tbuckley/cabot-search huggingface dataset:
Dissecting Clonal Hematopoiesis in Tissues of Patients with Classic Hodgkin Lymphoma
Authors: Alessandra Venanzi, Andrea Marra, Gianluca Schiavoni, Sara G. Milner, Roberto Limongello, Alessia Santi, Valentina Pettirossi, Simona Ultimo, Luisa Tasselli, Alessandra Pucciarini, Lorenza Falini, Sofia Sciabolacci, Maria Paola Martelli, Paolo Sportoletti, Stefano Ascani, Brunangelo Falini, Enrico Tiacci
Journal: Blood Cancer Discovery (2021)

Abstract Clonal hematopoiesis predisposes to hematologic malignancies. However, clonal hematopoiesis is understudied in classic Hodgkin lymphoma (cHL), a mature B-cell neoplasm exhibiting the most abundant microenvironment. We analyzed clonal hematopoiesis in 40 cHL cases by sequencing microdissected tumor cells and matched normal cells from blood and/or lymph nodes. Five patients had blood and/or tissue clonal hematopoiesis. In three of five patients (all failing first-line therapy), clonal hematopoiesis spread through the tissue microenvironment extensively, and featured mutant DNMT3AR882H, KRASG60D, and DNMT3AR882H+TET2Q1274* in 33%, 92%, and 60% of nonneoplastic cells, respectively. In the latter case, DNMT3A/TET2-mutant clonal hematopoiesis seeded the neoplastic clone, which was infected by the Epstein–Barr virus and showed almost no other somatic mutations exome-wide. In the former case, DNMT3A-mutant clonal hematopoiesis did not originate the neoplastic clone despite dominating the blood and B-cell lineage (∼94% leukocytes; ∼96% mature blood B cells), yet led to NPM1-mutated acute myeloid leukemia 6 years after therapy for cHL. Our results expand to cHL the spectrum of hematologic malignancies associated with clonal hematopoiesis. Significance: Clonal hematopoiesis can be present in the cHL tissue, can give rise to the tumor clone, and can spread to large parts of its microenvironment. Even when massive, clonal hematopoiesis does not always give rise to the neoplastic clone of multiple myeloid and lymphoid neoplasms occurring in the same patient.
Piezo1-mediated mechanosensation in bone marrow macrophages promotes vascular niche regeneration after irradiation injury
Authors: Xiaomei Zhang, Lijia Hou, Fengjie Li, Weiwei Zhang, Chun Wu, Lixin Xiang, Jiuxuan Li, Luping Zhou, Xiaojie Wang, Yang Xiang, Yanni Xiao, Shengwen Calvin Li, Li Chen, Qian Ran, Zhongjun Li
Journal: Theranostics (2022)

Background: Irradiation disrupts the vascular niche where hematopoietic stem cells (HSCs) reside, causing delayed hematopoietic reconstruction.The subsequent recovery of sinusoidal vessels is key to vascular niche regeneration and a prerequisite for hematopoietic reconstruction.We hypothesize that resident bone marrow macrophages (BM-Mφs) are responsible for repairing the HSC niche upon irradiation injury.Methods: We examined the survival and activation of BM-Mφs in C57BL/6 mice upon total body irradiation.After BM-Mφ depletion via injected clodronate-containing liposomes and irradiation injury, hematopoietic reconstruction and sinusoidal vascular regeneration were assessed with immunofluorescence and flow cytometry.Then enzyme-linked immunosorbent assay (ELISA) and flow cytometry were performed to analyze the contribution of VEGF-A released by BM-Mφs to the vascular restructuring of the HSC niche.VEGF-A-mediated signal transduction was assessed with transcriptome sequencing, flow cytometry, and pharmacology (agonists and antagonists) to determine the molecular mechanisms of Piezo1-mediated responses to structural changes in the HSC niche.Results: The depletion of BM-Mφs aggravated the post-irradiation injury, delaying the recovery of sinusoidal endothelial cells and HSCs.A fraction of the BM-Mφ population persisted after irradiation, with residual BM-Mφ exhibiting an activated M2-like phenotype.The expression of VEGF-A, which is essential for sinusoidal regeneration, was upregulated in BM-Mφs post-irradiation, especially CD206 + BM-Mφs.The expression of mechanosensory ion channel Piezo1, a response to mechanical environmental changes induced by bone marrow ablation, was upregulated in BM-Mφs, especially CD206 + BM-Mφs.Piezo1 upregulation was mediated by the effects of irradiation, the activation of Piezo1 itself, and the M2-like polarization induced by the phagocytosis of apoptotic cells.Piezo1 activation was associated with increased expression of VEGF-A and increased accumulation of NFATC1, NFATC2, and HIF-1α.The Piezo1-mediated upregulation in VEGF-A was suppressed by inhibiting the calcineurin/NFAT/HIF-1α signaling pathway.Conclusion: These findings reveal that BM-Mφs play a critical role in promoting vascular niche regeneration by sensing and responding to structural changes after irradiation injury, offering a potential target for therapeutic efforts to enhance hematopoietic reconstruction.
Autophagy mediates ER stress and inflammation in <i>Helicobacter pylori</i> -related gastric cancer
Authors: M.C. Mommersteeg, I. Simovic, B. Yu, S.A.V. van Nieuwenburg, I, M.J. Bruno, M. Doukas, E.J. Kuipers, M.C.W. Spaander, M.P. Peppelenbosch, N. Castaño-Rodríguez, G.M. Fuhler
Journal: Gut Microbes (2021)

Autophagy is a cellular degradation mechanism, which is triggered by the bacterium Helicobacter pylori. A single nucleotide polymorphism (SNP) in the autophagy gene ATG16L1 (rs2241880, G-allele) has been shown to dysregulate autophagy and increase intestinal endoplasmic reticulum (ER) stress. Here, we investigate the role of this SNP in H. pylori-mediated gastric carcinogenesis and its molecular pathways. ATG16L1 rs2241880 was genotyped in subjects from different ethnic cohorts (Dutch and Australian) presenting with gastric (pre)malignant lesions of various severity. Expression of GRP78 (a marker for ER stress) was assessed in gastric tissues. The effect of ATG16L1 rs2241880 on H. pylori-mediated ER stress and pro-inflammatory cytokine induction was investigated in organoids and CRISPR/Cas9 modified cell lines. Development of gastric cancer was associated with the ATG16L1 rs2241880 G-allele. Intestinal metaplastic cells in gastric tissue of patients showed increased levels of ER-stress. In vitro models showed that H. pylori increases autophagy while reducing ER stress, which appeared partly mediated by the ATG16L1 rs2241880 genotype. H. pylori-induced IL-8 production was increased while TNF-α production was decreased, in cells homozygous for the G-allele. The ATG16L1 rs2241880 G-allele is associated with progression of gastric premalignant lesions and cancer. Modulation of H. pylori-induced ER stress pathways and pro-inflammatory mediators by ATG16L1 rs2441880 may underlie this increased risk.
Epoprostenol now the focus of numerous clinical trials
Authors: W. A. Check
Journal: JAMA (1981)

Evidence is fast accumulating on the therapeutic value of one of the newest members of the prostaglandin family, epoprostenol, which was discovered in 1976. In the United States recently to deliver a lecture, John Vane, DSc, group research director at the Burroughs Wellcome Foundation, Beckenham, England, described for<i>JAMA</i>MEDICAL NEWS some of the clinical trials in which the compound has proved its value as an inhibitor of platelet aggregation. Vane received the Lasker Award in 1977 for his prominent role in the discovery of epoprostenol, also known as PGI2 and more commonly as prostacyclin. Other information on epoprostenol comes from a recent conference on prostaglandins in cerebrovascular and thrombotic disorders held in Chicago under the auspices of Rush Medical College and Northwestern University Medical School. Epoprostenol was actually discovered by Vane and Salvador Moncada during their search for thromboxane, the prostaglandin that<i>promotes</i>aggregation of platelets, in the endothelium
A PHARMACODYNAMIC COMPARISON OF PRASUGREL VERSUS TICAGRELOR IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND CORONARY ARTERY DISEASE: THE OPTIMUS (OPTIMIZING ANTIPLATELET THERAPY IN DIABETES MELLITUS)-4 STUDY
Authors: Francesco Franchi, Fabiana Rollini, Valeria Duarte, Jung Rae Cho, Niti Aggarwal, Jenny Hu, Megha Kureti, Ashwin Durairaj, Latonya Been, Martin Zenni, Luis A. Guzman, Theodore Bass, Dominick Angiolillo
Journal: Journal of the American College of Cardiology (2016)
Left ventricular systolic function during atrial fibrillation can be accurately determined using only a minimal number of cardiac cycles Tomotsugu Tabata, Richard A. Grimm, Neil L. Greenberg, Junko watanabe, Deborah A. Agler, Don W. Wallick, ShaoWei Zhuang, YouHua Zhang, Kent A. Mowrey, Todor N. Mazgalev, James D. Thoms. The Cleveland Clinic Foundation, Cleveland, OH
Journal: Journal of the American College of Cardiology (2001)
Pretreatment with ticlopidine or clopidogrel improves the safety profile of stenting: An analysis of 3037 patients Steven P. Marso, Cathryn A. Carroll, Michael M. Coen, Peter N. Tadros, Daniel L. Lips, Warren L. Johnson, Lee V. Giorgi, Barry D. Rutherford. Mid America Heart Institute, Kansas City
Journal: Journal of the American College of Cardiology (2001)
Cesarean section rates
Authors: C. A. Peach
Journal: JAMA (1991)

<h3>To the Editor. —</h3> I noted with interest the exchange of letters between Drs Overhulse and Stafford<sup>1</sup>regarding cesarean section rates. I was especially intrigued by Dr Stafford's contention that an increased risk of death exists for planned cesarean sections compared with vaginal deliveries. Because I did not recall any specific study of this subject, I immediately reviewed the article<sup>2</sup>cited by Dr Stafford. As I suspected, that author did not specifically address the subject of planned cesarean sections, but reviewed the maternal mortality and morbidity of cesarean section in general, without subclassification. Dr Stafford's citation of this article in support of his contention that planned cesarean sections have a higher mortality rate than vaginal delivery is, therefore, inappropriate. In similar fashion, Dr Stafford contends that "postcesarean section infection occurs in approximately 15% of cesarean deliveries even with antibiotic prophylaxis." Again, the article<sup>3</sup>cited does not refer
Abstract 288: Use of hiPSC-Derived Cardiomyocytes to Explore Functional Cardiotoxicities of Direct Acting Antiviral Nucleoside Based Structures
Authors: John P Imredy, Bharathi Balasubramanian, Armando Lagrutta, David B Olsen, Stephane Bogen, Paul G Bulger, Heather Vu, Qiuwei Xu
Journal: Circulation Research (2017)

Nucleoside-derived structures constitute important Direct-Acting Antivirals (DAAs) for Hepatitis C Virus (HCV) treatment. BMS-986094 (BMS-094: a 2’-C-modified guanosine (G) derivative prodrug) was discontinued in phase II due to heart/kidney failure and cardiomyopathy, whereas sofosbuvir (a 2’-C-modified uridine prodrug) is an effective HCV DAA. Given the importance of purine nucleosides in cardiac signaling, we investigated BMS-094 in the human induced pluripotent stem cell derived cardiomyocyte (hiPSC-CM) model (iCells, CDI Fujifilm). Beating myocyte monolayer impedance signals were monituored for up to 7 days in the RTCA Cardio platform (ACEA-Biosystems). BMS-094 was acutely myotoxic at high concentrations (≥ 17 μM), as evidenced by cessation of myocyte beating and loss of baseline impedance or ‘Cell Index’ (C.I.), a measure of cell adherence, within hours. On prolonged exposure to BMS-094 at concentrations not associated with loss of C.I. (&lt; 1 μM), we observed progressive, dose-dependent decreases in impedance amplitude (myocyte contractility) which were accompanied by increases in the spontaneous myocyte beating rate. The same beating phenotype could be elicited over a multi-day exposure duration by extracellular application of the BMS-094 core nucleoside (2’-C-methyl-guanosine) alone, but not by unmodified G. Loss of contractility with the G derivatives was accompanied by a decrease of the Ca 2+ transient amplitude in a Ca 2+ influx fluorescence assay (FDSS μCell, Hamamatsu). We investigated the impact of purine or pyrimidine base substitutions in the 2’-CMe-modified nucleoside: 2’-CMe-adenosine, -cytidine, -G, and -uridine. The uridine analog had the most limited effects on hiPSC-CMs beating parameters. The effect of 2’-CMe-cytidine on beating rate and impedance amplitude was similar to that of the G derivative, including a progressive multi-day onset. In contrast, 2’-CMe-adenosine slowed beating acutely, and led to loss of C.I. at higher concentrations. These results demonstrate the varied effects on CM function of base substitutions in antiviral nucleoside chemistry and support the utility of hiPSC-CMs as a model for screening in-vitro the potential cardiotoxicities of nucleoside derivative drugs.
Letter: Leeds infirmary blues.
Authors: R Mogg
Journal: BMJ (1975)

In your article you stress that genitourinary medicine should not be confused with urology, and would not encroach on the realm of urology.In spite of this you im- mediately state that the work of genito- urinary physicians could "expand to include infertility and other diseases of the genitourinary tract when appropriate."This could only be seen as an encroachment on the realm of the urologist.May I stress again the deep concern which the council and members of the British Association of Urological Surgeons feel regarding the change of title.In a recent issue of the B.M.7. a junior post in genitourinary medi- cine was advertised under "Venereology."Surely this is an anachronism.It would appeair that the time is now opportune for the whole subject to be dis- cussed logically not only by the Royal College of Physicians but in association with the Medical Society for the Study of Venereal Diseases, and more particularly with the British Association of Urological Surgeons.-Iam, etc.,
Highlights from this issue
Authors: The Triumvirate
Journal: Thorax (2022)

The TriumvirateIn the Northern hemisphere, February is one of the colder, darker months of the year (though thankfully shorter).Here we put a positive spin on the last month of meteorological winter and celebrate some Thorax highlights. SUPER BOWL SPIROMETRYTo our US cousins, February is marked by the super bowl -the annual contest between two leading American football teams.The big game typically attracts over 100 million viewers -more than the UK Football Association (FA) cup, played in May, which garners around 88 million.Match audiences are not the only thing which is bigger in the US.It appears that the same applies for lung function values in children with cystic fibrosis (CF).In this month's journal, Daniela Schlüter and colleagues (see page 136) present a comparison of lung function values from the UK and US registries.Using mixed effects regression analysis, the authors model lung function trajectories in children homozygous for F508del.After correcting for possible confounding variables, they find that lung function was higher in the US than the UK at age 6 years and remained higher throughout childhood.The inhaled mucoactive drugs dornase alfa and hypertonic saline were more frequently used in the US and the authors suggest that a possible causal role should be investigated further.There was no difference in nutrition between the US and UK children.No so for the super bowl which is the second biggest eating event in the US calendar after Thanksgiving!
Erratum
Journal: JNCI Journal of the National Cancer Institute (1974)

In “Investigations on the Effects of Chronic Cigarette-Smoke Inhalation in Syrian Golden Hamsters” by W. Dontenwill et al., the following correction should be made: Page 1783, second column, 16 lines from the top should read “Due to the design of the machine, the animals were offered about 40% of main-stream smoke with the breathing air (see ‘Discussion’)” (not “About 40% of the breathing air of the animals was main-stream smoke....”
Abstract 29: Isolation of Cardiomyocytes Undergoing Mitosis with Complete Cytokinesis
Authors: Hsiaoyun Y Milliron, Matthew Weiland, Megan Bowman, Stefan Jovinge
Journal: Circulation Research (2017)

Adult cardiomyocytes (CMs) fail to exit the cell cycle and result in polyploidization and multi-nucleation. This extremely limited renewal potential is a key barrier for cardiac regeneration after heart injury. The use of traditional cell cycle assays such as Ki67 or purine analogue administration does not allow for isolation of viable CMs in late-M phase. We hypothesize that a molecular beacon (MB)-based method could be developed to isolate a highly pure population of hiPSC-derived CMs capable of completing mitosis and cytokinesis. We first differentiated human PSCs into cardiomyocytes using the small molecules CHIR and IWR and then applied MBs targeting CDC20 mRNAs, followed by fluorescence-activated cell sorting (FACS). Validation of cell cycle-specific and mitosis-associated gene expressions of cell fractions sorted from G2 and M-phase were performed by RT-qPCR prior to transcriptional profiling by single-cell RNA sequencing. Gene set enrichment analysis (GSEA) confirmed the observation of the gene ontology (GO) analysis. The ‘GO_cytokinesis’ and the ‘GO_cell separation after cytokinesis’ gene sets were highly enriched and predominantly upregulated in the CDC20 (+) (M-phase) population compared with the CDC20 (-) (G2-phase) population. Furthermore, using these data sets we expect to develop robust surface marker based flow cytometry protocols at a number and purity allowing for statistically significant genome-wide integrative transcriptome and epigenome analysis. In conclusion, the isolation of CMs using CDC20 MB and DNA content dye proved to enrich for cells that were confirmed by GSEA to be CMs in cytokinesis.
Second versus first wave of COVID-19 in patients with MPN
Authors: Tiziano Barbui, Alessandra Iurlo, Arianna Masciulli, Alessandra Carobbio, Arianna Ghirardi, Greta Carioli, Marta Anna Sobas, Elena Maria Elli, Elisa Rumi, Valerio De Stefano, Francesca Lunghi, Monia Marchetti, Rosa Daffini, Mercedes Gasior Kabat, Beatriz Cuevas, Maria Laura Fox, Marcio Miguel Andrade-Campos, Francesca Palandri, Paola Guglielmelli, Giulia Benevolo, Claire Harrison, Maria Angeles Foncillas, Massimiliano Bonifacio, Alberto Alvarez-Larran, Jean-Jacques Kiladjian, Estefanía Bolaños Calderón, Andrea Patriarca, Keina Quiroz Cervantes, Martin Griessammer, Valentin Garcia-Gutierrez, Alberto Marin Sanchez, Elena Magro Mazo, Marco Ruggeri, Juan Carlos Hernandez-Boluda, Santiago Osorio, Gonzalo Carreno-Tarragona, Miguel Sagues Serrano, Rajko Kusec, Begona Navas Elorza, Anna Angona, Blanca Xicoy Cirici, Emma Lopez Abadia, Steffen Koschmieder, Daniele Cattaneo, Cristina Bucelli, Edyta Cichocka, Anna Masternak Kulikowska de Nałęcz, Fabrizio Cavalca, Oscar Borsani, Silvia Betti, Lina Benajiba, Marta Bellini, Natalia Curto-Garcia, Alessandro Rambaldi, Alessandro Maria Vannucchi
Journal: Leukemia (2022)
Infiltration of neutrophils in human coronary unstable plaques Takahiko Naruko, Makiko Ueda, Kazuo Haze, Akira Itoh, Masato Otsuka, Yuji Sakanoue, Yoshihiro Ikura, Masayuki Ogami. Osaka City General Hospital, Osaka, Japan, Osaka City University Medical School, Osaka, Japan
Journal: Journal of the American College of Cardiology (2001)
Human Walking
Authors: Clinton L. Compere
Journal: JAMA (1981)

In 150 easy-to-read pages, Dr Inman and his colleagues have condensed a vast amount of experimental data and knowledge about human gait. For 30 years, Dr Inman has been immersed in productive biomechanical research at the University of California. His contributions with regard to the functional anatomy of the ankle are well known and appreciated. The introduction to the publication<i>Human Walking</i>should be read by all clinical and research scientists interested in human ambulation. There has recently been an upsurge of research in human gait, and the basic experimental and practical information in the subsequent five chapters should be carefully reviewed as a background for future research, utilizing advanced computerization and electronics. The kinesiology of functional gait is covered in the chapters "Kinetics," "Kinematics," "Energy Consumption," and "Muscle Function." The figures are mostly diagrammatic, illustrating the text material in a simple manner. The chapter "Implications and Applications" applies the
Mortality and causes of death in LQT1 and LQT2 type of long QT syndrome based on systematic survey in finnish pedigrees Heikki Swan, Kirsi Piippo, P�ivi Laitinen, Kimmo Kontula, Matti Viitasalo, Lauri Toivonen. Helsinki University Department of Medicine, Helsinki, Finland
Journal: Journal of the American College of Cardiology (2001)
Fellowships, Grants, Awards
Journal: JNCI Journal of the National Cancer Institute (1994)

Fellowships, Grants, Awards JNCI: Journal of the National Cancer Institute, Volume 86, Issue 13, 6 July 1994, Pages 1033–1034, https://doi.org/10.1093/jnci/86.13.1033 Published: 06 July 1994
A New Abortifacient.
Journal: JAMA (1892)

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