect haplotype reconstruction. Loter is the less impacted software by increasing admixture time when considering simulated and admixed human genotypes. For simulations of admixed Populus genotypes, Loter and LAMP-LD are robust to increasing admixture times by contrast to RFMix. When comparing length of reconstructed and true ancestry tracts, Loter and LAMP-LD provide results whose accuracy is again more robust than RFMix to increasing admixture times. We apply Loter to individuals resulting from admixture between Populus trichocarpa and Populus balsamifera and lengths of ancestry tracts indicate that admixture took place ∼100 generations ago. We expect that providing a rapid and parameter-free software for local ancestry inference will make more accessible genomic studies about admixture processes.
Определение межклеточных контактов у больных с синдромом раздраженного кишечника
Authors: Yu.M. Stepanov, I.Ya. Budzak, Yu.A. Gaidar Yu.A. Gaidar
Journal: GASTROENTEROLOGY (2019)

В статье приведен анализ литературных данных о нарушении кишечной проницаемости как одного из патогенетических факторов синдрома раздраженного кишечника. Детально рассмотрено строение плотных контактов как важного элемента нормального функционирования кишечного барьера. Рассмотрены исследования, в которых предварительно изучали экспрессию компонентов плотных контактов у больных с синдромом раздраженного кишечника. Показаны результаты собственного исследования с оценкой экспрессии окклюдина у пациентов с синдромом раздраженного кишечника. Было установлено, что экспрессия окклюдина ниже у больных с синдромом раздраженного кишечника по сравнению со здоровыми лицами.
Abstract 45: Weight-related Discrimination Increases the Risk of Multi-system Physiological Dysregulation Among US Adults
Authors: Maya Vadiveloo, Josiemer Mattei
Journal: Circulation (2016)

Background: Obesity stigma is prevalent in the US. General discrimination has been shown to trigger a multi-system physiological dysregulation collectively referred to as allostatic load (AL), which independently predicts cardiovascular disease morbidity and mortality. However, it remains unclear whether weight-related discrimination influences AL. We aimed to examine the prospective associations between weight-related discrimination and AL and its individual systems among adults aged 25-75y participating in the national Midlife Development in the US (MIDUS) study over 10-years. Methods: Participants from the MIDUS Biomarker Substudy with self-reported information on weight discrimination were analyzed (n=986). At baseline and at 10-years follow-up, participants were asked about the frequency (never, rarely, sometimes, often) of perceived weight discrimination across nine scenarios. A continuous score assigned 1-2 points for discrimination experienced ‘sometimes’ or ‘often’, and an average of the two values at baseline and 10-years were used to estimate long-term discrimination. An AL score (range 0-7) represented the sum of the proportion of 24 dysregulated biomarkers or corresponding medication use within each of 7 systems (cardiovascular, sympathetic and parasympathetic nervous systems, hypothalamic pituitary axis, inflammatory, lipid and general metabolic activity, and glucose metabolism). Estimated relative risks (RR) were obtained from multivariable models adjusted for age, sex, race, education, household income, smoking, physical activity, race and sex discrimination, and baseline BMI. Results: Over 41% of the sample was obese, and 6% reported weight discrimination at 10-year follow-up. Both baseline and long-term perceived weight discrimination were associated with more than double the risk of high AL in final multivariable models (RR: 2.06, 95%CI: 1.20, 3.52 for baseline; 2.16, 95%CI: 1.39, 3.36 for long-term discrimination). The associations remained significant when the continuous weight discrimination score was assessed (β=0.11, p=0.01 for baseline; β=0.19, p=0.0001 for long-term discrimination). In sensitivity analyses, when BMI and waist:hip ratio were excluded from the AL definition, long-term weight discrimination remained associated with a 62% greater risk of high AL (1.62, 95%CI: 1.01, 2.62). Weight discrimination was significantly associated with metabolic/lipid dysregulation (1.56, 95%CI: 1.03, 2.41), glucose metabolism (1.99, 95% CI: 1.34, 2.96), and inflammatory parameters (1.76. 95% CI: 1.22, 2.54), but not with the other systems. Conclusions: Perceived weight discrimination doubles the risk of high AL. Public health campaigns and individual patient counseling that avoid obesity stigma may help improve obesity-related morbidity and mortality by modulating multi-system physiological dysregulation.
AB0137 ROLE OF VIMENTIN AS A TARGET OF ANTIBODIES AGAINST CARBAMYLATED PROTEINS IN RHEUMATOID ARTHRITISPATIENTS
Authors: Arbi Pecani, Tania Colasanti, Cristiano Alessandri, Martina Leopizzi, Riccardo Mancini, Fabrizio Conti, Guido Valesini, Francesca Romana Spinelli
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Patients with Rheumatoid Arthritis (RA) have an increased risk of cardiovascular diseases (CVD). Inflammation and autoantibodies indipendently promote endothelial dysfunction, which is the earliest, reversible stage of atherosclerosis. <i>In vitro</i> studies have demonstrated that antibodies against carbamylated proteins (anti-CarP), recently described in RA patients, can induce the production of proatherosclerotic molecules like <i>Vascular Cell Adhesion Molecule</i> (VCAM-1) and activate <i>Interleukin-1 Receptor-Associated Kinase</i> (IRAK-1), <i>Nuclear Factor kB</i> (NF-kB), <i>inducible Nitric Oxide Synthase</i> (iNOS) in endothelial cells (1,2). Moreover, anti-CarP are associated to endothelial dysfunction and subclinical atherosclerosis in RA patients (3). <h3>Objectives:</h3> Aims of the present study were: 1) to analyze the role of vimentin as a target of autoantibody response in the serum of patients with RA and 2) investigate the expression of vimentin and carbamylated proteins in endothelial cells. <h3>Methods:</h3> Consecutive RA patients were enrolled in this study. Vimentin was carbamylated and used as an antigen for the detection of anti-Vimentin Carbamylated antibodies (CarVim), through immunoenzymathic methods. Cells were incubated with anti-vimentin and carbamylated antibodies. The presence of vimentin and carbamylated proteins was investigated by immunofluorescence on the immortalized endothelial cell line EA.hy 926. <h3>Results:</h3> Eighty-eight (88) RA patients were enrolled in this study (F:M = 79:9, mean age = 56 ± 13 years). Anti-CarVim antibodies were present in 9% of the patients with a mean titre of di 442 aU/ML (IQR 303 aU/ml). Vimentin and carbamylated proteins were detected in the endothelial cells by immunofluorescence (Figure 1). <h3>Conclusion:</h3> The results of this study confirm that Vimentin is one of the antigenic targets of anti-CarP antibodies present in the serum of RA patients. The presence of carbamylated proteins and vimentin in endothelial cells suggests that anti-CarVim could bind the modified protein and determine endothelial activation and subsequent endothelial dysfunction. <h3>Reference</h3> [1] Pecani A &amp; Alessandri C et al, Arthr Res Ther 2016 [2] Pecani A et al, Reumatismo 2017 [3] Spinelli FR &amp; Pecani A et al, BMC Musculoskelet Disord 2017. <h3>Disclosure of Interests:</h3> None declared
Carbon nanotube electrodes for retinal implants: A study of structural and functional integration over time
Authors: Cyril G. Eleftheriou, Jonas B. Zimmermann, Henrik D. Kjeldsen, Moshe David-Pur, Yael Hanein, Evelyne Sernagor
Journal: Biomaterials (2016)

The choice of electrode material is of paramount importance in neural prosthetic devices. Electrodes must be biocompatible yet able to sustain repetitive current injections in a highly corrosive environment. We explored the suitability of carbon nanotube (CNT) electrodes to stimulate retinal ganglion cells (RGCs) in a mouse model of outer retinal degeneration. We investigated morphological changes at the bio-hybrid interface and changes in RGC responses to electrical stimulation following prolonged in vitro coupling to CNT electrodes. We observed gradual remodelling of the inner retina to incorporate CNT assemblies. Electrophysiological recordings demonstrate a progressive increase in coupling between RGCs and the CNT electrodes over three days, characterized by a gradual decrease in stimulation thresholds and increase in cellular recruitment. These results provide novel evidence for time-dependent formation of viable bio-hybrids between CNTs and the retina, demonstrating that CNTs are a promising material for inclusion in retinal prosthetic devices.
PF753 IMPACT OF ANTI‐THYMOCYTE GLOBULIN DOSES IN UNRELATED HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR PATIENTS WITH MYELOID NEOPLASM
Authors: J.Y. Nam, S.H. Bae, M.K. Kim, M.S. Hyun, J.H. Moon, S.K. Sohn
Journal: HemaSphere (2019)

Background: Anti‐thymocyte globulin (ATG) is widely used for the prophylaxis of graft‐versus‐host disease (GVHD) in hematopoietic stem cell transplantation (HSCT). However, there is still controversy regarding the optimal dose of ATG. Aims: We analyzed the impact of ATG doses in unrelated HSCT for patients with myeloid neoplasm. Methods: This was a retrospective multi‐center study that assessed the impact of ATG doses on clinical outcomes in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing an unrelated HSCT. The patients who received peripheral blood stem cells (PBSC) transplantation after conditioning regimens containing i.v. busulfan (BU), fludarabine and rabbit ATG between 2010 and 2017 were included in this study. Results: A total of 96 patents, median age 45 years, with AML (n = 74) or MDS (n = 22) were included in our analyses. 66 patients (69%) received a myeloablative regimen (i.v. BU&gt;6.4 mg/kg). High‐ATG (ATG 9 mg/kg), intermediate‐ATG (ATG 4.5–5 mg/kg) and low‐ATG (ATG 3 mg/kg) were given in 11, 49 and 36 patients, respectively. After a median follow‐up of 23 months, the cumulative incidence of extensive chronic GVHD was 9.1% in the high‐ATG group, 13.8% in the intermediate‐ATG group and 29.7% in the low‐ATG group (p = 0.31). The rate of 2‐year relapse‐free survival was significantly higher in the intermediate‐ATG group than other groups (30% in the high‐ATG group vs. 73.2% in the intermediate‐ATG group vs. 53.8% in the low‐ATG group, p = 0.048). The rate of 2‐year overall survival was similar (45.5%, 68.5% and 44.8%, respectively; p = 0.09). The rate of chronic GVHD–free and relapse‐free survival at 2 years was significantly higher in the intermediate‐ATG group (18.2% in the high‐ATG group vs. 53.8% in the intermediate‐ATG group vs. 18.8% in the low‐ATG group, p = 0.0086). Summary/Conclusion: Our study shows that the incidence of extensive chronic GVHD was similar regardless of the doses of ATG after transplantation of PBSC from unrelated donor for patients with AML or MDS. However, the rate of relapse‐free survival and the rate of a composite end point chronic GVHD–free and relapse‐free survival were significantly higher in the intermediate dose (4.5–5 mg/kg) of ATG group.
Abstract P200: Predictive Value of the Pressor Response to a Voluntary Apnea
Authors: James R Mason, Michael Smith, Dorene Niv, Roberto Cardarelli, Kimberly Fulda, Sherif Al-Farra, Donald Watenpaugh
Journal: Circulation (2013)

Previously, we have shown that chemoreflex control of sympathetic nerve activity (SNA) is hypersensitive in patients with obstructive sleep apnea (OSA), and this is manifest as an exaggerated SNA a...
Abstract 14238: Detection of Subclinical Left Ventricular Dysfunction in Obese Patients
Authors: Samuel L Kulifay, Selena Chandler, Ellianna Hoff, Jordan T Long, Brandon M Mikolich, Sebastian Boland, J. Ronald Mikolich
Journal: Circulation (2018)

Introduction: Abnormalities of left ventricular (LV) strain have been shown to occur prior to impairment of global left ventricular function, measured by global LV ejection fraction (EF). Although ...
Use of a Statewide Public Health Tool to Estimate Miles Driven by Intoxicated Drivers
Authors: Michaela A. West, Amber Smith, Tara Helm, Patty Reicks, Melissa Thorson, Jonathan Gipson
Journal: JAMA Surgery (2019)

This study uses data from the Place of Last Drink database and Google maps to assess the association of blood alcohol concentration with distance traveled and driver’s age among intoxicated drivers in Minnesota.
PF650 AGE DOES NOT CONFER DIFFERENT FEATURES AND OUTCOMES IN PATIENTS WITH NEWLY DIAGNOSED ACTIVE MULTIPLE MYELOMA YOUNGER THAN 66 YEARS OF AGE TREATED IN A RECENT PERIOD
Authors: V. Bove, S. Ranero, F. Villano, E. Riva
Journal: HemaSphere (2019)

Background: Multiple myeloma (MM) is a disease of the elderly, with median age at diagnosis of 66 years. However, 10% of patients are younger than 50 years. Publications regarding age as prognostic factor for clinical characteristics at diagnosis and outcomes are heterogeneous, with some authors reporting aggressive presentation and worse outcomes in young patients and others showing better outcomes. Aims: To describe clinical and laboratory characteristics, response to treatment and survival in active newly‐diagnosed MM (NDMM) under 66 years. To compare outcomes between &lt;51 and 51–65 years of age. Methods: Retrospective review of medical records of active MM diagnosed from jan2010 to dec2018 at Hospital de Clínicas, Montevideo, Uruguay. Smoldering MM and plasma cell leukemia were excluded. Characteristics at diagnosis were analyzed using descriptive statistics. Survival outcomes were calculated by Kaplan‐Meier method and compared using log‐rank test. In all cases, p &lt; 0,05 was considered significant. Results: 131 patients &lt;66 years were included, 36 (27.5%) &lt;51 years. Characteristics at diagnosis are shown in Table 1. Most patients were diagnosed at an advanced Durie‐Salmon and prognostic score (ISS) stages, showing no differences according to age. The mean monoclonal protein was lower in younger patients (p = 0,048). CRAB features and bone marrow infiltration were comparable. Bone plasmacytomas and extramedullary infiltration were more frequent in younger patients. Most used induction regimens were CyBorD and CTD in both groups. Rates of upfront autologous stem cell transplant (ASCT) consolidation were similar. Overall response rate (&gt; = PR [partial remission]) was 77,4% in &lt;51 and 79,9% in 51–65 years (p = 0,590) with comparable depth of response. Median progression free survival (PFS) was 25 months in &lt;51 years and 26 months in 51–65 years (p = 0,683). Mortality rate was 33.3% in &lt;51 years and 31.5% in older. The main causes of death were progression (53,2%) and infections 14,9%, similar in both groups. With a median follow up of 34 months, overall survival (OS) was 68,1%, median not reached in patients &lt;51 years and 75 months in patients 51 – 65 years (p = 0,528). Summary/Conclusion: Clinical and laboratory features are similar in NDMM patients &lt;50 and 51–65 years, although bone plasmacytoma and extramedullary disease were more frequent in the younger. However, this finding did not translate into differences in response or survival. Despite its efficacy and availability, upfront ASCT rate is low. image Disclosures: no conflicts of interest to declare. Funding: none.
Intervention strategies to inhibit protein carbonylation by lipoxidation‐derived reactive carbonyls
Authors: Giancarlo Aldini, Isabella Dalle‐Donne, Roberto Maffei Facino, Aldo Milzani, Marina Carini
Journal: Medicinal Research Reviews (2006)

Abstract Protein carbonylation induced by reactive carbonyl species (RCS) generated by peroxidation of polyunsaturated fatty acids plays a significant role in the etiology and/or progression of several human diseases, such as cardiovascular (e.g., atherosclerosis, long‐term complications of diabetes) and neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, and cerebral ischemia). Most of the biological effects of intermediate RCS, mainly α,β‐unsaturated aldehydes, di‐aldehydes, and keto‐aldehydes, are due to their capacity to react with the nucleophilic sites of proteins, forming advanced lipoxidation end‐products (ALEs). Because of the emerging deleterious role of RCS/protein adducts in several human diseases, different potential therapeutic strategies have been developed in the last few years. This review sheds focus on fundamental studies on lipid‐derived RCS generation, their biological effects, and their reactivity with proteins, with particular emphasis to 4‐hydroxy‐ trans ‐2‐nonenal (HNE)‐, acrolein (ACR)‐, malondialdehyde (MDA)‐, and glyoxal (GO)‐modified proteins. It also discusses the recently developed pharmacological approaches for the management of chronic diseases in which oxidative stress and RCS formation are massively involved. Inhibition of ALE formation, based on carbonyl‐sequestering agents, seems to be the most promising pharmacological tool and is reviewed in detail. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 6, 817–868, 2007
Tensorial blind source separation for improved analysis of multi-omic data
Authors: Andrew E. Teschendorff, Han Jing, Dirk S. Paul, Joni Virta, Klaus Nordhausen
Journal: Genome biology (2018)

There is an increased need for integrative analyses of multi-omic data. We present and benchmark a novel tensorial independent component analysis (tICA) algorithm against current state-of-the-art methods. We find that tICA outperforms competing methods in identifying biological sources of data variation at a reduced computational cost. On epigenetic data, tICA can identify methylation quantitative trait loci at high sensitivity. In the cancer context, tICA identifies gene modules whose expression variation across tumours is driven by copy-number or DNA methylation changes, but whose deregulation relative to normal tissue is independent of such alterations, a result we validate by direct analysis of individual data types.
Abstract 18653: Prognostic Impact of Early Induction of IABP in Patients With Acute Heart Failure
Authors: Ayano Yoshida, Kentaro Jujo, Yuichiro Minami, Motoko Kametani, Keiko Mizobuchi, Issei Ishida, Hiromu Kadowaki, Madoka Akashi, Shintaro Haruki, Hiroyuki Tanaka, Nobuhisa Hagiwara
Journal: Circulation (2017)

Background: Intra-aortic balloon pumping (IABP) provides potent supports on hemodynamic status of patients with cardiac shock through decreasing end-diastolic pressure and increasing cardiac output...