tbuckley/cabot-search huggingface dataset:
Abstract 13883: The Presence of Coronary Calcifications on the Chest CT Scan Performed to Diagnose Covid-19 is Associated With a Worse Prognosis
Authors: Jean Guillaume DILLINGER, Fatima Azzahra Benmessaoud, Theo Pezel, Sebastian Voicu, Georgios Sideris, Lounis Hamzi, Anthony Chauvin, Jean François Gautier, Damien Sène, Patrick Henry
Journal: Circulation (2020)

Introduction: With the coronavirus disease (COVID-19) outbreak, early identification of the most severely impacted patients is essential. Previous cardiovascular (CV) and metabolic diseases affect the COVID-19 prognosis. In high CV risk patients, coronary artery calcification (CAC) is associated with a higher incidence of CV outcomes. Hypothesis: To assess the association between the presence of CAC on the chest CT performed to diagnose COVID-19 and the occurrence of severe COVID-19 outcomes. Methods: Cross-sectional study on consecutive patients from 40 to 80 years of age, hospitalized for COVID-19 infection, with a chest CT without contrast injection performed on the day of admission. Patients with CV disease history were excluded. CAC was defined as any area ≥1mm2 with a density &gt;130 Hounsfield units on the known coronary track. The primary outcome was the rate of patients with severe progression, defined as a score of 5 to 7 on the WHO Blueprint expert group scale (noninvasive or invasive mechanical ventilation, extracorporeal membrane oxygenation, death) within 8 days following hospital admission. Results: 134 consecutive patients (60±8 years) were included. CAC was detected in 61 patients (46%). The primary outcome occurred in 29 (48%) of those 61 patients with CAC compared to 15 (21%) without CAC (HR 2.9; 95% CI [1.6 - 5.3]; p=0.0008). In patients ≤60 years (n=69), CAC was detected in 28% and the primary outcome occurred in 58% of patients with CAC compared to 16% without CAC (p=0.0006). In patients &gt;60 years (n=65), CAC was detected in 63% of patients. In this population, the primary outcome occurred in 43% of patients with CAC compared to 30% without CAC without significant interaction. Multivariate analysis showed that CAC was independently associated with poor prognosis (HR 3.4; 95% CI [1.5 - 7.8]; p= 0.004). Conclusions: The evidence of CAC on initial chest CT performed in patients with COVID-19 is associated with a worse prognosis.
Cbfa1,骨芽細胞-特異的-転写因子,は間葉系幹細胞のSRF調節平滑筋細胞の遺伝子転写を抑制する
Authors: Tanaka Toru, Sato Hiroko, Shimizu Takehisa, Doi Hiroshi, Iso Tatsuya, Kurabayashi Masahiko
Journal: Circulation (2006)
Functional validation of TERT and TERC variants of uncertain significance in patients with short telomere syndromes
Authors: Alejandro Ferrer, Abhishek A. Mangaonkar, Susanna Stroik, Michael T. Zimmermann, Ashley N. Sigafoos, Patrick S. Kamath, Douglas A. Simonetto, Mark E. Wylam, Eva M. Carmona, Konstantinos N. Lazaridis, Steve Peters, Keith Stewart, Eric W. Klee, Eric A. Hendrickson, Mrinal M. Patnaik
Journal: Blood Cancer Journal (2020)
Abstract 12538: Effect of High Intensity Interval Training on High-sensitivity C-reactive Protein in Breast Cancer Patients Undergoing Anthracycline-based Chemotherapy
Authors: Kyuwan Lee, Christina Dieli-Conwright
Journal: Circulation (2020)

Introduction: Anthracycline-based chemotherapies are widely used chemotherapeutic agents for treatment of breast cancers, but these agents increase inflammation in the cardiovascular system. Circulating levels of high sensitivity C-reactive protein (hsCRP) have been validated to assess the degree of inflammation in adults. While exercise has been shown to reduce hsCRP in patients with coronary artery diseases, it is unclear whether high intensity interval training (HIIT) reduces hsCRP in breast cancer patients undergoing anthracycline-based chemotherapy. Hypothesis: We hypothesized that a group of participants that performed the 8-week HIIT intervention would demonstrate maintenance in hsCRP level compared to a group of participants that did not perform HIIT. Methods: Thirty breast cancer survivors were randomized to either the HIIT or control (CON) group. The HIIT group participated in 8 weeks of supervised exercise sessions 3 times/week. The CON group was asked to maintain their current activity levels. Fasting (≥ 12 hours) blood (∽30 cc) was obtained from the antecubital and hsCRP was measured by immunoturbidimetric assay. A paired t-test and 2x2 (group x time) repeated measures ANOVA were used to evaluate changes in hsCRP. Results: At baseline, there were no group differences in age (46.9±9.8 yrs), BMI (31.0±7.5 kg/m 2 ) and blood pressure (123.4 ± 16.8/72.3.9 ± 5.6 mmHg; p&gt;0.05). Following 8 weeks, hsCRP did not significantly change (7.1±2.7 to 8.7±3.5 mg/L) in the HIIT group (p=0.21). However, there was a significant within-group change in the CON group (6.0±3.2 to 10.9.1±2.3 mg/L; p=0.02). There was no group x time interaction following 8 weeks (P=0.93). Conclusions: An 8-week HIIT intervention maintained circulating levels of hsCRP in breast cancer patients receiving anthracycline-based chemotherapy. Future large randomized controlled trials are warranted to investigate the impact of exercise-induced reductions in inflammation while undergoing anthracycline-based chemotherapy.
RNA-binding protein RALY reprogrammes mitochondrial metabolism via mediating miRNA processing in colorectal cancer
Authors: Lei Sun, Arabella Wan, Zhuolong Zhou, Dongshi Chen, Heng Liang, Chuwei Liu, Shijia Yan, Yi Niu, Ziyou Lin, Siyue Zhan, Shanfeng Wang, Xianzhang Bu, Weiling He, Xiongbin Lu, Anlong Xu, Guohui Wan
Journal: Gut (2020)

Objective Dysregulated cellular metabolism is a distinct hallmark of human colorectal cancer (CRC). However, metabolic programme rewiring during tumour progression has yet to be fully understood. Design We analysed altered gene signatures during colorectal tumour progression, and used a complex of molecular and metabolic assays to study the regulation of metabolism in CRC cell lines, human patient-derived xenograft mouse models and tumour organoid models. Results We identified a novel RNA-binding protein, RALY (also known as hnRNPCL2), that is highly associated with colorectal tumour aggressiveness. RALY acts as a key regulatory component in the Drosha complex, and promotes the post-transcriptional processing of a specific subset of miRNAs (miR-483, miR-676 and miR-877). These miRNAs systematically downregulate the expression of the metabolism-associated genes (ATP5I, ATP5G1, ATP5G3 and CYC1) and thereby reprogramme mitochondrial metabolism in the cancer cell. Analysis of The Cancer Genome Atlas (TCGA) reveals that increased levels of RALY are associated with poor prognosis in the patients with CRC expressing low levels of mitochondrion-associated genes. Mechanistically, induced processing of these miRNAs is facilitated by their N6-methyladenosine switch under reactive oxygen species (ROS) stress. Inhibition of the m 6 A methylation abolishes the RALY recognition of the terminal loop of the pri-miRNAs. Knockdown of RALY inhibits colorectal tumour growth and progression in vivo and in organoid models. Conclusions Collectively, our results reveal a critical metabolism-centric role of RALY in tumour progression, which may lead to cancer therapeutics targeting RALY for treating CRC.
YIPF5 mutations cause neonatal diabetes and microcephaly: progress for precision medicine and mechanistic understanding
Authors: Toni I. Pollin, Simeon I. Taylor
Journal: Journal of Clinical Investigation (2020)

Identifying genes that result in monogenic diabetes can provide insights that can build a scientific foundation for precision medicine. At present, nearly 20% of neonatal diabetes cases have unknown causes. In this issue of the JCI, De Franco and Lytrivi et al. sequenced the genome of two probands with a rare neonatal diabetes subtype that also associated with microcephaly and epilepsy. The authors revealed mutations in the YIPF5 gene. YIPF5 resides in the Golgi apparatus and is thought to play a critical role in vesicular trafficking. Notably, disrupting YIPF5 in β cell-based models induced ER stress signaling and resulted in the accumulation of intracellular proinsulin. We believe that utilizing registries and biobanks to reveal other monogenic atypical forms of diabetes is an important approach to gaining insight and suggest that an insulin sensitizer may alleviate ER stress associated with YIPF5 disruption by decreasing the demand for insulin secretion.
Advanced reperfusion strategies for patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation (ARREST): a phase 2, single centre, open-label, randomised controlled trial
Authors: Demetris Yannopoulos, Jason Bartos, Ganesh Raveendran, Emily Walser, John Connett, Thomas A Murray, Gary Collins, Lin Zhang, Rajat Kalra, Marinos Kosmopoulos, Ranjit John, Andrew Shaffer, R J Frascone, Keith Wesley, Marc Conterato, Michelle Biros, Jakub Tolar, Tom P Aufderheide
Journal: The Lancet (2020)
Abstract 14206: Assessing a Clinical Risk Score and the Impact of Race in Breast Cancer Patients at Risk of Cardiotoxicity
Authors: Zachary Brumberger, Mary Branch, Joseph Rigdon, Suji Vasu
Journal: Circulation (2020)

Introduction: Cardiotoxicity is a well-known risk in breast cancer patients treated with anthracyclines and trastuzumab. Ezaz et al. developed a clinical risk score (CRS) to risk stratify these patients. Despite evidence that African American (AA) race is a significant risk factor for cardiotoxicity, no study has assessed the impact of AA race on this CRS. Here we assess the discrimination ability of the Ezaz et al. CRS with the addition of AA race. Methods: This is a retrospective cohort utilizing a registry of 118 patients with stage I-IV breast cancer treated with anthracyclines and/or trastuzumab. Patients without baseline echocardiography data or with baseline LVEF &lt; 50% were excluded. The CRS from Ezaz et al. consisting of age, adjuvant chemotherapy, coronary artery disease, atrial fibrillation or flutter, diabetes mellitus, hypertension, and renal failure was calculated with the addition of AA race. Cardiotoxicity was defined by an LVEF decline of ≥ 10% to LVEF &lt; 53% from baseline. Results: In our 118 patient cohort, the mean age was 59 years, 23 (20%) AA patients, 65 (55%) patients considered low risk (scores of 0-3) and 53 (45%) considered moderate to high risk (scores ≥4). After a follow up of 3 months to 5 years, 14 (12%) patients developed cardiotoxicity. Table 1 lists the CRS changes in statistical characteristics and predictability with the addition of AA race. In comparing the models, the AUC c-statistic increased from 0.609 to 0.642 (95% CI 0.47-0.75, 95% CI 0.49-0.79 respectively; P value = 0.56) with the addition of AA race ( Figure 1 ). Conclusions: In this study, the Ezaz et al. CRS demonstrated improved discrimination and sensitivity with the addition of AA race. This study suggests AA race improves the predictive ability of the Ezaz et al. CRS. Given the limited size of our study, we promote that this should be hypothesis-driving and encourage further investigation on the path to develop an important risk stratification tool.
Chemokine Receptor Antagonists
Authors: Richard Horuk, Howard P. Ng
Journal: Medicinal Research Reviews (2000)

Chemokines belong to a large family of chemoattractant molecules involved in the directed migration of immune cells. They achieve their cellular effects by direct interaction with cell surface receptors. Chemokines appear to be involved in a variety of proinflammatory and autoimmune diseases and this makes them and their receptors very attractive therapeutic targets. This review highlights current efforts toward obtaining highly specific chemokine receptor antogonists and discusses their chemistry and potential role as disease modifiers. ©2000 John Wiley & Sons, Inc. Med Res Rev, 20, No. 2, 155–168, 2000
CLINICAL CHARACTERISTICS OF PERSONS WITH HIV AND VIRAL HEPATITIS B OR C INFECTED WITH SARS-COV-2
Authors: A. Nelson, S. Kottilil, A. Kohli
Journal: Hepatology (2020)

Background: The COVID-19, due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with abnormal liver tests suggestive of hepatocellular injury While the incidence of elevated serum liver biochemistries in hospitalized patients with COVID-19 ranges from 14% to 58%, the impact of concomitant viral hepatitis on outcomes, particularly in patients with underlying immune dysregulation due to HIV, who become infected with SARS-CoV-2 is not known Methods: The CURE HIV-COVID Registry was created by the Institute of Human Virology, University of Maryland, Baltimore (UMB) and Arizona Liver Health  RedCAP de-identified web-based surveys were utilized and the study was deemed to be non-human subjects research Clinicians were encouraged to enter data on the clinical course of their patients with HIV who presented with COVID-19 at time of recovery or improvement, hospitalization or death Patient demographics, HIV CD4 count and viral load, ARV regimen, concomitant medications, comorbidities, concurrent AIDS-defining illnesses, COVID-19 treatment and management, COVID-19 related laboratory values were also collected Results: As of July 17, 2020, the CURE-HIV COVID registry included nine cases of HIV patients with active viral hepatitis who became infected with COVID-19 Three patients had chronic hepatitis B, five chronic hepatitis C and one patient with both HBV and HCV  All cases had laboratory confirmed SARS-CoV-2 diagnosis by positive reverse-transcriptase- polymerase-chain-reaction 50% of patients were active drug users, 75% active smokers and 77 8% had an HIV VL<200 copies/mL 44 4% of patients were black, 37 5% Hispanic and average CD4 was 419 8 +/- 377 4 cells/mm3 (Table 1) Among patients with HIV and HCV 80% had symptoms of COVID-19 and 1 (20%) was asymptomatic 60% of patients with HIV and HCV had cardiovascular comorbidities or cirrhosis and 80% of these patients were hospitalized requiring supplemental oxygen Among three patients with HIV, HBV and COVID-19, 66 7% were symptomatic, all had comorbid cardiovascular disease, and none were hospitalized One patient HIV, HBV and HCV was symptomatic but was not hospitalized No patients with HIV, Hepatitis B and/or C and COVID-19 required mechanical ventilation or died Conclusion: Overall, in this small case series patients with HIV and Hepatitis B and/or C who had COVID-19 had good outcomes including low rates of hospitalization, ventilation, and death Patients had mild elevations in ALT and AST during their infection Patients with chronic hepatitis C had higher rates of cardiovascular comorbidities and hospitalizations and may require additional care if infected or counseling to prevent infection or complications Further data should be gathered to understand the prognosis of HIV patients with viral hepatitis with are infected with SARS-CoV-2, and additional data will be presented(Table Presented)
Abstract 15765: Clinical Significance of Submaximal Parameters of Exercise Stress Test in Characterizing Post-Fontan Patients
Authors: Daphney Kernizan, Gina DAloisio, Bradley Robinson, Takeshi Tsuda
Journal: Circulation (2020)

Background: Fontan patients have diminished exercise capacity relative to healthy peers. Peak oxygen consumption (pVO2) is a useful marker for maximum exercise capacity, though it may not be achievable in certain patients. We studied clinical validity of submaximal parameters in exercise stress test (EST) in post-Fontan patients. Methods: We retrospectively analyzed EST of post-Fontan patients and age-matched controls by cycle ergometer. We obtained peak values of heart rate (pHR), VO2, oxygen pulse (pOP), respiratory quotient (pRQ), and work rate (pWR). Submaximal parameters included ventilatory anaerobic threshold (VAT), slopes of VO2/HR changes (ΔVO2/ΔHR) and HR/WR changes (ΔHR/ΔWR), and oxygen uptake efficiency slope (OUES). Data are shown as mean ± standard deviation. Results: Twenty four single right ventricle (SRV), 12 single left ventricle (SLV), and 24 controls were studied (Table 1).pHR, pVO2, pOP, and pWR were significantly lower in Fontan patients than in controls, but with no significant difference between SRV and SLV. ΔVO2/ΔHR and OUES were significantly lower in Fontan group than controls, whereas VAT and pRQ were comparable in all three groups. VAT was preserved in Fontan groups. Lower slope of ΔVO2/ΔHR and decreased OUES in the Fontan group suggests an intrinsic exercise limitation or limited stroke volume (SV) increase. This was compensated by a higher HR response up to AT, exhibited by the higher slope of ΔHR/ΔWR despite lower pHR in the Fontan group. Conclusions: Peak exercise parameters were significantly lower in Fontan patients although pRQ and VAT were comparable among the three groups. The lower ΔVO2/ΔHR and pOP in Fontan patients suggest limited SV reserve in response to exercise. A combination of lower ΔVO2/ΔHR and higher ΔHR/ΔWR characterizes Fontan patient. Inclusion of submaximal exercise parameters brings additional value in specifying the physiological responses to exercise.
Synergistic anti-inflammatory and osteogenic n-HA/resveratrol/chitosan composite microspheres for osteoporotic bone regeneration
Authors: Limei Li, Mali Yu, Yao Li, Qing Li, Hongcai Yang, Meng Zheng, Yi Han, Di Lu, Sheng Lu, Li Gui
Journal: Bioactive Materials (2020)

The development of functional materials for osteoporosis is ultimately required for bone remodeling. However, grafts were accompanied by increasing pro-inflammatory cytokines that impaired bone formation. In this work, nano-hydroxyapatite (n-HA)/resveratrol (Res)/chitosan (CS) composite microspheres were designed to create a beneficial microenvironment and help improve the osteogenesis by local sustained release of Res. Study of in vitro release confirmed the feasibility of n-HA/Res/CS microspheres for controlled Res release. Notably, microspheres had anti-inflammatory activity evidenced by the decreased expression of pro-inflammatory cytokines TNF-α, IL-1β and iNOS in RAW264.7 cells in a dose dependent manner. Further, enhanced adhesion and proliferation of BMSCs seeded onto microspheres demonstrated that composite microspheres were conducive to cell growth. The ability to enhance osteo-differentiation was supported by up-regulation of Runx2, ALP, Col-1 and OCN, and substantial mineralization in osteogenic medium. When implanted into bone defects in the osteoporotic rat femoral condyles, enhanced entochondrostosis and bone regeneration suggested that the n-HA/Res/CS composite microspheres were more favorable for impaired fracture healing. The results indicated that optimized n-HA/Res/CS composite microspheres could serve as promising multifunctional fillers for osteoporotic bone defect/fracture treatment.
A novel model of alternative NF-κB pathway activation in anaplastic large cell lymphoma
Authors: Hongbo Wang, Wei Wei, Jing-Ping Zhang, Zhihui Song, Yangyang Li, Wenming Xiao, Yijun Liu, Mu-Sheng Zeng, Michael N. Petrus, Craig J. Thomas, Marshall E. Kadin, Masao Nakagawa, Thomas A. Waldmann, Yibin Yang
Journal: Leukemia (2020)
Abstract 17193: Acute and Short-Term Outcomes of Percutaneous Transcatheter Mitral Valve Replacement in Children
Authors: Nicola Maschietto, Ashwin Prakash, Pedro J Del Nido, Diego Porras
Journal: Circulation (2020)

Introduction: Despite the improvement of surgical techniques for mitral valve (MV) repair in children, mitral valve replacement (MVR) is sometimes still necessary. MVR and redo-MVR continue to be burdened by early postoperative mortality and long-term morbidity with only about 75% of these patients being alive or transplant-free 10 years after the initial MVR. Although trans-femoral mitral valve replacement (TMVR) is a well-established intervention in high surgical risk adults, only a few pediatric Valve-in-Valve (ViV) case reports have been published. Hypothesis: We hypothesized that trans-venous transcatheter mitral valve replacement is feasible, safe, and effective in pediatric patients. Methods: Retrospective analysis of pediatric patients who underwent TMVR at Boston Children's Hospital between October 2018 and May 2020 Results: 7 consecutive high surgical risk pediatric patients (median age 9 years, range 8-15) underwent TMVR (6 as ViV, 1 in a native MV). Each patient previously underwent multiple MV surgeries or MVR (median 4, range 2-5) and was highly symptomatic (Ross functional class 3 or 4). The indication for TMVR was mitral stenosis in 5 patients, regurgitation in 1, and mixed disease in 1. TMVR was successful in each patient, effectively reduced the left atrium hypertension (p=0.018), and was carried out without significant complications. Conclusion: Trans-venous trans-catheter mitral valve replacement is an attractive alternative to MVR in high surgical risk patients. In this small series, TMVR was acutely effective and safe, with very encouraging early results.
Abstract PO-007: PRMT5 inhibition sensitizes pancreatic cancer to gemcitabine in orthotopic and metastatic murine models
Authors: William J. Kane, Sara J. Adair, Sarbajeet Nagdas, Denis Liu, Xiaolong Wei, Mazhar Adli, Todd W. Bauer
Journal: Cancer Research (2020)

Abstract Purpose: The purpose of this study was to investigate protein arginine methyltransferase 5 (PRMT5) as a therapeutic target in combination with gemcitabine for pancreatic cancer in preclinical models. Procedures: In an orthotopic xenograft model, PRMT5 wild-type (WT) or knockout (KO) mPanc96 cells were injected into the pancreata of athymic nude mice. Mice were randomized to control or gemcitabine (100 mg/kg) arms. Tumor volume was measured with magnetic resonance imaging (MRI) at 21, 28, and 35 days post-injection. In a liver metastasis model, PRMT5 WT or KO mPanc96 cells were injected into the spleens of athymic nude mice followed by splenectomy after 10 minutes. Mice were randomized to control or gemcitabine (100 mg/kg) arms. Metastatic tumor burden within the liver was measured with in vivo bioluminescence imaging twice weekly for 19 days post-injection. Relative bioluminescence was calculated relative to post-injection day 2. Results: In the orthotopic model, untreated PRMT5 KO tumors exhibited a 46% reduction in tumor volume compared to untreated PRMT5 WT tumors (959 mm−3 vs. 1766 mm−3, p=0.009). Furthermore, gemcitabine-treated PRMT5 KO tumors exhibited a 30% reduction in tumor volume compared to gemcitabine-treated PRMT5 WT tumors (405 mm−3 vs. 579 mm−3, p=0.046). Compared to untreated PRMT5 WT tumors, gemcitabine-treated PRMT5 KO tumors exhibited a 77% reduction in tumor volume (405 mm−3 vs. 1766 mm−3, p=&amp;lt;0.001). In the liver metastasis model, untreated PRMT5 KO cells exhibited a 45% reduction in relative bioluminescence compared to untreated PRMT5 WT metastases (83.3 vs. 152.8, p=0.02). Additionally, gemcitabine-treated PRMT5 KO metastases exhibited a 52% reduction in relative bioluminescence compared to gemcitabine-treated PRMT5 WT metastases (17.2 vs. 36.0, p=0.02). Compared to untreated PRMT5 WT metastases, gemcitabine-treated PRMT5 KO metastases exhibited an 89% reduction in liver tumor burden (17.2 vs. 152.8, p=&amp;lt;0.001). Conclusions: PRMT5 genetic depletion significantly reduces pancreatic cancer growth in murine models of orthotopic growth and liver metastasis. Additionally, PRMT5 depletion improves gemcitabine response in these models. PRMT5 is a possible therapeutic target in pancreatic cancer treatment that necessitates further investigation. Citation Format: William J. Kane, Sara J. Adair, Sarbajeet Nagdas, Denis Liu, Xiaolong Wei, Mazhar Adli, Todd W. Bauer. PRMT5 inhibition sensitizes pancreatic cancer to gemcitabine in orthotopic and metastatic murine models [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-007.