tbuckley/cabot-search huggingface dataset:
SAT0053 Efficacy and safety of synvisc in severe knee osteoarthritis (oa): experience from a large cohort of patients followed in private rheumatological practice
Authors: A Wulwik, S Bertocci, V Raude-Leroy, PL Lleu
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> It is demonstrated that Synvisc® (S) (3 intra-articular injections at 1 week apart) improved algofunctional status of patients with knee OA. In this cohort study, the efficacy of S. was followed for up to 2 years in a specific population of patients with severe knee OA, confirmed clinically and radiologically. One half of those patients were candidates for a total knee replacement. <h3>Methods</h3> In all patients treated with S. between June 1998 and September 1999, demographic data and medical history were recorded. Following S. course, a rheumatological evaluation was performed to assess improvement and local safety. Then, a long-term follow-up was performed in May 2000, all patients completing a questionnaire recording their clinical status, global satisfaction, tolerance of S. and concomitant therapies consumption. Due to methodology of this study, patients? long-term follow-up ranked from 9 to 24 (mean = 15.5) months. <h3>Results</h3> Out of 117 patients treated, 81 (70%) completed the follow-up questionnaire. Baseline characteristics of those 81 patients are as follow: demographic data: mean age = 71 years; female = 57%; BMI = 27.5 kg/m<sup>²</sup>; medical history: mean disease duration = 8 years; femoro-tibial knee OA: 97% (isolated: 33% or associated with femoro-patelar knee OA: 64%); chondrocalcinose: 19% At baseline, 54% of patients had a ?severe? and 42% a ?very severe? knee OA according to physician. Nineteen patients (23%) were treated by S. in both knees and 15 (19%) received two courses of S. in the same knee (mean time between these two courses = 11 months). A clinically significant improvement (moderate, important or very important) was observed by the physician after 77% of S. courses, while this treatment was followed by transient local adverse events (pain, swelling) after only 15% of S. courses (3 IA injections). The analysis of patients? questionnaires showed that 49% reported a ?severe? pain and 22% a ?very severe? pain before treatment with S. The treatment was considered as globally satisfactory by 63% of patients, the main symptoms improved being pain on movement (56% of patients) and nocturnal pain (52%). Out of daily living? activities, ascending and descending stairs were improved in 51% and 46% of patients respectively. Most patients (53%) improved their maximum distance walked and 22% resumed their leisure activities. Moreover 90% of them reported a good tolerance of S. and 47% decreased their analgesics and NSAIDs consumption. <h3>Conclusion</h3> This study demonstrates the interest of high molecular viscosupplementation with Synvisc® in the management of severe knee OA patients. Of special interest, 32 patients (82%) out of 39 candidates for total knee replacement at baseline, were able to delay this surgical treatment.
Long-Term Outcomes of Imatinib Real-Life Treatment for Chronic Myeloid Leukemia- a 20-Year Review
Authors: Elzbieta Szczepanek, Ositadima Chukwu, Magdalena Kaminska, Hubert Wysoglad, Agnieszka Cenda, Joanna Waclaw, Magdalena Zawada, Magdalena Jakobczyk, Tomasz Sacha
Journal: Blood (2020)
A Systematic Review on Efficacy and Safety of Bortezomib Based Regimens for Treatment of Waldensterom Macroglobulinemia
Authors: Abdul Jabbar Dar, Qasim Khurshid, Muhaddis Ejaz Ahmad, Muhammad Ali Mirza, Farhan Khalid, Ali Jaan, Syed Maaz Abdullah, Muhammad Saad Farooqi, Atif Irfan Khan, Richi Kashyap, Anam Khan, Saad Javed, Fazeel Qamar, Faiz Anwer
Journal: Blood (2020)
Study Design and Initial Baseline Characteristics in Solace-Kids: Crizanlizumab in Pediatric Patients with Sickle Cell Disease
Authors: Matthew M. Heeney, David C. Rees, Mariane de Montalembert, Isaac Odame, R. Clark Brown, Yasser Wali, Thu Thuy Nguyen, Du Lam, Raquel Merino Herranz, Julie Kanter
Journal: Blood (2020)
Decline in HCV incidence in HIV positive MSM - progress to HCV micro-elimination in the UK?
Authors: Lucy Garvey, Graham Cooke, Colette Smith, Christof Stingone, Indrajit Ghosh, Subathira Dakshina, Lakshmi Jain, Laura Jane Waters, Tabitha Mahungu, Filippo Ferro, Chandni Sood, Carolyn Freeman, Sadna Ullah, Clare Phillips, Harriet Sharp, Ruth Burholt, Rageshri Dhairyawan, Yvonne Gilleece, Ashley Brown, Chloe Orkin, Alison Rodger, Sanjay Bhagani
Journal: Journal of Hepatology (2020)
비대상성 간경변을 동반한 진행성 간세포암종에서 간동맥내 저용량 5-fluorouracil 및 cisplatin 주입요법의 효과
Authors: 임태영, 정재연, Sung Won Cho, 심성준, 김종수, 최승준, 최정우, 권혁춘, 이기명, 김재근, Je Hwan Won, Byeong-moo Yoo, 이광재, 함기백, Kim Jin Hong
Journal: Clinical and Molecular Hepatology (2006)
Mechanisms Regulating Myeloma Cell Responsiveness to Antisense Oligonucleotides Targeting IRF4
Authors: Ryosuke Shirasaki, Esperanza M Algarín, Ricardo De Matos Simoes, Sondra L. Downey-Kopyscinski, Shizuka Yamano, Xiaolin Luo, Youngsoo Kim, Robert MacLeod, Constantine S. Mitsiades
Journal: Blood (2020)
Advances in Magnetic Nanoparticle‐Mediated Cancer Immune‐Theranostics
Authors: Hung‐Wei Cheng, Hsin‐Yi Tsao, Chih‐Sheng Chiang, San‐Yuan Chen
Journal: Advanced Healthcare Materials (2020)

Abstract Cancer immunotherapy is a cutting‐edge strategy that eliminates cancer cells by amplifying the host's immune system. However, the low response rate and risks of inducing systemic toxicity have raised uncertainty in the treatment. Magnetic nanoparticles (MNPs) as a versatile theranostic tool can be used to target delivery of multiple immunotherapeutics and monitor cell/tissue responses. These capabilities enable the real‐time characterization of the factors that contribute to immunoactivity so that future treatments can be optimized. The magnetic properties of MNPs further allow the implementation of magnetic navigation and magnetic hyperthermia for boosting the efficacy of immunotherapy. The multimodal approach opens an avenue to induce robust immune responses, minimize safety issues, and monitor immune activities simultaneously. Thus, the object of this review is to provide an overview of the burgeoning fields and to highlight novel technologies for next‐generation immunotherapy. The review further correlates the properties of MNPs with the latest treatment strategies to explore the crosstalk between magnetic nanomaterials and the immune system. This comprehensive review of MNP‐derived immunotherapy covers the obstacles and opportunities for future development and clinical translation.
Large Scale Ex Vivo Expansion of Γδ T Cells Using Artificial Antigen Presenting Cells for the Treatment of Acute Myeloid Leukemia
Authors: Justin C. Boucher, Bin Yu, Gongbo Li, Bishwas Shrestha, Jeffrey E. Lancet, David A. Sallman, Ana Marie Landin, Adam William Mailloux, Claudio Anasetti, Linda L. Kelley, Marco L. Davila, Nelli Bejanyan
Journal: Blood (2020)
Conformation-selective tau monoclonal antibodies inhibit tau pathology in primary neurons and a mouse model of Alzheimer’s disease
Authors: Garrett S. Gibbons, Soo-Jung Kim, Qihui Wu, Dawn M. Riddle, Susan N. Leight, Lakshmi Changolkar, Hong Xu, Emily S. Meymand, Mia O’Reilly, Bin Zhang, Kurt R. Brunden, John Q. Trojanowski, Virginia M. Y. Lee
Journal: Molecular Neurodegeneration (2020)

The spread of tau pathology in Alzheimer's disease (AD) is mediated by cell-to-cell transmission of pathological tau seeds released from neurons that, upon internalization by recipient neurons, template the misfolding of naïve cellular tau, thereby propagating fibrillization. We hypothesize that anti-tau monoclonal antibodies (mAbs) that selectively bind to pathological tau seeds will inhibit propagation of tau aggregates and reduce the spread of tau pathology in vivo.We inoculated mice with human AD brain-derived extracts containing tau paired helical filaments (AD-tau) and identified two novel mAbs, DMR7 and SKT82, that selectively bind to a misfolded pathological conformation of tau relative to recombinant tau monomer. To evaluate the effects of these mAbs on the spread of pathological tau in vivo, 5xFAD mice harboring significant brain Aβ plaque burden were unilaterally injected with AD-tau in the hippocampus, to initiate the formation of neuritic plaque (NP) tau pathology, and were treated weekly with intraperitoneal (i.p.) injections of DMR7, SKT82, or IgG isotype control mAbs.DMR7 and SKT82 bind epitopes comprised of the proline-rich domain and c-terminal region of tau and binding is reduced upon disruption of the pathological conformation of AD-tau by chemical and thermal denaturation. We found that both DMR7 and SKT82 immunoprecipitate pathological tau and significantly reduce the seeding of cellular tau aggregates induced by AD-tau in primary neurons by 60.5 + 13.8% and 82.2 + 8.3%, respectively, compared to IgG control. To investigate the mechanism of mAb inhibition, we generated pH-sensitive fluorophore-labeled recombinant tau fibrils seeded by AD-tau to track internalization of tau seeds and demonstrate that the conformation-selective tau mAbs inhibit the internalization of tau seeds. DMR7 and SKT82 treatment reduced hyperphosphorylated NP tau as measured with AT8 immunohistochemistry (IHC) staining, but did not achieve statistical significance in the contralateral cortex and SKT82 significantly reduced tau pathology in the ipsilateral hippocampus by 24.2%; p = 0.044.These findings demonstrate that conformation-selective tau mAbs, DMR7 and SKT82, inhibit tau pathology in primary neurons by preventing the uptake of tau seeds and reduce tau pathology in vivo, providing potential novel therapeutic candidates for the treatment of AD.
Efficacy of Post-Transplant Cyclophosphamide As Graft-Versus-Host Disease Prophylaxis after Peripheral Blood Stem Cell HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation; A Prospective Pilot Trial
Authors: Monzr M. Al Malki, Ni-Chun Tsai, Joycelynne Palmer, Saloomeh Mokhtari, Thai Cao, Haris Ali, Amandeep Salhotra, Shukaib Arslan, Ibrahim Aldoss, Nicole Karras, Haris M. Ali, Haris Ali, Anthony S. Stein, David S Snyder, Guido Marcucci, Stephen J. Forman, Ryotaro Nakamura
Journal: Blood (2020)
Qualitative Analysis of the Treatment Experience and Well-Being of Patients with Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL) Enrolled in 2 Trials of Lisocabtagene Maraleucel (liso-cel) during the Initial Stages of Therapy
Authors: Tanya Siddiqi, Ulrich Jaeger, Olga Moshkovich, Jennifer Devlen, Matthew Miera, Agnes Williams, Jens Hasskarl, Fei Fei Liu, Julia Braverman, Gilles Salles
Journal: Blood (2020)
AB0969 GAINED WEIGHT DURING PREGNANCY AND LOW BACK PAIN: IS IT REALLY ASSOCIATED?
Authors: M. Yasmine, S. Miladi, A. Fazaa, L. Souebni, S. Mariem, K. Ouenniche, S. Kassab, S. Chekili, K. Ben Abdelghani, A. Laatar
Journal: Annals of the Rheumatic Diseases (2020)

Background: Back pain is known to be a common complaint during pregnancy explained by gained weight in this period. Besides, the incidence of low back pain (LBP) in postpartum has also been quoted to be non-negligible even after delivery. Objectives: The aim of our study was to assess if the development of LBP during the post-partum period was correlated to gained weight after delivery. Methods: In this prospective study, we assessed a survey of 60 women under the age of 35 for back pain symptoms during the postpartum period from day 1 to 18 months. A structured questionnaire using Google form was used. Data from this survey were then correlated with gained weight and pregnancy outcome, as well as women’s history of LBP. Results: We interviewed 60 women during their post-partum period. The mean age was 27,9 years old [24, 35 years]. Women were on average at 9 months of post-partum [1, 18 months]. The median height was 1,6 meters [1,54-1,74m]. The median weight at the moment of the study was 63,2 kilograms [48-80kg]. Before pregnancy, body mass index was 23,5 Kg/m 2 [17-34 Kg/m 2 ]. The total gained weight at the end of pregnancy was 14 kg [12-29 kg]. Only 20% gained more than 15kg. LBP was experienced in 35% of cases with a mean delay of 3,2 months post-partum [1-8 months]. The prevalence of persistent LBP was noted in 26% of cases. However, no correlation was found between LBP and gained weight (p=0,07). Sixty five percent reported one or more significant episodes of back pain during their pregnancy. Significantly, more patients suffering from pain in pregnancy had history of previous back pain episodes when not pregnant (p&lt;0,001), as well as during previous pregnancies (p&lt;0,001). Conclusion: No correlation was found between gained weight and occurrence of LBP. The main factors associated with the development of back pain were previous episodes of back pain while non-pregnant or pregnant. Disclosure of Interests: None declared
AB0145 EFFECTS OF IMMUNOSUPPRESSIVE MEDICATION ON TYPE I INTERFERON ACTIVATION: IN VITRO ANALYSIS SHOWS A DOWNREGULATING EFFECT ON IFN ACTIVATION OF HYDROXYCHLOROQUINE AND ASPIRIN
Authors: M. J. Wahadat, M. Lourens, E. Huijser, C. G. Van Helden-Meeuwsen, S. Kamphuis, M. Versnel
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic Lupus Erythematosus (SLE) is prototypic Interferon (IFN) driven autoimmune disease characterized by an increased expression of type-I IFN stimulated genes, known as the IFN signature. The inhibitory effects of various drugs like Hydroxychloroquine and more recently Aspirin on IFN inducing pathways (1, 2) led to the idea that some standard of care drugs might decrease the IFN score in patients. Data on the in vitro effect of immunosuppressive medication on IFN activation are limited. Testing immunosuppressive agents for their effect on IFN activation in vitro will give insight into the mechanisms of IFN activation in vivo and the effect of immunosuppressive medication on this activation. Objectives: To study the effect of immunosuppressive medication on the type-I IFN signature in an in vitro model Methods: Freshly isolated human PBMCs were stimulated for 24 hours with or without CpG-A or Imiquimod (IQ) or transfected with the cGAS agonist G3-YSD to induce IFN upregulation through the TLR7/9- and DNA Sensing Receptor-pathway respectively. To assess the direct role of the medication on the downstream pathway of the IFNAR PBMCs were stimulated with IFN-a2b. Aspirin, diclofenac, HCQ, Mycophenolate Mofetil (MMF) and prednisone were added separately to these cultures followed by analysis of MxA by qPCR as a readout for IFN type I activation. Cell viability in all culture conditions was above 85%. Results: The type I IFN activation induced by CpG-A, IQ, G3-YSD and IFN-a2b was significantly reduced after addition of Aspirin. Addition of diclofenac showed a trend towards reduced levels in all conditions. HCQ was able to significantly reduce the TLR7/9 induced IFN activation by CpG-A and IQ while MMF and prednisone did not show an effect in any of the culture conditions. Conclusion: The IFN activation induced by the stimulation of various IFN inducing pathways was significantly reduced by Aspirin and HCQ in an in vitro model. Combining both clinical and in vitro data from our longitudinal cohort of childhood-onset SLE patients will elucidate the effect of different immunosuppressive drugs on the type-I IFN signature in these patients. References: [1]Kuznik A, Bencina M, Svajger U, Jeras M, Rozman B, Jerala R. Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines. J Immunol. 2011;186(8):4794-804. [2]Dai J, Huang YJ, He X, Zhao M, Wang X, Liu ZS, et al. Acetylation Blocks cGAS Activity and Inhibits Self-DNA-Induced Autoimmunity. Cell. 2019;176(6):1447-60 e14. Disclosure of Interests: None declared
Abstract 343: Glycogen Synthase Kinase 3β Localizes to the Cardiac Myofilament via Py216 and Dynamically Modulates Calcium Sensitivity
Authors: Marisa Stachowski, Maria Papadaki, Andrei Zlobin, Thomas Martin, Nitha Aima Muntu, Jody Martin, Christine S Moravec, Jonathan A Kirk
Journal: Circulation Research (2020)

Localization of kinases to sub-cellular compartments allows them dynamic control over specific subsets of their targets. We previously found GSK-3β could modulate myofilament Ca 2+ sensitivity. However, whether GSK-3β modulates Ca 2+ sensitivity in vivo , if it localizes to the myofilament, and the consequences, are unknown. In myofilament enriched LV tissue from human non-failing and heart failure (HF) patients (n = 66) we found GSK-3β does localize to the myofilament and is altered by sex, age, and HF. To determine its in vivo functional role, we used myocyte specific inducible GSK-3β knock-out mice for skinned myocyte force-calcium experiments and found that GSK-3β reduction reduced calcium sensitivity. Further, we measured function in human samples and found myofilament GSK-3β levels directly correlated to Ca 2+ sensitivity. To establish how GSK-3β binds to the myofilament, we performed co-IP and IHC with phosphorylated forms of GSK-3β. GSK-3β phosphorylated at Y216 had a high affinity for the myofilament and localized to the z-disc. Mutating Y216 to a phospho-mimetic increased binding to the myofilament while mutating it to a phospho-null ablated binding.To identify GSK-3β’s myofilament targets, we performed mass spectrometry on myofilament phospho-enriched samples from GSK-3β KO and WT mice. As GSK-3β modulated Ca 2+ sensitivity, we expected to detect thin filament proteins. However, in agreement with its localization to the z-disc, GSK-3β primarily phosphorylated z-disc proteins.In the GSK-3β KO mice, strain analysis revealed the posterior wall contracted significantly earlier than the anterior wall, indicating baseline mechanical dyssynchrony. The WT mice had synchronous contraction, and interestingly there was significantly higher myofilament GSK-3β in the anterior wall compared to the posterior wall, a difference we hypothesize maintains synchrony. Thus, losing this fine control over Ca 2+ sensitivity as in the GSK-3β KO mice would induce mechanical dyssynchrony. Overall, these findings reveal that GSK-3β dynamically localizes to the myofilament to modulate Ca 2+ sensitivity through Y216 phosphorylation. The consequence of this “fine tuning” maintains chamber level mechanical synchrony.
Minimal Residual Disease Eradication with Guadecitabine (SGI-110) in the Post-Transplant Setting
Authors: Betul Oran, Amin M. Alousi, Rohtesh S. Mehta, David Marin, Partow Kebriaei, Uday R. Popat, Amanda L. Olson, Jessica M McCarty, Jennifer D Ramos, Roland Bassett, Harold N. Keer, Peter F Thall, Richard E. Champlin
Journal: Blood (2020)
Effects of Prior Alkylating Therapies on Preinfusion Patient Characteristics and Starting Material for CAR T Cell Product Manufacturing in Late-Line Multiple Myeloma
Authors: Julie Rytlewski, Deepu Madduri, Jaymes Fuller, Timothy B. Campbell, Afshin Mashadi-Hossein, Ethan G. Thompson, Yue Jiang, Nathan Martin, Dipen Sangurdekar, Olivia Finney, Hans Bitter, Amit Agarwal, Shari Kaiser, Kristen Hege, Ronald J. Hause
Journal: Blood (2020)
Fotemustine-Based in Combination with Rituximab As First-Line Induction Chemotherapy for Newly Diagnosed Primary Central Nervous System Lymphoma:a Prospective Phaseii Trial
Authors: Jingjing Wu, Fenghua Gao, Lei Zhang, Xin Li, Ling Li, Xinhua Wang, Linan Zhu, Xudong Zhang, Xiaorui Fu, Zhenchang Sun, Meng Dong, Mengjie Ding, Hui Yu, Feifei Nan, Jiaqin Yan, Yu Chang, Xiaolong Wu, Zhiyuan Zhou, Mingzhi Zhang, Ken H. Young
Journal: Blood (2020)
ACSS3 represses prostate cancer progression through downregulating lipid droplet-associated protein PLIN3
Authors: Lijie Zhou, Zhengshuai Song, Junyi Hu, Lilong Liu, Yaxin Hou, Xiaoping Zhang, Xiong Yang, Ke Chen
Journal: Theranostics (2020)

Current endocrine therapy for prostate cancer (PCa) mainly inhibits androgen/androgen receptor (AR) signaling. However, due to increased intratumoural androgen synthesis and AR variation, PCa progresses to castration-resistant prostate cancer (CRPC), which ultimately becomes resistant to endocrine therapy. A search for new therapeutic perspectives is urgently needed. Methods: By screening lipid metabolism-related gene sets and bioinformatics analysis in prostate cancer database, we identified the key lipid metabolism-related genes in PCa. Bisulfite genomic Sequence Polymerase Chain Reaction (PCR) (BSP) and Methylation-Specific Polymerase Chain Reaction (PCR) (MSP) were preformed to detect the promoter methylation of ACSS3. Gene expression was analyzed by qRT-PCR, Western blotting, IHC and co-IP. The function of ACSS3 in PCa was measured by CCK-8, Transwell assays. LC/MS, Oil Red O assays and TG and cholesterol measurement assays were to detect the levels of TG and cholesterol in cells. Resistance to Enzalutamide in C4-2 ENZR cells was examined in a xenograft tumorigenesis model in vivo. Results: We found that acyl-CoA synthetase short chain family member 3 (ACSS3) was downregulated and predicted a poor prognosis in PCa. Loss of ACSS3 expression was due to gene promoter methylation. Restoration of ACSS3 expression in PCa cells significantly reduced LD deposits, thus promoting apoptosis by increasing endoplasmic reticulum (ER) stress, and decreasing de novo intratumoral androgen synthesis, inhibiting CRPC progression and reversing Enzalutamide resistance. Mechanistic investigations demonstrated that ACSS3 reduced LD deposits by regulating the stability of the LD coat protein perilipin 3 (PLIN3). Conclusions: Our study demonstrated that ACSS3 represses prostate cancer progression through downregulating lipid droplet-associated protein PLIN3.
Abstract 368: Mechanisms of Arrhythmogenic Substrates in Lipotoxic Heart
Authors: Laura Martinez -Mateu, Xusheng Zhang, Charles Leduc, Rudolph Leibel, Javier Saiz, Ademuyiwa Aromolaran
Journal: Circulation Research (2020)

Obesity is associated with dangerous pathologies including insulin resistance, hyperglycemia, and diabetes all of which are present as independent risks to developing fatal arrhythmias, which lead to sudden cardiac death. Cardiac lipotoxicity is a common mechanism that links these pathologies to cardiac dysfunction. The molecular mechanisms of cardiac lipotoxicity in obese heart are unknown. We investigated the effects of high-fat diet (HFD)-induced lipotoxicity on atrial electrical remodeling. Electrophysiology and rapid atrial pacing (RAP) were used to evaluate the effects of cardiac lipotoxicity in obese guinea pig hearts that show no signs of hyperglycemia or inflammation. HFD atria were associated with increased voltage-dependent potassium (I K ) and decreased L-type calcium current (I Ca,L ) densities, spontaneous beats, and increased vulnerability to atrial tachycardia with pacing. Further we see a marked reduction in I Kur and increased I K1 phenotype only after RAP. Human cardiac computer simulation studies underscore the translational relevance, as results were identical to data in lipotoxic guinea pig model. The data are the first to show that I K and I Ca,L underlie initiation of atrial arrhythmogenesis, while IK ur and IK 1 may act to sustain the arrhythmia. RNA sequencing assay in lipotoxic myocytes further revealed upregulation of PI3K and/or downregulation of AMPK as prime candidates for modulation of atrial ionic currents. The data provide a unique mechanism-based insight for targeted treatment options in patients.
Presentations and outcomes of central nervous system TB in a UK cohort: The high burden of neurological morbidity
Authors: Clare Logan, Claire Mullender, Miriam Mirfenderesky, Nicholas Feasey, Catherine Cosgrove, Peter Riley, Angela Houston, Tom Harrison, Tihana Bicanic, Phil Rich, Paul Hart, Síle F Molloy, Derek C. Macallan
Journal: Journal of Infection (2020)