tbuckley/cabot-search huggingface dataset:
Abstract 9126: Renal Venous Stasis Index Reflects Renal Congestion and Predicts Adverse Outcomes in Patients With Heart Failure
Authors: Himika Ohara, Akiomi Yoshihisa, Yukiko Sugawara, Yasuhiro Ichijo, Yu Hotsuki, Koichiro Watanabe, Yu Sato, Yusuke Kimishima, Tomofumi Misaka, Masayoshi Oikawa, ATSUSHI KOBAYASHI, Yasuchika Takeishi
Journal: Circulation (2021)

Background: It has been recently reported that the renal venous stasis index (RVSI) assessed by renal Doppler ultrasonography provides information to stratify pulmonary hypertension (PH) leading to right-sided heart failure. However, the clinical significance of RVSI on heart failure (HF) patients has not been fully examined. We aimed to clarify the associations of RVSI with parameters of cardiac function and right heart catheterization (RHC), as well as with prognosis, in patients with HF. Methods: We performed renal Doppler ultrasonography, echocardiography and RHC in hospitalized patients with HF (n = 388). The RVSI was calculated as follows: RVSI = (cardiac cycle time - venous flow time)/cardiac cycle time. These patients were divided into three groups based on RVSI: RVSI 0 group (RVSI = 0, n = 260, 67%), low RVSI group (0 &lt; RVSI ≤ 0.21, n = 65, 17%) and high RVSI group (RVSI &gt; 0.21, n = 63, 16%). We examined associations between RVSI and parameters of cardiac function and RHC, and followed up for cardiac events such as cardiac death and worsening HF. Results: There were significant correlations between RVSI and right atrial pressure (R = 0.253, P &lt;0.001), right atrial end-systolic area (R = 0.327, P &lt;0.001) and inferior vena cava diameter (R=0.327, P &lt;0.001), but not with cardiac index (R = -0.019, P = 0.769). During the follow-up periods (median 412 days), cardiac events occurred in 60 patients. In the Kaplan-Meier analysis, accumulated cardiac event rate increased with advancing RVSI (Figure, log-rank, P = 0.001). In the multivariable Cox proportional hazard analysis, cardiac event rate was independently associated with RVSI (hazard ratio, 1.874; 95% confidence interval, 1.023-3.435, P = 0.042). Conclusion: RVSI assessed by renal Doppler ultrasonography reflects right-sided overload and is associated with adverse prognosis in HF patients.
Clinical Outcomes of Adults and Young Adults (AYA) with Acute Lymphoblastic Leukemia (ALL): A Multicenter Analysis of Pediatric-Inspired Protocol (MASPORE) Vs Hyper-CVAD in Singapore
Authors: Sai Lon Wann, Tertius Tuy, Victor Ling Wei Teik, Christian Gallardo, Lip Leong Chong, Samuel Sherng Young Wang, Nurul Aidah Abdul Halim, Yar Myint Zay, Allen Eng Juh Yeoh, Sampath Venkata Sreekanth, Chin Hin Ng, Michelle Poon, Gee Chuan Wong, Melissa Ooi
Journal: Blood (2021)
Modeling clonal hematopoiesis in umbilical cord blood cells by CRISPR/Cas9
Authors: Friederike Christen, Raphael Hablesreiter, Kaja Hoyer, Cornelius Hennch, Antje Maluck-Böttcher, Angela Segler, Annett Madadi, Mareike Frick, Lars Bullinger, Franziska Briest, Frederik Damm
Journal: Leukemia (2021)

Abstract To investigate clonal hematopoiesis associated gene mutations in vitro and to unravel the direct impact on the human stem and progenitor cell (HSPC) compartment, we targeted healthy, young hematopoietic progenitor cells, derived from umbilical cord blood samples, with CRISPR/Cas9 technology. Site-specific mutations were introduced in defined regions of DNMT3A , TET2 , and ASXL1 in CD34 + progenitor cells that were subsequently analyzed in short-term as well as long-term in vitro culture assays to assess self-renewal and differentiation capacities. Colony-forming unit (CFU) assays revealed enhanced self-renewal of TET2 mutated ( TET2 mut ) cells, whereas ASXL1 mut as well as DNMT3A mut cells did not reveal significant changes in short-term culture. Strikingly, enhanced colony formation could be detected in long-term culture experiments in all mutants, indicating increased self-renewal capacities. While we could also demonstrate preferential clonal expansion of distinct cell clones for all mutants, the clonal composition after long-term culture revealed a mutation-specific impact on HSPCs. Thus, by using primary umbilical cord blood cells, we were able to investigate epigenetic driver mutations without confounding factors like age or a complex mutational landscape, and our findings provide evidence for a direct impact of clonal hematopoiesis-associated mutations on self-renewal and clonal composition of human stem and progenitor cells.
Letter to the editor: Genetically determined IBD is associated with decreased risk of Alzheimer’s disease: a Mendelian randomisation study
Authors: Xingzhi Guo, Li Chong, Xin Zhang, Rui Li
Journal: Gut (2021)

We read with great interest the observation of eminent colleague Chen et al showing that patients with IBD had a higher incidence of dementia, particularly Alzheimer’s disease (AD, HR=6.19).1 Due to various confounding factors (age of onset, treatment, smoking, body mass index, etc), it is usually hard to evaluate the causal link between IBD and AD using observational studies. Two-sample Mendelian randomisation (MR) treated genetic variants as instrumental variables (IVs) for exposures, effectively minimising the impact of confounding factors.

Using two-sample MR analysis, we adopt the publicly available summary statistics from large-scale genome-wide association studies (GWAS) to investigate the causal effect of IBD (Ncases=12 882; Ncontrols=21 770),2 including UC and Crohn’s disease (CD), on AD (Ncases=21 982, Ncontrols=41 944) of European descent.3 Briefly, single-nucleotide polymorphisms (SNPs) with p values less than 5E–08 for IBD were selected as IVs and were clumped based on the linkage disequilibrium (LD) structure (R2 <0.0001 within 10 000 kb, the 1000 Genomes Project European panel). In …
Highly immunogenic cancer cells require activation of the WNT pathway for immunological escape
Authors: Yoshiko Takeuchi, Tokiyoshi Tanegashima, Eiichi Sato, Takuma Irie, Atsuo Sai, Kota Itahashi, Shogo Kumagai, Yasuko Tada, Yosuke Togashi, Shohei Koyama, Esra A. Akbay, Takahiro Karasaki, Keisuke Kataoka, Soichiro Funaki, Yasushi Shintani, Izumi Nagatomo, Hiroshi Kida, Genichiro Ishii, Tomohiro Miyoshi, Keiju Aokage, Kazuhiro Kakimi, Seishi Ogawa, Meinoshin Okumura, Masatoshi Eto, Atsushi Kumanogoh, Masahiro Tsuboi, Hiroyoshi Nishikawa
Journal: Science Immunology (2021)

PD-1 blockade exerts antitumor effects by reinvigorating tumor antigen–specific CD8+ T cells. Whereas neoantigens arising from gene alterations in cancer cells comprise critical tumor antigens in antitumor immunity, a subset of non–small cell lung cancers (NSCLCs) harboring substantial tumor mutation burden (TMB) lack CD8+ T cells in the tumor microenvironment (TME), which results in resistance to PD-1 blockade therapy. To overcome this resistance, clarifying the mechanism(s) impairing antitumor immunity in highly mutated NSCLCs is an urgent issue. Here, we showed that activation of the WNT/β-catenin signaling pathway contributed to the development of a noninflamed TME in tumors with high TMB. NSCLCs that lacked immune cell infiltration into the TME despite high TMB preferentially up-regulated the WNT/β-catenin pathway. Immunologic assays revealed that those patients harbored neoantigen-specific CD8+ T cells in the peripheral blood but not in the TME, suggesting impaired T cell infiltration into the TME due to the activation of WNT/β-catenin signaling. In our animal models, the accumulation of gene mutations in cancer cells increased CD8+ T cell infiltration into the TME, thus slowing tumor growth. However, further accumulation of gene mutations blunted antitumor immunity by excluding CD8+ T cells from tumors in a WNT/β-catenin signaling-dependent manner. Combined treatment with PD-1 blockade and WNT/β-catenin signaling inhibitors induced better antitumor immunity than either treatment alone. Thus, we propose a mechanism-oriented combination therapy whereby immune checkpoint inhibitors can be combined with drugs that target cell-intrinsic oncogenic signaling pathways involved in tumor immune escape.
Therapeutic Targeting of TET-Dioxygenase Deficiency in Myeloid Malignancies
Authors: Yihong Guan, Anand D. Tiwari, Metis Hasipek, Dale Grabowski, Daniel Lindner, James G Phillips, Omar Mian, Mingjiang Xu, Jaroslaw P. Maciejewski, Babal K. Jha
Journal: Blood (2021)
Abstract 13418: Sociodemographic Disparities in Neighborhood Social Cohesion Among Adults With Atherosclerotic Cardiovascular Disease in the United States
Authors: Reed Mszar, Gowtham R Grandhi, Albert D Osei, Shiwani Mahajan, Javier Valero Elizondo, Zulqarnain Javed, Garima Sharma, Michael J Blaha, Elias Mossialos, Sadeer Al-Kindi, Adnan Hyder, Miguel Cainzos-Achirica, Khurram Nasir
Journal: Circulation (2021)

Introduction: Social environment and neighborhood factors, including perceived social cohesion, represent key determinants of health. While evidence has shown that low cohesion may be adversely associated with cardiovascular health and higher levels may be cardioprotective, few studies have assessed the association between cohesion and sociodemographic factors among adults with atherosclerotic cardiovascular disease (ASCVD). Methods: Using a U.S. nationally representative sample (National Health Interview Survey [NHIS], 2013-18), we examined the association between sociodemographic characteristics and neighborhood social cohesion in adults with ASCVD. Social cohesion was categorized based on the sum of the four subscales: 1) people in this neighborhood help each other out; 2) there are people I can count on; 3) people can be trusted; and 4) this is a close-knit neighborhood. The composite score was then split at or above and below the median. Results: Among 17,017 NHIS participants with ASCVD (representing 18.3 million adults annually), 8,988 (54%) reported low neighborhood social cohesion, corresponding to 9.9 million adults. A higher proportion of those aged 18-39 years (71%), non-Hispanic Black (67%) and Hispanic (68%) individuals, uninsured (71%) adults, and immigrants (65%) reported low social cohesion compared to other groups. In multivariable logistic regression, those aged 18-39 years and 40-64 years, non-Hispanic Black and Hispanic adults, individuals with a low-income, and immigrants had increased odds of low social cohesion (Figure). Overall, 80% of adults with 4 of these characteristics had low social cohesion. Conclusion: Sociodemographic factors are associated with disparities in neighborhood social cohesion among adults with ASCVD. Future studies should assess the causal relationship between social determinants and neighborhood cohesion, the consequences of low social cohesion, and potential approaches to ameliorate it.
Cyclin-Dependent Kinase 4/6 Inhibitor Palbociclib Synergizes with BCL2 Inhibitor Venetoclax in Experimental Models of Chemotherapy Refractory Mantle Cell Lymphoma
Authors: Diana Malarikova, Radek Jorda, Alexandra Dolnikova, Eva Pokorna, Dmitry Kazantsev, Ondrej Havranek, Karel Helman, Magdalena Klanova, Miroslav Strnad, Marek Trneny, Pavel Klener
Journal: Blood (2021)
Ranolazine Improves Autonomic Balance in Heart Failure when added to Guideline-Driven Therapy
Authors: Gary L. Murray, Joseph Colombo
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Background: The effect of ranolazine (RAN) on cardiac autonomic balance in congestive heart failure (CHF) was studied. Methods: Fifty-four CHF patients were randomized to (1) open-label RAN (RANCHF) added to usual therapy vs. (2) usual therapy (NORANCHF). Parasympathetic and sympathetic (P&amp;S) measurements were taken at baseline and at 12 months. Results: A total of 16/27 (59%) patients in both groups had initially abnormal P&amp;S measures, including high sympathovagal balance (SB), cardiovascular autonomic neuropathy (CAN) or both. High SB normalized in 10/12 (83%) RANCHF patients vs. 2/11 (18%) NORANCHF patients. SB became high in 5/11 (45%) NORANCHF vs. 1/11 (9%) RANCHF patients. CAN improved in 4/6 (67%) RANCHF patients vs. 5/7 (45%) NORANCHF patients. CAN developed in 1/11 (9%) RANCHF vs. 4/11 (36%) NORANCHF patients. Since improved P&amp;S in RANCHF patients seemed independent of improved brain natriuretic peptide and impedance cardiography (BioZ) measurements, 5 day RAN was given to 30 subjects without CHF but with high SB or CAN. P&amp;S improved in 90% of these subjects. Conclusions: RAN improves unfavorable P&amp;S activity in CHF possibly by a direct effect upon autonomic sodium channels.
Abstract 11029: Heart Failure, India and West - A Major Etiological Difference
Authors: Gaurav Chauhan, Bhanu Duggal, Pranay Gore, Ramlal Ola
Journal: Circulation (2021)

Introduction: We conducted the study in all cases of heart failure to assess contributions of the various major risk factor for heart failure in the Indian sub-continent as compared to the rest of the world. Hypothesis: Dilated cardiomyopathy is the most common etiology of heart failure in the Indian sub-continent unlike ischemic heart disease in the western world. Methods: A study population of 250 patients with heart failure of age &gt;18years with various risk factors and etiologies were included &amp; assessed as per standard norms. Patients with various etiologies were assessed over a period of 6 months. Results: Mean age at diagnosis of heart failure was 54years, 75% of patients were male of which 25.5% had diastolic heart failure whereas of the remaining 25% females, 42% had diastolic heart failure. In the study population, rheumatic etiology was there in 14/250 (5.6%) patients, CAD was present in 51/250 (20.4%) patient, dilated-cardiomyopathy in 101/250 (40.4%), restrictive-cardiomyopathy in 4/250 patients (1.6%), tachyarrhythmia-induced-cardiomyopathy in 3/250 (1.2%), CKD was there in 32/250 (12.8%) patients of which 24 patients, 75% patients had HFpEF, diabetes was seen in 57/250(22.8%) patients, of which the predominant population belong to HFrEF group 49/57 (85.9%), hypertension in 122/250 (48.8%) patients of which 53% of the patient was having HFpEF and the rest were in HFrEF. Smoking was there in 44/250(17.6%) patient population of which majority of patients belong to the HFpEF group 95.4% of all smokers. Conclusions: As compared to the western population affected cohorts with heart failure in Indians belong to a significantly younger age group (mean age 54years vs. 66years-NHANES-US-Survey and 62-years-SOLVD registry). Among the etiology, the predominant cause in Indians in hilly areas is Dilated-cardiomyopathy followed by ischemic(20%) and rheumatic(5.6%) in contrast to Ischemia as a predominant cause in the west.
Abstract 9064: The Increase of Tissue Echogenicity as the Pre-State of Steam Pops During Radiofrequency Catheter Ablation
Authors: Takahashi Satoshi, Takanao Mine, Fumitsugu Yoshikawa, Kenji Takai, Masanori Takada, Koichi Fujita, Yoshiharu Nishibori, Takao Maruyama
Journal: Circulation (2021)

Introduction: Steam pops (SPs) during radiofrequency catheter ablation (RFA) using force sensing catheters are infrequent but represent a potential severe complication such as embolic stroke, cardiac perforation. SPs remains unpredictable, and unclear in detailed phenomenon. Methods: In an ex vivo, we set the bovine myocardium to 36 °C in a constant temperature bath and performed an experiment in a water tank that generated a non-pulsatile flow. RFA using irrigation catheter was applied at catheter-tissue contact force (CF) 5, 10, 20g, 30g, 40g, and 50g for 30sec. The increase of tissue echogenicity (increased echo brightness) observed by intracardiac echocardiographic images using ViewFlex™ Xtra and impedance during RFA were evaluated with and without SPs. Results: SPs phenomenon appeared in 48 out of 137 sites (35%), and the increased echo brightness during RFA was observed in 89 lesions (65%). All lesions with SPs showed increased echo brightness before SPs (6.4±6.1sec before SPs). Sites with SPs showed stronger CF (30.8±14.8g vs. 22.9±15.9g, p=0.0047), higher initial impedance (78±12Ω vs. 73±9Ω, p=0.0063), greater impedance drops in 5 seconds after the beginning of RFA (13±7Ω, vs. 6±5Ω, p&lt;0.0001), and earlier appearance of increased echo brightness (9.7±6.2 vs 17.4±6.3 sec, p&lt;0.0001). Among 89 lesions with increased echo brightness, sites with SPs showed greater impedance drops in 5 seconds after the beginning of RFA (13±7Ω, vs. 7±6Ω, P&lt;0.0001). In ROC curve analysis of the impedance drops in 5 seconds after the beginning of RFA (AUC, 0.81; sensitivity, 85%; specificity, 71%), optimal cut-off value of SPs was 7.6Ω, and SPs were not observed in lesions with the impedance drops of 3Ω or less. (Figure) Conclusions: The increase of tissue echogenicity observed by ICE images show the pre-state of all steam pops during RFA. Steam pops could be avoided by checking the impedance drop at the initial stage of RFA under ICE monitoring.
Comprehensive Multi-Parameter Characterisation of Circulating Extracellular Vesicles from Rivaroxaban-Treated VTE Patients Reveals Reduced Inflammation and Ameliorated Endothelial Dysfunction
Authors: Luisa Weiss, Paulina Szklanna, Tadhg Prendiville, Karl Egan, Sarah Kelliher, Aine Lennon, Eugene Dillon, Alfonso Blanco, Barry Kevane, Sean Murphy, Fionnuala Ni Ainle, Patricia Maguire
Journal: Blood (2021)
Engineered Customizable Microvessels for Progressive Vascularization in Large Regenerative Implants
Authors: Cuidi Li, Xiaoyu Han, Zhenjiang Ma, Tianyang Jie, Jinwu Wang, Lianfu Deng, Wenguo Cui
Journal: Advanced Healthcare Materials (2021)

Inspired by the rapid angiogenesis of natural microvessels in vivo, engineered customizable microvessels (ECMVs) are developed which can naturally angiogenic sprout and induce vascular network formation via combing a celluar coaxial microfluidic extrusion technique with microsurgery post-process. ECMVs can be used for customization of primarily pre-vascularized soft tissue regenerative implants with personalized shape and vascular density with the aid of sacrificial printing technology. After collaborating with surrounding cells, ECMVs angiogenic sprouted and formed daughter vascular networks. Through techniques such as injection and suturing, ECMVs can also be introduced into large bone repair implants for pre-vascularization and osteogenesis promotion. Furthermore, the microvessel networks with personalized shapes are customized by connecting the coaxial microfluidic system to a 3D printer. It is further demonstrated that the vascularization promotion and anastomose with host vessels of the ECMVs in vivo. Thus, ECMVs provide a simple engineering strategy for rapid vascularization of clinically large regenerative soft/hard tissue implants.
<i>BTG1</i> Mutation Promotes Aggressive Lymphoma Development By Lowering the Threshold to MYC Activation and Generating "Super-Competitor" B Cells
Authors: Coraline Mlynarczyk, Matthew Teater, Juhee Pae, Theinmozhi Arulraj, Christopher R Chin, Ling Wang, Jonatan Ersching, Ekaterina Kots, Amy Chadburn, Ersilia Barin, Hui Xian Poh, Hannah M Isles, Chen Zhengming, Hao Shen, Arnab Bandyopadhyay, Kenneth B Hoehn, Diu T.T. Nguyen, Ashley S Doane, Huimin Geng, Muhammad H Rehman, Jonah Melnick, Wyatt Morgan, Olivier Elemento, Michael G Kharas, David W. Scott, Samie R Jaffrey, Michael Meyer-Hermann, George Khelashvili, Gabriel Victora, Ari Melnick
Journal: Blood (2021)
Abstract 11330: The Influence of Percent Biventricular Pacing on CRT Efficacy Compared to ICD Therapy on Outcomes and Reverse Remodeling
Authors: Anne-Christine H Ruwald, Arthur J Moss, Martin H Ruwald, Kenji Tanabe, Valentina Kutyifa, Andrew Brenyo, Christian Jons, Scott McNitt, James P Daubert, Amin Al-Ahmad, Paul J Wang, Wojciech Zareba
Journal: Circulation (2013)

Background: Previous studies have found optimal benefit of cardiac resynchronization therapy (CRT) with biventricular (BIV) pacing above 92%. However no study has investigated the threshold of effe...
STK3 promotes gastric carcinogenesis by activating Ras-MAPK mediated cell cycle progression and serves as an independent prognostic biomarker
Authors: Bonan Chen, Wai Nok Chan, Chun Wai Mui, Xiaoli Liu, Jinglin Zhang, Yifei Wang, Alvin H. K. Cheung, Aden K. Y. Chan, Ronald C. K. Chan, Kam Tong Leung, Yujuan Dong, Yi Pan, Huixing Ke, Li Liang, Zhaocai Zhou, Chi Chun Wong, William K. K. Wu, Alfred S. L. Cheng, Jun Yu, Kwok Wai Lo, Ka Fai To, Wei Kang
Journal: Molecular Cancer (2021)
A Pilot Study Using Nivolumab in Combination with Standard of Care Chemotherapy in Newly Diagnosed Peripheral T-Cell Lymphomas
Authors: Brad Haverkos, Jasmine Zain, Manali Kamdar, Alexander Neuwelt, Steven M. Bair, Jagar Jasem, Emily Berens, Clayton Smith, Diana Abbott, Pierluigi Porcu
Journal: Blood (2021)
A Novel B Cell Antigen Designated Lambda Myeloma Antigen (LMA) Has Been Identified Using Two Fully Human Monoclonal Antibodies (Mabs) That Bind to Similar Epitopes on Plasma Cells from Patients with Plasma Cell Dyscrasias
Authors: Mary Sartor, Daniel Y Hu, Thomas X Lemarchand, Luise Britz, Rosanne Dunn, David J Gottlieb
Journal: Blood (2021)
3D Tissue-Engineered Bone Marrow Culture Predicts Patient Response to Drugs in Multiple Myeloma
Authors: Kinan Alhallak, Amanda Jeske, Pilar De La Puente, Jennifer Sun, Mark A. Fiala, Feda Azab, Barbara Muz, Ilyas Sahin, Ravi Vij, John F. DiPersio, Abdel Kareem Azab
Journal: Blood (2021)
When Ischemic Heart Failure Complicated with Diabetes Mellitus
Authors: Yuchao Zhang, Shaoping Wang
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Diabetes and heart failure are mutually reinforcing factors. The treatment strategy and prognosis for patients with both diabetes and heart failure are inconclusive. This article reviews the current situation of ischemic heart failure complicated with diabetes, the pathophysiological relationship between diabetes and heart failure, and disease management. Especially, we highlight the latest result from CRISIS (Coronary Revascularization in Patients with Ischemic Heart Failure and Prevention of Sudden Cardiac Death) study, which finds that diabetes associates with greater ejection fraction improvement after revascularization in patients with reduced ejection fraction. This result implies the indication for revascularization in patients with heart failure who present with DM.