tbuckley/cabot-search huggingface dataset:
Dissecting the role of non-coding RNAs in the accumulation of amyloid and tau neuropathologies in Alzheimer’s disease
Authors: Ellis Patrick, Sathyapriya Rajagopal, Hon-Kit Andus Wong, Cristin McCabe, Jishu Xu, Anna Tang, Selina H. Imboywa, Julie A. Schneider, Nathalie Pochet, Anna M. Krichevsky, Lori B. Chibnik, David A. Bennett, Philip L. De Jager
Journal: Molecular Neurodegeneration (2017)

Given multiple studies of brain microRNA (miRNA) in relation to Alzheimer's disease (AD) with few consistent results and the heterogeneity of this disease, the objective of this study was to explore their mechanism by evaluating their relation to different elements of Alzheimer's disease pathology, confounding factors and mRNA expression data from the same subjects in the same brain region.We report analyses of expression profiling of miRNA (n = 700 subjects) and lincRNA (n = 540 subjects) from the dorsolateral prefrontal cortex of individuals participating in two longitudinal cohort studies of aging.We confirm the association of two well-established miRNA (miR-132, miR-129) with pathologic AD in our dataset and then further characterize this association in terms of its component neuritic β-amyloid plaques and neurofibrillary tangle pathologies. Additionally, we identify one new miRNA (miR-99) and four lincRNA that are associated with these traits. Many other previously reported associations of microRNA with AD are associated with the confounders quantified in our longitudinal cohort. Finally, by performing analyses integrating both miRNA and RNA sequence data from the same individuals (525 samples), we characterize the impact of AD associated miRNA on human brain expression: we show that the effects of miR-132 and miR-129-5b converge on certain genes such as EP300 and find a role for miR200 and its target genes in AD using an integrated miRNA/mRNA analysis.Overall, miRNAs play a modest role in human AD, but we observe robust evidence that a small number of miRNAs are responsible for specific alterations in the cortical transcriptome that are associated with AD.
Random mutagenesis of human deoxycytidine kinase for cancer gene therapy using megaprimer PCR of whole plasmid
Authors: Candice L. Willmon, Margaret E. Black
Journal: Cancer Research (2005)

3362  Human deoxycytidine kinase (dCK) is an important enzyme in the salvage pathway of deoxyribonucleosides. This enzyme displays broad substrate specificity and is capable of phosphorylating deoxycytidine analogs in addition to deoxycytidine. Deoxycytidine kinase is responsible for the initial phosphorylation of anti-neoplastic agents, such as gemcitabine. The goal of this project is to create mutant dCK enzymes with enhanced activity towards the prodrug, gemcitabine, for suicide gene therapy of cancer. Suicide gene therapy offers the advantage of selective eradication of tumor tissue while sparing normal tissue from damage. This is accomplished through the introduction of a gene encoding an enzyme into cancer cells followed by prodrug administration. Upon administration of the prodrug, the enzyme converts the prodrug selectively into its toxic form, thereby resulting in the elimination of cancer cells. To improve prodrug activation both error-prone polymerase chain reaction and regio-specific random mutagenesis using megaprimer PCR of whole plasmid (MEGAWHOP) were performed. These two random mutagenesis approaches are especially applicable to structure/function studies of enzymes, and can lead to the development of enzymes with altered or novel functions. In addition, MEGAWHOP allows for the rapid and efficient creation of a random library without the tedious cloning steps involved in traditional random mutagenesis protocols. Screening for dCK variants with increased sensitivity towards gemcitabine is ongoing. Transformants produced by MEGAWHOP will be surveyed for enhanced prodrug specificity in an E. coli complementation system. Variants with increased sensitivity towards gemcitabine will be further analyzed biochemically and in cell culture models. Data obtained from this mutagenesis study will reveal important structural and functional information regarding catalysis, structural integrity, and substrate specificity that will provide insight for further enzyme improvements and novel anti-cancer drug design. Additionally, the creation of improved dCK variants for gene therapeutic applications will (i) allow the use of low prodrug doses, (ii) reduce toxic side effects, and (iii) enhance tumor ablation. Furthermore, this research is significant because it will provide an exciting, novel alternative for gene therapy applications for a wide variety of cancers.
Abstract 151: Optical Coherence Tomography post-processing towards an automated quantification of coronary artery wall alteration subsequent to Kawasaki Disease
Authors: Maria Abdelali, Farida Cheriet, Audrey Dionne, Nagib Dahdah
Journal: Circulation (2015)

Introduction: Statistical mathematical processing of medical imaging promotes operator-independent interpretation. We sought to identify discriminative image features for a histological disambiguation of KD related coronary (CA) lesions. The ultimate goal is to develop a fully automated algorithm for the quantification of the degradation/healing state of the CA wall structure post KD. Methods: We analyzed OCT CA recordings from two KD patients with (KD + AN + ) and two patients with no history of CA aneurysm (KD + AN [[Unable to Display Character: &amp;#8211;]] ), vs a non KD patient (KD [[Unable to Display Character: &amp;#8211;]] ). Results: In KD [[Unable to Display Character: &amp;#8211;]] , regardless of the radial region of interest (ROI) position in the image, the OCT mean signal intensity presents centrifugally two peaks corresponding to the intima and media, constantly separated (17.1± 2.0 pixels) (fig. 1A). In KD + AN [[Unable to Display Character: &amp;#8211;]] the peaks may disappear (Fig. 1-B left medial hyperplasia) and the distance between remaining crests vary between ROIs (22.7±6.9 Pixels). In KD + AN + these peaks disappear (Figure1-C) and the signal intensity changes drastically between ROIs due to wall restructuration. Figure1-C shows a hatched signal that maybe that of a laminar structure. In this case the variation of gradient intensity may be a discriminative feature. Conclusion: Mathematical modeling of CA wall layers is feasible. While the consistency of the distance between media and intima peaks may discriminate KD [[Unable to Display Character: &amp;#8211;]] from KD + and while the gradient intensity may detect restructuration in KD + AN + , ongoing investigation to discriminate CA lesions include signal homogeneity, energy and contrast. Texture analysis with anatomical correlates (e.g., calcium, fibrosis and clots) may allow automated diagnoses.
PS1180 FOLLOW‐UP OF LOWER DOSE DASATINIB 50MG DAILY AS FRONTLINE THERAPY IN NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOID LEUKEMIA (CML‐CP)
Authors: K. Naqvi, E. Jabbour, J. Skinner, K. Anderson, M. Yilmaz, A. Ferrajoli, P. Bose, P. Thompson, Y. Alvarado, N. Jain, K. Takahashi, J. Burger, Z. Estrov, G. Borthakur, N. Pemmaraju, S. Dellasala, S. Paul, J. Cortes, H. Kantarjian
Journal: HemaSphere (2019)

Background: Dasatinib, a potent BCR‐ABL tyrosine kinase inhibitor (TKI), is approved for the treatment of chronic phase CML (CML‐CP) in the frontline and salvage settings. Notable side effects include pleural effusions and myelosuppression. We previously reported dasatinib 50 mg daily to be active and better tolerated than the approved 100 mg daily dose (CANCER. 2018 Jul 1;124(13):2740–2747). Aims: An update on the efficacy and toxicity profile of lower dose dasatinib 50 mg orally daily in patients with early CML‐CP. Methods: All patients presenting to our institution in early CML‐CP were eligible to participate. Prior TKI therapy for up to 1 month was allowed. Responses were assessed according to the European LeukemiaNet guidelines (Baccarani et al. Blood 2013 122.872:884). Results: From March 2016 to March 2018, 81 patients have been enrolled. Median age is 47 years (20–84). Patients categorized by Sokal risk are: low 53; intermediate 22 and high 6. Median follow‐up is 18 months (9–31). Cumulative response rates (n = 81) over time are shown in the gragh below. At 3 months, 96% patients achieved early molecular response ( BCR‐ABL PCR ≤10%). Median time to CCyR was 4.6 months, MMR 6.0 months, MR4.0 11.4 months and MR4.5 12.2 months. Eighteen patients had treatment interruption: pleural effusion 4 (possibly related 3, unrelated 1 due to pneumonia); gastrointestinal bleed 2; thrombocytopenia 3; transaminitis 2; renal dysfunction 1; asthma exacerbation 1; pneumonitis 1; lower extremity edema 1; myalgias 1, and pregnancy 2. Four patients had dose reductions: pleural effusion 3; myalgias 1. Four patients had dasatinib dose increased to 100 mg: lack of CCyR at 6 months, 3; lack of MMR at 12 months, 1. Four patients are off study: no response 2, pneumonitis 1, and insurance 1. None of the patients have transformed or died. Summary/Conclusion: These updated results continue to support dasatinib 50 mg daily as an effective and safe dose for early CML‐CP. image
PS1368 IGH AND IGK REARRANGEMENT AND IGH SOMATIC HYPERMUTATION ANALYSIS USING NEXT‐GENERATION SEQUENCING FOR THE DETECTION OF CLONALITY IN HIGH‐RISK KOREAN MULTIPLE MYELOMA PATIENTS
Authors: J. Lee, Y.K. Lee, M. Kim, H.J. Kim
Journal: HemaSphere (2019)

Background: Clonality assessment in patients with multiple myeloma (MM) is important both for initial diagnosis and detecting minimal residual disease. Next‐generation sequencing (NGS)‐based immunoglobulin gene rearrangement assays may be useful for assessing clonality, although their applicability has not been convincingly demonstrated. Aims: We intended to evaluate the primer set most widely used with the only commercially available NGS‐based clonality assay in high‐risk MM patients for the first time. Methods: Thirty bone marrow aspirate samples were included in the study. The samples were evaluated for IGH rearrangements and IGH somatic hypermutation using the LymphoTrack ® IGH‐FR1 assay (InVivoScribe, San Diego, CA) on a MiSeqDx instrument (Illumina, San Diego, CA). When kappa‐type cases showed negative IGH rearrangement (and somatic hypermutation), LymphoTrack ® IGK assay (InVivoScribe) was performed. Results: IGH‐FR1 and/or IGK assay detected clonality (demonstrated by rearrangements) in 22 out of 26 MM cases (84.6%) who were not lambda‐type light chain disease. Detailed analysis on IGH clonality/somatic hypermutations and IGK clonality is presented in Table 1. IGH clonality were observed in 20 of the 26 samples (76.5%), and among them 17 cases (85.0%) showed IGH somatic hypermutations. By testing IGK clonality on 5 kappa‐type samples which did not show any IGH clonality including 1 kappa‐type light chain disease, 2 samples (40.0%) showed IGK clonality. One out of 2 kappa‐type light chain disease cases and 1 out of 3 lambda‐type light chain disease cases showed IGH clonality, suggesting that the heavy chain clonality could have been missed in immunofixation electrophoresis assay. The IGH or IGK clonality was not statistically associated with heavy chain type or light chain type, even though all the 10 IgA‐type cases showed either IGH or IGK clonality. Neither the existence of IGH clonality nor its quantity (expressed as a percentage) was associated with the percentage of plasma cells in the specimens. Table 1. IGH clonality, IGH somatic hypermutation and IGK clonality according to the heavy chain and light chain types in 30 high‐risk Korean multiple myeloma samples. Summary/Conclusion: By combining the IGH‐FR1 assay and/or IGK assay, we detected clonality in approximately 85% of high‐risk Korean MM patients. Somatic hypermutations of IGH gene was observed in 85% cases with IGH clonality. Different sets of primers of immunoglobulin genes might increase the clonality detection rate in MM. image
Abstract 14818: Hyperactivity of Cardiac Sympathetic Nerve in the Remote Normal Region in Patients with a Prior Myocardial Infarction with Left Ventricular Remodeling
Authors: Nobuyuki Ohte, Hitomi Narita, Akihiko Iida, Hidekatsu Fukuta, Kazuaki Wakami, Toshihiko Goto, Tomomitsu Tani, Genjiro Kimura
Journal: Circulation (2011)

Left ventricular (LV) remodeling is observed in the remote normal region in the left ventricles after myocardial infarction (MI) and is closely involved in systolic heart failure. β-blocker adminis...
Chronic Food Antigen-Specific IgG-Mediated Hypersensitivity Reaction as A Risk Factor for Adolescent Depressive Disorder
Authors: Ran Tao, Zhicheng Fu, Lijun Xiao
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract Major depressive disorder (MDD) is the most common nonfatal disease burden worldwide. Systemic chronic low-grade inflammation has been reported to be associated with MDD progression by affecting monoaminergic and glutamatergic neurotransmission. However, whether various proinflammatory cytokines are abnormally elevated before the first episode of depression is still largely unclear. Here, we evaluated 184 adolescent patients who were experiencing their first episode of depressive disorder, and the same number of healthy individuals was included as controls. We tested the serum levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), IgE, 14 different types of food antigen-specific IgG, histamine, homocysteine, S100 calcium-binding protein B, and diamine oxidase. We were not able to find any significant differences in the serum levels of hs-CRP or TNF-α between the two groups. However, the histamine level of the patients (12.35 μM) was significantly higher than that of the controls (9.73 μM, P &amp;lt; 0.001, Mann–Whitney U test). Moreover, significantly higher serum food antigen-specific IgG positive rates were also found in the patient group. Furthermore, over 80% of patients exhibited prolonged food intolerance with elevated levels of serum histamine, leading to hyperpermeability of the blood–brain barrier, which has previously been implicated in the pathogenesis of MDD. Hence, prolonged high levels of serum histamine could be a risk factor for depressive disorders, and antihistamine release might represent a novel therapeutic strategy for depression treatment.
Abstract 17887: Impact of Complete Revascularization in Acute Coronary Syndromes: Insights From the Alberta Contemporary Acute Coronary Syndrome Patients Invasive Treatment Strategies (COAPT) Registry
Authors: Kevin Bainey, Padma Kaul, Wendimagegn Alemayehu, Paul Armstrong, Robert Welsh
Journal: Circulation (2016)

Introduction: Controversy exists regarding the benefits of complete revascularization (CR) compared to incomplete revascularization (IR) in acute coronary syndrome (ACS) patients with multi-vessel ...
Clinical, Histopathological, and Molecular Diagnostics in Lethal Lung Developmental Disorders
Authors: Marie Vincent, Justyna A. Karolak, Gail Deutsch, Tomasz Gambin, Edwina Popek, Bertrand Isidor, Przemyslaw Szafranski, Cedric Le Caignec, Paweł Stankiewicz
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Lethal lung developmental disorders are a rare but important group of pediatric diffuse lung diseases presenting with neonatal respiratory failure. On the basis of histopathological appearance at lung biopsy or autopsy, they have been termed: alveolar capillary dysplasia with misalignment of the pulmonary veins, acinar dysplasia, congenital alveolar dysplasia, and other unspecified primary pulmonary hypoplasias. However, the histopathological continuum in these lethal developmental disorders has made accurate diagnosis challenging, which has implications for recurrence risk. Over the past decade, genetic studies in infants with alveolar capillary dysplasia with misalignment of the pulmonary veins have revealed the causative role of the dosage-sensitive FOXF1 gene and its noncoding regulatory variants in the distant lung-specific enhancer at chromosome 16q24.1. In contrast, the molecular bases of acinar dysplasia and congenital alveolar dysplasia have remained poorly understood. Most recently, disruption of the TBX4-FGF10-FGFR2 epithelial-mesenchymal signaling pathway has been reported in patients with these lethal pulmonary dysplasias. Application of next-generation sequencing techniques, including exome sequencing and whole-genome sequencing, has demonstrated their complex compound inheritance. These data indicate that noncoding regulatory elements play a critical role in lung development in humans. We propose that for more precise lethal lung developmental disorder diagnosis, a diagnostic pathway including whole-genome sequencing should be implemented.
FRI0692 34. REHABILITATION HUMAN PAPILLOMA VIRUSSCREENING AND CHRONIC INFLAMMATORY ARTHRITIS: AN AUDIT
Authors: Ernesto Tovar-Sugrañes, Blanca Vidal-Alejandre, Raquel López-Poza, Mariano Andrés, Maria Paz Martínez-Vidal
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Patients with autoimmune diseases suffer from an immunosuppressive state related to a pro-inflammatory environment and therapies received. Immunosuppression is a known risk factor for developing virus-associated cancers, including at uterine cervix (1,2). One of the major risk and prognostic factors for cervical neoplasm is missing the screening and early detection programs of human papilloma virus (HPV) (3). This screening is recommended for immunosuppressed women to be performed annually between 21 and 65 years of age (4). <h3>Objectives</h3> To audit the degree of adherence to HPV-cervical cancer screening of patients with chronic arthritis in the rheumatology unit of a tertiary center. <h3>Methods</h3> A descriptive, cross-sectional study was performed. The medical records of adult, female patients, with clinical diagnosis of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), being followed in rheumatology clinics were reviewed. Assistance to screening clinics and cervical cytology and HPV-PCR results were revised to determine if patients had followed the screening program. Type of screening, number of visits and findings were also collected. A descriptive analysis is presented, with an estimate of the 95% confidence interval (95%CI) for the primary study variable. <h3>Results</h3> 233 medical histories (144 AR, 89 PsA) from patients with a median age of 55 years (p25-75 18-60) were included. Information related to the performance of cervical screening was found in the clinical records of 137 patients (58.8%, 95% CI 52.4-64.9%). Regarding the type of arthritis, the prevalence of performing cervical screening in RA and PsA was 60.4% and 56.2%, respectively, while rates of women attending the program at least twice were 45.1% for RA and 37.1% for PAs. In relation of screening findings, HPV infection was detected in 8 patients (5.8%), cervical dysplasia in 6 (4.4%), while no case of invasive cancer was detected. <h3>Conclusion</h3> Autoimmune and inflammatory diseases, along with the treatment employed, are associated with an increased risk of cervical HPV infection. Despite this, information regarding HPV cervical screening was collected in only half of patients. Both patients and their treating rheumatologists must be aware of this risk and adhere to cervical screening programs to achieve an early diagnosis and management. <h3>References</h3> [1] JAMA.2006;296:2823. 2) Int J Cancer.2013;132:1429. 3) Int J Cancer.2012;130:937. 4)Rev.Esp.Patol.2014;47(1):1-43. <h3>Disclosure of Interests</h3> None declared
AB1400-HPR EFFECT OF FOOT PAIN ON FUNCTION, FEAR OF FALLING AND QUALITY OF LIFE IN ELDERLY PEOPLE WITH KNEE OSTEOARTHRITIS
Authors: Merve Karapinar, Zeliha Baskurt, Ferdi Baskurt, Meric Unal
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Knee osteoarthritis (OA) is a frequently seen disorder affecting approximately 30% of people over 65 years. Foot pain often defined as pain in the foot and/or ankle, is also very common among older people. This problem may effect on mobility, falling risk and quality of life in elderly patient with knee OA. But there is no study investigate to effect of foot pain on the function, fear of falling and quality of life in elderly people with knee OA. <h3>Objectives</h3> Concurrent foot pain in elderly people with knee OA may be the potential to further increase disability and immobility. <h3>Methods</h3> Fifty patients with radiographic and clinic evidence of tibiofemoral OA (Kellgren-Lawrence score 2) were included. The Western Ontario and Mc Master University Osteoarthritis Index (WOMAC) questionnaire was used to assess pain and the functional status of the all patients. Foot pain was measured with the Manchester-Oxford Foot Questionnaire (MOFQ) and 100 mm Visual Analog scale (VAS). Patients were divided into two groups (with foot pain and without foot pain) based on patient-reported pain using VAS and MOFQ. Two groups with knee OA were compared for difference in patient functional assessment quality of life and fear of falling. To evaluate physical function measured by using the Time up Go Test (TUG), health related quality of life (HRQOL) measured by using EuroQOL five dimensions (EQ-5D) questionnaire and fear of falling measured by using Tinetti Falls Efficacy Scale. <h3>Results</h3> Within our sample of older adults with knee OA, 52% had foot pain (26/50). VAS scores of patients with knee OA and without foot pain were zero. Compared to the group without foot pain of similar age (<i>n</i> = 24), those with foot pain had reduced quality of life and profound mobility limitations and more fear of falling (<i>p</i>&lt; 0.001). <h3>Conclusion</h3> Older adults with knee OA and also foot pain have pronounced mobility limitations and increased fear of falling and also these are associated with a marked reduction in HRQOL. Future prospective research is required to build on this study. <h3>References</h3> [1] Stubbs, B., Binnekade, T., Eggermont, L., Sepehry, A. A., Patchay, S., &amp; Schofield, P. (2014). Pain and the risk for falls in community-dwelling older adults: systematic review and meta-analysis. Archives of physical medicine and rehabilitation, 95(1), 175-187 [2] Chen, J., Devine, A., Dick, I. M., Dhaliwal, S. S., &amp; Prince, R. L. (2003). Prevalence of lower extremity pain and its association with functionality and quality of life in elderly women in Australia. The Journal of Rheumatology, 30(12), 2689-2693. <h3>Disclosure of Interests</h3> None declared
Prediction of Stroke Risk by Detection of Hemorrhage in Carotid Plaques
Authors: Andreas Schindler, Regina Schinner, Nishaf Altaf, Akram A. Hosseini, Richard J. Simpson, Lorena Esposito-Bauer, Navneet Singh, Robert M. Kwee, Yoshitaka Kurosaki, Sen Yamagata, Kazumichi Yoshida, Susumu Miyamoto, Robert Maggisano, Alan R. Moody, Holger Poppert, M. Eline Kooi, Dorothee P. Auer, Leo H. Bonati, Tobias Saam
Journal: JACC. Cardiovascular imaging (2019)

The goal of this study was to compare the risk of stroke between patients with carotid artery disease with and without the presence of intraplaque hemorrhage (IPH) on magnetic resonance imaging.
Complete Tracheal Ring Deformity. A Translational Genomics Approach to Pathogenesis
Authors: Debora I. Sinner, Brenna Carey, Daniela Zgherea, K. M. Kaufman, Lauren Leesman, Robert E. Wood, Michael J. Rutter, Alessandro de Alarcon, Ravindhra G. Elluru, John B. Harley, Jeffrey A. Whitsett, Bruce C. Trapnell
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Complete tracheal ring deformity (CTRD) is a rare congenital abnormality of unknown etiology characterized by circumferentially continuous or nearly continuous cartilaginous tracheal rings, variable degrees of tracheal stenosis and/or shortening, and/or pulmonary arterial sling anomaly.