tbuckley/cabot-search huggingface dataset:
THU0012 Clonal analysis of vh and vl mrna in single b and plasma cells from rheumatoid arthritis synovium and peripheral blood
Authors: S Ruzickova, O Krystufkova, Z Cimburek, J Niederlova, J Sinkora, O Horvath, T Doerner, J Vencovsky
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Rheumatoid arthritis (RA) is characterised by a complex infiltration of many cell types including T and B lymphocytes, plasma cells, folicular dendritic cells, macrophages and other cells into synovial tissue of inflamed joints. Presence of B and plasma cells results in a local synthesis of multiple pathologic immunoglobulins contributing to the chronic joint inflammatory processes. <h3>Objectives</h3> To analyse mRNA from individual B and plasma cells isolated from synovium and peripheral blood of patients with RA, in order to investigate a clonality, VH and VL pairing and a molecular structure of produced antibodies. <h3>Methods</h3> RA synovial tissue after synovectomy was enzymatically digested. Single synovial B/plasma cells were sorted using immunofluorescent staining with anti-CD19, anti-IgM and anti-CD38. RA peripheral B cells were isolated in the same way without enzyme treatment. cDNA library from each single B and plasma cell was generated. Nested polymerase chain reaction was performed to analyse VH and VL gene usage. VH, DH and JH or VL and JL gene segments were assigned and somatic mutations determined by comparison to germline sequences on the V BASE/Genbank database. As a control peripheral B-lymphocytes from healthy donor were screened. <h3>Results</h3> Analysis of RA synovial mRNA revealed prevalence of C gamma rearranged transcripts that contained rearranged VH1, VH2, VH3, VH4, VH5 and VH6 genes. Utilisation of VH segments was similar between RA patients and normal subjects, but the accumulation of somatic mutations was elevated in RA synovial and peripheral B cells. Preferential utilisation of a limited number of VH and DH gene segments was found. There was an increased frequency of kappa light chains containing unusually long CDR3 when compared to normal peripheral B cells. mRNAs resulting from transcription of non-productive rearrangements were also detected as well as transcripts corresponding to isotype-switching. <h3>Conclusion</h3> Our findings are consistent with hypothesis that B cell response in RA synovium is probably antigen driven and oligoclonal. The project was supported by grant VS96129 from Czech Ministry of Education, Youth and Sport in the Czech Republic.
SP0109 How useful are conventional dmards and when should biologics, in particular tnf blocking agents, be used?
Authors: L Van de Putte
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> Rheumatoid arthritis is a chronic, systemic, inflammatory disease with polyarthritis as the most dominant clinical sign. Pharmacotherapy is, increasingly, the corner stone of treatment. Conventional drug treatment consists of NSAIDs, (combinations of) DMARDs and corticosteroids. In recent years dramatic changes have occurred in the treatment of the disease. These can be categorised as follows: Early treatment: it has become clear that (irreversible) joint damage occurs relatively early in the disease course. In addition recent studies have indicated that more advanced stages of the disease are more difficult to treat. More and more effective DMARDs. Some of these DMARDs have a relatively fast mode of action, allowing for more adequate drug titration towards efficacy. Another interesting development is the attempt towards side effect reduction. Successful examples are comedication with folic acid during methotrexate treatment and of biphosphonate during corticosteroid treatment. Target oriented therapies: whereas anti-T cell therapies so far have not been consistently successful, TNF blocking agents have revolutionised treatment of rheumatoid arthritis. These agents work fast and give a good response in over half of the patients. In addition it has been shown that these therapies have the potential of stopping (radiographic) joint damage. From a practical point of view there are at least a few problems: these therapies are rather expensive and long term follow-up data are not yet available. Especially the latter is important, since TNF plays an important role in inflammation and immunity and thefore chronic suppression may also have negative consequences. Furthermore, it is advised that during TNF blocking therapies, doctor and patiënt should be alert on the presence or development of infectious diseases. In view of the above considerations, current use of TNF blocking therapies should be restricted to patiënts with active disease, despite adequate DMARD therapy, including methotrexate. Possible future strategies will be discussed.
Does yoga reduce the risk of falls in older people?
Authors: Garry A Tew, Lesley Ward, Catherine Hewitt, Anne Tiedemann
Journal: BMJ (2020)

### What you need to know

Nearly a third of people aged over 65 years and over half of people older than 80 have a fall at least once a year.123 Falls and fall related injuries can be life changing and may result in chronic disability, admission to assisted living, or death. A fall can also precipitate a fear of falling, which may lead to restriction of activity and hence physical deconditioning. This in turn increases the risk of future falls.45

Clinical guidelines from several countries recommend multifactorial interventions for preventing falls in older people, with exercise as a key component.367 A recent Cochrane review (108 randomised controlled trials, 23 407 participants) concluded there is strong evidence that well designed exercise programmes reduce the number of falls by about a quarter among older people living in the community.8 Such programmes also reduce the number of people experiencing one or more falls. Exercise that mainly involved balance and functional training reduced falls.

Yoga is a mind-body practice that typically involves a combination of physical postures, breathing exercises, and concentration/meditation. Yoga has become a popular means of promoting physical and mental wellbeing9 and is shown to improve health related quality of life in older people.10 Evidence from observational studies suggests it is an acceptable and attractive form of exercise …
Abstract 1881: Immune mediated interaction between radiation and cetuximab in a syngeneic murine model of head and neck squamous cell carcinoma
Authors: Wonjong Jin, Amy K. Erbe, Ciara Schwarz, Abigail Jaquish, Bryce R. Anderson, Raghava N. Sriramaneni, Justin C. Jagodinsky, Paul A. Clark, Zachary S. Morris
Journal: Cancer Research (2020)

Abstract Purpose: Patients with head and neck squamous cell carcinoma (HNSCC) treated with anti-EGFR (cetuximab) mAb-based immunotherapy often acquire therapy-resistance, reducing clinical benefit. We evaluated the efficacy of a combined modality in situ vaccination regimen aimed at overcoming resistance to cetuximab using a syngeneic tumor model. Experimental Design: The murine HNSCC cell line MOC2 was transduced to express human EGFR (MOC2-huEGFR) and used as a syngeneic model of therapeutic resistance to cetuximab. The cells were tested for viability, radiosensitivity, and huEGFR-specific mAb binding efficacy in the presence of cetuximab. Antibody-dependent cellular cytotoxicity (ADCC) was tested by coculture of 51chromium-labeld MOC2-huEGFR with PBMC. Mice bearing these syngeneic tumors were treated with therapeutic regimens that included local radiation (RT), intratumoral (IT) cetuximab, and/or systemic immune checkpoint inhibitors, and tumor growth/survival rate were monitored. Result: Cetuximab induced antibody-dependent cellular cytotoxicity (ADCC) in MOC2-huEGFR and PBMC co-cultures, but showed no effect on cell proliferation or radiosensitivity. Combined RT and IT-cetuximab treatment induced tumor growth delay, which required huEGFR expression, NK cells, and FcγR expression. In addition, combined RT+IT-cetuximab therapy greatly induced tumor infiltration by both CD8 T cells and NK cells. RT promoted NK cell-mediated ADCC effects against 51chromium-labeld MOC2-huEGFR with increased IFNγ expression. Proliferating tumor cells gradually increased Pd-l1 mRNA expression, and RT enhanced cell surface PD-L1 in MOC2-huEGFR cells. Systemic anti-PD-L1 antibody or IT-cetuximab alone did not show antitumor response against MOC2-huEGFR bearing mice; however, significant tumor growth inhibition was observed with combined anti-PD-L1, RT, and IT-cetuximab. Conclusion: The MOC2-huEGFR HNSCC tumor model is immunologically “cold” and does not respond to either cetuximab or anti-PD-L1 therapies alone. In this model, we show that a combination of RT+cetuximab+anti-PD-L1 elicits a cooperative in situ vaccine effect. Combining RT, cetuximab and immune checkpoint blockade may enable anti-tumor immune response in HNSCC patients with immunologically cold, huEGFR-expressing tumors. Citation Format: Wonjong Jin, Amy K. Erbe, Ciara Schwarz, Abigail Jaquish, Bryce R. Anderson, Raghava N. Sriramaneni, Justin C. Jagodinsky, Paul A. Clark, Zachary S. Morris. Immune mediated interaction between radiation and cetuximab in a syngeneic murine model of head and neck squamous cell carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1881.
Development and testing of an artificial intelligence tool for predicting end-stage kidney disease in patients with immunoglobulin A nephropathy
Authors: Francesco Paolo Schena, Vito Walter Anelli, Joseph Trotta, Tommaso Di Noia, Carlo Manno, Giovanni Tripepi, Graziella D’Arrigo, Nicholas C. Chesnaye, Maria Luisa Russo, Maria Stangou, Aikaterini Papagianni, Carmine Zoccali, Vladimir Tesar, Rosanna Coppo, V. Tesar, D. Maixnerova, S. Lundberg, L. Gesualdo, F. Emma, L. Fuiano, G. Beltrame, C. Rollino, R. Coppo, A. Amore, R. Camilla, L. Peruzzi, M. Praga, S. Feriozzi, R. Polci, G. Segoloni, L. Colla, A. Pani, A. Angioi, L. Piras, J. Feehally, G. Cancarini, S. Ravera, M. Durlik, E. Moggia, J. Ballarin, S. Di Giulio, F. Pugliese, I. Serriello, Y. Caliskan, M. Sever, I. Kilicaslan, F. Locatelli, L. Del Vecchio, J.F.M. Wetzels, H. Peters, U. Berg, F. Carvalho, A.C. da Costa Ferreira, M. Maggio, A. Wiecek, M. Ots-Rosenberg, R. Magistroni, R. Topaloglu, Y. Bilginer, M. D’Amico, M. Stangou, F. Giacchino, D. Goumenos, M. Papasotiriou, K. Galesic, L. Toric, C. Geddes, K. Siamopoulos, O. Balafa, M. Galliani, P. Stratta, M. Quaglia, R. Bergia, R. Cravero, M. Salvadori, L. Cirami, B. Fellstrom, H. Kloster Smerud, F. Ferrario, T. Stellato, J. Egido, C. Martin, J. Floege, F. Eitner, T. Rauen, A. Lupo, P. Bernich, P. Menè, M. Morosetti, C. van Kooten, T. Rabelink, M.E.J. Reinders, J.M. Boria Grinyo, S. Cusinato, L. Benozzi, S. Savoldi, C. Licata, M. Mizerska-Wasiak, M. Roszkowska-Blaim, G. Martina, A. Messuerotti, A. Dal Canton, C. Esposito, C. Migotto, G. Triolo, F. Mariano, C. Pozzi, R. Boero, None Mazzucco, C. Giannakakis, E. Honsova, B. Sundelin, A.M. Di Palma, F. Ferrario, E. Gutiérrez, A.M. Asunis, J. Barratt, R. Tardanico, A. Perkowska-Ptasinska, J. Arce Terroba, M. Fortunato, A. Pantzaki, Y. Ozluk, E. Steenbergen, M. Soderberg, Z. Riispere, L. Furci, D. Orhan, D. Kipgen, D. Casartelli, D. GalesicLjubanovic, H. Gakiopoulou, E. Bertoni, P. Cannata Ortiz, H. Karkoszka, H.J. Groene, A. Stoppacciaro, I. Bajema, J. Bruijn, X. FulladosaOliveras, J. Maldyk, E. Ioachim, Daniela Abbrescia, Nikoleta Kouri, Maria Stangou, Aikaterini Papagianni, Francesco Scolari, Elisa Delbarba, Mario Bonomini, Luca Piscitani, Giovanni Stallone, Barbara Infante, Giulia Godeas, Desiree Madio, Luigi Biancone, Marco Campagna, Gianluigi Zaza, Isabella Squarzoni, Concetta Cangemi
Journal: Kidney International (2020)
Abstract 5030: Vitamin D exhibits therapeutic anti-tumor and anti-angiogenic potential by reducing VEGF levels and altering TIMP/MMP system in breast cancer
Authors: Khuloud Bajbouj, Jasmin Shafarin, Ahmad Sawan, Ahmed Shehada, Walaa Eldin Elkhalifa
Journal: Cancer Research (2020)

Abstract Background: Clinical and experimental observations suggest that Vitamin D deficiency associates with increased risk of breast cancer. Furthermore, studies concluded that Vitamin D precipitates in significant anti-neoplastic effects against breast, and inducing apoptosis and affecting angiogenesis in other types of cancer. However, the exact mechanism underlying this anti-angiogenic effect of Vitamin D is still elusive. This study aims to investigate the anti-cancer role of Vitamin D anti-cancer and its association with modulation of major factors involved in angiogenesis and metastasis in breast cancer cell lines. Experimental methods: The hormonally active form of vitamin D, 1α,25-dihydroxyvitamin D3 (calcitriol), was used to evaluate anti-proliferative effect, inhibition of cell cycle progression and apoptosis induction in two breast cancer cell lines, MCF-7 and MDA-MB-231. Furthermore, impact of calcitriol on expression and activity of tissue inhibitors of metalloproteinases (TIMP), major groups of the matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and tumor growth factor (TGF-β1) among others involved in tumor progression and angiogenesis were also examined. Results and Discussions: Calcitriol treatment (10 µM) significantly inhibited cell proliferation in a timely dependent manner. Both cell lines showed G1 cell cycle arrest, decreased levels of the cell death inhibitor, survivin, and apoptosis induction in response to calcitriol treatment. Proteome Profiler array analysis revealed that calcitriol resulted in reducing the levels of major pro-angiogenesis regulators, especially VEGF, TGF-β1, Urokinase-type plasminogen activator (uPA), and Amphiregulin. Analysis of mRNA and proteins expression upon calcitriol exposure showed an increase of TIMP1, TIMP2 and a decrease in MMP 2, 3 and 9 levels. Finally, quantitative analysis using ELISA revealed that calcitriol treatment reduced MMP2 and MMP9 activities. Conclusion: Our study demonstrates potential therapeutic property of calcitriol through inhibiting of pro-angiogenetic markers in breast cancer. Citation Format: Khuloud Bajbouj, Jasmin Shafarin, Ahmad Sawan, Ahmed Shehada, Walaa Eldin Elkhalifa. Vitamin D exhibits therapeutic anti-tumor and anti-angiogenic potential by reducing VEGF levels and altering TIMP/MMP system in breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5030.
Dissecting the heterogeneity of the alternative polyadenylation profiles in triple-negative breast cancers
Authors: Lei Wang, Guan-Tian Lang, Meng-Zhu Xue, Liu Yang, Li Chen, Ling Yao, Xiao-Guang Li, Peng Wang, Xin Hu, Zhi-Ming Shao
Journal: Theranostics (2020)

Background: Triple-negative breast cancer (TNBC) is an aggressive malignancy with high heterogeneity. However, the alternative polyadenylation (APA) profiles of TNBC remain unknown. Here, we aimed to define the characteristics of the APA events at post-transcription level among TNBCs. Methods: Using transcriptome microarray data, we analyzed APA profiles of 165 TNBC samples and 33 paired normal tissues. A pooled short hairpin RNA screen targeting 23 core cleavage and polyadenylation (C/P) genes was used to identify key C/P factors. Results: We established an unconventional APA subtyping system composed of four stable subtypes: 1) luminal androgen receptor (LAR), 2) mesenchymal-like immune-activated (MLIA), 3) basal-like (BL), 4) suppressed (S) subtypes. Patients in the S subtype had the worst disease-free survival comparing to other patients (log-rank p = 0.021). Enriched clinically actionable pathways and putative therapeutic APA events were analyzed among each APA subtype. Furthermore, CPSF1 and PABPN1 were identified as the master C/P factors in regulating APA events and TNBC proliferation. The depletion of CPSF1 or PABPN1 weakened cell proliferation, enhanced apoptosis, resulted in cell cycle redistribution and a reversion of APA events of genes associated with tumorigenesis, proliferation, metastasis and chemosensitivity in breast cancer. Conclusions: Our findings advance the understanding of tumor heterogeneity regulation in APA and yield new insights into therapeutic target identification in TNBC.
SARS-CoV-2 vaccine research and development: Conventional vaccines and biomimetic nanotechnology strategies
Authors: Lanxiang Huang, Yuan Rong, Qin Pan, Kezhen Yi, Xuan Tang, Qian Zhang, Wei Wang, Jianyuan Wu, Fubing Wang
Journal: Asian Journal of Pharmaceutical Sciences (2020)

The development of a massively producible vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, is essential for stopping the current coronavirus disease (COVID-19) pandemic. A vaccine must stimulate effective antibody and T cell responses in vivo to induce long-term protection. Scientific researchers have been developing vaccine candidates for the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) since the outbreaks of these diseases. The prevalence of new biotechnologies such as genetic engineering has shed light on the generation of vaccines against novel viruses. In this review, we present the status of the development of coronavirus vaccines, focusing particularly on the biomimetic nanoparticle technology platform, which is likely to have a major role in future developments of personalized medicine.
Abstract 5469: iCVA- A knowledge-based cancer variation annotation application
Authors: Gaurav Kumar, Melanie Kelly, Paolo Fortina, Adam Ertel
Journal: Cancer Research (2020)

Abstract A typical genomic sequencing experiment results in a long list of statistically significant variant candidates among protein-coding genes without any unifying biological theme. This leads to a daunting task of identifying the causal variants and genes to accurately diagnose the disease for clinical or research utility. While a number of downstream tools exist to aid in cancer genome annotation and interpretation, including Clinical Interpretations of Variants in Cancer (CIViC), ClinGen, Database of Curated Mutations (DoCM), Oncotator, and Variant Interpretation for Cancer (VIC), these only provide selective information (somatic/germline/gene-variant specific) or are time/resource consuming. To address this challenge, we developed a software called iCVA using the following methodology: 1) we obtained a priori defined gene sets for different cancer-inducing mechanisms such as pro-oncogenesis, tumor-suppression, DNA repair, angiogenesis, inflammation, metabolism, hypoxia, cell cycle and immune system. 2) genomic variation data were integrated from 1000 Genome, Exome Sequencing Project, Exome Aggregation Consortium (ExAC), ClinVar, dbSNP, GNOMAD, The Cancer Genome Atlas (TCGA), the Catalogue of Somatic Mutations in Cancer (COSMIC) and the International Cancer Gene Census (ICGC), and re-classified into a consensus classification according to ACMG guidelines. 3) Finally, we devised a reporting system to process mutation data from a sequencing experiment to utilize the harmonized pathway and mutational information integrated in a local database to identify and classify cancer-specific gene mutations. The iCVA reporting system classifies mutations as germline or somatic and then sub-classifies these into different cancer-specific mechanisms, including those known to be targetable through existing therapies. To our knowledge, iCVA is the first tool to provide a comprehensive report on cancer variants in a simplified and faster manner, to accelerate the genomic characterization of cancer samples analyzed by high-throughput DNA sequencing. Citation Format: Gaurav Kumar, Melanie Kelly, Paolo Fortina, Adam Ertel. iCVA- A knowledge-based cancer variation annotation application [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5469.
Modifiable Lifestyle Factors for Primary Prevention of CKD: A Systematic Review and Meta-Analysis
Authors: Jaimon T. Kelly, Guobin Su, La Zhang, Xindong Qin, Skye Marshall, Ailema González-Ortiz, Catherine M. Clase, Katrina L. Campbell, Hong Xu, Juan-Jesus Carrero
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Although CKD incidence is increasing, no evidence-based lifestyle recommendations for CKD primary prevention apparently exist. To evaluate evidence associating modifiable lifestyle factors and incidence of CKD, the authors undertook a systematic review and meta-analysis. Their analysis, which included 104 observational studies of 2,755,719 participants, demonstrated consistency of evidence for a number of measures associated with preventing CKD onset, including increasing dietary intake of vegetables and potassium (21% reduced odds and 22% reduced odds, respectively), increasing physical activity levels (18% reduced odds), moderating alcohol consumption (15% reduced risk), lowering sodium intake (21% increased odds), and stopping tobacco smoking (18% increased risk). In the absence of clinical trial evidence, these findings can help inform public health recommendations and patient-centered discussions in clinical practice about lifestyle measures to prevent CKD. Background Despite increasing incidence of CKD, no evidence-based lifestyle recommendations for CKD primary prevention apparently exist. Methods To evaluate the consistency of evidence associating modifiable lifestyle factors and CKD incidence, we searched MEDLINE, Embase, CINAHL, and references from eligible studies from database inception through June 2019. We included cohort studies of adults without CKD at baseline that reported lifestyle exposures (diet, physical activity, alcohol consumption, and tobacco smoking). The primary outcome was incident CKD (eGFR&lt;60 ml/min per 1.73 m 2 ). Secondary outcomes included other CKD surrogate measures (RRT, GFR decline, and albuminuria). Results We identified 104 studies of 2,755,719 participants with generally a low risk of bias. Higher dietary potassium intake associated with significantly decreased odds of CKD (odds ratio [OR], 0.78; 95% confidence interval [95% CI], 0.65 to 0.94), as did higher vegetable intake (OR, 0.79; 95% CI, 0.70 to 0.90); higher salt intake associated with significantly increased odds of CKD (OR, 1.21; 95% CI, 1.06 to 1.38). Being physically active versus sedentary associated with lower odds of CKD (OR, 0.82; 95% CI, 0.69 to 0.98). Current and former smokers had significantly increased odds of CKD compared with never smokers (OR, 1.18; 95% CI, 1.10 to 1.27). Compared with no consumption, moderate consumption of alcohol associated with reduced risk of CKD (relative risk, 0.86; 95% CI, 0.79 to 0.93). These associations were consistent, but evidence was predominantly of low to very low certainty. Results for secondary outcomes were consistent with the primary finding. Conclusions These findings identify modifiable lifestyle factors that consistently predict the incidence of CKD in the community and may inform both public health recommendations and clinical practice.