tbuckley/cabot-search huggingface dataset:
Abstract 17427: A Unique “Cellular Fibrillation” Status in Mouse Ventricular Myocytes
Authors: Lai-Hua Xie, Hairuo Wen, Zhenghang Zhao, Nadezhda Fefelova, Charelle Allen
Journal: Circulation (2011)

Different intracellular calcium (Ca i ) wave patterns have been observed in cardiac myocytes. However, their mechanisms and corresponding electrophysiological properties remain unclear. In the present study, we have generated various patterns of Ca i waves in isolated mouse ventricular myocytes under highly-activated Ca i cycling states, such as high external Ca concentration or in the present of -adrenergic stimulation (i.e. isoproterenol and Bay K8644). Our results revealed at least three distinct types of Ca wave dynamics: I) slow propagating planar waves; II) Repetitive single spiral waves; III) Multiple spiral/micro waves, in which average Ca i level remained high. All waves were completely blocked by tetracaine (1 mM), suggesting RyR leaking is the original source for the waves. Simultaneous recording of membrane potential under current-clamp mode revealed that these complex Ca i wave dynamics have several functional consequences. The cell exhibited individual or oscillatory EADs and/or DADs under the conditions with type I or type II Ca i waves. Interestingly, a unique “cellular fibrillation” status was associated with type III Ca i waves. Under this condition, the cell maintained a high Ca i level and a depolarized membrane potential (~ -20 mV) and thus lost its excitability and contractility. We also found that in the same cell, the Ca waves can be converted from one type to another by changing the Ca handling conditions. The multiple spiral/micro waves (type III) were transformed into slow-propagating, planar waves (type I) by a Ca/Na-free Tyrode's solution or by Gadolinium (Gd 3+ ), a nonselective TRPC channel blocker; but not by nifedipine (L-type Ca channel blocker), SEA0400 (Na-Ca exchange blocker) or TTX (Na channel blocker). Hyperpolarizing the cell membrane by external injection of an outward current also transformed type III to type I Ca waves, suggesting the facilitating role of membrane current in the generation of the cellular fibrillation status. Termination of the cellular fibrillation by blocking TRPC channel activity may provide new opportunities for the treatment of clinical ventricular fibrillation.
<i>CEBPA</i> mutations in 4708 patients with acute myeloid leukemia: differential impact of bZIP and TAD mutations on outcome
Authors: Franziska Taube, Julia Annabell Georgi, Michael Kramer, Sebastian Stasik, Jan Moritz Middeke, Christoph Röllig, Utz Krug, Alwin Krämer, Sebastian Scholl, Andreas Hochhaus, Tim H. Brümmendorf, Ralph Naumann, Andreas Petzold, Roger Mulet-Lazaro, Peter J. M. Valk, Björn Steffen, Hermann Einsele, Markus Schaich, Andreas Burchert, Andreas Neubauer, Kerstin Schäfer-Eckart, Christoph Schliemann, Stefan W. Krause, Mathias Hänel, Richard Noppeney, Ulrich Kaiser, Claudia D. Baldus, Martin Kaufmann, Sylvia Herold, Friedrich Stölzel, Katja Sockel, Malte von Bonin, Carsten Müller-Tidow, Uwe Platzbecker, Wolfgang E. Berdel, Hubert Serve, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig, Christian Thiede
Journal: Blood (2021)
Transcriptional regulation of N6-methyladenosine orchestrates sex-dimorphic metabolic traits
Authors: David A. Salisbury, David Casero, Zhengyi Zhang, Dan Wang, Jason Kim, Xiaohui Wu, Laurent Vergnes, Aashiq H. Mirza, Paola Leon-Mimila, Kevin J. Williams, Adriana Huertas-Vazquez, Samie R. Jaffrey, Karen Reue, Jianjun Chen, Tamer Sallam
Journal: Nature Metabolism (2021)
Lack of correlation between hepatitis C virus genotypes and clinical course of hepatitis C virus-related cirrhosis
Authors: L. Benvegnù, P. Pontisso, D. Cavalletto, F. Noventa, L. Chemello, A. Alberti
Journal: Hepatology (1997)

The influence of the hepatitis C virus (HCV)–genotype on liver disease severity was evaluated in 429 consecutive patients with chronic hepatitis C, including 109 with cirrhosis who were followed up prospectively, allowing for the assessment of the role of the HCV–genotype on disease outcome and on the development of hepatocellular carcinoma (HCC). HCV–1 was detected in 147 (46%) patients without cirrhosis and in 47 (43%) with cirrhosis (x not significant), being mainly HCV–1b. HCV–2 was found in 103 (32%) cases without cirrhosis and in 30 (27.5) with cirrhosis ( P : not significant), being mainly HCV–2a. HCV–3 was detected in 32 (10%) patients without cirrhosis and in 2 (2%) with cirrhosis ( P &lt; 0.005). Infection with more than one genotype (HCV–1/HCV–2 and HCV–1/HCV–3) was observed only in cirrhotic patients (6 of 109; 5.5%). During a mean follow–up of 67 ± 22 months, 21 (19%) patients with cirrhosis showed worsening in Child's stage, 5 (4.5%) underwent liver transplantation, 23 (21%) developed HCC, and 24 (22%) died of complication of liver disease; the overall incidence of at least one of these events was 38.5%. By the Kaplan–Meier method and log–rank test, the cumulative probability of developing each or at least one of the above events did not differ in relation to the genotype of infecting HCV, apart from patients with mixed genotype infection who showed a significantly higher incidence of death ( P &lt; .05). These data indicate that HCV–genotypes do not have a significant effect on the severity and outcome of liver disease in patients with chronic HCV–infection. Patients with cirrhosis who are also infected by HCV–1 and HCV–2 had a similar prognosis and progression to HCC, while patients infected by more than one genotype showed the most unfavorable course of disease.
Pulmonary circulation-mediated heart targeting for the prevention of heart failure by inhalation of intrinsically bioactive nanoparticles
Authors: Chao Liu, Liyuan Chen, Yongchang Ma, Kaiyao Hu, Peng Wu, Lina Pan, Haiyan Chen, Lanlan Li, Houyuan Hu, Jianxiang Zhang
Journal: Theranostics (2021)

Heart failure is a serious clinical and public health problem. Currently there is an unmet demand for effective therapies for heart failure. Herein we reported noninvasive inhalation delivery of nanotherapies to prevent heart failure. Methods: A reactive oxygen species (ROS)-scavenging material (TPCD) was synthesized, which was processed into antioxidative and anti-inflammatory nanoparticles (i.e., TPCD NP). By decoration with a mitochondrial-targeting moiety, a multilevel targeting nanotherapy TTPCD NP was engineered. Pulmonary accumulation of inhaled TPCD NP and underlying mechanisms were examined in mice. In vivo efficacies of nanotherapies were evaluated in mice with doxorubicin (DOX)-induced cardiomyopathy. Further, an antioxidative, anti-inflammatory, and pro-resolving nanotherapy (i.e., ATTPCD NP) was developed, by packaging a peptide Ac2-26. In vitro and in vivo efficacies of ATTPCD NP were also evaluated. Results: TPCD NP alleviated DOX-induced oxidative stress and cell injury by internalization in cardiomyocytes and scavenging overproduced ROS. Inhaled TPCD NP can accumulate in the heart of mice by transport across the lung epithelial and endothelial barriers. Correspondingly, inhaled TPCD NP effectively inhibited DOX-induced heart failure in mice. TTPCD NP showed considerably enhanced heart targeting capability, cellular uptake efficiency, and mitochondrial localization capacity, thereby potentiating therapeutic effects. Notably, TPCD NP can serve as bioactive and ROS-responsive nanovehicles to achieve combination therapy with Ac2-26, affording further enhanced efficacies. Importantly, inhaled TPCD NP displayed good safety at a dose 5-fold higher than the efficacious dose. Conclusions: Inhalation delivery of nanoparticles is an effective, safe, and noninvasive strategy for targeted treatment of heart diseases. TPCD NP-based nanotherapies are promising drugs for heart failure and other acute/chronic heart diseases associated with oxidative stress.
Effects of purified exosome product on rotator cuff tendon-bone healing in vitro and in vivo
Authors: Ye Ren, Shuwei Zhang, Yicun Wang, Daniel S. Jacobson, Ramona L. Reisdorf, Tomoyuki Kuroiwa, Atta Behfar, Steven L. Moran, Scott P. Steinmann, Chunfeng Zhao
Journal: Biomaterials (2021)
Abelacimab for Prevention of Venous Thromboembolism
Authors: Peter Verhamme, B. Alexander Yi, Annelise Segers, Janeen Salter, Daniel Bloomfield, Harry R. Büller, Gary E. Raskob, Jeffrey I. Weitz
Journal: New England Journal of Medicine (2021)

The role of factor XI in the pathogenesis of postoperative venous thromboembolism is uncertain. Abelacimab is a monoclonal antibody that binds to factor XI and locks it in the zymogen (inactive precursor) conformation.In this open-label, parallel-group trial, we randomly assigned 412 patients who were undergoing total knee arthroplasty to receive one of three regimens of abelacimab (30 mg, 75 mg, or 150 mg) administered postoperatively in a single intravenous dose or to receive 40 mg of enoxaparin administered subcutaneously once daily. The primary efficacy outcome was venous thromboembolism, detected by mandatory venography of the leg involved in the operation or objective confirmation of symptomatic events. The principal safety outcome was a composite of major or clinically relevant nonmajor bleeding up to 30 days after surgery.Venous thromboembolism occurred in 13 of 102 patients (13%) in the 30-mg abelacimab group, 5 of 99 patients (5%) in the 75-mg abelacimab group, and 4 of 98 patients (4%) in the 150-mg abelacimab group, as compared with 22 of 101 patients (22%) in the enoxaparin group. The 30-mg abelacimab regimen was noninferior to enoxaparin, and the 75-mg and 150-mg abelacimab regimens were superior to enoxaparin (P<0.001). Bleeding occurred in 2%, 2%, and none of the patients in the 30-mg, 75-mg, and 150-mg abelacimab groups, respectively, and in none of the patients in the enoxaparin group.This trial showed that factor XI is important for the development of postoperative venous thromboembolism. Factor XI inhibition with a single intravenous dose of abelacimab after total knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding. (Funded by Anthos Therapeutics; ANT-005 TKA EudraCT number, 2019-003756-37.).
<i>Notes from the Field:</i> Transmission of Pan-Resistant and Echinocandin-Resistant <i>Candida auris</i> in Health Care Facilities ― Texas and the District of Columbia, January–April 2021
Authors: Meghan Lyman, Kaitlin Forsberg, Jacqueline Reuben, Thi Dang, Rebecca Free, Emma E. Seagle, D. Joseph Sexton, Elizabeth Soda, Heather Jones, Daryl Hawkins, Adonna Anderson, Julie Bassett, Shawn R. Lockhart, Enyinnaya Merengwa, Preetha Iyengar, Brendan R. Jackson, Tom Chiller
Journal: MMWR Morbidity and Mortality Weekly Report (2021)
MO31-1 Surgical treatment for pulmonary oligometastases in the patients with pancreatic cancer who underwent pancreatectomy
Authors: Maeda Shingo, Ryoji Takada, Kenji Ikezawa, Kazuma Daiku, Yutaro Abe, Yugo Kai, Takuo Yamai, Nobuyasu Fukutake, Tasuku Nakabori, Hiroyuki Uehara, Hidenori Takahashi, Jiro Okami, Kazuyoshi Ohkawa
Journal: Annals of Oncology (2021)
US Trends in Opioid Access Among Patients With Poor Prognosis Cancer Near the End-of-Life
Authors: Andrea C. Enzinger, Kaushik Ghosh, Nancy L. Keating, David M. Cutler, Mary Beth Landrum, Alexi A. Wright
Journal: Journal of Clinical Oncology (2021)

PURPOSE Heightened regulations have decreased opioid prescribing across the United States, yet little is known about trends in opioid access among patients dying of cancer. METHODS Among 270,632 Medicare fee-for-service decedents with poor prognosis cancers, we used part D data to examine trends from 2007 to 2017 in opioid prescription fills and opioid potency (morphine milligram equivalents per day [MMED]) near the end-of-life (EOL), defined as the 30 days before death or hospice enrollment. We used administrative claims to evaluate trends in pain-related emergency department (ED) visits near EOL. RESULTS Between 2007 and 2017, the proportion of decedents with poor prognosis cancers receiving ≥ 1 opioid prescription near EOL declined 15.5% (relative percent difference [RPD]), from 42.0% (95% CI, 41.4 to 42.7) to 35.5% (95% CI, 34.9 to 36.0) and the proportion receiving ≥ 1 long-acting opioid prescription declined 36.5% (RPD), from 18.1% (95% CI, 17.6 to 18.6) to 11.5% (95% CI, 11.1 to 11.9). Among decedents receiving opioids near EOL, the mean daily dose fell 24.5%, from 85.6 MMED (95% CI, 82.9 to 88.3) to 64.6 (95% CI, 62.7 to 66.6) MMED. Overall, the total amount of opioids prescribed per decedent near EOL (averaged across those who did and did not receive an opioid) fell 38.0%, from 1,075 morphine milligram equivalents per decedent (95% CI, 1,042 to 1,109) to 666 morphine milligram equivalents per decedent (95% CI, 646 to 686). Simultaneously, the proportion of patients with pain-related ED visits increased 50.8% (RPD), from 13.2% (95% CI, 12.7 to 13.6) to 19.9% (95% CI, 19.4 to 20.4). Sensitivity analyses demonstrated similar declines in opioid utilization in the 60 and 90 days before death or hospice, and suggested that trends in opioid access were not confounded by secular trends in hospice utilization. CONCLUSION Opioid use among patients dying of cancer has declined substantially from 2007 to 2017. Rising pain-related ED visits suggests that EOL cancer pain management may be worsening.
Backstop Price Caps in Commercial Health Care Markets—Reply
Authors: Michael E. Chernew, Maximilian J. Pany
Journal: JAMA (2021)

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Abstract 13696: Elevated O-Glcnacylation : An Independent Driver of Cardiomyopathy
Authors: Priya Umapathi, Olurotimi Mesubi, Partha Banerjee, Natasha Zachara, Qinchuan Wang, Jonathan Granger, Elizabeth Luczak, Yuejin Wu, Liliana Florea, Conover Talbot, Gerald W Hart, Mark E Anderson
Journal: Circulation (2019)

Heart failure is a leading cause of death and is associated with increased O-GlcNAcylation (OGN). However, it is unknown if excessive OGN is a direct contributor to cardiomyopathy. OGN modifies pro...
Guanine Nucleotide‐Binding Protein G(i) Subunit Alpha 2 Exacerbates NASH Progression by Regulating Peroxiredoxin 1–Related Inflammation and Lipophagy
Authors: Zechuan Zhang, Zetao Ji, Jianbo He, Yijun Lu, Wenfang Tian, Chang Zheng, Huihui Chen, Quan Zhang, Fei Yang, Minglu Zhang, Yin Yin, Runqiu Jiang, Wen‐Ming Chu, Wenjie Zhang, Beicheng Sun
Journal: Hepatology (2021)

Background and Aims NASH is an advanced stage of liver disease accompanied by lipid accumulation, inflammation, and liver fibrosis. Guanine nucleotide-binding protein G(i) subunit alpha-2 (GNAI2) is a member of the "inhibitory" class of α-subunits, and recent studies showed that Gnai2 deficiency is known to cause reduced weight in mice. However, the role of GNAI2 in hepatocytes, particularly in the context of liver inflammation and lipid metabolism, remains to be elucidated. Herein, we aim to ascertain the function of GNAI2 in hepatocytes and its impact on the development of NASH. Approach and Results Human liver tissues were obtained from NASH patients and healthy persons to evaluate the expression and clinical relevance of GNAI2. In addition, hepatocyte-specific Gnai2-deficient mice (Gnai2hep−/−) were fed either a Western diet supplemented with fructose in drinking water (WDF) for 16 weeks or a methionine/choline–deficient diet (MCD) for 6 weeks to investigate the regulatory role and underlying mechanism of Gnai2 in NASH. GNAI2 was significantly up-regulated in liver tissues of patients with NASH. Following feeding with WDF or MCD diets, livers from Gnai2hep−/− mice had reduced steatohepatitis with suppression of markers of inflammation and an increase in lipophagy compared to Gnai2flox/flox mice. Toll-like receptor 4 signals through nuclear factor kappa B to trigger p65-dependent transcription of Gnai2. Intriguingly, immunoprecipitation, immunofluorescence, and mass spectrometry identified peroxiredoxin 1 (PRDX1) as a binding partner of GNAI2. Moreover, the function of PRDX1 in the suppression of TNF receptor-associated factor 6 ubiquitin-ligase activity and glycerophosphodiester phosphodiesterase domain-containing 5–related phosphatidylcholine metabolism was inhibited by GNAI2. Suppression of GNAI2 combined with overexpression of PRDX1 reversed the development of steatosis and fibrosis in vivo. Conclusions GNAI2 is a major regulator that leads to the development of NASH. Thus, inhibition of GNAI2 could be an effective therapeutic target for the treatment of NASH.
Abstract 15009: Can Machine Learning Predict Chest Pain Readmissions?
Authors: Anvi Raina, Hena Patel, Natasha Rana, Georges Compagnon, Proddutur R Reddy
Journal: Circulation (2019)

Background: Chest pain is a common emergency room presentation and a frequent cause of readmissions. Hospital readmissions are costly and associated with worse quality of life. Use of prediction al...
A comprehensive review on biomarkers associated with painful temporomandibular disorders
Authors: Mayank Shrivastava, Ricardo Battaglino, Liang Ye
Journal: International Journal of Oral Science (2021)

Abstract Pain of the orofacial region is the primary complaint for which patients seek treatment. Of all the orofacial pain conditions, one condition that possess a significant global health problem is temporomandibular disorder (TMD). Patients with TMD typically frequently complaints of pain as a symptom. TMD can occur due to complex interplay between peripheral and central sensitization, endogenous modulatory pathways, and cortical processing. For diagnosis of TMD pain a descriptive history, clinical assessment, and imaging is needed. However, due to the complex nature of pain an additional step is needed to render a definitive TMD diagnosis. In this review we explicate the role of different biomarkers involved in painful TMD. In painful TMD conditions, the role of biomarkers is still elusive. We believe that the identification of biomarkers associated with painful TMD may stimulate researchers and clinician to understand the mechanism underlying the pathogenesis of TMD and help them in developing newer methods for the diagnosis and management of TMD. Therefore, to understand the potential relationship of biomarkers, and painful TMD we categorize the biomarkers as molecular biomarkers, neuroimaging biomarkers and sensory biomarkers. In addition, we will briefly discuss pain genetics and the role of potential microRNA (miRNA) involved in TMD pain.
Psychologic Stress Drives Progression of Malignant Tumors via DRD2/HIF1α Signaling
Authors: Huijuan Liu, Jiahuan Yang, Yang Zhang, Jingxia Han, Yuyan Yang, Zihan Zhao, Xintong Dai, Hongqi Wang, Xiujuan Ding, Yanrong Liu, Weilong Zhong, Wenqing Gao, Tao Sun
Journal: Cancer Research (2021)

Abstract Although it is established that the sustained psychologic stress conditions under which patients with tumors often reside accelerates malignant progression of tumors, the molecular mechanism behind this association is unclear. In this work, the effect of psychologic stress on tumor progression was verified using a stress-stimulated tumor-bearing mouse model (Str-tumor). Both D2 dopamine receptor (DRD2) and hypoxia-inducible factor-1α (HIF1α) were highly expressed in the nucleus of Str-tumors. Treatment with trifluoperazine (TFP), a DRD2 inhibitor, elicited better antitumor effects in Str-tumors than the control group. These results indicate that DRD2 may mediate stress-induced malignant tumor progression. DRD2 interacted with von Hippel-Lindau (VHL) in the nucleus, and competitive binding of DRD2 and HIF1α to VHL resulted in reduced ubiquitination-mediated degradation of HIF1α, enhancing the epithelial-mesenchymal transition of tumor cells. TFP acted as an interface inhibitor between DRD2 and VHL to promote the degradation of HIF1α. In conclusion, DRD2 may promote the progression of malignant tumors induced by psychologic stress via activation of the oxygen-independent HIF1α pathway, and TFP may serve as a therapeutic strategy for stress management in patients with cancer. Significance: This work identifies DRD2 regulation of HIF1α as a mechanism underlying the progression of malignant tumors stimulated by psychologic stress and suggests that DRD2 inhibition can mitigate these stress conditions in patients. See related commentary by Bernabé, p. 5144
Public health effects of travel-related policies on the COVID-19 pandemic: A mixed-methods systematic review
Authors: Lama Bou-Karroum, Joanne Khabsa, Mathilda Jabbour, Nadeen Hilal, Zeinab Haidar, Pamela Abi Khalil, Rima Abdul Khalek, Jana Assaf, Gladys Honein-AbouHaidar, Clara Abou Samra, Layal Hneiny, Sameh Al-Awlaqi, Johanna Hanefeld, Fadi El-Jardali, Elie A. Akl, Charbel El Bcheraoui
Journal: Journal of Infection (2021)