tbuckley/cabot-search huggingface dataset:
FRI0142 Correlation between high levels of antibodies directed against the domain 1 of calpastatin and the presence of vasculitis in systemic lupus erythematosus
Authors: V Salle, O Vittecoq, F Jouen-Beades, JF Ménard, JP Ducroix, M Godin, X Le Loët, F Tron
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Calpastatin, an endogenous inhibitor of calpains, calcium-activated cysteine proteases, has been recently identified as a new auto-antigen.<sup>1,2</sup> Anti-calpastatin antibodies (ACAST) have been detected in venous thrombosis,<sup>3</sup> rheumatoid arthritis (RA) but also in other auto-immune diseases such as systemic lupus erythematosus (SLE), Sjogren syndrome or systemic sclerosis. The C-terminal 27 aminoacids fragment of calpastatin represents the major epitope recognised by these antibodies. However, other epitopes, particularly in the N-terminal region of the protein, including the domain 1 (D1), are targeted by antibodies in sera of RA patients.<sup>4</sup> The clinical relevance of ACAST D1 in SLE remain unknown. <h3>Objectives</h3> (i) to evaluate the prevalence of ACAST D1 in SLE; (ii) to correlate the presence of ACAST D1 with: 1- clinical manifestations and SLE activity index (SLEDAI); 2- anti-phospholipid antibodies (APL), i.e., anti-cardiolipin antibodies (ACL), lupus anticoagulant (LA), anti-beta2 glycoprotein I antibodies (aB2GPI), anti-annexin V antibodies (aANXV). <h3>Methods</h3> 84 patients with SLE who fulfilled the revised ACR criteria were included retrospectively. The following clinical features were studied: arthritis, nephritis, neurological and cardiac manifestations, vascular injury (arterial and venous thrombosis, fetal losses, vasculitis). The diagnosis of vasculitis was made by histological and angiographic data. For detection of ACAST D1, an ELISA was performed, using as antigen the recombinant domain 1 of calpastatin. ACL, aB2GPI, aANXV have also been detected by ELISA. <h3>Results</h3> The prevalence of ACAST D1, aB2GPI, aANXV, ACL and ACC was 9%, 14%, 12%, 43% and 48% respectively. Among the several clinical manifestations, the frequency of ACAST D1 was higher in vasculitis (23%). No statistically association was found between ACAST D1 and APL or the presence of thrombosis. However, high levels of ACAST D1 were positively correlated with the presence of vasculitis (p = 0.0085) and with disease activity (p &lt; 0.02). <h3>Conclusion</h3> ACAST D1 could participate in pathogenic mechanisms of inflammatory vascular lesions and could represent a marker of disease activity. <h3>References</h3> Després, <i>et al</i>. J Clin Invest. 1995;95:1891–6 Mimori, <i>et al</i>. Proc Natl Acad Sci USA. 1995;92:7267–71 Schlosser, <i>et al</i>. Thromb Haemost. 1997;77:11–13 Lackner KJ, <i>et al</i>. Br J Rheumatol. 1998;37:1164–71
Tissue and plasma tumor mutation burden (TMB) as predictive biomarkers in the CO.26 trial of durvalumab + tremelimumab (D+T) versus best supportive care (BSC) in metastatic colorectal cancer (mCRC).
Authors: Jonathan M. Loree, James T. Topham, Hagen F. Kennecke, Harriet Feilotter, Faeze Keshavarz-Rahaghi, Young S Lee, Weimin Li, Katie Quinn, Kimberly Banks, Daniel John Renouf, Derek J. Jonker, Dongsheng Tu, Christopher J. O'Callaghan, Eric Xueyu Chen
Journal: Journal of Clinical Oncology (2021)

61 Background: Pembrolizumab was recently granted tissue agnostic FDA accelerated approval for metastatic cancers with TMB≥10 mut/Mb. However, limited data supports immunotherapy in microsatellite stable (MSS) mCRC with TMB≥10 mut/Mb. We assessed tissue TMB and contrasted it to plasma derived TMB in the CO.26 trial. Methods: CO.26 was a phase 2 trial (2-sided ⍺ = 0.1 and 80% power) that randomized 180 patients (pts) 2:1 to D+T or BSC in refractory mCRC. Pre-treatment plasma was sequenced with the GuardantOMNI assay and archival tissue underwent exome sequencing with TMB assessed per the TMB harmonization project. MSI-H cases were excluded. For plasma TMB, we used a previously published cut point (≥28). Results: Overall survival (OS) but not progression free survival (PFS) was improved with D+T in the entire population. Of 180 pts, 163 were evaluable for plasma and 110 for tissue TMB. Median time between archival tissue and plasma collection was 3.1 yrs (IQR 1.9-5.1). Median tissue TMB was 6.6 muts/Mb (IQR 4.1-12.0), while median plasma TMB was 16.3 muts/Mb (IQR 9.4-25.9). Tissue and plasma TMB (r = -0.039, P = 0.69) were not correlated. Tissue TMB≥10 was not prognostic in the BSC arm (HR 1.01, 90%CI 0.52-1.92, P = 0.99) and OS was not improved in pts with tissue TMB≥10 (32/110 pts) following D+T vs BSC. A test of interaction suggested this threshold was not predictive (P = 0.85). Using a minimum P-value approach, no threshold supported high tissue TMB as predictive in MSS mCRC. In fact, the optimal cut point suggested low tissue TMB ( &lt; 4.1 muts/Mb) had the greatest benefit from D+T (P-interaction = 0.048) and pts with TMB ≥4.1 mut/Mb (HR 0.50, 90%CI 0.26-0.96, P = 0.083) trended to better OS in the BSC arm. In contrast, 35/163 pts (21%) were identified in a high plasma TMB group associated with worse OS (HR 2.56, 90%CI 1.45-4.54, P = 0.007) in the BSC arm but improved OS following D+T compared to BSC with P-interaction = 0.082. Only 1 response was noted following D+T in a pt with tissue TMB = 16 mut/Mb and plasma TMB = 13 mut/Mb. Conclusions: Archival tissue TMB≥10 mut/Mb does not appear predictive of D+T benefit in MSS mCRC. Plasma derived TMB may better reflect evolutionary changes following intervening therapy than archival tissue. Clinical trial information: NCT02870920. [Table: see text]
The President's Global Health Initiative
Authors: 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
The Supreme Court's Limitation of Managed-Care Liability
Authors: Wendy K. Mariner
Journal: New England Journal of Medicine (2004)

In June 2004, the U.S. Supreme Court ruled that managed-care organizations are not liable when patients have medical complications resulting from decisions to deny coverage for treatments recommended by the patients' doctors. In this article, Wendy Mariner discusses the implications of the Supreme Court decision for physicians and patients.
Monitoring meticillin resistant Staphylococcus aureus and its spread in Copenhagen, Denmark, 2013, through routine whole genome sequencing
Authors: M D Bartels, H Larner-Svensson, H Meiniche, K Kristoffersen, K Schønning, J B Nielsen, S M Rohde, L B Christensen, A W Skibsted, J O Jarløv, H K Johansen, L P Andersen, I S Petersen, D W Crook, R Bowden, K Boye, P Worning, H Westh
Journal: Eurosurveillance (2015)

Typing of meticillin resistant Staphylococcus aureus (MRSA) by whole genome sequencing (WGS) is performed routinely in Copenhagen since January 2013. We describe the relatedness, based on WGS data and epidemiological data, of 341 MRSA isolates. These comprised all MRSA (n?=?300) identified in Copenhagen in the first five months of 2013. Moreover, because MRSA of staphylococcal protein A (spa)-type 304 (t304), sequence type (ST) 6 had been associated with a continuous neonatal ward outbreak in Copenhagen starting in 2011, 41 t304 isolates collected in the city between 2010 and 2012 were also included. Isolates from 2013 found to be of t304, ST6 (n=14) were compared to the 41 earlier isolates. In the study, isolates of clonal complex (CC) 22 were examined in detail, as this CC has been shown to include the hospital-acquired epidemic MRSA (EMRSA-15) clone. Finally, all MRSA ST80 were also further analysed, as representatives of an important community-acquired MRSA in Europe. Overall the analysis identified 85 spa-types and 35 STs from 17 CCs. WGS confirmed the relatedness of epidemiologically linked t304 neonatal outbreak isolates. Several non-outbreak related patients had isolates closely related to the neonatal isolates suggesting unrecognised community chains of transmission and insufficient epidemiological data. Only four CC22 isolates were related to EMRSA-15. No community spread was observed among the 13 ST80 isolates. WGS successfully replaced conventional typing and added information to epidemiological surveillance. Creation of a MRSA database allows clustering of isolates based on single nucleotide polymorphism (SNP) calling and has improved our understanding of MRSA transmission.
Mask-wearing and control of SARS-CoV-2 transmission in the USA: a cross-sectional study
Authors: Benjamin Rader, Laura F White, Michael R Burns, Jack Chen, Joseph Brilliant, Jon Cohen, Jeffrey Shaman, Larry Brilliant, Moritz U G Kraemer, Jared B Hawkins, Samuel V Scarpino, Christina M Astley, John S Brownstein
Journal: The Lancet Digital Health (2021)

Face masks have become commonplace across the USA because of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic. Although evidence suggests that masks help to curb the spread of the disease, there is little empirical research at the population level. We investigate the association between self-reported mask-wearing, physical distancing, and SARS-CoV-2 transmission in the USA, along with the effect of statewide mandates on mask uptake.Serial cross-sectional surveys were administered via a web platform to randomly surveyed US individuals aged 13 years and older, to query self-reports of face mask-wearing. Survey responses were combined with instantaneous reproductive number (Rt) estimates from two publicly available sources, the outcome of interest. Measures of physical distancing, community demographics, and other potential sources of confounding (from publicly available sources) were also assessed. We fitted multivariate logistic regression models to estimate the association between mask-wearing and community transmission control (Rt<1). Additionally, mask-wearing in 12 states was evaluated 2 weeks before and after statewide mandates.378 207 individuals responded to the survey between June 3 and July 27, 2020, of which 4186 were excluded for missing data. We observed an increasing trend in reported mask usage across the USA, although uptake varied by geography. A logistic model controlling for physical distancing, population demographics, and other variables found that a 10% increase in self-reported mask-wearing was associated with an increased odds of transmission control (odds ratio 3·53, 95% CI 2·03-6·43). We found that communities with high reported mask-wearing and physical distancing had the highest predicted probability of transmission control. Segmented regression analysis of reported mask-wearing showed no statistically significant change in the slope after mandates were introduced; however, the upward trend in reported mask-wearing was preserved.The widespread reported use of face masks combined with physical distancing increases the odds of SARS-CoV-2 transmission control. Self-reported mask-wearing increased separately from government mask mandates, suggesting that supplemental public health interventions are needed to maximise adoption and help to curb the ongoing epidemic.Flu Lab, Google.org (via the Tides Foundation), National Institutes for Health, National Science Foundation, Morris-Singer Foundation, MOOD, Branco Weiss Fellowship, Ending Pandemics, Centers for Disease Control and Prevention (USA).
Outcomes of isolated distant lymph node metastases in colorectal cancer.
Authors: Vinod Kalapurackal Mathai, Soe Yu Aung, Vanessa Wong, Catherine Dunn, Jeremy David Shapiro, Azim Jalali, Rachel Wong, Margaret Lee, Jeanne Tie, Sumitra Ananda, Suzanne Kosmider, Stephanie Hui-Su Lim, Susan Caird, Matthew E. Burge, Andrew Peter Dean, Peter Gibbs, Louise M. Nott
Journal: Journal of Clinical Oncology (2021)

84 Background: The optimal management of isolated distant lymph node metastases (IDLNM) in metastatic colorectal cancer (mCRC) is not clearly established. Small case series and prior data from the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) registry support the use of radical treatment with curative intent (local resection, chemo-radiation or stereotactic radiotherapy), which may lead to better outcomes in mCRC patients with IDLNM. Aims: This study investigates the clinical characteristics and outcomes of mCRC patients with IDLNM treated with systemic therapies plus locoregional therapy with curative intent versus systemic therapies with palliative intent. Methods: Clinical data were collected and reviewed from the TRACC registry, a prospective, comprehensive registry for mCRC from multiple tertiary hospitals across Australia from 01/07/2009 to 30/06/2020. Clinicopathological characteristics, treatment modalities and survival outcomes were analyzed in patients with IDLNM and compared to patients with other organ metastases. Fisher exact test was used for significance tests and Kaplan Meier curves for survival analyses. Results: Of 3408 mCRC patients with a median follow-up of 38.0 months, 93 (2.7%) were found to have IDLNM. Compared to mCRC with other organ metastases, patients with IDLNM were younger (mean age: 62.1 vs 65.6 years, p=0.0200), more likely to have metachronous disease (57.0% vs 38.9%, p=0.0005), be KRAS wild-type (74.6% vs 53.9%, p=0.0012) and BRAF mutant (12.9% vs 6.2%, p=0.0100). There was no overall survival difference between with IDLNM and those with other organ metastases (median OS 27.24 vs 25.92 months, p=0.2300). Twenty-four patients (25.8%) with IDLNM received treatment with curative intent, with a trend towards improved overall survival compared to those with other organ metastases treated with curative intent (73.5 vs 62.7 months, p=0.8200). Amongst mCRC patients with IDLNM, those who received treatment with curative intent had a significantly better overall survival than those treated with palliative intent (73.5months vs 23.2 months, p=0.0070). Conclusions: Our findings suggest that there are differences in the patterns of presentation of IDLNM and other organ metastases. Radical treatment with curative intent options should be considered for mCRC patients with IDLNM where appropriate.
Relationship of LVEF and Myocardial Scar to Long-Term Mortality Risk and Mode of Death in Patients With Nonischemic Cardiomyopathy
Authors: Igor Klem, Michael Klein, Mohammad Khan, Eric Y. Yang, Faisal Nabi, Alexander Ivanov, Lubna Bhatti, Brenda Hayes, Edward A. Graviss, Duc T. Nguyen, Robert M. Judd, Raymond J. Kim, John F. Heitner, Dipan J. Shah
Journal: Circulation (2021)

Background: Nonischemic cardiomyopathy is a leading cause of reduced left ventricular ejection fraction (LVEF) and is associated with high mortality risk from progressive heart failure and arrhythmias. Myocardial scar on cardiovascular magnetic resonance imaging is increasingly recognized as a risk marker for adverse outcomes; however, left ventricular dysfunction remains the basis for determining a patient’s eligibility for primary prophylaxis with implantable cardioverter-defibrillator. We investigated the relationship of LVEF and scar with long-term mortality and mode of death in a large cohort of patients with nonischemic cardiomyopathy. Methods: This study is a prospective, longitudinal outcomes registry of 1020 consecutive patients with nonischemic cardiomyopathy who underwent clinical cardiovascular magnetic resonance imaging for the assessment of LVEF and scar at 3 centers. Results: During a median follow-up of 5.2 (interquartile range, 3.8, 6.6) years, 277 (27%) patients died. On survival analysis, LVEF ≤35% and scar were strongly associated with all-cause (log-rank test P =0.002 and P &lt;0.001, respectively) and cardiac death ( P =0.001 and P &lt;0.001, respectively). Whereas scar was strongly related to sudden cardiac death (SCD; P =0.001), there was no significant association between LVEF ≤35% and SCD risk ( P =0.57). On multivariable analysis including established clinical factors, LVEF and scar are independent risk markers of all-cause and cardiac death. The addition of LVEF provided incremental prognostic value but insignificant discrimination improvement by C-statistic for all-cause and cardiac death, but no incremental prognostic value for SCD. Conversely, scar extent demonstrated significant incremental prognostic value and discrimination improvement for all 3 end points. On net reclassification analysis, the addition of LVEF resulted in no significant improvement for all-cause death (11.0%; 95% CI, −6.2% to 25.9%), cardiac death (9.8%; 95% CI, −5.7% to 29.3%), or SCD (7.5%; 95% CI, −41.2% to 42.9%). Conversely, the addition of scar extent resulted in significant reclassification improvement of 25.5% (95% CI, 11.7% to 41.0%) for all-cause death, 27.0% (95% CI, 11.6% to 45.2%) for cardiac death, and 40.6% (95% CI, 10.5% to 71.8%) for SCD. Conclusions: Myocardial scar and LVEF are both risk markers for all-cause and cardiac death in patients with nonischemic cardiomyopathy. However, whereas myocardial scar has strong and incremental prognostic value for SCD risk stratification, LVEF has no incremental prognostic value over clinical measures. Scar assessment should be incorporated into patient selection criteria for primary prevention implantable cardioverter-defibrillator placement.
Phagocyte-mediated synapse removal in cortical neuroinflammation is promoted by local calcium accumulation
Authors: Mehrnoosh Jafari, Adrian-Minh Schumacher, Nicolas Snaidero, Emily M. Ullrich Gavilanes, Tradite Neziraj, Virág Kocsis-Jutka, Daniel Engels, Tanja Jürgens, Ingrid Wagner, Juan Daniel Flórez Weidinger, Stephanie S. Schmidt, Eduardo Beltrán, Nellwyn Hagan, Lisa Woodworth, Dimitry Ofengeim, Joseph Gans, Fred Wolf, Mario Kreutzfeldt, Ruben Portugues, Doron Merkler, Thomas Misgeld, Martin Kerschensteiner
Journal: Nature Neuroscience (2021)
WHO Launches Global Push to Eliminate Cervical Cancer
Authors: Bridget M. Kuehn
Journal: JAMA (2021)

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
Pharmacologically targeting molecular motor promotes mitochondrial fission for anti-cancer
Authors: Yi Qian, Meimei Zhao, Qinghua Han, Jingkang Wang, Lixi Liao, Heng Yang, Dan Liu, Pengfei Tu, Hong Liang, Kewu Zeng
Journal: Acta Pharmaceutica Sinica B (2021)

Mitochondrial shape rapidly changes by dynamic balance of fusion and fission to adjust to constantly changing energy demands of cancer cells. Mitochondrial dynamics balance is exactly regulated by molecular motor consisted of myosin and actin cytoskeleton proteins. Thus, targeting myosin-actin molecular motor is considered as a promising strategy for anti-cancer. In this study, we performed a proof-of-concept study with a natural-derived small-molecule J13 to test the feasibility of anti-cancer therapeutics
Case 3-2021: A 48-Year-Old Man with Transient Vision Loss
Authors: Sebastian H. Unizony, Hillary R. Kelly, Elizabeth K. O’Donnell, Sam Sadigh
Journal: New England Journal of Medicine (2021)

A 48-year-old man presented with acute vision loss that lasted 1 hour. His history included fatigue and weight loss of 4.5 kg in the past year, as well as bilateral jaw pain with chewing in the past 2 months. He had normocytic anemia and elevated levels of aminotransferases and alkaline phosphatase. A diagnostic test was performed.
alternative perspectives on omission bias
Authors: christopher j. anderson
Journal: Behavioral and Brain Sciences (2005)

the act/omission distinction is likely to lead to biases and be used as a moral heuristic. however, it is frequently difficult to determine whether this act/omission distinction is responsible for a judgment outside the lab. further, more encompassing theories of omission bias are needed to make progress in dealing with its harmful consequences. one such theory is briefly presented.