tbuckley/cabot-search huggingface dataset:
Aryl hydrocarbon receptor ligand production by the gut microbiota is decreased in celiac disease leading to intestinal inflammation
Authors: Bruno Lamas, Leticia Hernandez-Galan, Heather J. Galipeau, Marco Constante, Alexandra Clarizio, Jennifer Jury, Natalia M. Breyner, Alberto Caminero, Gaston Rueda, Christina L. Hayes, Justin L. McCarville, Miriam Bermudez Brito, Julien Planchais, Nathalie Rolhion, Joseph A. Murray, Philippe Langella, Linda M. P. Loonen, Jerry M. Wells, Premysl Bercik, Harry Sokol, Elena F. Verdu
Journal: Science Translational Medicine (2020)

Metabolism of tryptophan by the gut microbiota into derivatives that activate the aryl hydrocarbon receptor (AhR) contributes to intestinal homeostasis. Many chronic inflammatory conditions, including celiac disease involving a loss of tolerance to dietary gluten, are influenced by cues from the gut microbiota. We investigated whether AhR ligand production by the gut microbiota could influence gluten immunopathology in nonobese diabetic (NOD) mice expressing DQ8, a celiac disease susceptibility gene. NOD/DQ8 mice, exposed or not exposed to gluten, were subjected to three interventions directed at enhancing AhR pathway activation. These included a high-tryptophan diet, gavage with Lactobacillus reuteri that produces AhR ligands or treatment with an AhR agonist. We investigated intestinal permeability, gut microbiota composition determined by 16S rRNA gene sequencing, AhR pathway activation in intestinal contents, and small intestinal pathology and inflammatory markers. In NOD/DQ8 mice, a high-tryptophan diet modulated gut microbiota composition and enhanced AhR ligand production. AhR pathway activation by an enriched tryptophan diet, treatment with the AhR ligand producer L. reuteri, or pharmacological stimulation using 6-formylindolo (3,2-b) carbazole (Ficz) decreased immunopathology in NOD/DQ8 mice exposed to gluten. We then determined AhR ligand production by the fecal microbiota and AhR activation in patients with active celiac disease compared to nonceliac control individuals. Patients with active celiac disease demonstrated reduced AhR ligand production and lower intestinal AhR pathway activation. These results highlight gut microbiota-dependent modulation of the AhR pathway in celiac disease and suggest a new therapeutic strategy for treating this disorder.
Caloric restriction mimetics for the treatment of cardiovascular diseases
Authors: Sebastiano Sciarretta, Maurizio Forte, Francesca Castoldi, Giacomo Frati, Francesco Versaci, Junichi Sadoshima, Guido Kroemer, Maria Chiara Maiuri
Journal: Cardiovascular Research (2020)

Caloric restriction mimetics (CRMs) are emerging as potential therapeutic agents for the treatment of cardiovascular diseases. CRMs include natural and synthetic compounds able to inhibit protein acetyltransferases, to interfere with acetyl coenzyme A biosynthesis, or to activate (de)acetyltransferase proteins. These modifications mimic the effects of caloric restriction, which is associated with the activation of autophagy. Previous evidence demonstrated the ability of CRMs to ameliorate cardiac function and reduce cardiac hypertrophy and maladaptive remodelling in animal models of ageing, mechanical overload, chronic myocardial ischaemia, and in genetic and metabolic cardiomyopathies. In addition, CRMs were found to reduce acute ischaemia-reperfusion injury. In many cases, these beneficial effects of CRMs appeared to be mediated by autophagy activation. In the present review, we discuss the relevant literature about the role of different CRMs in animal models of cardiac diseases, emphasizing the molecular mechanisms underlying the beneficial effects of these compounds and their potential future clinical application.
Impact of prior treatment on feasibility and outcomes of Zenker’s peroral endoscopic myotomy (Z-POEM)
Authors: Omid Sanaei, Yervant Ichkhanian, Oscar V. Hernández Mondragón, Jose Nieto, Arunkumar Krishnan, Marcel Tantau, Alina Tantau, Pankaj N. Desai, Gregory G. Ginsberg, Monica Saumoy, Ameya Deshmukh, Mikhail Attaar, Jad Farha, Manol Jovani, Sarah S. Al-Ghamdi, Michael Ujiki, Mouen A. Khashab
Journal: Endoscopy (2020)

Abstract Background Zenker’s peroral endoscopic myotomy (Z-POEM) is a novel procedure for the management of symptomatic Zenker’s diverticulum. This study aims to report the technical feasibility and outcomes of Z-POEM in the management of Zenker’s diverticulum after prior failed interventions. Methods Patients with persistent or recurrent symptoms after prior endoscopic and/or surgical intervention for Zenker’s diverticulum were retrospectively included. The primary outcome was clinical success, defined as complete or near complete resolution of dysphagia (dysphagia score of 0 or 1) without the need for repeat endoscopic or surgical intervention during follow-up. Results Z-POEM was technically successful in 30/32 patients (93.8 %). Clinical success was achieved in 29/30 patients (96.7 %), and Z-POEM significantly reduced the median (interquartile range [IQR]) dysphagia score of patients from 2 (1 – 2) to 0 (0) (P &lt; 0.001) over a median duration of follow up of 166 days (IQR 39 – 566). Four patients (12.5 %) had adverse events (two inadvertent mucosotomies and two leaks found on post-procedural esophagrams). Conclusion Z-POEM is feasible, safe, and effective in the majority of patients with recurrent symptoms after prior surgical or endoscopic interventions.
TCT CONNECT-321 Prognostic Impact of Coronary Flow Reserve and Hyperemic Microvascular Resistance on Composite Major Adverse Cardiovascular Events
Authors: Takumi Toya, Michel Corban, Ji Young Park, Ali Ahmad, Ilke Ozcan, Faten Sebaali, Rajiv Gulati, Lilach Lerman, Amir Lerman
Journal: Journal of the American College of Cardiology (2020)
Gold Nanoparticles: Near Infrared‐Activatable Platinum‐Decorated Gold Nanostars for Synergistic Photothermal/Ferroptotic Therapy in Combating Cancer Drug Resistance (Adv. Healthcare Mater. 20/2020)
Authors: Andrea C. del Valle, Chih‐Kuang Yeh, Yu‐Fen Huang
Journal: Advanced Healthcare Materials (2020)

In article number 2000864 by Yu-Fen Huang and co-workers, platinum-decorated gold nanostars (Pt-AuNS) are presented as a novel metal nanoprodrug for combined photothermal-ferroptotic therapy to combat cancer drug resistance. Upon NIR irradiation, the active metallic (Pt and Au) payloads are released, inducing selective cancer cell death. The mechanism of action is attributed to the intracellular GSH depletion and GPX4 inactivation, leading to a subsequent accumulation of lipid hydroperoxides that executes ferroptosis.
High throughput single-cell detection of multiplex CRISPR-edited gene modifications
Authors: Elisa ten Hacken, Kendell Clement, Shuqiang Li, María Hernández-Sánchez, Robert Redd, Shu Wang, David Ruff, Michaela Gruber, Kaitlyn Baranowski, Jose Jacob, James Flynn, Keith W. Jones, Donna Neuberg, Kenneth J. Livak, Luca Pinello, Catherine J. Wu
Journal: Genome biology (2020)

Abstract CRISPR-Cas9 gene editing has transformed our ability to rapidly interrogate the functional impact of somatic mutations in human cancers. Droplet-based technology enables the analysis of Cas9-introduced gene edits in thousands of single cells. Using this technology, we analyze Ba/F3 cells engineered to express single or multiplexed loss-of-function mutations recurrent in chronic lymphocytic leukemia. Our approach reliably quantifies mutational co-occurrences, zygosity status, and the occurrence of Cas9 edits at single-cell resolution.
Outcomes According to ALK Status Determined by Central Immunohistochemistry or Fluorescence In Situ Hybridization in Patients With ALK-Positive NSCLC Enrolled in the Phase 3 ALEX Study
Authors: Tony Mok, Solange Peters, D. Ross Camidge, Johannes Noé, Shirish Gadgeel, Sai-Hong Ignatius Ou, Dong-Wan Kim, Krzysztof Konopa, Emanuela Pozzi, Ting Liu, Isabell R. Loftin, Crystal Williams, Alice T. Shaw
Journal: Journal of Thoracic Oncology (2020)

We retrospectively examined progression-free survival (PFS) and response by ALK fluorescence in-situ hybridization (FISH) status in patients with advanced ALK immunohistochemistry (IHC)-positive non-small-cell lung cancer (NSCLC) in the ALEX study.
Adiponectin restrains ILC2 activation by AMPK-mediated feedback inhibition of IL-33 signaling
Authors: Lu Wang, Yan Luo, Liping Luo, Dandan Wu, Xiaofeng Ding, Handong Zheng, Haisha Wu, Bilian Liu, Xin Yang, Floyd Silva, Chunqing Wang, Xing Zhang, Xianyun Zheng, Jindong Chen, Jonathan Brigman, Michael Mandell, Zhiguang Zhou, Feng Liu, Xuexian O. Yang, Meilian Liu
Journal: The Journal of Experimental Medicine (2020)

ILC2s are present in adipose tissue and play a critical role in regulating adipose thermogenesis. However, the mechanisms underlying the activation of adipose-resident ILC2s remain poorly defined. Here, we show that IL-33, a potent ILC2 activator, stimulates phosphorylation of AMPK at Thr172 via TAK1 in primary ILC2s, which provides a feedback mechanism to inhibit IL-33-induced NF-κB activation and IL-13 production. Treating ILC2s with adiponectin or an adiponectin receptor agonist (AdipoRon) activated AMPK and decreased IL-33-NF-κB signaling. AdipoRon also suppressed cold-induced thermogenic gene expression and energy expenditure in vivo. In contrast, adiponectin deficiency increased the ILC2 fraction and activation, leading to up-regulated thermogenic gene expression in adipose tissue of cold-exposed mice. ILC2 deficiency or blocking ILC2 function by neutralization of the IL-33 receptor with anti-ST2 diminished the suppressive effect of adiponectin on cold-induced adipose thermogenesis and energy expenditure. Taken together, our study reveals that adiponectin is a negative regulator of ILC2 function in adipose tissue via AMPK-mediated negative regulation of IL-33 signaling.
Glial Interfaces: Advanced Materials and Devices to Uncover the Role of Astroglial Cells in Brain Function and Dysfunction
Authors: Luca Maiolo, Vincenzo Guarino, Emanuela Saracino, Annalisa Convertino, Manuela Melucci, Michele Muccini, Luigi Ambrosio, Roberto Zamboni, Valentina Benfenati
Journal: Advanced Healthcare Materials (2020)

Abstract Research over the past four decades has highlighted the importance of certain brain cells, called glial cells, and has moved the neurocentric vision of structure, function, and pathology of the nervous system toward a more holistic perspective. In this view, the demand for technologies that are able to target and both selectively monitor and control glial cells is emerging as a challenge across neuroscience, engineering, chemistry, and material science. Frequently neglected or marginally considered as a barrier to be overcome between neural implants and neuronal targets, glial cells, and in particular astrocytes, are increasingly considered as active players in determining the outcomes of device implantation. This review provides a concise overview not only of the previously established but also of the emerging physiological and pathological roles of astrocytes. It also critically discusses the most recent advances in biomaterial interfaces and devices that interact with glial cells and thus have enabled scientists to reach unprecedented insights into the role of astroglial cells in brain function and dysfunction. This work proposes glial interfaces and glial engineering as multidisciplinary fields that have the potential to enable significant advancement of knowledge surrounding cognitive function and acute and chronic neuropathologies.
Brain Tumor Stem Cell Dependence on Glutaminase Reveals a Metabolic Vulnerability through the Amino Acid Deprivation Response Pathway
Authors: Ian J. Restall, Orsolya Cseh, Laura M. Richards, Trevor J. Pugh, H. Artee Luchman, Samuel Weiss
Journal: Cancer Research (2020)

Cancer cells can metabolize glutamine to replenish TCA cycle intermediates, leading to a dependence on glutaminolysis for cell survival. However, a mechanistic understanding of the role that glutamine metabolism has on the survival of glioblastoma (GBM) brain tumor stem cells (BTSC) has not yet been elucidated. Here, we report that across a panel of 19 GBM BTSC lines, inhibition of glutaminase (GLS) showed a variable response from complete blockade of cell growth to absolute resistance. Surprisingly, BTSC sensitivity to GLS inhibition was a result of reduced intracellular glutamate triggering the amino acid deprivation response (AADR) and not due to the contribution of glutaminolysis to the TCA cycle. Moreover, BTSC sensitivity to GLS inhibition negatively correlated with expression of the astrocytic glutamate transporters EAAT1 and EAAT2. Blocking glutamate transport in BTSCs with high EAAT1/EAAT2 expression rendered cells susceptible to GLS inhibition, triggering the AADR and limiting cell growth. These findings uncover a unique metabolic vulnerability in BTSCs and support the therapeutic targeting of upstream activators and downstream effectors of the AADR pathway in GBM. Moreover, they demonstrate that gene expression patterns reflecting the cellular hierarchy of the tissue of origin can alter the metabolic requirements of the cancer stem cell population. SIGNIFICANCE: Glioblastoma brain tumor stem cells with low astrocytic glutamate transporter expression are dependent on GLS to maintain intracellular glutamate to prevent the amino acid deprivation response and cell death.
Covid-19: Fauci awarded for “unprecedented public service” while Trump fires more insults
Authors: Janice Hopkins Tanne
Journal: BMJ (2020)

The US National Academy of Medicine has awarded Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), its first Presidential Citation for Exemplary Leadership.

At its virtual annual meeting on 19 October, the academy cited Fauci’s “unprecedented public service” for nearly 40 years at NIAID; as “trusted advisor to six US presidents during public health crises including HIV/AIDS, severe acute respiratory syndrome (SARS), anthrax, influenza, and Ebola; and firm and steady leadership during the covid-19 pandemic.” Fauci has provided “an unwavering, trusted voice to the nation and world on behalf of science based policy and public health,” the academy added.

Presidential citations are awarded to public service figures to recognise distinguished achievement.

But in his latest …
Matshidiso Moeti, first female WHO Regional Director
Authors: Tony Kirby
Journal: The Lancet Infectious Diseases (2020)

To escape South Africa's oppressive apartheid system, Matshidiso Moeti's parents, both public health doctors, decided to move the family from Johannesburg to Botswana to ensure their children had the best education possible. Today, she has one of the most important jobs in global health, as WHO Regional Director for Africa. "It was physics, not medicine, I really wanted to study at university, but some of my physics teachers were not very inspiring!" Moeti tells The Lancet Infectious Diseases.
TCT CONNECT-117 Impact of Pre-Existing Pacemaker on Survival and Echocardiographic Outcomes After Transcatheter Aortic Valve Replacement With SAPIEN-3 Valve
Authors: Yasser Sammour, Rama Dilip Gajulapalli, Hassan Lak, Sanchit Chawla, Cameron Incognito, Arnav Kumar, Kimi Sato, Jay Patel, James Yun, Zoran Popovic, Daniel Burns, Lars Svensson, Khaldoun Tarakji, Oussama Wazni, Grant Reed, Rishi Puri, Amar Krishnaswamy, Samir Kapadia
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-18 Frontline Strategies in ST-Segment Elevation Myocardial Infarction Management: Creating Artificial Intelligence Algorithms for ECG Diagnosis
Authors: Sameer Mehta, Francisco Fernandez, Carlos Villagran, Daniel Vieira, Gladys Pinto, Samantha Quintero, Yogaraja Vijayan, Carmen Sanchez, Lorena Pisana, Nino Coutelle
Journal: Journal of the American College of Cardiology (2020)
Elevated 68Ga-FAPI Accumulation in a Recurrent Angiomyolipoma
Authors: Chunxia Qin, Yongkang Gai, Qingyao Liu, Fuqiang Shao, Xiaoli Lan
Journal: Clinical Nuclear Medicine (2020)

Abstract 68 Ga-FAPI ( 68 Ga-labeled fibroblast activation protein inhibitor) PET imaging has been recently introduced for the diagnosis and staging in various malignant tumors. However, the reports about the utility of FAPI imaging in benign tumor are relatively rare. Here we report a case of pathologically proven recurrent angiomyolipoma in the left retroperitoneal area with low 18 F-FDG uptake but diffuse heterogeneous intense 68 Ga-FAPI uptake together with suspected lung metastases in a 53-year-old woman. Our case illustrates FAPI imaging could be helpful not only for detecting various malignant tumors but also for benign tumor like this case due to fibrotic activity in the disease.
Discovery of a dual inhibitor of NQO1 and GSTP1 for treating glioblastoma
Authors: Kecheng Lei, Xiaoxia Gu, Alvaro G. Alvarado, Yuhong Du, Shilin Luo, Eun Hee Ahn, Seong Su Kang, Bing Ji, Xia Liu, Hui Mao, Haian Fu, Harley I. Kornblum, Lingjing Jin, Hua Li, Keqiang Ye
Journal: Journal of Hematology & Oncology (2020)

Glioblastoma (GBM) is a universally lethal tumor with frequently overexpressed or mutated epidermal growth factor receptor (EGFR). NADPH quinone oxidoreductase 1 (NQO1) and glutathione-S-transferase Pi 1 (GSTP1) are commonly upregulated in GBM. NQO1 and GSTP1 decrease the formation of reactive oxygen species (ROS), which mediates the oxidative stress and promotes GBM cell proliferation.
Systemic allergic reactions induced by labile plant‐food allergens: Seeking potential cofactors. A multicenter study
Authors: Riccardo Asero, Renato Ariano, Arianna Aruanno, Claudio Barzaghi, Paolo Borrelli, Moira Busa, Giorgio Celi, Massimo Cinquini, Gabriele Cortellini, Francesca D’Auria, Marco De Carli, Camilla Di Paolo, Giulia Garzi, Fabio Lodi Rizzini, Monica Magnani, Giuseppina Manzotti, Alessandro Marra, Stefano Miceli Sopo, Francesco Murzilli, Eleonora Nucera, Elena Pinter, Valerio Pravettoni, Federica Rivolta, Angela Rizzi, Nicoletta Saporiti, Enrico Scala, Danilo Villalta, Mona‐Rita Yacoub, Giuliana Zisa
Journal: Allergy (2020)

Heat-and-pepsin-sensitive plant food allergens (PR-10 and profilin) sometimes cause systemic reaction.To detect the risk factors for systemic reactions induced by labile food allergens.A retrospective multicenter study was performed on patients with a documented history of systemic allergic reaction to labile plant food allergens and on age-matched controls with a history of oral allergy syndrome (OAS) induced by the same foods. Offending foods, their amount, and state (solid or liquid), and potential cofactors (nonsteroidal anti-inflammatory drugs, protonic pump inhibitors, exercise, alcohol, and fasting) were considered.We studied 89 patients and 81 controls. Sensitization to PR-10 or profilin, IgE to Bet v 1 and/or Bet v 2, and foods causing OAS were similar in the two groups. Twenty patients experienced >1 systemic allergic reaction. Tree nuts, Rosaceae, Apiaceae, and soymilk were the main offending foods. Seventeen (19%) patients were taking a PPI when the systemic reaction occurred (vs 5% in controls; P < .025). The ingestion of the offending food in liquid form (soymilk) was frequent among patients (15%) but unusual among controls (2%; P < .025). Soy milk-induced systemic reactions were independent of PPI treatment. Fasting and excess of allergen, but not NSAID and exercise, were other relevant cofactors for systemic reactions. Systemic reactions occurred without any identifiable cofactor in 39 (44%) cases.PR-10- and profilin-induced systemic reactions are facilitated by PPI, ingestion of large amounts of unprocessed foods, and fasting. Soybean beverages represent a risk for PR-10 hypersensitive patients and should be avoided.
Abstract 14004: Atrial Fibrillation in Transthyretin Amyloid Cardiomyopathy May Present With Controlled Ventricular Response: A Retrospective Study
Authors: Lindsey R Mitrani, Elissa A Driggin, Jeffeny De Los Santos, Stephen Helmke, Mathew S Maurer
Journal: Circulation (2019)

Introduction: Transthyretin amyloid (TTR) cardiomyopathy results from deposits of amyloid fibrils in the heart. There is an increased incidence of atrial fibrillation (AF) in patients with TTR. Hyp...
Neighborhood poverty and pediatric allogeneic hematopoietic cell transplantation outcomes: a CIBMTR analysis
Authors: Kira Bona, Ruta Brazauskas, Naya He, Leslie Lehmann, Hisham Abdel-Azim, Ibrahim A Ahmed, A Samer Al-Homsi, Mahmoud Aljurf, Staci D. Arnold, Sherif M Badawy, Minoo Battiwalla, Sara Beattie, Neel S. Bhatt, Jignesh Dalal, Christopher E. Dandoy, Miguel Angel Diaz, Haydar A. Frangoul, César O. Freytes, Siddhartha Ganguly, Biju George, David Gomez-Almaguer, Theresa Hahn, Rammurti T. Kamble, Jennifer M. Knight, C. Fred LeMaistre, Jason Law, Hillard M. Lazarus, Navneet S. Majhail, Richard F. Olsson, Jaime Preussler, Bipin N. Savani, Raquel Schears, Sachiko Seo, Akshay Sharma, Alok Srivastava, Amir Steinberg, David Szwajcer, Baldeep Wirk, Ayami Yoshimi, Nandita Khera, William A. Wood, Shahrukh Hashmi, Christine N. Duncan, Wael Saber
Journal: Blood (2020)
TCT CONNECT-180 Novel Pericardial Left Ventricular Assist Device (PALVAD) Assessment via Large Animal and Cadaveric Models
Authors: Diluka Premawardhana, Alexander Lodge, Siddhant Sachdev, Elisavet Karamanavi, Deevia Kotecha, John Lees, Alex Rothman, Julian Gunn, Piyal Samara-ratna, David Adlam
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-140 Direct Implantation of a Supra-Annular Self-Expanding Bioprostheses Has No Impact on 1-Year Clinical Outcomes
Authors: Georgios Benetos, Maria Drakopoulou, Maria Karmpalioti, Konstantinos Stathogiannis, Maria Xanthopoulou, George Latsios, Andreas Synetos, Ilias Kosmas, Georgios Katsimagklis, Antonios Mastrokostopoulos, Haim Danenberg, Dimitris Tousoulis, Konstantinos Toutouzas
Journal: Journal of the American College of Cardiology (2020)
Long Term Followup of Sickle Cell Disease Post Hematopoietic Stem Cell Transplant from Uganda
Authors: Musa K. Waiswa, Gaurav Kharya, Divya Bansal, Silky Jain, Edward Kasirye, Francis N. Ssali, David Ndawula, Henry Ddungu, Madeleine M Verhovsek, Deogratias Munube
Journal: Blood (2017)
Expression profiling of liver cell lines expressing entire or parts of hepatitis C virus open reading frame
Authors: Hideki Aizaki, Takashi Harada, Motoyuki Otsuka, Naohiko Seki, Mami Matsuda, Yue Wei Li, Hayato Kawakami, Yoshiharu Matsuura, Tatsuo Miyamura, Tetsuro Suzuki
Journal: Hepatology (2002)

Although hepatitis C virus (HCV) is a causative agent of liver diseases, its mechanism of pathogenesis is still unclear, mainly because of the lack of adequate cell culture systems to support HCV infection and replication. In this report, we describe development and characterization of human hepatoma cell lines constitutively expressing entire (Hep394) or parts (Hep352, Hep3294) of the HCV open reading frame (ORF). The viral and cellular proteolytic machinery involved in the viral precursor processing was consistently functional, and processed HCV proteins were synthesized in these established cell lines. By using a cDNA microarray analysis coupled with semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), we identified 12 genes up-regulated and 4 genes down-regulated in Hep394 cells. With regard to genes related to cell growth regulation, we found up-regulation of forkhead transcription factor FREAC-1, poly (A) binding protein PABP2, and Ras suppressor Rsu-1. Another category of changes in gene expression includes MHC antigens, which play an important role in the T-cell-mediated immune reaction in the liver. In conclusion, functional genomic approaches comparing expression among the different cell lines expressing parts of the HCV genome may promote our understanding of the molecular basis of pathogenicity of HCV infection. (Hepatology2002;36:1431-1438).