tbuckley/cabot-search huggingface dataset:
Abstract 11457: Overexpression of Thioredoxin-1 Ameliorates the Progression of Diabetic Cardiomyopathy by Preservation of Cardiac Function, Increased Survivability and Decreased Fibrosis in Aged Transgenic Mice
Authors: Sue-Ting Lim, Seetur R Pradeep, Mahesh Thirunavukkarasu, Santosh Swaminathan, Diego Accorsi, J Alexander Palesty, Nilanjana Maulik
Journal: Circulation (2021)

Introduction: Increased production of reactive oxygen species contributes to the etiology of diabetic complications. It acts as an intracellular antioxidant by scavenging reactive oxygen species (ROS) and protect the cells against oxidative stress and cell death. Hypothesis: To determine the long-term effect of streptozotocin (STZ) induced type 1 diabetes on aging Trx-1 transgenic mice related to survivability, heart function, fibrosis, and apoptosis up to 180 days (d) compared to its corresponding wild-type (WT C57Bl/6J). Method: WT and Trx-1 overexpressed mice (Trx-1 Tg/+ ) (8-12 weeks old) were injected with STZ (i.p. 50mg/kg.body weight(bw)-male; 75mg/kg.bw-female for 5 consecutive days) for induction of diabetes (Dia). Fasting blood sugar level (FBS) was measured 30d after the final injection, and FBS &gt;220mg/dL is used as the cut-off for diabetes. Echocardiography, Survival, FBS measurements were performed on 30, 60, 90, 120, 150, and 180d. Immunohistochemistry was performed on heart tissues (30, 90, and 180d). Results: Dia-Trx-1 Tg/+ mice maintained EF at 60d (61.14±2.3%), 120d (56.1±1.94%) and 180d (60.8±4.3%), when compared to 30d (64.4±1.94%) representing preserved cardiac functions. On the other hand, Dia-WT mice show significant progressive depression of EF at 60d (53.8±1.9%), 120d (48.8±2.1%), and 180d (48.9±1.5%), (p&lt;0.05) when compared to 30d (68.4±6.1%) Dia-WT. Moreover, Dia-Trx-1 Tg/+ mice show significantly higher EF than their corresponding Dia-WT counterparts at each time point measured after diabetic induction (n=8-12, p&lt;0.05). Dia-Trx-1 Tg/+ mice (n=71) also exhibited increased survival rate over Dia-WT (n=47) counterparts with a median survival of 150 days compared to 60 days (Log Rank test: p=0.004). Dia-Trx-1 Tg/+ mice also showed a significant reduction in cardiac fibrosis (4.18±1.08% vs. 17.5±5.1%; p=0.03, n=4) and TUNEL positive cells (3.81±1.49 vs. 7.66±1.46; p=0.03, n=4) when compared to their counterpart (Dia-WT) after 180d of diabetes. Conclusion: These results show that Trx-1 Tg/+ mice preserved cardiac functions, increased survival, decreased apoptosis and fibrosis up to 180d under diabetic conditions, and hence suggesting Trx-1 based treatment strategy could prevent heart failure in aging.
Abstract 13145: Impact of Chronic Obstructive Pulmonary Disease and Smoking on Clinical Outcomes After Percutaneous Coronary Intervention
Authors: Matteo Nardin, Davide Cao, Mauro Chiarito, Johny Nicolas, Carlo Andrea Pivato, Annerieke Tavenier, Samantha Sartori, Zhongjie Zhang, Hanbo Qiu, Prakash Krishnan, Nitin Barman, Joseph Sweeny, George Dangas, Roxana Mehran, Samin K Sharma, Annapoorna Kini
Journal: Circulation (2021)

Background: Chronic obstructive pulmonary disease (COPD) is the third cause of death worldwide and often coexists with cardiovascular disease. Smoking is a common risk factor which promotes both respiratory and atherosclerotic disease. Whether COPD patients are at higher risk for cardiovascular events irrespective of smoking habit is poorly understood. Hypothesis: To investigate the additive prognostic impact of COPD and smoking in a cohort of patients undergoing percutaneous coronary intervention (PCI). Methods: Consecutive patients undergoing PCI at Mount Sinai Hospital, NY, between 2012-2019 were included and stratified by the presence of COPD at baseline. Active smoking was defined as the presence of smoking anytime during the year prior to admission. There were no formal exclusion criteria, except for the absence of information on COPD and smoking status. The primary endpoint was the composite of all-cause death or myocardial infarction at one year of follow-up. Results: Of the 16,313 patients included in the analysis, 1,295 (7.94%) had COPD. Patients with COPD were older, more often Caucasian, and had higher burden of comorbidities including hypertension, cancer, chronic kidney disease, heart failure. Active smoking was more common in COPD patients compared to those without COPD (27.3% vs. 15.4%, p&lt;0.001). The primary endpoint occurred more frequently in COPD patients (4.6% vs. 2.0%; HR 2.3, 95% CI 1.7-3.1; p&lt;0.001), with a graded risk by smoking status ( FigureA ). Findings were consistent after multivariable adjustment ( FigureB ). Conclusion: In a large and contemporary cohort of patients undergoing PCI, those with COPD were at higher risk of death or myocardial infarction compared to those without COPD, and this risk was further enhanced among COPD patients who smoked.
Odds of Testing Positive for SARS-CoV-2 Following Receipt of 3 vs 2 Doses of the BNT162b2 mRNA Vaccine
Authors: Tal Patalon, Sivan Gazit, Virginia E. Pitzer, Ottavia Prunas, Joshua L. Warren, Daniel M. Weinberger
Journal: JAMA Internal Medicine (2021)

With the evidence of waning immunity of the mRNA vaccine BNT162b2 (Pfizer-BioNTech), a nationwide third-dose (booster) vaccination campaign was initiated in Israel during August 2021; other countries have begun to administer a booster shot as well.To evaluate the initial short-term additional benefit of a 3-dose vs a 2-dose regimen against infection of SARS-CoV-2.This preliminary retrospective case-control study used 2 complementary approaches: a test-negative design and a matched case-control design. Participants were included from the national centralized database of Maccabi Healthcare Services, an Israeli healthcare maintenance organization covering 2.5 million members. Data were collected between March 1, 2020, and October 4, 2021, and analyses focused on the period from August 1, 2021, to October 4, 2021, because the booster dose was widely administered from August 1 onward.Either 2 doses or 3 doses of the BNT162b2 vaccine.The reduction in the odds of a positive SARS-CoV-2 polymerase chain reaction (PCR) test at different time intervals following receipt of the booster dose (0-6, 7-13, 14-20, 21-27, and 28-65 days) compared with receiving only 2 doses.The study population included 306 710 members of Maccabi Healthcare Services who were 40 years and older (55% female) and received either 2 or 3 doses of the BNT162b2 vaccine and did not have a positive PCR test result for SARS-CoV-2 prior to the start of the follow-up period. During this period, there were 500 232 PCR tests performed, 227 380 among those who received 2 doses and 272 852 among those who received 3 doses, with 14 989 (6.6%) and 4941 (1.8%) positive test results in each group, respectively. Comparing those who received a booster and those who received 2 doses, there was an estimated odds ratio of 0.14 (95% CI, 0.13-0.15) 28 to 65 days following receipt of the booster (86% reduction in the odds of testing positive for SARS-CoV-2).Previous studies have demonstrated that vaccine-derived protection against SARS-CoV-2 wanes over time. In this case-control analysis, we showed an association between receipt of the booster dose and a reduction in the odds of testing positive for SARS-CoV-2, potentially counteracting waning immunity in the short term. Further monitoring of data from this population is needed to determine the duration of immunity following the booster.
Abstract 12815: Changes in Circulating microRNA-375 Levels in Response to Lifestyle Interventions and Improvements in Visceral Adiposity and Hepatic Fat Content: The CENTRAL Trial
Authors: Yoriko Heianza, Knut Krohn, Qiaochu Xue, Anat Yaskolka Meir, Stefanie Ziesche, Dan Schwarzfuchs, Uta Ceglarek, Matthias Bluher, Maria Keller, Peter Kovacs, Iris Shai, Lu Qi
Journal: Circulation (2021)

Introduction: MicroRNA (miRNAs) are short non-coding RNAs that regulate gene expression at the translational level. Circulating exosomal miRNAs have emerged as novel biomarkers of obesity, insulin resistance, and related metabolic abnormalities. miR-375 has been identified as a regulator of insulin secretion, and miR-375 may also be involved in regulating visceral adiposity and ectopic fat accumulation in the liver. Hypothesis: We aimed to investigate whether changes in circulating miR-375 induced by lifestyle interventions were related to improved visceral adiposity and hepatic fat depot among individuals with abdominal obesity. Methods: This study included adults with abdominal obesity from an 18-month diet and physical activity intervention study (the CENTRAL trial) and with available data on circulating miR-375-3p at baseline (n=222) and 18 months (n=152). Magnetic resonance imaging (MRI) was performed to assess body fat distribution and ectopic fat depots. Outcome measurements included 18-month changes in abdominal (total [TAT], visceral [VAT], deep subcutaneous [DSAT], superficial subcutaneous [SSAT]) adipose tissue area and intrahepatic fat content. Results: At baseline, higher levels of miR-375 were related to lower degrees of BMI ( p =0.0006), waist circumference ( p =0.0008), as well as abdominal adipose tissue area (TAT [ p =0.0024], VAT [ p =0.059], DSAT [ p =0.011], and SSAT [ p =0.0027]). There was a significant increase in circulating miR-375 levels after the 18-month lifestyle interventions ( P by paired t-test &lt; 0.0001). When we analyzed effects (β) of per 1 SD increase in miR-375 changes on the outcomes after adjusting for covariates including baseline levels of miR-375 and BMI, we found that greater increase in miR-375 was associated with larger reductions of VAT (β -8.09 [3.09] cm 2 , p =0.01), as well as DSAT (β -7.87 [2.21] cm 2 , p =0.001) and intrahepatic fat content (β -1.38% [0.5%], p =0.006) at 18 months. Conclusions: Circulating miR-375 levels significantly increased after the long-term lifestyle interventions, and greater increases in miR-375 were related to significant improvements in visceral adiposity and liver fat content that are closely related to insulin resistance in adults with abdominal obesity.
INNV-34. NEURO NARRATIVES: AN AUTOETHNOGRAPHIC ACCOUNT OF EXPERIENCING RESILIENCE WITH A BRAIN TUMOR
Authors: Christina Naegeli Costa
Journal: Neuro-Oncology (2021)

Abstract The current research uses autoethnography as a method to share my experience as a brain tumor patient. In this piece, I reference poems from the day of my diagnosis through my surgery, recovery, and following treatment to demonstrate the thematic factors that allowed me to cope and experience positive emotions as an oncology patient. Results included the factors of trust in medical care, utilizing social support, finding meaning and purpose, and self-love and gratitude. The implications of these factors in relation to resilience structures and discourses to better serve other oncology and chronic illness patients are discussed.
Abstract 12067: Prospective Utility of ST2 in Patients Hospitalized With Acute Decompensated Heart Failure
Authors: Brian Li, Michaela Dowley, Samantha Langley, Amy Hardy-Wallace, Paraic Cliffe, Stephen whiting, Pat Phen, Stuart Harris, Rossella Barbagallo, Jason Dungu, Henry Oluwasefunmi O Savage
Journal: Circulation (2021)

Introduction: The soluble ST2 (sST2) biomarker is upregulated in response to myocardial strain, remodeling and fibrosis, and may play a role in risk stratification of patients with decompensated Heart Failure with a Reduced Ejection Fraction (HFrEF). The widely accepted prognostic sST2 cut-off for chronic HF is 35ng/ml. What this value would be for acute HF is debated. Objectives: To determine the prognostic value of sST2 in patients admitted with acute decompensated HFrEF. Methods: Between January 2020 and June 2021, consecutive patients hospitalized with HFrEF had sST2 measured at admission (within 24 hours) and at recompensation, as part of the INST2ANT-HF study (UK REC no:19/EE/0269). To determine an appropriate prognostic cut-off, we evaluated the median sST2 in our group as a potential threshold. The primary outcome was mortality at one year. Cumulative incidences, and the relationship between several clinical variables were tested in a Cox multivariate model for the primary outcome and comparisons between groups for events was performed using the χ2 test. Results: In the first 34 consecutive patients (Male 64%, AF 38%) with complete follow up (FU) data, median (IQR) FU was 405 (262-438)days. Median (IQR) age, 77 (60-85)years, mean (SD) EF, 27.9(±12.1). Median (IQR) eGFR, 62 (50-83)ml/min/1.73m 2 . Median (IQR) admission sST2 was 68 (43-91)ng/ml and admission NTproBNP was 7307 (5019-12809)ng/L. The primary endpoint occurred more frequently in patients with admission sST2&gt;68ng/ml (p&lt;0.01) (Fig.1). Conclusion: Our data suggests that in an unselected population of patients admitted with acute decompensated HFrEF, an admission sST2 value &gt;68ng/ml has important prognostic value. Patients with high sST2 values on presentation require close follow up and a lower threshold for consideration of advanced HF therapies. A higher sST2 prognostic cut-off compared to CHF patients may hence be required for risk stratification.
Safety and Efficacy of Damoctocog Alfa Pegol Prophylaxis in Patients with Severe Hemophilia A: Interim Results of a Post-Marketing, Interventional Study
Authors: Pal Andre Holme, Lone Hvitfeldt Poulsen, Claudia Tueckmantel, Maria Teresa Alvarez Roman, Raimondo De Cristofaro
Journal: Blood (2021)
Abstract 12791: Facility Characteristics Associated With High-Performing Outpatient Diabetes and Cardiovascular Disease Risk Factor Program Awardees
Authors: James R Langabeer, Ray Niu, Renee Sednew, Alyssa Pressley, Katherine Overton, Debbie Heard, Michelle Scharnott
Journal: Circulation (2021)

Background: The American Heart Association (AHA) developed an outpatient recognition program centered around the care of patients with type 2 diabetes as part of the Know Diabetes by Heart initiative. The program offers two levels of recognition, Participant and Gold. With over 500 outpatient organizations in the program, specific facility characteristics and component protocols were analyzed to determine what variables increased a site’s likelihood of being a Gold awardee. Methods: The AHA Quality and Analytics team examined multiple data sets from 470 (203 Gold, 267 Participant) award winning facilities. 2020 recognition level was based on aggregate patient data from the 2019 calendar year and self-identified facility characteristics. Univariate regression modeling was carried out to determine facility characteristics that contributed to a site achieving Gold or Participant Target: Type 2 Diabetes award which are displayed in table 1. Results: Higher percentage of Gold-level recipients implemented more treatment plans and protocols for their patients compared to Participant-level recipients. This trend also exists in activities that elevated standard of care for all patients such as assessing for comorbidities, lifestyle modification, and motivation and depression. Conclusion: Facilities characterized as having multiple components in treatment protocols in T2D patients, diabetes self-management and education (DSME), and defined protocols for use of pharmacologic therapy had higher likelihood of achieving Gold award status. In contrast, smaller, non-academic, and high minority population organization were less likely to achieve Gold status, highlighting the care disparities that still need to be addressed. Resources focused on assisting facilities to adopt these evidence-based protocols could help organizations further elevate their T2D management practices, achieve improved patient outcomes and award levels for all organization types.
Abstract 10967: Prognostic Value of a Novel Index: Computational Pressure-Flow Dynamics Derived Fractional Flow Reserve in Stable Coronary Artery Disease Patients with Nonischemic Lesions
Authors: Kwan Yu LI, Lok Yee Jane Lam, Ka Lam Calvin Leung, Mei Zhen Wu, Qingwen Ren, Hang Long Li, Si-Yeung Yu, Yi Kei Stephanie Tse, Shuk Yin Yu, Pui Fai Wong, Yundi Feng, Yunlong Huo, Kai Hang Yiu
Journal: Circulation (2021)

Introduction: Computational pressure-flow dynamics derived fractional flow reserve (caFFR) is an angiographic-derived index to determine the fractional flow reserve (FFR) in patients with stable coronary artery disease (CAD), without the need of invasive pressure wire and hyperaemic stimulus in FFR. Although the safety of FFR-guided deferral of revascularization in non-ischemic lesions is well-established, clinical events still occur. The aim of the study is to investigate the prognostic implications of caFFR in those without significant ischemia. Methods: 513 stable CAD patients (mean age=64.3±11.1, 57.7% male) with all lesions being nonischemic, defined by caFFR&gt;0.75, without undergoing revascularization were recruited. The study population was divided into high (n=240) and low (n=273) caFFR groups, according to the median value of caFFR (0.89). The primary endpoint was 3-year major adverse cardiac events (MACE), defined as a composite of all-cause mortality, myocardial infarction (MI), target vessel revascularization (TVR) and hospitalization for heart failure. Results: A total of 44 composite events occurred, including 17 all-cause mortality, 2 MI, 8 TVR and 17 hospitalization for heart failure. Following multivariate adjustment, patients in low caFFR group had a significantly higher risk of MACE than those in high caFFR group (adjusted hazard ratio [HR], 3.02; 95% confidence interval [Cl], 1.19-7.71; P=0.02). Every 0.01 decrease in caFFR was associated with a higher risk of MACE (adjusted HR, 1.12; 95%Cl, 1.03-1.21; P&lt;0.01) cardiovascular mortality or TVR (adjusted HR, 1.16; 95%Cl, 1.04-1.32; P=0.02) and hospitalization for heart failure (adjusted HR, 1.18; 95%Cl, 1.04-1.34; P=0.01). Conclusions: In stable CAD patients without significant functional ischemia, caFFR provides valuable prognostic information on adverse cardiac outcomes. This novel index could enhance risk stratification in stable CAD patients with nonischemic lesions.
Understanding uncontrolled severe allergic asthma by integration of omic and clinical data
Authors: María Isabel Delgado‐Dolset, David Obeso, Juan Rodríguez‐Coira, Carlos Tarin, Ge Tan, José A. Cumplido, Ana Cabrera, Santiago Angulo, Coral Barbas, Milena Sokolowska, Domingo Barber, Teresa Carrillo, Alma Villaseñor, María M. Escribese
Journal: Allergy (2021)

Asthma is a complex, multifactorial disease often linked with sensitization to house dust mites (HDM). There is a subset of patients that does not respond to available treatments, who present a higher number of exacerbations and a worse quality of life. To understand the mechanisms of poor asthma control and disease severity, we aim to elucidate the metabolic and immunologic routes underlying this specific phenotype and the associated clinical features.Eighty-seven patients with a clinical history of asthma were recruited and stratified in 4 groups according to their response to treatment: corticosteroid-controlled (ICS), immunotherapy-controlled (IT), biologicals-controlled (BIO) or uncontrolled (UC). Serum samples were analysed by metabolomics and proteomics; and classifiers were built using machine-learning algorithms.Metabolomic analysis showed that ICS and UC groups cluster separately from one another and display the highest number of significantly different metabolites among all comparisons. Metabolite identification and pathway enrichment analysis highlighted increased levels of lysophospholipids related to inflammatory pathways in the UC patients. Likewise, 8 proteins were either upregulated (CCL13, ARG1, IL15 and TNFRSF12A) or downregulated (sCD4, CCL19 and IFNγ) in UC patients compared to ICS, suggesting a significant activation of T cells in these patients. Finally, the machine-learning model built including metabolomic and clinical data was able to classify the patients with an 87.5% accuracy.UC patients display a unique fingerprint characterized by inflammatory-related metabolites and proteins, suggesting a pro-inflammatory environment. Moreover, the integration of clinical and experimental data led to a deeper understanding of the mechanisms underlying UC phenotype.
EXTH-78. WP1874, A HIGHLY POTENT UNIQUE DNA BINDING AGENT WITH ENHANCED CNS UPTAKE
Authors: Rafal Zielinski, Roberto Cardenas-Zuniga, Maria Poimenidou, Magdalena Remiszewski, Edd Felix, Izabela Fokt, Stanislaw Skora, Wademar Priebe
Journal: Neuro-Oncology (2021)

Abstract As part of our drug discovery program, we have developed structure-based modular designs of unique DNA-binding agents. The approach combines DNA intercalating and DNA “minor-groove-binding” modules. We have discovered compound WP1244 that potentially binds up to 10 bp long sequences of DNA. The unique and intriguing feature of WP1244 is its high CNS uptake combined with the picomolar to low nanomolar cytotoxicity against ependymoma and glioblastoma multiforme (GBM) cell lines and demonstrated in vivo activity in the orthotopic model of GBM. To improve water solubility and develop an IV formulation, we have synthesized WP1874, a mesylate salt of WP1244, and initiated its preclinical characterization. WP1874, similarly to its parental compound, shows high cytotoxicity in ependymoma, GBM, and medulloblastoma cell lines with IC50 in low nanomolar range and it was up to 100 to 200 times more potent than doxorubicin. Interestingly, WP1874 does not appear to be cytotoxic against normal kidney cells (VeroC1008) with IC50 &amp;gt; 10 μM. Preliminary pharmacokinetic and biodistribution studies performed in CD-1 mice with intact brains revealed enhanced penetration of WP1874 to the brain with Cmax 1.5-fold greater than in plasma. Respectively, WP1874 Cmax in the brain was 2.3 ug/g (~2.0 μM) vs. 1.5 μg/ml (1.3 μM) in plasma. Acute toxicity in intravenously administered WP1874 was LD50 &amp;gt;15mg/kg. No mortalities or any apparent toxicity symptoms were recorded for six intravenous weekly doses of WP1874 at 2.5 or 5 mg/kg in CD-1, Balb/c, or nude athymic mice. Intraperitoneal administration was well-tolerated up to 5 mg/kg given three times a week for four cycles. High CNS uptake, excellent cytotoxicity against different brain cancer cell lines, and low toxicity in vivo and in vitro against normal cells warrant further investigation of WP1874 as a mechanically unique potential anticancer agent against CNS malignancies.
Use of Endpoints in Phase III Randomized Controlled Trials for Hematopoietic Stem Cell Transplantation over the Last 15 Years: A Systematic Review
Authors: Muhammad Umair Mushtaq, Moazzam Shahzad, Ezza Tariq, Muhammad Arslan, Sara Shahid, Raza Ur Rahman, Faryal Murtaza, Iqra Anwar, Qamar Iqbal, Sibgha Gull Chaudhary, Ramesh Balusu, Nausheen Ahmed, Peiman Hematti, Sunil Abhyankar, Joseph P. McGuirk, Leyla Shune
Journal: Blood (2021)