tbuckley/cabot-search huggingface dataset:
AB0479 PREGNANCY OUTCOMES IN PATIENTS WITH RHEUMATIC DISEASES.
Authors: Z. Alekberova, R. Goloeva, A. Lila
Journal: Annals of the Rheumatic Diseases (2020)

Background: Objectives: To evaluate pregnancy outcomes in patients with Behcet’s disease (BD), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic scleroderma (SSD). Methods: The study included 73 patients with rheumatic diseases (RDs) aged 18 to 40 years signing the informed consent form and completing dedicated thematic chart. The mean age of participants was 30.0 years - for BD patients; 33.5 years - for SLE, 33.5 – for RA; and 35.0 for SSD patients; mean disease duration was 4.5 years, 11.5 years 4.0 years and 6.0 years, respectively. 23 patients (11 BD patients, 5 SLE, 5 RA 5 and 2 SSD 2) out of 73 never had pregnancies, including 15 virgo patients and 4 patients who were planning pregnancy in the near future.158 pregnancies in 50 patients with rheumatic diseases (31 BD patients, 7 SLE, 6 RA, and 6 SSD pts) were retrospectively analyzed. Results: Outcomes of 159 pregnancies in RD patients were as follows: 95 (60%) on time births of full-term babies; 2 cases (1.2%) of early neonatal death in two BD females (premature deliveries at 28 and 32 gestational weeks of babies with signs of extreme prematurity who died 1 day after birth); 35 pregnancies were terminated before 10 weeks of gestation: 34 pregnancies (in 4 patients) - at the woman’s request, 1-for medical reasons (rubella at 7 weeks of gestation). Totally 27 cases of adverse pregnancy outcomes were documented in 20 patients (40% of 50 patients): 19 cases (in 14 patients) of intrauterine deaths, one case of ectopic pregnancy, 8 cases (in 6 patients) of early miscarriages (at 5, 6 and 10 weeks of gestation). There were no cases of antiphospholipid syndrome documented. Pregnancy outcomes in RD patients BD, n=31 SLE, n=7 RA, n=6 SSD, n=6 Pregnancy, n 107 16 17 18 Childbirth, n 71 9 9 6 Medical abortion, n 20 2 3 10 Intrauterine deaths, n 12 4 4 0 Miscarriage, n 4 1 1 2 Out of total 95 babies born to RD patients, two had recurrent aphthous stomatitis (in 2 BD patients), and one had congenital glaucoma (born to a mother with neuro-Behcet’s). 10 BD and 2 RA are patients multipara mothers who are raising 3 and more children. Conclusion: Rheumatic diseases are associated with high incidence of adverse pregnancy outcomes. Disclosure of Interests: None declared
Author Correction: Pan-cancer image-based detection of clinically actionable genetic alterations
Authors: Jakob Nikolas Kather, Lara R. Heij, Heike I. Grabsch, Chiara Loeffler, Amelie Echle, Hannah Sophie Muti, Jeremias Krause, Jan M. Niehues, Kai A. J. Sommer, Peter Bankhead, Loes F. S. Kooreman, Jefree J. Schulte, Nicole A. Cipriani, Roman D. Buelow, Peter Boor, Nadina Ortiz-Brüchle, Andrew M. Hanby, Valerie Speirs, Sara Kochanny, Akash Patnaik, Andrew Srisuwananukorn, Hermann Brenner, Michael Hoffmeister, Piet A. van den Brandt, Dirk Jäger, Christian Trautwein, Alexander T. Pearson, Tom Luedde
Journal: Nature Cancer (2020)
Interactions with a "Humanized" Mesenchymal Bone Marrow Stromal Niche In Vivo Modify the Patterns of Essential Genes for Myeloma Cells: Therapeutic Implications
Authors: Ryosuke Shirasaki, Sondra L. Downey-Kopyscinski, Ricardo De Matos Simoes, Olga Dashevsky, Sara Gandolfi, Megan Bariteau, Aviad Tsherniak, Francisca Vazquez, Maria Themeli, Jonathan D. Licht, Larry H. Boise, Richard W.J. Groen, Constantine S. Mitsiades
Journal: Blood (2020)
HORIZON (OP-106): Melflufen Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma with High-Risk Cytogenetics-Subgroup Analysis
Authors: María-Victoria Mateos, Albert Oriol, Alessandra Larocca, Joan Blade Creixenti, Michele Cavo, Paula Rodríguez-Otero, Xavier Leleu, Maxim Norkin, Omar Nadeem, John W. Hiemenz, Hani Hassoun, Cyrille Touzeau, Adrián Alegre Amor, Agne Paner, Christopher Maisel, Amitabha Mazumder, Anastasios Raptis, Noemí Puig, Johan Harmenberg, Bengt Gustavsson, Marcus Thuresson, Paul G. Richardson
Journal: Blood (2020)
Survival Analysis of Newly Diagnosed Transplant-Eligible Multiple Myeloma Patients in the Randomized Forte Trial
Authors: Francesca Gay, Pellegrino Musto, Delia Rota Scalabrini, Monica Galli, Angelo Belotti, Elena Zamagni, Luca Bertamini, Renato Zambello, Micol Quaresima, Giovanni De Sabbata, Giuseppe Pietrantuono, Mattia D'Agostino, Daniela Oddolo, Andrea Capra, Anna Marina Liberati, Salvatore Palmieri, Franco Narni, Massimo Offidani, Michele Cavo, Mario Boccadoro
Journal: Blood (2020)
Clinical Profile of IMGN632, a Novel CD123-Targeting Antibody-Drug Conjugate (ADC), in Patients with Relapsed/Refractory (R/R) Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Authors: Naveen Pemmaraju, Giovanni Martinelli, Elisabetta Todisco, Andrew A Lane, Evelyn Acuña-Cruz, Eric Deconinck, Eunice S. Wang, Kendra L. Sweet, David A Rizzieri, Luca Mazzarella, Daniel J. DeAngelo, Pau Montesinos, Corrado Tarella, Harry P. Erba, Marina Konopleva, Hagop M. Kantarjian, Callum M Sloss, Kara E Malcolm, Patrick A Zweidler-McKay, Naval Daver
Journal: Blood (2020)
SAT0244 Concomitant use of gastroprotective agents among users of nonsteroidal antiinflammatory drugs in italy
Authors: AP Caputi, SX Kong, P Mavros, E Ricci, A Russo
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Beside life-threatening gastrointestinal (GI) adverse events (e.g. perforation, ulcer or bleeding), non-steroidal anti-inflammatory drug (NSAID) use is associated with less severe GI symptoms, which may result in the concurrent use of GI protective agents (GPAs) and/or antacids and therefore increased medical costs. <h3>Objectives</h3> Analyse the patterns of use of GI protective agents among NSAID users. <h3>Methods</h3> During ten days of consultation, 913 NSAID users were identified among 20,668 patients seen by 103 general practitioners in the Sicily region of Italy from December 1998 to June 1999. Physicians filled out data collection forms regarding the type and indication of NSAIDs and the use of adjuvant therapy to prevent or treat adverse GI effects of NSAID therapy during the past 6 months. <h3>Results</h3> The mean age of the patients was 61 years and 61% were females. Indications for NSAID therapy included osteoarthritis/arthrosis in 61% of the patients, rheumatoid arthritis in 9%, and other reasons, most notably non-articular pain in 28%. Based on the number of prescriptions (Rx) and the number of patients (pts), the most frequently prescribed NSAID was nimesulide (24% Rx, 37% pts), followed by diclofenac (24% Rx, 32% pts), piroxicam (17% Rx, 24% pts), and ketoprofen (9% Rx, 12% pts) accounting for 75% of all NSAID prescriptions. The mean duration of all NSAID therapy varied between 60 to 120 days depending on the specific NSAIDs used by the patients during the 6 months prior to the visit. Of all NSAID users, 50.3% used a GI medication, including GPAs [including proton pump inhibitors (PPI), H2-antagonists, and misoprostol] and antacids (Rx or OTC). Although certain variations existed, the use of GPAs and antacids was consistent across all NSAIDs including those newer products such as ArthrotecÒ and meloxicam. Concomitant use of H2-antagonists occurred in 14% of all NSAID users, PPI in 8%, misoprostol in 15%, and antacids in 22%. The mean duration of GPA use varied between 73 to 96 days during the 6-month period. About 40% of H2 antagonists, 21% PPI, 86% misoprostol, and 62% antacids were prescribed to prevent NSAID adverse events and the remaining were for treatment. <h3>Conclusion</h3> Concurrent use of gastroprotective agents and antacids was observed in more than half of the patients taking NSAIDs, and their use was consistent across individual products. The concomitant use of GPAs and/or antacids with NSAIDs does not only incur inconvenience to the patients because of polypharmacy but also increase healthcare costs.
Efficacy and Safety of Nivolumab and AVD in Early-Stage Unfavorable Hodgkin Lymphoma: Extended Follow-up from the GHSG Phase II Nivahl Trial
Authors: Paul J Bröckelmann, Helen Goergen, Ulrich Keller, Julia Meissner, Karolin Trautmann, Teresa V Halbsguth, Stephanie Sasse, Martin Sökler, Andrea Kerkhoff, Stephan Mathas, Andreas Hüttmann, Matthias Bormann, Andreas Zimmermann, Michael Fuchs, Bastian von Tresckow, Christian Baues, Andreas Rosenwald, Wolfram Klapper, Carsten Kobe, Peter Borchmann, Andreas Engert
Journal: Blood (2020)
Impact of Mutated Genes By Next Generation Sequencing on Overall Survival in a Cohort of Peruvian Patients with AML/MDS
Authors: Antonio A Carrasco-Yalán, Joseph A. Pinto, Jorge J Valdés-Gómez, Tatiana Saldarriaga, Melissa Morales-Coloma, John W Pando-Mayta, Marylin Cuyutupac-Barja, Paloma Arias-Arana, Natalia I Vigo-Ames, Angela Arbizu-Chipana, Shirley Quintana, Franco Doimi, Cesar Samanez-Figari, Juan Haro-Vargas, Jorge Castillo-Aguirre, Marco Lopez, Daniel J Enriquez
Journal: Blood (2020)
DREAMM-2: Single-Agent Belantamab Mafodotin (Belamaf) Effects on Patient-Reported Outcome (PRO) Measures in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)
Authors: Rakesh Popat, Sagar Lonial, Peter M. Voorhees, Simona Degli Esposti, Ira Gupta, Joanna Opalinska, Sandhya Sapra, Boris Gorsh, Zangdong He, David M Kleinman, Debra Schaumberg, Angely Loubert, Juliette Meunier, Antoine Regnault, Laurie Eliason
Journal: Blood (2020)
Updated Results from the Phase I CRB-402 Study of Anti-Bcma CAR-T Cell Therapy bb21217 in Patients with Relapsed and Refractory Multiple Myeloma: Correlation of Expansion and Duration of Response with T Cell Phenotypes
Authors: Melissa Alsina, Nina Shah, Noopur S. Raje, Sundar Jagannath, Deepu Madduri, Jonathan L. Kaufman, David S. Siegel, Nikhil C. Munshi, Jacalyn Rosenblatt, Yi Lin, Andrzej Jakubowiak, Jagoda Jasielec, Alison Timm, Ashley Turka, Pingping Mao, Nathan Martin, Timothy B. Campbell, Kristen Hege, Hans Bitter, Fabio Petrocca, Jesus G. Berdeja
Journal: Blood (2020)
Daratumumab Plus Lenalidomide and Dexamethasone (DRd) Compared to Daratumumab Plus Pomalidomide and Dexamethasone (DPd) in Relapsed Lenalidomide-Exposed or Refractory Multiple Myeloma (MM) Patients: The Mayo Clinic Experience
Authors: Muhamad Alhaj Moustafa, Ricardo Parrondo, Mays F Abdulazeez, Vivek Roy, Taimur Sher, Victoria R. Alegria, Rahma M Warsame, Jeremy Larsen, Wilson I Gonsalves, Taxiarchis Kourelis, Prashant Kapoor, Rafael Fonseca, Francis K. Buadi, David Dingli, Suzanne R. Hayman, Craig B. Reeder, Arshi Agrawal, Asher A. Chanan-Khan, Sikander Ailawadhi
Journal: Blood (2020)
The problem isn’t Excel, it’s unprofessional software engineering
Authors: Harold Thimbleby
Journal: BMJ (2020)

Speculating on the causes of any major public health system failure is fascinating, but how people or systems corrupt or lose data isn’t important.1 Designing a critical system such as a national test and trace system that does not automatically and instantly notice (and block) data being corrupted or lost is simply inexcusable. Once a system is badly designed, many errors are …
Abstract 352: Optimization of a CRISPR Activation Human Pluripotent Stem Cell Line for Screening of Candidate Regulators of Cardiomyocyte Maturation
Authors: Elaheh Karbassi, Alessandro Bertero, Shin Kadota, Paul Fields, Lil Pabon, Hans Reinecke, Stephen Hauschka, Charles E Murry
Journal: Circulation Research (2020)

Human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) applications for cell therapy and disease modeling are limited due to the cells’ lack of resemblance structurally and functionally to adult cardiomyocytes. To understand hPSC-CM maturation, we characterized two established approaches to mature cardiomyocytes—long term culture (aging of cells in a dish) and in vivo transplantation to an infarcted adult rat heart. RNA sequencing of hPSC-CMs from these systems demonstrated that in vivo transplantation is much more effective in maturing hPSC-CMs, inducing a more adult-like cardiac gene program (e.g. upregulation of TNNI3, MYL2, SCN5A ), compared to cells kept in culture up to one year. Using this dataset, we identified candidate drivers of hPSC-CM maturation, including transcription factors and chromatin regulators, that we hypothesize are necessary to program hPSC-CMs to an adult-like state. To test the relationship between transcription factor regulation and hPSC-CM maturation, we developed a constitutive CRISPR activation (CRISPRa) pluripotent stem cell line to upregulate these transcriptional regulators upon addition of guide RNAs (gRNA). This cell line expresses nuclease-deficient Cas9 fused to the transcriptional activator VPR (dCas9-VPR), driven by the strong CAG promoter and targeted to the AAVS1 safe harbor site. In pluripotent stem cells, target genes are upregulated up to 150-fold when gRNA is present; however, after differentiation into cardiomyocytes, dCas9-VPR transgene expression is silenced, and dCas9-VPR levels are insufficient to activate gRNA-targeted genes. To optimize CRISPRa for cardiomyocyte applications, we are generating alternative stem cell lines with dCas9-VPR targeted to the human ROSA26 safe harbor site or driven by a cardiac-specific troponin T promoter, testing the regulation of transgene expression mediated by safe harbor site or promoter respectively. The characterization of these CRISPRa cell lines provides insights into CRISPR expression regulation and genome engineering strategies for applications in stem cells and hPSC-CMs. We will use this system to screen for maturation regulators and identify key combinations that are effective in programming hPSC-CMs towards an adult-like state.
Abstract 478: Connexin-43 Reduction Rescues Cardiac and Skeletal Muscle Pathology in a Novel Mouse Model of Duchenne Muscular Dystrophy Symptomatic Carriers
Authors: Julie Nouet, Eric Himelman, Diego Fraidenraich
Journal: Circulation Research (2020)

Duchenne muscular dystrophy (DMD) and its associated cardiomyopathy manifest in 8-10% of all female carriers however research remains male-centric. Although underrepresented, symptomatic females face the risk of cardiac, respiratory, and skeletal muscle problems. Basic research and clinical trials exclude female carriers therefore developments in treatment expose females to unknown safety and efficacy issues. The bottleneck is largely due to the absence of a faithful mouse model. To generate a mouse model, we injected mdx embryonic stem cells (ESCs) into wild-type (WT) blastocysts ( mdx /WT chimera). The cardiac and skeletal muscle phenotype recapitulates the same generated as a consequence of x-inactivation in human manifesting female patients. In the heart, mdx /WT chimeras develop fibrotic cardiomyopathy. In the skeletal muscle, we found evidence of fibrosis, inflammation and muscle weakness. We found that Connexin-43 (Cx43), the primary gap junctional protein in the heart, was pathologically enhanced and remodeled in mdx /WT chimeras. Cx43 was also enhanced in the dystrophic skeletal muscle. Genetic reduction of Cx43-copy number protected mdx /WT chimeras from cardiac and skeletal muscle fiber damage. The latter result was unexpected because Cx43 is not expressed in mature muscle fibers. Upon further investigation, Cx43 was localized to the mononuclear cells invading the interstitial space between dystrophic skeletal muscle fibers. Pathologically enhanced activity of Cx43 in mdx FACS-macrophages was observed via ethidium bromide uptake and the Cx43 hemichannel peptide mimetic, Gap19, inhibited Cx43 function in a dose-dependent manner. Because an excess of Cx43 has been associated with cell death, we believe that Cx43 reduction in invading mdx macrophages benefits the skeletal muscle of understudied DMD carriers, perhaps by a paracrine mechanism involving macrophage-skeletal muscle fiber communication.
Face masks, vision, and risk of falls
Authors: Elmar C Kal, William R Young, Toby J Ellmers
Journal: BMJ (2020)

Public health experts and international organisations increasingly recommend wearing masks to help limit the spread of covid-19. 1Safe and comfortable use of masks is therefore essential to maximise adoption and compliance.Formal guidance and associated media coverage have focused on discomfort and communication issues, 2 with little attention paid to the effect of wearing masks on risk of falling.Although guidance recommends that older adults wear masks because they are an at risk group, it is this population for whom the effects of masks on walking safety are likely to be most pronounced.Aside from obstructing vision for glasses wearers (by causing spectacles to fog up), face masks invariably block parts of the lower peripheral visual field, even in people who do not wear glasses.Visual information from the lower peripheral field is important for detecting and avoiding nearby hazards, and for placing our steps safely. 3 Wearing a face mask reduces the wearer's opportunity to use this important sensory information during walking and may therefore increase the chance of tripping or falling. 3 4Evidence exists that multifocal glasses (which similarly obstruct lower visual field, through blurring) can reduce safety when negotiating obstacles and stairs.
SAT0075 Efficacy of intra-articular hyaluronic acid injections in knee osteoarhritis
Authors: F Ardic, D Bolulu, O Topuz, S Cubukcu
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Our objective was to assess the effects of intra-articular injections of hyaluronic acid (HA) (Hylan G-F 20: Synvisc) on symptoms and functional outcome of knee osteoarthritis (OA). <h3>Methods</h3> A total of 60 injections were performed in 17 patients involving 20 knees. These patients with symptomatic, radiological knee OA were randomly assigned to treatment with HA or placebo. Treatment group consisted of 12 patients received three weekly injections of HA into one or both (if bilateral symptomatic) knees (15 knees total). Control group consisted of 5 patients who received three intra-articular injections of 2-ml physiological saline with weekly intervals (5 knees total). Fifteen-minute walking period, range of motion, need of drug and painless walking time were noted at weeks 1,2,3,8. Pain at walking, resting, night and motion were evaluated by Visual Analogue Scale (VAS). Also, WOMAC Osteoarthritis Indexes (Pain by WOMAC-A, stiffness by WOMAC-B, activities of daily living by WOMAC-C) were evaluated by Likert scales in the same weekly intervals. <h3>Results</h3> Statistically significant improvements (p &lt; 0.001) in WOMAC-A-3 (3rd week), WOMAC-A-8(8th week), WOMAC-B-3, WOMAC-B-8, VAS walking-2,3,8, VAS resting?8, VAS motion-2,3,8, painless walking time-8,15 min walking period-8, need of drug-2,3,8 were found. When compared with control group, statistically significant improvement was noted (p &lt; 0.05) at WOMAC-A-8, WOMAC-C-8, VAS walking-8, VAS resting ?3,8 painless walking time-2,3,8, need of drug-8. No side effect was encountered in both of the groups. <h3>Conclusion</h3> Early signs of efficacy of intra-articular injections of HA for knee OA was beginning in the 2nd week. But this early improvement is not significant when compared with control group. The real effects of the HA treatment were seen at the 8th week. It is concluded that Hylan G-F 20 provided good clinical benefit for knee OA patients and the clinical improvement was prominent after 8 weeks.
Efficacy and Safety of Selinexor for Acute Myeloid Leukemia: A Systematic Review
Authors: Mydah Sajid Hashmi, Muhammad Ans Sharif, Ali Jaan, Umer Salman, Summera Aziz, Asna Shahab, Zahoor Ahmed, Muhammad Junaid Tariq, Mobeen Zaka Haider, Faiz Anwer
Journal: Blood (2020)
FRI0119 Hla-dm polymorphism in systemic lupus erythematosous (sle)
Authors: C Da Silva Simoes, J Morel, MT Salles, O Avinens, J Sany, JF Eliaou, B Combe
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> HLA-DR (DRB1*15 and DRB1*03) component is weakly associated to SLE and other genes and genetic regions are investigated in order to better characterise the genetic predisposition to the disease. DMA and DMB genes are located within the HLA class II region. The alpha beta heterodimer encoded by these genes is directly involved in the HLA class II-restricted antigen presentation pathway. Limited nucleotide polymorphism has been described in the 3rd exon of the DMA and DMB genes. <h3>Objectives</h3> To look for an association between DM polymorphism and SLE, the DMA and DMB allele distribution was compared between patients and controls from the same geographic area. <h3>Methods</h3> 73 SLE patients were selected according the 1997 ACR criteria. 147 unrelated control individuals were randomly selected (random controls: RC). A second group of 88 unrelated controls who were closely matched for DRB1 genotypes with patients was defined (matched controls: MC) in order to determine whether the association between SLE and certain DM alleles resulted from direct influence of the DM genes or indirect influence through linkage disequilibrium with alleles at the DRB1 locus. All the individuals were typed for DR and DM by SSOs after genomic DNA extraction of peripheral mononuclear cells and PCR. The significance of differences in phenotype frequencies was determined by Fischer’s exact tests with Bonferoni correction. <h3>Results</h3> 49.3% of the patients carry either DRB1*15/16 (21.9%) or DRB1*03 alleles (27.4%), or both. DMA*0103, DMA*0104 and DMB*0102 were found to be more frequent in SLE patients compared to RC (p = 0.0012, p = 0.0012, p = 0.0097, respectively). Similarly the frequency of these alleles was increased in patients compared to MC (p = 0.0058, p = 0.0013, p = 0.017, respectively) suggesting a direct influence of DM genes on SLE susceptibility. This direct influence was confirmed by showing no significant difference of DM allele frequencies between RC and MC. Finally, after stratification of the patients and the MC according to the DRB1 genotypes, DMA*0104 was increased in DRB1*15/16, DRB1*03 negative patients. <h3>Conclusion</h3> These data show an association between SLE susceptibility and DMA*0103, *0104, DMB*0102. The influence of these alleles cannot be explained by linkage disequilibrium with SLE-associated alleles.