tbuckley/cabot-search huggingface dataset:
Abstract P203: Metabolomic Markers Of Gestational Weight Gain In Overweight And Obese Pregnant Women-a Longitudinal Study
Authors: Jin Dai, Jihong Liu, Nansi Boghossian, Feng Luo, Xiaoqian Sun, Oliver Fiehn, Liwei Chen
Journal: Circulation (2022)

Background: Optimal gestational weight gain (GWG) is critical for fetal development and maternal health. Few studies have investigated metabolomic markers of GWG. Thus, we performed a metabolome-wide association study with GWG among pregnant women in the US. Methods: This longitudinal study included overweight or obese pregnant women (pre-pregnancy BMI ≥ 25) enrolled in the Health in Pregnancy and Postpartum study in early pregnancy (mean gestational week (GW) at baseline=12). Fasting plasma samples were collected both at baseline (N=39) and 32 GW (N=29). Untargeted metabolomic profiling was conducted using three different analytical platforms, including GC-TOF MS, HILIC-QTOF MS/MS, and CSH-QTOF MS/MS. Linear regressions were performed to identify metabolites at each time point and the change between two time points (i.e., metabolites 32 wk - metabolites baseline )/metabolites baseline ) that were individually associated with total GWG, a difference between delivery weight and pre-pregnancy weight. The least absolute shrinkage and selection operator (LASSO) regressions were conducted to select metabolites that were jointly associated with total GWG. Results: The mean (SD) age of 39 women enrolled was 30.4 (5.4) years and 38.5% were Blacks. A total of 769 known metabolites were profiled and annotated. Eight metabolites at 32 GW, including PC (34:4), LPC (22:5), isoleucine, arachidonic acid, TAG (52:6), TAG (58:7), and glyceric acid were positively whereas 3-Hydroxybutyrylcarnitine was negatively associated with GWG in both linear regressions (FDR &lt; 0.1) and LASSO regressions (with no-zero coefficients) after adjusting for age, race, parity, and pre-pregnancy BMI (Figure 1). Metabolites at around 12 GW or changes between two time points were not associated with GWG (all FDRs ≥ 0.1). Conclusions: We identified eight metabolites at 32 GW that were significantly associated with total GWG in this longitudinal study of overweight and obese pregnant women. Future studies are warranted to replicate our findings.
A Burning Question
Authors: Alexander S. Rabin, Caroline W. Davis, Anays M. Sotolongo, Michael J. Falvo, John J. Osterholzer
Journal: New England Journal of Medicine (2022)

A 35-year-old man presented to a Veterans Affairs pulmonary clinic with exertional dyspnea and cough. The patient's symptoms began 4 years before presentation and had progressed over time.
Spontaneous Coronary Artery Dissection: Insights From Cardiac Magnetic Resonance and Extracoronary Arterial Screening
Authors: Emmanuel Androulakis, Alessia Azzu, Panagiotis Papagkikas, Alexios Antonopoulos, Abtehale Al-Hussaini, Dudley Pennell, Raad Mohiaddin
Journal: Circulation (2022)
Risk reduction of severe outcomes in vaccinated COVID-19 cases: an analysis of surveillance data from Estonia, Ireland, Luxembourg and Slovakia, January to November 2021
Authors: Gaetano Marrone, Nathalie Nicolay, Nick Bundle, Tommi Karki, Gianfranco Spiteri, Heleene Suija, Kerstin-Gertrud Kärblane, Joël Mossong, Anne Vergison, Maria Avdicova, Adriana Mecochova, Gillian Cullen, Piaras O’Lorcain, Lucia Pastore Celentano, Tarik Derrough, Julien Beauté
Journal: Eurosurveillance (2022)

Despite high COVID-19 vaccine coverage in the EU/EEA, there are increasing reports of SARS-CoV-2 infections and hospitalisations in vaccinated individuals. Using surveillance data from Estonia, Ireland, Luxembourg and Slovakia (January-November 2021), we estimated risk reduction of severe outcomes in vaccinated cases. Increasing age remains the most important driver of severity, and vaccination significantly reduces risk in all ages for hospitalisation (adjusted relative risk (aRR): 0.32; 95% confidence interval (CI): 0.26-0.39) and death (aRR: 0.20; 95% CI: 0.13-0.29).
Lymphoscintigraphic Findings of Scrotal Lymphangioma
Authors: Guohua Shen, Anren Kuang
Journal: Clinical Nuclear Medicine (2022)

Abstract As congenital lymphatic malformations, lymphangiomas commonly occur in the neck, tongue, and extremities, whereas scrotum is one of the least frequent sites. For this lymphatic flow disease, lymphoscintigraphy is regarded as a useful imaging method. Herein, in a child with scrotal cysts, scrotal region activity was detected in lymphoscintigraphy, consistent with likely lymphatic disorder. The postsurgical pathology confirmed the diagnosis of lymphangioma.
48P Efficacy of osimertinib (osi) on (prevention of) bone metastases (mets) and skeletal related events (SREs) in patients (pts) with epidermal growth factor receptor mutated (EGFRm+) non-small cell lung cancer (NSCLC)
Authors: A. Brouns, A.V. Veelen, M. Veerman, C. Steendam, S. Dursun, S. Croes, A-M.C. Dingemans, L. Hendriks
Journal: Annals of Oncology (2022)
Abstract EP65: Left Coronary Artery Cross-sectional Area And Traditional Cardiovascular Risk Factors Among Asymptomatic South Asians: Results From The MASALA Study
Authors: Akemi Brown, Jeffrey Carr, Sangeeta Nair, James G Terry, Feng Lin, Alka M Kanaya
Journal: Circulation (2022)

Background: South Asians have a higher atherosclerotic cardiovascular disease (ASCVC) burden than other race/ethnic groups that is not fully explained by traditional risk factors. Smaller coronary artery luminal diameter has been proposed as a potential reason for this higher risk among South Asians. A few studies have measured coronary artery diameter in South Asians demonstrating smaller coronary luminal diameter explained by smaller body size. However, these studies were done symptomatic individuals with high burden of coronary plaque, and stenosis and vascular tone is known to impact lumen diameter. No studies have measured coronary artery external diameters in asymptomatic South Asians. Methods: We analyzed data from 513 participants, between ages of 42 and 68 years, enrolled in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study (2016-2018). We analyzed coronary cross-sectional area (CSA) with thin slice non-contrast cardiac CT scans. This is equivalent to the outermost (adventitial) boundary measured with intravascular ultrasound of the coronary arteries. We computed mean CSA in the proximal and mid LAD segments perpendicular to the centerline of the vessel. We examined bivariate associations of traditional cardiovascular risk factors and coronary artery calcium (CAC) with LAD CSA. We then created multivariable models adjusted for age and sex to determine independent correlations with LAD CSA. Results: We used data from 285 men and 228 women with mean age 56±7 years. The overall mean LAD CSA was 22.8±6.8 mm 2 for men and 17.6±6.2 mm 2 for women. In bivariate analysis, higher LAD CSA was associated with male sex, and higher age, BMI, waist circumference, systolic and diastolic blood pressures, fasting glucose, total and LDL-cholesterol, CAC scores, statin medication use, and lower HDL-cholesterol. In multivariable models, only male sex (β 0.044, p&lt;0.001), hypertension (β 0.024, p&lt;0.001), and BMI (β 0.003 per kg/m 2 , p &lt;0.001) were significantly associated with LAD CSA. High CAC was marginally associated with LAD CSA (CAC&gt;100: B 0.015 p = 0.065) while age, diabetes, and cholesterol levels were not independently associated with LAD CSA. Conclusion: These preliminary results suggest that LAD CSA is highly correlated with sex, body size, and hypertension, but not other metabolic risk factors that are more aberrant among South Asians. Long-term follow-up will determine whether LAD CSA is an important contributor to cardiovascular disease events among South Asians.
129P Regulatory dendritic cells correlate with an altered T cell distribution and regulatory T cell phenotype in metastatic lymph nodes of NSCLC patients
Authors: A. Raniszewska, I. Kwiecien, E. Rutkowska, R. Sokolowski, J. Bednarek, P. Rzepecki, J. Domagala-Kulawik
Journal: Annals of Oncology (2022)
CD4<sup>+</sup>FoxP3<sup>+</sup>CD73<sup>+</sup> regulatory T cell promotes cardiac healing post-myocardial infarction
Authors: Rulin Zhuang, Qingshu Meng, Xiaoxue Ma, Shanshan Shi, Shiyu Gong, Jing Liu, Mimi Li, Wenchao Gu, Dan Li, Xumin Zhang, Zhulin Wang, Xinyu Ge, Jiayou Tang, Fang Lin, Xiaoting Liang, Liang Zheng, Zhongmin Liu, Xiaohui Zhou
Journal: Theranostics (2022)

Rationale: Despite recent studies indicating a crucial role of ecto-5′-nucleotidase (CD73) on T cells in cardiac injury after ischemia/reperfusion, the involvement of CD73 + regulatory T cells (Tregs) in cardiac repair post-myocardial infarction (MI) remains unclear.We sought to investigate the contribution of CD73 on Tregs to the resolution of cardiac inflammation and remodeling after MI.Methods: Cardiac function, tissue injury, Tregs percentage in injured hearts, and purinergic signaling changes in cardiac FoxP3 + Tregs were analyzed after permanent descending coronary artery ligation.CD73 knockout Tregs were used to determine the function of CD73 on Tregs.Peripheral blood mononuclear cells (PBMCs) from acute myocardial infarction (AMI) patients and matched non-MI subjects were assessed via flow cytometry.Results: Cardiac Tregs exhibited distinction of purinergic signaling post MI with dramatically high level of CD73 compared to the sham Tregs.CD73 deficiency decreased the tissue tropism, and impaired the immunosuppressive and protective function of Tregs in cardiac healing.Administration of low-dose of IL-2/anti-IL-2 complex resulted in FoxP3 + CD73 + Tregs expansion in the heart and contributed to the recovery of cardiac function.CD73 derived from FoxP3 + Tregs could bind to FoxP3 -effector T-cells and inhibit the production of multiple inflammatory cytokines.In AMI patients, CD73 expressions on both CD4 + cells and FoxP3 + Tregs decreased in PBMCs.Moreover, CD73 expressions on CD4 + T cells were negatively correlated with the levels of NT pro-BNP and myocardial zymogram in serum.Conclusions: Our findings indicated the importance of FoxP3 + CD73 + Tregs in inflammation resolution and cardiac healing post-MI.
Epigenetic Upregulation of H19 and AMPK Inhibition Concurrently Contribute to S-Adenosylhomocysteine Hydrolase Deficiency-Promoted Atherosclerotic Calcification
Authors: Xin Dai, Si Liu, Lokyu Cheng, Ting Huang, Honghui Guo, Dongliang Wang, Min Xia, Wenhua Ling, Yunjun Xiao
Journal: Circulation Research (2022)

Background: S-adenosylhomocysteine (SAH) is a risk factor of cardiovascular disease; inhibition of SAH hydrolase (SAHH) results in SAH accumulation and induces endothelial dysfunction and atherosclerosis. However, the effect and mechanism of SAHH in atherosclerotic calcification is still unclear. We aimed to explore the role and mechanism of SAHH in atherosclerotic calcification. Methods: The relationship between SAHH and atherosclerotic calcification was investigated in patients with coronary atherosclerotic calcification. Different in vivo genetic models were used to examine the effect of SAHH deficiency on atherosclerotic calcification. Human aortic and murine vascular smooth muscle cells (VSMCs) were cultured to explore the underlying mechanism of SAHH on osteoblastic differentiation of VSMCs. Results: The expression and activity of SAHH were decreased in calcified human coronary arteries and inversely associated with coronary atherosclerotic calcification severity, whereas plasma SAH and total homocysteine levels were positively associated with coronary atherosclerotic calcification severity. Heterozygote knockout of SAHH promoted atherosclerotic calcification. Specifically, VSMC-deficient but not endothelial cell–deficient or macrophage-deficient SAHH promoted atherosclerotic calcification. Mechanistically, SAHH deficiency accumulated SAH levels and induced H19-mediated Runx2 (runt-related transcription factor 2)-dependent osteoblastic differentiation of VSMCs by inhibiting DNMT3b (DNA methyltransferase 3b) and leading to hypomethylation of the H19 promoter. On the contrary, SAHH deficiency resulted in lower intracellular levels of adenosine and reduced AMPK (AMP-activated protein kinase) activation. Adenosine supplementation activated AMPK and abolished SAHH deficiency–induced expression of H19 and Runx2 and osteoblastic differentiation of VSMCs. Finally, AMPK activation by adenosine inhibited H19 expression by inducing Sirt1 (sirtuin-1)-mediated histone H3 hypoacetylation and DNMT3b-mediated hypermethylation of the H19 promoter in SAHH deficiency VSMCs. Conclusions: We have confirmed a novel correlation between SAHH deficiency and atherosclerotic calcification and clarified a new mechanism that epigenetic upregulation of H19 and AMPK inhibition concurrently contribute to SAHH deficiency–promoted Runx2-dependent atherosclerotic calcification.
Abstract MP09: Partnering With Employers To Provide Worksite-based Health Assessments In Rural Communities
Authors: Ashley Burch, Fernando Chivela, Elisabeth Lee, Paul Shackelford, Paul Bolin
Journal: Circulation (2022)

Introduction: Office-based healthcare delivery with limited hours of operation can be a deterrent to seeking medical care for many individuals. Innovative approaches to healthcare delivery, particularly health assessment and screenings, could improve patient engagement and ultimately yield better long-term public health outcomes. Hypothesis: Compared to national averages, elevated rates of undiagnosed and uncontrolled disease will be found among participants living in a rural area with known high endemic disease through worksite-based health assessments. Methods: Between December 2020 and October 2021, we partnered with 13 business for on-the-jobsite health screening clinics. Participants completed a series of questionnaires and a physical assessment. Disease screenings included diabetes, hypertension, kidney disease, cholesterol, sleep apnea, and stroke risk. Results were available immediately following the screening. Physicians conducted one-on-one consultations with participants to discuss their results and advise them, as needed, on treatment and management of their condition. Results: A total of 463 individuals (44.7% white) (54.4% male) were screened. On-site lab results identified 41 (9.0%) participants with an indicator of diabetes (HbA1c ≥6.5) that were previously undiagnosed*. An additional 44 (9.6%) participants had been previously diagnosed with diabetes, but testing results indicated their diabetes was not well controlled (HbA1c ≥6.5). Undiagnosed hypertension (SBP ≥140) was found in 114 (24.7%) participants and 93 (20.2%) participants had diagnosed but uncontrolled hypertension. We also identified 33 (15.9%) participants with indicators of chronic kidney disease (urine protein ≥1), 13 (3.9%) participants with high cholesterol (total cholesterol ≥240), 122 (26.3%) participants with moderate increased risk of heart attack or stroke (CHA 2 DS 2 -VASc ≥2), and 27 (22.0%) with moderate to severe risk of obstructive sleep apnea (STOP-BANG ≥4). Conclusion: Of over 450 individuals screened, nearly a quarter of participants revealed a moderate increased risk of heart attack or stroke. Nearly half of participants had uncontrolled or undiagnosed hypertension and twenty percent of participants suffered from uncontrolled or undiagnosed diabetes. Our mobile, on-the-jobsite health screening clinics provide patients with convenient, walk-in service, immediate results, and physician consultation as a bridge to accessing ongoing care. This screening strategy addresses issues of complexity, cost, and privacy and captures individuals who may otherwise underutilize or avoid engagement with the healthcare system. Longer-term follow-up is planned to determine the public health impact of these on-the-jobsite health screenings. *Percentage based off number screened per condition
Antibodies from convalescent plasma promote SARS-CoV-2 clearance in individuals with and without endogenous antibody response
Authors: Maddalena Marconato, Irene A. Abela, Anthony Hauser, Magdalena Schwarzmüller, Rheliana Katzensteiner, Dominique L. Braun, Selina Epp, Annette Audigé, Jacqueline Weber, Peter Rusert, Eméry Schindler, Chloé Pasin, Emily West, Jürg Böni, Verena Kufner, Michael Huber, Maryam Zaheri, Stefan Schmutz, Beat M. Frey, Roger D. Kouyos, Huldrych F. Günthard, Markus G. Manz, Alexandra Trkola
Journal: Journal of Clinical Investigation (2022)

BACKGROUND. Neutralizing antibodies are considered a key correlate of protection by current SARS-CoV-2 vaccines. The manner in which human infections respond to therapeutic SARS-CoV-2 antibodies, including convalescent plasma therapy, remains to be fully elucidated.
Vaccination Coverage with Selected Vaccines and Exemption Rates Among Children in Kindergarten — United States, 2020–21 School Year
Authors: Ranee Seither, Jessica Laury, Agnes Mugerwa-Kasujja, Cynthia L. Knighton, Carla L. Black
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

State and local school vaccination requirements serve to protect students against vaccine-preventable diseases (1). This report summarizes data collected for the 2020-21 school year by state and local immunization programs* on vaccination coverage among children in kindergarten in 47 states and the District of Columbia (DC), exemptions for kindergartners in 48 states and DC, and provisional enrollment or grace period status for kindergartners in 28 states. Vaccination coverage† nationally was 93.9% for 2 doses of measles, mumps, and rubella vaccine (MMR); 93.6% for the state-required number of doses of diphtheria, tetanus, and acellular pertussis vaccine (DTaP); and 93.6% for the state-required doses of varicella vaccine. Compared with the 2019-20 school year, vaccination coverage decreased by approximately one percentage point for all vaccines. Although 2.2% of kindergartners had an exemption from at least one vaccine,§ an additional 3.9% who did not have a vaccine exemption were not up to date for MMR. The COVID-19 pandemic affected schools' vaccination requirement and provisional enrollment policies, documentation, and assessment activities. As schools continue to return to in-person learning, enforcement of vaccination policies and follow-up with undervaccinated students are important to improve vaccination coverage.
Understanding Health Inequalities Through the Lens of Social Epigenetics
Authors: Chantel L. Martin, Lea Ghastine, Evans K. Lodge, Radhika Dhingra, Cavin K. Ward-Caviness
Journal: Annual Review of Public Health (2022)

Longstanding racial/ethnic inequalities in morbidity and mortality persist in the United States. Although the determinants of health inequalities are complex, social and structural factors produced by inequitable and racialized systems are recognized as contributing sources. Social epigenetics is an emerging area of research that aims to uncover biological pathways through which social experiences affect health outcomes. A growing body of literature links adverse social exposures to epigenetic mechanisms, namely DNA methylation, offering a plausible pathway through which health inequalities may arise. This review provides an overview of social epigenetics and highlights existing literature linking social exposures—i.e., psychosocial stressors, racism, discrimination, socioeconomic position, and neighborhood social environment—to DNA methylation in humans. We conclude with a discussion of social epigenetics as a mechanistic link to health inequalities and provide suggestions for future social epigenetics research on health inequalities.
A crisis of generalizability or a crisis of constructs?
Authors: Kevin M King, Aidan G C Wright
Journal: Behavioral and Brain Sciences (2022)

Abstract Psychologists wish to identify and study the mechanisms and implications of nomothetic constructs that reveal truths about human nature and span across operationalizations. To achieve this goal, psychologists should spend more time carefully describing and measuring constructs across a wide range of methods and measures, and less time rushing to explain and predict.
Mechanical Control of Cell Differentiation: Insights from the Early Embryo
Authors: Celeste M. Nelson
Journal: Annual Review of Biomedical Engineering (2022)

Differentiation is the process by which a cell activates the expression of tissue-specific genes, downregulates the expression of potency markers, and acquires the phenotypic characteristics of its mature fate. The signals that regulate differentiation include biochemical and mechanical factors within the surrounding microenvironment. We describe recent breakthroughs in our understanding of the mechanical control mechanisms that regulate differentiation, with a specific emphasis on the differentiation events that build the early mouse embryo. Engineering approaches that reproducibly mimic the mechanical regulation of differentiation will permit new insights into early development and applications in regenerative medicine.
External Ophthalmomyiasis Due to <i>Oestrus ovis</i>
Authors: Nicolas Abihaidar, Thibaud Garcin
Journal: New England Journal of Medicine (2022)

A 53-year-old man presented with itching of the right eye after gardening near a sheep farm. On examination, numerous mobile, translucent larvae were observed on the cornea and conjunctiva, as shown in a video. The larvae were removed and identified as Oestrus ovis, the sheep bot fly.
Gastric Cancer CAR T-cell Target Antigen ID'd
Journal: Cancer Discovery (2021)

Chimeric antigen receptor (CAR) T-cell therapy has had limited efficacy against solid tumors, but a CAR T-cell therapy targeting isoform 2 of the tight junction membrane protein claudin 18, preferentially expressed on stomach mucosal cells, showed acceptable safety and promising efficacy against advanced digestive system cancers in a phase I trial.