tbuckley/cabot-search huggingface dataset:
Abstract 13667: Programming to S1PR1 <sup>+</sup> Endothelial Cell Population Promotes the Restoration of Vascular Integrity <i>in vivo</i>
Authors: Zahid Akhter, Jagdish Chandra Joshi, Vijay Avin Balaji Ragunathrao, Richard L Proia, Asrar B Malik, Dolly Mehta
Journal: Circulation (2020)

Introduction: Increased endothelial permeability and failure to repair is the hallmark of several vascular diseases including acute lung injury (ALI). However, little is known about the intrinsic pathways that activate the endothelial cell (EC) regenerative programs facilitating thereby tissue repair. Studies have invoked a crucial role of sphingosine-1-phosphate (S1P) in resolving endothelial hyperpermeability through activation of the G-protein coupled receptor, sphingosine-1-phosphate receptor 1 (S1PR1). Hypothesis: We postulate that S1PR1 + EC serve as an endogenous means to prevent endothelial injury. Methods: Studies were made using EC-S1PR1 null mice and S1PR1-GFP reporter mice to trace the generation and characteristics of S1PR1 + EC by exploiting immuno-histochemical analysis and FACS. RNA-seq analysis was performed to identify the genetic signature of S1PR1 + EC. Combination of genetic and pharmacological strategies were included for mechanistic study. Transplantation of S1PR1 + EC and edema measurement was performed in EC-S1PR1 null mice. Results: We observed in a mouse model of endotoxemia that LPS via generation of S1P induced the programming of S1PR1 lo EC to S1PR1 + EC, comprising 80% of lung EC. Their generation preceded the vascular repair phase and these cells were required for reestablishing the endothelial barrier function. Thus, conditional deletion of S1PR1 in EC spontaneously increased lung vascular permeability. RNA-seq analysis of S1PR1 + EC showed enrichment of genes regulating S1P synthesis and transport, sphingosine kinase 1 (SPHK1) and SPNS2, respectively, as well as transcription factors EGR1 and STAT3. EGR1 and STAT3 were essential for transcribing SPHK1 and SPNS2, respectively to increase S1P concentration that served to amplify S1PR1 + EC transition. Transplantation of S1PR1 + EC into injured lung vasculature of EC-S1PR1 -/- mice restored endothelial integrity. Conclusions: Findings illustrate that generation of a specialized S1PR1 + EC population has the potential to activate key endothelial regenerative program mediating vascular endothelial repair raising the possibility of activating this pathway to restore vascular homeostasis in inflammatory lung injury.
Oncolytic vaccinia virus reinvigorates peritoneal immunity and cooperates with immune checkpoint inhibitor to suppress peritoneal carcinomatosis in colon cancer
Authors: Yu Seong Lee, Won Suk Lee, Chang Woo Kim, Seung Joon Lee, Hannah Yang, So Jung Kong, John Ning, Kyung-Mee Yang, Beodeul Kang, Woo Ram Kim, Hong Jae Chon, Chan Kim
Journal: Journal for ImmunoTherapy of Cancer (2020)

Peritoneal carcinomatosis (PC) is a common and devastating manifestation of colon cancer and refractory to conventional anticancer therapeutics. During the peritoneal dissemination of colon cancer, peritoneal immunity is nullified by various mechanisms of immune evasion. Here, we employed the armed oncolytic vaccinia virus mJX-594 (JX) to rejuvenate the peritoneal antitumor immune responses in the treatment of PC.PC model of MC38 colon cancer was generated and intraperitoneally treated with JX and/or anti-programmed cell death protein 1 (PD-1) antibody. The peritoneal tumor burden, vascular leakage, and malignant ascites formation were then assessed. Tumors and peritoneal lavage cells were analyzed by flow cytometry, multiplex tissue imaging, and a NanoString assay.JX treatment effectively suppressed peritoneal cancer progression and malignant ascites formation. It also restored the peritoneal anticancer immunity by activating peritoneal dendritic cells (DCs) and CD8+ T cells. Moreover, JX selectively infected and killed peritoneal colon cancer cells and promoted the intratumoral infiltration of DCs and CD8+ T cells into peritoneal tumor nodules. JX reinvigorates anticancer immunity by reprogramming immune-related transcriptional signatures within the tumor microenvironment. Notably, JX cooperates with immune checkpoint inhibitors (ICIs), anti-programmed death-1, anti-programmed death-ligand 1, and anti-lymphocyte-activation gene-3 to elicit a stronger anticancer immunity that eliminates peritoneal metastases and malignant ascites of colon cancer compared with JX or ICI alone.Intraperitoneal immunotherapy with JX restores peritoneal anticancer immunity and potentiates immune checkpoint blockade to suppress PC and malignant ascites in colon cancer.
18F-Sodium Fluoride PET/CT Findings in Osteitis Condensans Ilii
Authors: Sharjeel Usmani, Najeeb Ahmed, Fareeda al Kandari
Journal: Clinical Nuclear Medicine (2020)

Abstract Osteitis condensans ilii (OCI) is a benign cause of low back pain for which no clear etiology has been identified. We report cases of 2 women with breast cancer referred for 18 F-NaF PET/CT for skeletal staging. Both cases show characteristic findings of OCI on CT images, with 18 F-NaF PET uptake in symptomatic patient and no uptake in asymptomatic. 18 F-NaF PET CT can be useful in evaluating back pain and may be used as an adjunctive biological maker for assessing OCI as a potential cause of pain.
Abstract 15714: Intra-cardiac Pressure Estimation Using Subharmonic Aided Pressure Estimation (SHAPE) - A Clinical Evaluation
Authors: Cara Esposito, Michael P Savage, Praveen Mehrotra, Ira Cohen, David L Fischman, Priscilla Machado, Maureen McDonald, Nicholas J Ruggiero, Paul Walinsky, Alec Vishnevsky, Flemming Forsberg, Marguerite Davis, Kristopher Dickie, Jaydev K Dave
Journal: Circulation (2020)

Introduction: Subharmonic aided pressure estimation (SHAPE) utilizes ambient pressure sensitivity of subharmonic signals from ultrasound contrast agents. The objective was to evaluate SHAPE with Definity (Lantheus Medical Imaging, Inc.) and Sonazoid (GE Healthcare) microbubbles for intra-cardiac pressure estimation. Hypothesis: Errors between SHAPE and pressures obtained during cardiac catheterization ≤ 5 mmHg. Methods: IRB approved this study. Consenting patients received an infusion of Definity (56 patients; 2 vials in 50 mL of saline; infusion rate: 4-10 mL/min) or Sonazoid (77 patients; rate (mL/hour) = 0.18 x weight in kg co-infused with saline at 120 mL/hour) during cardiac catheterization. Subharmonic data was acquired using a SonixTablet (PA 4/2 array; BK Ultrasound) synchronously with pressures from the left and right ventricles and the aorta (for left heart catheterizations only). Subharmonic data (in dB) was converted to pressure values (in mmHg) using calibration factors (mmHg/dB) based on data obtained from the aorta - utilizing pressures from the aorta either during the catheterization procedure or pressures obtained using a SphygmoCor (AtCor Medical Pty. Ltd.) device after the catheterization procedure. Clinically relevant pressures between the SHAPE technique and the pressure catheter were compared. Results: Correlation coefficient between the subharmonic and pressure data was -0.8 ± 0.1. With Definity, mean absolute errors ranged from 2.9 ± 1.5 to 5.0 ± 4.2 mmHg and from 4.4 ± 5.7 to 23.7 ± 28.3 mmHg for calibration factors utilizing aortic pressures from pressure catheter and SphygmoCor, respectively. For Sonazoid microbubbles, these errors ranged from 7.9 ± 12.0 to 10.1 ± 12.4 mmHg and from 7.2 ± 11.5 to 15.0 ± 23.2 mmHg, respectively. Two adverse events occurred during Definity infusion; these were resolved with return to baseline conditions. Conclusion: SHAPE may be useful for estimating intra-cardiac pressures noninvasively.
Abstract 1635: In Vivo Color Mapping Of Shear Stress Along Coronary Arterial Lumen With Multi-detector Computed Tomography
Authors: Yusaku Fukumoto, Takafumi Hiro, Takashi Fujii, Mitsuyuki Hiromoto, Masakazu Tanaka, Michio Yamada, Masunori Matsuzaki
Journal: Circulation (2007)

Background and Purpose: Shear stress is one of the important physical factors in the process of atherosclerosis. However, noninvasive and in-vivo visualization of shear stress distribution along the coronary lumen has been technically difficult, because it is not so possible to assess true three-dimensional (3D) geometrical structure as well as local flow profile in coronary artery for each patient. Recent technology of multi-detector computed tomography (MDCT) can provide an accurate representation of 3D architecture of coronary lumen as well as plaque distribution. This study was to develop a noninvasive way of color mapping of shear stress in coronary artery using a 64-row MDCT, and to preliminarily evaluate its clinical feasibility. Methods: Three-dimensional geometric architecture from patients with mild coronary artery disease was first obtained to develop a 3D mesh polygon model of each left and right coronary artery architecture. The mesh data was then used to perform a shear stress color mapping with a computational fluid-dynamical simulation of finite element model. The spatial resolution ( mesh size ) was 0.05 mm 2 . The flow was considered to be a constant laminar one, and the pulsatile motion was neglected. The relationship between shear stress and plaque accumulation was then examined. Results: According to the MDCT, atherosclerotic plaque formation was frequently observed in the distal potion at the first and second curvature of right coronary artery, and in the outer side of the bifurcation of the left anterior descending and the circumflex coronary artery. The colorized mapping of shear stress revealed that shear stress tended to be lower at the site of plaque accumulation within coronary artery. Conclusion: This method of 3D representation of shear stress distribution along coronary lumen with a 64-row MDCT might be useful for assessing the role of shear stress in atherosclerotic plaque formation or its progression / regression.
CD147 regulates antitumor CD8+ T-cell responses to facilitate tumor-immune escape
Authors: Yatong Chen, Jing Xu, Xiaodong Wu, Hui Yao, Zhou Yan, Ting Guo, Wenjing Wang, Peixiao Wang, Yu Li, Xiangmin Yang, Hao Li, Huijie Bian, Zhi-Nan Chen
Journal: Cellular and Molecular Immunology (2020)
A narrative exploration of the importance of intersectionality in a Black trans woman’s mental health experiences
Authors: Stephanie Anne Shelton, Aryah O. S. Lester
Journal: International Journal of Transgender Health (2020)

Background: The current United States presidential administration's statements and policies have, in a shockingly short time, catastrophically affected people of color and LGBTQIA + communities. And although these numerous discriminatory policies and policy revisions have negatively affected both US people of color and LGBTQIA + people, trans women of color have been disproportionately affected. Even more specifically, when focusing on vulnerability to violence-including murder-it is Black trans women who are most directly affected by the intersections of transphobia and racism in the US. This article explores a Black trans woman's experiences with mental health professionals across two decades and different regions of the US. Aims: This article argues for the necessity of understanding trans people's mental health experiences as necessarily intersectional, in order to more fully appreciate and address the degrees to which factors such as race, socioeconomic class, and geographic context matter in trans people's efforts to access ethical and effective mental healthcare. Methods: Using a theoretical framework informed by Kimberlé Crenshaw's single-axis concept, the authors fully center Aryah's intersectional experiences and counter a single-axis in exploring trans mental health issues, our article relies on a narrative-based approach. As narrative inquiry is a broad field, we selected Butler-Kisber's narrative analytic approach, "Starting with the Story" as our method. The narratives are pulled from approximately 10 intensive qualitative interviews over the course of several months. Discussion: These narratives disrupt the common threads in the literature that ignore the degrees to which race and class matter alongside being a trans woman. In addition, as we noted that nearly all of the mental health literature relied on large-scale survey-based data, this article offers a qualitative narrative exploration of Aryah's experiences and works to humanize trans mental health challenges and needs, while emphasizing the multilayered oppressions and obstacles that affected Aryah.
Clinical characteristics of 51,815 patients presenting with positive and negative SARS-CoV-2 swab results in primary health care settings: Priority populations for vaccination
Authors: Ehab Hamed, Ahmed Sameer Alnuaimi, Mohamed Ahmed Syed, Mohamed Abd Elhamid, Saad Thamer Sedeeq, Bayan Alemrayat, Amina Ali Mohamed Muktar, AlAnoud Saleh AlFehaidi, Hamda Abdulla A/Qotba
Journal: Journal of Infection (2020)

Continuous variables are represented with median and IQR, nominal variables with frequency and column percentage (of valid cases).For continuous variables, where not all cases have data, the number of valid cases is shown.P-values are calculated with Mann-Whitney-U test for continuous variables and Fisher's Exact Test for nominal variables.Area under the Receiver Operating Characteristics (AUROCs) are shown for each biomarker, for each outcome, including 95% confidence intervals.BMI -body mass index; CRP -C-reactive protein; PCT -procalcitonin; AUROC -area under the receiver operating characteristic.
Abstract 17130: Systemic Infection From Non-Pocket Source is Associated With Worse Outcomes Compared With Pocket Source
Authors: MUHAMMAD ZUBAIR KHAN, Kay Khine, Heath Saltzman, Steven P Kutalek, Ashwani Gupta
Journal: Circulation (2020)

Introduction: Systemic infection can occur in patients with cardiac devices due to spread from pocket infection or a non-pocket source. Data comparing outcomes of systemic infection from pocket vs. non-pocket source are lacking Hypothesis: We hypothesized that systemic infection from non-pocket source is associated with worse outcomes compared with pocket source. Methods: We collected data for all patients with systemic infection, who underwent transvenous lead extraction (TLE) between April 2004 and June 2015. Patients were divided into 2 groups- systemic infection from pocket source and non-pocket source. Results: Out of total 700 TLE procedures for infectious indication, 407 patients (58.1%) had evidence of systemic infection. Out of these, 167 (41%) had systemic infection from pocket source and 240 (59%) had systemic infection from non-pocket sources. Patients with pocket source were older (69.7± 13.4 vs. 66.3± 13.5 years, p value 0.011), less likely to be on dialysis (8.4% vs. 23.8%), and more likely to have CRT system (39.5% vs. 23.8%). Pocket source group had higher incidence of coagulase negative staphylococcus infection (32.3% vs. 19.6%) and presence of abandoned leads (32.3% vs. 10.8%).Patients with non-pocket source were more likely to have endocarditis (81.7% vs. 55.1%). There was no difference in TLE procedure outcomes, complications during hospital stay, and 30-day mortality (10.3% vs. 13.7%, p value 0.330). However, 1-year mortality was significantly higher in patients with non-pocket source (41% vs. 28.1%, p value 0.019). Kaplan-Meier survival curves showed worse survival in non-pocket source group up to 6 years of follow up. Conclusions: In conclusion, there is no difference in procedural or short-term outcomes between patients with systemic infection from pocket vs. non-pocket source after TLE. However, patients with systemic infection from non-pocket source are more likely to have endocarditis and have worse long-term mortality.
Abstract 222: Effects of the COVID-19 Pandemic on Care of Out-of-Hospital Cardiac Arrests in Detroit
Authors: Shobi Mathew, Adam D Chalek, Brian J Oneil, Robert B Dunne
Journal: Circulation (2020)

Introduction: March 10 th , 2020 marked the first positive case of SARS-CoV-2 in Detroit. EMS protocol changes were implemented by March 25 th , 2020 in response to the virus. These modifications restricted intubation and allowed medical control to terminate resuscitation in cases of suspected COVID-19 after 10 minutes of CPR without ROSC. Due to global changes in pre-hospital cardiac arrest care caused by COVID-19, we conducted an analysis to determine OHCA characteristics of patients and fatality rates in the COVID-19 era. Methods: CARES data was analyzed between March 10 th , 2019 - April 30 th , 2019 and March 10 th , 2020 - April 30 th, 2020 for comparison before and during the pandemic. Patient demographics, location of arrest, initial rhythms, bystander CPR, EMS interventions and field termination were compared between the two time points. No major factors occurred in 2019 that would potentially skew that data. Descriptive statistics were utilized. Results: A total of 475 CARES patients were included during the study period. Total arrests surged in the COVID-19 era from 180 to 295. OHCA for individuals greater than 50 increased from 130 to 243. An initial rhythm of PEA tripled (10 to 30) during COVID-19, possibly due to hypoxia. The percentage of patients with a shockable rhythm declined (7.8 to 5.1). Bystander CPR decreased from 28.9% (52) to 18.3% (54), secondary to an increase of arrests being in non-public places and concern about disease transmission. Nursing home cardiac arrests increased during COVID from 19 to 73, from the previous year. Placement of an endotracheal tube or supraglottic airway by a basic or advanced unit decreased from 68.3% (123) in pre-COVID-19 era to 37.0% (109) in the current state of the pandemic. Termination of resuscitation in the field occurred over 3-fold from the previous year, an absolute increase from 64 to 204. Conclusion: There was a 61% increase in cardiac arrests during COVID-19 in Detroit. The pandemic and subsequent protocol changes greatly altered practice. COVID-19 has likely directly and indirectly, due to fear of going to the hospital, affected the number of out-of-hospital cardiac arrests. Additional review is being conducted to further delineate arrest etiologies.
The Genomic HyperBrowser: inferential genomics at the sequence level
Authors: Geir K Sandve, Sveinung Gundersen, Halfdan Rydbeck, Ingrid Glad, Lars Holden, Marit Holden, Knut Liestol, Trevor Clancy, Egil Ferkingstad, Morten Johansen, Vegard Nygaard, Eivind Tostesen, Arnoldo Frigessi, Eivind Hovig
Journal: Genome biology (2010)

The immense increase in the generation of genomic scale data poses an unmet analytical challenge, due to a lack of established methodology with the required flexibility and power. We propose a first principled approach to statistical analysis of sequence-level genomic information. We provide a growing collection of generic biological investigations that query pairwise relations between tracks, represented as mathematical objects, along the genome. The Genomic HyperBrowser implements the approach and is available at http://hyperbrowser.uio.no .
Two-Stage Turnbull-Cutait Pull-Through Coloanal Anastomosis for Low Rectal Cancers
Authors: Antonio Manenti, Luca Reggiani-Bonetti, Gianrocco Manco
Journal: JAMA Surgery (2020)

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Abstract PO-042: FGFR1 expression correlates inversely with the in vitro and in vivo efficacy of FGFR inhibitors in pancreatic cancer
Authors: Qingxiang Lin, Andrea Serratore, Eugene Kandel, Robert M. Straubinger
Journal: Cancer Research (2020)

Abstract Aberrant functions of fibroblast growth factor receptors (FGFR) have been implicated in the tumor progression of pancreatic cancer (PaCA). However, the mechanisms of FGFR action and the therapeutic utilities of FGFR inhibitors (FGFRi) in PaCA remain largely under-investigated. Here the mechanisms of FGFR inhibition in PaCA were investigated using pan-FGFRi that are under clinical development and specific shRNA against individual FGFRs. FGFRi treatment, such as BGJ398 and AZD4547, significantly inhibited cell proliferation, migration, and invasion, and cell expression of key markers associated with cell survival and invasiveness was suppressed, in multiple PaCA cell lines. Gemcitabine (Gem) is the standard-of-care for PaCA, and the development of Gem resistance (GemR) compromises its efficacy, thereby Gem only provides modest survival benefits. We found that FGFRi was effective in inhibiting cell proliferation, migration of strongly GemR cells and tumors (named as MIA-GR8 cells and MIA-GR8 tumors) that were all derived by increasing Gem exposure from MIA PaCa-2 cells in vitro and selected by Gem in vivo. These results suggest its potential clinical utility as a class of alternative drug candidates in tumors that acquired GemR. Downregulation of GemR markers mediated by FGFRi treatment in GemR cells also suggested its therapeutic application of FGFRi in combination with Gem, in order to overcome GemR. Mechanistically, the molecular mechanisms of individual FGFR were investigated. shRNA-mediated inhibition of FGFR2 or FGFR3 did not decrease cell growth, and the overexpression of FGFR1 promoted cell migration rather than proliferation. Furthermore, the efficacy of FGFRi treatment was investigated in multiple cell lines and patient-derived xenograft. The inhibitory effects of BGJ398 in PANC-1 cell growth and migration were compromised by exogenic overexpression of FGFR1, and its efficacy on cell viability suppression was correlated with FGFR1 in multiple cell lines. In patient-derived xenografts, the efficacy of FGFRi on tumor growth inhibition was also correlated with FGFR1 expression. These data provide evidence that precision medicine which targets FGFR using FGFRi in PaCA tumors which express relatively modest or low amount of FGFR1 could be more effective than that with a high FGFR1 expression. Citation Format: Qingxiang Lin, Andrea Serratore, Eugene Kandel, Robert M. Straubinger. FGFR1 expression correlates inversely with the in vitro and in vivo efficacy of FGFR inhibitors in pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-042.