tbuckley/cabot-search huggingface dataset:
Interrogation of human hematopoiesis at single-cell and single-variant resolution
Authors: Jacob C. Ulirsch, Caleb A. Lareau, Erik L. Bao, Leif S. Ludwig, Michael H. Guo, Christian Benner, Ansuman T. Satpathy, Vinay K. Kartha, Rany M. Salem, Joel N. Hirschhorn, Hilary K. Finucane, Martin J. Aryee, Jason D. Buenrostro, Vijay G. Sankaran
Journal: Nature Genetics (2019)
IMMU-70. GLOBAL IMMUNE FINGERPRINTING IN GLIOBLASTOMA REVEALS IMMUNE-SUPPRESSION SIGNATURES ASSOCIATED WITH PROGNOSIS
Authors: Tyler Alban, Alvaro Alvarado, Mia Sorensen, Defne Bayik, Josephine Volovetz, Emily Serbinowski, Erin Mulkearns-Hubert, Maksim Sinyuk, James Hale, Giovana Onzi, Mary McGraw, Pengjing Huang, Mathew Grabowski, Connor Wathen, Tomas Radivoyevitch, Harley Kornblum, Bjarne W Kristensen, Michael Vogelbaum, Justin Lathia
Journal: Neuro-Oncology (2018)

Therapeutic resistance in glioblastoma (GBM) is linked to cancer stem cells and signaling pathway alterations, but the role of local and systemic immune suppression during disease progression is less understood. To determine how the immune system as a whole is altered in GBM patients, a CyTOF panel of 25 immune markers was developed for immune fingerprinting of peripheral blood mononuclear cells (PBMCs). CyTOF analysis was performed on select patients with either favorable or poor prognosis from a cohort of newly diagnosed GBM patients, from whom PBMCs were collected throughout disease progression. Multi-dimensional cluster analysis identified a reduction of Monocytic Myeloid-Derived Suppressor Cells (M-MDSCs) in the patient with favorable prognosis, while the patient with poor prognosis had higher levels of M-MDSCs. Additionally, when LGG patients were compared to GBM patients, LGG patients had more Dendritic cells and Natural Killer cells as compared to GBM patients. To understand whether this elevation in MDSC was unique to GBM or whether MDSCs were high across primary and secondary brain tumors, a cohort of 259 patient PBMC samples was analyzed. GBM patients had a significant elevation in MDSCs in blood, but not immunosuppressive T regulatory cells as compared to non-malignant brain tumors. To determine whether MDSCs in the GBM microenvironment also correlate with survival, a cohort of patients with matched primary and secondary resections were analyzed for MDSCs by immunofluorescence, which determined that intra-tumoral MDSCs correlate with poor prognosis in recurrent samples, while general myeloid infiltration correlated with a good prognosis. These studies identify low MDSC immune signatures that are linked to enhanced pro-inflammatory cells and overlap between GBM patients with a good prognosis and LGG patients, promoting the idea of targeting MDSCs in GBM patients to alter their immune status to that of a lower grade tumor.
Clinical Outcomes of Hospitalized Adult Patients With Dermatologic Manifestations of Protein Malnutrition and Zinc Deficiency
Authors: Jonathan J. Lee, Sara Mater, Carlos Morillo-Hernandez, Timothy Patton, Arthur C. Huen, Jonhan Ho, Joseph C. English
Journal: JAMA Dermatology (2019)

Despite adequate or excess total caloric intake, protein-energy malnutrition and micronutrient deficiencies in minerals such as zinc and other essential vitamins can occur due to increased physiological demand and consumption of nutrient-poor
THU0085 RHEUMATOID ARTHRITIS AND ALLERGIC DISEASES
Authors: Vanessa Kronzer, Cynthia S. Crowson, Jeffrey Sparks, Robert Vassallo, John Davis
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Historically, RA was considered a T<sub>H</sub>1 disease while asthma and allergy were considered T<sub>H</sub>2 diseases (1). However, several studies show an association between RA and asthma (2), and more recently, allergic disease (3). <h3>Objectives:</h3> We first aimed to determine the association between RA and asthma after controlling for important confounders including allergic disease, urban environment, and passive smoke exposure. Second, we aimed to determine the association between RA and various allergy types. <h3>Methods:</h3> This case-control study identified 1,023 cases of RA (175 incident) within a single-center biobank population using a rules-based algorithm that combined self-report with two diagnosis codes. Exposures were self-reported on biobank questionnaires. Logistic regression models calculated the association of exposures with RA, adjusting for potential confounders. <h3>Results:</h3> Asthma was associated with RA after adjusting for allergies, urban environment, and passive smoke exposure (OR 1.28, 95% CI 1.04 to 1.58). History of allergic disease was also associated with RA (OR 1.30, 95% CI 1.12 to 1.51), especially food allergy (OR 1.38, OR 1.08 to 1.75, see Figure 1). Results from the incident RA cohort mirrored these findings, though the association with asthma was not significant (OR 1.17, 95% CI 0.66 to 2.06). <h3>Conclusion:</h3> Asthma and allergies may be associated with increased risk of RA. It is possible a broader problem with immune dysregulation underlies both RA and allergic diseases, and having one predisposes to the other. <h3>References:</h3> [1] Singh VK, Mehrotra S, Agarwal SS. The paradigm of Th1 and Th2 cytokines: its relevance to autoimmunity and allergy. Immunol Res. 1999;20(2):147-61. [2] Sheen YH, Rolfes MC, Wi CI, Crowson CS, Pendegraft RS, King KS, et al. Association of Asthma with Rheumatoid Arthritis: A Population-Based Case-Control Study. J Allergy Clin Immunol Pract. 2018;6(1):219-26. [3] Lai NS, Tsai TY, Koo M, Lu MC. Association of rheumatoid arthritis with allergic diseases: A nationwide population-based cohort study. Allergy Asthma Proc. 2015;36(5):99-103. <h3>Acknowledgement:</h3> Funding for this project was provided by the Rheumatology Research Foundation Resident Research Preceptorship. We would also like to acknowledge the Mayo Clinic Center for Individualized Medicine <h3>Disclosure of Interests:</h3> Vanessa Kronzer: None declared, Cynthia S. Crowson: None declared, Jeffrey Sparks Grant/research support from: Bristol-Myers Squibb, Amgen, Consultant for: Optum, Robert Vassallo: None declared, John Davis Grant/research support from: Pfizer
Abstract 14197: The Development of a New Real-time in vivo Imaging System With Two Photon Microscopy for Analyses Subcellular Dynamics of Injured Rat Heart
Authors: Ryohei Matsuura, Shigeru Miyagawa, Akima Harada, Yuri Shimozaki, Kazumasa Yamaki, Sho Sanami, Junichi Kikuta, Masaru Ishii, Yoshiki Sawa
Journal: Circulation (2017)

Introduction: We established in vivo imaging system of two photon microscopy by using an original stabilizer to make the heart of a rat or mouse visible easily at a subcellular level. Furthermore, ...
AB0953 EAR INVOLVEMENT IN PATIENTS AFFECTED BY JUVENILE IDIOPATHIC ARTHRITIS
Authors: Giovanni Conti, Giulia La Barbera, Carmela Visalli, Giuseppe Alberti, Paola De Pasquale, Francesco Borgia, Francesco Ciodaro
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Few clinical studies in pediatric patients have shown a possible link between hearing loss and Juvenile idiopathic arthritis (JIA). It could be related to the involvement of the joints of the ossicular chain as a result of the autoimmune inflammatory process in the middle and inner ear <h3>Objectives</h3> The aim of this study was to assess the frequency of hearing impairment in patients affected by JIA versus a healthy control group. <h3>Methods</h3> We studied 64 ears of 32 JIA patients (25 girls and 7 boys, mean age 15 years, age range 8-19 years) from June to December 2018. The mean disease duration was 7 years (+/- 4 DS). Polyarticular JIA was diagnosed in 6 patients, oligoarthritis JIA in 19; 5 patients had psoriatic arthritis and 2 spondyloarthritis. The control group consisted of 60 ears of 30 healthy children, sex-and age-matched. Patients with previous otitis media at least 3 months and/or ear surgery were excluded. The study was approved by the local ethics committee and parents and/or patients signed their informed consent. All subjects underwent audiological examination involving otomicroscopy, audiometry, tympanometry and stapedius reflex. Rheumatologic evaluation included joint examination with application of a measure of functional ability (disability) using the Childhood Health Assessment Questionnaire (CHAQ). The investigators were blinded about JIA type, severity, duration, and treatments of the patients. <h3>Results</h3> 11/32 (34%) JIA patients had abnormal audiological exam. Hypoacusia was significatively more frequent (p&lt;0,05) in JIA patients (15/64 ears=23%) respect to the control group. In particular, hypoacusia was associated to psoriasic arthritis (6/15 ears). Conductive hearing loss was detected in 12/15 involved ears, while sensorineural type in 3/15. In the JIA group, according to the Jerger classification for tympanometry, abnormal findings were observed in 7 ears. The stapedius reflexes were absent in only one patient (3%). JIA patients with hypoacusia had a greater CHAQ (0.4+/-0.3) than JIA patients with normal audiometry (0.18+/-0.29). <h3>Conclusion</h3> The presence of hearing impairment and/or abnormal tympanogram suggests early involvement of the tympanic-ossicular complex, especially in patients with psoriatic arthritis. These findings could be a marker of the JIA activity. Therefore, it is advisable that JIA patients perform periodic audiological examination to early detect eventual hearing impairment, in order to prevent hearing loss in adult age. <h3>References</h3> [1] M.EG Amani: Acta Oto-Laryngolica 2016 [2] A.I.C. Cruz: Reumatologia Clinica 2017 [3] F Borgia: Acta Derm Venerreol 2018 <h3>Disclosure of Interests</h3> None declared
CD55 regulates self-renewal and cisplatin resistance in endometrioid tumors
Authors: Caner Saygin, Andrew Wiechert, Vinay S. Rao, Ravi Alluri, Elizabeth Connor, Praveena S. Thiagarajan, James S. Hale, Yan Li, Anastasia Chumakova, Awad Jarrar, Yvonne Parker, Daniel J. Lindner, Anil Belur Nagaraj, J. Julie Kim, Analisa DiFeo, Fadi W. Abdul-Karim, Chad Michener, Peter G. Rose, Robert DeBernardo, Haider Mahdi, Keith R. McCrae, Feng Lin, Justin D. Lathia, Ofer Reizes
Journal: The Journal of Experimental Medicine (2017)

Effective targeting of cancer stem cells (CSCs) requires neutralization of self-renewal and chemoresistance, but these phenotypes are often regulated by distinct molecular mechanisms. Here we report the ability to target both of these phenotypes via CD55, an intrinsic cell surface complement inhibitor, which was identified in a comparative analysis between CSCs and non-CSCs in endometrioid cancer models. In this context, CD55 functions in a complement-independent manner and required lipid raft localization for CSC maintenance and cisplatin resistance. CD55 regulated self-renewal and core pluripotency genes via ROR2/JNK signaling and in parallel cisplatin resistance via lymphocyte-specific protein tyrosine kinase (LCK) signaling, which induced DNA repair genes. Targeting LCK signaling via saracatinib, an inhibitor currently undergoing clinical evaluation, sensitized chemoresistant cells to cisplatin. Collectively, our findings identify CD55 as a unique signaling node that drives self-renewal and therapeutic resistance through a bifurcating signaling axis and provides an opportunity to target both signaling pathways in endometrioid tumors.
Another Warning Sign: High Nicotine Content in Electronic Cigarettes Disrupts Mucociliary Clearance, the Essential Defense Mechanism of the Lung
Authors: Mehmet Kesimer
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

in dramatic bacterial clearance in the Pseudomonas case ( 9), but intravenous-only administration did not result in eradication of MRSA in the experimental model (8).A higher lung necrosis score was associated with nonsurvival (see Figure E3 in Reference 8), raising concerns about intravenous delivery of both phage and antibiotic to the lumen of cavitary pneumonia.Phage therapy is not neutral for the host: phages may transcytose host cells and stimulate Toll-like receptor 9 and other pattern recognition molecules (13).Generally, phage infusions or mucosal applications are well tolerated without an inflammatory signal, as was seen in the mouse model (8).More importantly, neutralizing antibodies are common in individuals exposed to naturally occurring phages, and may blunt the benefit of intravenous therapeutic phage therapy.Because aerosolization is less likely to induce neutralizing antiphage antibodies and less likely to be blunted by preformed antibodies, this route may be preferred for pneumonia treatment in the critically ill.Validation of the benefit of routine phage treatment of AMR pneumonia requires much more work.Only further data will demonstrate whether phage therapy is truly a new chapter in pneumonia treatment or just another interesting footnote.
Lentivirus Gene Therapy for Autoimmune Pulmonary Alveolar Proteinosis
Authors: H Palau, C Meng, A Bhargava, A Pilou, N Atsumi, A Byrne, I Pringle, R Ashworth, M Chan, D Gill, S Hyde, C Morgan, E Alton, U Griesenbach
Journal: Molecular Therapy (2019)
AB1185 RADIOLOGICAL INDEX IN THE FLAT VERTEBRAE
Authors: Raul Maria Veiga Cabello, Maria Del Pilar Ahijado Guzman
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Spine is a mechanical structure, which disposes their vertebral bodies in harmony with their stature, and progressively increasing in magnitude from the cervical to the lumbar spine (1). Defects in type II collagen gene are described, and in these cases, flat vertebra can be found, defined with flattening of the vertebral body, with irregular surface or with nodules of Schmorl, in isolation or in a maximum of two vertebral bodies, to distinguish it from Scheuermann's disease (2). Image 1. <h3>Objectives</h3> Current vertebral indexes, don't measure a relation between a person height and his vertebra, and if the harmony of the individual is accepted, an index that combines these variables must be created in order to guaranteeing the objectivity of the resultant value. <h3>Methods</h3> Patients attending physician since 1994, both sexes, 20-55 years old, in whom Type II collagen disease or vertebral dysplasia was suspected, were selected for the study. A control group was created from patients that didn't fulfill the last inclusion criteria. Their medical histories were taken. Eighth dorsal flat vertebra in a lateral chest radiograph were assessed by tripleobserver (two rheumatologists and one radiologist) according to the defined criteria. In all selected patients, a DEXA osteoporosis screening was performed, being chest trauma exclusion criteria. Finally, a descriptive study was carried out and a comparative study of average of vertebral index of the eight dorsal vertebra (VIDV8) results was applied: VIDV8 = 10 x LVD8/(HVD8 x stature). Image 2. <h3>Results</h3> 174 subjects were analyzed, 84 in the study group and 90 in the control one, both homogeneous and without statistically significant differences in sex, age and height, with an average value in the study group of 47.15 years old, 48.8% women, 80.5 kg and 1,64 m. In control group: 44.5 years old, 52.2% women, 78.5 kg and 1,65 m. The VIDV8 value, did not show any significant difference compared to the previous variables, except for patient cohort, with an average value of 10.1 Meters-1 in control group, and 12.5 Meters-1 in pathological one (p &lt;0.001). To a value of 11,108 Meters-1 the sensitivity is 90.5% and specificity 92.2%. <h3>Conclusion</h3> The VIDV8 is stable for the variables sex, age, height, and weight. To an outcome of 11,108 Meters-1, it discriminates both groups with sensitivity of 90.5% and specificity of 92.2%, in order to avoid the ambiguity of the explorer. <h3>References</h3> [1] .White AA, Panjabi MM. Clinical Biomechanics of the Spine. 2nd ed, Lippincott Williams &amp; Wilkins, 1990. [2] Rimoin DL, Lachman RS; The condrodysplasias, Practise of Medical Genetics. Edited by AEH Emery, DL Rimoin. New York, Churchill Livingston, 1990. <h3>Disclosure of Interests</h3> None declared
PB2154 TIME TO FIRST PLATEAU AS A PROGNOSTIC PREDICTOR IN MULTIPLE MYELOMA
Authors: O. Kirkizlar, E. Umit, M. Baysal, V. Bas, S. Gulsaran, U. Demirci, A. M. Demir
Journal: HemaSphere (2019)

Background: As novel treatments emerge, prognostic assessment has become the backbone of patients with multiple myeloma (MM). Depth and duration of response have been associated with survival and recently, evaluation residual disease status has been related with both progression free and overall survival. Aims: We aimed investigated the relation with time to plateau, which has been proposed by MayoClinic with survival in our patient group. Methods Data of 105 patients with MM, diagnosed and treated at our clinic between 2015 and 2018 were enrolled in a retrospective manner. All patients received bortezomib‐cyclophosphamide and dexametazone as first line therapy. Time to plateau was defined as best response date to the first line therapy. Results: Mean age was 65,86 years (28‐93). 49 patients were female (46,7%) while 56 were male (53,3). 29 patients had IgA disease while 74 were Ig G and 2 were light chain MM. 68 patients had International Scoring System (ISS) III disease (64,8%) while 27 had ISS II (25,7%) and 10 had ISS I disease (9,5%). Mean time to plateau was 6,74 months (4‐15) while mean overall survival was 44,87 months (8‐145). As all patients who were physically fit and &lt;70 years of age have moved to autologous stem cell transplantation, we could not evaluate a duration of initial response. Patients who required less than 6 months (65 patients) to reach a plateau status had a mean survival of 47,51 months while patients requiring 6‐12 months had 41.23 months and patients who needed more than 12 months had a mean survival of 36 months. Summary/Conclusion: Despite the observation of MayoClinic, we did not observe a relation with slow responders and prolonged survival. On the contrary, we observed that patients who respond to first line therapy had a longer survival, probably related with more chemosensitive disease.
SP0181 TREATMENT OF GCA
Authors: John H. Stone
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> The treatment of giant cell arteritis (GCA) has taken a dramatic leap forward over the past 18 months, with the start of the era of interleukin-6 inhibition for the treatment of this disease. For the first time in 70 years, rheumatologists now have a highly-effective alternative to continuous therapy with doses of glucocorticoids that are often unacceptably high, leading inevitably to steroid-related toxicity. Clinicians now have many questions about the optimal approach to treatment in this new era: When should IL-6 inhibition begin? How quickly should glucocorticoids be tapered? Should prednisone be stopped completely? Can tocilizumab ever be discontinued? How does one monitor for the possibility of disease flare? This session will address all of these questions using a data-driven approach, with reference to new data from the GiACTA trial <h3>Disclosure of Interests:</h3> John H. Stone Grant/research support from: F. Hoffmann-La Roche, Genentech, Xencor, Consultant for: Chugain, F. Hoffmann-La Roche, Genentech, Xencor
Human Migration and the Spread of the Nematode Parasite Wuchereria bancrofti
Authors: Scott T Small, Frédéric Labbé, Yaya I Coulibaly, Thomas B Nutman, Christopher L King, David Serre, Peter A Zimmerman
Journal: Molecular Biology and Evolution (2019)

The human disease lymphatic filariasis causes the debilitating effects of elephantiasis and hydrocele. Lymphatic filariasis currently affects the lives of 90 million people in 52 countries. There are three nematodes that cause lymphatic filariasis, Brugia malayi, Brugia timori, and Wuchereria bancrofti, but 90% of all cases of lymphatic filariasis are caused solely by W. bancrofti (Wb). Here we use population genomics to reconstruct the probable route and timing of migration of Wb strains that currently infect Africa, Haiti, and Papua New Guinea (PNG). We used selective whole genome amplification to sequence 42 whole genomes of single Wb worms from populations in Haiti, Mali, Kenya, and PNG. Our results are consistent with a hypothesis of an Island Southeast Asia or East Asian origin of Wb. Our demographic models support divergence times that correlate with the migration of human populations. We hypothesize that PNG was infected at two separate times, first by the Melanesians and later by the migrating Austronesians. The migrating Austronesians also likely introduced Wb to Madagascar where later migrations spread it to continental Africa. From Africa, Wb spread to the New World during the transatlantic slave trade. Genome scans identified 17 genes that were highly differentiated among Wb populations. Among these are genes associated with human immune suppression, insecticide sensitivity, and proposed drug targets. Identifying the distribution of genetic diversity in Wb populations and selection forces acting on the genome will build a foundation to test future hypotheses and help predict response to current eradication efforts.
AB0835 BONE MINERAL LOSS DURING ULCERATIVE COLITIS : PREVALENCE AND RISK FACTORS
Authors: Hela Kchir, Maha Mtir, Dhilel Issaoui, Dhouha Cherif, dhia kaffel, Nadia Maamouri
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Patients with ulcerative colitis (UC) are at increased risk of bone mineral loss, leading to osteoporosis and osteopenia. Etiopathogenetic factors may be divided into factors specific to the underlying inflammatory process, and factors resulting from the disease process, such as, malabsorption of nutrients vitamins and minerals,decreases in weight,and the use of bone toxic medications. Objectives: to evaluate the prevalence and possible risk factors for bone mineral density disorders in patients with UC. <h3>Methods</h3> A retrospective study from January 2000 to December 2018, including all patients with UC followerd in our department. Bone mineral density was determined by dual energy X-ray absorptiometry. <h3>Results</h3> Seventy eight patients were included in our study (36 men, 26 premenopausal, and 17 postmenopausal women) with an average age of 47.5 years. Forty osteodensitometries (DXA) were performed : 17 were normal ( 42.5%), 13 patients had osteopenia (32.5%) and 10 suffered from osteoporosis (25%). Among the 23 patients having a bone mineral loss, the average Z-score were (-0.8 SD) in the femoral neck and (-1.78 SD) in the lumbar (L2-L4) spine whereas the average T-score were (-1.23 SD) in the femoral neck and (-2.15 SD) in the lumbar (L2-L4) spine. Osteoporotic patients included 12 men, 5 premenopausal, and 6 postmenopausal women with an average age of 53.04 years. The research of risk factors has shown that 14 patients with bone mineral loss (60.86%) underwent systemic corticosteroid treatment with an average duration of 6 months. Tobacco intoxication has been mentioned in 8 cases (34.78%) and alcoholism in 6 cases (26.08%). Otherwise, patients with bone mineral loss showed a lower body mass index (average BMI =19.46) than patients with normal bone density (average BMI = 23.64). Anemia has been reported in 11 cases with low bone density (47.82%) and low level of albumin as noted In 8 cases (34.78%). No osteoporotic fractures has been reported. Pan-ulcerative Colitis was reported in 11 cases (47.82%) and acute severe ulcerative colitis in 10 cases (43.47%). <h3>Conclusion</h3> Our study shows that more than half of our patients having ulcerative colitis (UC) who had an osteodensitometry presented bone demineralization (osteoporosis or osteopenia ). It seems to be associated with a low BMI, an extended and severe form of UC,and the cumulative corticoid doses. <h3>Disclosure of Interests</h3> None declared