tbuckley/cabot-search huggingface dataset:
Curation and expansion of Human Phenotype Ontology for defined groups of inborn errors of immunity
Authors: Matthias Haimel, Julia Pazmandi, Raúl Jiménez Heredia, Jasmin Dmytrus, Sevgi Köstel Bal, Samaneh Zoghi, Paul van Daele, Tracy A. Briggs, Carine Wouters, Brigitte Bader-Meunier, Florence A. Aeschlimann, Roberta Caorsi, Despina Eleftheriou, Esther Hoppenreijs, Elisabeth Salzer, Shahrzad Bakhtiar, Beata Derfalvi, Francesco Saettini, Maaike A.A. Kusters, Reem Elfeky, Johannes Trück, Jacques G. Rivière, Mirjam van der Burg, Marco Gattorno, Markus G. Seidel, Siobhan Burns, Klaus Warnatz, Fabian Hauck, Paul Brogan, Kimberly C. Gilmour, Catharina Schuetz, Anna Simon, Christoph Bock, Sophie Hambleton, Esther de Vries, Peter N. Robinson, Marielle van Gijn, Kaan Boztug
Journal: Journal of Allergy and Clinical Immunology (2021)

Accurate, detailed, and standardized phenotypic descriptions are essential to support diagnostic interpretation of genetic variants and to discover new diseases. The Human Phenotype Ontology (HPO), extensively used in rare disease research, provides a rich collection of vocabulary with standardized phenotypic descriptions in a hierarchical structure. However, to date, the use of HPO has not yet been widely implemented in the field of inborn errors of immunity (IEIs), mainly due to a lack of comprehensive IEI-related terms.
Natural gene therapy by reverse mosaicism leads to improved hematology in <scp>Fanconi</scp> anemia patients
Authors: María José Ramírez, Roser Pujol, Juan Pablo Trujillo‐Quintero, Jordi Minguillón, Massimo Bogliolo, Paula Río, Susana Navarro, José A. Casado, Isabel Badell, Estela Carrasco, Judith Balmaña, Albert Català, Julián Sevilla, Cristina Beléndez, Bienvenida Argilés, Mónica López, Cristina Díaz de Heredia, Gayatri Rao, Eileen Nicoletti, Jonathan D. Schwartz, Juan A. Bueren, Jordi Surrallés
Journal: American Journal of Hematology (2021)

Abstract Fanconi anemia (FA) is characterized by chromosome fragility, bone marrow failure (BMF) and predisposition to cancer. As reverse genetic mosaicism has been described as “natural gene therapy” in patients with FA, we sought to evaluate the clinical course of a cohort of FA mosaic patients followed at referral centers in Spain over a 30‐year period. This cohort includes patients with a majority of T cells without chromosomal aberrations in the DEB‐chromosomal breakage test. Relative to non‐mosaic FA patients, we observed a higher proportion of adult patients in the cohort of mosaics, with a later age of hematologic onset and a milder evolution of (BMF). Consequently, the requirement for hematopoietic stem cell transplant (HSCT) was also lower. Additional studies allowed us to identify a sub‐cohort of mosaic FA patients in whom the reversion was present in bone marrow (BM) progenitor cells leading to multilineage mosaicism. These multilineage mosaic patients are older, have a lower percentage of aberrant cells, have more stable hematology and none of them developed leukemia or myelodysplastic syndrome when compared to non‐mosaics. In conclusion, our data indicate that reverse mosaicism is a good prognostic factor in FA and is associated with more favorable long‐term clinical outcomes.
Abstract 15999: Machine Learning to Identify Patients at High Risk for Peripheral Arterial Disease From Electronic Health Record Data
Authors: Mark Sonderman, Eric Farber-Eger, Aaron W Aday, Matthew S Freiberg, Joshua A Beckman, Quinn Wells
Journal: Circulation (2020)

Introduction: Peripheral arterial disease (PAD) is a common and underdiagnosed disease associated with significant morbidity and increased risk of major adverse cardiovascular events. Targeted screening of individuals at high risk for PAD could facilitate early diagnosis and allow for prompt initiation of interventions aimed at reducing cardiovascular and limb events. However, no widely accepted PAD risk stratification tools exist. Hypothesis: We hypothesized that machine learning algorithms can identify patients at high risk for PAD, defined by ankle-brachial index (ABI) &lt;0.9, from electronic health record (EHR) data. Methods: Using data from the Vanderbilt University Medical Center EHR, ABIs were extracted for 8,093 patients not previously diagnosed with PAD at the time of initial testing. A total of 76 patient characteristics, including demographics, vital signs, lab values, diagnoses, and medications were analyzed using both a random forest and least absolute shrinkage and selection operator (LASSO) regression to identify features most predictive of ABI &lt;0.9. The most significant features were used to build a logistic regression based predictor that was validated in a separate group of individuals with ABI data. Results: The machine learning models identified several features independently correlated with PAD (age, BMI, SBP, DBP, pulse pressure, anti-hypertensive medication, diabetes medication, smoking, and statin use). The test statistic produced by the logistic regression model was correlated with PAD status in our validation set. At a chosen threshold, the specificity was 0.92 and the positive predictive value was 0.73 in this high-risk population. Conclusions: Machine learning can be applied to build unbiased models that identify individuals at risk for PAD using easily accessible information from the EHR. This model can be implemented either through a high-risk flag within the medical record or an online calculator available to clinicians.
Abstract 17375: The Potential Role of Stress-Associated Neurobiological Metabolism in the Cardiovascular Sequelae of Sleep Apnea
Authors: Ahmed Ghoneem, Michael Osborne, Shady Abohashem, Hadil Zureigat, Tawseef Dar, Taimur Abbasi, Nicki Naddaf, Emma Akuffo, Ahmed A Tawakol
Journal: Circulation (2020)

Introduction: Obstructive and central sleep apnea (SA) induce sleep fragmentation and associates with HTN and cardiovascular diseases (CVDs). Sleep fragmentation is known to increase stress. Further, heightened stress-associated neurobiological metabolism (particularly amygdalar activity - AmygA), potentiates atherosclerosis. However, it is unknown: 1) whether SA increases AmygA in humans, or 2) whether AmygA mediates the link between SA and its CV consequences (HTN and CVD). Hypothesis: SA associates with higher AmygA which in turn associates with hypertension (HTN) and myocardial infarction (MI). Methods: We studied a cohort of 36424 participants within the Partners Biobank. Diagnoses of MI and sleep apnea and relevant clinical data were obtained from International Statistical Classification of Diseases and Related Health Problems (ICD-10) codes. A subset of 1520 patients provided clinically indicated 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. AmygA was measured using validated measures. Results: Of 36424 participants, 6596 (18.1%) had SA, 20881(57.3%) had HTN and 4033 (11.1%) had MI. OSA significantly associated with HTN (OR [95%CI]: 3.2 [2.95, 4.48], p&lt;0.0001) and MI (1.30 [1.21, 1.41], p&lt;0.001) in multivariable models. SA associated with AmygA (β [95%CI]: 0.183 [0.058, 0.337], p=0.006). AmygA associated with HTN (1.18 [1.02, 1.38], p= 0.028). Further, AmygA associated with MI (1.28 [1.11, 1.46], p=0.0005). Moreover, AmygA mediated the association between SA and HTN and between SA and MI (p&lt;0.05 for both, figs 1a and 1b). Conclusion: Our findings suggest that SA increases the risk of HTN &amp; MI via a mechanism that involves heightened amygdalar activity. This potential mechanism may inform novel treatments.
Abstract P022: Self-reported Polycystic Ovary Syndrome Is Associated With Higher Odds Of Metabolic Syndrome In Women Aged 18-76 Years From The Hispanic Community Health Study/Study Of Latinos
Authors: Hridya C Rao, Lindsay Fernandez-Rhodes, Michelle Meyer, Michelle Kominiarek, Linda Gallo, Raveen Syan, Krista Perreira
Journal: Circulation (2021)

Introduction: Polycystic Ovary Syndrome (PCOS) is associated with increased Metabolic Syndrome (MetS), however, these findings have not been characterized in Hispanic/Latina women who are disproportionately burdened by obesity and cardiovascular disease risk compared to non-Hispanic whites. It is also unclear if this association is moderated by elevated high-sensitivity C-Reactive Protein (hs-CRP) levels, a marker for inflammation and a predictor of cardiovascular disease. Hypothesis: In Hispanic/Latina women, we hypothesized that 1) PCOS (self-reported diagnosis and signs) is associated with a higher prevalence of MetS compared to those not reporting PCOS 2) elevated hs-CRP is associated with MetS, and 3) the PCOS-MetS association is moderated by elevated hs-CRP. Methods: We used information from reproductive and economic questionnaires and venous blood measurements collected in Hispanic Community Health Study/Study of Latinos (2008-2017), a U.S. community-based cohort study of Hispanic/Latino adults. PCOS was operationalized as either 1) signs of PCOS (e.g., menstrual cycles &gt;35 days, irregular cycles (at age 20 to 40 years old when not using birth control pills or other hormone medications and not pregnant or breastfeeding) or 2) having answered “yes” to a self-reported question on PCOS. MetS was operationalized as ≥3 elevated subcomponents of MetS (i.e., waist circumference, hypertension, insulin resistance, lipid profile, and triglycerides). A hs-CRP value ≥3.0 mg/L was considered elevated. We adjusted for the complex survey study design, age, study center, Hispanic/Latina background, and age at immigration in all models. Results: The overall (unweighted N=9582) age ranged from 18 to 76 years (mean=41.74, SD=14.18). The prevalence of PCOS (self-reported diagnosis and signs) was 12% (1008/7366), prevalence of MetS was 40% (2380/3495), prevalence of elevated-hsCRP was 44% (3704/4667). PCOS was associated with a significantly higher odds of MetS before (OR 1.35, 95% CI: 1.06-1.71) and after adjusting for elevated-hsCRP (OR 1.29, 95%CI: 1.02-1.65). Elevated hs-CRP is significantly associated with MetS (OR 2.31, 95%CI: 1.95-2.76). There was no significant interaction effect of hs-CRP in the PCOS-MetS association. Conclusions: Prevalence of PCOS (self-reported and signs) was 12% in our sample of Hispanic/Latina women, which is consistent with the previous findings in non-Hispanic whites. Both PCOS (self-reported diagnosis and signs) and elevated hs-CRP were significantly associated with higher prevalence of MetS and could indicate women at metabolic disease risk.
Casein Kinase II Inhibition By CX-4945 and Epigenetic Modulation By Decitabine Demonstrate Significant Antiproliferative Activity As Single Agents As Well As in Combination in Acute B-Lymphoblastic Leukemia Cells
Authors: Anna Richter, Catrin Roolf, Sina Sender, Weibo Kong, Gudrun Knübel, Anett Sekora, Yvonne Saara Gladbach, Mohamed Hamed, Georg Fuellen, Brigitte Vollmar, Irmela Jeremias, Jens P. Panse, Hugo Murua Escobar, Christian Junghanss
Journal: Blood (2017)
Restrictive Policies Threaten Efforts to Stop 2 West Virginia HIV Outbreaks
Authors: Bridget M. Kuehn
Journal: JAMA (2021)

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Modulating HIV-1 envelope glycoprotein conformation to decrease the HIV-1 reservoir
Authors: Jyothi K. Rajashekar, Jonathan Richard, Jagadish Beloor, Jérémie Prévost, Sai Priya Anand, Guillaume Beaudoin-Bussières, Liang Shan, Dietmar Herndler-Brandstetter, Gabrielle Gendron-Lepage, Halima Medjahed, Catherine Bourassa, Fleur Gaudette, Irfan Ullah, Kelly Symmes, Andrew Peric, Emily Lindemuth, Frederic Bibollet-Ruche, Jun Park, Hung-Ching Chen, Daniel E. Kaufmann, Beatrice H. Hahn, Joseph Sodroski, Marzena Pazgier, Richard A. Flavell, Amos B. Smith, Andrés Finzi, Priti Kumar
Journal: Cell Host & Microbe (2021)

Small CD4-mimetic compounds (CD4mc) sensitize HIV-1-infected cells to antibody-dependent cellular cytotoxicity (ADCC) by facilitating antibody recognition of epitopes that are otherwise occluded on the unliganded viral envelope (Env). Combining CD4mc with two families of CD4-induced (CD4i) antibodies, which are frequently found in plasma of HIV-1-infected individuals, stabilizes Env in a conformation that is vulnerable to ADCC. We employed new-generation SRG-15 humanized mice, supporting natural killer (NK) cell and Fc-effector functions to demonstrate that brief treatment with CD4mc and CD4i-Abs significantly decreases HIV-1 replication, the virus reservoir and viral rebound after ART interruption. These effects required Fc-effector functions and NK cells, highlighting the importance of ADCC. Viral rebound was also suppressed in HIV-1+-donor cell-derived humanized mice supplemented with autologous HIV-1+-donor-derived plasma and CD4mc. These results indicate that CD4mc could have therapeutic utility in infected individuals for decreasing the size of the HIV-1 reservoir and/or achieving a functional cure.
Abstract 038: Cumulative Exposure To Sleep Disordered Breathing From Childhood Through Young Adulthood Is Associated With Impaired Endothelial Function
Authors: Julio Fernandez-Mendoza, Zhaohui Gao, Myra Qureshi, Baadal A Vachhani, Jiangang Liao, Kristen Brandt, Fan He, Susan Calhoun, Alexandros Vgontzas, Duanping Liao, Edward O Bixler
Journal: Circulation (2021)

Introduction: Clinical and population-based studies in adults have shown that sleep disordered breathing (SDB) is associated with impaired endothelial function. However, there is a lack of population-based studies demonstrating an association between SDB and endothelial dysfunction in young adults using a developmental approach. Hypothesis: Exposure to SDB since childhood is associated with long-term impaired flow-mediated dilation (FMD) in young adulthood. Methods: We tested this hypothesis in a subsample of the Penn State Child Cohort, a population-based study of 700 children (median age 9y), of whom 421 were followed-up 6-13 years later during adolescence (median age 16y), and 178 have been followed-up 11-19 years later during young adulthood (median age 24y). Subjects (54.5% female, 20.8% racial/ethnic minority) underwent in-lab polysomnography to ascertain the apnea/hypopnea index (AHI) at all three time points, and ultrasounds to assess FMD in young adulthood. Based on the AHI truncated at ≥5 events/hour of sleep to include subjects already on positive airway pressure therapy, we averaged the exposure to AHI over the three time points (cAHI). The study outcomes were FMD, as a continuous measure, and endothelial dysfunction, defined as FMD&lt;10.3% based on the median of the sample. Linear and logistic regression models simultaneously adjusted for sex, age, race/ethnicity, overweight and length of follow-up. Results: The mean cAHI was 1.31 (1.35) ranging from 0 to 5 and the mean FMD was 0.11 (0.04) ranging from 0.03 to 0.25. Linear models showed that cAHI was associated with significantly lower FMD in young adulthood (β = -0.006; 95% CI = -0.011, -0.0013; p = 0.014). To test the robustness of the analysis, we applied the same model with the square root of FMD as the outcome and similar results were obtained (β = -0.009; 95% CI = -0.016, -0.0017; p = 0.015). Logistic models showed that each point increase in cAHI was associated with 51% higher odds of endothelial dysfunction in young adulthood (OR = 1.51; 95% CI = 1.14, 2.06; p = 0.006). Conclusions: The preliminary data of this ongoing longitudinal study indicates that exposure to SDB during early stages of life is associated with increased risk for cardiovascular disease in young adults from the general population.
Poster Exhibition : Short-Term Combination Therapy by Clevudine and Adefovir Versus Clevudine Monotherapy in the Treatment of Chronic Hepatitis B
Authors: Kee Sup Song, Do Young Kim, Jun Yong Park, Jung Min Lee, Hye Young Chang, Sook In Chung, Hye Rim Ju, Sung Hoon Choi, Won Sang Rho, Sang Hoon Ahn, Kwang Hyub Han
Journal: Clinical and Molecular Hepatology (2009)
간경병증 환자에서 복수천자가 폐기능에 미치는 영향
Authors: 금민수, 김영탁, 최성곤, 이창형, 권영오, 김성국, 최용환, 정준모 ( Min Su Geum), Young Tak Kim, Sung Gon Choi, Chang Hyeong Lee, Young Oh Kweon, Sung Kook Kim, Yong Hwan Choi, Joon Mo Chung
Journal: Clinical and Molecular Hepatology (1997)

Background/Aims '. Paracentesis is an acceptable therapeutic modality for the symptomatic relief of dyspnea or abdominal fullness due to tense ascites in patients with cirrhosis. Whereas studies about the effects of paracentesis focused on the changes about hemodynamics, electrolytes and renal function in great detail, the effects of paracentesis on the changes about respiratory system have undergone limited investigations which are defined large-volume paracentesis. Methods .' We performed pulmonary function tests with arterial blood gas analysis just before and 24 hr after paracentesis. The paracentesis of average 2,300ml was carried out in ten liver cirrhosis patients with tense ascites who were free from underlying cardiopulmonary impairment. Results '. 1. The results of pulmonary function test just before paracentesis were as followings; FVC( functional vital capacity), FEV1(forced expiratory volume in 1 sec), FEF25  75(forced expiratory effort 25%  75%) and TLC(total lung capacity) were decreased as 78%, 79%, 62.3% and 89% of normal control value respectively, whereas RV(residual volume) was not decreased. DLCO(lung diffusion capacity of carbon monoxide)was decreased as 61.6%. 2. The results of pulmona function test 24 hr after paracentesis were as followings,' The symptomatic relief of dyspnea was achieved in all participated ten patients. Among lung volume parameters, FVC and VC were increased significantly(p=0.003, p=0.004). Whereas TLC was increased without statistical significance(p=0.228), and RV and FRC(functional residual capacity) showed no change. FEV1 was increased significantly(p=0.039), but FEF25  75 and the ratio of FEF1/FVC showed no change. DLCO was not increased. PaOy(partial pressure of oxygen in arterial blood) was impr'oved without statistical significance. Conclusions .' These results suggest that  the patients of liver cirrhosis with ascites have restrictive ventilatory impairment with additional obstructive ventilatory impairment. After paracentesis, the restrictive ventilatop impairment is improved by the relief of diaphragmatic motion limitation caused by ascites. Also, paracentesis of(not large volume, like 5000ml, but) relatively small volume, of 2000  3000ml can achieve objective improvement of dyspnea due to tense ascites.
Abstract MP46: The Associations Between Adverse Pregnancy Outcomes And Cardiovascular Delivery Complications: The National Inpatient Sample
Authors: Anum Minhas, Michelle Ogunwole, Michael Miller, Arthur J Vaught, Pensee Wu, Mamas A Mamas, Martha Gulati, Di Zhao, Allison Hays, Erin Michos
Journal: Circulation (2021)

Background: Women with adverse pregnancy outcomes (APOs) are at increased risk of long-term cardiovascular (CV) disease, but less is known about the spectrum of acute CV outcomes in women with various APOs. We evaluated the risk of CV events at delivery in women with gestational diabetes (GDM), gestational hypertension and preeclampsia/eclampsia (PEC), overall and by race/ethnicity, in a US sample. Methods: We used the 2016-2017 National Inpatient Sample survey data from the Agency for Healthcare Research and Quality (AHRQ). ICD10-CM diagnosis codes were used to identify women with a delivery hospitalization and to identify CV outcomes. We examined demographics and prevalence of CV events at delivery by the 3 APOs. Logistic regression was used to determine risk of various adverse CV events at delivery by APO, adjusted for age, income and hospital location. To generate national estimates, sampling weights provided by AHRQ were used. Results: Among 3,776,531 deliveries in 2016-2017, GDM was the most common APO (n=552,975; 7.3%). GDM occurred more frequently in Hispanics and Asians/Pacific Islanders (23% and 11%, respectively), while PEC occurred more frequently in Blacks (20%). While there was greater occurrence of CV events with all 3 APOs, after adjustment, only PEC was significantly associated with increased odds of adverse CV events [peripartum cardiomyopathy: OR 3.87 (95% CI 3.30-4.55), congestive heart failure: OR 4.04 (3.52-4.63), acute ischemic heart disease: OR 3.67 (2.65-5.08) and arrhythmias: OR 1.39 (1.22-1.59)]. Risk was elevated for Whites, Blacks, Hispanics and Asians/Pacific Islanders, although there was heterogeneity of the magnitude of risk by race/ethnicity ( Table ). Discussion: Women with APOs, especially PEC, are more likely to experience acute CV complications at hospital delivery than women without APOs. While Black women are more likely to develop PEC, women of all race/ethnicities with PEC are at risk of CV complications.
Abstract 15216: Longitudinal Changes in Peak Aortic Valve Velocity in Late Life: Atherosclerosis Risk in Communities (ARIC) Study
Authors: Kirstine Ravnkilde, Brian Claggett, Hicham Skali Lami, Suma Konety, Dalane Kitzman, Thomas Mosley, VIJAY NAMBI, Kunihiro Matsushita, Amil M Shah
Journal: Circulation (2020)

Background: Aortic stenosis (AS) is a growing health problem within the aging population. We aimed to quantify longitudinal changes in aortic valve hemodynamics in late life. Methods: We studied 2,512 community-based elderly participants in the Atherosclerosis Risk in Communities (ARIC) study who underwent uniform echocardiographic imaging at study visits 5 (2011-2013) and 7 (2018-2019). Peak aortic valve (AV) velocity was assessed by continuous wave spectral Doppler from the apical 5 chamber view. Participants with heart failure or in atrial fibrillation at either echocardiographic examination were excluded. Results: Mean age at Visit 5 was 74 ± 4 years, 41% were male, 24% black, and the mean AV velocity at Visit 5 was 1.27 ± 0.28 m/s. Over median 6.6 [IQR: 6.1-7.0] years, AV velocity increased by 0.15 ± 0.32 m/s and the mean velocity at Visit 7 was 1.43 ± 0.43 m/s. Of 2,454 participants with peak AV velocity &amp;lt; 2.0 m/s at Visit 5, 123 (5%) developed a peak AV velocity &amp;gt; 2.0 m/s at Visit 7 (mean 2.45 ± 0.46 m/s). In models accounting for blood pressure and heart rate at both study visits, Visit 5 predictors of transitioning to a peak AV velocity &amp;gt; 2.0 m/s included age, male sex, white race, BMI, higher NT-proBNP and hs-troponin T, and greater LA volume index and E/e’ ratio ( Table ). Conclusions: Peak AV velocity increases over 6 years in late life, with ~5% developing a peak velocity &amp;gt; 2.0 m/s. Demographics, higher cardiac biomarkers, and worse diastolic function predict increases in peak AV velocity in late life. These data have important implications for the development of age-related aortic stenosis.