tbuckley/cabot-search huggingface dataset:
Corticosteroids and cellulose purification improve, respectively, the in vivo translation and vaccination efficacy of sa-mRNAs
Authors: Zifu Zhong, Séan McCafferty, Lisa Opsomer, Haixiu Wang, Hanne Huysmans, Joyca De Temmerman, Stefan Lienenklaus, João Paulo Portela Catani, Francis Combes, Niek N. Sanders
Journal: Molecular Therapy (2021)

Synthetic mRNAs are an appealing platform with multiple biomedical applications ranging from protein replacement therapy to vaccination. In comparison with conventional mRNA, synthetic self-amplifying mRNAs (sa-mRNAs) are gaining interest because of their higher and longer-lasting expression. However, sa-mRNAs also elicit an innate immune response, which may complicate their clinical application. Approaches to reduce the innate immunity of sa-mRNAs have not been studied in detail. Here we investigated, in vivo, the effect of several innate immune inhibitors and a novel cellulose-based mRNA purification approach on the type I interferon (IFN) response and the translation and vaccination efficacy of our formerly developed sa-mRNA vaccine against Zika virus. Among the investigated inhibitors, we found that corticosteroids and especially topical application of clobetasol at the sa-mRNA injection site was the most efficient in suppressing the type I IFN response and increasing the translation of sa-mRNA. However, clobetasol prevented formation of antibodies against sa-mRNA-encoded antigens and should therefore be avoided in a vaccination context. Residual dsRNA by-products of the in vitro transcription reaction are known inducers of immediate type I IFN responses. We additionally demonstrate a drastic reduction of these dsRNA by-products upon cellulose-based purification, reducing the innate immune response and improving sa-mRNA vaccination efficacy.
SAT0145 Personality structure in patients with primary fibromyalgia and reumatoid arthritis
Authors: G Vezyroglou, J Myriokefalitakis, G Papadimitriou, A Kotrotsios, C Antoniadis, K Michelidakis
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Psychiatric symptoms occur in patients with chronic pain. It is well known that patients with rheumatoid arthritis present symptoms of depression to various degrees of intensity. Primary fibromyalgia syndrome is a form of non articular rheumatism characterised by generalised aches, pains, tender points, stiffness, and fatigue. There is an interest association between depression and pain. <h3>Objectives</h3> The present study examines the personality structure of the patients with primary fibromyalgia syndrome and rheumatoid arthritis. <h3>Methods</h3> Fifty (50) patients with rheumatoid arthritis and twenty-five (25) with fibromyalgia combared with fifty (50) non-patients without pain. All patients presented the basic criteria and symptoms for rheumatoid arthritis (based in diagnostic criteria of the ARA revised at 1987 and the ACR 1990 diagnostic criteria for the fibromyalgia). The psychometric instruments are; a) HDHQ [Hostility and Direction of Hostility]. b) The SCL-90R [Symptom Check List-90R]. c) DSSI-SAD[Delusions Symptoms Inventory-State of Anxiety and Depression]. <h3>Results</h3> The patients with primary fibromyalgia presents higher scores of depression and somatization than patients with rheumatoid arthritis. <h3>Conclusion</h3> Probably the patients with rheumatoid arthritis are reasonable and accepted from this parents because is evident in our disability. <h3>References</h3> Moutsopoulos H, Chused TM, Mann D, Clippell JH, <i>et al</i>. Sjogren's syndrome. Ann Int Med. 1980;92:212 Krol B, Sanderman R, Suurmeijer TP. Social support and quality of life concepts measurement and research. Patient Educ Couns. 1993;20:101–20
Lung and thymic carcinoids: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up☆
Authors: E. Baudin, M. Caplin, R. Garcia-Carbonero, N. Fazio, P. Ferolla, P.L. Filosso, A. Frilling, W.W. de Herder, D. Hörsch, U. Knigge, C.M. Korse, E. Lim, C. Lombard-Bohas, M. Pavel, J.Y. Scoazec, A. Sundin, A. Berruti
Journal: Annals of Oncology (2021)
Atezolizumab plus Bevacizumab: A Novel Breakthrough in Hepatocellular Carcinoma
Authors: Florian Castet, Catherine E. Willoughby, Philipp K. Haber, Josep M. Llovet
Journal: Clinical Cancer Research (2021)

Abstract The combination of atezolizumab and bevacizumab increases overall survival compared with sorafenib in advanced hepatocellular carcinoma (HCC). Its approval by the FDA has launched a new era of combination therapies in advanced and earlier settings that are likely to reshape the management of HCC across all disease stages. See related article by Casak et al., p. 1836
Abstract 14497: Unbiased Discovery Proteomics Approach Using Mass Spectrometry in Search of Peripheral Biomarkers in Patients With Ischemia From Coronary Microvascular Dysfunction
Authors: Armin Nowroozpoor, Basmah Safdar, David D Gutterman
Journal: Circulation (2019)

Introduction: Coronary microvascular dysfunction (CMD) involves impaired vasoreactivity of coronary arterioles and imparts poor prognosis. We used a discovery approach for direct quantitative asses...
Covid-19 pandemic and the social determinants of health
Authors: Lauren Paremoer, Sulakshana Nandi, Hani Serag, Fran Baum
Journal: BMJ (2021)

Covid-19The road To equiTy and solidariTy Covid-19 pandemic and the social determinants of healthLauren Paremoer and colleagues call for action to create a fairer and more sustainable post-covid world• A post-covid world must ensure equity, social justice, solidarity, and a shift in the balance of power and resources to people living in poverty and otherwise marginalised on 2 August
Incidence and Predictors of Mental Health Outcomes Among Survivors of Adolescent and Young Adult Cancer: A Population-Based Study Using the IMPACT Cohort
Authors: Riddhita De, Rinku Sutradhar, Paul Kurdyak, Suriya Aktar, Jason D. Pole, Nancy Baxter, Paul C. Nathan, Sumit Gupta
Journal: Journal of Clinical Oncology (2021)

Risk and predictors of long-term mental health outcomes in survivors of adolescent and young adult (AYA) cancers are poorly characterized. Mental health is consequently neglected in long-term follow-up.We identified all AYA in Ontario, Canada age 15-21 years when diagnosed with one of six common cancers between 1992-2012 using a population-based database, and compared them with matched controls. Linkage to provincial healthcare data allowed analysis of rates of outpatient (family physician and psychiatrist) visits for psychiatric indications and time to severe psychiatric events (emergency room visit, hospitalization, and suicide). Demographic-, disease-, and treatment-related predictors of adverse outcomes, including treatment setting (adult v pediatric), were examined.Among 2,208 survivors and 10,457 matched controls, 5-year survivors experienced higher rates of outpatient mental health visits than controls (671 visits per 1,000 person-years v 506; adjusted rate ratio [RR] 1.3; 95% CI, 1.1 to 1.5; P = .006). Risk of a severe psychiatric episode was also increased among survivors (adjusted hazard ratio [HR], 1.2; 95% CI, 1.1 to 1.4, P = .008). Risk of a psychotic disorder-associated severe event was doubled in survivors (HR, 2.0, 95% CI, 1.3 to 2.4; P = .007) although absolute risk remained low (15-year cumulative incidence 1.7%; 95% CI, 1.0 to 2.7). In multivariable analysis, survivors treated in adult centers experienced substantially higher outpatient visit rates compared with those treated in pediatric settings (RR 1.8; 95% CI, 1.0 to 3.1; P = .04).Survivors of AYA cancer are at substantially increased risk of adverse mental health outcomes, with those treated in adult centers at particular risk. Although absolute incidence was low, survivors were at increased risk of psychotic disorder-associated severe events. Long-term mental health surveillance is warranted, as is research into effective interventions during or after cancer treatment.
Community Outbreak Investigation of SARS-CoV-2 Transmission Among Bus Riders in Eastern China—More Detailed Studies Are Needed
Authors: Paul Anantharajah Tambyah, John Conly, Andreas Voss
Journal: JAMA Internal Medicine (2021)

Ye Shen, PhD; Changwei Li, PhD; Hongjun Dong, MD; Zhen Wang, MD; Leonardo Martinez, PhD; Zhou Sun, MD; Andreas Handel, PhD; Zhiping Chen, MD; Enfu Chen, MD; Mark H. Ebell, MD, MS; Fan Wang, MA; Bo Yi, MD; Haibin Wang, MD; Xiaoxiao Wang, MD; Aihong Wang, MD; Bingbing Chen, MD; Yanling Qi, PhD; Lirong Liang, MD, PhD; Yang Li, PhD; Feng Ling, MD; Junfang Chen, MD; Guozhang Xu, MD
Impact of Early Surgery and Staging Classification on Survival in Asymptomatic Very Severe Aortic Stenosis
Authors: Sung-Ji Park, Sahmin Lee, Seung-Ah Lee, Dae-Hee Kim, Hyung-Kwan Kim, Geu-Ru Hong, Jong-Min Song, Cheol-Hyun Chung, Seung Woo Park, Duk-Hyun Kang
Journal: Journal of the American College of Cardiology (2021)
Abstract 13343: Impact of Renal Function on Bleeding Risk in Patients With Non-Valvular Atrial Fibrillation Treated With Direct Oral Anticoagulants
Authors: Tomoaki Kobayashi, Yohei Sotomi, Akio Hirata, Atsushi Hirayama, Yoshiharu Higuchi
Journal: Circulation (2019)

Background: Renal dysfunction is one of the high bleeding risk factors in patients with atrial fibrillation(AF). The impact of renal function on bleeding risk is, however, still to be investigated ...
Exploiting the GTEx resources to decipher the mechanisms at GWAS loci
Authors: Alvaro N. Barbeira, Rodrigo Bonazzola, Eric R. Gamazon, Yanyu Liang, YoSon Park, Sarah Kim-Hellmuth, Gao Wang, Zhuoxun Jiang, Dan Zhou, Farhad Hormozdiari, Boxiang Liu, Abhiram Rao, Andrew R. Hamel, Milton D. Pividori, François Aguet, Lisa Bastarache, Daniel M. Jordan, Marie Verbanck, Ron Do, Matthew Stephens, Kristin Ardlie, Mark McCarthy, Stephen B. Montgomery, Ayellet V. Segrè, Christopher D. Brown, Tuuli Lappalainen, Xiaoquan Wen, Hae Kyung Im
Journal: Genome biology (2021)

The resources generated by the GTEx consortium offer unprecedented opportunities to advance our understanding of the biology of human diseases. Here, we present an in-depth examination of the phenotypic consequences of transcriptome regulation and a blueprint for the functional interpretation of genome-wide association study-discovered loci. Across a broad set of complex traits and diseases, we demonstrate widespread dose-dependent effects of RNA expression and splicing. We develop a data-driven framework to benchmark methods that prioritize causal genes and find no single approach outperforms the combination of multiple approaches. Using colocalization and association approaches that take into account the observed allelic heterogeneity of gene expression, we propose potential target genes for 47% (2519 out of 5385) of the GWAS loci examined.
The United States' Engagement in Global Tobacco Control
Authors: Thomas J. Bollyky, Lawrence O. Gostin
Journal: JAMA (2010)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Partha Kar: The end of the tunnel, and the bumps on the way
Authors: Partha Kar
Journal: BMJ (2021)

Partha Kar: The end of the tunnel, and the bumps on the way Partha Kar consultant in diabetes and endocrinologyAt the start of this new year, even as we're buffeted by the unwelcome news of a more infective strain of covid, it feels at times as if we're nearing the end of a long tunnel, with light just around the corner.Vaccines are being approved, and the health service is ramping up systems to ensure that vulnerable groups are protected.
SAT0224 Peripheral nerve involvement in hcv-infected patients with and without mixed cryoglobulinemia
Authors: S Sampaolo, L Ambrosone, G Sanges, L De Martino, S Migliaresi, G Di Iorio, G Valentini
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In contrast to cutaneous vasculitis, the morphology of which is well known, that of peripheral nerve lesions in HCV-positive mixed cryoglobulinemia (MC) patients are still under debate.<sup>1,2</sup> <h3>Objectives</h3> To evaluate the pathological processes underlying the peripheral nerve damage in HCV-infected patients, with and without MC. <h3>Methods</h3> From 14 HCV-infected patients (10 with MC and 4 without), all with clinically peripheral neuropathy, a sural nerve biopsy was obtained. Diseases other than HCV infection were excluded. The tissue samples were processed according to standard methods to perform morphologic and morphometric evaluation, on light and electronmicroscopic study. An immunohistochemical evaluation was carried out using labelled antisera against immunoglobulins (IgA, IgG, IgM), complement proteins (C1q, C3, terminal complex C5–9), and cellular antigens (CD3, CD11a-b-c, CD20, CD45, CD68). <h3>Results</h3> In all nerve biopsies an axonal involvement without a distinctive vasculitis was found. Scarce perivascular infiltration by monuclear cells was observed, particularly around perineural blood vessels; extravasation of red cells was also found in the endoneurial vessels. Immunohistochemical study pointed out deposits of immunoglobulins and complement in sub-perineurial vessels, and infiltrations by mononuclear cells, mainly macrophages and CD4 T cells. Demyelinating neuropathy was only observed in patients without MC. <h3>Conclusion</h3> Our data suggest that in HCV-infected patients different physiopathological processes are involved in induction of peripheral nerve damage. A potential direct pathogenic role of HCV should be investigated. <h3>References</h3> Bonetti B, <i>et al</i>. J Neuroimmunol. 1997;73:145 Bonetti B, <i>et al</i>. Virchows Arch. 1999;434:533
SAT0019 Comparison of different imaging techniques in the diagnosis of spondylarthropathies
Authors: N Arýtan, P Atagündüz, T Biren, HT Turoðlu, H Direskeneli
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Diagnosis of radiological sacroiliitis is difficult in the early stages with plain radiographs. Advanced methods such as computed tomography (CT), scintigraphy and magnetic resonance imaging (MRI) are suggested for this purpose. <h3>Objectives</h3> To compare the role of different imaging techniques in the diagnosis of spondylarthropathy (SpA) patients with inflammatory low back pain. <h3>Methods</h3> Thirty-four sacroiliac joints in 17 SpA patients who fulfilled the 1984 European Spondylarthropathy Classification Criteria and had inflammatory low back pain were investigated. Plain radiography, quantitative scintigraphy and MRI were performed for sacroiliac imaging. Plain radiography findings were evaluated blindly by a radiologist and rated on a 0–5 scale according to the modified New York criteria for radiological sacroiliitis. Quantitative sacroiliac scintigraphy was performed with Tc-99m hydroxy methylene diphosphonate (HMDP) and sacroiliac joint/sacrum uptake ratio for each joint was its sacroiliac index (SII). The value of SII &gt;136 was considered as sacroiliitis. The patients also underwent MRI of sacroiliac joints with FSE T2 and SE T1 weighed images. <h3>Results</h3> Among SpA patients the sensitivity of scintigraphy, MRI and plain radiography was 79%, 59% and 32% respectively. In 32% of 34 sacroiliac joints in which sacroiliitis was demonstrated with scintigraphy, no pathologic changes were present with MRI. On the other hand, 6% of joints were positive with MRI, but negative with scintigraphy. In cases where plain radiography showed normal radiographs, scintigraphy showed abnormalities in 44% while MRI showed abnormalities in only 18% of the joints. We couldn't find any relationship between the sacroiliac index and plain radiography scores. <h3>Conclusion</h3> These results suggest that the sensitivity of scintigraphy was higher than plain radiography and MRI, especially in early sacroiliitis patients with SpA.
Fecal microbiome and metabolome differ in healthy and food-allergic twins
Authors: Riyue Bao, Lauren A. Hesser, Ziyuan He, Xiaoying Zhou, Kari C. Nadeau, Cathryn R. Nagler
Journal: Journal of Clinical Investigation (2021)

BACKGROUND. There has been a striking generational increase in the prevalence of food allergies. We have proposed that this increase can be explained, in part, by alterations in the commensal microbiome.
Real-world safety data and differentiation of second-line (2L) 5-fluorouracil (5-FU) based regimens among patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).
Authors: George P. Kim, Paul Cockrum, Aleksander Chudnovsky, Andy Surinach, Zev A. Wainberg, Shu Wang, Amin Yakubu
Journal: Journal of Clinical Oncology (2021)

390 Background: Chemotherapy related adverse events (AEs) can impact the treatment of patients, reducing quality of life and leading to dose delays and treatment discontinuation. This study examined the proportion of patients (pts) with mPDAC treated with 5-FU-based regimens in the 2L setting who experienced AEs during treatment. Methods: Data were extracted for pts diagnosed with mPDAC who initiated 2L treatment between January 2016 and July 2020 from the Flatiron Health electronic health database. Pts included in the study were treated with FOLFIRINOX (FFX), FOLFOX, FOLFIRI, or a regimen containing liposomal irinotecan. The occurrence of grade 3 (G3) and grade 4 (G4) neutropenia, G3/G4 elevated alanine transaminase (ALT) and anemia where transfusion was indicated were determined using lab results and the grading criteria from the Common Terminology Criteria for Adverse Events v4.03. The occurrence of diarrhea, fatigue, nausea and vomiting (N/V), and neuropathy were identified from structured diagnosis records through ICD-10-CM codes. Duration of therapy (DOT) was assessed for each regimen. Descriptive statistics for AEs and DOT were reported. Results: Of the 804 pts included in the study, 28.4% (n=228) received FFX, 39.8% (n=320) received regimens containing liposomal irinotecan, 24.8% (n=199) received FOLFOX, and 7.1% (n=57) received FOLFIRI. The median DOT (IQR) was 86 days (d) (43 – 206), 79d (41 – 169), 72d (43 – 166), and 84d (46 – 148) for pts who received FFX, liposomal irinotecan, FOLFOX, and FOLFIRI, respectively. G3/G4 neutropenia (&lt;1000/mm3) presented in 28.1% (n=64) of pts treated with FFX, 11.9% (n=38) of pts treated with liposomal irinotecan, 17.1% (n=34) of pts treated with FOLFOX, and 36.8% (n=21) of pts treated with FOLFIRI. NV occurred in 14.9% (n=34), 13.1% (n=42), 12.6% (n=25), and 10.5% (n=6), respectively. The full AE results are summarized in the table. Conclusions: In this assessment of often dose-limiting AEs among pts with mPDAC treated in 2L, pts who received liposomal irinotecan had the lowest proportion of neutropenia. No clear pattern was noted for N/V, neuropathy, fatigue, anemia, and elevated ALT. Further research is necessary to determine the real-world cost implications of AEs in this patient population. [Table: see text]
SAT0225 THE POSITIVITY FOR HISTOPATHOLOGIC ASSESSMENT IN SALIVARY GLANDS SHOWED LITTLE IMPACTS ON CLINICAL FEATURES FOR ESTABLISHED PRIMARY SJÖGREN’S SYNDROME IN A CERTAIN ETHNIC POPULATION
Authors: Y. Park, J. Lee, J. H. Koh, J. Kim, Y. K. Sung, J. Y. Choe, S. S. Lee, S. C. Shim, J. M. Kim, S. R. Kwon, S. H. Park, S. K. Kwok
Journal: Annals of the Rheumatic Diseases (2020)

Background: The presence and the severity of focal lymphocytic sialadenitis in minor salivary glands is a pathognomonic feature in primary Sjögren’s syndrome (pSS). However, it has not been determined whether performing of minor salivary gland biopsy (MSGB) in a setting of serologically and clinically established pSS give us additional clinical information. Objectives: To investigate the necessity of MSGB in established pSS patients with the anti-Ro/SSA antibody. Methods: We extracted 185 patients with anti-Ro/SSA antibody-positive pSS from the Korean Initiative of primary Sjögren’s Syndrome, a prospective cohort. We assigned them into two groups, 161 patients with focus score ≥1 and other 24 with focus score &lt; 1. The two groups were compared in various clinical aspects including the severity of glandular dysfunctions, systemic disease activities, extra-glandular manifestations, and other clinical indices and laboratory values. We also evaluated relationship between focus score and clinically important variables in pSS. Results: Between two groups, there were no significant differences in the severity of secretory dysfunctions, the frequency of extra-glandular manifestations, systemic disease activities represented by various clinical indices, and laboratory findings possibly predicting the risk for lymphoma. Rather, the Sjögren’s syndrome disease damage index was higher in the group with focus score &lt; 1. Among all variables, serum immunoglobulin G level solely showed the correlation with focus score. Conclusion: Given that little influence on clinical phenotypes, unconditional performing of MSGB should be reconsidered for serologically and clinically established pSS, especially in low-risk area for lymphoproliferative diseases. Disclosure of Interests: None declared
AB0158 Musculoskeletal pain in children and adolescents
Authors: MM Costa, P Nero, E Branco, J Branco
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> The purpose of this study was the determination of the frequency and consequence of musculoskeletal pain in urban children and adolescents. <h3>Methods</h3> This study was performed in unselected population of two urban schools. Two Rheumatologists visited 479 children (216 boys and 263 girls) in their school. Mean age was 11+2.4 years, range 6–17 yr. The survey included a detailed interview on the basis of a standardised questionnaire and physical examination. The severity of their pain was assessed by visual analogue scale and a subjective disability index. <h3>Results</h3> About 30.3 percent (145/479) of cases had musculoskeletal pain. The pain was located at lower extremity in 74% of children. Thirty-one case (21.4%) had spinal pain and 19 (13.1%) had upper extremity pain. The severity of their pain, by visual analogue scale, had a mean 3.2+1.8 (range 0.1–8) and ¾ of cases had disability. Pain relapses weekly in 38% and persists part of a day in 74%. Twenty eight percent (40/145) consulted their physician and 31 children consumed drugs. The physical activity and schoolbag carriage was associated with pain in 61% (89/145) of cases. There were no statistically significant demographic differences among cases with and without musculoskeletal pain, except for sex, as is shown in the Table 1: <h3>Conclusion</h3> In our population lower extremity pain was more prevalent. It had a relapsing character and determines disability and consumption of medical services. The relationship with physical activity (practice of sports) was referred by children and was evaluated in other study.