tbuckley/cabot-search huggingface dataset:
Abstract 76: Experimentally Increasing Titin’s Compliance in a Mouse Model of Heart Failure with Preserved Ejection Fraction Ameliorates Diastolic Dysfunction
Authors: Mei Methawasin, Joshua G Strom, Rebecca E Slater, Vanessa Fernandez, Chandra Saripalli, Henk L Granzier
Journal: Circulation Research (2016)

Increasing titin length in the heart through functional deletion of the RNA recognition motif (RRM) of RBM20 protein leads to a reduction of left ventricular (LV) chamber stiffness in sedentary mice. We tested the therapeutic effect of upregulating compliant titins by creating diastolic dysfunction in a mouse model with inducible RBM20 inhibition (MerCreMer;cRbm20ΔRRM). Under transcriptional control of an MHC6 promoter, RBM20 function of MerCreMer;cRbm20ΔRRM mice was inhibited in time- and cardiac-specific manners. Adult male MerCreMer;cRbm20ΔRRM mice had undergone transaortic constriction (TAC) surgery with Deoxycorticosterone acetate (DOCA) pellet implantation. Two weeks after TAC+DOCA surgery, mice developed LV hypertrophy and diastolic dysfunction as demonstrated by echocardiography. Four weeks after surgery, pressure volume analysis revealed that LV chamber stiffness was markedly increased in TAC+DOCA mice (140% increased versus sham). However, the TAC+DOCA mice with RBM20 inhibition developed less severe LV chamber stiffness (29% increased versus sham). Passive stiffness measurements showed a reduction of cardiomyocyte stiffness in TAC+DOCA mice with RBM20 inhibition. Inhibition of the RBM20-based splicing system results in expression of compliant mutant N2BA titin which consequently lead to reduction of cardiomyocyte stiffness and LV chamber stiffness in a mouse model with diastolic dysfunction.
Consider carotid endarterectomy
Authors: M Adiseshiah
Journal: BMJ (1994)

patients may also be taking an antidepressant with anticholinergic properties and, almost routinely, receive an anticholinergic drug such as procyclidine to prevent or alleviate rigidity.Though some patients with anticholinergic intoxication will be "hot as a hare, blind as a bat, red as beetroot, and mad as a hatter," in psychiatric practice they will more probably be noticed to have a fever and will be diagnosed as having the neuroleptic malignant syndrome.Patients considered to have this syndrome should always be examined for the physical hallmarks of anticholinergic intoxication, particularly pupillary dilatation and dry skin and mucous membranes.The investigation and treatment of this condition are considerably less enigmatic than those of the neuroleptic malignant syndrome and have been well described by Lipowski.3
Vaccinia virus E3 prevents sensing of Z-RNA to block ZBP1-dependent necroptosis
Authors: Heather Koehler, Samantha Cotsmire, Ting Zhang, Siddharth Balachandran, Jason W. Upton, Jeffery Langland, Daniel Kalman, Bertram L. Jacobs, Edward S. Mocarski
Journal: Cell Host & Microbe (2021)
Effects of Fluid Rehydration Strategy on Correction of Acidosis and Electrolyte Abnormalities in Children With Diabetic Ketoacidosis
Authors: Arleta Rewers, Nathan Kuppermann, Michael J. Stoner, Aris Garro, Jonathan E. Bennett, Kimberly S. Quayle, Jeffrey E. Schunk, Sage R. Myers, Julie K. McManemy, Lise E. Nigrovic, Jennifer L. Trainor, Leah Tzimenatos, Maria Y. Kwok, Kathleen M. Brown, Cody S. Olsen, T. Charles Casper, Simona Ghetti, Nicole S. Glaser
Journal: Diabetes Care (2021)

Fluid replacement to correct dehydration, acidosis, and electrolyte abnormalities is the cornerstone of treatment for diabetic ketoacidosis (DKA), but little is known about optimal fluid infusion rates and electrolyte content. The objective of this study was to evaluate whether different fluid protocols affect the rate of normalization of biochemical derangements during DKA treatment. The current analysis involved moderate or severe DKA episodes (n = 714) in children age <18 years enrolled in the Fluid Therapies Under Investigation in DKA (FLUID) Trial. Children were assigned to one of four treatment groups using a 2 × 2 factorial design (0.90% or 0.45% saline and fast or slow rate of administration). The rate of change of pH did not differ by treatment arm, but Pco2 increased more rapidly in the fast versus slow fluid infusion arms during the initial 4 h of treatment. The anion gap also decreased more rapidly in the fast versus slow infusion arms during the initial 4 and 8 h. Glucose-corrected sodium levels remained stable in patients assigned to 0.90% saline but decreased in those assigned to 0.45% saline at 4 and 8 h. Potassium levels decreased, while chloride levels increased more rapidly with 0.90% versus 0.45% saline. Hyperchloremic acidosis occurred more frequently in patients in the fast arms (46.1%) versus the slow arms (35.2%). In children treated for DKA, faster fluid administration rates led to a more rapid normalization of anion gap and Pco2 than slower fluid infusion rates but were associated with an increased frequency of hyperchloremic acidosis.
Abstract 418: Categorization of Post-Cardiac Arrest Patients According to the Pattern of Amplitude-Integrated Electroencephalography After Return of Spontaneous Circulation: Analysis of Long-Term Prognosis
Authors: Kazuhiro Sugiyama, Kazuki Miyazaki, Yuichi Hamabe
Journal: Circulation (2019)

Introduction: Amplitude-integrated electroencephalography (aEEG) is a type of quantitative EEG easily interpreted by emergency physicians and intensivists at the bedside. We previously reported that categorizing post-cardiac arrest patients according to the pattern of aEEG, after return of spontaneous circulation (ROSC), could help predict the neurological function at hospital discharge (Critical Care. 2018;20:226). In post-cardiac arrest patients, increasing importance is being placed on long-term prognosis. In this study we evaluated the neurological outcome of patients in each category from our previous study, one year after cardiac arrest. Methods: We assessed the outcomes of patients who received post-cardiac arrest care, including targeted temperature management (TTM) and aEEG monitoring, in our tertiary emergency center, between March 2013 and April 2017. The patients were divided into four categories: C1 included those who displayed continuous normal voltage (CNV), within 12 hours of ROSC, and the best aEEG pattern in post-cardiac arrest patients; C2 included those who recovered CNV between 12 and 36 hours after ROSC; C3 included those with no CNV up to 36 hours after ROSC; and C4 included those who revealed burst suppression any time after ROSC. A good outcome was defined as a cerebral performance category (CPC) of 1 or 2, one year after cardiac arrest. Results: A total of 60 patients, with a median age of 60 years, were assessed; of them, 41 (68%) had an initial shockable rhythm. A good outcome was recorded in 18/19 (95%) C1 patients, 8/14 (57%) C2 patients, 1/10 (10%) C3 patients, and 0/14 C4 patients. Three patients could not be categorized because the recording period was too short. Conclusion: The categorization of post-cardiac arrest patients according to the pattern of aEEG after ROSC may be useful to predict long-term neurological function. C1 patients had excellent prognosis, while C3 and C4 patients had poor prognosis. However, one patient in the C3 group had CPC 3 at hospital discharge and then recovered to CPC 2 within one year. Withdrawal of care should be considered cautiously, using a multimodal approach, for patients in this category. C2 patients have borderline prognosis and are targets for intensive post-cardiac neurological care.
Letter to the Editor from Colle<i>et al</i>
Authors: Raphael Colle, Thierry Andre, Yves Menu
Journal: Journal for ImmunoTherapy of Cancer (2021)

In their article, Fucà et al highlight that early tumor shrinkage and depth of response predict the prognosis of patients with metastatic colorectal cancer (mCRC) microsatellite instability (MSI-H)/deficient mismatch repair (dMMR) treated by immune checkpoint inhibitors (ICI). We are surprised that no cases of pseudoprogression (PSPD) were reported in their study. PSPDs were described under ICI in patients treated for MSI/dMMR mCRC. In a cohort of 123 patients treated with anti-PD1±antiCTL-4 for MSI/dMMR mCRC, we reported 12 patients with PSPD, representing 10% of the cohort. Of 12 patients with PSPD, 8 secondary achieved an objective response and were alive and free of progression at the data lock. Conversely, in Fucà's article, no PSDP was observed and the patients with primary radiological progression (21.7%) had a poor overall survival. These differences between the two series could be probably explained by the following points. First, Fucà et al use RECIST 1.1 criteria for radiological evaluation. Second, the first imaging was done after 8-9 weeks of treatment in Fucà's article, which may be late to detect PSPD. In conclusion, if the first evaluation is made during the first 3 months of treatment, using iRECIST criteria seems mandatory to avoid stopping treatment prematurely, especially in patients receiving anti-PD1 alone.
Outcomes of Hematopoietic Stem Cell Transplantation after Chronic Graft Versus Host Disease and Evaluation of Revised Failure Free Survival in a Retrospective Analysis from Two Referral Centers.
Authors: Simona Pagliuca, Flore Sicre De Fontbrune, Antonio M Risitano, David Michonneau, Alban Villate, Rudy Birsen, Camille Rouzaud, Aurelien Sutra del Galy, Nabergoj Mitja, Regis Peffault De Latour, Gérard Socié, Marie Robin
Journal: Blood (2017)
A Functional BCI Model by the P2731 working group: Physiology
Authors: Ali Hossaini, Davide Valeriani, Chang S. Nam, Raffaele Ferrante, Mufti Mahmud
Journal: Brain-Computer Interfaces (2021)

The development of Brain–Computer Interfaces (BCIs) requires specialists in various fields, including engineering, computer science, medicine and neuroscience. Each of these disciplines possesses a specific and sometimes differing terminology, which creates obstacles to mutual understanding and research collaboration. The IEEE P2731 working group aims to improve communication among BCI researchers by developing a functional model and standard glossary that can be used in all relevant fields. This article describes the anatomical regions of the brain and physiological processes commonly used by BCI applications. It serves as an introduction to neurophysiology for engineers and other non-specialists, and it offers background to articles on the IEEE P2731 Functional Model and Glossary available elsewhere in this special issue.
Abstract 363: In Situ Cardiac Cellular Reprogramming Using Adenoviral Vectors: Implication for Clinical Myocardial Regeneration
Authors: Megumi Mathison, Vivek P Singh, Maria J Chiuchiolo, Deepthi Sanagasetti, Yun Mao, Vivekkumar B Patel, Jianchang Yang, Stephen M Kaminsky, Ronald G Crystal, Todd K Rosengart
Journal: Circulation Research (2016)

Objective: The reprogramming of cardiac fibroblasts into induced cardiomyocytes (iCMs) improves ventricular function in myocardial infarction models. Only integrating chronic expression vectors have thus far been used to administer reprogramming genes, potentially limiting clinical applicability. We hypothesized that reprogramming could be achieved using non-integrating, acute expression adenoviral vectors. Methods: Adenoviral (Ad) and lentiviral vectors encoding Gata4 (G), Mef2c (M) and Tbx5 (T) were validated in vitro . Sprague Dawley rats then underwent coronary artery ligation and Ad-mediated administration of vascular endothelial growth factor to provide infarct prevascularization. Three weeks later, Ad or lentivirus encoding G, M, or T or an equivalent dose of a null vector was administered. Outcomes were analyzed by serial echocardiography, and by terminal MRI and histology. Results: Ad and lentivirus vectors provided equivalent in vitro GMT expression by Western blotting and AdGMT induced expression of the cardiomyocyte marker cTnT in approximately 7% of cardiac fibroblasts, compared to 4% of cells infected with LentiGMT. Sections of infarcted myocardium from rats that had been treated with AdGMT or LentiGMT demonstrated higher density of cells expressing the cardiomyocyte marker MHY7 compared to AdNull treated animals (p&lt;0.05). Echocardiography demonstrated that AdGMT significantly increased ejection fraction compared to AdNull (AdGMT: 21% ± 3%, LentiGMT: 14% ± 5%, AdNull: -0.4% ± 2%; p&lt;0.05). Conclusions: Adenoviral vectors are at least as effective as lentiviral vectors in inducing cardiac fibroblast transdifferentiation into iCMs and improving cardiac function in post-infarct rat hearts. The utility of short-term expression Ad vectors represents an important potential tool in inducing cardiac cellular reprogramming clinically.
Advances and highlights in biomarkers of allergic diseases
Authors: Ismail Ogulur, Yagiz Pat, Ozge Ardicli, Elena Barletta, Lacin Cevhertas, Ruben Fernandez‐Santamaria, Mengting Huang, Manal Bel Imam, Jana Koch, Siyuan Ma, Debbie J. Maurer, Yasutaka Mitamura, Yaqi Peng, Urszula Radzikowska, Arturo O. Rinaldi, Juan Rodriguez‐Coira, Pattraporn Satitsuksanoa, Stephan R. Schneider, Alexandra Wallimann, Damir Zhakparov, Reihane Ziadlou, Marie‐Charlotte Brüggen, Willem van de Veen, Milena Sokolowska, Katja Baerenfaller, Luo Zhang, Mubeccel Akdis, Cezmi A. Akdis
Journal: Allergy (2021)

During the past years, there has been a global outbreak of allergic diseases, presenting a considerable medical and socioeconomical burden. A large fraction of allergic diseases is characterized by a type 2 immune response involving Th2 cells, type 2 innate lymphoid cells, eosinophils, mast cells, and M2 macrophages. Biomarkers are valuable parameters for precision medicine as they provide information on the disease endotypes, clusters, precision diagnoses, identification of therapeutic targets, and monitoring of treatment efficacies. The availability of powerful omics technologies, together with integrated data analysis and network-based approaches can help the identification of clinically useful biomarkers. These biomarkers need to be accurately quantified using robust and reproducible methods, such as reliable and point-of-care systems. Ideally, samples should be collected using quick, cost-efficient and noninvasive methods. In recent years, a plethora of research has been directed toward finding novel biomarkers of allergic diseases. Promising biomarkers of type 2 allergic diseases include sputum eosinophils, serum periostin and exhaled nitric oxide. Several other biomarkers, such as pro-inflammatory mediators, miRNAs, eicosanoid molecules, epithelial barrier integrity, and microbiota changes are useful for diagnosis and monitoring of allergic diseases and can be quantified in serum, body fluids and exhaled air. Herein, we review recent studies on biomarkers for the diagnosis and treatment of asthma, chronic urticaria, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, food allergies, anaphylaxis, drug hypersensitivity and allergen immunotherapy. In addition, we discuss COVID-19 and allergic diseases within the perspective of biomarkers and recommendations on the management of allergic and asthmatic patients during the COVID-19 pandemic.
Nonsense-Mediated RNA Decay Is a Unique Vulnerability of Cancer Cells Harboring <i>SF3B1</i> or <i>U2AF1</i> Mutations
Authors: Abigael Cheruiyot, Shan Li, Sridhar Nonavinkere Srivatsan, Tanzir Ahmed, Yuhao Chen, Delphine S. Lemacon, Ying Li, Zheng Yang, Brian A. Wadugu, Wayne A. Warner, Shondra M. Pruett-Miller, Esther A. Obeng, Daniel C. Link, Dalin He, Fei Xiao, Xiaowei Wang, Julie M. Bailis, Matthew J. Walter, Zhongsheng You
Journal: Cancer Research (2021)

Abstract Nonsense-mediated RNA decay (NMD) is recognized as an RNA surveillance pathway that targets aberrant mRNAs with premature translation termination codons (PTC) for degradation, however, its molecular mechanisms and roles in health and disease remain incompletely understood. In this study, we developed a novel reporter system to accurately measure NMD activity in individual cells. A genome-wide CRISPR-Cas9 knockout screen using this reporter system identified novel NMD-promoting factors, including multiple components of the SF3B complex and other U2 spliceosome factors. Interestingly, cells with mutations in the spliceosome genes SF3B1 and U2AF1, which are commonly found in myelodysplastic syndrome (MDS) and cancers, have overall attenuated NMD activity. Compared with wild-type (WT) cells, SF3B1- and U2AF1-mutant cells were more sensitive to NMD inhibition, a phenotype that is accompanied by elevated DNA replication obstruction, DNA damage, and chromosomal instability. Remarkably, the sensitivity of spliceosome mutant cells to NMD inhibition was rescued by overexpression of RNase H1, which removes R-loops in the genome. Together, these findings shed new light on the functional interplay between NMD and RNA splicing and suggest a novel synthetic lethal strategy for the treatment of MDS and cancers with spliceosome mutations. Significance: This study has developed a novel NMD reporter system and identified a potential therapeutic approach of targeting the NMD pathway to treat cancer with spliceosome gene mutations.
Abstract 334: Point-Of-Care Ultrasound in the Assessment of Optic Nerve Sheath Diameter After Out-Of-Hospital Cardiac Arrest
Authors: Pavitra Kotini-Shah, Sarah E Kim, Richard Gordon, Benjamin Karfunkle, Pratik B Doshi, Misha Granado, Henry E Wang, Terry L Vanden Hoek
Journal: Circulation (2019)

Introduction: Hypoxic-ischemic injury from cardiac arrest may cause cerebral edema, leading to increased intracranial pressure (ICP) and brain tissue damage. Optic nerve sheath diameter (ONSD) is associated with elevated ICP. Limited clinical studies have reported ONSD changes in the early post-resuscitation time frame. We sought to evaluate the utility of bedside ocular ultrasound measurements in the assessment of post-cardiac arrest brain injury. Methods: We studied adult out-of-hospital cardiac arrests treated at an urban academic ED and achieving return of spontaneous circulation (ROSC) between May 2018 to May 2019. We included witnessed and unwitnessed arrest as well as shockable and non-shockable rhythms. After ROSC, trained emergency physicians performed bedside ultrasonographic assessment of bilateral ONSD at 1, 6, 24, 48, and 72 hours using an ocular preset on a 15MHz linear probe. ONSD measurements at these time frames were compared between groups stratified by rhythm type and neurological outcome. Cerebral performance category (CPC) was measured at 72 hours and at discharge. Results: Out of 48 eligible patients, 15 were excluded from the study due to lack of consent or available ultrasound images. We included 33 patients, of which 11 were female and 22 were male, with a median age of 57 (IQR 20). There were 19 with an initial rhythm of asystole or pulseless electrical activity (PEA), 9 with ventricular fibrillation arrests, and 5 with an unclear rhythm. At 1 hour, patients with CPC 1-2 had smaller ONSD compared to patients with CPC 3-5 (5.5mm vs 6.1mm, p=0.03). At 72 hour, patients with CPC score of 1-2 had an average reduction in ONSD of 1.6mm verses 0.29mm increase in patients with CPC 3-5. Despite small sample size, a trend towards higher ONSD were seen in patients with non-shockable vs shockable rhythm. Females were also consistently found to have smaller ONSD measurements in all time periods compared to males. Conclusions: This is the first study in the USA to perform analysis using ONSD measurements in cardiac arrest patients. Preliminary analysis of this on-going pilot revealed a greater improvement in ONSD diameters in patients with a favorable neurological outcome. OSND may have utility in prognostication of the post-arrest state.
Animaux Venimeux et Venins.
Journal: JAMA (1922)

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Abstract 295: Importance of the Rate of Platelet Activation by Thrombin for Regulating the Size of Thrombi Formed Under Low Blood Flow Velocity Conditions
Authors: Shinichi Goto, Kengo Ayabe, Youth Kawamura, Noriko Tamura, Shinya Goto
Journal: Circulation Research (2016)

Background: Platelets, coagulation cascade including thrombin and fibrin, and fibrinolysis by plasmin along with blood flow are known to play regulatory roles in thrombogenesis. However, quantitative and interactive contribution of these factors are not fully understood. Method: We developed a computer simulation model of thrombi at sites of vessel injury by implementing quantitative parameters of blood flow, platelet, coagulation cascade and fibrinolysis. In this model, we defined thrombi as the area where the amount of activated platelet become 80% or more of the global platelet count of 3.0х10 5 /mm 3 upon vessel damage We have measured the 3-dimensional size of thrombi as defined in various conditions with various parameters of flow velocity, rate of platelet activation by thrombin, rate of thrombin production on the surface of activated platelets, rate of fibrinolysis and rate of plasmin production. Results: Rate of platelet activation by thrombin had the largest influence on the size of thrombi under low flow rate condition of 0.5 (cm/sec) (Fig1 A). When blood flow rate increased to 2.0 (cm/sec), the absolute importance of this parameter decreased (Fig1 B). Conclusion: Our results show that the rate of platelet activation by thrombin, which are signaled with PAR-1 receptor in human, has a marked effect on the size of thrombi in low flow rate condition suggesting the benefit of blocking this receptor in low blood flow condition such as venous thrombosis.