tbuckley/cabot-search huggingface dataset:
Novel Biochemical Markers of Glycemia to Predict Pregnancy Outcomes in Women With Type 1 Diabetes
Authors: Claire L. Meek, Diana Tundidor, Denice S. Feig, Jennifer M. Yamamoto, Eleanor M. Scott, Diane D. Ma, Jose A. Halperin, Helen R. Murphy, Rosa Corcoy
Journal: Diabetes Care (2021)

OBJECTIVE The optimal method of monitoring glycemia in pregnant women with type 1 diabetes remains controversial. This study aimed to assess the predictive performance of HbA1c, continuous glucose monitoring (CGM) metrics, and alternative biochemical markers of glycemia to predict obstetric and neonatal outcomes. RESEARCH DESIGN AND METHODS One hundred fifty-seven women from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) were included in this prespecified secondary analysis. HbA1c, CGM data, and alternative biochemical markers (glycated CD59, 1,5-anhydroglucitol, fructosamine, glycated albumin) were compared at ∼12, 24, and 34 weeks’ gestation using logistic regression and receiver operating characteristic (ROC) curves to predict pregnancy complications (preeclampsia, preterm delivery, large for gestational age, neonatal hypoglycemia, admission to neonatal intensive care unit). RESULTS HbA1c, CGM metrics, and alternative laboratory markers were all significantly associated with obstetric and neonatal outcomes at 24 weeks’ gestation. More outcomes were associated with CGM metrics during the first trimester and with laboratory markers (area under the ROC curve generally &amp;lt;0.7) during the third trimester. Time in range (TIR) (63–140 mg/dL [3.5–7.8 mmol/L]) and time above range (TAR) (&amp;gt;140 mg/dL [&amp;gt;7.8 mmol/L]) were the most consistently predictive CGM metrics. HbA1c was also a consistent predictor of suboptimal pregnancy outcomes. Some alternative laboratory markers showed promise, but overall, they had lower predictive ability than HbA1c. CONCLUSIONS HbA1c is still an important biomarker for obstetric and neonatal outcomes in type 1 diabetes pregnancy. Alternative biochemical markers of glycemia and other CGM metrics did not substantially increase the prediction of pregnancy outcomes compared with widely available HbA1c and increasingly available CGM metrics (TIR and TAR).
FRI0121 Anti-endothelial cell auto-antibodies and soluble markers of endothelial cell dysfunction in systemic lupus erythemetosus
Authors: R Dupuy, F Resplandy, M Seigneur, T Schaeverbeke, J Constans, MR Boisseau, C Conri
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In systemic lupus erythematosus (SLE), disease severity may be related to factors such as endothelial cell damage. <h3>Objectives</h3> We tested the hypothesis that anti-endothelial cell antibodies (AECA) and plasma markers of endothelial cell dysfunction would be related to disease severity in SLE. <h3>Methods</h3> Accordingly we measured AECA by human umbilical vein endothelial cell binding, endothelial markers von Willebrand factor, soluble thrombomodulin, soluble E-selectin by ELISA, and disease severity by SLEDAI and SLICC/ACR in 35 patients with SLE. <h3>Results</h3> Despite high levels of IgG AECA (p &lt; 0.001), compared to 21 healthy controls, we found a positive correlation only between IgG AECA and the SLEDAI index (r = 0.393, p = 0.021). We did?t find elevation of soluble markers of endothelial cell dysfunction compared to healthy controls. <h3>Conclusion</h3> We conclude that IgG AECA seem to be related to disease activity in SLE, possibly in a pathogenic rôle. Conversely, plasma markers of endothelial cell damage seem to be an epiphenomenon and may only be related to excess inflammation in these patients.
miR103a-3p in extracellular vesicles from FcεRI-aggregated human mast cells enhances IL-5 production by group 2 innate lymphoid cells
Authors: Shota Toyoshima, Tomomi Sakamoto-Sasaki, Yusuke Kurosawa, Koremasa Hayama, Akira Matsuda, Yasuo Watanabe, Tadashi Terui, Yasuhiro Gon, Kenji Matsumoto, Yoshimichi Okayama
Journal: Journal of Allergy and Clinical Immunology (2021)
mRNA COVID-19 vaccine is well tolerated in patients with cutaneous and systemic mastocytosis with mast cell activation symptoms and anaphylaxis
Authors: Tiago Azenha Rama, André Moreira, Mariana Castells
Journal: Journal of Allergy and Clinical Immunology (2021)

viral neutralization.For example, non-neutralizing influenzaspecific antibodies can mediate complement fixation, phagocytosis, and antibody-dependent cellular cytotoxicity (ADCC).IVIG produced before the 2009 H1N1 pandemic had moderate titers of cross-reactive ADCC antibodies that eliminated H1N1infected respiratory cells in vitro. 3IVIG can also have antiinflammatory effects that target immune-mediated pathology frequently seen during and after infection.Thus, evidence supports therapeutic antiviral and anti-inflammatory activity of IVIG beyond neutralization.Data on the clinical utility of IVIG in COVID-19 are limited.IVIG from 1 manufacturer contained antibodies with reactivity to components of various coronaviruses but neutralization studies were not performed. 4 Over time, of course, all commercial immunoglobulin will contain SARS-CoV-2 antibodies.A case report described prompt recovery in a patient with severe COVID-19 after receiving plasma exchange and IVIG, suggesting that plasma exchange may clear pathogenic or inflammatory mediators while IVIG provides immunomodulatory and antiviral effects. 5 Although limited by study size and confounding variables, other case series reported that IVIG improved clinical outcomes in severe COVID-19, supporting its potential as adjuvant therapy. 6,7n summary, even prepandemic IVIG contains cross-reactive SARS-COV-2 RBD, but does not neutralize viral spread.Nonetheless, activities beyond neutralization such as ADCC, complement activation, and anti-inflammation may warrant its use in COVID-19.
MUC1-C integrates activation of the IFN-γ pathway with suppression of the tumor immune microenvironment in triple-negative breast cancer
Authors: Nami Yamashita, Mark Long, Atsushi Fushimi, Masaaki Yamamoto, Tsuyoshi Hata, Masayuki Hagiwara, Atrayee Bhattacharya, Qiang Hu, Kwok-Kin Wong, Song Liu, Donald Kufe
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Immune checkpoint inhibitors (ICIs) have had a profound impact on the treatment of many tumors; however, their effectiveness against triple-negative breast cancers (TNBCs) has been limited. One factor limiting responsiveness of TNBCs to ICIs is a lack of functional tumor-infiltrating lymphocytes (TILs) in ‘non-inflamed’ or ‘cold’ tumor immune microenvironments (TIMEs), although by unknown mechanisms. Targeting MUC1-C in a mouse transgenic TNBC tumor model increases cytotoxic tumor-infiltrating CD8+ T cells (CTLs), supporting a role for MUC1-C in immune evasion. The basis for these findings and whether they extend to human TNBCs are not known. Methods Human TNBC cells silenced for MUC1-C using short hairpin RNAs (shRNAs) were analyzed for the effects of MUC1-C on global transcriptional profiles. Differential expression and rank order analysis was used for gene set enrichment analysis (GSEA). Gene expression was confirmed by quantitative reverse-transcription PCR and immunoblotting. The The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets were analyzed for effects of MUC1 on GSEA, cell-type enrichment, and tumor immune dysfunction and exclusion. Single-cell scRNA-seq datasets of TNBC samples were analyzed for normalized expression associations between MUC1 and selected genes within tumor cells. Results Our results demonstrate that MUC1-C is a master regulator of the TNBC transcriptome and that MUC1-C-induced gene expression is driven by STAT1 and IRF1. We found that MUC1-C activates the inflammatory interferon (IFN)-γ-driven JAK1→STAT1→IRF1 pathway and induces the IDO1 and COX2/PTGS2 effectors, which play key roles in immunosuppression. Involvement of MUC1-C in activating the immunosuppressive IFN-γ pathway was extended by analysis of human bulk and scRNA-seq datasets. We further demonstrate that MUC1 associates with the depletion and dysfunction of CD8+ T cells in the TNBC TIME. Conclusions These findings demonstrate that MUC1-C integrates activation of the immunosuppressive IFN-γ pathway with depletion of TILs in the TNBC TIME and provide support for MUC1-C as a potential target for improving TNBC treatment alone and in combination with ICIs. Of translational significance, MUC1-C is a druggable target with chimeric antigen receptor (CAR) T cells, antibody-drug conjugates (ADCs) and a functional inhibitor that are under clinical development.
Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts
Authors: Angel YS Wong, Brian MacKenna, Caroline E Morton, Anna Schultze, Alex J Walker, Krishnan Bhaskaran, Jeremy P Brown, Christopher T Rentsch, Elizabeth Williamson, Henry Drysdale, Richard Croker, Seb Bacon, William Hulme, Chris Bates, Helen J Curtis, Amir Mehrkar, David Evans, Peter Inglesby, Jonathan Cockburn, Helen I McDonald, Laurie Tomlinson, Rohini Mathur, Kevin Wing, Harriet Forbes, Rosalind M Eggo, John Parry, Frank Hester, Sam Harper, Stephen JW Evans, Liam Smeeth, Ian J Douglas, Ben Goldacre
Journal: Annals of the Rheumatic Diseases (2021)

Objectives To assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform. Methods We conducted two cohort studies from 1 March to 14 June 2020. Working on behalf of National Health Service England, we used routine clinical data in England linked to death data. In study 1, we identified people with an NSAID prescription in the last 3 years from the general population. In study 2, we identified people with rheumatoid arthritis/osteoarthritis. We defined exposure as current NSAID prescription within the 4 months before 1 March 2020. We used Cox regression to estimate HRs for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, accounting for age, sex, comorbidities, other medications and geographical region. Results In study 1, we included 536 423 current NSAID users and 1 927 284 non-users in the general population. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR 0.96, 95% CI 0.80 to 1.14) in the multivariable-adjusted model. In study 2, we included 1 708 781 people with rheumatoid arthritis/osteoarthritis, of whom 175 495 (10%) were current NSAID users. In the multivariable-adjusted model, we observed a lower risk of COVID-19 related death (HR 0.78, 95% CI 0.64 to 0.94) associated with current use of NSAID versus non-use. Conclusions We found no evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about the routine therapeutic use of NSAIDs.
Optimized RNA-targeting CRISPR/Cas13d technology outperforms shRNA in identifying functional circRNAs
Authors: Yang Zhang, Tuan M. Nguyen, Xiao-Ou Zhang, Limei Wang, Tin Phan, John G. Clohessy, Pier Paolo Pandolfi
Journal: Genome biology (2021)

Abstract Short hairpin RNAs (shRNAs) are used to deplete circRNAs by targeting back-splicing junction (BSJ) sites. However, frequent discrepancies exist between shRNA-mediated circRNA knockdown and the corresponding biological effect, querying their robustness. By leveraging CRISPR/Cas13d tool and optimizing the strategy for designing single-guide RNAs against circRNA BSJ sites, we markedly enhance specificity of circRNA silencing. This specificity is validated in parallel screenings by shRNA and CRISPR/Cas13d libraries. Using a CRISPR/Cas13d screening library targeting &gt; 2500 human hepatocellular carcinoma-related circRNAs, we subsequently identify a subset of sorafenib-resistant circRNAs. Thus, CRISPR/Cas13d represents an effective approach for high-throughput study of functional circRNAs.
Extracorporeal Membrane Oxygenation and Coronavirus Disease 2019
Authors: Rafal Kopanczyk, Omar H. Al-Qudsi, Amar M. Bhatt
Journal: JAMA Surgery (2021)

Asif K. Mustafa, MD, PhD; Philip J. Alexander, MD; Devang J. Joshi, MD; Deborah R. Tabachnick, MD; Chadrick A. Cross, MD; Pat S. Pappas, MD; Antone J. Tatooles, MD
Abstract P141: Biological and Socioeconomic Determinants of Dysglycaemia in Canadian Youth
Authors: Allison Feely, Celia Rodd, Allison Dart, Atul Sharma, Jonathan McGavock
Journal: Circulation (2017)

Background: Population-based rates of prediabetes or dysglycaemia (i.e. elevated A1C) among low-risk youth are not well described. Moreover, the biological and socioeconomic determinants of an elevated A1C in youth remain poorly understood. Methods: Youth aged 6-19 years who participated in the first (2007-2009) or second (2009-2011) cycles of the Canadian Health Measures Survey (CHMS) were included in our analyses. The primary outcome, dysglycaemia was defined using A1C guidelines established by the American Diabetes Association (ADA: 5.7%-6.4%) and Canadian Diabetes Association (CDA: 6.0%-6.4%). Various biological and socioeconomic determinants were compared between healthy and dysglycaemic youth using two sample t-tests and χ 2 tests (Table 1). Multivariable logistic regression was used to calculate adjusted odds ratios for dysglycaemia. Age stratified regression was performed to adjust for physical activity. All analyses were unweighted. Results: Of the 3449 youth studied, 785 (22.8%) and 179 (5.2%) displayed dysglycaemia according to ADA and CDA definitions, respectively. Youth with dysglycaemia (ADA definition) were more likely to be male (55.4 v 50.6%, p=0.02), non-white (24.8 v 14.6%, p&lt;0.001) and obese (16.2 v 10.8%, p&lt;0.001). Dysglycaemia in youth was more common in those living in households with middle income adequacy (32.6 v 26.8%, p=0.006) and lower levels of parental education (high school or less, 15 vs 11.4%, p=0.007). Similar associations were found using CDA definition. In the adjusted logistic regression model (age ≥12y), significant predictors were age, race, income adequacy, geographic region, obesity (OR=1.60, 95% CI: 1.08-2.35) and physical activity (monthly frequency of activity longer than 15 minutes, OR=0.97, 95% CI: 0.95-0.99). Conclusion: Nearly 1 of every 5 youth in Canada are at risk for type 2 diabetes, based on early elevated A1C. Elevated A1C in youth is associated with social determinants of health and some lifestyle factors and both should be addressed in prevention efforts.
Efficacy of 3 Major Ketogenic Diet Therapies in Children With Drug-Resistant Epilepsy—Reply
Authors: Vishal Sondhi, Sheffali Gulati
Journal: JAMA Pediatrics (2021)

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Atrial Fibrillation or Sinus Rhythm?: Controversy and Contradiction in Quality of Life Outcomes⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Rodney H. Falk
Journal: Journal of the American College of Cardiology (2006)
Erratum. Health Care Utilization of Homeless Minors With Diabetes in New York State From 2009 to 2014. Diabetes Care 2020;43:2082–2089
Authors: Rie Sakai-Bizmark, Laurie A. Mena, Dennys Estevez, Eliza J. Webber, Emily H. Marr, Lauren E.M. Bedel, Jennifer K. Yee
Journal: Diabetes Care (2021)

To comply with the Healthcare Cost and Utilization Project (HCUP) Data Use Agreement, several cells in Table 1 of this article containing case number values ≤10 should have been masked. Therefore, numbers in the cells subject to this regulation have been removed. The following explanation was added under …
THU0039 Local il-17 gene therapy accelerates collagen arthritis with severe bone erosion and rank ligand and rank expression in synovial infiltrate and at bone erosion sites
Authors: E Lubberts, L Joosten, P Schwarzenberger, B Oppers, L Van den Bersselaar, JK Kolls, WB Van den Berg
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To examine the effects of local IL-17 application in the knee joint of type II collagen immunised mice on the induction of bone erosion. <h3>Methods</h3> Collagen induced arthritis (CIA) was induced in male DBA-1 mice by immunising intradermally at the base of the tail with suboptimal dose of bovine type II collagen. On day 21, mice were given a booster injection (i.p.) of the same dose of type II dissolved in PBS. Just before expected onset, mice were intraarticularly (i.a.) injected into the right knee joint with 10^7 pfu of either an IL-17 expressing (AdIL-17) or control (AdControl) recombinant human type 5 adenovirus vector. Five days after the i.a. injection of the viral vector, arthritis was monitored visually and joint pathology was examined by histology. Formation of osteoclast-like cells was determined by tartrate-resistant acid phosphatase (TRAP) staining. In addition, RANKL and RANK protein expression was evaluated by specific immunohistochemistry. <h3>Results</h3> Local IL-17 over-expression in the knee joint of type II collagen immunised mice promotes synovial inflammation. Five days after viral injection of AdIL-17, histologic analysis showed aggravation of bone erosion in the patella and femur/tibia region compared with the control vector group. Induction of bone destruction by IL-17 was accompanied with marked TRAP activity in the bone marrow and at bone erosion sites, indicating that IL-17 accelerates the formation of osteoclast-like cells. Interestingly, local IL-17 promotes local protein expression of RANKL and its receptor RANK in the synovial infiltrate and at bone erosion sites compared with the control vector group. <h3>Conclusion</h3> These data shows that local IL-17 gene therapy during onset of collagen arthritis promotes osteoclastic bone erosion accompanied with accelerated expression of local RANKL and its receptor RANK. These findings suggest IL-17 to be a potent stimulator of osteoclastogenesis during arthritis.
FRI0177 The spectrum of clinical manifestations of antiphospholipid antibody syndrome in the general hospital
Authors: TI Reitblat, E Dorodnikov, I Polishchuk, D Zamir, E Kahana
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> APS is recognised with growing incidence in many fields of medicine. It is clinically and immunologically diverse condition and may affect any organ of the body and display a broad spectrum of manifestations. The majority of published studies have been reported from a tertiary referral hospitals. We decided to study the incidence and clinical spectrum of APS in a general hospital. <h3>Objectives</h3> To examine the spectrum of clinical manifestations of antiphospholipid antibody syndrome (APS) in the acute general hospital of the southern area of Israel. <h3>Methods</h3> Clinical records of patients who were discharged with diagnosis of APS during the years 1990–2000 were reviewed. <h3>Results</h3> A total of 22 patients fulfilled criteria of APS (accordingly to Asherson?s criteria, 1988) with 38 clinical events. Primary APS was found in 15 patients and secondary in 7 patients. There were 19 female and 3 male, mean age was 42.1 years (from 29 to 56). Most of the patients (20 out of 22) were diagnosed after 1995, showing increased awareness of this syndrome among the stuff. 16 thrombotic events occurred: 6 stroke (27%), 4 acute myocardial infarction (18%), 3 venous thromboembolic event (13.6%), 3 recurrent abortion (13.6%). 32 nonthrombotic events were found: 8 headache (36.3%), 6 thrombocytopenia (27%), 3 skin rashes (13.6%), 1 amaurosis fugax (4.5%), 1 catastrophic APS (4.5%) 1 progressive supranuclear pulsy (PSP) (4.5%). All patients suffering from acute myocardial infarction were patients with SLE, thus showing that APS is an additional risk factor for ischaemic heart disease in such patients. Headache was an additional symptom in the patients, diagnosed as having APS – in all 6 patients with stroke, one with amaurosis fugax and one with venous thromboembolic event. Patient with PSP features had magnetic resonance imaging of brain and blood test results characteristic to APS (our unpublished data). <h3>Conclusion</h3> The study shows that APS is not an uncommon disease. It is important for the internist and the specialist to be aware of the clinical manifestations of APS. Its inclusion in the differential diagnosis of arterial or venous thrombosis with or without thrombocytopenia in patients is obligatory at the present time.