tbuckley/cabot-search huggingface dataset:
Abstract 13172: Using Machine Learning to Identify Transcriptomic Biomarkers That Differentiate Early vs Late Stage of Atherosclerosis
Authors: Colin Price, James Hixson, Do-Kyun Kim, Richard Vander Heide, Yue Wang, Jennifer E Van Eyk, David M Herrington, Andrew Warren, Chunhong Mao
Journal: Circulation (2021)

Introduction: We used a machine learning approach to explore the transcriptomic signaling component of atherosclerosis. This approach can be viewed as complementary to classical differential-expression-based RNA-Seq approach while defining some of its limitations and providing insight into the cellular basis of atherosclerosis. Methods: Abdominal aorta specimens (n=242) from 128 Coroner’s autopsy cases were graded by pathologists and classified as normal (nl), fatty streak (fs), fibrous plaque (fp), or complex fibrous plaque (fc). The pathology samples were sorted into two groups for comparison: normal/early (nl/fs) vs late stage (fp/fc) of atherosclerosis. The RNA-Seq data were analyzed using an ensemble of machine learning methods to identify a set of genes that differentiate the normal/early and late pathology stages. Three feature selection algorithms (recursive feature elimination, random forest optimization and regularized linear regression) were employed to assign a total ranking to the importance of genes for pathology classification. Five different classifiers (Naive Bayes, Logistic Regression, Random Forest, Support Vector Machine and Decision Tree) were trained and XGboost model was used for ensemble learning. We used the resulting performance characterization relative to the clinically established ground truth to validate the characteristic genes and abundances selected by this model. Results: The ensemble machine learning approach identified a set of gene features that best explain late versus normal/early stage of atherosclerosis in a 5-fold cross validation experimental design. XG-boosting shallow learners give stable performance across sample splits and more consistently high F1 scores. We found that the performance of the resulting model was highly correlated with the degree of the disease severity, indicating a relationship between concerted transcript abundance and the presentation of disease phenotype. Conclusions: Our machine learning approach identifies ensemble biomarkers that differentiate early vs late stage atherosclerosis. Our results also indicated a potential transcriptomic basis for the severity of disease phenotype as embodied by histopathology grading not included in the training data.
The role of growth and nutrition in the early origins of spirometric restriction in adult life: a longitudinal, multicohort, population-based study
Authors: Nipasiri Voraphani, Debra A Stern, Jing Zhai, Anne L Wright, Marilyn Halonen, Duane L Sherrill, Jenny Hallberg, Inger Kull, Anna Bergström, Clare S Murray, Lesley Lowe, Adnan Custovic, Wayne J Morgan, Fernando D Martinez, Erik Melén, Angela Simpson, Stefano Guerra
Journal: The Lancet Respiratory Medicine (2021)
Clinical Characteristics of Incident Lymphoma in Malawi before and after Implementation of Universal Anti-Retroviral Therapy
Authors: Yolanda Gondwe, Evaristar Kudowa, Tamiwe Tomoka, Cara Randall, Amy Lilly, Edwards Kasonkanji, Bongani Kaimila, Takondwa Zuze, Noel Mumba, Stephen Kimani, Maurice Mulenga, Satish Gopal, Yuri Fedoriw, Matthew Painschab
Journal: Blood (2021)
STING signaling activation inhibits HBV replication and attenuates the severity of liver injury and HBV-induced fibrosis
Authors: Yuqi Li, Minjing He, Ziyu Wang, Zhiyun Duan, Zhiwei Guo, Ziteng Wang, Ruijie Gong, Tianhao Chu, Jiabin Cai, Bo Gao
Journal: Cellular and Molecular Immunology (2021)
Abstract 12521: Atherosclerotic Cardiovascular Disease Risk and Small Dense Low-Density Lipoprotein Cholesterol in Men, Women, African Americans and Non-African Americans
Authors: Ernst J Schaefer, Hiroaki J Ikezaki, Margaret R Diffenderfer, Elise Lim, L. Adrienne Cupples, Ching-Ti Liu, Ron H Hoogeveen, Weihua Guan, Michael Y Tsai, Christie H Ballantyne
Journal: Circulation (2021)

Introduction: Increased small dense low-density lipoprotein cholesterol (sdLDL-C) has been reported to be a significant atherosclerotic cardiovascular disease (ASCVD) risk factor Hypothesis: SdLDL-C is an independent ASCVD risk factor in men, women, African Americans, and non-African Americans. Methods: A total of 15,933 participants (median age 62 years, 56.7% female, 19.7% African-American, free of inclusive ASCVD at baseline) pooled from three studies (Atherosclerosis Risk in Communities Study, Framingham Offspring Study, and Multi-Ethnic Study of Atherosclerosis) were followed for 10 years for incident hard ASCVD and inclusive ASCVD (includes angioplasty and/or coronary artery bypass). These endpoints occurred in 6.1% and 9.7% of subjects, respectively. Information on all standard risk factors was obtained, and serum sdLDL-C levels were measured at baseline using automated analysis. The utility of traditional cardiovascular risk factors and sdLDL-C in 10-year hard and inclusive ASCVD risk was assessed-using univariate and multivariable regression analyses. Results: All standard risk factors were significant for hard and inclusive ASCVD in men, women, African-Americans and non-African-Americans on univariate statistical analysis. SdLDL-C was a significant risk factor when added to the pooled cohort equation for hard and inclusive ASCVD in all subjects, and for inclusive ASCVD in all subgroups, and significantly improved the C-Statistic and affected the net reclassification index for all subjects (p&lt;0.0001). When subjects with elevated sdLDL-C levels of &gt; 50 mg/dL were compared to those with optimal levels of &lt;25 mg/dL after adjustment for all standard risk factors, the hazard ratios (HR) and confidence intervals (CI) for incident inclusive ASCVD were all significant at p&lt;0.01: all subjects (HR 1.54, CI 1.30-1.83), men (HR 1.59, CI 1.27-1.99), women (HR 1.51, CI 1.05-1.27), non-African-Americans (HR 1.49, CI 1.24-1.80[CLA3] ), and African-Americans (HR 1.88, CI 1.23-2.89). Conclusions: An elevated sdLDL-C value &gt; 50 mg/dL was independently associated with a 50% increased 10-year inclusive ASCVD risk in all subjects regardless of sex or race[MD1] , and therefore is an important ASCVD risk enhancer.
Abstract 10034: Trends, Predictors, and Outcomes After Transcatheter Aortic Valve Implantation in Patients with Baseline Right Bundle Branch Block, from National Inpatient Sample
Authors: Salman Zahid, Muhammmad Khan, Waqas Ullah, Muhammad U Khan, Muhammad Atif Khan, AAMER UBAID, Satish Pendela, Mian Tanveer Ud Din, Hamza Muhammadzai, Jeremiah Depta, Sudarshan Balla
Journal: Circulation (2021)

Introduction: Contemporary data on the outcomes after Transcatheter Aortic Valve Implantation (TAVI) in patients with a baseline right bundle branch block (RBBB) remains limited. Methods: We analyzed National Inpatient Sample (NIS) data from the year 2011 to 2018. Results: Of the patients who underwent TAVI, 3472 (1.6%) had baseline right bundle branch block and 212467 (98.4%) did not. The patients who had baseline RBBB were older at 83 years [Interquartile range (IQR), 77-87] vs 82 [75-87]) and had higher male gender representation (66.7 % vs 52.2%) (p&lt;0.01 for all). Rates of permanent pacemaker implantation was significantly higher in the RBBB group compared to no RBBB group (30.5% vs 10.80%, p&lt;0.01). Median Cost of care ($53206 vs $48429) and length of stay (5 vs 4 days) were considerably higher for patients with RBBB when compared to the comparison group (p&lt;0.01 for all). Logistic regression analysis showed that age greater 75 [OR] 1.26 [95% CI 1.21-1.31], male sex [OR] 1.12 [95% CI 1.09-1.15] , atrial fibrillation [OR] 1.29 [95% CI 1.07-1.57], coronary artery disease [OR] 1.07 [95% CI 1.04-1.11] diabetes [OR] 1.07 [95% CI 1.02-1.12], hypertension [OR] 1.10 [95% CI 1.05-1.15] obesity [OR] 1.10 [95% CI 1.05- 1.1.16] and renal failure (OR, 1.12 [CI, 1.09-1.15] were significant predictors of PPM implantation post TAVI in patients with a RBBB at baseline. Conclusions: In conclusion we report that RBBB is associated with increased pacemaker implantation after TAVI. Factors like age greater than 75, male gender, coronary artery disease, diabetes, hypertension, obesity, and renal failure are associated with higher incidence of PPM implantation.
Phase 2 Study of Nivolumab in Epstein-Barr Virus (EBV)-Positive Lymphoproliferative Disorders and EBV-Positive Non-Hodgkin Lymphomas
Authors: Elif Yilmaz, Rahul Lakhotia, Stefania Pittaluga, Jagan R. Muppidi, James D. Phelan, Sarah Evans, Amynah Pradhan, Amy Hillsman, Seth M. Steinberg, Elaine S. Jaffe, Wyndham H. Wilson, Mark Roschewski, Christopher Melani
Journal: Blood (2021)
NCMP-15. IMMUNE CHECKPOINT INHIBITOR ENCEPHALITIS: A RETROSPECTIVE COHORT STUDY
Authors: Nathan Clarke, Merry Chen
Journal: Neuro-Oncology (2021)

Abstract OBJECTIVE To review our institution’s experience with immune check point inhibitors (ICI) in patients with all cancer types and describe the incidence and outcomes of encephalitis associated with its use. METHODS We performed a single-center retrospective chart-review identifying patients who developed encephalitis within 12 weeks of treatment with an ICI. RESULTS Between 2011 to 2020 we identified 842 unique patients treated with an ICI with 32 patients (3.8%) developing encephalitis associated with treatment. The median time to diagnosis was 20 days post infusion (13-24 days IQR) and 3 infusions (2-4 IQR). No specific treatment was more significantly associated with encephalitis than the rest with the combination of ipilimumab and nivolumab (10 of 176, 5.68%) being the most common, and single agent nivolumab (9 of 222, 4.05%) and pembrolizumab (8 of 271, 2.95%) being slightly less frequent. By class PD-1 inhibitors were the most common treatment associated (n=18, 3.76%), however there was no one specific class more significantly associated with increased rates of encephalitis when comparing this to inhibitors of PD-L1 (n=2, 1.16%), CTLA-4 (n=2, 5.00%), or combination of PD-1/CTLA-4 (n=10, 6.02%) (p=0.26). Patients were treated with discontinuation of the therapy alone (n=7), high dose steroids alone (n=10), or a combination of high dose steroids, IVIG, or plasma exchange (n=15). The effects were typically reversible or non-disabling with the average 90-day ECOG score being 1.8. There were 8 patients (25%) who developed severe debility (n=4) or death (n=4). CONCLUSION Encephalitis is a rare complication associated with ICI therapies. Overall, there was no apparent specific drug or class more at risk of causing this complication. As ICI therapy is used more in practice, we will likely see a greater number of cases of ICI encephalitis and need to be aware of how it presents, diagnose, and treat appropriately to avoid permanent disability.
EPCO-28. SINGLE-CELL RNA SEQUENCING IDENTIFIES INTRATUMORAL HETEROGENEITY AND ACTIVATION OF PRO-INVASIVE PATHWAYS IN NON-FUNCTIONING PITUITARY ADENOMAS
Authors: Saket Jain, Elaina Wang, Husam Babikir, Karin Shamardani, Aaron Diaz, Manish K Aghi
Journal: Neuro-Oncology (2021)

Abstract Pituitary adenomas (PA) are one of the most common primary brain tumors and comprise 15% of brain neoplasms. Most PAs are histologically benign but can cause significant morbidity. The genetic profile of PAs is poorly understood. We used single-cell RNA sequencing using the 10X genomic platform to investigate cellular heterogeneity in twelve non-functioning pituitary adenoma samples from nine patients including site-specific (core vs edge) samples from three patients. Our analysis identified discrete clusters of cells associated with activation of specific functional pathways including lipid metabolism, angiogenic, and antigen presentation and processing pathways regardless of location within the tumor. MALT1, a lncRNA associated with increased proliferation and metastasis was ubiquitously expressed amongst these samples. Analysis of the core vs edge samples showed two specific clusters with activated invasion-promoting pathways including PI3k/AKT signaling, Wnt signaling (Wnt6 and FZD4), and epithelial-mesenchymal transition (TGFB1, SMAD1, ZEB1, and SNAI2) in the edge of the tumors. The activated Wnt signaling cascade drove a proinflammatory tumor microenvironment induced by the expression of IL-1, IL-17, and Toll-like receptors (TLR6 and TLR7/8) resulting in suppression of Tregs. Copy number variation analysis using the CONICS-CNV algorithm highlighted distinct chromosomal alterations within our samples that led to insight into clonal variations within each tumor with loss of chromosome 2 an early event in tumorigenesis and gain/loss of chromosome 19 as late events. Mapping the copy number variation analysis with the somatic variant analysis using the Vartrix algorithm identified novel driver mutations within these tumors. These findings help define the molecular fingerprint of pituitary adenomas and provide insights which could be utilized for better management of these tumors.
Publication Productivity and Bibliometric Profiling—A Potentially Gender-Biased Approach
Authors: Adrien N. Bernstein, Pauline Filippou, Angela B. Smith
Journal: JAMA Surgery (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
NCMP-16. MANAGEMENT AND LONG-TERM OUTCOMES OF PATIENTS WITH RECURRENT STROKE-LIKE EPISODES AFTER CRANIAL RADIOTHERAPY
Authors: Bryan Neth, Daniel Lachance, Joon Uhm, Michael Ruff
Journal: Neuro-Oncology (2021)

Abstract Stroke-Like Migraine Attacks after Radiation Therapy (SMART) is a descriptive clinical entity consisting of transient hemispheric dysfunction. We were interested in pragmatic management patterns for patients with Recurrent Stroke-Like Episodes (R-SLE) of transient negative neurologic symptoms after cranial radiotherapy (RT) to define optimal management strategy and assess long-term outcomes. We conducted a retrospective review of all patients with recurrent negative neurologic symptoms after cranial RT who were treated at Mayo Clinic (Rochester), with follow-up extending until February 2021. Descriptive statistics and Chi-Square analysis was performed to assess for differences between patients with clinical cessation of symptoms, death, progressive encephalopathy and therapeutic class, patient and primary treatment characteristics (i.e. whole brain RT). We identified 27 patients with R-SLE after RT. 25 patients were included in analyses. Median age at diagnosis was 28.7 years (3.0-65.8 years, SD: 15.0 years). Median time from RT to symptom onset was 14.6 years (3.3-30.5 years, SD: 8.9 years). The most common presentations included hemiparesis (55.6%), hemisensory loss (22.2%), transient visual field loss (33.3%), encephalopathy (18.5%), and aphasia (22.2%). Antiseizure medications were most used for management of R-SLE (92%) followed by anti-platelets (68%), verapamil (52%), statins (48%), glucocorticoids (24%), antivirals (20%), and ACE inhibitors/angiotensin receptor blockers (16%). Beta blockers were not used. Verapamil use was frequently associated with clinical cessation of recurrent events with cessation being achieved in 64.7% of patients on verapamil versus 35.3% not on verapamil (p=0.0638). Other medical interventions did not approach clinical or statistical significance. Progressive encephalopathy was more common in patients without clinical cessation (87.5% vs. 23.5%, p=0.0026). All patients who died at last follow-up had progressive encephalopathy. We found cessation of recurrent negative neurologic symptoms after cranial RT in most patients. Verapamil use was associated with clinical cessation. Progressive encephalopathy was more common in patients without clinical cessation of recurrent events.
Abstract 10641: Changes in Oxygen Uptake Parameters Across High-Intensity Intervals Prescribed Using Rating of Perceived Exertion in Cardiac Rehabilitation
Authors: Virginia G Content, Shane Hammer, Joshua Smith, Thomas P Olson
Journal: Circulation (2021)

Introduction: High intensity interval training (HIIT) during early outpatient cardiac rehabilitation (CR) improves peak oxygen uptake (VO 2 ) and reduces mortality in patients with cardiovascular disease. In a CR setting, prescribing interval intensity using rating of perceived exertion (RPE) is more feasible than using percent of VO 2peak . Additionally, prescribing HIIT with RPE may allow for progressive changes in the VO 2 response throughout a single HIIT session. However, the acute cardiopulmonary responses during individual intervals of HIIT prescribed via RPE in CR are unknown. Hypothesis: We hypothesized that VO 2peak would increase and time-to-peak (TTP) would shorten across high-intensity intervals during a single HITT session prescribed with RPE. Methods: Patients with CAD (N=14; 2 women; 56±9 yrs; 30.46±4.7 kg/m 2 ) referred to CR after an acute coronary event completed a minimum of 25 supervised HIIT sessions during which VO 2 was measured continuously. Each HIIT session included 5 or more (6±1 sessions) 1-minute high intensity intervals (target RPE: 15-17) separated by a 3 to 5-minute low intensity interval (target RPE: &lt;12). The first and last HIIT sessions were used for analysis. VO 2peak was defined as the highest 3-breath averaged VO 2 during or up to 1 minute following each high intensity interval. Results: RPE was 15±2 and 11±2 during the high and low intensity intervals, respectively. Compared to the first HIIT session, VO 2peak was greater during the high intensity intervals of the last HIIT session (25.4±1.5 vs. 21.8±1.1 mL/kg/min; p=0.04). During the first and last HIIT sessions, VO 2peak increased across high intensity intervals (p&lt;0.001). Although TTP was not significantly reduced across intervals during the first HIIT session (p=0.14), TTP was reduced across intervals during the last HIIT session (first interval: 67±19 vs. last interval: 58±9 s; p&lt;0.01). Conclusions: Prescribing HIIT with RPE resulted in increased VO 2peak across high intensity intervals within single HIIT sessions and shortened TTP during high intensity intervals across CR. These findings provide evidence for a priming effect on VO 2peak during HIIT which may contribute to greater cardiopulmonary adaptations in CAD patients.
Abstract 12326: Obesity Increases Heart Failure Incidence and Mortality:Observational and Mendelian Randomisation Studies Totalling Over 1 Million Individuals
Authors: Marianne Benn, Sarah C Marott, Anne Tybjaerg-hansen, Borge G Nordestgaard
Journal: Circulation (2021)

Introduction: Whether high body mass index (BMI) causally influences development and prognosis of heart failure has implications for clinical practice. Hypothesis: We tested the hypotheses that high BMI causally influences heart failure incidence and mortality. Methods: Using observational and Mendelian randomization causal, genetic analyses, we studied 106,121 individuals from the Copenhagen General Population Study, 18,407 from the Copenhagen City Heart Study, and 977,323 from publicly available databases. Results: In observational analyses in the Copenhagen studies with 10 years of median follow-up, multivariable adjusted hazard ratios per 1 kg/m 2 increment of BMI were 1.06 (95% confidence interval: 1.05-1.07; p&lt;0.001; n=124,528; events=6,589) for heart failure incidence, 1.04 (1.03-1.06; p&lt;0.001; n=124,528; events=1,237) for heart failure mortality, and 1.01 (1.00-1.01; p&lt;0.001; n=124,528; events=24,144) for all-cause mortality. In genetic analyses in the Copenhagen studies, the age and sex adjusted causal risk ratios per 1 kg/m 2 increment of BMI were 1.19 (1.05-1.36; p=0.008; n=118,200; events=6,541) for heart failure incidence, 1.27 (0.82-1.98; p=0.28; n=118,200; events=889) for heart failure mortality, and 1.11 (1.02-1.22; p=0.022; n=118,200; events=16,814) for all-cause mortality. Finally, combining genetic data from the Copenhagen studies, the Genetic Investigation of ANthropometric Traits (GIANT), the Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES), and the UK Biobank, the unadjusted causal risk ratios per 1 kg/m 2 increment of BMI were 1.39 (1.27-1.52; p&lt;0.001; n=1,095,523; events=53,850) for heart failure incidence, 1.18 (1.00-1.38; p=0.05; n=576,853; events=2,373) for heart failure mortality, and 1.02 (1.00-1.04; p=0.03; n=576,853; events=44,734) for all-cause mortality. Conclusions: High body mass index causally increases the risk of both heart failure incidence and mortality. Obesity should be recognised as a causal factor for development of heart failure, heart failure mortality, and all-cause mortality in treatment guidelines.
Triple-Negative Myelofibrosis: Disease Features, Response to Treatment and Outcomes
Authors: Luis E. E. Aguirre, Akriti G Jain, Somedeb Ball, Najla Al Ali, Sara Marie Tinsley-Vance, David A. Sallman, Kendra Sweet, Jeffrey E. Lancet, Eric Padron, Andrew T. Kuykendall, Rami S. Komrokji
Journal: Blood (2021)