tbuckley/cabot-search huggingface dataset:
Abstract 011: Cardiovascular Risk Prediction Using Machine Learning In A Large Japanese Cohort
Authors: Matthew B Matheson, Yoko Kato, Shinichi Baba, Christopher Cox, João A Lima, Bharath Ambale Venkatesh
Journal: Circulation (2021)

Introduction: Screening for cardiovascular diseases (CVD) at middle age entails precise event prediction to orient risk stratification, resource allocation and insurance policy. Machine learning may be useful to characterize CVD risk and predict outcomes by identifying unique markers of incident CVD. We tested the ability of random survival forests (RSF) to identify the most important markers of incident CVD among adults enrolled in a mandatory screening program. Methods: We examined a dataset comprising annual health checkup, medication, and disease outcome data on 154,957 adults over the age of 40, collected by Toshiba between 2011 and 2017. Health checkup data included laboratory measurements of biomarkers, health history, and lifestyle questionnaires. CVD outcomes, classified as any of acute ischemic heart disease, myocardial infarction, angina pectoris and atherosclerotic heart disease, were recorded after initial health checkup using ICD-10 coding. In the absence of CVD outcomes, subjects’ latest available health check visit was used as the censoring date. Data was split into training (70%, n=108,470) and test (30%, n=46,487) sets, with RSF utilized to impute missing covariate data and determine the characteristics most predictive of CVD outcomes based on minimum depth of maximal subtree. Results: Subjects were 65% (100,376 of 154,957) male with a median age of 47 years at baseline. A total of 1,669 events occurred in the group over a median follow-up period of 5 years. The RSF error rate stabilized around 1000 trees; we grew the training forest with 1200. The c-index at 2, 4, and 6 years was 85%, 84%, and 82% respectively; prediction error calculated by Brier score was 16.4% at six years. The most important predictors of CVD outcomes were prior heart disease, history of CV procedures and age. HDL cholesterol, HBA1c levels, and use of anti-hypertensive medications were the next 3 most important predictors. Conclusions: Determination of key variables predictive of cardiac endpoints will help guide individuals, health practitioners and policy makers in identifying higher-risk subjects and implementing early interventions and testing to reduce risk. The RSF method greatly facilitates the development of a predictive algorithm to be used for these purposes.
Magnitude and Time-Trend Analysis of Postendoscopy Esophageal Adenocarcinoma: A Systematic Review and Meta-analysis
Authors: Tarek Sawas, Abdul Mounaem Majzoub, James Haddad, Thomas Tielleman, Tarek Nayfeh, Rena Yadlapati, Siddharth Singh, Jennifer Kolb, Ravy K. Vajravelu, David A. Katzka, Sachin Wani
Journal: Clinical Gastroenterology and Hepatology (2021)
HYPERTENSION AND CONTRACEPTION USE AMONG WOMEN OF CHILD-BEARING AGE IN THE UNITED STATES FROM 2001-2018
Authors: Lara Kovell, Claire V. Meyerovitz, Didem Ayturk, Sharina Person, Stephen P. Juraschek, Tiffany A. Moore Simas
Journal: Journal of the American College of Cardiology (2021)
Abstract 238: In-Hospital Cardiac Arrest: The Dynamic Clinical Course During Advanced Cardiac Life Support
Authors: Eirik Skogvoll, David G Buckler, Trond Nordseth, Maria Brønstad, Trygve Eftestøl, Jan T Kvaløy, Unai Irusta, Benjamin S Abella
Journal: Circulation (2018)

Background: Sudden cardiac arrest may present with one of three clinical states (rhythms): Ventricular fibrillation/tachycardia (VF/VT), Pulseless Electrical Activity (PEA), or Asystole (ASY). During Advanced Cardiac Life Support (ACLS), the patient may also transition between the other states or reach temporary ROSC (defined as an organized electrical rhythm without chest compressions &gt;= 1 min). Finally, either sustained ROSC or death will ensue. The aim of study was to investigate and quantify the dynamic characteristics of this process and compare with previous studies. Methods: As part of a CPR quality assessment initiative, we prospectively registered the development of clinical states using defibrillators that records the ECG as well as ongoing chest compressions. These recordings were analyzed in a multi-state statistical framework. Instantaneous transition rates were obtained by smoothing the Nelson-Aalen estimator of cumulative intensities. Results: We analyzed 201 episodes in 168 patients between 2008 and 2009 at the Hospital of the University of Pennsylvania (51% women; median age 60, IQR 49-73 years). Most episodes (62%) took place in the Medical ICU, and represented multiple etiologies. PEA was the most frequent presenting rhythm (69%); VF/VT and ASY contributed with 15 % each. In the 191 episodes with complete information about the clinical course, the transition rate from PEA to ROSC was 0.11 episodes/min (approximately 11%), the rate of PEA recurring from temporary ROSC was 0.12/min. These transition rates are both about 40 % higher than observed earlier. The prevalence of sustained ROSC was 0.6 (60%) at about 25 min (figure: 0 to 45 min of CPR). Conclusion: We provide quantitative overview of the dynamic process of clinical state transitions during in-hospital cardiac arrest in adults. Compared to earlier studies from American and Norwegian Hospitals, we found higher transition rates between PEA to ROSC, and a high prevalence of sustained ROSC.
USP48 Is Upregulated by Mettl14 to Attenuate Hepatocellular Carcinoma via Regulating SIRT6 Stabilization
Authors: Lutao Du, Yang Li, Min Kang, Maoxiao Feng, Yidan Ren, Hongliang Dai, Yumin Wang, Yunshan Wang, Bo Tang
Journal: Cancer Research (2021)

Abstract Exploiting cancer metabolism for the clinical benefit of patients with hepatocellular carcinoma (HCC) is a topic under active investigation. Ubiquitin-specific peptidase 48 (USP48), a member of the ubiquitin-specific protease family, is involved in tumor growth, inflammation, and genome stability. However, the role of USP48 in HCC tumorigenesis remains unknown. In this study, we report that expression of USP48 is downregulated in diethylnitrosamine-induced liver tumorigenesis in mice as well as in human HCC. USP48 physically bound and stabilized SIRT6 by K48-linked deubiquitination at the K33 and K128 sites of SIRT6, which impeded metabolic reprogramming to hamper HCC tumorigenesis. Moreover, methyltransferase-like 14 (Mettl14)–induced m6A modification participated in the regulation of USP48 in HCC by maintaining USP48 mRNA stability. Our work uncovers the tumor-suppressive function of the Mettl14–USP48–SIRT6 axis via modulation of glycolysis, providing new insights into the critical roles of metabolic activities in HCC and identifying an attractive target for future treatment studies. Significance: These findings demonstrate that USP48 is regulated by Mettl14-induced m6A modification and stabilizes SIRT6 to attenuate HCC glycolysis and malignancy.
A novel cell-penetrating peptide targeting calpain-cleavage of PSD-95 induced by excitotoxicity improves neurological outcome after stroke
Authors: Sara Ayuso-Dolado, Gema M. Esteban-Ortega, Óscar G. Vidaurre, Margarita Díaz-Guerra
Journal: Theranostics (2021)

Postsynaptic density protein-95 (PSD-95) is a multidomain protein critical to the assembly of signaling complexes at excitatory synapses, required for neuronal survival and function.However, calpainprocessing challenges PSD-95 function after overactivation of excitatory glutamate receptors (excitotoxicity) in stroke, a leading cause of death, disability and dementia in need of efficient pharmacological treatments.A promising strategy is neuroprotection of the infarct penumbra, a potentially recoverable area, by promotion of survival signaling.Interference of PSD-95 processing induced by excitotoxicity might thus be a therapeutic target for stroke and other excitotoxicityassociated pathologies.Methods: The nature and stability of PSD-95 calpain-fragments was analyzed using in vitro assays or excitotoxic conditions induced in rat primary neuronal cultures or a mouse model of stroke.We then sequenced PSD-95 cleavage-sites and rationally designed three cell-penetrating peptides (CPPs) containing these sequences.The peptides effects on PSD-95 stability and neuronal viability were investigated in the cultured neurons, subjected to acute or chronic excitotoxicity.We also analyzed the effect of one of these peptides in the mouse model of stroke by measuring infarct size and evaluating motor coordination and balance.Results: Calpain cleaves three interdomain linker regions in PSD-95 and produces stable fragments corresponding to previously described PSD-95 supramodules (PDZ1-2 and P-S-G) as well as a truncated form SH3-GK. Peptide TP95414, containing the cleavage site in the PDZ3-SH3 linker, is able to interfere PSD-95 downregulation and reduces neuronal death by excitotoxicity.Additionally, TP95414 is delivered to mice cortex and, in a severe model of permanent ischemia, significantly improves the neurological outcome after brain damage.Conclusions: Interference of excitotoxicity-induced PSD-95-processing with specific CPPs constitutes a novel and promising therapeutic approach for stroke treatment.
ESTIMATING CARDIOVASCULAR EVENT RATES IN U.S. VETERANS USING THE SMART RISK SCORE
Authors: Subhash Banerjee, David A. Jacob, Rick A. Weideman, Helene R. Weideman, Kevin C. Kelly, Amer Alaiti, Bertis B. Little, Emmanouil S. Brilakis
Journal: Journal of the American College of Cardiology (2021)
Dysregulated Transcriptional Upregulation of Cell-Cycle Regulators By KLF1 Mutation E325K Induces Cell-Cycle Arrest in Erythroid Cells Differentiated from the Congenital Dyserythropoietic Anemia (CDA)-Patient Specific Induced Pluripotent Stem Cells
Authors: Hiroshi Kohara, Taiju Utsugisawa, Hiromi Ogura, Ai Sugawara, Ogawa Yoshie, Chika Sakamoto, Hitoshi Kanno, Kenzaburo Tani
Journal: Blood (2017)
Abstract 18351: Reentrant Atrial Tachycardia in Congenital Heart Disease Patients, Role of a Crista Leak
Authors: Aarti Dalal, Prince Kannankeril, Andrew Radbill, Frank Fish
Journal: Circulation (2016)

Introduction: Atrial tachycardias (AT) occur commonly in adult patients with congenital heart disease (CHD). Common mechanisms include macroreentry utilizing the cavo-tricuspid isthmus or atriotomy...
VALIDATION AND PERFORMANCE OF POINT-OF-CARE RAPID CYP2C19 GENOTYPING IN THE TAILOR-PCI MULTICENTER INTERNATIONAL RANDOMIZED CLINICAL TRIAL
Authors: Linnea Baudhuin, Laura Train, Shaun Goodman, Gary Lane, Ryan Lennon, Verghese Mathew, Vishu Murthy, Tamim Nazif, Derek So, John Sweeney, Alan Wu, Charanjit Rihal, Michael Farkouh, Naveen Pereira
Journal: Journal of the American College of Cardiology (2021)
COMPARISONS OF ECHOCARDIOGRAPHIC AND INVASIVE AORTIC GRADIENT ASSESSMENT IN AORTIC STENOSIS, DEGENERATED SURGICAL BIOPROSTHESIS, NATIVE AND VALVE-IN-VALVE TAVR: A MULTICENTER STUDY
Authors: Houman Khalili, Amr Abbas, Thomas Pilgrim, Taishi Okuno, Sammy Elmariah, Karim Al-Azizi, George Hanzel, Thomas Waggoner, Ramy Mando, Anthony Bavry, Philippe Pibarot, Michael Mack, Francis Shannon
Journal: Journal of the American College of Cardiology (2021)
SURGICAL REPAIR OF ANOMALOUS AORTIC ORIGIN OF A CORONARY ARTERY (AAOCA) IN CHILDREN: POST-OPERATIVE HIGH-RISK ANATOMIC FEATURES ON CT ANGIOGRAPHY IN A PROSPECTIVE COHORT
Authors: Tam Doan, Shagun Sachdeva, Carlos Bonilla-Ramirez, Dana Reeves-O’Neal, Prakash Masand, Rajesh Krishnamurthy, Siddharth Jadhav, Carlos Mery, Ziyad Binsalamah, Silvana Molossi
Journal: Journal of the American College of Cardiology (2021)
THE ASSOCIATION OF PRE-TRANSPLANT ATRIAL FIBRILLATION WITH IN-HOSPITAL OUTCOMES IN PATIENTS UNDERGOING ORTHOTOPIC LIVER TRANSPLANTATION: A PROPENSITY SCORE MATCHING ANALYSIS
Authors: Michael Dangl, Jelani Grant, Louis Vincent, Bertrand Ebner, Jennifer Maning, Odunayo Olorunfemi, Neal Olarte, Gerardo Zablah, Rhea Sancassani, Rosario Colombo
Journal: Journal of the American College of Cardiology (2021)
Urinary bladder cancer as a late sequela of traumatic spinal cord injury
Authors: Ralf Böthig, Christian Tiburtius, Wolfgang Schöps, Michael Zellner, Oliver Balzer, Birgitt Kowald, Sven Hirschfeld, Roland Thietje, Aki Pietsch, Ines Kurze, Martin Forchert, Thura Kadhum, Klaus Golka
Journal: Military Medical Research (2021)

Abstract Background Traumatic spinal cord injury (SCI) is also a combat-related injury that is increasing in modern warfare. The aim of this work is to inform medical experts regarding the different course of bladder cancer in able-bodied patients compared with SCI patients based on the latest medical scientific knowledge, and to present decision-making aids for the assessment of bladder cancer as a late sequela of traumatic SCI. Methods A study conducted between January 1998 and December 2019 in the BG Trauma Hospital Hamburg formed the basis for the decision-making aids. Urinary bladder cancer was diagnosed in 40 out of 7396 treated outpatient and inpatient SCI patients. General patient information, latency period, age at initial diagnosis, type of bladder management and survival of SCI patients with bladder cancer were collected and analysed. T category, grading and tumour entity in these patients were compared with those in the general population. Relevant bladder cancer risk factors in SCI patients were analysed. Furthermore, relevant published literature was taken into consideration. Results Initial diagnosis of urinary bladder cancer in SCI patients occurs at a mean age of 56.4 years (SD ± 10.7 years), i.e. , approximately 20 years earlier as compared with the general population. These bladder cancers are significantly more frequently muscle invasive (i.e., T category ≥ T2) and present a higher grade at initial diagnosis. Furthermore, SCI patients show a significantly higher proportion of the more aggressive squamous cell carcinoma than that of the general population in areas not endemic for the tropical disease schistosomiasis. Consequently, the survival time is extremely unfavourable. A very important finding, for practical reasons is that, in the Hamburg study as well as in the literature, urinary bladder cancer is more frequently observed after 10 years or more of SCI. Based on these findings, a matrix was compiled where the various influencing factors, either for or against the recognition of an association between SCI and urinary bladder cancer, were weighted according to their relevance. Conclusions The results showed that urinary bladder cancer in SCI patients differs considerably from that in able-bodied patients. The presented algorithm is an important aid in everyday clinical practice for assessing the correlation between SCI and bladder cancer.
Respiratory syncytial virus seasonality and prevention strategy planning for passive immunisation of infants in low-income and middle-income countries: a modelling study
Authors: You Li, David Hodgson, Xin Wang, Katherine E Atkins, Daniel R Feikin, Harish Nair
Journal: The Lancet Infectious Diseases (2021)

BackgroundRespiratory syncytial virus (RSV) represents a substantial burden of disease in young infants in low-income and middle-income countries (LMICs). Because RSV passive immunisations, including maternal vaccination and monoclonal antibodies, can only grant a temporary period of protection, their effectiveness and efficiency will be determined by the timing of the immunisation relative to the underlying RSV seasonality. We aimed to assess the potential effect of different approaches for passive RSV immunisation of infants in LMICs.MethodsWe included 52 LMICs in this study on the basis of the availability of RSV seasonality data and developed a mathematical model to compare the effect of different RSV passive immunisation approaches (seasonal approaches vs a year-round approach). For each candidate approach, we calculated the expected annual proportion of RSV incidence among infants younger than 6 months averted (effectiveness) and the ratio of per-dose cases averted between that approach and the year-round approach (relative efficiency).Findings39 (75%) of 52 LMICs included in the study had clear RSV seasonality, defined as having more than 75% of annual RSV cases occurring in 5 or fewer months. In these countries with clear RSV seasonality, the seasonal approach in which monoclonal antibody administration began 3 months before RSV season onset was only a median of 16% (IQR 13–18) less effective in averting RSV-associated acute lower respiratory infection (ALRI) hospital admissions than a year-round approach, but was a median of 70% (50–97) more efficient in reducing RSV-associated hospital admissions per dose. The seasonal approach that delivered maternal vaccination 1 month before the season onset was a median of 27% (25–33) less effective in averting hospital admissions associated with RSV-ALRI than a year-round approach, but was a median of 126% (87–177) more efficient at averting these hospital admissions per dose.InterpretationIn LMICs with clear RSV seasonality, seasonal approaches to monoclonal antibody and maternal vaccine administration might optimise disease prevention by dose given compared with year-round administration. More data are needed to clarify if seasonal administration of RSV monoclonal antibodies or maternal immunisation is programmatically suitable and cost effective in LMICs.FundingThe Bill & Melinda Gates Foundation, World Health Organization.
Impairment of p53 function in response to 4-hydroxyequilenin in mammary epithelial cells
Authors: Muriel Cuendet, Judy L. Bolton
Journal: Cancer Research (2005)

1206  Long-term exposure to synthetic and endogenous estrogens has been associated with the development of cancer in several tissues. One potential mechanism of estrogen carcinogenesis involves catechol formation and these catechols are further oxidized to electrophilic/redox active o-quinones, which have the potential to both initiate and promote the carcinogenic process. 4-Hydroxyequilenin (4-OHEN), a major phase I metabolite of several estrogens present in Premarin®, is considerably more cytotoxic, carcinogenic, and mutagenic as compared to the catechol estrogen metabolites of endogenous estrogens. Previously, we showed that 4-OHEN autoxidized to an o-quinone and caused a variety of damage to DNA. Allowing more time between the induction of DNA damage and the entry of a damaged cell into the DNA synthetic phase of the cell cycle protects that cell from mutagenesis. Central to this response is the establishment of a G1/S checkpoint. This checkpoint is mediated by the cyclin-dependent kinase inhibitor p21-WAF1, a direct downstream target for transcriptional activation by p53. In this study, we looked at the p53 signaling pathway. Surprisingly, exposure to 4-OHEN did not induce the classical response to a DNA damaging agent in a mammary epithelial cell line. In EN-3 cells, a 4-OHEN transformed cell line derived from MCF-10A cells, a 24 h treatment with 4-OHEN did not induce a G1/S checkpoint and cells with damaged DNA accumulated in the S phase. Doses of 10 μM induced a decrease in p53 expression in the nuclear fraction and prevented the cells from accumulating p53 protein in its mature, wild type conformation, while enhancing the accumulation of p53 protein in a mutant conformation. Our results showed that derangement of p53 conformational integrity manifested as a loss of DNA binding. Stabilization of p53 in cells activates, through consensus p53 binding sites, a number of genes that have been implicated as functional targets in p53-induced cell growth repression or apoptosis. The WAP/CIP1 gene, which encodes the p21 protein, is the major mediator of p53-dependent G1/S arrest and, in agreement with our results, its expression was decreased after treatment with 4-OHEN. On the contrary, a 3 h treatment induced a G1/S checkpoint that prevented further entry of cells into the DNA synthetic phase of the cell cycle. Also, we observed an increase in p53 expression in the nuclear fraction, p53 activation and an increase in p21 expression. These results show that a short exposure to 4-OHEN induced a classical response to a DNA damaging agent with p53 activation and G1 arrest. Interestingly, it also demonstrated that a longer treatment with 4-OHEN evaded the p53-mediated cellular protective mechanism of G1 arrest and this stealth characteristic may contribute to 4-OHEN’s potent carcinogenic action.
NEXT DAY DISCHARGE VS EARLY DISCHARGE AFTER TAVR: SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Rahul Gupta, Sugandhi Mahajan, Umair Tariq, Bilal Saqi, Nikhil Mehta, Aaqib Malik, Apurva Vyas, Nainesh Patel
Journal: Journal of the American College of Cardiology (2021)
PREDICTIVE ACCURACY OF ACTION-ICU SCORE IN A LATIN-AMERICAN COHORT OF PATIENTS WITH NON-ST SEGMENT ELEVATION ACUTE MYOCARDIAL INFARCTION
Authors: Juan Felipe Vasquez, Carolina Idrovo-Turbay, Alberto Navarro, Ramón Medina, Marisol Carreno, Luis E. Giraldo, Nicolás Ariza, Daniel Isaza-Restrepo
Journal: Journal of the American College of Cardiology (2021)
MULTINATIONAL SURVEY ON MANAGEMENT OF PATIENTS WITH PATENT FORAMEN OVALE AND LEFT CIRCULATION THROMBOEMBOLISM
Authors: Maciej Debski, Amr Abdelrahman, Halia Alshehri, Marloe Prince, Andrew Wiper, Shajil Chalil, Dariusz Dudek, Christopher White, David Hildick-Smith, David Roberts
Journal: Journal of the American College of Cardiology (2021)
Characterization of the major allergen, Que ac 1, from sawtooth oak pollen
Authors: Kyoung Yong Jeong, Jongsun Lee, Ji Eun Yuk, Jong Han Park, Fatima Ferreira, Min Kyu Sang, Yong Seok Lee, Lothar Vogel, Kyung Hee Park, Jung‐Won Park
Journal: Allergy (2021)

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Prolonged Progression Free Survival and Time to Next Treatment Are Achievable Outcomes in Patients with Systemic AL Amyloidosis Treated with Novel Agent Chemotherapy: Analysis of the Alchemy Study
Authors: Richa Manwani, Darren Foard, Shameem Mahmood, Sajitha Sachchithanantham, Marianna Fontana, Carol Whelan, Candida Quarta, Thirusha Lane, Helen Lachmann, Julian Gillmore, Philip Hawkins, Ashutosh D. Wechalekar
Journal: Blood (2017)