tbuckley/cabot-search huggingface dataset:
Abstract 10072: Stroke Topology and Neurodevelopment in Infants with Congenital Heart Disease: Does it Differ by Cardiac Physiology?
Authors: Thiviya Selvanathan, Ting Guo, Min Sheng, Mike Seed, Anne Synnes, Shabnam Peyvandi, Liza Pulcine, Vann Chau, Linh G Ly, James Barkovich, Patrick S McQuillen, Steven P Miller
Journal: Circulation (2021)

Objectives: Vulnerability to brain injury in infants with congenital heart disease (CHD) may differ by CHD lesion. However, the link between arterial ischemic stroke (AIS) and neurodevelopment, and whether it differs by CHD lesion, is unknown. We sought to determine whether: (1) Stroke topology differs between infants with Transposition of the Great Arteries (TGA) and single ventricle physiology (SVP), and relationship with neurodevelopment;(2) Associations between stroke volume and neurodevelopment are CHD lesion specific. Methods: 64 of 312 CHD infants (TGA n=38, SVP n=26) studied prospectively with pre- and/or post-operative brain MRIs had AIS. AIS were segmented on 3DT1 and/or ADC images. 39 infants completed 18-month neurodevelopmental assessments with Bayley Scales (2 nd or 3 rd Edition); scores were adjusted to account for differences between versions. Adverse neurodevelopment was defined as &lt;85 points. We used multivariable linear regression models to study associations between AIS volume and neurodevelopment, stratifying by CHD lesion and adjusting for study site. Probability maps demonstrating areas vulnerable to AIS and odds ratio maps reflecting likelihood of a lesion predicting adverse outcomes were developed. Results: Most AIS were in MCA territories, with a left-sided predominance (Fig 1A). Stroke volume did not differ between CHD groups (p=0.8). Basal ganglia lesions were most predictive of cognitive (max OR=11) and motor (max OR=6) outcomes (Fig 1B). Stratifying by CHD lesion, AIS volume predicted 18-month cognitive outcomes in infants with TGA (β=-0.6, 95%CI -1.0-(-0.1), p=0.02) but not SVP (β=7.9, 95%CI -72-88). AIS volume did not predict motor outcomes in infants with TGA (β=-0.6, 95%CI -1.6-0.3) or SVP (β=-19.7, 95%CI -91-52). Conclusions: Neonatal AIS topology does not differ between infants with TGA and SVP. AIS location and size are important predictors of neurodevelopment at 18 months though this association differs by CHD lesion.
15P Preliminary results of histone deacetylase inhibitor tucidinostat combined with PD-1 inhibitor sintilimab in non-small cell lung cancer failed to standard therapies
Authors: Y. Wang, G. Yang, H. Xu, S. Zhang, Y. Yang, F. Xu, S. Lei, X. Ai, H. Li, X. Hao, J. Li
Journal: Annals of Oncology (2022)
Modulating the immune response to reduce hypertension-associated cardiovascular damage
Authors: Daniel Henrion
Journal: Journal of Clinical Investigation (2022)

Cardiovascular diseases are a leading cause of mortality and disability worldwide. Hypertension, a major risk factor for these diseases, remains difficult to treat despite numerous drugs being available. In this issue of the JCI, Failer et al. show that the endogenous antiinflammatory agent developmental endothelial locus-1 (DEL-1) decreased blood pressure and cardiac and aortic hypertrophy in mouse models of hypertension through reduction in αvβ3 integrin-dependent metalloproteinase activity and immune cell recruitment, leading to reduced production of proinflammatory cytokines in cardiovascular tissues. This study offers an alternative in the treatment of hypertension-mediated organ damage through the immunomodulatory effect of DEL-1.
Intraductal Papilloma With Carcinoma of the Breast Described by Dedicated Breast 18F-FDG PET
Authors: Mutsumi Noritake, Akimitsu Yamada, Shoji Yamanaka, Daisuke Utsunomiya, Tomio Inoue
Journal: Clinical Nuclear Medicine (2022)

Abstract Intraductal papilloma (IDP) is a benign tumor of the breast. However, IDP has been reported to show high uptake of 18 F-FDG using whole-body PET. We experienced IDP with low-grade ductal carcinoma in situ using dedicated breast PET, which is more sensitive than whole-body PET. The 18 F-FDG uptake of the whole tumor was high, and differentiation between the carcinoma and the residual benign lesion was difficult. This is the first report of IDP detected with dedicated breast PET. Diagnosis of IDP is sometimes controversial; papilloma may show glucose uptake similar to that of low-grade carcinoma.
Improvement of Standardization of Molecular Analyses in Hematology: The 10-year GBMHM French Experience
Authors: Anne Sophie Alary, Carole Maute, Olivier Kosmider, Pierre Sujobert, Audrey Gauthier, Elizabeth Macintyre, Claude Preudhomme, Sandrine Hayette, Damien Luque-Paz, Fanny Baran-Marszak, Frederic Davi, Eric Lippert, Pascale Cornillet-Lefebvre, Marie Helene Delfau-Larue, Bruno Cassinat, Jean Michel Cayuela, Pascale Flandrin-Gresta
Journal: HemaSphere (2021)

Molecular tests have become an indispensable tool for the diagnosis and prognosis of hematological malignancies and are subject to accreditation according to the International Standard ISO 15189. National standardization of these techniques is essential to ensure that patients throughout France benefit from the same care. We report here on the experience of the GBMHM (Groupe des Biologistes Moléculaires des Hémopathies Malignes). By organizing External Evaluation of Quality (EEQ) programs and training meetings, the GBMHM has contributed to improvement and standardization of molecular tests in 64 French laboratories. A retrospective analysis of the quality-control results of 11 national campaigns spanning 10 years was performed for the 3 most frequently prescribed tests: BCR-ABL1, JAK2 V617F, and lymphoid clonality. For each test, particular attention was placed on comparing methodologies and their evolution throughout the period. The establishment of the BCR-ABL1, JAK2 V617F, and lymphoid clonality EEQ programs and the associated training meetings have initiated a process of collective standardization concerning the methods of implementation (JAK2 V617F) and the interpretation and formulation of results (lymphoid clonality). In addition, it resulted in objective improvement in technical performance (BCR-ABL1). Our evaluation of the impact of these EEQ programs demonstrates that it is possible to obtain reproducible values across different laboratories in France by applying national recommendations. To our knowledge, this is the first publication that evaluates the impact of a national quality assurance program on improving molecular results in hematology.
The 2022 Child Nutrition Reauthorization — An Opportunity to Advance Children’s Health
Authors: Dariush Mozaffarian, Daniel R. Glickman
Journal: New England Journal of Medicine (2022)

Interview with Dr. Hilary Seligman on reforming the Supplemental Nutrition Assistance Program to reduce food insecurity in the United States. (11:03)Download In 2022, Congress will undertake the process of reviewing and advancing legislation related to major child nutrition programs. Actions taken as part of Child Nutrition Reauthorization could support child health and health equity.
Evaluation of near-Infrared fluorescence-conjugated peptides for visualization of human epidermal receptor 2-overexpressed gastric cancer.
Authors: Kyoungyun Jeong, Seong-Ho Kong, Seong-Woo Bae, Cho Rong Park, Felix Berlth, Jae Hwan Shin, Yoon-Sang Lee, Hye Won Yun, Eunhee Koo, Yun-Suhk Suh, Do Joong Park, Hyuk-Joon Lee, Han-Kwang Yang
Journal: Journal of Clinical Oncology (2022)

338 Background: HER2 is highly overexpressed in many kinds of cancers with a poor prognosis. Recently, near-infrared (NIR) fluorescence-based imaging is a growing field for both pre-clinical and clinical application. In this study, we aimed to synthesize Human Epidermal Receptor2 (HER2)-specific near-infrared (NIR) fluorescence probes and evaluate their applicability in cancer-specific image-guided surgeries using an animal model. Methods: An NIR dye emitting light of 800 nm (IRDye800CW, Li-COR, USA) was conjugated to trastuzumab and HER2-specific affibody using click mechanism. HER2 affinity was assessed by the surface plasmon resonance technique. HER2 positive/negative gastric cancer cell lines (NCI-N87 and SNU-601) were subcutaneously implanted into female BALB/c-nu (6 to 8 weeks old) mice. The biodistribution and fluorescence signal intensity were measured by Lumina II (Perkin Elmer, MA, USA) and a laparoscopic NIR camera (InTheSmart, Seoul, Korea) after injecting the probes intravenously. Results: Trastuzumab-IRDye800CW showed higher affinity to HER2 (K(D) = 2.093(3)pM) than unconjugated trastuzumab(K(D) = 25.75pM). The significant signal of fluorescence was targeted to the HER2-positive tumors at 24hr after injection, while no or low signal retention was observed in negative group. The peak appears at 24hr after injection. On the other hand, small difference of affinity was shown between HER2-target affibody-IRDye800CW (K(D) = 4.71nM) and unlabeled pure affibody(K(D) = 1.42nM). The renal clearance of HER2-target affibody conjugated with IRDye800CW was so fast that we could not detect the signal. Conclusions: Our results suggest that trastuzumab conjugated with IRDye800CW can be a feasible tool to monitor HER2 status in pre-clinical cancer imaging. Moreover, this probe can provide complementary means for assessment of HER2 expression in gastric cancer patients and/or be used to further detection of HER2-positive lesions during image-guided surgery.
Clinical and molecular implications of RGS2 promoter genetic variation in severe asthma
Authors: Juan Carlos Cardet, Donghwa Kim, Eugene R. Bleecker, Thomas B. Casale, Elliot Israel, David Mauger, Deborah A. Meyers, Elizabeth Ampleford, Gregory A. Hawkins, Yaping Tu, Stephen B. Liggett, Victor E. Ortega, Bruce Levy, Wanda Phipatanakul, Nizar Jarjour, Sally Wenzel, Mario Castro, John Fahy, Benjamin Gaston, William Teague, Serpil Erzurum, Anne-Marie Irani, Wendy Moore, Anne Fitzpatrick
Journal: Journal of Allergy and Clinical Immunology (2022)
Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer
Authors: Patrick M. Forde, Jonathan Spicer, Shun Lu, Mariano Provencio, Tetsuya Mitsudomi, Mark M. Awad, Enriqueta Felip, Stephen R. Broderick, Julie R. Brahmer, Scott J. Swanson, Keith Kerr, Changli Wang, Tudor-Eliade Ciuleanu, Gene B. Saylors, Fumihiro Tanaka, Hiroyuki Ito, Ke-Neng Chen, Moishe Liberman, Everett E. Vokes, Janis M. Taube, Cecile Dorange, Junliang Cai, Joseph Fiore, Anthony Jarkowski, David Balli, Mark Sausen, Dimple Pandya, Christophe Y. Calvet, Nicolas Girard
Journal: New England Journal of Medicine (2022)

Neoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non–small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings.
Brain White Matter Microstructure as a Risk Factor for Cognitive Decline After Chemotherapy for Breast Cancer
Authors: Michiel B. de Ruiter, Liesbeth Reneman, Jacobien M. Kieffer, Hester S. A. Oldenburg, Sanne B. Schagen
Journal: Journal of Clinical Oncology (2021)

Cognitive decline is frequently observed after chemotherapy. As chemotherapy is associated with changes in brain white matter microstructure, we investigated whether white matter microstructure before chemotherapy is a risk factor for cognitive decline after chemotherapy.Neuropsychologic tests were administered before and 6 months (n = 49), 2 years (n = 32), and 3 years (n = 32) after chemotherapy in patients with breast cancer receiving anthracycline-based chemotherapy (BC + CT group), at matched intervals to patients with BC who did not receive systemic therapy (BC - CT group: n = 39, 23, and 19, respectively) and to no-cancer controls (NC group: n = 37, 29, and 28, respectively). Using multivariate normative comparison, we evaluated to what extent the cognitive profiles of patients deviated from those of controls. Fractional anisotropy (FA), derived from magnetic resonance diffusion tensor imaging, was used to measure white matter microstructure before treatment. FA was evaluated as a risk factor for cognitive decline, in addition to baseline age, fatigue, cognitive complaints, and premorbid intelligence quotient. We subsequently ran voxel-wise diffusion tensor imaging analyses to investigate white matter microstructure in specific nerve tracts.Low FA independently predicted cognitive decline early (6 months, P = .013) and late (3 years, P < .001) after chemotherapy. FA did not predict cognitive decline in the BC - CT and NC groups. Voxel-wise analysis indicated involvement of white matter tracts essential for cognitive functioning.Low FA may reflect low white matter reserve. This may be a risk factor for cognitive decline after chemotherapy for BC. If validated in future trials, identification of patients with low white matter reserve could improve patient care, for example, by facilitating targeted, early interventions or even by influencing choices of patients and doctors for receiving chemotherapy.
Abstract 11105: Real Time Racial Microaggression and Physiological Stress Responses Among Young and Middle Aged Black Adults
Authors: Soohyun Nam, Sangchoon Jeon, Monica Ordway, LaRon Nelson, David Vlahov
Journal: Circulation (2021)

Introduction: Perceived racial discrimination has been associated with dysregulation of sympathetic-adrenal-medullary (SAM) and hypothalamic-pituitary-adrenal (HPA) axis, two major physiological stress response systems linked to cardiovascular disease outcomes. Most studies, to date, used cross-sectional data that captured retrospective measures of lifetime racial discrimination associated with current physiological stress responses. Relative to overt racial discrimination, a subtle form of racial discrimination, known as microaggression is more prevalent, yet most commonly measured retrospectively, and understudied. The purpose of this pilot study was to examine the relationship between microaggression measured in real-time and physiological stress responses. Methods: Twelve healthy Black adults (mean age=43.4 years) completed baseline surveys, and self-collected saliva 4x a day for 4 days to measure cortisol and alpha amylase (AA) as a proxy of HPA and SAM systems, respectively. Real-time microaggression was measured using ecological momentary assessments (EMA) sent to participants 5x a day for 7 days. Multilevel models were conducted to examine the relationship between microaggressions and the SAM and HPA axis activities. Results: In the bivariate analyses, the area under the curve with respect to ground (AUCg: total cortisol output throughout the day) was significantly associated with the same day microaggression (r=.40, p=.02). Microaggression was associated with cortisol awakening response (CAR) on the same day (r=.34, p=.04). In multilevel models, microaggression was associated with wake-up cortisol level on the same day (β=.22, p=.05). Microaggression was also associated with wake-up AA levels both the same day (β=.58, p&lt;.01) and the next day (β=.40, p=.05). Conclusions: Microaggression was associated with same day and next day physiological stress responses. We determined that concurrent use of salivary biomarkers and EMA was feasible methods to examine the temporal relationship between microaggression and physiological stress responses. Future work will include the development of an intervention that buffers the physiologic stress response related to microaggression to improve cardiovascular health.
RAF1 amplification: an exemplar of MAPK pathway activation in urothelial carcinoma
Authors: Sean Clark-Garvey, William Y. Kim
Journal: Journal of Clinical Investigation (2021)

Despite recent therapeutic gains in the treatment of advanced bladder cancer, the overall survival in patients with metastatic disease remains poor and further therapeutic discovery is needed. Advanced bladder cancer is a molecularly heterogeneous disease, and the identification of driver genetic alterations has led to effective targeted therapeutic agents, such as fibroblast growth factor receptor (FGFR) inhibitors. In this issue of the JCI, Bekele et al. identify a subtype of muscle-invasive bladder cancer (MIBC) that harbors RAF1 amplification. The authors showed that RAF1 inhibition, with pan-RAF inhibitors, and the combination of RAF1 inhibition with MEK inhibition were efficacious in preclinical models harboring RAF1 amplifications as well as in tumors with HRAS and NRAS mutations. This study highlights RAF1 amplification as a driver event in bladder cancer and establishes the central role of the MAPK pathway in bladder tumorigenesis.
Estimating Nephron Number from Biopsies: Impact on Clinical Studies
Authors: Darya Morozov, Neda Parvin, Mark Conaway, Gavin Oxley, Edwin J. Baldelomar, Aleksandra Cwiek, Kim deRonde, Scott C. Beeman, Jennifer R. Charlton, Kevin M. Bennett
Journal: Journal of the American Society of Nephrology (2021)

Accumulating evidence supports an association between nephron number and susceptibility to kidney disease. However, it is not yet possible to directly measure nephron number in a clinical setting. Recent clinical studies have used glomerular density from a single biopsy and whole kidney cortical volume from imaging to estimate nephron number and single nephron glomerular filtration rate. However, the accuracy of these estimates from individual subjects is unknown. Furthermore, it is not clear how sample size or biopsy location may influence these estimates. These questions are critical to study design, and to the potential translation of these tools to estimate nephron number in individual subjects.
Abstract P052: Identifying Barriers To Healthy Eating In Pregnant Women With Hypertension, Hypertensive Disorders Of Pregnancy, Or Risk Factors For Hypertensive Disorders Of Pregnancy.
Authors: Diana Sibai, Sravya Shankara, Didem Ayturk, Sheikh Moinul, Katherine Lynch, David D McManus, Lara C Kovell
Journal: Circulation (2022)

Introduction: Heart healthy diets are important in the prevention and treatment of hypertension (HTN). In pregnant women, the lifestyle barriers to healthy eating are not well-described in literature. Hypothesis: There are personal, environmental, and economic barriers impacting adherence to a healthy diet in pregnant women with HTN, hypertensive disorders of pregnancy (HDP), or risk factors for HDP. Methods: Pregnant women, aged 20-50 (N=28), diagnosed with HTN, HDP, or risk factors for HDP were recruited from a large academic medical center. Participants completed an electronic survey assessing personal, environmental, and economic barriers to healthy eating. A 5-point Likert scale was used, ranging from strongly agree to strongly disagree. Results: The average age of participants was 31.8 (SD=4.5) from urban (34.6%), suburban (34.6%), and rural (30.8%) communities. Finances and time were major barriers to healthy eating, reported by 39.3% and 28.6% of participants, respectively, with 17.8% reporting that they could not afford to eat healthy consistently for all meals (Figure 1). Additionally, 10.7% and 7.1% were unaware of factors promoting healthy eating such as awareness of outside healthy eating resources and confidence in their ability to eat healthy given a new pregnancy. Meanwhile, 28.6% and 17.9% reported ambivalence towards these factors. Conclusion: Time management and financial costs emerged as the greatest challenges to healthy eating in pregnant women with or at risk for HDP. These barriers, in addition to certain factors promoting healthy eating, may represent areas of intervention that can help mitigate the obstacles to healthy eating in this vulnerable group.
A New Standard Immunosuppression Regimen in Severe Aplastic Anemia
Authors: Phillip Scheinberg
Journal: New England Journal of Medicine (2022)

Organ failure is a major cause of illness and death across medical conditions. In particular, primary failure of the bone marrow can result in various cytopenias. Aplastic anemia is the prototype of the bone marrow failure syndromes that are characterized by hypocellular marrow and pancytopenia, and severe aplastic anemia is fatal if untreated.1 Since the 1980s, clinical and experimental data have indicated an autoimmune cause in the majority of idiopathic cases of aplastic anemia.1 In a minority of cases, genetic defects that are associated with inherited forms of aplastic anemia usually manifest with characteristic physical signs in childhood.2 In immune . . .
Abstract P193: Life’s Simple 7 Risk Factors and Cardiovascular Disease Among Gender Minority Populations in the 2019 BRFSS
Authors: Grace C Bellinger, Lauren B Beach
Journal: Circulation (2022)

Gender minority (GM) populations encompass individuals who identify with a gender different from their sex assigned at birth. This includes transgender adults, which make up 0.6% of the U.S. population. Despite cardiovascular disease being the leading cause of morbidity and mortality worldwide, there is little research on the cardiovascular health of GM populations. GM adults may be at higher risk for myocardial infarction, coronary heart disease, and stroke compared to their cisgender peers due to minority stress and the impact of stigma on health. The Behavioral Risk Factor Surveillance System (BRFSS) is a federal survey administered by state health departments and the CDC. The BRFSS has offered an optional standardized Sexual Orientation and Gender Identity (SOGI) module with measures to identify transgender respondents since 2014 and 30 states included the module in 2019. Life’s Simple 7 criteria are used in preventive medicine and public health to describe ideal cardiovascular health. The seven associated risk factors are smoking, obesity, physical inactivity, poor dietary habits, high cholesterol, high blood pressure, and high blood glucose. The 2019 BRFSS included core modules related to each of the risk factors and therefore provides a unique opportunity to investigate the cardiovascular health of GM respondents. BRFSS data (N = 177,322) were used to determine prevalence rates of cardiovascular risk factors and disease among GM compared to cisgender adults. R was used to conduct weighted estimates and regressions comparing behavioral and clinical cardiometabolic risk factors and events by gender identity (cisgender male, cisgender female, transgender male-to-female, transgender female-to-male, and transgender gender nonconforming). On average, GM respondents were younger, more racially/ethnically diverse, less likely to have graduated college, less likely to be straight, and reported lower annual household incomes than cisgender males or females. After adjusting for age, race/ethnicity, education, income, and sexual orientation, gender nonconforming transgender adults were less likely than both cisgender males (adjusted odds ratio = 1.17, 95% confidence interval: (1.02, 1.34)) and cisgender females (1.15 (1.00, 1.32)) to report exercise in the last 30 days. Gender nonconforming transgender adults were less likely to report a diagnosis of diabetes than cisgender males (0.97 (0.94, 1.00)). No significant differences between gender minority and majority adults were detected for cardiovascular events after adjusting for demographic variables and Life’s Simple 7 risk factors. This may be due to the age difference between the cisgender and GM groups, since older adults have higher risk of cardiovascular disease. Analyses may have been underpowered due to small GM sample sizes, emphasizing the importance of all states including the optional standardized SOGI module.