tbuckley/cabot-search huggingface dataset:
Letter to the Editor: The Porto‐Hepatic Spectrum of Cirrhotic Encephalopathy
Authors: Maria‐Angeles Aller, Jaime Arias, Javier Blanco‐Rivero
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. To the Editor: In his interesting article,(1) Elliot B. Tapper proposes that the prediction of overt hepatic encephalopathy in cirrhosis is based on portal hypertension, among other risk factors.1 Thus, it should be considered that portal hypertension per se is induced by mechanotransduction inflammation in the mesenteric venous system.2 This splanchnic endothelial inflammation related to mechanical energy can spread to the cells located in the subendothelial space. One of the cellular types that are increased in the subendothelial space in portal hypertension is the mast cell.3 The mast cells have the ability of changing their phenotype depending on the neighborhood in which they are recruited.4 Also, mast cells have a dual action, pro‐ and anti‐inflammatory. In portal hypertension, the mast cells activated by mechanical energy could have a key role in triggering a neurovascular inflammatory response with vasodilation and consequently increasing forward venous flow. Also, mast cells release angiogenic factors that induce collateral porto‐systemic circulation. Inflammatory splanchnic mast cells can stimulate the enteric nervous plexus and the autonomic nervous system. Through this afferent pathway, this signal activated by mechanotransduction can reach the central nervous system (CNS) and can induce an inflammatory neurological impairment.5 Indeed, mast cells can cross the hematoencephalic barrier reaching the brain. Therefore, an additional etiopathogenic mechanism in the early development of hepatic encephalopathy could be the inflammatory portal hypertensive response. If so, it would be more appropriate referring this early pathological condition in portal hypertension as portal hypertensive encephalopathy.5 In particular, portal hypertension would initially sensitize the CNS (first hit or portal hypertensive encephalopathy) and then, when the liver disease occurs (second hit), hepatic encephalopathy would develop. Hence, the condition considered as hepatic encephalopathy should be studied as a process of a mixed etiopathogeny that is portal and hepatic. Thus, a more appropriate name for this neurological condition could be “porto‐hepatic encephalopathy” (Fig. 1). Furthermore, in portal hypertension and in liver disease, mast cells could act through an adaptive mechanism to physical and metabolic noxious injuries.Figure 1: Schematic representation of the etiopathogenic spectrum of the encephalopathy related to both portal hypertension and chronic liver disease.
RNA integrity number (RIN) - towards standardization of RNA quality assessment
Authors: Odilo M. Mueller, Andreas Schroeder, Samar Lightfoot, Ruediger Salowsky, Susanne Stocker
Journal: Cancer Research (2004)

1649  RNA quality assessment has been identified as one of the most critical elements in order to obtain meaningful gene expression data via microarray or real-time PCR experiments. Current advances in microfluidics have improved RNA quality measurements tremendously by allowing a more detailed look at RNA degradation patterns by providing electrophoretic traces of RNA samples. However, the interpretation of such electropherograms still requires a certain level of experience and can vary from one researcher to the next. A so-called “RNA integrity number” (RIN) algorithm is introduced that assigns a user-independent integrity number to each RNA sample. The RIN has been developed using neural networks by “teaching” this algorithm with a large number of RNA integrity data. It was found that the RIN is more reliable than the ribosomal ratio, when assessing the integrity of RNA samples. The RIN is shown to be largely independent of RNA concentration, instrument (Agilent 2100 bioanalyzer), and most importantly, the origin of the RNA sample. Using the RIN, researchers can work towards standardization of the important RNA integrity measurement ensuring reproducibility and reliability of gene expression experiments.
Genetic risk prediction of atrial fibrillation in a contemporary heart failure cohort
Authors: M. Kloosterman, B. T. Santema, C. Roselli, A. L. Koekemoer, S. P. R. Romaine, C. P. Nelson, I. C. Van Gelder, C. S. P. Lam, P. Van der Harst, I. E. Sama, D. J. Van Veldhuisen, A. A. Voors, N. J. Samani, M. Rienstra
Journal: European Journal of Heart Failure (2019)
Enhancement of Risk Prediction With Machine Learning
Authors: Jennifer A. Rymer, Sunil V. Rao
Journal: JAMA Network Open (2019)

Bobak J. Mortazavi, PhD; Emily M. Bucholz, MD, PhD, MPH; Nihar R. Desai, MD, MPH; Chenxi Huang, PhD; Jeptha P. Curtis, MD; Frederick A. Masoudi, MD, MSPH; Richard E. Shaw, MA, PhD; Sahand N. Negahban, PhD; Harlan M. Krumholz, MD, SM
Using MALDI-TOF mass spectrometry for tracking of minimal residual disease in peripheral blood from patients with multiple myeloma.
Authors: Marion Eveillard, Even Rustad, Mikhail Roshal, Yanming Zhang, Amanda Ciardiello, Neha Korde, Malin Hultcrantz, Hani Hassoun, Eric L. Smith, Alexander M. Lesokhin, Sham Mailankody, Carl Ola Landgren, Katie Thoren
Journal: Journal of Clinical Oncology (2019)

e19525 Background: Minimal residual disease (MRD) negativity after completed therapy is associated with longer progression-free survival (PFS) in patients with multiple myeloma (MM). Current standard of care for MRD testing use flow cytometry and/or next generation sequencing (NGS)-based assays applied on bone marrow (BM) aspirate samples. To develop a strategy for MRD tracking in peripheral blood (PB), we were motivated to evaluate MALDI-TOF head-to-head with established bone marrow-based MRD assays. Methods: We used MALDI-TOF mass spectrometry to detect M-proteins in PB. Our cohort included patients who had serum samples available at 2 timepoints including during active disease and within 60 days of MRD results as determined by flow cytometry of BM aspirates. The cohort enrolled 71 patients (26 females, 45 males) with a median age of 61 years (37-78 years). Twenty-seven patients had high-risk cytogenetics at baseline. Patients were classified at diagnosis as ISS1 (n = 38), ISS2 (n = 18) or ISS3 (n = 6). The flow cytometry based MRD assay was performed using MSKCCs 10-color, single-tube method. MALDI-TOF analysis was performed as described by Mills et al. Samples taken during active disease were used to identify the mass/charge ratio of the M-protein at baseline and in follow-up samples. MALDI-TOF results were compared to flow cytometry bone marrow-based MRD results. Results: The median time between diagnosis and the MRD timepoint was 13.4 months (3.4-91 months). MALDI-TOF in PB and flow cytometry BM-based MRD results were concordant for 44/71 (62%) patients (8+/+, 36 -/- respectively) while 27 were discordant (10 +/-, 17-/+). Fifty-four of 71 patients were in complete response (CR) (45/54 in sCR) at the time of MRD. MALDI-TOF was still positive in 13 of these 54 CR patients. In this cohort, the median PFS since MRD assessment was not reached in the 2 subgroups of double negative patients (n = 31) or in patients with a positive result in at least one technique (n = 23) with a median follow-up of 11.2 months (0-34.6 months). Conclusions: In 44/71 (62%) samples, MALDI-TOF of PB results and flow cytometry BM-based MRD results were concordant. MALDI-TOF of PB may be useful for detecting measurable residual disease and for the monitoring of MM patients during maintenance therapy with the future goal to rule out early recurrent disease.
Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Incident Diabetes and Microvascular Disease
Authors: Andres Cardenas, Marie-France Hivert, Diane R. Gold, Russ Hauser, Ken P. Kleinman, Pi-I D. Lin, Abby F. Fleisch, Antonia M. Calafat, Xiaoyun Ye, Thomas F. Webster, Edward S. Horton, Emily Oken
Journal: Diabetes Care (2019)

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are suspected endocrine disruptors widely detected across populations. We examine the extent to which PFASs are associated with diabetes incidence and microvascular disease. Secondarily, we tested whether a lifestyle intervention modifies associations and decreases concentrations.
Abstract 10957: Sevoflurane Pre-conditioning Ameliorates Myocardial Ischemia/Reperfusion Injury via Cox-2 Expression Inhibition in a Cav-3-dependent, AMPK-Independent Pathway
Authors: Jianli Zhao, Yanqing Zhang, Wayne Bond Lau, Feng Wang, Liyuan Jiao, Lili Wang, Baojiang Liu, Yajing Wang
Journal: Circulation (2012)

The inhaled anesthetic sevoflurane has been demonstrated to activate AMP-activated protein kinase (AMPK), upregulate caveolin-3 (Cav3), and protect against myocardial ischemia/reperfusion (MI/R) in...
Oncogenic MYC Induces the Impaired Ribosome Biogenesis Checkpoint and Stabilizes p53 Independent of Increased Ribosome Content
Authors: Carmen Morcelle, Sandra Menoyo, Francisco D. Morón-Duran, Albert Tauler, Sara C. Kozma, George Thomas, Antonio Gentilella
Journal: Cancer Research (2019)

The role of MYC in regulating p53 stability as a function of increased ribosome biogenesis is controversial. On the one hand, it was suggested that MYC drives the overexpression of ribosomal proteins (RP)L5 and RPL11, which bind and inhibit HDM2, stabilizing p53. On the other, it has been proposed that increased ribosome biogenesis leads the consumption of RPL5/RPL11 into nascent ribosomes, reducing p53 levels and enhancing tumorigenesis. Here, we show that the components that make up the recently described impaired ribosome biogenesis checkpoint (IRBC) complex, RPL5, RPL11, and 5S rRNA, are reduced following MYC silencing. This leads to a rapid reduction in p53 protein half-life in an HDM2-dependent manner. In contrast, MYC induction leads to increased ribosome biogenesis and p53 protein stabilization. Unexpectedly, there is no change in free RPL5/RPL11 levels, but there is a striking increase in IRBC complex bound to HDM2. Our data support a cell-intrinsic tumor-suppressor response to MYC expression, which is presently being exploited to treat cancer. SIGNIFICANCE: Oncogenic MYC induces the impaired ribosome biogenesis checkpoint, which could be potentially targeted for cancer treatment.
Nonarrhythmic Sudden Cardiac Death in Chronic Heart Failure—A Preventable Event?
Authors: Milton Packer
Journal: JAMA Cardiology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Production of autologous monocytes stimulated ex vivo with peg-interferon alfa 2b and interferon gamma 1b for intraperitoneal administration in phase I clinical trial.
Authors: Anna Duemler, Daniel S Green, Steven L. Highfill, David Stroncek, Kathryn Zoon, Christina M. Annunziata
Journal: Journal of Clinical Oncology (2019)

5 Background: Monocytes are myeloid cells that reside in the blood and bone marrow and respond to inflammation. At the site of inflammation, monocytes express cytokines and chemokines. Monocytes are cytotoxic to tumor cells in the presence of pro-inflammatory cytokines such as Interferon Alpha and Interferon Gamma. We previously showed that monocytes stimulated with both interferons (IFNs) result in synergistic killing of ovarian cancer cells. We aimed to develop this cell therapy product for clinical application. Methods: Counter flow elutriation was performed on healthy donors. The monocyte-containing, RO-fraction was assessed for total monocyte number, purity, viability, and cytotoxicity with and without cryopreservation. All 5 fractions from the elutriation procedure were also assessed by flow cytometry to measure the percent of immune cell subsets. This procedure is now implemented in a clinical trial where 8 patients completed the apheresis and elutriation process for a total of 13 runs. Results: Iterative monocyte isolation using counter flow elutriation with or without cryopreservation can yield over 2 billion monocytes for each subject with high purity. We show that monocytes are stable, viable, and retain cytotoxic functions when cultured with IFNs. Flow cytometric analysis shows expected heterogeneity in the collected monocytes. In each case, the elutriation run met pre-set release criteria for both total monocyte number and purity requirements for the therapeutic product. Conclusions: We demonstrated that large scale isolation of monocytes can be achieved with elutriation from either healthy donors or patients with advanced, chemotherapy resistant ovarian cancer. Monocytes can be cryopreserved and maintain viability and cytotoxic function in the final cell therapy product prior to infusion. We translated these observations to a currently accruing clinical trial using adoptive cell transfer of autologous monocytes stimulated ex-vivo with IFNs and infused into the peritoneal cavity of patients with advanced, chemotherapy resistant, ovarian cancer. (Protocol NCT00327067). Clinical trial information: NCT02948426.
68Ga-DOTATATE Uptake in Pancreatic Metastasis of Renal Cell Carcinoma Mimicking Pancreatic Neuroendocrine Tumor
Authors: Cigdem Soydal, Demet Nak, Mine Araz, Ahmet Demirkazik, Nuriye Ozlem Kucuk
Journal: Clinical Nuclear Medicine (2019)

Abstract A 61-year-old man, with a history of prior clear cell renal cell carcinoma in remission, was referred to 68 Ga-DOTATATE PET/CT for the further evaluation of pancreatic tail mass. 68 Ga-DOTATATE PET/CT showed pathologically intense uptake on the pancreatic mass; subsequent biopsy of the pancreatic mass confirmed the diagnosis of clear cell renal cell carcinoma metastasis. 68 Ga-DOTATATE uptake is not specific for neuroendocrine tumors. In the presence of prior malignancy, it should be kept in mind that malignancies apart from neuroendocrine tumors express somatostatin receptors, and they can show 68 Ga-DOTATATE uptake.
Abstract 14785: Heart Rate and Subclinical Left Ventricular Dysfunction: Insights From the Cardiovascular Abnormalities and Brain Lesions (CABL) Study
Authors: Koki Nakanishi, Zhezhen Jin, Cesare Russo, Shunichi Homma, Mitchell S Elkind, Tatjana Rundek, Aylin Tugcu, Ralph L Sacco, Marco R Di Tullio
Journal: Circulation (2017)

Background: Increased heart rate (HR) is a strong predictor of unfavorable cardiovascular outcomes, although the mechanisms are still unknown. We hypothesized that increased HR may be associated wi...
Abstract 121: Metabolic Regulation of Ischemia/Reperfusion: Role of the Unfolded Protein Response
Authors: Zhao Wang
Journal: Circulation Research (2016)

Myocardial infarction is a leading cause of death worldwide. The most effective approach to mitigate cardiac damage is timely and efficient restoration of occlusion in coronary artery. This process, ischemia/reperfusion (I/R), triggers additional damage (I/R damage), which may substantially contribute to the final cardiac infarction. Despite extensive efforts and paramount clinical interests, effective therapeutics remains vacant. A better understanding of the pathology of I/R damage is therefore urgently required. Most processes in I/R are potent inducers of the unfolded protein response (UPR), a cellular adaptive process to accommodate protein-folding stress. We have shown that the most conserved branch of the UPR, the Xbp1s pathway, is strongly induced by I/R. Using both gain- and loss-of-function approaches, we revealed that Xbp1s is necessary and sufficient to protect heart against I/R injury. We went further to discover that Xbp1s is a direct upstream transcriptional factor for multiple, key enzymes of the hexosamine biosynthetic pathway (HBP). The final production of HBP, UDP-GlcNAc, is the obligate substrate for O-GlcNAc protein modification, a prominent post-translational modification. Acute induction of O-GlcNAc modification confers strong protection against various stresses. Upregulation of Xbp1s therefore induces the HBP, UDP-GlcNAc production, consequent O-GlcNAc protein modification, and more importantly, cardioprotection against I/R damage. We found that modulation of the necroptosis pathway participates in Xbp1s-mediated cardioprotection. Elucidation of the pathology of I/R injury will greatly advance our understanding of underlying mechanisms and help identify potential therapeutic targets to tackle the devastating coronary heart disease.
Cardiovascular safety of nintedanib in subgroups by cardiovascular risk at baseline in the TOMORROW and INPULSIS trials
Authors: Imre Noth, Marlies Wijsenbeek, Martin Kolb, Francesco Bonella, Lizette Moros, Daniel Wachtlin, Tamera J. Corte
Journal: European Respiratory Journal (2019)

Nintedanib is a tyrosine kinase inhibitor used to treat idiopathic pulmonary fibrosis (IPF). We investigated the cardiovascular safety of nintedanib using pooled data from the TOMORROW and INPULSIS trials.Cardiovascular events were assessed post hoc in patients with a history of atherosclerotic cardiovascular disease (CVD) and/or one or more cardiovascular risk factors at baseline ("higher cardiovascular risk") and patients with no history of atherosclerotic CVD and no cardiovascular risk factors at baseline ("lower cardiovascular risk").Incidence rates were calculated for 1231 patients (n=723 nintedanib and n=508 placebo), of whom 89.9% had higher cardiovascular risk. Incidence rates of major adverse cardiovascular events were similar in the nintedanib and placebo groups in patients with higher cardiovascular risk (3.88 (95% CI 2.58-5.84) and 3.49 (95% CI 2.10-5.79) per 100 patient-years, respectively) and lower cardiovascular risk (4.78 (95% CI 1.54-14.82) and 5.37 (95% CI 1.73-16.65) per 100 patient-years, respectively). Incidence rates of myocardial infarction in the nintedanib and placebo groups, respectively, were 3.03 (95% CI 1.91-4.81) and 1.16 (95% CI 0.48-2.79) per 100 patient-years in patients with higher cardiovascular risk and 1.59 (95% CI 0.22-11.29) and 1.78 (95% CI 0.25-12.64) per 100 patient-years in patients with lower cardiovascular risk. Incidence rates of other ischaemic heart disease in the nintedanib and placebo groups, respectively, were 1.85 (95% CI 1.02-3.34) and 3.28 (95% CI 1.94-5.54) per 100 patient-years in patients with higher cardiovascular risk and 0 and 1.80 (95% CI 0.25-12.78) per 100 patient-years in patients with lower cardiovascular risk.These data help to establish the cardiovascular safety profile of nintedanib in IPF.
Implanted Phrenic Stimulation Impairs Local Diaphragm Myofiber Reinnervation in Amyotrophic Lateral Sclerosis
Authors: Raquel Guimarães-Costa, Marie-Cécile Niérat, Isabelle Rivals, Capucine Morélot-Panzini, Norma Beatriz Romero, Fabrice Menegaux, François Salachas, Jésus Gonzalez-Bermejo, Thomas Similowski, Gaëlle Bruneteau, Maria del Mar Amador, Jean Christophe Antoine, Marie Christine Arne-Bes, Valérie Attali, Katell Beauvais, Veronique Brunaud-Danel, Gaelle Bruneteau, Jean-Philippe Camdessanche, William Camu, Laurence Carluer, Julien Cassereau, Maud Chapart, Bruno Chenuel, Nathalie Chereau, Pascal Cintas, Pierre Clavelou, Philippe Corcia, André Cornette, Philippe Couratier, Isabelle Court-Fortune, Antoine Cuvelier, Christophe Delclaux, Claude Desnuelle, Sophie Di Maria, Catherine Fargeot, Brigitte Fauroux, Armelle Finet-Monnier, Marie Celine Fleury, Carmen Gaillat, Marjolaine Georges, Maurice Giroud, Jesus Gonzalez-Bermejo, Annick Greil, Muriel Guerrier, Nicolas Guillaume, Nathalie Guy, Didier Hannequin, Valérie Juillien, Raul Juntas-Morales, Romain Kessler, Yvan Kolev, Julien Lagarde, Geraldine Lautrette, Pierre Le Cam, Nadine LeForestier, Gwendal Lemasson, Thimothée Lenglet, Pascal Magro, Anne Mallart, Olivier Martinaud, Vincent Meininger, Fabrice Menegaux, Nicole Meslier, Pierre Moirot, Capucine Morelot-Panzini, Yann Nadjar, Myriam Niel-Duriez, Marie-Cecile Nierat, Severine Noullet, Nicolas Pageot, Thierry Perez, Christophe Perrin, Odile Pillet, Sophie Pittion, Jean Pouget, Pierre-François Pradat, Hélène Prigent, Claudio Rabec, Jean-Damien Ricard, Norma Romero, Catherine Royer, François Salachas, Barbara Schaup, Kamila Sedkaoui, Thomas Similowski, Marie-Hélène Soriani, Christian Straus, Marie-Laure Tanguy, Christine Tranchant, Nadia Vandenberghue, Annie Vershueren, Fausto Viader, Anne-Cecile Wienalek-Bachelet
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Understanding the peripheral cellular immunome in patients with breast cancer.
Authors: Karenia Landa, Eda Holl, Victoria Frazier, Eun-Sil Shelley Hwang, Smita Nair
Journal: Journal of Clinical Oncology (2019)

7 Background: Neoadjuvant chemotherapy (NAC) for breast cancer (BC) is being increasingly used in patients with stage I/II disease. Although previously reserved for patients with locally advanced disease, its use in patients with localized disease allows for higher rates of breast-conserving procedures and provides insight into tumor biology. A complete pathologic response (pCR) to NAC correlates with better clinical outcomes; sadly, many patients do not achieve pCR. The advent of immunotherapy has provided cancer patients with additional treatment options. To optimize immunotherapy in BC we must understand the peripheral cellular immunome (immune subsets and activation status) of patients as they undergo standard of care therapy (SOC). Methods: Our population includes patients with stages I-III BC undergoing SOC. Samples were collected pre- and post-NAC, post-surgery and at 2-month follow-up (FU). Results: Flow cytometry analysis for 11 patients was performed at each time-point to examine percentages of circulating immune cells (see Table). We grouped samples in 3 categories: human epidermal growth factor receptor 2 (HER2+) positive, HER2 negative (HER2-) and triple-negative (TN) tumors. 3 out of 11 patients had pCR (1 HER2+, 1 HER2-, 1 TN); they had highest percentage of circulating CD56+ NK cells during treatment course. Conclusions: We observed striking changes in the immunome of women with stage I-III BC undergoing NAC. Although our findings are preliminary, given our sample size, we observed distinct trends within each immune cell population in specific tumor receptor subtypes. These trends could serve to guide our therapies, allow for better patient selection and predict treatment response in patients. [Table: see text]