tbuckley/cabot-search huggingface dataset:
Peroral endoscopic myotomy and simultaneous endoscopic diverticuloseptotomy in a case of achalasia with diverticula
Authors: Wen Li, Fang Liu, Liang Wu
Journal: Endoscopy (2019)

A 58-year-old man with symptoms of dysphagia and regurgitation was admitted for treatment. Evaluation with endoscopy and contrast esophagogram revealed achalasia cardia with a small mid-esophageal diverticulum and a large epiphrenic diverticulum ([Fig. 1], [Fig. 2]). Peroral endoscopic myotomy (POEM) and a simultaneous endoscopic diverticuloseptotomy were performed in this case ([Video 1]). Firstly, submucosal injection and mucosal incision were made at about 5 cm above the epiphrenic diverticulum. Secondly, a submucosal tunnel was created pointing toward the diverticular septum and extended on both sides of the septum, i. e., the diverticular and esophageal lumen side ([Fig. 3]). Thirdly, complete myotomies of the muscle layer of the diverticular septum and the esophagus were performed separately. Due to technical difficulty, a small mucosal perforation occurred at the most narrow, twisted, and spasmodic part of the distal esophagus ([Fig. 4]). In the final step, the small mucosal injury and the entry of the tunnel were closed with endoclips. An X-ray contrast study 5 days after POEM revealed a free flow of contrast medium across the gastroesophageal junction and a collapsed epiphrenic diverticulum ([Fig. 5]). There was substantial improvement in the patient’s clinical symptoms as well. At the 3-month follow-up, the patient reported complete resolution of dysphagia.
A Phase 2a Study of the LSD1 Inhibitor Img-7289 (bomedemstat) for the Treatment of Myelofibrosis
Authors: Kristen Pettit, Aaron T. Gerds, Abdulraheem Yacoub, Justin M. Watts, Maciej Tartaczuch, Terrence J Bradley, Jake Shortt, William S. Stevenson, Natasha Joan Curtin, James M. Rossetti, Kate Burbury, Georges Natsoulis, Amber Jones, Moshe Talpaz, Jennifer Peppe, David M Ross, Hugh Young Rienhoff
Journal: Blood (2019)
Rapid and sustained response to immune checkpoint inhibition in cutaneous squamous cell carcinoma after allogenic hematopoietic cell transplant for sézary syndrome
Authors: Karam Khaddour, Amy Musiek, Lynn A. Cornelius, Farrokh Dehdashti, Peter Westervelt, Ryan Fields, George Ansstas
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Cutaneous squamous cell carcinoma (cSCC) is not uncommon in association with indolent malignancies that were treated with prior radiotherapy and after allogenic bone marrow transplantation. On the other hand, cutaneous T-cell lymphoma (CTCL) is a subtype of non-Hodgkin's lymphoma which is characterized by an indolent course, with relative refractoriness to conventional chemotherapies and radiotherapy, and occasionally referred for allogeneic hematopoietic cell transplantation (allo-HCT). Recently, the use of immune checkpoint inhibitors has gained attention in the treatment of both cutaneous squamous cell carcinoma and hematological malignancies. However, many patients with hematological malignancies eventually undergo allo-HCT, raising the concern of potential adverse events (graft versus host disease) due to manipulation of the immune system with use of checkpoint inhibitors. <h3>Case presentation</h3> We describe a patient with relapsed refractory CTCL (Sézary Syndrome) who underwent allo-HCT with persistence of disease post-transplant. The patient additionally developed a progressively worsening lesion on the right shoulder which was biopsied and showed poorly differentiated carcinoma (cSCC). Pembrolizumab was started for the treatment of cSCC. After second cycle of treatment, the cSCC lesion responded dramatically to the&nbsp;use of immune checkpoint inhibitor. Also, the patient experienced significant resolution of pruritus and generalized erythema. During 24 months of follow up after initial treatment with checkpoint inhibition immunotherapy, the patient showed durable response of both cSCC and CTCL, as well as restoration of full donor chimerism, without obvious worsening of graft versus host disease (GVHD). <h3>Conclusion</h3> This is the first case to our knowledge of rapid and durable response of both cSCC and CTCL to immune checkpoint inhibition after allo-HCT. Although this report highlights the potential for significant response to this class of medication, further studies are required to confirm the efficacy and safety of this approach in patients with CTCL after allo-HCT given the potential concern of GVHD.
Clinically Significant Bleeding With Ticagrelor Versus Clopidogrel in Korean Patients With Acute Coronary Syndromes Intended for Invasive Management
Authors: Duk-Woo Park, Osung Kwon, Jae-Sik Jang, Sung-Cheol Yun, Hanbit Park, Do-Yoon Kang, Jung-Min Ahn, Pil Hyung Lee, Seung-Whan Lee, Seong-Wook Park, Si Wan Choi, Sang-Gon Lee, Hyuck-Jun Yoon, Taehoon Ahn, Moo Hyun Kim, Deuk Young Nah, Sung Yun Lee, Jei Keon Chae, Seung-Jung Park
Journal: Circulation (2019)

Background: Owing to the differential propensity for bleeding and ischemic events with response to antiplatelet therapy, the safety and effectiveness of potent P2Y12 inhibitor ticagrelor in East Asian populations remain uncertain. Methods: In this multicenter trial, 800 Korean patients hospitalized for acute coronary syndromes with or without ST elevation and intended for invasive management were randomly assigned to receive, in a 1:1 ratio, ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (600 mg loading dose, 75 mg daily thereafter). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to PLATO (Platelet Inhibition and Patient Outcomes) criteria at 12 months. Results: At 12 months, the incidence of clinically significant bleeding was significantly higher in the ticagrelor group than in the clopidogrel group (11.7% [45/400] vs 5.3% [21/400]; hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.34 to 3.79; P =0.002). The incidences of major bleeding (7.5% [29/400] vs 4.1% [16/400], P =0.04) and fatal bleeding (1% [4/400] vs 0%, P =0.04) were also higher in the ticagrelor group. The incidence of death from cardiovascular causes, myocardial infarction, or stroke was not significantly different between the ticagrelor group and the clopidogrel group (9.2% [36/400] vs 5.8% [23/400]; HR, 1.62; 95% CI, 0.96 to 2.74; P =0.07). Overall safety and effectiveness findings were similar with the use of several different analytic methods and in multiple subgroups. Conclusions: In Korean acute coronary syndrome patients intended to receive early invasive management, standard-dose ticagrelor as compared with clopidogrel was associated with a higher incidence of clinically significant bleeding. The numerically higher incidence of ischemic events should be interpreted with caution, given the present trial was underpowered to draw any conclusion regarding efficacy. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02094963.
Novel technique for endoscopic submucosal dissection using an elastic thread delivery hood
Authors: Kinya Fujita, Masahiro Takeshita, Eiji Moriyama, Satoshi Ochiai
Journal: Endoscopy (2019)

Because endoscopic submucosal dissection (ESD) is a challenging technique to perform, various traction techniques have been developed [1] [2] [3] [4] [5]. We designed a new hood – the Dual Traction Hood (Adachi Co., Ltd., Osaka, Japan and Nomura Medical Device Co., Ltd., Nagano, Japan) – which holds dual elastic threads in its thin side pockets ([Fig. 1]).
Dasatinib‐Loaded Erythrocytes Trigger Apoptosis in Untreated Chronic Myelogenous Leukemic Cells: A Cellular Reservoir Participating in Dasatinib Efficiency
Authors: Kelly Airiau, Béatrice Turcq, Stéphane Bouchet, Elodie Laharanne, Jean‐Philippe Vial, Gabriel Etienne, François‐Xavier Mahon, Francis Belloc
Journal: HemaSphere (2018)

Dasatinib is an ABL1 tyrosine kinase inhibitor (TKI) with a short in vivo plasmatic half-life but with good efficiency, which is not fully understood. We investigated the possibility that circulating erythrocytes store and then provide dasatinib to target cells. In vitro coincubation of dasatinib-treated cells with naïve leukemic cells followed by analysis of kinase inhibition, apoptosis induction, fluorescent molecule exchanges, and dasatinib dosage were performed. Cells incubated with clinically relevant concentrations of dasatinib for a short time retained, after a washout procedure, an intracellular pool of dasatinib which was transferable to naïve BCR-ABL1 expressing cells and induced their apoptosis. This was verified in total blood where the huge cellular volume of erythrocytes constituted a large reservoir of dasatinib able to induce apoptosis in naïve BCR-ABL1 cell lines and primitive chronic myeloid leukemia (CML) CD34+ cells. This dasatinib transfer necessitated a contact between donor and acceptor cells. A component exchange occurred during this contact, carrying dasatinib and other TKIs such as nilotinib or the fluorescent sunitinib. An active pool of dasatinib could be buried inside the circulating erythrocytes, out of reach of detoxifying mechanisms, but still available for target cells and thus extending the acute effect of the plasmatic pool of the drug.
Single-cell analysis of RORα tracer mouse lung reveals ILC progenitors and effector ILC2 subsets
Authors: Maryam Ghaedi, Zi Yi Shen, Mona Orangi, Itziar Martinez-Gonzalez, Lisa Wei, Xiaoxiao Lu, Arundhoti Das, Alireza Heravi-Moussavi, Marco A. Marra, Avinash Bhandoola, Fumio Takei
Journal: The Journal of Experimental Medicine (2019)

Lung group 2 innate lymphoid cells (ILC2s) drive allergic inflammation and promote tissue repair. ILC2 development is dependent on the transcription factor retinoic acid receptor–related orphan receptor (RORα), which is also expressed in common ILC progenitors. To elucidate the developmental pathways of lung ILC2s, we generated RORα lineage tracer mice and performed single-cell RNA sequencing, flow cytometry, and functional analyses. In adult mouse lungs, we found an IL-18Rα+ST2− population different from conventional IL-18Rα−ST2+ ILC2s. The former was GATA-3intTcf7EGFP+Kit+, produced few cytokines, and differentiated into multiple ILC lineages in vivo and in vitro. In neonatal mouse lungs, three ILC populations were identified, namely an ILC progenitor population similar to that in adult lungs and two distinct effector ILC2 subsets that differentially produced type 2 cytokines and amphiregulin. Lung ILC progenitors might actively contribute to ILC-poiesis in neonatal and inflamed adult lungs. In addition, neonatal lung ILC2s include distinct proinflammatory and tissue-repairing subsets.
Exome Sequencing of Relapsed Multiple Myeloma Combined with Pooled CRISPR/Cas9 Screens Identifies Gene Mutations Associated with Drug-Specific Resistance
Authors: Stephan Bohl, Laura K. Schmalbrock, Imke Bauhuf, Anna Dolnik, Tamara J. Blätte, Stefanie Lindner, Tatjana Meyer, Sarah Knödler, Denise Miller, Miriam Kull, Christian Langer, Hartmut Döhner, Dirk Heckl, Lars Bullinger, Jan Krönke
Journal: Blood (2019)
Incidence of Late Failure Following Myeloablative Conditioning with BuCy2 and Matched Sibling Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia.
Authors: Shubham Pant, Sayed Mehdi Hamadani, Pamela Crilley, Jeffrey Szer, Anthony J. Dodds, Dustin E. Stevenson, Gary Phillips, Patrick Elder, Ian Nivison-Smith, Belinda Avalos, Sam Penza, David Topolsky, R. Sobecks, Matt Kalaycio, Brian J. Bolwell, Edward Copelan
Journal: Blood (2008)
Immunomodulation: new avenues for treatment
Authors: Laurence Astill Wright
Journal: BMJ (2019)

Song et al’s thought provoking paper and the accompanying editorial by Bisson highlight the life limiting sequelae of chronic hypothalamic pituitary adrenal (HPA) axis dysregulation secondary to post-traumatic stress disorder (PTSD).12 While these chronic inflammatory effects of PTSD are also associated with huge cardiac morbidity and mortality,3 and an increase in …
In vitro selection predicts malaria parasite resistance to dihydroorotate dehydrogenase inhibitors in a mouse infection model
Authors: Rebecca E. K. Mandt, Maria Jose Lafuente-Monasterio, Tomoyo Sakata-Kato, Madeline R. Luth, Delfina Segura, Alba Pablos-Tanarro, Sara Viera, Noemi Magan, Sabine Ottilie, Elizabeth A. Winzeler, Amanda K. Lukens, Francisco Javier Gamo, Dyann F. Wirth
Journal: Science Translational Medicine (2019)

Resistance has developed in Plasmodium malaria parasites to every antimalarial drug in clinical use, prompting the need to characterize the pathways mediating resistance. Here, we report a framework for assessing development of resistance of Plasmodium falciparum to new antimalarial therapeutics. We investigated development of resistance by P. falciparum to the dihydroorotate dehydrogenase (DHODH) inhibitors DSM265 and DSM267 in tissue culture and in a mouse model of P. falciparum infection. We found that resistance to these drugs arose rapidly both in vitro and in vivo. We identified 13 point mutations mediating resistance in the parasite DHODH in vitro that overlapped with the DHODH mutations that arose in the mouse infection model. Mutations in DHODH conferred increased resistance (ranging from 2- to ~400-fold) to DHODH inhibitors in P. falciparum in vitro and in vivo. We further demonstrated that the drug-resistant parasites carrying the C276Y mutation had mitochondrial energetics comparable to the wild-type parasite and also retained their fitness in competitive growth experiments. Our data suggest that in vitro selection of drug-resistant P. falciparum can predict development of resistance in a mouse model of malaria infection.
Development of An HIV1-Based Lentiviral Vector Able to Transduce Both Human and Rhesus Blood Cells.
Authors: Naoya Uchida, Kareem Washington, Jun Hayakawa, Matthew Hsieh, Aylin C. Bonifacino, Allen E. Krouse, Mark E. Metzger, Robert E. Donahue, John F. Tisdale
Journal: Blood (2008)
Multiparameter Flow Cytometry Identifies Dysplasia in Granulocytic, Monocytic, and Erythrocytic Lineages and Blasts in Patients with Myelodysplastic Syndromes: Correlation with Cytomorphology and Cytogenetics.
Authors: Wolfgang Kern, Daniela Voskova, Claudia Schoch, Wolfgang Hiddemann, Susanne Schnittger, Torsten Haferlach
Journal: Blood (2004)
Up Regulation of transendothelial migration on Hematopoietic Progenitor Cells (HPC) and neutrophils by Leukotreine B4 (LTB4) via elevated Endothelial Permeability
Authors: Yeung-Chul Mun, Soo A. Oh, Moon Young Choi, Jee-Young Ahn, Kyoung-Eun Lee, Eun-Sun Yoo, Chu-Myong Seong
Journal: Blood (2008)
Dendritic Cells, Generated and Matured, after Elutriation, in Clinical Grade Bags, Differ in Immune Functions When Compared to Classical DCs Generated in Plates.
Authors: Redouane Rouas, Haidar Akl, Bassam Badran, Larissa Di Pietrantonio, Hugues Duvillier, Philippe Martiat, Philippe Lewalle
Journal: Blood (2008)
The Role of Antiviral Treatment in Hepatitis C Virus (HCV)-Related Non-Hodgkin Lymphoma: An Update of a Multicenter Study.
Authors: Daniele Vallisa, Patrizia Bernuzzi, Luca Arcaini, Antonio Lazzaro, Elena Trabacchi, Elisa Anselmi, Anna Lisa Arcari, Carlo Moroni, Raffaella Berte, Alessandro Malingher, Mario Lazzarino, Luigi Cavanna
Journal: Blood (2005)
Dramatic Improvement in CR Rate and CR Duration with Imatinib in Adult and Elderly Ph+ ALL Patients: Results of the GIMEMA Prospective Study LAL0201.
Authors: Marco Vignetti, Paola Fazi, Giovanna Meloni, Annalisa Chiarenza, Michele Malagola, Francesco Fabbiano, Anna Recchia, Maria G. Kropp, Massimo Offidani, Salvatore Palmieri, Daniela Cilloni, Giuseppe Torelli, Giuseppe Cimino, Roberto Foà, Michele Baccarani, Franco Mandelli
Journal: Blood (2004)
Impact of oxytocin on skin ageing
Authors: S.‐Y. Cho, A.Y. Kim, J. Kim, D.‐H. Choi, E.D. Son, D.W. Shin
Journal: British Journal of Dermatology (2019)

Intrinsic skin aging is skin aging affected by natural factors within the body, such as hormones, rather than by external factors like UV light or smoking. Skin ageing causes the appearance of wrinkles, skin sagging and reduced elasticity. Like elsewhere in the body, skin ageing involves an increase in the proportion of cells undergoing cellular senescence (a type of deterioration due to age). Senescent skin cells called dermal fibroblasts have several characteristics that are different to cells that are not senescent, including having what is known as a senescence‐associated secretory phenotype (SASP). Oxytocin (OT) is a neuropeptide hormone that has many beneficial effects in the body, including protection against age‐related disorders. However, less is known about the role of OT in intrinsic skin aging. The authors looked into the role of oxytocin in prevention against senescence in skin cells called normal human dermal fibroblasts (NHDFs), taken from female donors of different ages. They found that OT suppressed SASP‐induced senescence in NHDFs derived from young but not old female donors. The authors were also able to learn more about the processes within the body by which OT suppresses SASP and why it affects younger women differently to older women. Their results demonstrate that oxytocin may be effective in the prevention of skin aging.
Oxidized low density lipoprotein (LDL) stimulates ovarian carcinoma proliferation that is inhibited by the LXR agonist T0901317
Authors: Daniel Scoles, Haimei Wang, Andrew Li, James Pavelka, Liping Zhang, Alfredo Trento, Beth Karlan
Journal: Cancer Research (2007)

3465  Obesity negatively impacts the survival of ovarian cancer patients. We recently reported outcomes data from 216 ovarian cancer patients and demonstrated that obesity was associated with reduced progression free and overall survival, and that obesity was an independent predictor of survival. To investigate the underlying mechanism that accounts for this association, we examined the effect of oxidized low density lipoprotein (LDL) and the liver X receptor (LXR) agonist T0901317 on ovarian cancer cell growth. Increases in oxidized LDL are associated with obesity and other obesity-related disorders including atherosclerosis and diabetes. The LXR nuclear receptors (LXRα and LXRβ) are dietary cholesterol sensors that when activated stimulate lipid efflux from cells by activating ATP binding cassette transporter genes (ABCA1 and others). T0901317 is a synthetic nonsteroidal ligand to LXR that mediates lipid efflux by ABCA1, and in mouse models, increases plasma HDL, stimulates cholesterol excretion, and reduces liver cholesterol. We treated 3 ovarian cancer cell lines (CAOV3, OVCAR3 and SKOV3) with oxidized LDL and measured the resultant changes in proliferation by MTT assays. A dose-dependent increase in cellular proliferation was seen with increasing oxidized LDL concentration. We determined that concentrations of T0901317 between 100-250 ng/ml significantly inhibited the proliferation of all 3 cell lines while higher doses had no effects. Combinations of oxidized LDL and T0901317 were investigated: CAOV3, OVCAR3 and SKOV3 growth was stimulated with 50 μg/ml oxidized LDL but this effect was almost completely reversed with the addition of 100 ng/ml T0901317. Among the three lines, OVCAR3 was most responsive to oxidized LDL with 40% growth stimulation but only 10% in the presence of T0901317. T0901317 reversal of oxidized LDL-mediated proliferation confirmed that intracellular LDL was responsible for growth stimulation. We are now investigating how oxidized LDL might reduce the sensitivity of these ovarian carcinoma cell lines to cisplatin. There are few studies on the effects of cholesterol on cancer proliferation and the beneficial effects of statins on cancer growth. These data demonstrate that proliferation of ovarian cancer cells can be stimulated by cholesterol. Dietary or genetically mediated increases in circulating cholesterol in obese ovarian cancer patients may contribute to the aggressive ovarian cancer biology observed in clinical studies.
Constitutive Activation of Akt and mTOR by Flt3 Internal Tandem Duplications Mediates Myeloid Leukemogenesis and Can Be Inhibited by Rapamycin.
Authors: Christian H. Brandts, Bulent Sargin, Miriam Rode, Christoph Biermann, Beate Lindtner, Joachim Schwable, Horst Buerger, Carsten Muller-Tidow, Chunaram Choudhary, Martin McMahon, Wolfgang E. Berdel, Hubert L. Serve
Journal: Blood (2004)
Expression of Erythropoietin Receptor (EPO-R) and In Vitro Functional Effects of Epoetin in B-Cell Malignancies.
Authors: Amir Abdalla, Parviz Kokhaei, Lotta Hansson, Manfred Kubbies, Anton Haselbeck, Eva Mikaelsson, Helena Jernberg-Wiklund, Håkan Mellstedt, Anders Österborg Österborg
Journal: Blood (2005)
Abstract 16002: Small Dense High-Density Lipoprotein Particle Number Relates to Coronary Plaque Burden Independent of Traditional Cardiovascular Risk Factors in Psoriasis
Authors: Aparna Sajja, Aditya Goyal, Agastya D Belur, Jonathan H Chung, Joshua P Rivers, Amit K Dey, Tushina Jain, Anshuma Rana, Justin A Rodante, Charlotte L Harrington, Gregory E Sanda, Heather L Teague, Alexander V Sorokin, Yvonne Baumer, Martin P Playford, David A Bluemke, Marcus Y Chen, Nehal N Mehta
Journal: Circulation (2017)

Introduction: Psoriasis (PSO) is a chronic inflammatory disorder associated with increased cardiovascular (CV) risk and lipoprotein dysfunction. Small dense HDL particle number (s-HDLp) has been sh...
Abstract 17301: Clinical and Procedural Outcomes With the SAPIEN 3 versus the SAPIEN XT Prosthetic Valves in Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis
Authors: Ramyashree Tummala, Kinjal Banerjee, Stephanie Mick, Amar Krishnaswamy, Jonathon White, Maan Fares, Anand Mehta, Zoran Popovic, Samir Kapadia
Journal: Circulation (2017)

Introduction: The SAPIEN 3 valve (S3V) was designed to overcome the shortcomings of its predecessor, the SAPIEN XT (SXT) valve. We conducted a meta-analysis to compare their clinical outcomes and p...
Continued Treatment with An Outpatient Maintenance Schedule of Decitabine in Older AML Patients Ineligible for Induction Chemotherapy: Results of the 00331 Phase II Multicenter Trial
Authors: Michael Lübbert, Mathias Schmid, Björn Rüter, Ulrich Germing, Volker Rethwisch, Arnold Ganser, Uwe Platzbecker, Oliver Galm, Wolfram Brugger, Pierre W Wijermans, Claudia Schmoor, Hartmut Döhner
Journal: Blood (2008)
Gender dysphoria: scientific oversight falling between responsible institutions should worry us all
Authors: Richard Byng, Susan Bewley
Journal: BMJ (2019)

The troubles around the Gender Identity Development Service’s study12 seem to be symptomatic of our wider collective failure to determine whether, and when, we should prescribe puberty blockers, or cross sex hormones, to children and young people identifying as transgender.

The ethics of research conduct belongs to the Health Research Authority (HRA), and the quality of science is an important consideration when …
Time- and Dose-Response Relationships of Imatinib Mesylate (Glivec) Therapy for Chronic Hypereosinophilic Syndromes.
Authors: Renato Bassan, Sara Acerboni, Silvia Mappa, Piera Viero, Federica Delaini, Giuseppe Rossi, Valentina Rossi, A. Vannucchi, Eros Di Bona, Emanuela Ruggeri, Anna Salvi, Ursula Giussani, Francesca Rancati, Tamara Intermesoli, Alessandro Rambaldi, Tiziano Barbui
Journal: Blood (2005)
Measles: 142 000 people died in 2018, mostly aged under 5
Authors: Elisabeth Mahase
Journal: BMJ (2019)

More than 142 000 people died from measles in 2018 around the world, and most deaths occurred in those under 5 years old, show figures from the World Health Organization and the US Centers for Diseases Control and Prevention (CDC).1

Although the latest estimates reported a worldwide surge in measles cases, almost half of all cases were accounted for by just five countries: the Democratic Republic of the Congo, Liberia, Madagascar, Somalia, and Ukraine.

WHO’s statistical modelling for 2018 estimated 9 769 400 measles cases and 142 300 related deaths, up from 7 585 900 cases and 124 000 deaths in 2017. However, those totals were far lower than in 2000, when an estimated 28 219 100 …