tbuckley/cabot-search huggingface dataset:
Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients 60 Years of Age and Younger: Results of the Intergroup ANOCEF-GOELAMS Randomized Phase II PRECIS Study
Authors: Caroline Houillier, Luc Taillandier, Sylvain Dureau, Thierry Lamy, Mouna Laadhari, Olivier Chinot, Cecile Moluçon-Chabrot, Pierre Soubeyran, Remy Gressin, Sylvain Choquet, Gandhi Damaj, Antoine Thyss, Julie Abraham, Vincent Delwail, Emmanuel Gyan, Laurence Sanhes, Jérôme Cornillon, Reda Garidi, Alain Delmer, Marie-Laure Tanguy, Ahmad Al Jijakli, Pierre Morel, Pascal Bourquard, Marie-Pierre Moles, Adrien Chauchet, Thomas Gastinne, Jean-Marc Constans, Adriana Langer, Antoine Martin, Patricia Moisson, Lucette Lacomblez, Nadine Martin-Duverneuil, Daniel Delgadillo, Isabelle Turbiez, Loïc Feuvret, Nathalie Cassoux, Valérie Touitou, Damien Ricard, Khê Hoang-Xuan, Carole Soussain
Journal: Journal of Clinical Oncology (2019)

To determine the efficacy and toxicity of chemoimmunotherapy followed by either whole-brain radiotherapy (WBRT) or intensive chemotherapy and autologous stem-cell transplantation (ASCT) as a first-line treatment of primary CNS lymphoma (PCNSL).Immunocompetent patients (18 to 60 years of age) with untreated PCNSL were randomly assigned to receive WBRT or ASCT as consolidation treatment after induction chemotherapy consisting of two cycles of R-MBVP (rituximab 375 mg/m2 day (D) 1, methotrexate 3 g/m2 D1; D15, VP16 100 mg/m2 D2, BCNU 100 mg/m2 D3, prednisone 60 mg/kg/d D1-D5) followed by two cycles of R-AraC (rituximab 375 mg/m2 D1, cytarabine 3 g/m2 D1 to D2). Intensive chemotherapy consisted of thiotepa (250 mg/m2/d D9; D8; D7), busulfan (8 mg/kg D6 through D4), and cyclophosphamide (60 mg/kg/d D3; D2). WBRT delivered 40 Gy (2 Gy/fraction). The primary end point was 2-year progression-free survival. Cognitive outcome was the main secondary end point. Analysis was intention to treat in a noncomparative phase II trial.Between October 2008 and February 2014, 140 patients were recruited from 23 French centers. Both WBRT and ASCT met the predetermined threshold (among the first 38 patients in each group, at least 24 patients were alive and disease free at 2 years). The 2-year progression-free survival rates were 63% (95% CI, 49% to 81%) and 87% (95% CI, 77% to 98%) in the WBRT and ASCT arms, respectively. Toxicity deaths were recorded in one and five patients after WBRT and ASCT, respectively. Cognitive impairment was observed after WBRT, whereas cognitive functions were preserved or improved after ASCT.WBRT and ASCT are effective consolidation treatments for patients with PCNSL who are 60 years of age and younger. The efficacy end points tended to favor the ASCT arm. The specific risk of each procedure should be considered.
<i>Circulation Research</i> Editors’ Yearly Report: 2002
Authors: Eduardo Marbán, Roberto Bolli, Gerda Breitwieser, Rudi Busse, Hal Dietz, Masao Endoh, Toren Finkel, David Kass, Charles Lowenstein, Marlene Rabinovitch, Gordon Tomaselli, Kara Hansell Keehan
Journal: Circulation Research (2003)
Duration of antibiotic treatment for common infections in English primary care: cross sectional analysis and comparison with guidelines
Authors: Koen B Pouwels, Susan Hopkins, Martin J Llewelyn, Ann Sarah Walker, Cliodna AM McNulty, Julie V Robotham
Journal: BMJ (2019)

Abstract Objective To evaluate the duration of prescriptions for antibiotic treatment for common infections in English primary care and to compare this with guideline recommendations. Design Cross sectional study. Setting General practices contributing to The Health Improvement Network database, 2013-15. Participants 931 015 consultations that resulted in an antibiotic prescription for one of several indications: acute sinusitis, acute sore throat, acute cough and bronchitis, pneumonia, acute exacerbation of chronic obstructive pulmonary disease (COPD), acute otitis media, acute cystitis, acute prostatitis, pyelonephritis, cellulitis, impetigo, scarlet fever, and gastroenteritis. Main outcome measures The main outcomes were the percentage of antibiotic prescriptions with a duration exceeding the guideline recommendation and the total number of days beyond the recommended duration for each indication. Results The most common reasons for antibiotics being prescribed were acute cough and bronchitis (386 972, 41.6% of the included consultations), acute sore throat (239 231, 25.7%), acute otitis media (83 054, 8.9%), and acute sinusitis (76 683, 8.2%). Antibiotic treatments for upper respiratory tract indications and acute cough and bronchitis accounted for more than two thirds of the total prescriptions considered, and 80% or more of these treatment courses exceeded guideline recommendations. Notable exceptions were acute sinusitis, where only 9.6% (95% confidence interval 9.4% to 9.9%) of prescriptions exceeded seven days and acute sore throat where only 2.1% (2.0% to 2.1%) exceeded 10 days (recent guidance recommends five days). More than half of the antibiotic prescriptions were for longer than guidelines recommend for acute cystitis among females (54.6%, 54.1% to 55.0%). The percentage of antibiotic prescriptions exceeding the recommended duration was lower for most non-respiratory infections. For the 931 015 included consultations resulting in antibiotic prescriptions, about 1.3 million days were beyond the durations recommended by guidelines. Conclusion For most common infections treated in primary care, a substantial proportion of antibiotic prescriptions have durations exceeding those recommended in guidelines. Substantial reductions in antibiotic exposure can be accomplished by aligning antibiotic prescription durations with guidelines.
Pharmacological Inhibition of Nlk (Nemo-like Kinase) Rescues Erythropoietic Defects in Pre-Clinical Models of Diamond Blackfan Anemia
Authors: Mark C Wilkes, Jun Chen, Kavitha Siva, Gianluca Veretti, Daniel P. Dever, Minyoung Youn, Hee-Don Chae, Jacqueline D Mercado, Mallika Saxena, Anupama Narla, Bertil Glader, Matthew Porteus, Claire E Repellin, Hanna T Gazda, Manuel Serrano, Johan Flygare, Kathleen M. Sakamoto
Journal: Blood (2018)
Autologous Stem Cell Transplantation Is Effective in Chemosensitive HIV-Associated Lymphoma Irrespective of Previous Therapy and Histological Subtype
Authors: Alessandro Re, Nicola Bianchetti, Chiara Cattaneo, Salvatore Casari, Chiara Pagani, Annalisa Peli, Emanuele Focà, Pierino ferremi Leali, Camillo Almici, Francesco Castelli, Giuseppe Rossi
Journal: Blood (2018)
Novel ELISA for thrombospondin type 1 domain-containing 7A autoantibodies in membranous nephropathy
Authors: Christelle Zaghrini, Barbara Seitz-Polski, Joana Justino, Guillaume Dolla, Christine Payré, Noémie Jourde-Chiche, Anne-Els Van de Logt, Caroline Booth, Emma Rigby, Jennie Lonnbro-Widgren, Jenny Nystrom, Christophe Mariat, Zhao Cui, Jack F.M. Wetzels, GianMarco Ghiggeri, Laurence H. Beck, Pierre Ronco, Hanna Debiec, Gérard Lambeau
Journal: Kidney International (2019)
<i>Notes from the Field:</i> Enteroinvasive <i>Escherichia coli</i> Outbreak Associated with a Potluck Party — North Carolina, June–July 2018
Authors: Carolyn T.A. Herzig, Aaron T. Fleischauer, Brian Lackey, Nicole Lee, Thomas Lawson, Zack S. Moore, John Hergert, Victoria Mobley, Jennifer MacFarquhar, Tammra Morrison, Nancy Strockbine, Haley Martin
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

On July 2, 2018, the North Carolina Division of Public Health was notified that approximately three dozen members of an ethnic Nepali refugee community had been transported to area hospitals for severe gastrointestinal illness after attending a potluck party on June 30.
Trends in Opioid Use Among Older Survivors of Colorectal, Lung, and Breast Cancers
Authors: Talya Salz, Jessica A. Lavery, Allison N. Lipitz-Snyderman, Denise M. Boudreau, Natalie Moryl, Erin F. Gillespie, Deborah Korenstein
Journal: Journal of Clinical Oncology (2019)

PURPOSE Cancer survivors may be at increased risk for opioid-related harms. Trends in opioid use over time since diagnosis are unknown. METHODS Using data from SEER and Medicare, we conducted multilevel logistic regression analyses to compare chronic opioid use (≥ 90 consecutive days) among opioid-naïve survivors of colorectal, lung, and breast cancers diagnosed from 2008 to 2013 and matched with noncancer controls. Among cases and controls with chronic use, we compared rates of high-dose opioid use (average ≥ 90 morphine milligram equivalents daily). RESULTS We included 46,789 survivors and 138,136 noncancer controls. In the first year after the index date (survivor’s diagnosis date), chronic use among colorectal and lung cancer survivors exceeded chronic use among controls (colorectal cancer: odds ratio, 1.34; 95% CI, 1.22 to 1.47; lung cancer: odds ratio, 2.55; 95% CI, 2.34 to 2.77). Differences in chronic use between survivors and controls declined each year after the index date. Chronic use among breast cancer survivors was less than that of controls each year after the index date. Survivors with chronic use were more likely to have a high daily dose than controls with chronic use in the first 3 to 5 years. CONCLUSION Among three large populations of older cancer survivors, chronic opioid use varied by cancer. However, by 6 years after diagnosis, survivors were no longer more likely to be chronic users than controls. Strategies for appropriate pain management during and after cancer treatment should take into account the risks associated with chronic high-dose opioid use.
Abstract P6-13-01: Withdrawn
Authors: WJ Janni, N Harbeck, B Rack, O Gluz, A Schneeweiss, R Kates, T Fehm, H Kreipe, S Kümmel, R Würstlein, A Hartkopf, M Clemens, T Reimer, T Friedl, L Häberle, P Fasching, U Nitz
Journal: Cancer Research (2018)

Abstract This abstract was withdrawn by the authors.
Myeloablative Conditioning with Alemtuzumab in Matched Related Donor Hematopoietic Cell Transplant for Sickle Cell Disease Prevents Graft-Versus-Host Disease without Compromising Engraftment
Authors: Tami D John, Khaled Yassine, Swati Naik, Ghadir Sasa, Bilal Omer, Caridad A. Martinez, Priti Tewari, Robert A. Krance, Kathryn S Leung
Journal: Blood (2018)
Microfluidic Isolation of Circulating Tumor Cells and Cancer Stem-Like Cells from Patients with Pancreatic Ductal Adenocarcinoma
Authors: Jose I. Varillas, Jinling Zhang, Kangfu Chen, Isis I. Barnes, Chen Liu, Thomas J. George, Z. Hugh Fan
Journal: Theranostics (2019)

Background: Pancreatic ductal adenocarcinoma (PDAC) requires multimodal therapeutic approaches and disease monitoring for effective treatment.Liquid biopsy biomarkers, including circulating tumor cells (CTCs) and cancer stem-like cells (CSCs), hold promise for evaluating treatment response promptly and guiding therapeutic modifications.Methods: From 24 patients with metastatic PDAC (stage IV, M1) undergoing active systemic treatment, we collected 78 blood samples at different time points for CTC and CSC isolation using a microfluidic platform functionalized with antibodies against a CTC biomarker, epithelial cell adhesion molecule (EpCAM), or a CSC biomarker, CD133.These isolated cells were further verified, via fluorescent staining and imaging, using cytokeratin (CK), CD45, and nucleic acid stain 4',6-diamidino-2-phenylindole (DAPI).Results: The majority (84.4%) of patient blood samples were positive for CTCs (EpCAM + CK + CD45 -DAPI + ) and 70.8% of patient blood samples were positive for CSCs (CD133 + CK + CD45 -DAPI + ), using the highest baseline value of healthy samples as threshold.The CTC subtypes (EpCAM + CK + CD45 -DAPI + CD133 + and EpCAM + CK + CD45 -DAPI + CD133 -) and CSC subtypes (CD133 + CK + CD45 -DAPI + EpCAM + and CD133 + CK + CD45 -DAPI + EpCAM -) were also analyzed using immunochemical methods.In several cases, CSCs exhibited cytokeratin expression that did not express EpCAM, indicating that they will not be detected using EpCAM-based isolation. Conclusion:The microfluidic platform enabled the reliable isolation of CTCs and CSCs from PDAC patient samples, as well as their subtypes.Complementary assessment of both CTCs and CSCs appears advantageous to assess the profile of tumor progressing in some cases.This research has important implications for the application and interpretation of approved methods to detect CTCs.
The ambition of the <i>European Respiratory Journal</i>: chapter 3
Authors: Marc Humbert, Anh Tuan Dinh-Xuan, Elin L. Reeves, Matthew G. Broadhead, Neil J. Bullen
Journal: European Respiratory Journal (2014)

As the title suggests, this is the third New Year “ambition” editorial of the current 5-year European Respiratory Journal (ERJ) editorial cycle. As we approach the half-way point, it is time not only to look back at 2014, but also to take stock of what has been achieved in the past 2 years and to set the agenda for what is still to be done. We will review the objectives we set in the previous editorials [1, 2] and look at some of the exceptional articles published in 2014. The ERS's flagship journal is making great headway <http://ow.ly/DRPyz>
Cystic fibrosis papers of the year 2007
Authors: Ian M Balfour-Lynn
Journal: Journal of the Royal Society of Medicine (2008)

The literature search was conducted using PubMed (www.ncbi.nlm.nih.gov/sites/entrez), entering the search term ‘cystic fibrosis’, for the period 1 January to 13 November 2007. There were 1228 papers identified; when limits were set for ‘clinical trial’ and ‘randomized controlled trial’ 63 papers remained. In addition, three meta-analyses were identified. The papers selected for this review are a personal choice of studies with important or interesting clinical messages.
Prebiotic Iron Originates the Peptidyl Transfer Origin
Authors: Shin-Yi Lin, Ying-Chi Wang, Chiaolong Hsiao
Journal: Molecular Biology and Evolution (2019)

The ribosome is responsible for protein synthesis in all living organisms. It is best known to exist around 3.5-3.7 Ga whereat life on Earth inhabited anoxic environment with abundant soluble irons. The RNAs and proteins are the two biopolymers that constitute the ribosome. However, both proteins and RNAs require metal cations to fold and to function. There are four Mg-microcluster (Mg2+-μc) structures conserved in core of large subunit, and the 23S ribosomal RNA (rRNA) was shown to catalyze electron transfer in an anoxic environment in the presence of Fe2+. The Mg2+-μc features two idiosyncratic Mg2+ ions that are chelated and bridged by a common phosphate group and along with that, the adjacent residues of RNA backbone together forming ten-membered chelation ring(s). Here, we utilized four rRNA fragments of the large subunit 23S rRNA of Haloarcula marismortui, that includes the residues that form the four Mg2+-μc's. These four rRNA fragments are shown competent to assemble with Mg2+. Our results show that when these rRNA fragments fold or assembly in the presence of Fe2+ under anoxic conditions, each Fe2+-microcluster can catalyze electron transfer. We propose that Fe2+-microclusters of the ribosome, which use Fe2+ as a cofactor to regulate electron transfer, are pivotal and primordial and may be an origin in evolution of the ribosome.
Iron Oxide Nanoflowers @ CuS Hybrids for Cancer Tri-Therapy: Interplay of Photothermal Therapy, Magnetic Hyperthermia and Photodynamic Therapy
Authors: Alberto Curcio, Amanda K. A. Silva, Sonia Cabana, Ana Espinosa, Benoit Baptiste, Nicolas Menguy, Claire Wilhelm, Ali Abou-Hassan
Journal: Theranostics (2019)

Innovative synthesis routes revolutionized nanomaterial combination and design possibilities resulting in a new generation of fine-tuned nanoparticles featuring exquisite shape and constitution control.However, there is still room for improvement when it comes to the development of multi-functional nanoparticle agents merging a plurality of therapeutic functions to tackle tumors simultaneously by synergic mechanisms.Herein, we report the design of an optimized nanohybrid for cancer tri-therapy featuring a maghemite (γ-Fe2O3) nanoflower-like multicore nanoparticle conceived for efficient magnetic hyperthermia (MHT) and a spiky copper sulfide shell (IONF@CuS) with a high near-infrared (NIR) absorption coefficient suitable for photothermal (PTT) and photodynamic therapy (PDT).Methods: Spiky-like IONF@CuS nanohybrids were obtained through a straightforward and scalable water-based template sacrificial synthesis, which allows the shell shape control by tuning polyvinylpyrrolidone (PVP) concentration.A comprehensive characterization of nanohybrid size, shape and structural properties was carried out by combining complementary TEM, SEM, HR-TEM, EELS, XRD and NTA.The all-in-one therapeutic multi-functionality was assessed on cancer cells and on tumor-bearing nude mice.Results: Tests carried out on IONF@CuS nanohybrid aqueous dispersion demonstrated their impressive efficiency to convert light (conversion coefficient = 42 ± 6 %) and magnetic stimulation (SAR ~ 350 W g -1 ) into heat as well as to induce concurrent reactive oxygen species (ROS) formation upon laser irradiation.Such capabilities were further confirmed in cellular environment by in vitro tests and at the organism level by in vivo tests in a murine tumor model.Notably, complete tumor regression was obtained for the PTT mode at low Cu concentration.Overall, these results allowed determining windows of applicability for each therapy individually or in combination.Conclusions: Altogether, the obtained data evidence the successful synthesis of a unique tri-therapeutic nanoparticle featuring highly relevant assets for clinical translation such as reduced nanoparticle administered dose, reduced laser power exposure, reduced magnetic field frequency, and the possibility of serial heating cycles and therapy monitoring by photoacoustic (PA) and magnetic resonance imaging (MRI).Furthermore, the integration of the dual heating capability (MHT + PTT) with the PDT insult offers a unique asset to tackle tumors by multiple cytotoxic strategies in order to improve the therapeutic outcome in a broader spectrum of clinical conditions.
Klotho, fibroblast growth factor‐23, and the renin–angiotensin system — an analysis from the PEACE trial
Authors: Brian A. Bergmark, Jacob A. Udell, David A. Morrow, Petr Jarolim, Julia F. Kuder, Scott D. Solomon, Marc A. Pfeffer, Eugene Braunwald, Marc S. Sabatine
Journal: European Journal of Heart Failure (2019)
European Association of Urology Guidelines on Renal Cell Carcinoma: The 2019 Update
Authors: Börje Ljungberg, Laurance Albiges, Yasmin Abu-Ghanem, Karim Bensalah, Saeed Dabestani, Sergio Fernández-Pello, Rachel H. Giles, Fabian Hofmann, Milan Hora, Markus A. Kuczyk, Teele Kuusk, Thomas B. Lam, Lorenzo Marconi, Axel S. Merseburger, Thomas Powles, Michael Staehler, Rana Tahbaz, Alessandro Volpe, Axel Bex
Journal: European Urology (2019)
Bence-Jones Proteins and Light Chains of Immunoglobulins
Authors: Alan Solomon
Journal: New England Journal of Medicine (1976)

Considerable progress in our understanding of the functional implications of the immunochemical, biochemical, physicochemical, metabolic, and genetic properties of normal immunoglobulins has been achieved through the study of Bence-Jones proteins, myeloma proteins, Waldenström macroglobulins, and their subunits. These homogeneous proteins are produced by neoplastic immunoglobulin-synthesizing cells characteristically present in the bone marrow or lymphoid tissue of patients with multiple myeloma and related plasma cell-lymphocytic dyscrasias. Because they can be readily isolated and purified from serum and urine specimens and because they are generally available in quantities sufficient for detailed analyses, these proteins have become invaluable research material for studies designed . . .
Improvement in affinity and thermostability of a fully human antibody against interleukin-17A by yeast-display technology and CDR grafting
Authors: Wei Sun, Zhaona Yang, Heng Lin, Ming Liu, Chenxi Zhao, Xueying Hou, Zhuowei Hu, Bing Cui
Journal: Acta Pharmaceutica Sinica B (2019)

Monoclonal antibodies (mAbs) are widely used in many fields due to their high specificity and ability to recognize a broad range of antigens. IL-17A can induce a rapid inflammatory response both alone and synergistically with other proinflammatory cytokines. Accumulating evidence suggests that therapeutic intervention of IL-17A signaling offers an attractive treatment option for autoimmune diseases and cancer. Here, we present a combinatorial approach for optimizing the affinity and thermostability of a novel anti-hIL-17A antibody. From a large naïve phage-displayed library, we isolated the anti-IL-17A mAb 7H9 that can neutralize the effects of recombinant human IL-17A. However, the modest neutralization potency and poor thermostability limit its therapeutic applications. In vitro affinity optimization was then used to generate 8D3 by using yeast-displayed random mutagenesis libraries. This resulted in four key amino acid changes and provided an approximately 15-fold potency increase in a cell-based neutralization assay. Complementarity-determining regions (CDRs) of 8D3 were further grafted onto the stable framework of the huFv 4D5 to improve thermostability. The resulting hybrid antibody 9NT/S has superior stabilization and affinities beyond its original antibody. Human fibrosarcoma cell-based assays and in vivo analyses in mice indicated that the anti-IL-17A antibody 9NT/S efficiently inhibited the secretion of IL-17A-induced proinflammatory cytokines. Therefore, this lead anti-IL-17A mAb might be used as a potential best-in-class candidate for treating IL-17A related diseases.
A woman with recurrent anaemia and jaundice
Authors: Muhajir Mohamed, Wan Danial Noor
Journal: BMJ (2019)

A 41 year old white woman presented to the emergency department. She described fever, cough, and exercise intolerance, yellowish discolouration of her eyes, and pain in the left upper quadrant that had been ongoing for three days. She had experienced three similar episodes in the past five years. Each episode resolved completely after treatment with antibiotics prescribed by her general practitioner. She had no other notable medical conditions or family history.

She appeared pale and had scleral icterus. Her spleen was enlarged and palpable below the left costal margin, firm in consistency, and mildly tender on palpation. Results of laboratory investigations are shown in table 1.

View this table:

Table 1 
Results of laboratory investigations



Examination of peripheral blood film revealed abnormalities in red blood cell morphology (fig 1).



Fig 1 
Blood film



Ultrasonography of the abdomen confirmed splenomegaly with spleen size of 16 cm.

1.  What is the most likely diagnosis?

2.  How can you diagnose this condition?

3.  How is this condition managed?

### 1. What is the likely diagnosis?

Hereditary spherocytosis presenting with haemolytic crisis.

There is marked spherocytosis and polychromasia on peripheral blood smear (fig 2). The negative direct antiglobulin test and splenomegaly are suggestive of hereditary spherocytosis. In patients with hereditary spherocytosis, development of anaemic symptoms and jaundice in association with a rapid drop in haemoglobin …
Uncovering the Molecular Signature of Pathogenic Tissue-Infiltrating T Cells during Acute Graft-Versus-Host Disease
Authors: Victor Tkachev, Scott N Furlan, E. Lake Potter, Hengqi Zheng, Daniel J Hunt, Lucrezia Colonna, Agne Taraseviciute, Judith M Carlson, Kayla Betz, Alison Yu, Michelle Hoffman, Audrey Baldessari, Sarah Herrin, Joe Olvera, Chad Littlewood, Christopher English, Bruce R. Blazar, Mario Roederer, Leslie Kean
Journal: Blood (2018)