tbuckley/cabot-search huggingface dataset:
AB0865-HPR FREQUENCY OF DEPRESSION IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: L. Cano Garcia, S. Manrique Arija, F. Godoy-Navarrete, A. M. Cabezas-Lucena, G. Diaz-Cordobes, N. Mena-Vázquez
Journal: Annals of the Rheumatic Diseases (2021)

Objectives: Cross-sectional observational study of a series of SLE patients selected from the Rheumatology consultations. Methods: age ≥18 years with SLE (ACR 1997 criteria) capable of understanding and willing to take the questionnaires. Protocol: All patients with SLE undergoing follow-up in the rheumatology clinic are recorded in a database. A telephone call was made to all the patients included in the database and those patients who responded to the call and gave their verbal consent for the collection of data from their clinical history and completed the Goldberg questionnaire were finally included. The nurse was in charge of explaining the questionnaire to the patients. Variables: the main outcome variable was depression assessed by Goldberg (≥2 depression) and other variables were: previous diagnosis of depression, Charlson index, polypharmacy, psychiatric medication, referral to mental health or primary care, SLEDAI and SLICC. Descriptive, bivariate statistical analysis and multivariate logistic regression analysis (VD: Goldberg depression). Results: 89 patients with SLE were included (95.5% women, mean age 49.44 ± 13.2 years and 18.28 ± 9.19 years of disease). The mean (SD) of the Goldberg scale in all the patients was 3.2 ± 2.9 and a total of 45 patients (50.4%) met criteria of depression according to Goldberg’s screening, of which 19 (21.3%) patients had a previous diagnosis of depression. Only 9 patients (10.1%) had had a mental health follow-up and 22 patients (24.7%) were being followed by the family doctor. A total of 87 patients (97.8%) presented polypharmacy: severe polypharmacy 59 (66.3%) and 33 (37.1%) psychiatric medication. The most used psychiatric medication was: 7 (7.8%) bromazepam, 6 (6.7%) citalopram, 5 (5.6%) diazepam. Regarding comorbidities, the Charlson index was 1.82 ± 1.21, also highlighting that 34 (27%) of the sample had Sjögren syndrome. In the multivariate analysis, polypharmacy (OR, 1.8 [95% CI, 1.0-3.1]) and Sjogren’s syndrome (OR, 3.8 [95% CI, 1.0-10.7]) were independently associated with depression by Goldberg. Conclusion: Depression is underdiagnosed and undertreated in patients with SLE. Depression is associated with polypharmacy and the perception of patients with SLE of being ill. It is important to correctly treat depression in the context of SLE comorbidity due to its great impact on quality of life. Disclosure of Interests: None declared
Spatial concordance of DNA methylation classification in diffuse glioma
Authors: Niels Verburg, Floris P Barthel, Kevin J Anderson, Kevin C Johnson, Thomas Koopman, Maqsood M Yaqub, Otto S Hoekstra, Adriaan A Lammertsma, Frederik Barkhof, Petra J W Pouwels, Jaap C Reijneveld, Annemieke J M Rozemuller, Jeroen A M Beliën, Ronald Boellaard, Michael D Taylor, Sunit Das, Joseph F Costello, William Peter Vandertop, Pieter Wesseling, Philip C de Witt Hamer, Roel G W Verhaak
Journal: Neuro-Oncology (2021)

Intratumoral heterogeneity is a hallmark of diffuse gliomas. DNA methylation profiling is an emerging approach in the clinical classification of brain tumors. The goal of this study is to investigate the effects of intratumoral heterogeneity on classification confidence.We used neuronavigation to acquire 133 image-guided and spatially separated stereotactic biopsy samples from 16 adult patients with a diffuse glioma (7 IDH-wildtype and 2 IDH-mutant glioblastoma, 6 diffuse astrocytoma, IDH-mutant and 1 oligodendroglioma, IDH-mutant and 1p19q codeleted), which we characterized using DNA methylation arrays. Samples were obtained from regions with and without abnormalities on contrast-enhanced T1-weighted and fluid-attenuated inversion recovery MRI. Methylation profiles were analyzed to devise a 3-dimensional reconstruction of (epi)genetic heterogeneity. Tumor purity was assessed from clonal methylation sites.Molecular aberrations indicated that tumor was found outside imaging abnormalities, underlining the infiltrative nature of this tumor and the limitations of current routine imaging modalities. We demonstrate that tumor purity is highly variable between samples and explains a substantial part of apparent epigenetic spatial heterogeneity. We observed that DNA methylation subtypes are often, but not always, conserved in space taking tumor purity and prediction accuracy into account.Our results underscore the infiltrative nature of diffuse gliomas and suggest that DNA methylation subtypes are relatively concordant in this tumor type, although some heterogeneity exists.
Abstract 54: The Effect of Nicotine and Menthol in Secondhand Smoke on Endothelial Function
Authors: Jiangtao Liu*, Pooneh Nabavizadeh*, Ronak Derakhshandeh, Xiaoyin Wang, Stanton A Glantz, Matthew L Springer
Journal: Circulation Research (2017)

Introduction: We have previously shown that even one minute of exposure to secondhand smoke (SHS) of tobacco and marijuana can impair arterial flow-mediated dilation (FMD) in rats. The identity of specific constituents of SHS that cause vascular toxicity remains unclear. Nicotine is a vasoconstrictor that potentially can affect vascular function. Menthol is a cigarette additive popular with African Americans, women, youth, and other ethnicities. Menthol interacts with smoke constituents and irritants such as acrolein through receptor ion channels and also affects the metabolism rate of nicotine. Hypothesis: We tested three hypotheses pertaining to acute effects of brief exposures to SHS: (1) nicotine increases the extent of endothelial functional impairment; (2) menthol decreases the extent of endothelial functional impairment; and (3) there is an interaction between the effects of nicotine and menthol. Methods: We exposed 8 groups of rats (n=8-10/group) for 10 minutes to two different levels of SHS from the following four different types of research reference tobacco: conventional nicotine (~15 mg/g tobacco), reduced nicotine (~0.4 mg/g tobacco), and both conventional and reduced nicotine with added menthol (~1.15 mg/g tobacco) in a 2x2 factorial (ANOVA) design. We also examined a clean air negative control group (n=9). FMD was measured before and after exposures in each rat. To calculate FMD, the femoral artery diameter was measured with micro-ultrasound before and after a 5-min transient ischemia induced by an external vascular occluder. FMD was quantified as the % vasodilation. Results: FMD was not affected in the clean air controls (p=0.13). Higher nicotine levels were associated with increased % reduction of FMD impairment (19.22±9.53% vs. 41.07±4.54% (SD); p=0.047). Adding menthol was associated with decreased % reduction of FMD impairment (40.52±4.85% vs. 18.50±9.81%; p=0.048). These two effects were independent (p for nicotine x menthol interaction = 0.6). Conclusion: Reduction of nicotine level and addition of menthol each lessen the acute impairment of FMD in rats exposed briefly to tobacco SHS.
Nodular regenerative hyperplasia in X-linked agammaglobulinemia: An underestimated and severe complication
Authors: Cristiane J. Nunes-Santos, Christopher Koh, Anjali Rai, Keith Sacco, Beatriz E. Marciano, David E. Kleiner, Jamie Marko, Jenna R.E. Bergerson, Michael Stack, Maria M. Rivera, Gregory Constantine, Warren Strober, Gulbu Uzel, Ivan J. Fuss, Luigi D. Notarangelo, Steven M. Holland, Sergio D. Rosenzweig, Theo Heller
Journal: Journal of Allergy and Clinical Immunology (2021)
POS0790 RELATIONSHIPS BETWEEN SALIVA IMMUNOGLOBULINS FREE LIGHT CHAINS CONCENTRATION AND CLINICAL, IMMUNOLOGICAL, HISTOLOGICAL PARAMETERS IN PATIENT WITH PRIMARY SJOGREN’S SYNDROME
Authors: E. Kuvardin, I. Kholopova, E. Belyakova, I. Grigor’eva, I. Bekhtereva, A. Maslyanskiy, Y. Krivolapov, S. Lapin
Journal: Annals of the Rheumatic Diseases (2021)

Background: Patients with primary Sjogren’s syndrome (pSS) exhibit biological signs of B cell activation such as serum polyclonal hypergammaglobulinaemia, increased levels of free light chains (FLC) and positivity for autoantibodies. B-cells may comprise up to 50% cells of lymphocytic infiltrates in salivary glands of patents with the disease. For that reasons measuring saliva B-cells products might have diagnostic value in pSS. Objectives: To evaluate relationships between saliva free light chains concentration and clinical, immunological, histological parameters in patient with pSS. Methods: Saliva and blood FLC concentrations were measured in patient with pSS (n = 24) and healthy volunteers (n = 11). Patients fulfilled the ACR/EULAR 2016 criteria of pSS. Saliva collected during assessment unstimulated salivary flow was used for analysis. Quantitative assessment of CD3 + , CD4 + , CD8 + , CD20 + , CD21 + , CD68 + , CD138 + cells was performed in minor salivary glands of 9 patient by immunohistochemistry. Cells quantity was calculated in 4 mm 2 (area of section). Results: FLC concentration in saliva of pSS patients was higher than in healthy volunteers (p&lt;0,01). Medians of saliva κ - and λ – free light chains concentrations in patients and healthy persons were 1,08 mg/L [25-;75- percentiles 0,58;1,91], 1,038 mg/L [0,55;2,03] and 0,36 mg/L [0,32; 0,54], 0,35 mg/L [0,21; 0,52] respectively. Median of saliva κ: λ chains ratio in pSS patient was 0,94 [0,6;1,5]. The ratio didn’t differ from healthy persons (p=0,24). Saliva κ – and λ – free light chain concentrations in patient with pSS correlated with patients age ( r s = 0,51, p=0,033 and r s =0,43, p= 0,011, respectively) and unstimulated salivary flow ( r s = -0,48, p=0,02 and r s =-0,49, p= 0,017, respectively). Concentration of κ – free light chain correlated with number of CD138 + -cells ( r s = 0,733, p=0,025). Interesting that saliva λ – free light chain concentration didn’t correlate with quantity of plasmatic cells. Conclusion: Measuring saliva FLC concentration might be offered as diagnostic marker of pSS. Concentration κ – free light chain can directly mirror the glands quantity of plasmatic cells. References: [1]Nocturne, Gaëtane; Mariette, Xavier (2018): B cells in the pathogenesis of primary Sjögren syndrome. In Nature reviews. Rheumatology 14 (3), pp. 133–145. DOI: 10.1038/nrrheum.2018.1. Disclosure of Interests: None declared
Mrf-2/Arid5Bの遺伝的変動は日本人個体群における冠状動脈アテローム性硬化症のリスクを与える
Authors: Wang Guoqin, Imai Yasushi, Watanabe Masafumi, Manabe Ichiro, Kohro Takahide, Monzen Koshiro, Hayashi Dobun, Maemura Koji, Yamazaki Tsutomu, Nagai Ryozo
Journal: Circulation (2007)
Genome‐wide association study identifies <i>TNFSF15</i> associated with childhood asthma
Authors: Kyung Won Kim, Dong Yun Kim, Dankyu Yoon, Ka‐Kyung Kim, Haerin Jang, Nathan Schoettler, Eun Gyul Kim, Mi Na Kim, Jung Yeon Hong, Jeom‐Kyu Lee, Sangwoo Kim, Carole Ober, Heon Yung Gee, Myung Hyun Sohn
Journal: Allergy (2021)

Genome-wide association studies (GWASs) of asthma have identified several risk alleles and loci, but most have been conducted in individuals with European-ancestry. Studies in Asians, especially children, are still lacking. We aimed to identify susceptibility loci by performing the first GWAS of asthma in Korean children with persistent asthma.We used a discovery set of 741 children with persistent asthma as cases and 589 healthy children and 551 healthy adults as controls to perform a GWAS. We validated our GWAS findings using UK Biobank data. We then used the Genotype-Tissue Expression database to identify expression quantitative trait loci of candidate variants. Finally, we quantified proteins of genes associated with asthma.Variants at the 17q12-21 locus and SNPs in CYBRD1 and TNFSF15 genes were associated with persistent childhood asthma at genome-wide thresholds of significance. Four SNPs in the TNFSF15 gene were also associated with childhood-onset asthma in British white participants in the UK Biobank data. The asthma-associated rs7856856-C allele, the lead SNP, was associated with decreased TNFSF15 expression in whole blood and in arteries. Korean children with asthma had lower serum TNFSF15 levels than controls, and those with the asthma risk rs7856856-CC genotype exhibited the lowest serum TNFSF15 levels overall, especially asthmatic children.Our GWAS of persistent childhood asthma with allergic sensitization identified a new susceptibility gene, TNFSF15, and replicated associations at the 17q12-21 childhood-onset asthma locus. This novel association may be mediated by reduced expression of serum TNFSF15 and loss of suppression of angiogenesis.
Data-Driven Kidney Transplant Phenotyping as a Histology-Independent Framework for Biomarker Discovery
Authors: Konrad Buscher, Barbara Heitplatz, Veerle van Marck, Jian Song, Sophie Loismann, Rebecca Rixen, Birte Hüchtmann, Sunil Kurian, Erik Ehinger, Dennis Wolf, Klaus Ley, Hermann Pavenstädt, Stefan Reuter
Journal: Journal of the American Society of Nephrology (2021)

In transplant medicine, clinical decision making largely relies on histology of biopsy specimens. However, histology suffers from low specificity, sensitivity, and reproducibility, leading to suboptimal stratification of patients. We developed a histology-independent immune framework of kidney graft homeostasis and rejection.We applied tailored RNA deconvolution for leukocyte enumeration and coregulated gene network analysis to published bulk human kidney transplant RNA transcriptomes as input for unsupervised, high-dimensional phenotype clustering. We used framework-based graft survival analysis to identify a biomarker that was subsequently characterized in independent transplant biopsy specimens.We found seven immune phenotypes that confirm known rejection types and uncovered novel signatures. The molecular phenotypes allow for improved graft survival analysis compared with histology, and identify a high-risk group in nonrejecting transplants. Two fibrosis-related phenotypes with distinct immune features emerged with reduced graft survival. We identified lysyl oxidase-like 2 (LOXL2)-expressing peritubular CD68+ macrophages as a framework-derived biomarker of impaired allograft function. These cells precede graft fibrosis, as demonstrated in longitudinal biopsy specimens, and may be clinically useful as a biomarker for early fibrogenesis.This study provides a comprehensive, data-driven atlas of human kidney transplant phenotypes and demonstrates its utility to identify novel clinical biomarkers.
CCL17-producing cDC2s are essential in end-stage lupus nephritis and averted by a parasitic infection
Authors: Laura Amo, Hemanta K. Kole, Bethany Scott, Chen-Feng Qi, Juan Wu, Silvia Bolland
Journal: Journal of Clinical Investigation (2021)

Lupus nephritis is a severe organ manifestation in systemic lupus erythematosus leading to kidney failure in a subset of patients. In lupus-prone mice, controlled infection with Plasmodium parasites protects against the progression of autoimmune pathology including lethal glomerulonephritis. Here, we demonstrate that parasite-induced protection was not due to a systemic effect of infection on autoimmunity as previously assumed, but rather to specific alterations in immune cell infiltrates into kidneys and renal draining lymph nodes. Infection of lupus-prone mice with a Plasmodium parasite did not reduce the levels or specificities of autoreactive antibodies, vasculitis, immune complex–induced innate activation, or hypoxia. Instead, infection uniquely reduced kidney-infiltrating CCL17-producing bone marrow–derived type 2 inflammatory dendritic cells (iDC2s). Bone marrow reconstitution experiments revealed that infection with Plasmodium caused alterations in bone marrow cells that hindered the ability of DC2s to infiltrate the kidneys. The essential role for CCL17 in lupus nephritis was confirmed by in vivo depletion with a blocking antibody, which reduced kidney pathology and immune infiltrates, while bypassing the need for parasitic infection. Therefore, infiltration into the kidneys of iDC2s, with the potential to prime local adaptive responses, is an essential regulated event in the transition from manageable glomerulonephritis to lethal tubular injury.
Impact of prior JAK-inhibitor therapy with ruxolitinib on outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis: a study of the CMWP of EBMT
Authors: Nicolaus Kröger, Giulia Sbianchi, Tiarlan Sirait, Christine Wolschke, Dietrich Beelen, Jakob Passweg, Marie Robin, Radovan Vrhovac, Grzegorz Helbig, Katja Sockel, Eibhlin Conneally, Marie Thérèse Rubio, Yves Beguin, Jürgen Finke, Paolo Bernasconi, Elena Morozova, Johannes Clausen, Peter von dem Borne, Nicolaas Schaap, Wilfried Schroyens, Francesca Patriarca, Nicola Di Renzo, Zeynep Arzu Yeğin, Patrick Hayden, Donal McLornan, Ibrahim Yakoub-Agha
Journal: Leukemia (2021)

Abstract JAK1/2 inhibitor ruxolitinib (RUX) is approved in patients with myelofibrosis but the impact of pretreatment with RUX on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) remains to be determined. We evaluated the impact of RUX on outcome in 551 myelofibrosis patients who received HSCT without ( n = 274) or with ( n = 277) RUX pretreatment. The overall leukocyte engraftment on day 45 was 92% and significantly higher in RUX responsive patients than those who had no or lost response to RUX (94% vs. 85%, p = 0.05). The 1-year non-relapse mortality was 22% without significant difference between the arms. In a multivariate analysis (MVA) RUX pretreated patients with ongoing spleen response at transplant had a significantly lower risk of relapse (8.1% vs. 19.1%; p = 0.04)] and better 2-year event-free survival (68.9% vs. 53.7%; p = 0.02) in comparison to patients without RUX pretreatment. For overall survival the only significant factors were age &gt; 58 years ( p = 0.03) and HLA mismatch donor ( p = 0.001). RUX prior to HSCT did not negatively impact outcome after transplantation and patients with ongoing spleen response at time of transplantation had best outcome.
POS0940 THE IMPACT OF TUMOUR NECROSIS FACTOR-ALPHA INHIBITOR TREATMENT ON WNT SIGNALING INHIBITORS, NOGGIN AND CYTOKINE LEVELS IN AXIAL SPONDYLOARTHRITIS
Authors: N. Atas, B. Çakir, F. Bakir, M. Uçar, H. Satiş, G. T. Güz, H. Babaoglu, R. Bilici Salman, A. Avanoglu Guler, H. Karadeniz, S. Haznedaroglu, B. Goker, M. A. Ozturk, A. Tufan
Journal: Annals of the Rheumatic Diseases (2021)

Background: Axial spondyloarthritis (axSpA) is a common chronic inflammatory disease of the axial skeleton. Some cytokines have important roles in initiation and progression of disease and are elevated in active disease. Additionally, Wnt signaling pathway inhibitors and noggin also appear to be involved in pathogenesis of ankylosing spondylitis. Anti-tumor necrosis factor-alpha (TNF) agents have dramatically improved the clinical outcome of axSpa; however, acceptable clinical improvement is not achieved in all patients and capacity of anti-TNF to slow or prevent structural damage still remains controversial. Objectives: To evaluate the effect of anti-TNF on inflammatory and noninflammatory milieu in patients with axSpA. Methods: In this prospective study we included 30 biologic treatment naive adult patients with axSpA and 30 healthy controls. All patients with high disease activity were treated with anti-TNF therapy for 6 months. Laboratory and clinical evaluation of all patients were performed at baseline and after 6 months of anti-TNF treatment. Following cytokines and wnt/BMP antagonists were measured; TNF-Alpha, COX-2, IL-6, IL-17, IL-22, IL-23, IL-33, dickkopf-1, sclerostin, noggin. Results: The mean age of patients with axSpA and healthy controls were 38.1±13.3 and 37.7±7.7 years, respectively (p&gt;0.005). At baseline, the median (IQR) TNF-alpha was higher in axSpA patients when compared to healthy controls, 34.4 pg/ml (31.4-37.03) vs 18.1 pg/ml (12.1-28.4), (p&lt;0.001), while the median (IQR) dickkopf-1 and sclerostin were lower in axSpA patients, 446.7 pg/ml (356.9-529.3) vs 1088.7 pg/ml (951.7-1244.4), (p&lt;0.001) and 312.4 pg/ml (140.8-412.7) vs 412.3 pg/ml (295.4-512.8), (p&lt;0.001), respectively. IL-17, IL-22, IL-33, dickkopf-1 and sclerostin increased with anti-TNF treatment (table 1). Conclusion: Elevation of some cytokines which are important in pathogenesis of axSpA and nonincrease in noggin with anti-TNF drugs may affect effectiveness of anti-TNF treatment. Table 1. Changes of cytokines, dickkopf-1, sclerostin and noggin with anti-TNF treatment. Pre-Anti-TNF Post-Anti-TNF P value IL-6 45(39.1-68.8) 47.6(27.3-61.1) 0.750 IL-17 93.3 (85.1-104.8) 102.1(86.6-114.6) 0.026 IL-22 159,2 (151,9-178.4) 183.5(156.3-304.6) 0.033 IL-23 36.5 (26.1-52.9) 41.3(28.4-55.5) 0.658 IL-33 127.8 (106.6-186.1) 147.06(128.5-213.4) 0.016 COX2 0.176 (0-0.374) 0.202(0.051-1.151) 0.469 TNFalpha 34.4(31.4-37.03) 30.7(12.8-35.6) 0.004 Dickkopf-1 446.7(356.9-529.3) 881.3(663.1-972.2) &lt;0.001 Sclerostin 312.4 (140.8-412.7) 405.1(276.3-452.5) 0.018 Noggin 48.3(17.04-153.9) 31.2(11.3-103.7) 0.264 Disclosure of Interests: None declared
Minicircles for a two-step blood biomarker and PET imaging early cancer detection strategy
Authors: Elise R. Robinson, Gayatri Gowrishankar, Aloma L. D'Souza, Azadeh Kheirolomoom, Tom Haywood, Sharon S. Hori, Hui-Yen Chuang, Yitian Zeng, Spencer K. Tumbale, Amin Aalipour, Corinne Beinat, Israt S. Alam, Ataya Sathirachinda, Masamitsu Kanada, Ramasamy Paulmurugan, Katherine W. Ferrara, Sanjiv S. Gambhir
Journal: Journal of Controlled Release (2021)
Whole-Exome Sequencing of Radiation-Induced Thymic Lymphoma in Mouse Models Identifies Notch1 Activation as a Driver of p53 Wild-Type Lymphoma
Authors: Chang-Lung Lee, Kennedy D. Brock, Stephanie Hasapis, Dadong Zhang, Alexander B. Sibley, Xiaodi Qin, Jeremy S. Gresham, Isibel Caraballo, Lixia Luo, Andrea R. Daniel, Matthew J. Hilton, Kouros Owzar, David G. Kirsch
Journal: Cancer Research (2021)

Abstract Mouse models of radiation-induced thymic lymphoma are widely used to study the development of radiation-induced blood cancers and to gain insights into the biology of human T-cell lymphoblastic leukemia/lymphoma. Here we aimed to identify key oncogenic drivers for the development of radiation-induced thymic lymphoma by performing whole-exome sequencing using tumors and paired normal tissues from mice with and without irradiation. Thymic lymphomas from irradiated wild-type (WT), p53+/−, and KrasLA1 mice were not observed to harbor significantly higher numbers of nonsynonymous somatic mutations compared with thymic lymphomas from unirradiated p53−/− mice. However, distinct patterns of recurrent mutations arose in genes that control the Notch1 signaling pathway based on the mutational status of p53. Preferential activation of Notch1 signaling in p53 WT lymphomas was also observed at the RNA and protein level. Reporter mice for activation of Notch1 signaling revealed that total-body irradiation (TBI) enriched Notch1hi CD44+ thymocytes that could propagate in vivo after thymocyte transplantation. Mechanistically, genetic inhibition of Notch1 signaling in immature thymocytes prevented formation of radiation-induced thymic lymphoma in p53 WT mice. Taken together, these results demonstrate a critical role of activated Notch1 signaling in driving multistep carcinogenesis of thymic lymphoma following TBI in p53 WT mice. Significance: These findings reveal the mutational landscape and key drivers in murine radiation-induced thymic lymphoma, a classic animal model that has been used to study radiation carcinogenesis for over 70 years.
Redox-responsive nanoassembly restrained myeloid-derived suppressor cells recruitment through autophagy-involved lactate dehydrogenase A silencing for enhanced cancer immunochemotherapy
Authors: Chunyu Xia, Man Li, Guangyao Ran, Xuhui Wang, Zhengze Lu, Ting Li, Xian Tang, Zhirong Zhang, Qin He
Journal: Journal of Controlled Release (2021)