tbuckley/cabot-search huggingface dataset:
Abstract 12476: The Paradoxical Effects of MMP12 Inhibition on the Development of Abdominal Aortic Aneurysms and Aortic Dissections
Authors: Karina Di Gregoli, Sarah J George, Vincent Dive, Jason L Johnson
Journal: Circulation (2018)

Aortic Dissections (AD) and Abdominal Aortic Aneurysms (AAA) account for 2-5% of deaths worldwide and progression of both aorto-pathologies is characterised by increased activity of matrix metallop...
Estimation of the Carbon Footprint Associated With Attendees of the American Psychiatric Association Annual Meeting
Authors: Joshua R. Wortzel, Alec Stashevsky, Jeremy D. Wortzel, Beth Mark, Janet Lewis, Elizabeth Haase
Journal: JAMA Network Open (2021)

This cross-sectional study uses data from the 2018 and 2019 American Psychiatric Association (APA) annual meetings to assess the carbon dioxide equivalent emissions associated with the conferences and how they may be reduced.
Contribution of a European‐Prevalent Variant near <i>CD83</i> and an East Asian–Prevalent Variant near <i>IL17RB</i> to Herpes Zoster Risk in Tofacitinib Treatment: Results of Genome‐Wide Association Study Meta‐Analyses
Authors: Nan Bing, Huanyu Zhou, Xing Chen, Tomohiro Hirose, Yuta Kochi, Yumi Tsuchida, Kazuyoshi Ishigaki, Shuji Sumitomo, Keishi Fujio, Baohong Zhang, Hernan Valdez, Michael S. Vincent, David Martin, James D. Clark
Journal: Arthritis & Rheumatology (2021)

Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA), psoriatic arthritis, and ulcerative colitis, and has been previously investigated for psoriasis (PsO). This meta-analysis of genome-wide association studies (GWAS) was performed to identify genetic factors associated with increased risk/faster onset of herpes zoster (HZ) in subjects with RA or PsO receiving tofacitinib treatment, and to determine potential mechanisms that could be attributed to the varying rates of HZ across ethnicities.In an ethnicity/indication-specific, trans-ethnic, trans-population meta-analysis of GWAS in subjects with RA or PsO from phase II, phase III, and long-term extension studies of tofacitinib, 8 million genetic variants were evaluated for their potential association with time to an HZ event and incidence of an HZ event (case versus control) with tofacitinib treatment, using Cox proportional hazard and logistic regression analyses, respectively.In total, 5,246 subjects were included (3,168 with RA and 2,078 with PsO). After adjustment for age, baseline absolute lymphocyte count, genetically defined ethnicity, and concomitant methotrexate use (in RA subjects only), 4 loci were significantly associated with faster onset of HZ in European subjects (P < 5 × 10-8 ), including a single-nucleotide polymorphism (SNP) near CD83 (frequency of risk allele ~2% in European subjects versus ~0.1% in East Asian subjects). In the trans-ethnic, trans-population meta-analysis, the CD83 SNP remained significant. Four additional significant loci were identified in the meta-analysis, among which a SNP near IL17RB was associated with faster onset of HZ (meta-analysis hazard ratio 3.6 [95% confidence interval 2.40-5.44], P = 7.6 × 10-10 ; frequency of risk allele ~12% in East Asian subjects versus <0.2% in European subjects).Genetic analysis of tofacitinib-treated subjects with RA or PsO identified multiple loci associated with increased HZ risk. Prevalent variants near the immune-relevant genes CD83 and IL17RB in European and East Asian populations, respectively, may contribute to risk of HZ in tofacitinib-treated subjects.
SAT0140 SAFETY OF TOFACITINIB THERAPY IN HBSAG CARRIERS WITH RHEUMATOID ARTHRITIS: A PROSPECTIVE STUDY
Authors: L. Fang, Z. Lin, Z. Liao, O. Jin, Y. Pan, J. Gu
Journal: Annals of the Rheumatic Diseases (2020)

Background: Targeted synthetic DMARDs (ts-DMARDs) are becoming more available and affordable in developing countries, where the prevalence of hepatitis B virus (HBV) infection is still an important public health issue. The safety of ts-DMARDs therapy in terms of the reactivation of hepatitis B virus (HBV) infection need more concern. Rare data from a prospective study focus on the use of ts-DMARDs in patients with concurrent rheumatoid arthritis (RA) and HBV infection were available by now. Objectives: To evaluate the influence of tofacitinib on reactivation of HBV infection in HBsAg carriers with RA. Methods: In this 52 weeks observation, HBsAg carriers with active RA (DAS28&gt;5.1) despite failed combined treatment with MTX and other non-biological DMARDs were enrolled. Patients must have normal liver function prior to study. All patients received therapy with tofacitinib (5mg twice daily) and concomitant MTX (10-12.5mg/w). Entecavir was prescribed preventively for patients who had a baseline HBV load &gt;2000 copy/ml (group 1), and Lamivudin for patients with HBV load ≤ 2000 copy/ml (group 2). Liver enzymes (AST/ALT) and HBV viral load were monitored every 4 weeks. Increased viral load and abnormal liver function were managed according to expert opinion. Results: Thirteen patients (10 female) were recruited. Nine patients had a baseline viral load &gt;2000 copy/ml (group 1, with preventive Entecavir), and the other 4 patients had a viral load ≤ 2000 copy/ml (group 2, with preventive Lamivudin). Two patients from group 1 discontinued tofacitinib at week 12 due to ineffectiveness, and both continued taking Entecavir for another 3 months after the discontinuation of tofacitinib. No reactivation of hepatitis B was observed in patients from group 1. One patients (female, 54 years old) from group 2 underwent a mild increase of both ALT and AST (67 and 56 IU/L, respectively) at week 16. An elevated viral load (4.9e6 copies/ml, baseline 1.4e3) and a HBV YMDD mutant was also found. The tofacitinib treatment continued. After prescription of Adefovir (combined with the pre-existing Lamivudin), both liver enzyme and viral load decreased to normal range in 8 weeks and remained normal throughout the study. Conclusion: An aggressive Tofacitinib + MTX therapy may be a safe option for HBsAg carriers with cs-DMARDs refractory RA. More active and effective prophylaxis strategy may be recommended to reduce the risk of HBV reactivation during the treatment. References: [1]Chen YM, Huang WN, Wu YD, et al. Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofacitinib: a real-world study. Ann Rheum Dis 2018; 77:780-2. Disclosure of Interests: : None declared
<i>Colonosight</i>: Multitarget RNA-FIT assay for noninvasive detection of advanced colorectal neoplasia.
Authors: Erica Kay Barnell, Yiming Kang, Andrew Ross Barnell, Kimberly Ray Kruse, Jared Fiske, Zachary R Pittz, Adnan Khan, Faith L. Holmes, Thomas A Heubner, Malachi Griffith, Obi Griffith, Aadel A Chaudhuri, Elizabeth Marie Wurtzler
Journal: Journal of Clinical Oncology (2021)

25 Background: Effective colorectal cancer (CRC) prevention and screening requires sensitive detection of all advanced neoplasias (colorectal cancer and advanced adenomas). Existing noninvasive screening approaches cannot accurately detect precancerous adenomas with high sensitivity. Here we describe a multi-factor assay (RNA-FIT test) that combines 8 stool-derived eukaryotic RNA (seRNA) biomarkers, patient demographic information (smoking status), and a fecal immunochemical test (FIT) to sensitively detect advanced colorectal neoplasias and other precancerous adenomas in a 1,305 average risk (45-75 age) prospective cohort. Methods: Average-risk patients undergoing colorectal cancer screening were prospectively evaluated with the RNA-FIT assay prior to an optical colonoscopy. RNA-FIT test results were generated using an ordinal regression model and results were compared to the colonoscopy findings. The model was initially assessed via 5-fold internal cross-validation of the training set and the ultimate model performance was assessed on a hold out testing set. Results: Of the 1,305 eligible patients recruited, 939 were included in the training set and 366 samples were reserved for the hold out testing set. When evaluating all 5 folds of the training set, internal cross validation attained a 61% sensitivity for advanced neoplasias (n = 69), 22% sensitivity for other adenomas (n = 279), 80% specificity for hyperplastic polyps (n = 155) and 86% specificity for no findings on a colonoscopy (n = 436). When employed on the testing set, the RNA-FIT test attained a 62% sensitivity for advanced neoplasias (n = 52), 27% sensitivity for other adenomas (n = 139), 78% specificity for hyperplastic polyps (n = 74) and 84% specificity for no findings on a colonoscopy (n = 101). Sensitivity for colorectal cancer and advanced adenomas with high-grade dysplasia / carcinoma in-situ was 100% in both the training set (n = 6) and hold out testing set (n = 5). Sensitivity for villous / tubulovillous adenomas was 65% in the training set (n = 23) and 60% in the hold out testing set (n = 15). Additional retrospective sample collection from patients with CRC is ongoing to further validate assay sensitivity for CRC. Conclusions: The RNA-FIT assay demonstrated clinically relevant detection of all advanced neoplasia, including early carcinomas, advanced adenomas, and other precancerous lesions. This assay could represent a noninvasive option to prevent colorectal cancer development through precancerous adenoma detection.
ABC of complementary medicine: Hypnosis and relaxation therapies
Authors: A. Vickers, C. Zollman
Journal: BMJ (1999)

A wide variety of complementary therapies claim to improve health by producing relaxation. Some use the relaxed state as a means of promoting psychological change. Others incorporate movement, stretches, and breathing exercises. Relaxation and “stress management” are found to a certain extent within conventional medicine. They are included here because they are generally not well taught in conventional medical curriculums and because of the overlap with other, more clearly complementary, therapies.
Impact of the Extent of Lymph Node Dissection on Precise Staging and Survival in Clinical I–II Pure-Solid Lung Cancer Undergoing Lobectomy
Authors: Donglai Chen, Yiming Mao, Junmiao Wen, Jian Shu, Fei Ye, Yunlang She, Qifeng Ding, Li Shi, Tao Xue, Min Fan, Yongbing Chen, Chang Chen
Journal: Journal of the National Comprehensive Cancer Network (2021)

Background: This study sought to determine the optimal number of examined lymph nodes (ELNs) and examined node stations (ENSs) in patients with radiologically pure-solid non–small cell lung cancer (NSCLC) who underwent lobectomy and ipsilateral lymphadenectomy by investigating the impact of ELNs and ENSs on accurate staging and long-term survival. Materials and Methods: Data from 6 institutions in China on resected clinical stage I–II (cI–II) NSCLCs presenting as pure-solid tumors were analyzed for the impact of ELNs and ENSs on nodal upstaging, stage migration, recurrence-free survival (RFS), and overall survival (OS). Correlations between different endpoints and ELNs or ENSs were fitted with a LOWESS smoother, and the structural break points were determined by Chow test. Results: Both ELNs and ENSs were identified as independent prognostic factors for OS (ENS hazard ratio [HR], 0.690; 95% CI, 0.597–0.797; P &lt;.001; ELN HR, 0.950; 95% CI, 0.917–0.983; P =.004) and RFS (ENS HR, 0.859; 95% CI, 0.793–0.931; P &lt;.001; ELN HR, 0.960; 95% CI, 0.942–0.962; P &lt;.001), which were also associated with postoperative nodal upstaging (ENS odds ratio [OR], 1.057; 95% CI, 1.002–1.187; P =.004; ELN OR, 1.186; 95% CI, 1.148–1.226; P &lt;.001). A greater number of ELNs and ENSs correlated with a higher accuracy of nodal staging and a lower probability of stage migration. Cut-point analysis revealed an optimal cutoff of 18 LNs and 6 node stations for stage cI–II pure-solid NSCLCs, which were validated in our multi-institutional cohort. Conclusions: Extensive examination of LNs and node stations seemed crucial to predicting accurate staging and survival outcomes. A threshold of 18 LNs and 6 node stations might be considered for evaluating the quality of LN examination in patients with stage cI–II radiologically pure-solid NSCLCs.
Quarantine and testing strategies in contact tracing for SARS-CoV-2: a modelling study
Authors: Billy J Quilty, Samuel Clifford, Joel Hellewell, Timothy W Russell, Adam J Kucharski, Stefan Flasche, W John Edmunds, Katherine E Atkins, Anna M Foss, Naomi R Waterlow, Kaja Abbas, Rachel Lowe, Carl A B Pearson, Sebastian Funk, Alicia Rosello, Gwenan M Knight, Nikos I Bosse, Simon R Procter, Georgia R Gore-Langton, Alicia Showering, James D Munday, Katharine Sherratt, Thibaut Jombart, Emily S Nightingale, Yang Liu, Christopher I Jarvis, Graham Medley, Oliver Brady, Hamish P Gibbs, David Simons, Jack Williams, Damien C Tully, Stefan Flasche, Sophie R Meakin, Kevin Zandvoort, Fiona Y Sun, Mark Jit, Petra Klepac, Matthew Quaife, Rosalind M Eggo, Frank G Sandmann, Akira Endo, Kiesha Prem, Sam Abbott, Rosanna Barnard, Yung-Wai D Chan, Megan Auzenbergs, Amy Gimma, C Julian Villabona-Arenas, Nicholas G Davies
Journal: The Lancet Public Health (2021)
Best practices for correctly identifying coronavirus by transmission electron microscopy
Authors: Hannah A. Bullock, Cynthia S. Goldsmith, Sara E. Miller
Journal: Kidney International (2021)

This guidance provides clear, concise strategies for identifying coronaviruses by transmission electron microscopy of ultrathin sections of tissues or infected tissue cultures. These include a description of virus morphology as well as cell organelles that can resemble viruses. Biochemical testing and caveats are discussed. Numerous references provide information for documentation and further study.
Cascade Catalytic Nanoplatform Based on “Butterfly Effect” for Enhanced Immunotherapy
Authors: Yanjiang Shao, Zeying Wang, Yutong Hao, Xueli Zhang, Ning Wang, Kunlun Chen, Junbiao Chang, Qianhua Feng, Zhenzhong Zhang
Journal: Advanced Healthcare Materials (2021)

Abstract The unique tumor microenvironment (TME) characteristics such as immunosuppression impeded traditional cancer treatments. In contrast, developing cascade catalytic nanoplatforms by fully making use of substances in TME for cancer therapy may deserve full credit. Herein, a cascade catalytic nanoplatform based on glucose oxidase (GOD) modified mesoporous iron oxide nanoparticles (IONP) loaded with Artemisinin (ART) is developed, which is designed as IONP‐GOD@ART. GOD can catalyze the oxidization of glucose into gluconic acid and H 2 O 2 , which not only realizes tumor starvation therapy, but also provides H 2 O 2 for IONP mediated Fenton reaction. Simultaneously, mesoporous IONP releases Fe 2+ and Fe 3+ ions in acidic TME. On the one hand, iron ions undergo Fenton reaction to generate hydroxyl radicals for chemodynamic therapy. On the other hand, the endoperoxide bridge in ART is broken in presence of Fe 2+ and further generates reactive oxygen species (ROS) to achieve therapeutic purpose. In this sense, IONP‐GOD@ART manipulates TME characteristics and leads to “butterfly effect”, which brings out a large amount of ROS for eliciting immunogenic cell death, inducing M1‐TAMs polarization, and further reprogramming immunosuppressive TME for enhanced immunotherapy. By this delicate design, the cascade catalytic nanoplatform of IONP‐GOD@ART realizes potent cancer immunotherapy for tumor regression and metastasis prevention.
Validity and reliability of Patient-Reported Outcomes Measurement Information System Global Health scale in adults with atopic dermatitis
Authors: Gabrielle Schwartzman, Donald Lei, Muhammad Yousaf, Sherief R Janmohamed, Paras P Vakharia, Rishi Chopra, Rajeev Chavda, Sylvie Gabriel, Kevin R Patel, Vivek Singam, Robert Kantor, Derek Y Hsu, Jonathan I Silverberg
Journal: Journal of the American Academy of Dermatology (2021)
OP0020 Tumour necrosis factor alpha acts directly on osteoclast formation by synovial mcrophages and monocytes in rheumatoid arthritis
Authors: Y Fujikawa, O Kudo, H Taira, I Itonaga, T Torisu
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown aetiology that results in progressive destruction of bone and cartilage in affected joints. It has been reported that in mouse bone marrow cell cultures TNF-alpha directly induces osteoclast formation and IL-1alpha stimulates osteoclast activation, and that this osteoclast formation and activation is independent of osteoprotegerin ligand (OPGL) signalling system.<sup>1,2</sup> <h3>Objectives</h3> TNF-alpha and IL-1alpha considered master cytokines in the process of RA but little is known about the direct effects of these cytokines on development of human osteoclasts. This study aims to determine the role of TNF-alpha and IL-1alpha, on synovial macrophage- and monocyte-osteoclast differentiation in RA. <h3>Methods</h3> Macrophages and monocytes isolated from RA patients were cultured with TNF-alpha and/or IL-1alpha on glass coverslips and dentine slices in the presence of M-CSF. Anti-TNFalpha, anti-IL-1alpha and osteoprotegerin (OPG) was added to this cultures. Cultures were assessed for cytochemical and functional evidence of osteoclast differentiation. <h3>Results</h3> The addition of TNF-alpha and M-CSF was sufficient to induce RA synovial macrophage- and monocyte-osteoclast differentiation in the absence of OPGL. This was evidenced by the formation of tartrate-resistant acid phosphatase (TRAP), vitronectin receptor, cathepsin K-positive multinucleated cells on glass coverslips and lacunar resorption pits on dentine slices. When IL-1alpha was added to this cultures together with TNF-alpha, the number of lacunar resorption pits were increased. It was found that anti-TNF-alpha inhibited osteoclast formation by RA synovial macrophages and monocytes and that although the number of TRAP-positive multinucleated cells was not changed, inhibition of pit formation was seen when anti-IL-1alpha was added to RA macrophage and monocyte cultures. OPG, however, showed no effect on osteoclast formation and activation induced by TNF-alpha and IL-1alpha. <h3>Conclusion</h3> This study has shown that TNF-alpha induces RA synovial macrophage- and monocyte-osteoclast differentiation and that IL-1alpha activates osteoclasts to resorb bone. This osteoclast formation and activation is independent of OPGL signalling system. The new mechanism, inflammatory bone resorption, may represent an important role in the RA joint destruction and osteoporosis. <h3>References</h3> Kobayashi K, Takahashi N, Jimi E, <i>et al</i>. Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med. 2000;191: 275–86 Azuma Y, Kaji K, Katogi R, Takeshita S, Kudo A. Tumor necrosis factor-alpha induces differentiation of and bone resorption by osteoclasts. J Biol Chem. 2000;275:4858–64
Relationship between lipoproteins, thrombosis, and atrial fibrillation
Authors: Wern Yew Ding, Majd B Protty, Ian G Davies, Gregory Y H Lip
Journal: Cardiovascular Research (2021)

The prothrombotic state in atrial fibrillation (AF) occurs as a result of multifaceted interactions, known as Virchow's triad of hypercoagulability, structural abnormalities, and blood stasis. More recently, there is emerging evidence that lipoproteins are implicated in this process, beyond their traditional role in atherosclerosis. In this review, we provide an overview of the various lipoproteins and explore the association between lipoproteins and AF, the effects of lipoproteins on haemostasis, and the potential contribution of lipoproteins to thrombogenesis in AF. There are several types of lipoproteins based on size, lipid composition, and apolipoprotein category, namely: chylomicrons, very low-density lipoprotein, low-density lipoprotein (LDL), intermediate-density lipoprotein, and high-density lipoprotein. Each of these lipoproteins may contain numerous lipid species and proteins with a variety of different functions. Furthermore, the lipoprotein particles may be oxidized causing an alteration in their structure and content. Of note, there is a paradoxical inverse relationship between total cholesterol and LDL cholesterol (LDL-C) levels, and incident AF. The mechanism by which this occurs may be related to the stabilizing effect of cholesterol on myocardial membranes, along with its role in inflammation. Overall, specific lipoproteins may interact with haemostatic pathways to promote excess platelet activation and thrombin generation, as well as inhibiting fibrinolysis. In this regard, LDL-C has been shown to be an independent risk factor for thromboembolic events in AF. The complex relationship between lipoproteins, thrombosis and AF warrants further research with an aim to improve our knowledge base and contribute to our overall understanding of lipoprotein-mediated thrombosis.
The clinical and molecular characteristics of patients with personal or family history of gastrointestinal malignancies/polyposis and checkpoint kinase 2 (CHEK2) mutations.
Authors: Sana Ozair, Cassandra Gurganus, Veena Krishnan, Gideon T Dosunmu, Delmer Alfredo Montoya Motino, Leander Grimm, Thuy Phung, Jessa Blount, Cindy Nelson, Moh'd M. Khushman
Journal: Journal of Clinical Oncology (2021)

44 Background: Checkpoint Kinase 2 (CHEK 2) encodes the protein CHK2, a serine/threonine kinase involved in pathways that conduct DNA repair as well as apoptosis in response to initial DNA damage. Germline mutations in the CHEK2 gene are associated with several malignancies such as colon, breast, stomach, prostate, kidney, thyroid and soft tissue cancers. Here, we describe the clinical and molecular characteristics of patients with personal or family history of gastrointestinal (GI) malignancies/polyposis and CHEK2 gene mutations. Methods: This is an IRB-approved retrospective chart-review study. Between 2016 and 2020, 1011 unique genetic counseling visits were conducted. Germline testing was recommended by a certified genetic counselor if medically necessary. All patients with a germline CHEK2 mutation were identified (N = 16). Patients with a CHEK2 mutation and personal and family history of GI malignancies/polyposis were further explored and their clinical and molecualr characteristics are summarized. Results: The reasons for referral to the Cancer Genetics Counseling Services in patients with pathogenic CHEK2 mutations were personal history of colon cancer (N = 3) and family history of colon cancer (N = 4). One patient with the CHEK2 c.1100delC mutation had a personal history of juvenile polyposis syndrome and a family history of colon cancer. In our cohort, 11 out of 16 (69%) patients had a CHEK2 mutation and personal or family history of GI malignancies/polyposis. The median age was 57 years old (25-80). Six (55%) patients were males. All (100%) patients were Caucasians. Seven (64%) patients had a pathogenic germline CHEK2 mutation and 4 (36%) patients had a variant of unknown significance (VUS). Among patients with pathogenic germline CHEK2 mutations (N = 7), 5 (72%) patients had CHEK2 c.1100delC mutation, 1 (14%) patient had CHEK2 c.190G &gt; A mutation and 1 (14%) patient had CHEK2 c.470T &gt; C mutation. The CHEK2 VUS mutations seen in our cohort were CHEK2 c.539G &gt; A, CHEK2 p.V395L, CHEK2 gain of exons 3-15 and CHEK2 c.1421G &gt; A mutations. Conclusions: All patients in our cohort with CHEK2 mutations were Caucasians. The majority of our patients (69%) had an underlying personal or family history of GI malignancies/polyposis. In patients with personal or family history of GI malignancies/polyposis and CHEK2 mutation, 64% were found to have pathogenic CHEK2 mutations. The most common diagnosed CHEK2 mutation in our cohort was CHEK2 c.1100delC mutation.