tbuckley/cabot-search huggingface dataset:
Promoting COVID-19 vaccine acceptance: recommendations from the Lancet Commission on Vaccine Refusal, Acceptance, and Demand in the USA
Authors: Saad B Omer, Regina M Benjamin, Noel T Brewer, Alison M Buttenheim, Timothy Callaghan, Arthur Caplan, Richard M Carpiano, Chelsea Clinton, Renee DiResta, Jad A Elharake, Lisa C Flowers, Alison P Galvani, Rekha Lakshmanan, Yvonne A Maldonado, SarahAnn M McFadden, Michelle M Mello, Douglas J Opel, Dorit R Reiss, Daniel A Salmon, Jason L Schwartz, Joshua M Sharfstein, Peter J Hotez
Journal: The Lancet (2021)

Since the first case of COVID-19 was identified in the USA in January, 2020, over 46 million people in the country have tested positive for SARS-CoV-2 infection. Several COVID-19 vaccines have received emergency use authorisations from the US Food and Drug Administration, with the Pfizer-BioNTech vaccine receiving full approval on Aug 23, 2021. When paired with masking, physical distancing, and ventilation, COVID-19 vaccines are the best intervention to sustainably control the pandemic. However, surveys have consistently found that a sizeable minority of US residents do not plan to get a COVID-19 vaccine. The most severe consequence of an inadequate uptake of COVID-19 vaccines has been sustained community transmission (including of the delta [B.1.617.2] variant, a surge of which began in July, 2021). Exacerbating the direct impact of the virus, a low uptake of COVID-19 vaccines will prolong the social and economic repercussions of the pandemic on families and communities, especially low-income and minority ethnic groups, into 2022, or even longer. The scale and challenges of the COVID-19 vaccination campaign are unprecedented. Therefore, through a series of recommendations, we present a coordinated, evidence-based education, communication, and behavioural intervention strategy that is likely to improve the success of COVID-19 vaccine programmes across the USA.
Understanding the Importance of the Lay Responder Experience in Out-of-Hospital Cardiac Arrest: A Scientific Statement From the American Heart Association
Authors: Katie N. Dainty, Brianna Colquitt, Farhan Bhanji, Elizabeth A. Hunt, Tiffany Jefkins, Marion Leary, Joseph P. Ornato, Robert A. Swor, Ashish Panchal
Journal: Circulation (2022)

Bystander cardiopulmonary resuscitation (CPR) is critical to increasing survival from out-of-hospital cardiac arrest. However, the percentage of cases in which an individual receives bystander CPR is actually low, at only 35% to 40% globally. Preparing lay responders to recognize the signs of sudden cardiac arrest, call 9-1-1, and perform CPR in public and private locations is crucial to increasing survival from this public health problem. The objective of this scientific statement is to summarize the most recent published evidence about the lay responder experience of training, responding, and dealing with the residual impact of witnessing an out-of-hospital cardiac arrest. The scientific statement focuses on the experience-based literature of actual responders, which includes barriers to responding, experiences of doing CPR, use of an automated external defibrillator, the impact of dispatcher-assisted CPR, and the potential for postevent psychological sequelae. The large body of qualitative and observational studies identifies several gaps in crucial knowledge that, if targeted, could increase the likelihood that those who are trained in CPR will act. We suggest using the experience of actual responders to inform more contextualized training, including the implications of performing CPR on a family member, dispelling myths about harm, training and litigation, and recognition of the potential for psychologic sequelae after the event.
Abstract P149: The Relationship Between Daytime Sleepiness, Exhaustion, Fatigue, And Arterial Stiffness. The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Michael A Newton, Gerardo M Heiss, Emma Barinas-Mitchell, Pamela L Lutsey, Hirofumi Tanaka, Kapuaola S Gellert, Lee Stoner, Michelle L Meyer
Journal: Circulation (2022)

Background: Excessive Daytime Sleepiness (EDS) is positively associated with the risk of cardiovascular disease (CVD) events and CVD mortality. However, the association between EDS and subclinical markers of CVD, such as arterial stiffness, is not fully understood and could have implications for CVD screening. EDS is multifactorial in origin, thus we incorporated measures of exhaustion and fatigue in order to comprehensively assess the association of lethargy and central artery stiffness. We examined the separate relationships between EDS, exhaustion, fatigue, and aortic stiffness via carotid-femoral pulse wave velocity (cfPWV) in a large population-based study. Methods: A cross-sectional analysis of ARIC Study participants (n=2500, mean age: 79.7, 57.2% female) who underwent arterial stiffness measurements (cfPWV) and completed the Epworth Sleep Scale (ESS) questionnaire in 2016-2019. EDS was defined as ESS 11. Exhaustion was derived from the Center for Epidemiological Study’s Depression (CES-D) scale, with positive exhaustion corresponding to increased effort in daily activities and noticeable difficulty in getting “going’. Fatigue was assessed at annual follow up calls in 2012-2013 and calculated as a summary score with participants responses about feeling tired in various scenarios in the past 7 days noted as a numeric value (1-5: never, rarely, sometimes, often or always). We used multivariable linear regression to estimate the association between ESS, exhaustion, and fatigue with cfPWV, adjusting for age, race-study center, body mass index, diabetes, heart rate, mean arterial pressure, and blood-pressure medication use. We evaluated potential effect modification by race, sex, diabetes, and hypertension. Results are presented as unstandardized beta coefficients (β) and 95% confidence intervals (CI). Results: A total of 14.2% participants reported EDS, 17.2% reported exhaustion, and the average fatigue score was 8.0. ESS was not associated with cfPWV when adjusting for covariates (β; 95% CI: -1.4; -4.7, 1.9). Similarly, EDS was not associated with cfPWV (β; 95% CI: -4.9; -40.4, 30.6), nor was there an association between ESS quartiles and cfPWV. However, both exhaustion (β; 95% CI: 40.4; 7.8, 73.0) and fatigue (β; 95% CI: 5.4; 0.6, 10.3) were positively associated with cfPWV after adjusting for covariates. There was no evidence of effect modification by race, sex, diabetes, or hypertension. Conclusion: EDS was not associated with arterial stiffness. A (positive) association was observed for both exhaustion and fatigue with cfPWV, suggesting a need for further investigation of fatigue related conditions and arterial stiffness in older adults.
A study of dupilumab in Chinese patients with atopic dermatitis
Journal: British Journal of Dermatology (2022)

Atopic dermatitis is a common skin condition in which the process of inflammation becomes imbalanced. Affected people have eczema‐like lesions and intense itching. Although mild atopic dermatitis can be successfully treated with creams and ointments, moderate and severe disease often requires treatment with corticosteroids and immunosuppressants that affect the entire body. However, these treatments often cause undesirable side‐effects and cannot be used for long periods of time.
Special Considerations for Healthy Lifestyle Promotion Across the Life Span in Clinical Settings: A Science Advisory From the American Heart Association
Authors: Penny M. Kris-Etherton, Kristina S. Petersen, Jean-Pierre Després, Lynne Braun, Sarah D. de Ferranti, Karen L. Furie, Scott A. Lear, Felipe Lobelo, Pamela B. Morris, Frank M. Sacks
Journal: Circulation (2021)

At a population level, engagement in healthy lifestyle behaviors is suboptimal in the United States. Moreover, marked disparities exist in healthy lifestyle behaviors and cardiovascular risk factors as a result of social determinants of health. In addition, there are specific challenges to engaging in healthy lifestyle behaviors related to age, developmental stage, or major life circumstances. Key components of a healthy lifestyle are consuming a healthy dietary pattern, engaging in regular physical activity, avoiding use of tobacco products, habitually attaining adequate sleep, and managing stress. For these health behaviors, there are guidelines and recommendations; however, promotion in clinical settings can be challenging, particularly in certain population groups. These challenges must be overcome to facilitate greater promotion of healthy lifestyle practices in clinical settings. The 5A Model (assess, advise, agree, assist, and arrange) was developed to provide a framework for clinical counseling with consideration for the demands of clinical settings. In this science advisory, we summarize specific considerations for lifestyle-related behavior change counseling using the 5A Model for patients across the life span. In all life stages, social determinants of health and unmet social-related health needs, as well as overweight and obesity, are associated with increased risk of cardiovascular disease, and there is the potential to modify this risk with lifestyle-related behavior changes. In addition, specific considerations for lifestyle-related behavior change counseling in life stages in which lifestyle behaviors significantly affect cardiovascular disease risk are outlined. Greater attention to healthy lifestyle behaviors during every clinician visit will contribute to improved cardiovascular health.
Abstract MP77: Circulating Magnesium And Risk Of Major Adverse Cardiac Events Among Patients With Atrial Fibrillation In The Aric Cohort
Authors: Linzi Li, Pamela L Lutsey, Mary R Rooney, Lin Y Chen, Elsayed Z Soliman, Alvaro Alonso
Journal: Circulation (2022)

Background: Serum magnesium (Mg) has been reported to be inversely associated with the risk of atrial fibrillation (AF), coronary artery disease (CAD), and major adverse cardiovascular events (MACE). However, whether high serum Mg is associated with a lower risk of MACE, heart failure (HF), stroke, and all-cause mortality among AF patients remains unclear. Methods: We evaluated prospectively 503 participants of the Atherosclerosis Risk in Communities (ARIC) Study with available serum Mg and a diagnosis of AF at the time of Mg measurement participating in visit 2 (1990-1992, n = 90) or visit 5 (2011-2013, n = 403). Serum Mg was modeled in tertiles and as a continuous variable in standard deviation units. Endpoints (HF, MI, stroke, cardiovascular (CV) death, all-cause mortality, and MACE) were identified and modeled separately using Cox proportional hazard regression adjusting for potential confounders. Results: During a mean follow-up of 7.0 years, there were 105 HF, 50 MI, 36 stroke, 119 CV deaths, 160 total deaths, and 285 MACE. After adjustment for demographic and clinical variables, participants in the 2 nd and 3 rd tertiles of serum Mg had lower rates of most endpoints, with the strongest inverse association for the incidence of MI (Table). Serum Mg modeled linearly as a continuous variable did not show clear associations with endpoints. Due to limited number of events, precision of most estimates of association was relatively low. Conclusion: Higher serum Mg was associated with lower risk of developing incident MI and, to a lesser extent, other cardiovascular endpoints. Further studies in larger AF patient cohorts are needed to evaluate the role of serum Mg in preventing adverse CV outcomes in these patients.
Effectiveness of Inactivated COVID-19 Vaccines Against Illness Caused by the B.1.617.2 (Delta) Variant During an Outbreak in Guangdong, China
Authors: Min Kang, Yao Yi, Yan Li, Limei Sun, Aiping Deng, Ting Hu, Jiayi Zhang, Jun Liu, Mingji Cheng, Shen Xie, Min Luo, Jing Jiang, Yawen Jiang, Shixing Tang, Jianfeng He
Journal: Annals of Internal Medicine (2022)

Real-world evidence on inactivated COVID-19 vaccines against the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2 is limited, leaving an important gap in the evidence base about inactivated COVID-19 vaccines for use by immunization programs.
A Tale of Two Histologies: Dissecting the Biology of Lineage Transformation in Lung Cancer
Authors: Catherine B. Meador, Christine M. Lovly
Journal: Cancer Discovery (2021)

Abstract Summary: Lineage plasticity is an important, and likely underappreciated, mechanism of treatment resistance in lung cancer. Here, Quintanal-Villalonga and colleagues integrate results from multiomic analyses to provide key new insights into the biology of lineage plasticity. See related article by Quintanal-Villalonga et al., p. 3028.
Increased 68Ga-FAPI Uptake by Mediastinal Benign Teratoma on 68Ga-FAPI PET/CT
Authors: Dengsai Peng, Junhao Wu, Tao Zhang, Yue Chen, Zhi Hu
Journal: Clinical Nuclear Medicine (2022)

Abstract Mediastinal teratoma is a relatively rare disease that usually contains tissue from the endoderm, mesoderm, and ectoderm. We report a finding that mediastinal benign teratoma showed intense FAPI activity on 68 Ga-FAPI PET/CT, which may lead to misdiagnosis of this benign lesion. It is necessary to realize that benign teratoma is also one of the reasons for the intense FAPI uptake in mediastinal masses, so as not to be misdiagnosed as a malignant tumor.
B01: STROMAL CELL-NEUTROPHIL INTERACTIONS PROMOTE A PRO-TUMOR ENVIRONMENT IN MULTIPLE MYELOMA
Authors: M de Jong, C Fokkema, T van Heusden, N Papazian, S Tahri, Z Kellermayer, P Vermeulen, M van Duin, P van de Woestijne, A Broijl, P Sonneveld, T Cupedo
Journal: HemaSphere (2022)

Cancer development and progression are accompanied by alterations in the local microenvironment. In multiple myeloma (MM), interactions between myeloma cells and their niche are considered critical for disease pathobiology. Recently, we showed that the MM bone marrow (BM) is characterized by inflammatory mesenchymal stromal cells (iMSCs) that transcribe MM survival factors such as IL6, as well as myeloid cell modulation factors such as CCL2, ANXA1, C3 and chemokines that bind CXCR1 and 2. As myeloid cells have been implicated in the pathophysiology of various malignancies, we hypothesized that iMSCs attract and influence myeloid populations in the MM BM. Using flow cytometry, we observed increased expression of CXCR1/2 on CD15+ neutrophils in MM compared to those of controls. In addition, BM neutrophils in MM were activated, as evidenced by a switch to the active form of CD11b and the shedding of CD62L. As these findings suggested possible neutrophil – iMSC interactions, we set out to identify MM-associated alterations in neutrophils by scRNA sequencing of the full BM granulocytic lineage (n = 6 MM, and 4 controls). Immature and mature neutrophils in MM had increased transcription of genes encoding receptors for iMSC-derived signals, including IL6R, FPR and C3AR1. Moreover, we confirmed the activated state of neutrophils through elevated transcription of OSM, SLPI, and IL1B. These data suggest a contribution of iMSCs to neutrophil activation. This was confirmed by coculture of iMSCs and naïve neutrophils, which lead to shedding of neutrophilic CD62L. Further analysis of our transcriptional data revealed that a subpopulation of activated MM neutrophils expressed interferon (IFN)-response genes, including IFIT1, IFIT2 and ISG15. Importantly, by analyzing single cell immune datasets of MM bone marrow, we observed IFN-responsive neutrophils to be the only hematopoietic population transcribing TNFSF13B, encoding the MM-survival factor BAFF. Stimulation of naïve neutrophils with IFNγ or IFNβ induced TNFSF13B transcription, but did not lead to BAFF secretion. This led us to hypothesize that BAFF release by activated neutrophils might be regulated by the inflammatory stromal environment. To test this hypothesis we cultured IFNγ-stimulated neutrophils in the presence of either non inflammatory MSCs or IL1β-activated iMSCs. Whilst the presence of iMSCs could induce BAFF release by neutrophils, non-inflammatory MSCs did not have this effect. Together these data suggest that stromal – immune interactions in MM are driving a tumor-supportive environment by inducing local release of plasma cell survival factors.
Enhanced ASGR2 by microplastic exposure leads to resistance to therapy in gastric cancer
Authors: Hyeongi Kim, Javeria Zaheer, Eui-Ju Choi, Jin Su Kim
Journal: Theranostics (2022)

Background: Microplastics (MPs) are a new global environmental threat. Previously, we showed the biodistribution of MPs using [64Cu] polystyrene (PS) and PET in mice. Here, we aimed to identify whether PS exposure has malignant effects on the stomach and induces resistance to therapy. Methods: BALB/c nude mice were fed 1.72 × 104 particles/mL of MP. We investigated PS accumulation in the stomach using radioisotope-labeled and fluorescent-conjugated PS. Further, we evaluated whether PS exposure induced cancer stemness and multidrug resistance, and whether it affected tumor development, tumor growth, and survival rate in vivo using a 4-week PS-exposed NCI-N87 mouse model. Using RNA-Seq analysis, we analyzed whether PS exposure induced gene expression changes in gastric tissues of mice. Results: PET imaging results showed that a single dose of [64Cu]-PS remained for 24 h in the mice stomach. The 4-week daily repetitive dose of fluorescent conjugated PS was deposited in the gastric tissues of mice. When PS was exposed, a 2.9-fold increase in migration rate was observed for NCI-N87 cells. Immunocytochemistry results showed decreased E-cadherin and increased N-cadherin expression, and flow cytometry, qPCR, and western blot analysis indicated a 1.9-fold increase in N-cadherin expression after PS exposure. Further, PS-induced multidrug resistance to bortezomib, paclitaxel, gefitinib, lapatinib, and trastuzumab was observed in the NCI-N87 mouse model due to upregulated CD44 expression. RNA-seq results identified increased asialoglycoprotein receptor 2 (ASGR2) expression after PS exposure, and ASGR2 knockdown decreased cell proliferation, migration, invasion, and drug resistance. Conclusion: We demonstrated that ASGR2 enhanced cancer hallmarks on PS exposure and induced resistance to chemo- and monoclonal antibody-therapy. Our preclinical findings may provide an incentive for further epidemiological studies on the role of MP exposure and its association with gastric cancer.
Abstract MP76: Association Of Elevated High-sensitive Cardiac Troponin T And Low Ankle-brachial Index With Incident Cardiovascular Events. The Multi-ethnic Study Of Atherosclerosis And The Cardiovascular Health Study
Authors: Yacob Tedla, Steven Driver, Moyses Szklo, Lewis H Kuller, Joao Lima, Erin D Michos, Christopher Defilippi, Philip Greenland
Journal: Circulation (2022)

Introduction: Elevated high-sensitive cardiac troponin T (hs-cTnT&gt;14 ng/L) and low ankle-brachial index (ABI &lt; 0.9) are known to be associated with cardiovascular diseases (CVD) but their joint effect on the risk of CVD events is unknown. Methods: We used data from the MESA and CHS among 10,900 participants free of CVD events at baseline (mean age 66.3 years, 44.7% males). Incident coronary heart disease (CHD) was defined as fatal or non-fatal myocardial infarction or revascularization and incident CVD was defined as CHD, transient ischemic attack, stroke, or atrial fibrillation. Hazard ratio (HR) and 95% CI was calculated from a Cox regression model. Interaction on the additive scale was assessed using relative excess risk due to interaction (RERI) and interaction on the multiplicative scale was assessed by Likelihood ratio (LR) test. Results: At baseline (2000-2002 for MESA and 1989-1990 for CHS), 10.2% of participants had elevated hs-cTnT and 7.5% had low ABI. During 26.1 years of total follow-up (median follow-up 18.4 years), there were 3,911 incident CVD events. The risk of CHD and CVD was higher in participants with both elevated hs-cTnT and low ABI [CHD HR: 2.1 (1.5, 2.9), CVD HR: 2.1 (1.7, 2.5)], only elevated hs-cTnT [CHD HR: 1.7 (1.4, 2.0), CVD HR: 1.6 (1.5, 1.8)], and only low ABI [CHD HR: 1.8 (1.5, 2.2), CVD HR: 1.5 (1.3, 1.7)] than those with unelevated hs-cTnT and normal ABI. Interaction on the multiplicative scale was observe in both adjusted and unadjusted models for CHD (unadjusted LR test p-value=0.002, adjusted LR test p-value=0.042) and only in unadjusted model for CVD (LR test p-value=0.001). No significant additive interaction was detected for both CHD and CVD (RERI p-value≥0.25 for unadjusted and adjusted models). Conclusion: Having both elevated cTnT and low ABI was associated more strongly with CVD events than only elevated cTnT or low ABI. Antagonistic multiplicative interaction was found indicating the observed joint effect of elevated cTnT and low ABI was smaller than the expected combined individual effects.
Abstract P119: Conceptualizing Cultural Safety When Implementing A Community Based Substance Use Intervention Study Among Urban Native American Youth
Authors: Rose Wimbish-Tompkins
Journal: Circulation (2022)

Background: This study was conducted in the United States of America among Urban Native American (NA) youth attending two urban NA youth programs within the State of Florida. Aim: To culturally tailor the evidence-based Lowe (2016) Keetoowah-Cherokee Talking Circle intervention for substance use prevention among Keetoowah-Cherokee youth to that of an Urban Taking Circle (UTC) intervention for use among urban NA youth. Method: The integration of a culturally relevant theory, Native-Reliance, a community-based program approach, and cultural safety principles guided the intervention study method. The study implemented a 2-condition quasi experimental design and utilized convenience and snowball sampling methods for recruiting 100 urban NA youth as study participants. Participants originated from two urban NA community programs and were randomized by program site. Statistical analysis using multivariate analysis of variance (MANOVA) provided the means for determining if there were significant differences between the scores on measures at pre-intervention (baseline) and post-intervention. Results: Data findings indicated there is a direct relationship between the urban NA youth participants’ interests in engaging in drug use, alcohol consumption, and commercial tobacco smoking. However, additional findings provide evidence that a culturally based intervention was significantly more effective for the reduction of these substance use interests and general well-being than a non-culturally based intervention for urban NA youth. Conclusion: Study findings also indicated that supporting Urban NA youths’ utilization of urban NA values and beliefs promoted healthy behavior. Culturally safe interventions that support urban NA youth as a means in reducing harm associated with high-risk behaviors, such as substance use, is strongly recommended. Impact Statement: During each phase of the study, its method established assurance of cultural safety by operationalizing Native Reliance Theory. Therefore, an in-depth examination of the study methods with cultural safety principles is presented in context and warranted.