tbuckley/cabot-search huggingface dataset:
Abstract P226: Longitudinal Work Hour Patterns Associated With Diabetes Risk
Authors: Tia S Lal, Sadie H Conway, Ruosha Li, William B Perkison, Feng Zhang, David Aguilar
Journal: Circulation (2021)

Introduction: Evidence shows a positive correlation between work hour (WH) duration and incident diabetes (DM). However, little is known about the association between longitudinal WH patterns and the risk of incident DM. Hypothesis: We hypothesized that the greatest risk of DM would be observed in consistently long WH patterns and that age, sex, and ethnicity would modify the relationship between WH patterns and incident DM. Methods: We utilized a representative sample of 15,843 U.S. adults from the Panel Study of Income Dynamics who reported weekly WH for a minimum of five years between 1985-2017 and did not have a history of DM prior to reporting five years of WH data. Latent class linear mixed modeling was used to identify distinct longitudinal WH trajectory patterns. Multivariable logistic regression analyses were then used to examine the association between WH patterns and incident DM, with initial adjustments made for sex, age, ethnicity, education, income-to-needs ratio, and occupation. We also tested for statistical interactions between WH patterns and baseline age, sex, and ethnicity. Results: Over a mean follow-up of 17.5 years, four WH trends were identified: standard, full-time (61.1%), increasing (11.5%), quickly decreasing (11.3%), and gradually decreasing (16.1%). Age (interaction p=0.013), but not ethnicity nor sex, modified the association between WH patterns and incident DM. In age stratified analyses, adults aged 18-29 showed no significant association between WH patterns and DM. In adults aged 30-39, a gradually decreasing WH trend showed lower DM risk compared to those working standard hours (OR=0.59; 95% CI: 0.45 - 0.77). Among those ≥40 years, both quickly decreasing (OR=0.66; 95% CI: 0.50 - 0.87) and gradually decreasing (OR=0.45; 95% CI: 0.34 - 0.60) WH patterns were associated with lower risk of DM compared to those working standard hours. Conclusion: Compared to individuals working standard WH over many years, decreasing WH patterns were associated with a lower risk of incident DM.
Polygenic Liability and Recurrence of Depression in Patients With First-Onset Depression Treated in Hospital-Based Settings
Authors: Katherine L. Musliner, Esben Agerbo, Bjarni J. Vilhjálmsson, Clara Albiñana, Thomas D. Als, Søren D. Østergaard, Preben B. Mortensen
Journal: JAMA Psychiatry (2021)

This cohort study examines the association of polygenic risk score for major depression with risk of recurrence in individuals diagnosed with unipolar depression in hospital-based settings and estimates the absolute risk of recurrence based on polygenic risk.
Abstract 13069: NLRP3 Inflammasome Promotes Vasculitis of Kawasaki Disease
Authors: Fumiya Anzai, Hiroaki Kimura, Yasuchika Takeishi, Masafumi Takahashi
Journal: Circulation (2020)

Introduction: Kawasaki disease (KD) is a systemic febrile syndrome which causes coronary arteritis. Candida albicans water-soluble fraction (CAWS) is a mannoprotein-β-glucan complex obtained from the culture supernatant of Candida albicans , and frequently used as a murine KD model, because administration ofCAWS induces coronary arteritis. NLRP3 inflammasome is a large multiprotein complex (NLRP3, ASC and caspase-1), and regulates the release of the potent inflammatory cytokine IL-1β. We hypothesized that NLRP3 inflammasome-mediated IL-1β had a pivotal role in the pathogenesis of CAWS-induced vasculitis. Methods and Results: In vivo : The protein level of IL-1β in the hearts was increased by CAWS administration. Activation of caspase-1 was detected around the coronary arteries by FLICA assay. Histological study showed that incidence and severity of CAWS-induced vasculitis, macrophage infiltration, and fibrosis were suppressed in NLRP3-, ASC- and IL-1β-deficient mice (Fig. A). In vitro : Bone marrow-derived dendritic cells (BMDCs) produced IL-1β by CAWS stimulation, which was suppressed by the anti-Dectin-2 antibody or caspase-1 inhibitor. The CAWS-induced IL-1β production was also suppressed in NLRP3-, ASC-, and caspase-1-deficient BMDCs (Fig. B). CAWS induced mitochondrial reactive oxygen species (mtROS) production, and Mito-TEMPO, a mtROS inhibitor, suppressed CAWS-induced caspase-1 activation (Fig. C) and IL-β production. In addition, CAWS-induced mtROS production was suppressed by Syk or JNK inhibitor. Furthermore, Syk or JNK inhibitor suppressed CAWS-induced NF-κB activation and subsequent IL-1β production. Conclusion: These findings demonstrated that NLRP3 inflammasome activation through Dectin-2/Syk/JNK-mediated mtROS plays a pivotal role in CAWS-induced vasculitis. CAWS also induced priming signal through Dectin-2/Syk/JNK/NF-κB pathway. Our finding indicates NLRP3 inflammasome as a new therapeutic target of KD.
Impact of COVID-19 vaccination program on seroprevalence in blood donors in England, 2021
Authors: Heather J Whitaker, Suzanne Elgohari, Cathy Rowe, Ashley David Otter, Tim Brooks, Ezra Linley, Iain Hayden, Sonia Ribeiro, Jacqueline Hewson, Anissa Lakhani, Eleanor Clarke, Camille Tsang, Colin NJ Campbell, Mary Ramsay, Kevin Brown, Gayatri Amirthalingam
Journal: Journal of Infection (2021)
Abstract 16007: Myeloid-specific Deletion in Lipid Phosphate Phosphatase3 (plpp3) Increases Cardiac Inflammation
Authors: Himi Tripathi, Kazuhiro Shindo, Renee Donahue, Erhe Gao, Andrew J Morris, Susan S Smyth, Ahmed Abdel-latif
Journal: Circulation (2020)

Introduction and Hypothesis: Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality worldwide. The innate immune response plays a major role in cardiac remodeling after AMI. Lysophosphatidic acid (LPA), produced by autotaxin (ATX) and degraded by Lipid phosphate phosphatase 3 (LPP3), regulates monocytosis and promotes inflammation. However, the role of LPP3 in post-AMI inflammation is not understood. Here, we investigated the possible role of Myeloid-specific Plpp3 KO mice in cardiac and systemic inflammation and resulting in adverse cardiac remodeling post-MI. Methods and Results: To generate mice with Myeloid-specific Plpp3 deletion , female Plpp3 fl/fl mice were crossed to male Plpp3 mice expressing Cre recombinase under the control of the LysM promoter to generate lysm-plpp3. mice. These mice and their littermate control underwent MI or sham surgery. Inflammatory cell content was assessed using flow cytometry and immunohistochemistry. Cardiac function and scar size were assessed by echocardiography and Mason Trichrome staining, respectively. Increased number of Ly6C hi monocytes (CD45 + /Ly6C/G hi /CD115 hi ) and pro-inflammatory macrophages (CD45 + /F4-80 + /CD11b + ) (CD45 + /F4-80 + /CD86 + ), in cardiac tissue of Cre+LysM mice was observed compared to Cre-fl/fl littermate controls during peak post-MI inflammation, as assessed by flow cytometry ( Fig.1A-C ). This increase in inflammatory cells and inflammation may be the consequence of the significant increase in bone marrow and spleen progenitor cell count and proliferation. Moreover, Cre+LysM mice cardiac functional recovery was also reduced significantly ( Fig. 1D-F ) as assessed by echocardiography. Conclusion: Myeloid-specific Plpp3 deletion increases the deleterious effects of inflammation on the ischemic myocardium and ATX/ LPA signaling could represent a novel therapeutic target for future clinical studies of coronary heart diseases.
Approach to Asymptomatic Case of Bicuspid Aortic Valve with Coarctation and Massive Aortic Arteriopathy: a Ticking Time Bomb
Authors: K.V Charan Reddy, Ajit Menon, Parag Bhalgat, Abhishek Shah, Sanjeev Vichare
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

The combination of aortic coarctation (CoA) and bicuspid aortic valve (BAV) is associated with high risk of ascending aortic dilatation and type A aortic dissection. Most of the patients having combined lesions remain asymptomatic until adulthood and are incidentally diagnosed. Several questions regarding their treatment strategies remain unanswered. Both single-and two-stage surgical procedures have been described in medical literature, to treat CoA and BAV. Lately, combined endovascular therapy (Balloon angioplasty or Stent implantation) and surgery, has become a good alternative in selected cases. Here, we describe such a asymptomatic case of BAV with massive aneurysmal root dilatation and CoA, which was managed with endovascular stenting and surgery.
Comprehensive Review of AL amyloidosis: some practical recommendations
Authors: Rama Al Hamed, Abdul Hamid Bazarbachi, Ali Bazarbachi, Florent Malard, Jean-Luc Harousseau, Mohamad Mohty
Journal: Blood Cancer Journal (2021)

Amyloid light chain (AL) amyloidosis is among the more common and more severe of the amyloidoses usually involving the slow proliferation of a bone-marrow-residing plasma cell (PC) clone and the secretion of unstable immunoglobulin-free light chains (FLC) that infiltrate peripheral tissues and result in detrimental end-organ damage. Disease presentation is rather vague, and the hallmark of treatment is early diagnosis before irreversible end-organ damage. Once diagnosed, treatment decision is transplant-driven whereby ~20% of patients are eligible for autologous stem cell transplantation (ASCT) with or without bortezomib-based induction. In the setting of ASCT-ineligibility, bortezomib plays a central role in upfront treatment with the recent addition of daratumumab to the current emerging standard of care. In general, management of AL amyloidosis is aimed at achieving deep, durable responses with very close monitoring for early detection of relapse/refractory disease. This article provides a comprehensive review of the management of patients with AL amyloidosis including goals of therapy, current treatment guidelines in the setting of both ASCT-eligibility and ineligibility, treatment response monitoring recommendations, toxicity management, and treatment of relapse/refractory disease.
Antibodies against human endogenous retrovirus K102 envelope activate neutrophils in systemic lupus erythematosus
Authors: Maria Tokuyama, Bronwyn M. Gunn, Arvind Venkataraman, Yong Kong, Insoo Kang, Tasfia Rakib, Michael J. Townsend, Karen H. Costenbader, Galit Alter, Akiko Iwasaki
Journal: The Journal of Experimental Medicine (2021)

Neutrophil activation and the formation of neutrophil extracellular traps (NETs) are hallmarks of innate immune activation in systemic lupus erythematosus (SLE). Here we report that the expression of an endogenous retrovirus (ERV) locus ERV-K102, encoding an envelope protein, was significantly elevated in SLE patient blood and correlated with autoantibody levels and higher interferon status. Induction of ERV-K102 in SLE negatively correlated with the expression of epigenetic silencing factors. Anti-ERV-K102 IgG levels in SLE plasma correlated with higher interferon stimulated gene expression, and further promoted enhanced neutrophil phagocytosis of ERV-K102 envelope protein through immune complex formation. Finally, phagocytosis of ERV-K102 immune complexes resulted in the formation of NETs consisting of DNA, neutrophil elastase, and citrullinated histone H3. Together, we identified an immunostimulatory ERV-K envelope protein that in an immune complex with SLE IgG is capable of activating neutrophils.
Effect of Computed Tomography Versus Invasive Coronary Angiography on Statin Adherence
Authors: Sarah Feger, Laura Elzenbeck, Nina Rieckmann, Andrea Marek, Henryk Dreger, Mark Beling, Elke Zimmermann, Matthias Rief, Benjamin J.W. Chow, Pál Maurovich-Horvath, Michael Laule, Rudolf Tauber, Marc Dewey
Journal: JACC. Cardiovascular imaging (2021)
90TiP Monalizumab and trastuzumab in metastatic HER2-positive breast cancer: MIMOSA-trial
Authors: V.C.M. Geurts, L. Voorwerk, K. Sikorska, M.G. Van Dongen, I. Kemper, I.A.M. Mandjes, J.B.A.G. Haanen, G.S. Sonke, M. Kok
Journal: Annals of Oncology (2021)
Myeloid lncRNA <i>LOUP</i> mediates opposing regulatory effects of RUNX1 and RUNX1-ETO in t(8;21) AML
Authors: Bon Q. Trinh, Simone Ummarino, Yanzhou Zhang, Alexander K. Ebralidze, Mahmoud A. Bassal, Tuan M. Nguyen, Gerwin Heller, Rory Coffey, Danielle E. Tenen, Emiel van der Kouwe, Emiliano Fabiani, Carmelo Gurnari, Chan-Shuo Wu, Vladimir Espinosa Angarica, Henry Yang, Sisi Chen, Hong Zhang, Abby R. Thurm, Francisco Marchi, Elena Levantini, Philipp B. Staber, Pu Zhang, Maria Teresa Voso, Pier Paolo Pandolfi, Susumu S. Kobayashi, Li Chai, Annalisa Di Ruscio, Daniel G. Tenen
Journal: Blood (2021)
Abstract 16141: Women Have More Bleeding Events and Intracranial Hemorrhage Than Men Post LVAD Implantation
Authors: Nirupama Vellanki, kevin kennedy, Edward W Grandin, Jose Nunez, Shweta R Motiwala, Pablo A Quintero, Lisa M Fleming, Loryn Feinberg, Arthur Reshad Garan, Marwa Sabe
Journal: Circulation (2020)

Intro: Women have been shown to have higher risk of bleeding after adverse cardiovascular events. Bleeding events are a major cause of morbidity and mortality in patients with continuous flow left ventricular assist devices (cf-LVADs). There are few studies that have demonstrated that women with cf-LVADs may be at higher risk of bleeding, however the sex differences in specific bleeding events has not been studied in a large multi-center patient population of patients with cf-LVADs. We sought to investigate the relationship between sex and specific types of bleeding events in patients with cf-LVADs. Methods: We included 16,534 patients from the INTERMACS registry, a national multicenter database of patients implanted with cf-LVAD between 2012-2017. Using a cox proportional hazards model, we assessed the relationship between sex and bleeding events after adjusting for relevant covariates*. Bleeding events were further stratified for the type of bleeding including GI bleeding, intracranial hemorrhage, and non-GI/CNS bleeding. Results: Women were more likely to have a bleeding event than men post-LVAD implantation (HR 1.19 p&lt;0.0001). While the majority of bleeding events were GI bleeds, there was no significant difference in risk between men and women (p 0.7). After adjusting for covariates, women were more likely to have an intracranial hemorrhage (HR 1.38, p 0.002) and to have non-GI/non-CNS bleeding (HR 1.25, p&lt;0.0001). Conclusion: Females are more likely than men to develop bleeding events post cf-LVAD implantation. While there was no significant sex difference in GI bleeding, women were more likely to have intracranial bleeding and non-GI/non-CNS bleeding.
Abstract 050: Maternal Risk Of Incident Embolism Following Hypertensive Disorders Of Pregnancy Or Pre-pregnancy Hypertension In South Carolina
Authors: Angela M Malek, Dulaney A Wilson, Tanya N Turan, Julio Mateus, Daniel T Lackland, Kelly J Hunt
Journal: Circulation (2021)

Introduction: Hypertensive disorders of pregnancy (HDP) and pre-pregnancy hypertension are associated with increased maternal morbidity and mortality, and information on racial/ethnic disparities is lacking. The association of HDP and pre-pregnancy hypertension with incident maternal embolism was examined within five years of delivery and for the study period (≤14 years) overall and by race/ethnicity. Methods: Women with a live, singleton birth in South Carolina (2004-2016) aged 12-49 years were included in a retrospective cohort study (n=433,625; non-Hispanic white [NHW; 58.7%], non-Hispanic black [NHB; 31.8%)] and Hispanic [9.5%]). HDP were defined by hospitalization/emergency department (ED) visit data (pre-eclampsia, eclampsia, gestational hypertension) or birth certificates (gestational hypertension). Pre-pregnancy hypertension was also defined by these data sources. Hospitalization/ED visit data and death certificates defined fatal and non-fatal incident embolism. Cox proportional hazards models were used with covariate adjustment. Results: In women with ≥1 pregnancy, 81.6% never experienced pre-pregnancy hypertension or HDP, 0.4% had pre-pregnancy hypertension without superimposed HDP, 15.7% had HDP alone, and 2.3% had pre-pregnancy hypertension with superimposed HDP. Incident embolism risk was elevated ≤14 years after delivery for women with HDP alone (HR=1.21, 95% CI: 1.12-1.30) and with pre-pregnancy hypertension with superimposed HDP (HR=1.44, 95% CI: 1.26-1.65) compared to neither condition. Pre-pregnancy hypertension alone was not associated with incident embolism risk (HR=1.23, 95% CI: 0.84-1.80). The table shows the joint impact of racial/ethnicity and the exposure categories. Discussion: Fatal and non-fatal embolism up to 14 years after delivery was increased for HDP regardless of pre-pregnancy hypertension suggesting a long-term impact. Incident embolism event rates were highest for NHB women and lowest for Hispanic women across all HDP exposure categories.
The covid-19 vaccine patent waiver: a crucial step towards a “people’s vaccine”
Authors: Gregg Gonsalves, Gavin Yamey
Journal: BMJ (2021)

The purpose of this study was to evaluate differences between patients receiving <sup>18</sup>F-fluciclovine and <sup>68</sup>Ga-prostate-specific membrane antigen (<sup>68</sup>Ga-PSMA-11) for biochemically recurrent prostate cancer at a tertiary medical center. <b>Methods:</b> All <sup>18</sup>F-fluciclovine and <sup>68</sup>Ga-PSMA-11 PET studies performed at the University of California San Francisco from October 2015 to January 2020 were reviewed. Age, race/ethnicity, primary language, body mass index, insurance type, and home address were obtained through the electronic medical record. A logistic regression model was used to evaluate the predictor variables. <b>Results:</b> In total, 1,502 patients received <sup>68</sup>Ga-PSMA-11 and 254 patients received <sup>18</sup>F-fluciclovine. Black patients had increased odds of receiving imaging with <sup>18</sup>F-fluciclovine versus <sup>68</sup>Ga-PSMA-11 compared with non-Hispanic White patients (odds ratio, 3.88; 95% CI, 1.90–7.91). There were no other statistically significant differences. <b>Conclusion:</b> In patients receiving molecular imaging for prostate cancer at a single U.S. tertiary medical center, access to <sup>68</sup>Ga-PSMA-11 for Black patients was limited, compared with non-Hispanic White patients, by a factor of nearly 4.
Abstract P148: Initiation And Switching Of Direct Oral Anticoagulants Among Medicare Beneficiaries With Cancer And Atrial Fibrillation
Authors: Shirin Ardeshirrouhanifard, Huijun An, Ravi Goyal, Mukaila Raji, Caleb Alexander, Hemalkumar Mehta
Journal: Circulation (2021)

Objective: Despite population-level increases in use of direct oral anticoagulants (DOACs) over the last decade, less is known about their use among individuals with cancer and non-valvular atrial fibrillation (NVAF). We quantified DOAC initiation and switching among such individuals. Methods: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2009 to 2016 and included patients aged ≥66 years diagnosed with cancer (breast, bladder, colorectal, esophagus, lung, ovary, kidney, pancreas, prostate, stomach or uterus). We limited the cohort to continuously enrolled beneficiaries with newly diagnosed NVAF following cancer diagnosis (from 2010 to 2016) who did not have any oral anticoagulant use during the 12-months prior to their NVAF diagnosis. We evaluated the initiation of warfarin or DOACs within 3 months of the incident NVAF diagnosis. Among warfarin users, we determined switching rates to DOACs and among DOACs users, we determined switching rates to warfarin. Descriptive statistics were used for all the analyses. Results: Of 1,028,784 Medicare beneficiaries with cancer, 158,744 (15.4%) were diagnosed with atrial fibrillation. After applying all inclusion criteria, the final study cohort included 19,513 cancer patients diagnosed with incident NVAF. Lung (20.2%), Breast (19.2%), prostate (19.2%) and colorectal (16.0%) cancer accounted for over three-fourths of the cohort. Overall, 7,604 patients (39%) initiated oral anticoagulants. Among these patients, 4,223/7,604 (55.5%) and 3,381/7,604 (44.5%) initiated DOACs and warfarin, respectively. Patients who initiated DOACs had lower Charlson comorbidity score (1.0 ± 1.4 vs. 1.3 ± 1.5) and CHA 2 DS 2 -VASc score (4.4 ± 1.7 vs. 4.8 ± 1.7) compared to warfarin users. Initiation of DOACs varied by cancer type; for example, 13.6% (55/405) of patients with stomach cancer initiated DOACs, whereas 29.8% (1120/3755) of patients with prostate cancer initiated DOACs. Among patients who initiated any oral anticoagulants, the use of DOACs increased from 22% (110/501) in 2011 to 75.3% (1335/1772) in 2016, whereas warfarin use declined from 78% (391/501) to 24.7% (437/1772). The switching rate among warfarin initiators to DOACs (623/3381, 18.4%) was higher than the switching rate among DOACs initiators to warfarin (281/4223, 6.7%). Conclusion: Among cancer patients with newly diagnosed NVAF, the use of DOACs has markedly increased from 2011 to 2016, with a corresponding decline in the use of warfarin. Moreover, cancer patients are more likely to switch from warfarin to DOACs. Our findings highlight the dynamic life cycle of these products and the value of real-world assessments of their comparative safety and effectiveness among Medicare beneficiaries.
Patterns and Determinants of Low-Value Preoperative Testing in Michigan
Authors: Nicholas L. Berlin, Monica L. Yost, Bonnie Cheng, James Henderson, Eve Kerr, Hari Nathan, Lesly A. Dossett
Journal: JAMA Internal Medicine (2021)

This cohort study examines use of preoperative testing before 3 low-risk ambulatory surgical procedures across diverse practice settings in Michigan.
MAPK-ERK is a central pathway in T-cell acute lymphoblastic leukemia that drives steroid resistance
Authors: Jordy C. G. van der Zwet, Jessica G. C. A. M. Buijs-Gladdines, Valentina Cordo’, Donna O. Debets, Willem K. Smits, Zhongli Chen, Jelle Dylus, Guido J. R. Zaman, Maarten Altelaar, Koichi Oshima, Beat Bornhauser, Jean-Pierre Bourquin, Jan Cools, Adolfo A. Ferrando, Josef Vormoor, Rob Pieters, Britta Vormoor, Jules P. P. Meijerink
Journal: Leukemia (2021)
A SARS-CoV-2 targeted siRNA-nanoparticle therapy for COVID-19
Authors: Adi Idris, Alicia Davis, Aroon Supramaniam, Dhruba Acharya, Gabrielle Kelly, Yaman Tayyar, Nic West, Ping Zhang, Christopher L.D. McMillan, Citradewi Soemardy, Roslyn Ray, Denis O’Meally, Tristan A. Scott, Nigel A.J. McMillan, Kevin V. Morris
Journal: Molecular Therapy (2021)
Abstract 13041: Stroke Mobile Apps: What About "FAST" and Other Risk Factors?
Authors: Gloria Wu, Binita S Pandya, harleen bhatti, Arunima Vijay
Journal: Circulation (2020)

Do Stroke Apps Include FAST? Background: There are 325,000 mobile health apps, with 3.7 billion downloads annually. Stroke is a major health problem in America, affecting 795,000 annually. Yet, 1 in 3 Americans cannot name the stroke warning signs. Hypothesis: Mobile health apps that mention stroke fail to include FAST criteria and fail to provide information about stroke risk factors. Methods: “Stroke” was used as a search term for iOs and Droid apps. We evaluated free apps, and Stroke warning signs,(F=face droop, A= arm weakness, S=speech, T= call 911, FAST). We looked for risk factors such as Cholesterol (Chol), fasting blood sugar (FBS), smoking, hypertension (HTN), atrial fibrillation (AF), ethnicity, gender, and age. Results: We found 500 apps that mentioned stroke, of those, only 7 apps specifically list the FAST criteria. The number of apps mentioning key risk factors are listed: Chol: 3/8, FBS 2/8, Smoking 4/8, HTN 5/8, Vision Loss 6/8, Gender 4/8, Ethnicity:2/8, Afib 3/8. Only 1 app mentioned heart.org, and none mentioned Stroke.org or “cvriskcalculator.” Conclusion: Only a small proportion of mobile apps mentioning stroke list the FAST criteria, possibly delaying patients and families from taking appropriate rapid action. Apps also need to have more information about important risk factors for stroke. Improved visibility of these apps is needed to increase public awareness of Stroke. References:Research2Guidance. 325000 mobile health apps available in 2017.https://research2guidance.com/325000-mobile-health-apps-available-in-2017/. Accessed May 17, 2020.