tbuckley/cabot-search huggingface dataset:
Glycemic Status and Reperfusion Injury in Patients With ST-Segment Elevation Myocardial Infarction
Authors: Martin Reindl, Ivan Lechner, Christina Tiller, Magdalena Holzknecht, Andreas Rangger, Agnes Mayr, Markus Theurl, Gert Klug, Christoph Brenner, Axel Bauer, Bernhard Metzler, Sebastian J. Reinstadler
Journal: JACC. Cardiovascular imaging (2021)
Super-resolution visualization and modeling of human chromosomal regions reveals cohesin-dependent loop structures
Authors: Xian Hao, Jyotsana J. Parmar, Benoît Lelandais, Andrey Aristov, Wei Ouyang, Christian Weber, Christophe Zimmer
Journal: Genome biology (2021)

The 3D organization of the chromatin fiber in cell nuclei plays a key role in the regulation of gene expression. Genome-wide techniques to score DNA-DNA contacts, such as Hi-C, reveal the partitioning of chromosomes into epigenetically defined active and repressed compartments and smaller "topologically associated" domains. These domains are often associated with chromatin loops, which largely disappear upon removal of cohesin. Because most Hi-C implementations average contact frequencies over millions of cells and do not provide direct spatial information, it remains unclear whether and how frequently chromatin domains and loops exist in single cells.We combine 3D single-molecule localization microscopy with a low-cost fluorescence labeling strategy that does not denature the DNA, to visualize large portions of single human chromosomes in situ at high resolution. In parallel, we develop multi-scale, whole nucleus polymer simulations, that predict chromatin structures at scales ranging from 5 kb up to entire chromosomes. We image chromosomes in G1 and M phase and examine the effect of cohesin on interphase chromatin structure. Depletion of cohesin leads to increased prevalence of loose chromatin stretches, increased gyration radii, and reduced smoothness of imaged chromatin regions. By comparison to model predictions, we estimate that 6-25 or more purely cohesin-dependent chromatin loops coexist per megabase of DNA in single cells, suggesting that the vast majority of the genome is enclosed in loops.Our results provide new constraints on chromatin structure and showcase an affordable non-invasive approach to study genome organization in single cells.
Abstract 16520: Predictors of Thirty Day Readmission in a Vulnerable and Underserved Urban Heart Failure Population
Authors: Alexandra B Steverson, Paul Marano, Caren Chen, Yifei Ma, Rachel Stern, Jonathan D Davis, Priscilla Hsue, Lucas S Zier
Journal: Circulation (2020)

Introduction: Heart failure (HF) readmission quality metrics disproportionately impact reimbursement in safety net hospitals. Prior research has demonstrated the effect of medical comorbidities on readmission, however, there is a paucity of data on predictors of readmission in vulnerable and underserved HF patients. We sought to evaluate the effect of demographics, medical and social comorbidities on risk of 30 day readmission in an academic safety net hospital in San Francisco. Methods: We performed a retrospective chart review from 2018 to 2020. Patients were included if treated for HF while on inpatient cardiology or medicine services and were assigned an ICD-10 discharge code for HF. Patients less than 21 years old were excluded. Demographics and comorbidities were obtained through evaluation of ICD-10 discharge codes and chart review. Multivariate modeling was used to determine predictors of 30 day readmission. Results: The study population included 383 patients in which the mean age was 60±13 years and 73% (n=282) were male. 44% (170) were Black, 23% (88) were Latinx, 33% (127) were not housed, 97% (371) had public insurance, and 21% (81) had a diagnosis of mental illness. 46% (177) had CAD, 76% (291) hypertension, and 36% (177) DM. Substance use was common with 30% (114) using methamphetamines, 36% (138) cocaine, 18% (69) opioids, and 35% (135) alcohol. On multi-variate analysis, EF less than 40% (75%, 285) was the only medical comorbidity associated with an increased risk of readmission (OR 1.86, 1.1-3.1, p= 0.018). Social variables associated with increased risk of readmission included identifying as Black (OR 2.26, 1.03-5.0, p= 0.043) or Latinx (OR 3.43, 1.41-7.59, p= 0.006), homelessness (OR 3.02, 1.76-5.18, p=&lt;0.001), and specific substance use: methamphetamine (OR 2.23, 1.39-3.57, p=0.001), cocaine (OR 1.63, 1.03-2.57, p= 0.037), opioids (OR 1.81, 1.05-3.13, p= 0.033), and alcohol (OR 2.26, 1.43-3.58, p= 0.001). Conclusion: Race, housing status and substance use were more strongly associated with readmission risk than medical comorbidities in a population of urban, vulnerable and underserved HF patients. Interventions to improve HF readmission metrics should consider addressing racial and social disparities in similar populations.
Abstract 14824: Identifying Gender Differences in Physical Frailty Phenotypes in Heart Failure: A Focus on Physiological, Clinical, and Symptom Characteristics
Authors: Quin E Denfeld, Beth A HABECKER, S. A Camacho, Mary Davis, Nandita Gupta, Shirin O Hiatt, Mary E Medysky, Jonathan Q Purnell, Kerri Winters-Stone, Christopher S Lee
Journal: Circulation (2020)

Introduction: Although women with heart failure (HF) are potentially more likely to be physically frail compared with men with HF, the underlying contributors to this gender difference are poorly understood. The purpose of this study was to characterize gender differences in physical frailty phenotypes in HF with a focus on physiological, clinical, and symptom characteristics. Methods: We prospectively enrolled adults with Class I-IV HF. Physical frailty was measured with the Frailty Phenotype Criteria: unintentional weight loss, weakness, slowness, physical exhaustion, and low physical activity; those who met 0-2 criteria were not physically frail, and those who met 3-5 criteria were physically frail. Body composition was measured using dual energy x-ray absorptiometry. Clinical data were extracted from the medical record. Symptoms of dyspnea, sleep-related impairment, pain interference, depression, and anxiety were assessed. Simple comparative statistics and multivariate logistic regression were used to identify gender differences in physical frailty. Results: The average age of the sample (n = 115) was 63.6±15.7 years, 49% were women, and 73% had non-ischemic etiology. About 43% of the sample was physically frail. Women were 4.5 times as likely to be physically frail compared with men, adjusting for covariates (OR = 4.52, 95%CI [1.69, 12.08], p = 0.003). Both physically frail men and women had significantly more type 2 diabetes and worse dyspnea symptoms compared with non-physically frail men and women, respectively. Physically frail men had significantly lower appendicular muscle mass, higher percent body fat, trunk fat, and appendicular fat, and lower hemoglobin compared with non-physically frail men (all p &lt; 0.05). Physically frail women had significantly higher comorbidity burden and worse sleep-related impairment, pain interference, and depressive symptoms compared with non-physically frail women (all p &lt; 0.05). Conclusions: Women are significantly more likely to be physically frail in HF. Physical frailty in men with HF may be primarily characterized by comorbidities and sarcopenic obesity; whereas physical frailty in women with HF may be predominantly characterized by comorbidities and worse symptoms.
Abstract 16402: Epa and Dha Suppressed Myocardial Infarction-induced Systolic Dysfunction by Inhibiting P300 Hat Activity
Authors: Masafumi Funamoto, Yoichi Sunagawa, Yasufumi Katanasaka, Kana Shimizu, Yusuke Miyazaki, nurmila sari, Satoshi Shimizu, Kiyoshi Mori, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
Journal: Circulation (2020)

Introduction: p300, an intrinsic histone acetyltransferase (HAT), has a crucial role in the pathological cardiac hypertrophy and the development of heart failure in vivo . Although many studies have shown a cardioprotective effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), omega-3 fatty acids, little is known about the effects of these acids on cardiac hypertrophy. Aim: This study investigated whether EPA and DHA inhibited the development of heart failure in rats with myocardial infarction (MI). Methods and Results: To investigate the effects on cardiomyocyte hypertrophy in cultured cardiomyocytes, neonatal rat cultured cardiomyocytes were stimulated with phenylephrine (PE). EPA or DHA significantly inhibited PE-induced cardiomyocyte hypertrophy. EPA and DHA repressed to the same extent PE-induced acetylation of histone H3 in cultured cardiomyocytes. An in vitro HAT assay was performed to determine the direct inhibition of p300-HAT activity. The results revealed that EPA and DHA significantly inhibited p300-HAT activity. To assess whether EPA and DHA suppress p300-HAT activity directly in cultured cardiomyocytes, p300 was overexpressed in cultured cardiomyocytes. Treatment with EPA or DHA inhibited the overexpression of p300-induced cardiomyocyte hypertrophy in cultured cardiomyocytes. MI-operated rats (FS &lt; 40%) were randomly assigned to 3 groups: vehicle, EPA (1 g/kg) and DHA (1 g/kg). One week after MI operation, oral administrations were repeated for 6 weeks. Echocardiographic analysis demonstrated that EPA and DHA significantly improved MI-induced cardiac dysfunction. In addition, Masson's trichrome staining showed that EPA and DHA inhibit MI-induced fibrosis response in MI rats. EPA and DHA repressed MI-induced hypertrophic response gene transcriptions such as ANF and BNP with RT-PCR. Western blotting demonstrated that inhibited MI-induced H3K9 acetylation in rats . Conclusion: EPA and DHA suppressed hypertrophic responses to the same extent, through the direct inhibition of p300-HAT activity and repressed MI-induced development of heart failure.
Normalization of cholesterol metabolism in spinal microglia alleviates neuropathic pain
Authors: Juliana M. Navia-Pelaez, Soo-Ho Choi, Luciano dos Santos Aggum Capettini, Yining Xia, Ayelet Gonen, Colin Agatisa-Boyle, Lauriane Delay, Gilson Gonçalves dos Santos, Glaucilene F. Catroli, Jungsu Kim, Jenny W. Lu, Benjamin Saylor, Holger Winkels, Christopher P. Durant, Yanal Ghosheh, Graham Beaton, Klaus Ley, Irina Kufareva, Maripat Corr, Tony L. Yaksh, Yury I. Miller
Journal: The Journal of Experimental Medicine (2021)

Neuroinflammation is a major component in the transition to and perpetuation of neuropathic pain states. Spinal neuroinflammation involves activation of TLR4, localized to enlarged, cholesterol-enriched lipid rafts, designated here as inflammarafts. Conditional deletion of cholesterol transporters ABCA1 and ABCG1 in microglia, leading to inflammaraft formation, induced tactile allodynia in naive mice. The apoA-I binding protein (AIBP) facilitated cholesterol depletion from inflammarafts and reversed neuropathic pain in a model of chemotherapy-induced peripheral neuropathy (CIPN) in wild-type mice, but AIBP failed to reverse allodynia in mice with ABCA1/ABCG1–deficient microglia, suggesting a cholesterol-dependent mechanism. An AIBP mutant lacking the TLR4-binding domain did not bind microglia or reverse CIPN allodynia. The long-lasting therapeutic effect of a single AIBP dose in CIPN was associated with anti-inflammatory and cholesterol metabolism reprogramming and reduced accumulation of lipid droplets in microglia. These results suggest a cholesterol-driven mechanism of regulation of neuropathic pain by controlling the TLR4 inflammarafts and gene expression program in microglia and blocking the perpetuation of neuroinflammation.
Mental disorders and risk of COVID-19-related mortality, hospitalisation, and intensive care unit admission: a systematic review and meta-analysis
Authors: Benedetta Vai, Mario Gennaro Mazza, Claudia Delli Colli, Marianne Foiselle, Bennett Allen, Francesco Benedetti, Alessandra Borsini, Marisa Casanova Dias, Ryad Tamouza, Marion Leboyer, Michael E Benros, Igor Branchi, Paolo Fusar-Poli, Livia J De Picker
Journal: The Lancet Psychiatry (2021)
Abstract P181: Prediction Of Left Ventricular Diastolic Dysfunction Using Electrocardiographic Machine Learning In Asian Young Male Adults
Authors: Gen-Min Lin
Journal: Circulation (2021)

Left ventricular diastolic dysfunction (LVDD) occurs at initial stage of heart failure. Electrocardiographic (ECG) criteria and machine learning for ECG features with or wihtout biological features have been applied successfully to predict LVDD in middle- and old-aged individuals. The purpose of this study is to clarify the performance of machine learning in young adults. In a large sample of 2,206 military males in Hualien, Taiwan, aged 17-43 years, the prevalence of LVDD is 4.26%. Five machine learning classifiers including random forest (RF), support vector machine (SVM), gradient boosting decision tree (GBDT), multi-layer perceptron (MLP) and logistic regression (LR) for the input of 26 ECG features with or without other 6 biological features (age, anthropometrics, and blood pressures) to link the output of LVDD are compared with the corrected QT interval (QTc) calculated by the Bazett’s formula, a traditional ECG criterion for LVDD. The definition of LVDD is based on either one of the echocardiographic criteria: (1) the E/A ratio of the mitral inflow &lt;0.8; (2) the lateral mitral annulus velocity, e’ &lt;10 cm/s; and (3) the E/e’ ratio &gt;14. The area under the receiver operating characteristic (ROC) curve in machine learning of the RF, SVM, GBDT, MLP and LR for ECG only are 84.1%, 78.7%, 77.9%, 77.6% and 75.4%, which are all superior to 64.6% in the QTc interval. If the specificity is fixed around 70-80%, the sensitivity of these mahine learning classifiers for ECG only are 81.0%, 76.2%, 71.4%, 71.4% and 71.4%, which are all higher than 47.6% in the QTc interval. This study suggests that using machine learning for ECG features only to predict LVDD in Asian young adults is reliable and thereby it is possible for people to take an early preventive action on heart failure.
Abstract MP12: Proteomic Predictors Of High-density Lipoprotein Cholesterol Response To Regular Exercise
Authors: Jacob L Barber, Guoshuai Cai, Jeremy M Robbins, Robert E Gerszten, Prashant Rao, Claude Bouchard, Mark A Sarzynski
Journal: Circulation (2021)

Introduction: Regular exercise beneficially increases plasma HDL-C levels at the group level. However, variation in individual HDL-C responses to exercise highlight a need for predictive biomarkers of exercise response. Hypothesis: We hypothesized that baseline abundance of circulating proteins is predictive of HDL-C response to exercise and that identified proteins are part of a complex biological network of exercise response. Methods: We measured over 5,000 circulating proteins using an aptamer-affinity based platform (SomaScan) in 667 black and white adults from the HERITAGE Family Study. Fasting plasma HDL-C was measured at baseline and following 20 weeks of supervised endurance exercise training. To predict exercise induced changes in HDL-C using baseline abundance of circulating proteins, models were created using LASSO regression and a 70/30 training test data split with 10-fold cross validation. Biological pathways, networks, and functions involving proteins identified in predictive modeling were investigated by ingenuity pathway analysis (IPA) and integrated molecular pathway level analysis (IMPaLA). Results: Regular exercise significantly increased HDL-C in the sample by 1.5 ± 4.6 mg/dL (p&lt;0.0001), however marked inter-individual differences in response were present (range: -19.5 to +17.4 mg/dL). LASSO regression of circulating proteins only yielded a model of 120 proteins with similar but stronger predictive power to a model of 19 clinical traits (root mean square error = 4.52 and 5.3 mg/dL respectively). LASSO regression of both clinical and proteomic predictors resulted in a final model of baseline HDL-C and 116 circulating proteins, with an improved root mean square error of 4.11 mg/dL. Furthermore, this panel of 116 proteins was able to explain 40.0% of the variance in exercise induced changes in plasma HDL-C, while clinical predictors alone (including baseline HDL-C) explained only 3.9%. Pathway analysis of these 116 proteins identified several biological processes including pathways involved in the progression towards atherosclerosis, angiogenesis, mTOR signaling, and mitochondrial fatty acid synthesis. Conclusions: Circulating proteins may allow for prediction of exercise induced changes in HDL-C. Additionally, proteins predictive of HDL-C response to exercise are associated with important biological pathways and may provide insights into the molecular mechanisms of the benefits of regular exercise.
Abstract 16021: Troponin Testing and One-year Hospital Readmission
Authors: Sarah Payne, Travis Haneke, Yissela Escobedo, Jerry Fan, Ethan Fry, Jeffrey Michel, Robert J Widmer
Journal: Circulation (2020)

Introduction: Troponin I (TnI) elevation is an important tool for detecting cardiac injury, though it is not disease specific and can be elevated in other conditions such as sepsis or heart failure. Predictive models suggest that TnI elevation correlates with increased mortality, however, it is unclear if TnI testing or elevation has value for predicting readmissions. Hypothesis: We hypothesized inpatient TnI testing would correlate with 30-day hospital readmissions. Methods: Patient data was collected from January 1st , 2016 through December 31st , 2016 and was comprised of 54,039 patients. Analysis was performed on TnI positive patients and correlated with 30-day hospital readmission rates among the entire cohort as well as those subdivided by ICD-10 codes into acute myocardial infarction (AMI), sepsis, pulmonary disease, and cardiac non-AMI. A subsequent propensity-matched logistic regression was performed among the entire cohort with TnI testing as well as resultant positive TnI to calculate odds ratios (OR) and 95% confidence intervals (CI). Results: Among the entire cohort, 4,572 patients (8.5%) were readmitted within 30 days. TnI testing was associated with increased readmission within 30 days (3,428/30,173; 11.4%; p&lt;0.0001). Logistic regression analysis revealed an increased odds ratio for 30-day readmission of 2.24 (95% CI [2.08-2.41]; p&lt;0.0001) among those with TnI draw. In those with a resultant positive troponin, however, the odds of 30-day readmission were 1.04 (95% CI [0.95-1.14]; p=0.4006). Although there was no significant increase in 30-day readmission among the AMI cohort who had troponin draw (n=1,722; OR 3.66, 95% CI [0.97-32.53], p=0.12), there were significant increases among those admitted for sepsis (n=4,834; OR 2.41, 95% CI [1.84-3.22], p&lt;0.0001), pulmonary disease (n=2,120; OR 3.92, 95% CI [2.07-8.55], p&lt;0.0001), and cardiac non-AMI (n=9,808; OR 2.34, 95% CI [2.15-2.56], p&lt;0.0001). Conclusions: Hospital readmission within 30 days is associated with TnI testing and may be further predictive in non-AMI ICD-10 diagnoses such as sepsis, pulmonary disease, and non-AMI cardiac disease. However, a positive TnI may not be a useful objective data point for prediction of hospital readmission within 30 days.
Person-centred experiential therapy versus cognitive behavioural therapy delivered in the English Improving Access to Psychological Therapies service for the treatment of moderate or severe depression (PRaCTICED): a pragmatic, randomised, non-inferiority trial
Authors: Michael Barkham, David Saxon, Gillian E Hardy, Mike Bradburn, Deanna Galloway, Nyantara Wickramasekera, Anju D Keetharuth, Peter Bower, Michael King, Robert Elliott, Lynne Gabriel, Stephen Kellett, Susan Shaw, Toni Wilkinson, Janice Connell, Phillippa Harrison, Kerry Ardern, Lindsey Bishop-Edwards, Kate Ashley, Sally Ohlsen, Stephen Pilling, Glenn Waller, John E Brazier
Journal: The Lancet Psychiatry (2021)
マイコバクテリア過敏性肺炎には肺CD11b+CD11c+細胞のTLR9-MyD88が必要である
Authors: H Daito, T Kikuchi, T Sakakibara, K Gomi, T Damayanti, J Zaini, N Tode, M Kanehira, S Koyama, S Fujimura, M Ebina, K J Ishii, S Akira, T Takai, A Watanabe, T Nukiwa
Journal: European Respiratory Journal (2011)
Abstract 12698: Sodium-containing versus Sodium-trace Preparations of Ivig for Children With Kawasaki Disease in Acute Phase
Authors: Takanori Suzuki, Nobuaki Michihata, Tetsushi Yoshikawa, Kazuyoshi Saito, Kiyohide Fushimi, Hideki Matsui, Hideo Yasunaga
Journal: Circulation (2020)

Objectives: Kawasaki disease (KD) is an acute systemic vasculitis that most commonly causes acquired cardiac disease in children in developed countries. The most highly recommended treatment for KD is 2 g/kg intravenous immunoglobulin (IVIG). Hyponatremia in patients with KD in the acute phase is known to be associated with IVIG resistance and coronary artery abnormalities (CAA). There are two types of IVIG, sodium-containing (high Na) and sodium-trace (low Na) preparations. However, few studies have compared the effects of these two preparations for superiority. The purpose of this study was to compare outcomes between high and low Na IVIG preparations in KD children using a national inpatient database in Japan. Methods: We used the Diagnostic Procedure Combination database to identify KD patients treated with IVIG between 2010 and 2017. We identified those receiving high and low Na preparations of IVIG as an initial treatment. Outcomes included proportion of CAA, IVIG resistance, adverse effects, length of stay, and medical cost. Propensity score-matched analyses were conducted to compare the outcomes between the two groups. Instrumental variable analyses were performed to confirm the results. Results: We identified 47,292 patients with KD and created 23646 propensity score-matched pairs between the high and low Na IVIG groups. There were significant differences in proportions of CAA (2.5% vs. 2.9%; p=0.016) and IVIG resistance (23.8% vs. 24.9%; p=0.006) between the two groups. However, there were no significant differences in length of stay or medical cost. The instrumental variable analyses confirmed that high Na IVIG was significantly associated with lower proportion of CAA compared with low Na IVIG (odds ratio, 1.69; p&lt;0.001). Conclusions: The present study suggests that high Na IVIG is potentially effective for reducing the proportion of CAA in KD patients. Prospective studies are warranted to confirm the effectiveness observed in this study.