tbuckley/cabot-search huggingface dataset:
Abstract 16979: Hemodynamic Comparison of Tricuspid Ring Annuloplasty vs. Hetzer Annuloplasty Technique to Repair Functional Tricuspid Regurgitation
Authors: Alan Amedi, Daisuke Onohara, Muralidhar Padala
Journal: Circulation (2020)

Introduction: Surgical repair of functional tricuspid regurgitation (FTR) is increasingly performed, and the techniques are evolving. Annuloplasty is currently the technique of choice, with different techniques yielding varied results, and thus require optimization. Objective: In this study, we sought to compare tricuspid valve function and kinematics after ring annuloplasty and Hetzer’s double orifice repair in an ex vivo model of FTR. Methods: Ten pig hearts were mounted into a right heart simulator, and studied at 70 bpm while maintaining the total volume of working fluid. FTR was created by increasing afterload, which caused acute right ventricular dilation and TV tethering. Tricuspid valve annuloplasty (TVA) was performed with a 26mm MC 3 ring. Hetzer procedure was performed with pledgeted sutures that approximated the anteroposterior and septal annular segments. Flow probes were used to measure FTR, and leaflet kinematics with echocardiography. Results: FTR of 17.7±9.2mL(p&lt;0.0001) after RV dilation. Repair with TVA and Hetzer reduced FTR to 8.8±6.8ml(p=0.7142) and 7.8±6.9ml(p=0.0919), respectively, but did not eliminate it. Septal leaflet excursion angle decreased by 48.1% with FTR (p=0.04 vs. baseline ) . Repair with TVA and Hetzer increased the angle to 17.3±6.7°(p=0.0312) and 21.5±8.3°(vs FTR, p=0.0034), respectively. The Hetzer improved septal leaflet mobility better than TVA (p=0.0145). The posterior leaflet excursion angle decreased by 49.2% compared to baseline to 18.4±10.5° (p=0.0060) and both TVA and Hetzer significantly improved mobility to 33.6±8.4° (p=0.0081) and 31.6±15.6° (p=0.0256), respectively. Anterior leaflet mobility decreased after FTR by 60.7% to 18.1±8.2°. The effect of these repairs on the sub-valvular apparatus was negligible. Conclusion: TVA and Hetzer both reduced regurgitation but did not eliminate it. Septal and posterior leaflet mobility was improved, while the anterior leaflet remained tethered.
Addressing Shortages in Pediatric Emergency Care—The Evolution of Health Care Access
Authors: Gillian R. Schmitz
Journal: JAMA Network Open (2021)

Christopher L. Bennett, MD, MA; Janice A. Espinola, MPH; Ashley F. Sullivan, MS, MPH; Krislyn M. Boggs, MPH; Carson E. Clay; Moon O. Lee, MD, MPH; Margaret E. Samuels-Kalow, MD, MPhil, MSHP; Carlos A. Camargo Jr, MD, DrPH
Checkpoint kinase 1 regulates diallyl trisulfide induced mitotic arrest in human prostate cancer cells
Authors: Anna Herman-Antosiewicz, Shivendra V. Singh
Journal: Cancer Research (2005)

1574  Epidemiological data continues to support the notion that increased consumption of Allium vegetables may reduce the risk for different types of malignancies including cancer of the prostate. Moreover, allium vegetable derived organosulfur compounds, such as diallyl trisulfide (DATS; CH2=CH-CH2-(S)3-CH2-CH=CH2), are highly effective in affording protection against cancer development in animal models. Evidence is mounting to indicate that garlic-derived organosulfur compounds can suppress proliferation of cultured cancer cells by inhibiting cell cycle progression and causing apoptosis induction. Previous studies including those from our laboratory have offered novel insights into the mechanism of apoptosis induction by DATS. For instance we showed previously that DATS-induced apoptosis in PC-3 and DU145 human prostate cancer cells was associated with c-jun N-terminal kinase mediated phosphorylation of Bcl-2, which reduced Bax-Bcl-2 interaction to trigger activation of caspase-9/3. In the present study, we extended these observations and determined the mechanism by which DATS inhibits cell cycle progression using PC-3 cells as a cellular model. We found that exposure of PC-3 cells to 20 or 40 μM DATS resulted in a time-dependent enrichment of G2/M phase cells that was accompanied by accumulation of cyclin B1, degradation of cell division cycle 25C (Cdc25C), and increased phosphorylation of Cdc25C at Ser-216 and cyclin-dependent kinase 1 (Cdk1) at Tyr-15. DATS treatment also caused activating phosphorylation of checkpoint kinase 1 (Chk1; Ser-317) and Chk2 (Thr-68), which are intermediaries of DNA damage checkpoint and implicated in Ser-216 phosphorylation of Cdc25C. The Ser-216 phosphorylation of Cdc25C phosphatase, which plays a pivotal role in activation of Cdk1/cyclin B1, negatively regulates its activity. In addition, DATS treated PC-3 cells exhibited features characteristic of mitotic arrest including disruption of the tubulin network, chromatin condensation and increased Ser-10 phosphorylation of histone H3. DATS-induced Cdc25C and Cdk1 phosphorylation and mitotic arrest, but not G2 phase arrest, was significantly attenuated by depletion of Chk1 protein using Chk1 targeted siRNA duplexes. On the other hand, Chk2 protein knockdown did not have any appreciable effect on G2 or M phase arrest caused by DATS. In conclusion, these results suggest existence of a Chk1-Cdc25C-Cdk1 independent mechanism responsible for DATS-induced G2 arrest. Furthermore, we provide evidence to indicate that Chk1 kinase is necessary to arrest cells that escape G2 block at the early stages of mitosis (supported by NIH grants CA101753 and CA076348).
The Advisory Committee on Immunization Practices’ Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine in Adolescents Aged 12–15 Years — United States, May 2021
Authors: Megan Wallace, Kate R. Woodworth, Julia W. Gargano, Heather M. Scobie, Amy E. Blain, Danielle Moulia, Mary Chamberland, Nicole Reisman, Stephen C. Hadler, Jessica R. MacNeil, Doug Campos-Outcalt, Rebecca L. Morgan, Matthew F. Daley, José R. Romero, H. Keipp Talbot, Grace M. Lee, Beth P. Bell, Sara E. Oliver
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

In May 2021, after a systematic review of all available data, the Advisory Committee on Immunization Practices made an interim recommendation for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12–15 years for the prevention of COVID-19.
Abstract 16160: Invasive Approach for Cocaine Associated Non-ST-Elevation Myocardial Infarction is Associated With Reductions in Major Adverse Cardiac Events and Worsening Emergent Revascularization
Authors: ZACHARY ZUZEK, Shilpkumar Arora, Rahul Jaswaney, Chinmay Jani, SIDAKPAL PANAICH, Mohammed Osman, Brian Hoit, Richard A Josephson, David A Zidar, Mehdi Shishehbor
Journal: Circulation (2020)

Introduction: Impact of an invasive approach in patients with cocaine associated non-ST-elevation myocardial infarction (CANSTEMI) is unknown. Hypothesis: To determine the effects of an invasive approach on patients with CANSTEMI. Methods: Nationwide Readmissions Database (NRD) from years 2016-2017 was utilized for hypothesis. We utilized ICD-10 CM codes I21.4 in primary diagnosis field and F14 in secondary fields to identify CANSTEMI. Coronary angiogram (CA) with or without percutaneous coronary intervention (PCI) was considered an invasive approach. The primary outcome was a composite of major adverse cardiac events (MACE) at one year. Secondary outcomes included all-cause mortality, MI readmission, stroke readmission, and emergent revascularization at one year. Cox-Proportional Hazard regression was used to adjust for demographic and comorbid confounders. Results: A total of 7,372 patients were identified of which 4,332 (58.8%) underwent invasive treatment. Patients with obesity, hyperlipidemia, tobacco use, and a personal and family history of CAD were more likely to undergo an invasive approach. Conversely, patients with CKD stage 3 or more and anemia were less likely to undergo invasive treatment. The primary outcome was significantly reduced with an invasive approach compared to a non-invasive approach. Similarly, all-cause mortality and MI readmission were also significantly reduced with an invasive approach. An invasive approach was associated with increased emergent revascularization compared to a noninvasive approach. On further stratification of an invasive approach, CA and PCI both were individually associated with improved MACE outcomes and PCI only was associated with increased emergent revascularization. Conclusions: In conclusion, an invasive approach with CA with or without PCI for CANSTEMI was associated with reductions in morbidity and mortality. PCI only was associated with an increase in emergent revascularization.
Identification of immune‐activating metabolite for enhancing T cell therapy of cancer
Authors: Boyi Cong, Zenghui Cui, Xuetao Cao
Journal: Cancer Communications (2021)

In this Research Highlight, we summarized the results from a study by Wu et al. published in Nature Cell Biology which uncovered that asparagine (Asn), a non-essential amino acid in mammalians, is able to enhance the TCR-mediated activation and efficacy of CD8+ T cells towards tumour through lymphocyte-specific protein tyrosine kinase (LCK) signalling. This study provides insights into the physiological function of Asn in T cell activation and effector functions, showing the encouraging possibility of key metabolites for empowering cancer immunotherapy.
Abstract 15230: Sex and Racial Differences in Normative Reference Ranges and Healthy Aging on Diastolic Function in Ethnic Asians: 2016 Ase Guideline Revisited
Authors: Sheng Nan Chang, Kuo-Tzu Sung, Wen-Hung Huang, Jou-Wei Lin, Shih-Chieh Chien, Ta-Chuan Hung, Cheng-huang Su, Chia-Ti Tsai, Yen-Wen Wu, Fu-Tien Chiang, Hung-I Yeh, Juey-Jen Hwang, Chung-lieh Hung
Journal: Circulation (2020)

Introduction: However, the reference ranges for echocardiography might be varying due to ethnicity, gender and age. Therefore, the normal reference ranges obtained from the healthy Asians are important for clinical utility of echocardiography in Asia. Methods: Population-based echocardiography dataset from 6,023 healthy ethnic Asians (47.1±10.9 years, 61.3% men) were divided into 6 age decades: ≤29, 30-39, 40-49, 50-59, 60-69 and ≥70 years. We explored age- and sex-related structural/functional alterations according to 2016 American Society of Echocardiography (ASE) diastolic dysfunction (DD) criteria and their correlates with clinical N-terminal pro-brain natriuretic peptide (NT-proBNP) cut-off for heart failure (HF). Racial comparisons were made using data from London Life Sciences Prospective Population (LOLIPOP) study. Results: Age- and sex-based normative reference ranges (including mean, median, 10% and 90% lower and upper reference values) were extracted from our large healthy population. In fully adjusted models, advanced age (treated as linear) was independently associated with cardiac structural remodeling and worsened diastolic parameters: larger indexed LA volume (LAVi), lower e’, higher E/e’, and higher TR velocity; all p &lt;0.001), and were broadly more prominent in women (P interaction : &lt;0.05). in general, markedly lower e’, higher E/e’ and smaller LAVi were observed in ethnic Asians compared to Whites. DD defined by 2016 ASE criteria, despite at low prevalence (0.42%) in current healthy population, increased drastically with advanced age and performed perfectly in excluding abnormal NT-proBNP (≥125 pg/ml) (Specificity: 99.8%, NPV: 97.6%). Conclusions: This is to date the largest cohort exploring the normative reference values using guideline-centered diastolic parameters from healthy Asians, with senescence process played as central role in diastolic dysfunction. Observed sex and ethnic differences in defining healthy diastolic cut-offs likely impact future clinical definition for DD.
170P Pattern and prognosis of fatal cardiac events in locoregional and distant stages in female breast cancer patients: SEER- based analysis
Authors: M.H.O. Safi, D. Trapani, M. Alradhi, A. Al-Danakh, X. Shan, F. Ping, A. Al-Masni, Y. Jamalat, N. Al-Sabai, A. Al-Dhaibani, A. Al-Samawi, M. Al-Sameai, A. Al-Sharabi, J. Liu
Journal: Annals of Oncology (2021)
Abstract 14830: Edge-to-edge Transcatheter Mitral Valve Repair is Associated With Lower Pulmonary Artery Pressure in Cardiomems <sup>TM</sup> -monitored Patients With Heart Failure and Mitral Regurgitation
Authors: David Shavelle, J Thomas T Heywood, Ajay Srivastava, Rahul Agarwal, Julie Prillinger, Matthew J Price
Journal: Circulation (2020)

Introduction: Transcatheter mitral valve repair (TMVr) reduces heart failure (HF) hospitalizations and improves survival in patients with HF and secondary mitral regurgitation (MR), but the hemodynamics of TMVr are not well studied. Patients with a pulmonary artery pressure (PAP) monitor (CardioMEMS TM ) provide a unique opportunity to study ambulatory hemodynamics following TMVr. Methods: TMVr implants occurring July 2014 to Sept 2019 were identified from Medicare claims data and were linked to PAP data from CardioMEMS TM . Patients with CardioMEMS TM implant ≥3 mo prior to TMVr and with ≥3 mo PAP data post TMVr were included. Diastolic PAP (DPAP) and area under the curve (AUC) at 3 and 6 mo post TMVr were compared to 4 wks prior to TMVr (baseline). Analysis was repeated for those with elevated baseline DPAP, defined as ≥15 mmHg. Results: The cohort included 32 patients (74 ± 8 yrs, 66% male) with high prevalence of hypertension, ischemic heart disease, AF, and kidney disease. LVEF was available in 17 patients (32 ± 14%). Compared to baseline, DPAP was significantly lower at 3 mo (-2.1 ± 4.7 mmHg, p=0.019) and remained lower at 6 mo post TMVr (-2.5 ± 6.7 mmHg, p=0.070). AUC showed a cumulative reduction in DPAP of -129 ± 257 mmHg-days (p=0.008) at 3 mo and -438 ± 719 mmHg-days (p=0.005) at 6 mo post TMVr. Similar trends were observed for mean PAP. Sub-group analyses suggested lower DPAP after TMVr in patients with elevated baseline DPAP (3 mo Δ: -2.6 ± 4.6 mmHg, p=0.009; 6 mo Δ: -3.8 ± 6.3 mmHg, p=0.014, 3 mo AUC: -158 ± 255 mmHg-day, p=0.004; 6 mo AUC: -575 ± 721 mmHg-day, p=0.002). Conclusions: In CardioMEMS TM -monitored patients with significant MR, TMVr is associated with a clinically relevant and sustained reduction in DPAP, including patients with an elevated baseline DPAP. Although the clinical and survival benefits of TMVr are paramount, these data add to our understanding of the hemodynamic improvements of TMVr. CardioMEMS TM is an additional tool to improve filling pressures in those with HF.
Abstract P141: Association Of Obesity And Cigarette Smoking With Markers Of Inflammation And Thrombosis
Authors: Adebamike A Oshunbade, Seth T Lirette, Arsalan Hamid, Daisuke Kamimura, Rodney Kipchumba, Andrew DeFilippis, Edmund K Kerut, Javed Butler, Kenneth R Butler, Thomas Mosley, Michael Hall
Journal: Circulation (2021)

Association of obesity and cigarette smoking with markers of inflammation and thrombosis Background: The association between obesity with inflammation and thrombosis has been understudied. The combined association of obesity and cigarette smoking with inflammation and thrombosis also has not been systematically investigated in a well characterized cohort. Methods: We investigated 2549 participants from the Genetic Epidemiology Network of Arteriopathy (GENOA) study (mean age 61±10 years, 64% women, 51% African American). Participants were classified by body mass index (BMI) as normal BMI (n=371), overweight (n= 864), or obese (n= 1314). Obese participants were further classified by self-reported smoking status as having never smoked (n= 747), smoked in the past (n= 454), and currently smoking (n= 113). We compared adjusted associations among these groups with 18 biomarkers of inflammation and 8 biomarkers of thrombosis using generalized estimating equations. Results: After adjusting for potential confounders, individuals who were obese but had never smoked had higher levels of high sensitivity CRP, serum amyloid A, TNFR1 and TNFR2, IL-6, fibrinogen, and VWF compared to participants with normal BMI that were had never smoked (all p&lt;0.05). However, individuals with obesity currently smoking had higher levels of these biomarkers compared to those who never smokers, particularly within the domains of systemic inflammation and cytokines (Table). Compared with participants without obesity who never smoked, the odds of hsCRP &gt;10 milligram/liter in individuals with obesity was 3.6 times for those who currently smoked, and 2.7 times for those who never smoked. Conclusions: In adjusted analyses, obesity is associated with several proinflammatory biomarkers; but when combined with cigarette smoking, this relationship becomes stronger. These findings underscore the need to recommend smoking cessation and weight loss in patients with both of these important risk factors.
Abstract 13320: Direct Cardiac Actions of Empagliflozin Improve Mitochondrial Oxidative Phosphorylation and Attenuate Pressure-overload Heart Failure
Authors: Xuan Li, Jussara M do Carmo, Zhen Wang, Alexandre A da Sivla, Alan J Mouton, Ana M Omoto, Michael E Hall, John E Hall
Journal: Circulation (2020)

Introduction: The underlying mechanisms by which empagliflozin (EMPA) and other sodium glucose co-transporter 2 (SGLT2) inhibitors attenuate heart failure (HF) are still poorly understood. However, this protection does not appear to be fully explained by their antihyperglycemic or diuretic effects. Hypothesis: EMPA attenuates HF by direct effects on the heart to improve its metabolism and function. Methods: C57BL/6J mice (4-6 months) were subjected to transverse aortic constriction (TAC) or sham surgeries. Two weeks after TAC, EMPA (10 mg/kg/day) or vehicle was administered daily for 4 additional weeks. Cardiac function was assessed by echocardiography and cardiac substrate metabolism measured in isolated perfused hearts. Transmission electron microscopy was used to evaluate mitochondrial morphology and molecular docking analysis to predict potential cardiac targets of EMPA. Results: EMPA increased survival and attenuated adverse left ventricle remodeling and cardiac fibrosis after TAC. EMPA also attenuated left ventricular systolic dysfunction (ejection fraction 51.6 vs. 40.2% p&lt;0.05; fraction shortening 28.8 vs 18.4% p&lt;0.05). EMPA rescued impaired glucose and fatty acid oxidation in failing hearts, while reducing glycolysis. Molecular docking analysis and isolated perfused heart experiments indicated that EMPA can directly bind glucose transporters in the heart to reduce glycolysis, and enhance AMP-activated protein kinase. EMPA treatment enhanced mitochondrial biogenesis, restored mitochondria cristae integrity, increased expression of endogenous antioxidants, and reduced cellular apoptosis caused by leakage of cytochrome C from mitochondria into the cytosol. These beneficial cardiac effects of EMPA occurred despite no alterations in fasting blood glucose, body weight, or daily urine volume. Conclusions. Our study demonstrated that EMPA may directly bind glucose transporters and reduce excessive glycolysis in failing hearts. EMPA enhanced mitochondrial biogenesis, improved mitochondrial oxidative phosphorylation, and reduced mitochondria-mediated apoptosis, thereby attenuating cardiac dysfunction and progression of HF.
Accurate and Sensitive Analysis of Minimal Residual Disease in Acute Myeloid Leukemia Using Deep Sequencing of Single Nucleotide Variations
Authors: Erik Delsing Malmberg, Mariana Buongermino Pereira, Anna Rehammar, Jonas Abrahamsson, Tore Samuelsson, Sara Ståhlman, Julia Asp, Lars Palmqvist, Erik Kristiansson, Linda Fogelstrand
Journal: Blood (2017)
Poster Presentation : Patients with Unresectable Hepatocellular Carcinoma Beyond Milan Criteria: Should We Tace or Liver Transplant? (초)
Authors: Jong Man Kim, Choon Hyuck David Kwon, Jae Won Joh, Mill Jae Shin, Eun Young Kim, Ju Ik Moon, Gum O Jung, Gyu Seong Choi, Sung Joo Kim, Suk Koo Lee
Journal: Clinical and Molecular Hepatology (2009)
Abstract P087: Goldberger's Electrocardiographic Criteria For Left Ventricular Dysfunction Associated With Increased Mortality
Authors: Kang Rui Xiang, Elsayed Z Soliman, Prashant Bhave, Matthew J Singleton
Journal: Circulation (2021)

Goldberger’s Electrocardiographic Criteria for Left Ventricular Dysfunction Associated with Increased Mortality Introduction: The ability of the Goldberger electrocardiographic (ECG) triad criteria to detect left ventricular dysfunction (LVD) is well-established. However, the prognostic significance of this triad as a predictor of poor outcomes is not known. Hypothesis: We hypothesized that the Goldberger ECG-LVD triad is associated with increased all-cause mortality and cardiovascular mortality in the general population. Methods: This analysis included 8,426 participants (60.5 ± 13.6 years, 51.5% women, 50% non-Hispanic white) from the Third National Health and Nutrition Examination Survey. The Goldberger ECG-LVD triad was defined as follows: high precordial QRS voltage (SV1 or SV2 + RV5 or RV6 ≥3500 μV); low limb lead QRS voltage (mean QRS amplitude in each of the limb leads ≤ 800 μV); and poor R wave progression (RV4/SV4 &lt;1). Mortality was ascertained using the National Death Index. Results: At baseline, 1,384 (47.3%) of the participants had at least one of the criteria of Goldberger triad (1,193 had only one and 191 participants had 2 or more). During a median follow up of 13.8 years, 3,184 deaths occurred, of which 1,405 were cardiovascular. In multivariable-adjusted Cox proportional hazards models, presence of at least one of the Goldberger triad criteria (vs. none) was associated with increased risk of all-cause (HR 1.17, 95% CI 1.08 – 1.26, p = &lt;0.0001) and cardiovascular mortality (1.19, 1.06 – 1.33, p = 0.003). Conclusion: The Goldberger ECG-LVD triad for left ventricular dysfunction is associated with increased all-cause and cardiovascular mortality and may offer prognostic value, in addition to its diagnostic utility.
Comment on Dawson-Hughes et al. Intratrial Exposure to Vitamin D and New-Onset Diabetes Among Adults With Prediabetes: A Secondary Analysis From the Vitamin D and Type 2 Diabetes (D2d) Study. Diabetes Care 2020;43:2916–2922
Authors: Mayer B. Davidson
Journal: Diabetes Care (2020)

This letter concerns the secondary analysis (1) of the Vitamin D and Type 2 Diabetes (D2d) study (2). The D2d study was a randomized controlled trial to determine whether vitamin D supplementation (4,000 IU per day) reduced the risk of diabetes among adults with prediabetes (2). In an intention-to-treat analysis, vitamin D nonsignificantly reduced new-onset diabetes by 12% compared with the placebo (2). A secondary analysis was subsequently …