tbuckley/cabot-search huggingface dataset:
Abstract 12020: Heterogeneity and Plasticity of Cardiac Fibroblasts Governing Reparative Lymphangiogenesis After Myocardial Infarction: A New Therapeutic Approach for Heart Failure
Authors: Yuimi Matsuoka, Bertrand D Segard, Tomomi Imamura, Kodai Kimura, Ayana Ikeda, Makoto Matsuyama, Mami Arai, Takeshi Machino, Akira Sato, Nobuyuki Murakoshi, Takahiro Iwamiya
Journal: Circulation (2021)

Introduction: Cardiac lymphangiogenesis has attracted attention as a therapeutic target after myocardial infarction (MI). Lymphangiogenic remodeling has been observed after MI in adult and fetal hearts; however, reparative lymphangiogenic remodeling is only observed in fetal hearts. The factors that determine the fate of this phenomenon have not been fully elucidated. Hypothesis: We demonstrated that a specific population of VCAM1 + human fetal cardiac fibroblasts (fCFs) restore cardiac function post-MI by lymphangiogenesis. Thus, we hypothesize that adult cardiac fibroblasts (aCFs), compared to fCFs, possess a different distribution of fibroblasts with differing lymphangiogenic potential. Furthermore, we also hypothesize that aCFs can be exogenously manipulated to acquire fCFs-like reparative lymphangiogenic potential, which can be used as a cell therapy for heart failure. Methods: Flow cytometry assessed CD90 and VCAM1 expression of aCFs and fCFs. To shift aCFs towards a fCF phenotype, TNF-α and IL-4 were added to culture medium. aCF subpopulations were intramyocardially injected in nude rats and swine post-MI with subsequent echocardiography. Myocardial tissue staining (Sirius Red, LYVE1) and RNA-seq were performed to identify the molecular mechanism. Results: aCFs and fCFs exhibited different distributions of CD90 and VCAM1 expression, where aCFs showed lower CD90 and VCAM1 expression. The addition of TNF-α and IL-4 shifted the localization of VCAM1 + aCFs towards a fCF distribution by activation of NF-κB. VCAM1 + CD90 + fCFs-like aCFs provided a sustained improvement in left ventricular ejection fraction and showed reduced fibrosis and increased lymphangiogenesis. This effect was recapitulated in a large animal model. In terms of the molecular mechanism, 13 candidate genes were identified. Conclusions: These findings suggest that the heterogenous and plastic polarity of aCFs and fCFs determines the fate of the lymphangiogenic response after MI and that this response can be regulated by 13 genes. This artificial creation of the VCAM1 + fCFs-like fibroblast environment after MI has enabled a clinical trial for a new cell therapy for inducing reparative lymphangiogenesis (clinical trial ID: jRCT2033210078).
Abstract 11354: Registry Based Mid-Term Mortality After Stenting of Distal Left Main Stenosis with Regular, Third Generation Drug Eluting Stent or Dedicated Bifurcation Stent or Surgery
Authors: Dobrin Vassilev, Galina Zlatancheva, Monika Shumkova, Pavel Nikolov, Kiril Karamfiloff, Robert Gil
Journal: Circulation (2021)

Background: The aim of the current study was to identify predictors of cardiac mortality at mid-term follow up after PCI (DES vs. dedicated bifurcation stent) or CABG. Methods: All patients with distal LM stenosis≥50% were included in prospective registry starting from 01.2015.The exclusion criteria for registry are cardiogenic shock,a priory life expectancy duration &lt; 1 year,lack of inform consent.All patients were prospectively followed about the alive status through the national security number data base. Results: For three year follow up period (median 35 months, IQR 18-50) 303 patients were included.220 patients were stented with 3 rd generation DES, 43 with dedicated bifurcation stent BiOSS (Balton, Poland),and rest were sent for CABG.The mean age was 67 ± 10 years,72% were males,37% diabetics,all with hypertension, 97% dyslipidemia,15% PAD,9% COPD,16% carotid artery disease,previous MI 28%,previous PCI 50% - without significant difference between three groups.The frequency of acute coronary syndrome during admission was 11%-without difference in frequency between groups.The patient referred to CABG had significantly lower left ventricular EDV and ESV,more severe mitral regurgitation and kinetic disturbances,higher SYNTAX score and longer lesion length.On univariate COX regression analysis, the following factors were associated with mortality:age, NYHA class,GFR,baseline troponin,hemoglobin,LV EF,mitral regurgitation,kinetics disturbances,treatment with beta blockers,ACE inhibitors,statin,atrial fibrillation,SYNTAX score,lesion length.The type of treatment was not associated with differences in mortality.On COX multiple regression survival analysis independent predictors of survival were:age (HR=1.036, CI 1.005-1.068, p= .023);COPD (HR= 2.313, CI 1.170-4.572, p= .016);GFR (HR= .988, CI .978-1.000, p= .048);hemoglobin(HR= .970, CI .955- .986, p= .000);left ventricular EF (HR= .958, CI .832- .985, p= .003). Conclusions: The type of treatment was not associated with mid-term mortality.Our data demonstrate that dedicated bifurcation stent could be used safely for distal LM stenosis treatment with similar safety as 3 rd generation DES.
PATH-43. RAMAN SPECTROSCOPY AS A TOOL IN NEUROSURGERY
Authors: Felix Kleine Borgmann, Gilbert Georg Klamminger, Laurent Mombaerts, Karoline Klein, Finn Jelke, Giulia Mirizzi, Redouane Slimani, Michel Pilot, Andreas Husch, Michel Mittelbronn, Frank Hertel
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Raman Spectra have been shown to be sufficiently characteristic to their samples of origin that they can be used in a wide range of applications including distinction of intracranial tumors. While not replacing pathological analysis, the advantage of non-destructive sample analysis and extremely fast feedback make this technique an interesting tool for surgical use. METHODS We sampled intractanial tumors from more than 300 patients at the Centre Hospitalier Luxembourg over a period of three years and compared the spectra of different tumor entities, different tumor subregions and healthy surrounding tissue. We created machine-learning based classifiers that include tissue identification as well as diagnostics. RESULTS To this end, we solved several classes in the intracranial tumor classification, and developed classifiers to distinguish primary central nervous system lymphoma from glioblastoma, which is an important differential diagnosis, as well as meningioma from the surrounding healthy dura mater for identification of tumor tissue. Within glioblastoma, we resolve necrotic, vital tumor tissue and peritumoral infiltration zone.We are currently developing a multi-class classifier incorporating all tissue types measured. CONCLUSIONS Raman Spectroscopy has the potential to aid the surgeon in the surgery theater by providing a quick assessment of the tissue analyzed with regards to both tumor identity and tumor margin identification. Once a reliable classifier based on sufficient patient samples is developed, this may even be integrated into a surgical microscope or a neuronavigation system.
SCHIZOPHRENIA IN RELATION TO BLOOD GROUPS ABO AND BLOOD TYPES Rh. D. AND MN
Authors: C. R. LAFFERTY, WILMA J. KNOX
Journal: American Journal of Psychiatry (1958)

In comparing blood groupings and the Rh.D. factor in Negro schizophrenics with controls and with former findings, interesting differences were noted: 1. Significant differences were found between schizophrenic subjects and control subjects in two of the three studies, one of which used Negro subjects and the other, white subjects. 2. The Rh.D. factor rather than the blood group accounted for the differences between schizophrenics and normals in two of the studies. 3. The Rh.D. factor operated differently in the Negro groups than in the white groups. Negro schizophrenics showed a greater proportion of Rh negative, and white schizophrenics showed a greater proportion of Rh positive. 4. The Negro control group and the white control group had different distributions of the Rh.D. factor and of blood group characteristics; therefore, data from Negro and white subjects could not be appropriately combined.
B cell receptor isotypes differentially associate with cell signaling, kinetics, and outcome in chronic lymphocytic leukemia
Authors: Andrea N. Mazzarello, Eva Gentner-Göbel, Marcus Dühren-von Minden, Tatyana N. Tarasenko, Antonella Nicolò, Gerardo Ferrer, Stefano Vergani, Yun Liu, Davide Bagnara, Kanti R. Rai, Jan A. Burger, Peter J. McGuire, Palash C. Maity, Hassan Jumaa, Nicholas Chiorazzi
Journal: Journal of Clinical Investigation (2021)

In chronic lymphocytic leukemia (CLL), the B cell receptor (BCR) plays a critical role in disease development and progression, as indicated by the therapeutic efficacy of drugs blocking BCR signaling. However, the mechanism(s) underlying BCR responsiveness are not completely defined. Selective engagement of membrane IgM or IgD on CLL cells, each coexpressed by more than 90% of cases, leads to distinct signaling events. Since both IgM and IgD carry the same antigen-binding domains, the divergent actions of the receptors are attributed to differences in immunoglobulin (Ig) structure or the outcome of signal transduction. We showed that IgM, not IgD, level and organization associated with CLL-cell birth rate and the type and consequences of BCR signaling in humans and mice. The latter IgM-driven effects were abrogated when BCR signaling was inhibited. Collectively, these studies demonstrated a critical, selective role for IgM in BCR signaling and B cell fate decisions, possibly opening new avenues for CLL therapy.
Abstract 13896: Trends in Aortic Dissection Mortality Rates by Sex and Age in the United States, 1999-2019
Authors: Salik Nazir, Ayla Cash, Abdul Minhas, Robert W Ariss, Hani Jneid
Journal: Circulation (2021)

Introduction: Despite evolving medical risk assessment and surgical interventions, acute aortic dissection (AD) remains a life-threatening condition with a high mortality. Here, we report sex and age-stratified AD mortality rates in the United States. Methods: Death certificate data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database were used to determine all-cause AD-related mortality trends from 1999 to 2019 among adults older than twenty-five. For the age stratified analysis, crude mortality rates (CMRs) per 100,000 people were calculated for five sub-groups (25-39, 40-54, 55-69, 70-84, and ≥ 85 years old). For the sex stratified analysis, age-adjusted mortality rates (AAMRs) per 100,000 people were calculated for males and females. Annual percentage change (APC) with 95% confidence intervals (CI) were calculated for both analyses. Results: Female AAMRs decreased between 1999 and 2012 (APC -1.5 [95% CI -1.8 to -1.1]) and increased between 2012 and 2019 (APC 3.1 [95% CI 2.3 to 4]). Similarly, male AAMRs decreased between 1999 and 2013 (APC -1.6 [95% CI -2 to -1.3]) and increased between 2013 and 2019 (APC 2.6 [95% CI 1.4-3.8]). Male AAMRs were consistently higher than female AAMRs (Figure 1). CMRs for those 25-39 and 40-54 increased significantly between 1999 and 2019 (APC 1.3 [95% CI 0.9 to 1.8] and APC 1.3 [95% CI 0.9 to 1.7], respectively). Among individuals 55-69, 70-84, and ≥85 years old, CMRs between 1999 and 2012 decreased significantly. However, CMRs for these three groups increased significantly between 2012 and 2019, with those ≥85 years old having the highest APC during this period (APC 3.8 [95% CI 2.4 to 5.2]). Conclusions: AD death rates are increasing among all sex and age subgroups over the past decade. To mitigate the burden of AD-related mortality, future studies are needed to examine the reasons for these observed trends.
NCOG-22. RETROSPECTIVE ANALYSIS OF VISUAL OUTCOMES AFTER BEVACIZUMAB-BASED THERAPY IN OPTIC PATHWAY GLIOMA
Authors: Benjamin Siegel, Tobey MacDonald, David Wolf
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Patients with optic pathway glioma (OPG) are vulnerable to debilitating visual impairment. Consequently, vision stabilization is a primary treatment goal. Bevacizumab has demonstrated promising effects on radiographic tumor burden, but less is known about its impact on vision. Our objective was to characterize visual outcomes associated with bevacizumab-based therapy (BBT) in OPG. METHODS This is a single-institution, retrospective review of patients treated with BBT for OPG from 2011 to 2020. Ophthalmologic and radiographic data were abstracted before and after treatment. Clinically significant visual acuity (VA) impairment was defined as logMAR &amp;gt; 0.5 and change in VA was defined as change from baseline of logMAR ≥ 0.2. RESULTS Sixteen patients (13 sporadic OPG, 3 NF1-associated OPG) with evaluable vision outcomes were identified. Treatment indications were radiographic progression (N=15) and vision deterioration (N=4). Prior to BBT, 15 (94%) had failed at least one chemotherapy regimen. BBT regimens included bevacizumab/irinotecan (N=12), bevacizumab monotherapy (N=3) and bevacizumab/vinblastine (N=1). Nine patients (56%) had baseline VA impairment. Thirteen patients (81%) had stable or improved vision after BBT, including 8 of 9 with baseline VA impairment and all 4 patients with vision deterioration as a treatment indication. Eleven patients (69%) had radiographic progression following BBT (Median time-to-progression 66 weeks, IQR 27 weeks), 9 of whom had stable vision at time of progression. There were no associations between VA and age at treatment, NF1-status, histology, or BBT regimen. CONCLUSIONS BBT was associated with favorable visual outcomes for most patients with OPG in this modest retrospective cohort. Consistent with prior research, radiographic and ophthalmologic outcomes were discordant; a majority of patients experienced progressive disease despite stable vision. Next steps include (1) assessing visual field and optical coherence tomography outcomes in the same cohort and (2) comparing outcomes for BBT with other common therapies including carboplatin/vincristine and vinblastine.
Abstract P478: Farnesyl Transferase Inhibitor Tipifarnib Reduces Circulating Exosomes And Protects Against Pressure Overload-mediated Cardiac Hypertrophy
Authors: Vandana Mallaredy
Journal: Circulation Research (2021)

Clinically, Hypertrophic cardiomyopathy (HCM) in response to pathophysiological stress is one of the major initiating factors for the onset of cardiac remodeling leading to heart failure. Studies have revealed that HCM characterized by left ventricular hypertrophy, hypercontractility, and impaired relaxation is mainly driven by an intricate crosstalk among the multiple cellular and molecular mechanisms, which leads to heart failure. In agreement with this observation, we investigated if the Tipifarnib-mediated reduction/alteration of circulating exosomes mediates cardiac cell communication during HCM. Several studies have shown Tipifarnib as a potential Farnesyl transferase inhibitor. However, in recent past Tipifarnib has been shown to target exosomes biogenesis by several mechanisms such as inhibiting Ras pathway, ESCRT complex etc. Tipifarnib treatment in mice significantly reduced the number of circulating plasma exosomes. We examined the response of Tipifarnib treatment (10 mg/kg body weight) in C57BL6J male mice subjected to transverse aortic constriction (TAC) surgery. Untreated TAC mice had worsening of systolic Left Ventricular function at 4 weeks that further deteriorated at 8 weeks, while the treatment with Tipifarnib substantially improved cardiac functions by reducing cardiac hypertrophy and fibrosis. Exosomes isolated from the serum of sham and TAC mice with or without tipifarnib were used for in vitro cell based analyses. We observed that the exosomes isolated from Tipifarnib treated TAC mice reduced isoproterenol (ISO)-induced cardiomyoblast hypertrophy and fibrosis-associated genes in adult cardiac fibroblasts. Taken together, our studies suggest Tipifarnib protects against pressure overload induced cardiac remodeling and dysfunction by altering hypertrophic and fibrotic gene expression, by potentially reducing circulating exosomes or by altering exosome contents. Ongoing studies will clarify the molecular mechanisms of these observations.
Abstract 10802: Validation of Artificial Intelligence for Assessing Right Ventricular Function by Transthoracic Echocardiography Compared to Cardiac MRI
Authors: Brian C Hsia, Ashton Lai, Rajeev Samtani, Solomon Bienstock, Steve Liao, Eric Stern, Gina LaRocca, Javier Sanz, Stamatios Lerakis, Gregg W Stone, Lori Croft, Martin Goldman
Journal: Circulation (2021)

Introduction: Cardiac MRI (CMR) is the gold standard for right ventricular function (RVF) because echo assessment is limited. Potential echo parameters to assess RVF include RV fractional area change (FAC), RV free wall strain (FWS), and tricuspid annular plane systolic excursion (TAPSE) on apical 4-chamber (A4C) view. We compared a new Artificial Intelligence method that tracks the RV almost instantaneously in a single 4-chamber view (AI, LVivo RV®, DiA Imaging, Figure) to quantify RVF vs CMR. Methods: We compared AI RVF against CMR in 125 pts. Abnormal LVEF and RVEF were defined as &lt;57% and &lt;49% respectively. Echo closest to CMR date was analyzed with AI RV to obtain FAC, FWS, and TAPSE. We defined abnormal RVF by DiA Imaging’s predetermined thresholds. Sensitivities and specificities for abnormal RVF and chi-square (χ 2 ) tests were calculated for each variable against CMR RVEF. Results: Of the 125 pts, 55 (44%) were female with median age 55 [Q1 44, Q3 67] years. Thirty pts (24%) had abnormal RVEF and 78 (62.4%) had abnormal LVEF by CMR. All pts with abnormal RVEF had abnormal LVEF. Compared to CMR, AI RV sensitivities and specificities for abnormal RVEF were: FAC 87% and 60%, FWS 80% and 61%, TAPSE 77% and 54%, any 2 criteria 83% and 61%, and all 3 criteria 63% and 69%. AI RV χ 2 values were: FAC 19.9 (p&lt;0.001), FWS 15.4 (p&lt;0.001), TAPSE 8.4 (p=0.004), any 2 criteria 18.0 (p&lt;0.001), and all 3 criteria 10.4 (p=0.001). Conclusions: This is the first validation of a novel AI method (LVivo RV®) that can detect RV dysfunction using 3 standard RV measurements from a single A4C view with good sensitivity and specificity compared to volumetric CMR as the gold standard.
Abstract 13329: Isolation of Matured Human iPSC-Derived Ventricular Cardiomyocytes Using Synthetic microRNA Switch
Authors: Takeshi Hatani, Yuta Tsujisaka, Kenji Miki, Takeshi Kimura, Hirohide Saito, Yoshinori Yoshida
Journal: Circulation (2021)

Background: For disease modeling and drug screening using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), matured iPSC-CMs are required to understand the underlying mechanism of diseases and to get the candidate drug’s deleterious features. We have shown that synthetic mRNAs encoding a fluorescent protein tagged with complementary sequences against specifically expressed microRNA (miRNA-switch) can be efficiently used for purification. Using miRNA-switch, we evaluated the selection method of matured iPSC-CMs from iPSC-CMs. Methods: We used miR-208a as a specific miRNA of CMs and miR-Matured CM (miR-MCM). We synthesized miR-208a-responsive GFP-coding mRNA (miR-208a-GFP switch), and miR-MCM-iRFP670 switch and control tagBFP mRNA and transfected them into iPSC-CMs. Results: After transfection of these mRNA, 25±5% of miR-208a positive cells were positive for miR-MCM. We also compared miR-208a positive and miR-MCM positive cells to miR-208a positive and miR-MCM negative cells by qPCR and electron microscopy (EM). MiR-208a-positive and miR-MCM-positive cells showed significantly higher expression of matured CM-related genes such as MYH7 and MYL2. In EM observation, miR-208a-positive and miR-MCM-positive cells showed M-bands, while miR-208a-positive and miR-MCM-negative cells did not display M-bands. Conclusions: We demonstrated that miR-MCM could be used for the marker of matured iPSC-CMs. The synthetic miR-switch for miR-MCM efficiently isolate matured iPSC-CMs, enabling its application in disease modeling and drug screening using differentiated cells from iPSCs.
Biodegradable magnesium barrier membrane used for guided bone regeneration in dental surgery
Authors: Patrick Rider, Željka Perić Kačarević, Akiva Elad, Drazen Tadic, Daniel Rothamel, Gerrit Sauer, Fabien Bornert, Peter Windisch, Dávid Botond Hangyási, Balint Molnar, Emely Bortel, Bernhard Hesse, Frank Witte
Journal: Bioactive Materials (2021)

Barrier membranes are commonly used as part of the dental surgical technique guided bone regeneration (GBR) and are often made of resorbable collagen or non-resorbable materials such as PTFE. While collagen membranes do not provide sufficient mechanical protection of the covered bone defect, titanium reinforced membranes and non-resorbable membranes need to be removed in a second surgery. Thus, biodegradable GBR membranes made of pure magnesium might be an alternative. In this study a biodegradable pure magnesium (99.95%) membrane has been proven to have all of the necessary requirements for an optimal regenerative outcome from both a mechanical and biological perspective. After implantation, the magnesium membrane separates the regenerating bone from the overlying, faster proliferating soft tissue. During the initial healing period, the membrane maintained a barrier function and space provision, whilst retaining the positioning of the bone graft material within the defect space. As the magnesium metal corroded, it formed a salty corrosion layer and local gas cavities, both of which extended the functional lifespan of the membrane barrier capabilities. During the resorption of the magnesium metal and magnesium salts, it was observed that the membrane became surrounded and then replaced by new bone. After the membrane had completely resorbed, only healthy tissue remained. The in vivo performance study demonstrated that the magnesium membrane has a comparable healing response and tissue regeneration to that of a resorbable collagen membrane. Overall, the magnesium membrane demonstrated all of the ideal qualities for a barrier membrane used in GBR treatment.
INNV-01. THE CASE OF LEPTOMENINGEAL CARCINOMATOSIS RELATED HYDROCEPHALUS MANAGED WITH SYSTEMIC AND INTRATHECAL CHEMOTHERAPY
Authors: Maya Hrachova, Maciej Mrugala
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Leptomeningeal carcinomatosis (LC) is an end-stage sequela of metastatic cancer that commonly leads to severe neurological symptoms due to hydrocephalus and commonly treated with surgery or radiation. As these procedures are invasive and have associated risks, chemotherapy could be a great alternative. We report a case of a hydrocephalus related to LC in a patient with Stage IV breast cancer that resolved after the administration of HD-MTX and intrathecal cytarabine. CASE A 64-year-old right-handed woman with Stage IV ER positive, PR positive, HER2 negative invasive lobular carcinoma of the left breast on chemotherapy with palbociclib and alpelisib who presented with mild occipital headaches, diplopia and imbalance. Imaging revealed an extensive abnormal leptomeningeal enhancement withing the posterior fossa compatible with leptomeningeal carcinomatosis. CSF cytology was consistent with metastatic adenocarcinoma. Liquid biopsy detected circulating tumor cells. During the admission for the cycle 1 of systemic chemotherapy with HD-MTX and intrathecal cytarabine, neurological status deteriorated as she became stuporous due to the newly developed moderate obstructive and communicating hydrocephalus. Surgical innervation was considered but given her response to serial Ommaya taps and dexamethasone, we proceeded with observation. Symptomatic improvement was noted within few days and confirmed on imaging showing the resolution of previously seen hydrocephalus. DISCUSSION This case highlights the role of non-invasive combination of systemic and intrathecal chemotherapy in patients with LC-related hydrocephalus aimed to preserve patient’s quality of life. No relevant disclosures.