tbuckley/cabot-search huggingface dataset:
Abstract P431: <i>Trypanosoma Cruzi</i> Induces Alterations In The Piwi-interacting Rna Expression Profile Of Human Cardiomyocytes During The Early Phase Of Infection
Authors: Kayla J Rayford, Ayorinde Cooley, Maria F Lima, Pius N Nde
Journal: Circulation Research (2021)

Trypanosoma cruzi , the causative agent of Chagas Heart Disease, is an intracellular parasite that was originally endemic to Central and South America. However, due to globalization, the disease is now present in most industrialized countries. About 40% of T. cruzi infected individuals will develop a form of cardiomyopathy including aneurysms, arrythmias, fibrosis, hypertrophy. Host gene expression profile has been shown to be significantly dysregulated to facilitate parasite infection and pathogenesis. The role of gene expression regulatory molecules such as small noncoding RNAs during infection has yet to be fully elucidated. In this study, we aim to evaluate if the parasite can regulate the expression profile of an emerging class of small non-coding RNAs, piwi-interacting RNAs (piRNAs), during the early phase of T. cruzi infection in primary human cardiacmyocytes (PHCM). We challenged PHCM with invasive T. cruzi trypomastigotes and purified RNA for RNA sequencing and analysis. We found that an average of 21,595,866 clean reads (88.4%) mapped to the human reference genome. We observed that the parasite induced significant differential expression of 217 host piRNAs using NOISeq. Furthermore, we employed miRanda and RNA22 to predict mRNA targets of the differentially expressed piRNA. We utilized WEBGESTALT to map piRNAs of interest to their biological pathways. In silico analysis showed that both dysregulated known and novel piRNAs could target several genes of interest including NFATC2, which has been reported to play an important role in the onset of cardiomyopathies reported in Chagasic patients. Our novel findings are the first to show that T. cruzi can induces differential expression of piRNAs during the early phase PHCM infection.
Abstracts
Authors: Didier Ebo, Leander de Puysseleyr, Athina van Gasse, Jessy Elst, Marie-Line van Der Poorten, Margaretha Faber, Christel Mertens, Michel van Houdt, Margo Hagendorens, Luc Sermeus, Joana Vitte, Moïse Michel, Lene Garvey, Mariana Castells, Charles Tacquard, Paul-Michel Mertes, Lawrence B Schwartz, Vito Sabato
Journal: Allergy (2021)

disease has not been studied but mortality among children is very low.It has been suggested that during the COVID-era no asthma medical reduction, or lung function studies should be done routinely.The COVID-19 has affected health care services word wide, and many clinics has ceased office appointments and stopped to taking new patients. 3However, only few clinics reported more negative asthma disease control during COVID-era.Our objective was evaluate in our pediatric allergology unit whether COVID-19 was affected to physician patient contacts or feedback of care.This was an observatory study examining number of patient contacts and patient satisfaction.
Treatments for the Early-Stage Hepatocellular Carcinoma: Laparoscopic Liver Resection or Percutaneous Radiofrequency: How to Make a Decision?
Authors: Jinli Zheng, Wei Xie, Yunfeng Zhu, Li Jiang
Journal: Liver Cancer (2021)

Hepatectomy is still as the first-line treatment for the early stage HCC, but the complication rate is higher than p-RFA and the overall survival rate is comparable in these two treatments. Therefore, the patients with small single nodular HCCs could get more benefit from p-RFA, and we need to do further research about p-RFA.
Anticoagulation Practices Using Activated Clotting Time in Veno-Venous Extracorporeal Membrane Oxygenation for Patients with Respiratory Failure: A Systematic Review and Met-Analysis
Authors: Kanak Parmar, Wasawat Vutthikraivit, Amritpal Singh, Christina Morataya, Gaspar Del Rio Pertuz, Annia Cavazos, Lukman Tijani, Kenneth Nugent, Erwin Argueta
Journal: Blood (2021)
RADT-19. CLINICAL OUTCOMES OF RADIATION THERAPY FOR BRAIN STEM GLIOMA
Authors: Khin Pyone, Lay Myint, Tint Hnin, Aye Khaing
Journal: Neuro-Oncology (2021)

Abstract PURPOSE/OBJECTIVES Brain stem gliomas are up to 20% of all brain tumor in children and unusual in adults. Radiotherapy is mainstay of treatment. Surgery for brain stem glioma is difficult because of anatomical location. This study was performed to evaluate the clinical outcomes of radiotherapy in brain stem glioma. METHODS Retrospective analysis of brain stem glioma patients treated with radiation therapy (54Gy/30 fractions of IMRT/ 3D CRT) with or without surgery or chemotherapy or other agents. RESULTS Twenty-four patients (median age 11.8 years) were treated between 2016 and 2020. Male to female ratio was 2:3. Surgical approach (biopsy and partial removal) was done in 16 patients. Histology revealed that anaplastic ependymoma in 2 patients, low grade astrocytoma in 2 patients, anaplastic astrocytoma in 8 patients, glioblastoma in 4 patients and remaining 8 patients had no histologic diagnosis. Radiotherapy (dose- 54Gy/ 30 fractions) was given with the technique of IMRT or 3D CRT. At the time of follow up, 8 patients had local recurrence, 10 patients died of due to disease and recurrence, 14 patients were alive. Among alive patients, 2 patients were treated with chemotherapy and 12 patients with temozolomide for 12 cycles. Patients who received temozolomide got improvement in performance status and reduced clinical symptoms; among them, 6 patients had more than 50% objective tumor response in radiological findings for follow-up 3-6 months after radiotherapy. The 2-years overall survival (OS) rate was 58.3% and 2-years Event-free Survival (EFS) rate was 50%. The median survival time was 14 months. There is no grade 3 or greater acute and late toxicities. CONCLUSION As the LMIC country with limited resources, our results of radiotherapy followed by temozolomide in brain stem glioma have optimal outcomes. However, prospective studies of this select group of patients with larger number and longer follow up is required.
Abstract 10062: Administrative Data Algorithms Can Identify Patients with Advanced Heart Failure
Authors: Shannon M Dunlay, Amy Glasgow, Saul Blecker, Che Ngufor, Philip Schulte, Margaret M Redfield
Journal: Circulation (2021)

Introduction: Advanced or “Stage D” heart failure (Adv HF) patients are at high risk of poor outcomes. However, recognition of Adv HF is limited as diagnostic criteria are complex. Administrative algorithms to identify Adv HF could enable better understanding of who has advanced HF and lead to enhanced therapeutics development, dissemination, and outcomes. Methods: In a population-based cohort of all Olmsted County, Minnesota residents with ≥1 HF billing code 2007-2017 (n=9881), we identified all patients with Adv HF (n=753) by applying the gold standard European Society of Cardiology Adv HF criteria via manual medical review by a HF cardiologist. The Adv HF index date was the date the patient first met all ESC criteria. We then developed candidate algorithms to identify Adv HF using only administrative data (billing codes and HF prescriptions or comorbidities known to affect HF outcomes), applied them to the entire HF cohort and assessed their ability to identify patients with Adv HF on or after their Adv HF index date. Results: A single hospitalization (Hsp) for HF or ventricular arrhythmias (VA, 2007-2017) identified all patients with Adv HF (sensitivity 100%), but the PPV was low (36.4%). Requiring more Hsp, other signs of Adv HF such as hyponatremia, acute kidney injury, hypotension or high-dose diuretic use decreased the sensitivity but improved specificity and PPV. As Adv HF was relatively uncommon, negative predictive values (NPV) were high regardless of algorithm characteristics. Conclusions: Algorithms using administrative data can identify patients with Adv HF with clinically useful accuracy.
EXTH-08. STAT3 AT THE CROSSROADS OF INNATE IMMUNE ACTIVATION IN GLIOBLASTOMA
Authors: Christina von Roemeling, Lan Hoang-Minh, Bently Doonan, Chenglong Li, Duane Mitchell
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Innate immune cells comprise the majority of the immune microenvironment in glioblastoma (GBM) tumors where they are chiefly thought to foster a hospitable environment for cancer cells by regulating immune suppression and driving resistance to immunotherapy. Of these, myeloid-derived suppressor cells (MDSCs) are regarded as one of the most potent contributors to immune suppression in GBM and thus have become a focus of targeted therapy. Signal transducer and activator of transcription 3 (STAT3) is a key phenotypic regulator of MDSCs. Therefore, we sought to examine if targeted STAT3 inhibition may augment the immunogenicity of these tumors. HYPOTHESIS: Targeted STAT3 inhibition reduces GBM tumor infiltration by MDSCs. METHODS Using syngeneic murine models of GBM, we performed pharmacological inhibition analyses using a specific small molecule inhibitor of STAT3, LLL12B. Circulating numbers of immune cells were assessed in tumor bearing animals with or without concomitant focal radiation. Treated tumors were examined for immune infiltrates, and additional phenotyping analyses were performed. Therapeutic responses to LLL12B alone and in combination with immune checkpoint blockade were evaluated. RESULTS STAT3 is activated in the bone marrow of tumor-bearing animals, preferentially by Gr-1 positive granulocytic myeloid cells. Increased circulating numbers of these cells were also detected. These observations were markedly enhanced in tumor-bearing animals following cranial irradiation. Therapeutic inhibition with LLL12B could mitigate these effects, indicating a dependency on STAT3. Within the tumor compartment, granulocytic myeloid cells that successfully infiltrated following treatment demonstrated a pro-inflammatory phenotype denoted by interferon-gamma expression. Improved survival was also observed following combination treatment with LLL12B and radiation or immune checkpoint blockade. CONCLUSIONS These findings advocate a critically important role for STAT3 in regulating granulocytic myeloid cell mobilization and trafficking to GBM tumors. It further illustrates the plasticity of these cells within these tumors, which may be useful in designing successful immunotherapeutic strategies.
Association of Adherent-invasive <i>Escherichia coli</i> with severe Gut Mucosal dysbiosis in Hong Kong Chinese population with Crohn’s disease
Authors: Zhilu Xu, Xiangqian Dong, Keli Yang, Caroline Chevarin, Jingwan Zhang, Yu Lin, Tao Zuo, Lok Cheung Chu, Yang Sun, Fengrui Zhang, Francis Kl Chan, Joseph Jy Sung, Jun Yu, Anthony Buisson, Nicolas Barnich, Jean-Frédéric Colombel, Sunny Hei Wong, Yinglei Miao, Siew C Ng
Journal: Gut Microbes (2021)

Adherent invasive Escherichia Coli (AIEC) has been implicated in the pathogenesis of Crohn's disease (CD) in Western populations. Whether the presence of AIEC is also seen in CD populations of different genetic susceptibility and has negative impact on host microbiota ecology and therapeutics are unclear. AIEC presence was assessed in ileal tissues of 60 Hong Kong Chinese patients with CD and 56 healthy subjects. Mucosa microbiota was analyzed by 16s rRNA sequencing. Impact of AIEC on the gut microbiota was determined in a mouse model. AIEC was significantly more prevalent in ileal tissues of patients with CD than controls (30% vs 7.1%). Presence of AIEC in ileal tissues was associated with more severe mucosa microbiota dysbiosis in CD with decreased diversity and lower abundance of Firmicutes including butyrate producing Roseburia and probiotic Bacillus. A random forest model predicted the presence of AIEC with area under the curve of 0.89. AIEC exacerbated dysbiosis in dextran sodium sulfate (DSS)-induced colitis mice and led to resistance to restoration of normal gut microbiota by fecal microbiota transplantation (FMT). Proportion of donor-derived bacteria in AIEC-colonized mice was significantly lower than that in uninfected mice. AIEC was prevalent and associated with severe mucosa microbiota dysbiosis in CD in Hong Kong Chinese population. The presence of AIEC impeded restoration of normal gut microbiota. AIEC may serve as a keystone bacterium in CD and impact the efficacy of FMT.
Abstract 13154: Association of Serial Health Status Measurements With Clinical Events: Insights From the ISCHEMIA Trial
Authors: John Saxon, John Spertus, Philip Jones, Daniel B Mark, Sripal Bangalore, Gregg W Stone, Harmony R Reynolds, Judith S Hochman, David J Maron
Journal: Circulation (2021)

Introduction: The Seattle Angina Questionnaire (SAQ), a disease-specific health status measure, has been shown to predict future clinical outcomes in patients with chronic coronary disease (CCD) at a single point in time. The prognostic value of serial SAQ scores in patients with CCD is unknown. Methods: Serial assessments of the 7-item SAQ were obtained in the ISCHEMIA trial of patients with CCD and moderate/severe ischemia. Using Cox regression, we examined the association of baseline and 3-month SAQ-7 Summary Scores (SAQ7-SS) with CV death, MI or unstable angina hospitalization over a 12 month period (between 3 and 15 months after randomization) in patients randomized to conservative treatment. We fit several models including: (a) baseline score only; (b) 3-month score only; (c) 3-month change only; (d) baseline and 3-month score; (e) 3-month change and score. Results: The mean age was 64.3 years in 2095 patients randomized to conservative care with SAQ scores at 1 and 3 months; 78% were men. Twelve-month event rates were 3.3% overall; 2.9% with a 3-month SAQ7-SS ≥75, and 6.9% in those with 3-month scores &lt;50. In unadjusted analyses, higher scores at baseline, 3 months, and greater 3-month improvement were associated with fewer clinical events (Figure 1a). In landmark analyses combining serial scores, neither baseline nor change were significant after adjustment for 3-month score (Figures 1b and 1c). Conclusions: We found that the most recent SAQ score was more predictive of subsequent clinical events than prior scores or changes. Following patients’ health status not only provides an assessment of their current angina control, but also a continuously updatable insight into their risk for subsequent cardiac events.
Abstract 9806: Cardiac Remodeling Post Transcatheter Aortic Valve Replacement: A Comparison Between Veteran and Non-Veteran Populations
Authors: Dhairya Jarsania, Jonathan Meyer, Aamir Twing, Sanket Gokhale, Brody D Slostad, Helena Dickens, Elliott Groves, Mayank M Kansal, Adhir R Shroff
Journal: Circulation (2021)

Background: Transcatheter aortic valve replacement (TAVR) is increasingly utilized in the treatment of aortic valve disease. We assess echocardiographic changes over time to evaluate cardiac remodeling following TAVR between Veteran (VA) and non-VA populations. Methods: Retrospective analysis of 121, single operator TAVR procedures completed between March 2018 and June 2020 at the University of Illinois Hospital in Chicago, IL. Patients included those referred from the affiliated Jessie Brown Veteran Affairs hospital with the following inclusion criteria: transthoracic echocardiogram (TTE) at baseline and 6-month follow-up. Chi-Square tests were used to analyze categorical variables, paired t-tests for continuous variables, and multivariate analysis for subgroups. Results: One hundred and fifteen patients (VA: 59, non-VA: 56) were included in this study. The population had a mean age of 77.0 vs 73.2, BMI of 28.2 vs 30.4, 96.6% vs 56.6% male (p&lt;0.001), and 57.6% vs 33.9% White (p=0.011) between VA and non-VA patients respectively. Overall, there was no significant difference in chamber dimensions, LVEF, and RVSP; however, there was a significant decrease in wall thickness. Multivariate subgroup analysis showed no significant difference between groups except for RVSP. Conclusion: Overall, our study shows positive cardiac remodeling post TAVR, but there is no significant difference when comparing VA to non-VA populations. Although additional studies with larger sample sizes are warranted, the lack of disparity between these subgroups is reassuring.
Abstract 11254: Lin28a Promotes Persistence of Mononucleated Diploid Cardiomyocytes and Cardiac Regeneration After Injury
Authors: Vagner O Rigaud, Robert Hoy, Justin Kurian, Clare Zarka, Michael Behanan, Mohsin Khan
Journal: Circulation (2021)

Developmental cardiac tissue holds a remarkable capacity to regenerate after injury and consists of regenerative mononuclear and diploid cardiomyocytes (MNDCMs). Upon maturation, MNDCMs become binucleated or polyploid and exit the cell cycle. Interestingly, CM metabolism undergoes a profound shift that coincides with the cessation of regeneration in the postnatal heart. However, whether reprogramming metabolism promotes persistence of regenerative MNDCMs enhancing cardiac function and regeneration after injury is unknown. Here, we identify a novel role for RNA-binding protein LIN28a, a master regulator of cellular metabolism, in cardiac regeneration following injury. LIN28a was found as primarily active during cardiac developmental stages and rapidly decreases after birth. LIN28a reintroduction at P0, P3, P5, and P7 decreased maturation-associated polyploidization, nucleation, and cell size enhancing CM cell cycle activity (Ki67+, pHH3+, and AurB+ cells) in LIN28a transgenic pups compared to WT littermates. Moreover, LIN28a overexpression extended CM cell cycle activity beyond P7 concurrent with increased cardiac function 30 days after apical resection. In the adult heart, LIN28a overexpression attenuated CM apoptosis, enhanced CM cell cycle activity, cardiac function, and survival in mice 12 weeks after myocardial infarction compared to WT littermate controls. Alternatively, LIN28a small molecule inhibitor attenuated the pro-regenerative effects of LIN28a on the heart. Mechanistically, Neonatal rat ventricular myocytes (NRVMs) overexpressing LIN28a showed increased glycolysis, ATP production, and activity of metabolic enzymes compared to control. Collectively, LIN28a reprograms CM metabolism and promotes persistence of regenerative MNDCMs in the injured heart enhancing pro-regenerative processes thereby linking CM metabolism to the regulation of ploidy/nucleation and regeneration in the heart.
Abstract 10499: The Heart Failure-Induced Long Non-Coding RNA Heat4 Reduces the Inflammatory Response of Non-Classical Monocytes and Mediates Regeneration After Vascular Injury
Authors: Jasmin M Kneuer, Tim Meinecke, Maximilian Nicolas Moebius-Winkler, Ronald Weiss, Jan Haas, Tania Garfias-Veitl, Stephan von Haehling, Till Keller, Holger Thiele, Philipp Lurz, Timo Speer, Ulrich Laufs, Jes-Niels Boeckel
Journal: Circulation (2021)

Background and Purpose: Activation of the immune system correlates with the severity and the prognosis of patients with heart failure (HF). This study aims to identify and characterize long non-coding RNAs (lncRNAs) as a potential mechanistic link between the pathophysiology of HF and the activation of the immune system. Methods and Results: Using next-generation sequencing, we identified the lncRNA Heat4 to be 2-fold upregulated in the blood of patients with HF compared to controls (N=4; p&lt;0.05). Heat4 induction was validated in an independent second patient cohort via qPCR (HF: N=63; Controls: N=38; p&lt;0.05). Magnetic-activated cell sorting revealed non-classical monocytes as the primary cellular source of Heat4 (N=4; 3.37-fold compared to classical monocytes; p&lt;0.05). This finding was verified by single-cell RNA sequencing. Overexpression of Heat4 in monocytes decreased inflammation, as indicated by a reduction of Interleukin 1β (IL1β) expression (N=6; 38.71% reduction). Accordingly, reduction of Heat4 caused upregulation of IL1β levels (N=5; 1.51-fold; p&lt;0.05). In vivo , overexpression of Heat4 in human monocytes increased vascular regeneration after injury of the carotid artery in NOD-SCID mice (N=6; 1.85-fold compared to injection of control monocytes; p&lt;0.05). Conclusion: The long non-coding RNA Heat4 is elevated in the blood of HF patients. Mechanistically, Heat4 limits the extent of the inflammatory response of non-classical monocytes and leads to a faster regeneration after vascular injury. Therefore, lncRNAs such as Heat4 may provide novel targets for future heart failure treatments.
Immunoglobulin (Ig)A seropositivity against SARS-CoV-2 in healthcare workers in Israel, 4 April to 13 July 2020: an observational study
Authors: Yaniv Lustig, Carmit Cohen, Asaf Biber, Hanaa Jaber, Yael Becker Ilany, Victoria Indenbaum, Sharon Amit, Michal Mandelboim, Ella Mendelson, Gili Regev-Yochay
Journal: Eurosurveillance (2021)

Introduction The COVID-19 pandemic has put healthcare workers (HCW) at significant risk. Presence of antibodies can confirm prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Aim This study investigates the prevalence of IgA and IgG antibodies against SARS-CoV-2 in HCW. Methods Performance of IgA and IgG antibody ELISA assays were initially evaluated in positive and negative SARS-CoV-2 serum samples. IgA and IgG antibodies against SARS-CoV-2 were measured in 428 asymptomatic HCW. We assessed the risk of two groups: HCW with high exposure risk outside work (HROW) residing in areas where COVID-19 was endemic (n = 162) and HCW with high exposure risk at work (HRAW) in a COVID-19 intensive care unit (ICU) (n = 97). Results Sensitivities of 80% and 81.2% and specificities of 97.2% and 98% were observed for IgA and IgG antibodies, respectively. Of the 428 HCW, three were positive for IgG and 27 for IgA. Only 3/27 (11%) IgA-positive HCW had IgG antibodies compared with 50/62 (81%) in a group of previous SARS-CoV-2-PCR-positive individuals. Consecutive samples from IgA-positive HCW demonstrated IgA persistence 18–83 days in 12/20 samples and IgG seroconversion in 1/20 samples. IgA antibodies were present in 8.6% of HROW and 2% of HRAW. Conclusions SARS-CoV-2 exposure may lead to asymptomatic transient IgA response without IgG seroconversion. The significance of these findings needs further study. Out of work exposure is a possible risk of SARS-CoV-2 infection in HCW and infection in HCW can be controlled if adequate protective equipment is implemented.
<i>COVID-19 Vaccination after Allogeneic Stem Cell Transplantation: Real Word Data on Safety and Efficacy. a Single Center Experience.</i>
Authors: Adela Neagoie, Charlotte Sommer, Andrea Gantner, Verena Wais, Jacqueline Schnell, Hannah Simon, Andreas Viardot, Hartmut Döhner, Donald Bunjes, Elisa Sala
Journal: Blood (2021)