tbuckley/cabot-search huggingface dataset:
Intravital imaging and single cell transcriptomic analysis for engraftment of mesenchymal stem cells in an animal model of interstitial cystitis/bladder pain syndrome
Authors: Hwan Yeul Yu, Seungun Lee, Hyein Ju, Youngkyu Kim, Jung-Hyun Shin, HongDuck Yun, Chae-Min Ryu, Jinbeom Heo, Jisun Lim, Sujin Song, Sanghwa Lee, Ki-Sung Hong, Hyung-Min Chung, Jun Ki Kim, Myung-Soo Choo, Dong-Myung Shin
Journal: Biomaterials (2021)

Mesenchymal stem cell (MSC) therapy is a promising treatment for various intractable disorders including interstitial cystitis/bladder pain syndrome (IC/BPS). However, an analysis of fundamental characteristics driving in vivo behaviors of transplanted cells has not been performed, causing debates about rational use and efficacy of MSC therapy. Here, we implemented two-photon intravital imaging and single cell transcriptome analysis to evaluate the in vivo behaviors of engrafted multipotent MSCs (M-MSCs) derived from human embryonic stem cells (hESCs) in an acute IC/BPS animal model. Two-photon imaging analysis was performed to visualize the dynamic association between engrafted M-MSCs and bladder vasculature within live animals until 28 days after transplantation, demonstrating the progressive integration of transplanted M-MSCs into a perivascular-like structure. Single cell transcriptome analysis was performed in highly purified engrafted cells after a dual MACS−FACS sorting procedure and revealed expression changes in various pathways relating to pericyte cell adhesion and cellular stress. Particularly, FOS and cyclin dependent kinase-1 (CDK1) played a key role in modulating the migration, engraftment, and anti-inflammatory functions of M-MSCs, which determined their in vivo therapeutic potency. Collectively, this approach provides an overview of engrafted M-MSC behavior in vivo, which will advance our understanding of MSC therapeutic applications, efficacy, and safety.
Mutational Landscape in Myeloproliferative Neoplasms: Implications on Prognosis and Clinical Management
Authors: Aaron T. Gerds
Journal: Journal of the National Comprehensive Cancer Network (2021)

Mutations are a critical piece in understanding how myeloproliferative neoplasms (MPNs) occur, specifically the pathobiology of JAK/STAT activation. Mutations play such an important role, in fact, that they are a key part of the diagnostic classification for these diseases. Furthermore, the mutational landscape of MPNs affects both the prognosis and the biology of disease progression. Current research in the field is focused on understanding how and why these mutations occur, as well as how to attack them to address disease at the time of progression or even before disease progression has occurred.
Abstract 9111: The Impact of Covid-19 Pandemic on the Treatment of Myocardial Infarction- A Single Center Experience
Authors: Ahmad Al-abdouh, Anas Bizanti, Oluwaseun Fashanu, Akhila Mohan, Raveena Edwards, Anne Sill, David Wang
Journal: Circulation (2021)

Introduction: The corona virus disease-2019 (COVID-19) pandemic has been associated with decrease in the rate of myocardial infarction (MI), and this is likely related to patients delaying seeking care due to COVID-19 concerns. Methods: In this retrospective observational study, we compared all patient encounters who presented with MI to Ascension Saint Agnes Hospital, Baltimore, MD from March to December 2020 with a cohort of patient encounters who presented with MI during an equivalent period in 2019. We analyzed the data using Statistical Package for Social Sciences (SPSS) and used two sample t-test and Chi-square x 2 to compare the outcomes between the two cohorts as appropriate. Results: We had 275 MI admissions that met our inclusion criteria. When comparing MI encounters in 2020 with encounters in 2019, there were no significant differences in mortality (2.1% vs. 4.5%, p=0.274), acute renal failure(14.9% vs. 18.7%, p=0.403), or intensive care unit admission (7.1% vs. 7.5%, p=0.892). There were no significant differences in modalities of treatment including cardiac catheterization (94.3% vs. 95.5%, p=0.652), or medical treatment alone (13.5% vs. 18.7%, p=0.241) in 2020 vs. 2019. Referrals for coronary artery bypass graft surgery (CABG) were significantly higher in 2020 than in 2019 (8.5% vs. 3.0%, p=0.050). When comparing patients who presented during the first 5 months of the pandemic (March-July) with patients who presented in the last 5 months of the pandemic in 2020 (August - December); there were significant decrease in rate of cardiac catheterization (90.5% vs. 98.5%, p = 0.041), and significant increase in rate of medical treatment alone (18.9% vs. 7.5%, p = 0.047) in the first 5 months. Conclusions: The first five months of the pandemic were associated with a significant decrease in rates of pursuing cardiac catheterization along with an increase rates of medical treatment alone compared with the following five months.
Abstract 11776: Deeper Than the Pandemic: A Retrospective Study Evaluating Outcomes and Mortality Rates on Hospitalized SARS-CoV-2 Negative Patients Presenting With Non-ST Elevation Myocardial Infarction
Authors: Manvir Wadhwa, Harjeet Singh, Scott Kubomoto, Ayutyanont Napatkamon, Heineke Hyunju, Mimi S Biswas
Journal: Circulation (2021)

Introduction: The SARS-CoV-2 pandemic has left an ever-lasting impression on the healthcare system, however, less attention has been paid to hospitalized patients without SARS-CoV-2. This study evaluated hospitalized, non- COVID patients presenting with NSTEMI and the affect on trends in mortality rate, initial troponin value, and length of stay compared to the prior non-pandemic period Hypothesis: During the pandemic period, length of stay and mortality were increased compared to the prior non-pandemic year. Methods: This retrospective multi-center study involved a total of 62,690 patients admitted across 151 hospitals within the HCA network. Eligible patients had a negative SARS-CoV-2 polymerase chain reaction (PCR) upon admission. Using the time period of March - May of both 2019 and 2020, a total of 43,129 patients were investigated in 2019 and 19,561 patients in 2020. Results: Initial troponin values were higher in the non-pandemic year of 2019 (3.0 +/- 11.97, std error: 0.0645, p = 0.001) when compared to those of the pandemic period of 2020 (2.69 +/- 9.88, std error: 0.0075, p = 0.001). However, outcomes including mortality and length of stay were found to be worse in 2020 compared to 2019 (Mortality: 7.53% vs 6.65% respectively p= &lt;.001 ) &amp; (length of stay: 6.97 +/- 7.77 days vs 6.00 +/- 7.15 days respectively, p= &lt;0.001). Multivariable Logistic Regression analysis revealed that those NSTEMI patients hospitalized in 2020 had a 13% higher likelihood of mortality compared those in 2019 (OR 1.13 [95% CI (1.05, 1.21), p= &lt;0.001), independent of demographic, comorbidities, or home use statins, anti-platelet agents, or beta blockers. Additionally, length of stay in 2020 was increased by +0.935 days compared to 2019 (std error 0.063, p= &lt;0.001) while holding other factors constant. Conclusions: This study demonstrated hospitalized NSTEMI patients without SARS-CoV-2 suffered an increase in mortality rates and length of stay compared to the prior year despite having lower troponin values. Multiple factors may have contributed to the burden faced by hospitals including delays in presentation, lack of outpatient care, and fear of contracting the virus while hospitalized. Further investigation into the impact of the pandemic remains vital for future of healthcare
Abstract P315: Shortening The Thick Filament By Partial Deletion Of Titin’S C-zone Alters Cardiac Function By Reducing The Operating Sarcomere Length Range Of The Heart.
Authors: Mei Methawasin, Gerrie P Farman, Shawtarohgn Granzier-Nakajima, Joshua G Strom, John E Smith, Henk L Granzier
Journal: Circulation Research (2021)

Titin’s C-zone is the inextensible part of titin that binds along the thick filament at its cMyBP-C -containing region. Previously it was shown that deletion of titin’s super-repeats C1 and C2 ( Ttn ΔC1-2 mouse model) results in shorter thick filaments and contractile dysfunction, but LV chamber stiffness is normal. Here we studied the contraction-relaxation kinetics from the time-varying elastance of the left ventricle (LV) and from cellular work loops of intact loaded cardiac myocytes. Ca 2+ transients were also measured as well as crossbridge cycling kinetics and Ca 2+ sensitivity of force. It was found that intact cardiomyocytes of Ttn ΔC1-2 mice exhibit systolic dysfunction and impaired relaxation. The time-varying elastance of the LV chamber showed that the kinetics of LV activation are normal but that relaxation is slower in Ttn ΔC1-2 mice. The slowed relaxation was, in part, attributable to an increased myofilament Ca 2+ sensitivity and slower early Ca 2+ reuptake. Dynamic stiffness at the myofilament level showed that cross-bridge kinetics are normal, but that the number of force-generating cross-bridges is reduced. In vivo sarcomere length (SL) measurements in the mid-wall region of the LV revealed that the operating SL range is shifted in Ttn ΔC1-2 mice towards shorter lengths. This normalizes the apparent cell and LV chamber stiffness but reduces the number of force generating cross-bridges due to suboptimal thin and thick filament overlap. Thus the contractile dysfunction in Ttn ΔC1-2 mice is not only due to shorter thick filaments but also to a reduced operating sarcomere length range. Overall these results reveal that for normal cardiac function, thick filament length regulation by titin’s C-zone is critical.
Abstract 12773: Sources of Health Information and Health-Seeking Patterns of Filipinos in Rural Communities in the Philippines
Authors: Lorraine S Evangelista, Elizabeth Lorenzo
Journal: Circulation (2021)

Background: Rural healthcare delivery and access have various obstacles due to limited infrastructure for health promotion, limited health information sources, reliance on medical advice from multiple sources, and a lack of skilled rural healthcare practitioners. The disparity in access to healthcare is ultimately why healthcare in rural communities is inadequate. Aims: This cross-sectional study describes sources of health information and health-seeking behaviors (e.g., type of healthcare provider, response to illness) of adults (aged ≥ 18) living in rural, largely underserved communities in the Philippines. Methods: Participants completed a survey assessing health information sources and health-seeking habits. Descriptive statistics and χ 2 -tests were used to compare age groups (young vs. old 60]) and sex. Results: Surveys were completed by 1203 persons (65% female, age 50 ±18 years). The preferred source of health information was friends and family (57%), followed by social media (28%) and healthcare providers (15%). Participants said they sought healthcare largely from physicians (60%), herbalists (12%), nurses (5%), and quack doctors (5%) or a combination of providers (12%). When they were ill, the majority (70%) visited a healthcare provider, while 48%, 39%, and 30% self-medicate, sought advice from a rural health clinic, or pray, respectively. There were no variations in the sources of information, care provider preferences, or illness response between the sexes. Younger persons were more inclined to seek health information on social media and from a physician. By contrast, older persons were more likely to seek advice from friends and relatives and contact a herbalist or quack physician. Conclusions: Our results highlight the need for well-structured programs and campaigns to address the population's demands understandably. Additionally, it emphasizes the importance of enhancing the quality of information available to rural communities and integrating friends and relatives, social media, and healthcare providers to provide evidence-based health information. Finally, more research is required to identify why so many people sought medical advice from friends and family members rather than licensed healthcare professionals.
Abstract 14395: Transcriptomes of Thrombi Retrieved by Mechanical Thrombectomy Can Distinguish Ischemic Stroke Subtypes
Authors: Vincent M Tutino, Sarah Fricano, Muhammad Waqas, Adnan H Siddiqui, Kerry E Poppenberg
Journal: Circulation (2021)

Introduction: Determination of stroke etiology is crucial for prevention of secondary ischemic events. Diagnostic workups are intensive and expensive, and in cryptogenic cases are fruitless. Hypothesis: We hypothesize that thrombi from strokes of different etiologies have unique transcriptomic profiles. Methods: In 76 patients undergoing mechanical thrombectomy, we collect retrieved thrombi and extracted RNA on the PerkinElmer Chemagic 360. 48 samples of sufficient quality underwent 100-cycle, paired-end RNAseq on the Illumina NovaSeq6000. Transcriptomes with &lt; 10M assigned reads were excluded; counts were normalized by transcripts per million. Significant differentially expressed genes (DEGs) between stroke subtypes (defined by Trial of Org 10172 in Acute Stroke Treatment) were identified by a false discovery rate-corrected F-test (q-value)&lt;0.05 and an absolute fold-change&gt;2. Bioinformatics and gene ontology enrichment analyses were performed to understand the pathobiology of DEGs. Results: We analyzed transcriptomes from 38 thrombi; 6 large artery atherosclerosis (LAA), 20 cardioembolism (CE), 5 other vasculopathy (OV), and 7 cryptogenic. Comparing CE to LAA, we found 218 DEGs that were related to greater Immune System Processes, Coagulation, and Regulation of Macrophage Activation. OV vs. LAA showed 414 DEGs, which reflected increased Regulation of Wound Healing, Biological Adhesion, and Cell Migration. Comparing CE to OV revealed 341 DEGs that were related to increased Cell Activation and Leukocyte Activation. Principal component analysis showed separation between these subtypes and that cryptogenic samples may be related to CE or OV. Conclusion: Transcriptomes of stroke thrombi can delineate etiology. CE thrombi are more inflammatory, while OV thrombi reflect wound healing responses. Cryptogenic thrombi may be related to multiple etiologies.
Modifiable risk factors for neurocognitive and psychosocial problems after Hodgkin lymphoma
Authors: AnnaLynn M. Williams, Sedigheh Mirzaei Salehabadi, Mengqi Xing, Nicholas S. Phillips, Matthew J. Ehrhardt, Rebecca Howell, Yutaka Yasui, Kevin C. Oeffinger, Todd Gibson, Eric J. Chow, Wendy Leisenring, Deokumar Srivastava, Melissa M. Hudson, Leslie L. Robison, Gregory T. Armstrong, Kevin R. Krull
Journal: Blood (2021)
Abstract 12572: Low Incidence of Cardiovascular Events in Patients With Metastatic Sarcoma Using Upfront Dexrazoxane and High-Dose Doxorubicin
Authors: Joshua D Mitchell, Brian Van Tine, Angela C Hirbe, Peter Oppelt, Ashley Frith, Richa Rathore, Fei Wan, Shellie Berry, Michele Landeau, George Heberton, John Gorcsan, Peter Huntjens, Yoku Soyama, Justin M Vader, Jose Alvarez-Cardona, Kathleen Zhang, Daniel Lenihan, Ronald Krone
Journal: Circulation (2021)

Background: Prognosis for soft tissue sarcoma (STS) remains poor with a progression free survival of 4.6 months. Doxorubicin is a central and effective treatment option, though cardiotoxicity frequently limits dosing. Dexrazoxane has been shown to protect the heart but questions of possible reduced tumor efficacy have limited dexrazoxane to be used only after administration of 300 mg/m2 of doxorubicin. We explored the use of up-front dexrazoxane to mitigate the cardiotoxic effects of doxorubicin in a single-arm non-inferiority trial patients with STS. Methods: Patients with metastatic or unresectable STS without prior anthracycline treatment were eligible for enrollment. The study was powered to demonstrate that dexrazoxane does not prevent a decrease of progression free survival (PFS), with a PFS more than 3.7 months considered non-inferior. Secondary aims included cardiac related mortality and the incidence of heart failure or cardiomyopathy. Patients were allowed to continue on doxorubicin beyond 600mg/m2 if they were deriving benefit and were not demonstrating evidence of cardiac dysfunction. Patients with concerns about cardio-toxicity were referred to a cardio-oncologist. Results: 62 patients were started on study treatment and had at least one year of follow-up. Patients received a median of five cycles (375 mg/m2, range 75-3075 mg/m2) of doxorubicin. The upfront use of dexrazoxane with doxorubicin demonstrated a PFS of 5.5 months (95% CI 4.2-8.4 months). No patients required cardiac hospitalization on protocol. Two patients developed new LV dysfunction with LV ejection fraction below 50% on core lab evaluation with recovery in one and persistent LVEF &lt; 50% in one. There were no deaths attributed to doxorubicin. Conclusion: Up-front dexrazoxane prevented severe cardiac systolic dysfunction in patients receiving high cumulative doses of doxorubicin without reducing progression free survival (5.5 months vs 4.6 months in historical controls).
EXTH-75. APPLICATION OF TUMOR TREATING FIELDS (TTFIELDS) TO THE HEAD AND TORSO OF MICE WITH THE DEDICATED INOVIVO SYSTEM
Authors: Shiri Davidi, Roni Blatt, Mijal Munster, Anna Shteingauz, Yaara Porat, Adel Zeidan, Tal Marciano, Zeev Bomzon, Moshe Giladi, Uri Weinberg, Yoram Palti
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Tumor Treating Fields (TTFields) therapy is an approved anti-cancer treatment for glioblastoma and mesothelioma. TTFields are delivered to patients continuously by two sets of arrays placed on opposite sides of the body at the tumor region to generate two perpendicular electric fields. Previously, in vivo studies of TTFields were limited due to the lack of a dedicated system that could maintain continuous and adequate contact of the arrays with the animal’s skin as well as the stress imposed on the animals by individual housing and the motility limitations they experience during treatment. METHODS Different electrode layouts were explored to optimize the intensity of the electric fields delivered to the target locations (therapeutic threshold &amp;gt;1 V/cm). The ability of various adhesive materials and wire coiling prevention strategies to increase TTFields device usage was examined. Stress reduction with different housing methods was evaluated via clinical examination of the animals. RESULTS Optimal array layouts were identified based on simulation data for TTFields delivery to the torso or the head of the mouse. Compacting conductors into a single printed circuit cable connected to a novel electric swivel machine resulted in fewer wire entanglements, and the improved adhesives resulted in fewer array replacements, overall elevating device usage. Improved cage design permitted pairs of mice to maintain social interactions while individually housed. Less weight loss was seen for animals housed in the dyadic relative to the standard solitary cages, indicating reduced stress. CONCLUSIONS The inovivo system provides means for continuous delivery of therapeutic levels of TTFields to the head and torso of mice while minimizing animal stress and increasing device usage. The new head arrays enable application of TTFields to the head of mice for the first time, allowing expansion of glioblastoma treatment research.
MYC break-apart FISH probe set reveals frequent unbalanced patterns of uncertain significance when evaluating aggressive B-cell lymphoma
Authors: Marie-France Gagnon, Kathryn E. Pearce, Patricia T. Greipp, Xinjie Xu, Nicole L. Hoppman, Rhett P. Ketterling, Ellen D. McPhail, Rebecca L. King, Linda B. Baughn, Jess F. Peterson
Journal: Blood Cancer Journal (2021)
Abstract 12579: Empagliflozin and the Risk of Atherosclerotic Events and Hospitalization for Heart Failure: Updated Analysis From the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study
Authors: Phyo Htoo, Helen Tesfaye, Mehdi Najafzadeh, Sebastian Schneeweiss, Dureshahwar Jawaid, Deborah J Wexler, Robert Glynn, Lisette Koeneman, Anouk Deruaz Luyet, Julie Paik, Elisabetta Patorno
Journal: Circulation (2021)

The EMPA-REG OUTCOME trial reported cardioprotective effects of empagliflozin (EMPA) in patients with established cardiovascular diseases (CVD). We evaluated the association between EMPA and the risk of cardiovascular events, versus GLP1 receptor agonist (GLP-1RA) or DPP4 inhibitor (DPP-4i) in the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) study of type 2 diabetes (T2D) patients in routine care, updating a prior analysis using data from 08/2014 through 09/2018. Using 2 commercial and Medicare claims databases, we identified 88,826 pairs of 1:1 propensity score-matched (PSM) T2D patients ≥18 years initiating EMPA or a GLP-1RA [Cohort 1], and 69,610 pairs initiating EMPA or a DPP-4i [Cohort 2]. Our outcomes were (i) a composite of atherosclerotic cardiovascular diseases (ASCVD): MI, stroke, unstable angina and coronary revascularization and (ii) heart failure hospitalization in primary discharge (HHF-Primary) or any position (HHF-Any). In each cohort, we estimated hazard ratios (HR) and 1-year numbers needed to treat (NNT), accounting for death as a competing risk, pooled across databases adjusting for &gt;140 baseline covariates. After PSM, exposure groups had similar characteristics (Table 1). Compared to GLP-1RA, EMPA had a similar risk of ASCVD [HR (95% CI): 1.05 (0.96,1.15)] and a decreased risk of HHF-Primary: 0.64 (0.54,0.76) and HHF-Any: 0.83 (0.77,0.90). One-year NNTs for EMPA vs GLP-1RA were 235 for HHF-Primary and 133 for HHF-Any. Results for EMPA vs DPP-4i were similar: ASCVD [0.94 (0.85,1.03)], HHF-Primary [0.46 (0.38,0.55)] and HHF-Any [0.66 (0.60,0.72)]. One-year NNTs for EMPA vs DPP-4i were 100 for HHF-Primary and 52 for HHF-any. Results for the individual components of the ASCVD outcome were consistent. The updated analysis from EMPRISE showed that relative to GLP-1RA or DPP-4i, EMPA was associated with a similar risk of ASCVD and a reduced risk of HHF in routine care, with more precise estimates compared to prior analyses.
Abstract 14243: The Apelin Mimetic Peptide (2Nal) Partially Inhibits the Transient Outward Potassium Current (Ito) in Rat Cardiomyocytes; a Potential Pharmacological Agent Against Brugada Syndrome
Authors: Juan Antonio Contreras Vite, Alexandre Murza, Kien TRAN, Philippe Sarret, Mannix Auger-messier, Olivier Lesur, Eric Marsault, Robert Dumaine
Journal: Circulation (2021)

Introduction: Brugada syndrome (BrS) is an inherited disease characterized by ventricular cardiac arrhythmias leading to sudden cardiac death. One potential cause for arrhythmias is a disruption of the balance between the depolarizing fast sodium inward current (I Na ) and its opposing transient outward currents (I to ) favoring a faster repolarization during phase one of the action potential (AP). Hypothesis: BrS is mainly associated with a reduction in I Na amplitude caused by dominant mutations in the gene SCN5A encoding cardiac sodium channels. However, recent studies have shown that gain-of-function mutations in KCND3, the gene encoding Kv4.3 channels, increase I to amplitude. Therefore, targeting I to to modulate the balance of current during phase one of the AP represents a promising therapeutic approach to BrS, Methods: We used Patch-Clamp technique to test the effect of 2Nal, a newly synthesized peptide derived from apelin, on I to in rat ventricular cardiomyocytes. Apelin is an endogenous neurotransmitter with strong inotropic effects on cardiac cells. Results: We found that apelin had no effect on I to . In contrast, 2Nal maximally inhibited 46.9% ± 3.4 (n=9) of I to with an IC 50 =0.29 nM but did not change its kinetics, thus indicating that 2Nal acts as a partial blocker. The voltage dependence of potassium channels availability was not modified, suggesting that 2Nal simply reduced the conductance of each channel contributing to I to . Conclusions: Because of its partial antagonist effect on ITo, 2Nal provide a safety margin that could be potentially useful for the treatment of Brugada syndrome.