tbuckley/cabot-search huggingface dataset:
A Three-Arm Randomized Phase II Study of Bendamustine/Rituximab with Bortezomib Induction or Lenalidomide Continuation in Untreated Follicular Lymphoma: ECOG-ACRIN E2408
Authors: Andrew M. Evens, Fangxin Hong, Thomas M. Habermann, Ranjana H. Advani, Randy D. Gascoyne, Thomas E. Witzig, Andrew Quon, Erik A. Ranheim, Stephen M. Ansell, Puneet Singh Cheema, Philip A. Dy, Timothy E. O'Brien, Jane N. Winter, Terrence P. Cescon, Julie E. Chang, Brad S. Kahl
Journal: Clinical Cancer Research (2020)

Abstract Purpose: We sought to improve upon frontline bendamustine/rituximab (BR) induction therapy followed by rituximab maintenance in untreated high-risk follicular lymphoma (FL). Patients and Methods: Patients were randomized to BR induction followed by 2-year rituximab maintenance (BR-R), BR with bortezomib and rituximab maintenance (BVR-R), or BR followed by lenalidomide (1 year) with rituximab maintenance (BR-LR). Dual primary objectives were complete remission (CR) rate and 1-year disease-free survival (DFS); 289 patients enrolled (NCT01216683). Results: For induction, 92%, 87%, and 86% of patients randomized to BR-R, BVR-R, or BR-LR received six cycles, respectively. CR rate with BR versus BVR induction was 62% versus 75%, respectively (P = 0.04). One-year DFS rates with BR-R versus BR-LR were 85% versus 67%, respectively (P = 0.0009). This was due to an imbalance in CR rates post-BR induction and discontinuation due to adverse events (AEs). The most common grade 3–4 AEs for BVR versus BR were neutropenia and sensory neuropathy (12% vs &amp;lt;1%); 83% of the latter occurred with intravenous bortezomib. The most common grade 3–4 AEs related to LR versus rituximab maintenance were neutropenia 66% versus 21%, respectively (P &amp;lt; 0.0001), and febrile neutropenia 10% versus 2%, respectively (P = 0.05). The overall treatment-related mortality was 1.4%. With 5-year median follow-up, 3-year PFS rates for BR-R, BVR-R, and BR-LR were 77%, 82%, and 76%, respectively (P = 0.36) with OS rates of 87%, 90%, and 84%, respectively (P = 0.79). For prognostication, CR rate and POD-24 were associated with survival. Conclusions: Altogether, neither bortezomib added to BR induction nor lenalidomide added to rituximab maintenance immediately post-BR induction is recommended in untreated FL.
AB1118 OPEN MUSCLE BIOPSY AS A SAFE AND USEFUL MEANS OF DIAGNOSING VASCULITIS: A SINGLE-CENTER EXPERIENCE OF 210 BIOPSY CASES
Authors: T. Mori, N. Yokogawa, K. Shimada
Journal: Annals of the Rheumatic Diseases (2020)

Background: We previously reported the utility of open muscle biopsies in diagnosing vasculitis [1]. The number of open muscle biopsies performed at our department has increased to over 200. The purpose of the present study was to evaluate the diagnostic utility of vasculitis and the safety of the open muscle biopsies. Objectives: To clarify the diagnostic utility of vasculitis and the safety profile of the open muscle biopsy. Methods: We retrospectively examined all cases of open muscle biopsy performed between May 2012 and June 2018 in our department. The biopsy results, the presence or absence of adverse events, and blood test data at the time of the biopsy were extracted from the patients’ electronic medical records. Results: Between May 2012 and June 2018, 210 open muscle biopsies were performed, 120 of which were done for vasculitis diagnosis. Diagnostic histopathological findings were obtained in 42 of the 120 cases (35%). The definitive diagnosis in these cases was microscopic polyangiitis (30 cases), eosinophilic granulomatosis with polyangiitis (seven cases), granulomatosis with polyangiitis (one case), polyarteritis nodosa (three cases), and other vasculitis (one case). In 57 cases with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) ≥ 10 U/ml, 31 cases (54.3%) showed histopathology of vasculitis. In six cases with protainase-3-ANCA (PR3-ANCA) ≥ 10 U/ml, histopathology of vasculitis was found in one case (16.7%). In all 210 open muscle biopsy cases, complications included minor wound dehiscence (11 cases) and small subcutaneous hematoma (six cases), which were able to be managed by local treatment. Albumin was significantly lower in the patients with wound dehiscence (mean 3.2 vs 2.7, p = 0.049) Serious complications included anaphylaxis due to local anesthesia (one case), compartment syndrome due to hematoma (one case), hematoma requiring surgical removal (one case), and arterial hemorrhage requiring surgical intervention (one case). The patients in the latter three hemorrhagic cases were receiving antiplatelet drugs. Conclusion: An open muscle biopsy is useful for diagnosing vasculitis, especially for MPO-ANCA-positive anca-associated vasculitis. Its safety profile is acceptable. Serious adverse events are rare, but the procedure should be performed carefully when patients are receiving antiplatelet drugs. References: [1]Nunokawa T. et al. The use of muscle biopsy in the diagnosis of systemic vasculitis affecting small to medium-sized vessels: A prospective evaluation in Japan. Scand. J. Rheumatol. 2016;45:210–214 Disclosure of Interests: None declared
“Lipidomics”: Mass spectrometric and chemometric analyses of lipids
Authors: Zhuojun Wu, Giulia Ilaria Bagarolo, Sven Thoröe-Boveleth, Joachim Jankowski
Journal: Advanced Drug Delivery Reviews (2020)

Lipids are ubiquitous in the human organism and play essential roles as components of cell membranes and hormones, for energy storage or as mediators of cell signaling pathways. As crucial mediators of the human metabolism, lipids are also involved in metabolic diseases, cardiovascular and renal diseases, cancer and/or hepatological and neurological disorders. With rapidly growing evidence supporting the impact of lipids on both the genesis and progression of these diseases as well as patient wellbeing, the characterization of the human lipidome has gained high interest and importance in life sciences and clinical diagnostics within the last 15 years. This is mostly due to technically advanced molecular identification and quantification methods, mainly based on mass spectrometry. Mass spectrometry has become one of the most powerful tools for the identification of lipids. New lipidic mediators or biomarkers of diseases can be analysed by state-of-the art mass spectrometry techniques supported by sophisticated bioinformatics and biostatistics. The lipidomic approach has developed dramatically in the realm of life sciences and clinical diagnostics due to the available mass spectrometric methods and in particular due to the adaptation of biostatistical methods in recent years. Therefore, the current knowledge of lipid extraction methods, mass-spectrometric approaches, biostatistical data analysis, including workflows for the interpretation of lipidomic high-throughput data, are reviewed in this manuscript.
Cardiac Energy Harvesting: Multifunctional Pacemaker Lead for Cardiac Energy Harvesting and Pressure Sensing (Adv. Healthcare Mater. 11/2020)
Authors: Lin Dong, Andrew B. Closson, Congran Jin, Yuan Nie, Andrew Cabe, Danny Escobedo, Shicheng Huang, Ian Trase, Zhe Xu, Zi Chen, Marc D. Feldman, John X. J. Zhang
Journal: Advanced Healthcare Materials (2020)

Self-sustainable energy generation represents a new frontier of power solution for implantable biomedical devices (IMDs). In article number 2000053 by Zi Chen, Marc D. Feldman, John X. J. Zhang, and co-workers, an integrated cardiac energy harvesting and pressure sensing strategy is developed by using the porous P(VDF-TrFE) films with a self-assembly helical structure. It provides a multifunctional, transformative while practical power and diagnosis solution for cardiac pacemakers and the next generation of IMDs.
RSK-3 promotes cartilage regeneration via interacting with rpS6 in cartilage stem/progenitor cells
Authors: Shuai Zhang, Md Rana Hamid, Ting Wang, Jinqi Liao, Liru Wen, Yan Zhou, Pengfei Wei, Xuenong Zou, Gang Chen, Junhui Chen, Guangqian Zhou
Journal: Theranostics (2020)

Rationale: Cartilage stem/progenitor cells (CSPC) are a promising cellular source to promote endogenous cartilage regeneration in osteoarthritis (OA). Our previous work indicates that ribosomal s6 kinase 3 (RSK-3) is a target of 4-aminobiphenyl, a chemical enhancing CSPC-mediated cartilage repair in OA. However, the primary function and mechanism of RSK-3 in CSPC-mediated cartilage pathobiology remain undefined. Methods: We systematically assessed the association of RSK-3 with OA in three mouse strains with varying susceptibility to OA (MRL/MpJ>CBA>STR/Ort), and also RSK-3-/- mice. Bioinformatic analysis was used to identify the possible mechanism of RSK-3 affecting CSPC, which was further verified in OA mice and CSPC with varying RSK-3 expression induced by chemicals or gene modification. Results: We demonstrated that the level of RSK-3 in cartilage was positively correlated with cartilage repair capacities in three mouse strains (MRL/MpJ>CBA>STR/Ort). Enhanced RSK-3 expression by 4-aminobiphenyl markedly attenuated cartilage injury in OA mice and inhibition or deficiency of RSK-3 expression, on the other hand, significantly aggravated cartilage damage. Transcriptional profiling of CSPC from mice suggested the potential role of RSK-3 in modulating cell proliferation. It was further shown that the in vivo and in vitro manipulation of the RSK-3 expression indeed affected the CSPC proliferation. Mechanistically, ribosomal protein S6 (rpS6) was activated by RSK-3 to accelerate CSPC growth. Conclusion: RSK-3 is identified as a key regulator to enhance cartilage repair, at least partly by regulating the functionality of the cartilage-resident stem/progenitor cells.
Efficacy and safety of peroral cholangioscopy with intraductal lithotripsy for difficult biliary stones: a systematic review and meta-analysis
Authors: Thomas R. McCarty, Rishabh Gulati, Tarun Rustagi
Journal: Endoscopy (2020)

Abstract Background Peroral cholangioscopy with intraductal lithotripsy facilitates optically guided stone fragmentation of difficult biliary stones refractory to conventional endoscopic therapy. The aim of this study was to evaluate the efficacy and safety of peroral cholangioscopy with intraductal lithotripsy for difficult biliary stones. Methods Searches of PubMed, EMBASE, Web of Science, and Cochrane databases were performed in accordance with PRISMA and MOOSE guidelines. Measured outcomes included overall fragmentation success, single-session fragmentation and duct clearance, and rate of adverse events. Sensitivity and subgroup analyses were performed based upon cholangioscopy technique and type of lithotripsy (laser versus electrohydraulic). Heterogeneity was assessed with I 2 statistics. Publication bias was ascertained by funnel plot and Egger regression testing. Results 35 studies were included with 1762 participants (43.4 % men; mean age 61.5 [standard deviation (SD) 11.0]). Prior cholecystectomy had been performed in 37 % of patients, with a mean number of 1.6 (SD 0.5) ERCPs performed prior to lithotripsy. Mean stone size was 1.8 (SD 0.3) cm. Peroral cholangioscopy with intraductal lithotripsy achieved an overall stone fragmentation success of 91.2 % (95 %CI 88.1 % – 93.6 %; I 2 = 63.2 %) with an average of 1.3 [SD 0.6] lithotripsy sessions performed. Complete single-session fragmentation success was 76.9 % (95 %CI 71.6 % – 81.4 %; I 2 = 74.3 %). The adverse events rate was 8.9 % (95 %CI 6.5 % – 12.2 %; I 2 = 60.6 %). Mean procedure time for peroral cholangioscopy was 67.1 (SD 21.4) minutes. There was no difference in overall fragmentation rate or adverse events; however, laser lithotripsy was associated with a higher single-session fragmentation rate and shorter procedure time compared with electrohydraulic lithotripsy. Conclusions Peroral cholangioscopy with intraductal lithotripsy appears to be a relatively safe and effective modality for difficult biliary stones.
Radius-X: An Expanded Treatment Protocol of Midostaurin in Adults with Newly Diagnosed FLT3-Mutation-Positive Acute Myeloid Leukemia Eligible for Standard Chemotherapy
Authors: Gail J. Roboz, Stephen A. Strickland, Mark R. Litzow, Andrew Dalovisio, Alexander E. Perl, Gaetano Bonifacio, Kelly Haines, Alysha Barbera, Das Purkayastha, Kendra Sweet
Journal: Blood (2017)
AB1001 CHANGES IN THE PARATHYROID HORMONE LEVEL IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS
Authors: N. Shevchenko, Y. Khadzhynova
Journal: Annals of the Rheumatic Diseases (2020)

Background: It is proved that rheumatic diseases are accompanied by pronounced changes in calcium-phosphorus metabolism, which underlies the development of osteopenia syndrome. If in previous years glucocorticosteroid therapy (GCS) was considered to be the main reason for this, then the role of pro-inflammatory agents (activity of the pathological process), provision with vitamin D (VitD), and the effect of basic therapy are currently being discussed. It is also known that a decrease blood level of vitamin D leads to a violation of the absorption of calcium and phosphorus, a further increase in the level of parathyroid hormone, which underlies the risk of a decrease in bone mineral density. Objectives: To study the level of parathyroid hormone in children with juvenile idiopathic arthritis, its relationship with the course of the disease and vitamin D status. Methods: 91 patients with JIA (61 girls and 30 boys), with polyarticular (n = 41), oligoarticular (n = 29) and undifferentiated (n = 18) variants of JIA were examined. The age of the patients was 10.5 ± 1.7 years. The duration of the disease was 4.1 ± 1.1 years. All children receive basic methotrexate therapy. The control group included 25 peers of the corresponding gender. JADAS27 was counted, the levels of 25-hydroxycalciferol (25-OH D) and PTH were determined by chemiluminescent method. Corresponded to the content of vitamin D in blood serum, the normal level was noted in 14 patients, insufficiency - in 41 patients, deficiency - in 32 patients. Results: The level of PTH in children with JIA remained within physiological values (30.6 ± 2.1 pg/ml; from 12.7 to 61.8 pg/ml) despite the high frequency of a VitD decrease in blood (80.2%). The level of PTH was not significant in groups of patients with a different level of vitamin D (32.8 ± 2.1 pg/ml at deficiency group; 29.2 ± 2.4 pg/ml at insufficiency group; 29.1 ± 1.8 pg/ml at a normal level of VitD group). PTH was comparable and did not differ in children of different sexes. The highest level of PTH was in patients with a polyarticular variant of JIA (34.2 ± 4.5 pg / ml, p&lt;0.05), which was accompanied by the lowest level of vitamin D (20.9 ± 2.1 ng / ml, p &lt;0, 05) in the same group. There was obtained reliable correlations of activity indicators (JADAS27) taking into account Vit D and PTH, as well as with diseases duration and age of patients (p &lt;0.05). Conclusion: A study of the level of PTH in children with JIA did not show a significant increase depending on the vitamin D status in these patients. However, the age-related state of PTH is associated with the activity of the pathological process, the prevalence of articular syndrome and prolonged illness. Disclosure of Interests: None declared
The Survival Impact of Lenalidomide Maintenance Chemotherapy in Multiple Myeloma Patients Treated with Autologous Stem Cell Transplant and Bortezomib-Based Induction: An Analysis of Real World Data
Authors: Hannah Cherniawsky, Irwindeep Sandhu, Michael P. Chu, Joanne D. Hewitt, Ismail Ismail, Andrew Belch, Linda M. Pilarski, Tatiana Nikitina, Christopher P. Venner
Journal: Blood (2017)
Erythropoietic protoporphyria.
Journal: BMJ (1979)

care.Cardiac puncture during the second trimester has been used to destroy an affected fetus without apparent harm to the normal twin, who was later delivered safely.8Though the risk of miscarriage of the normal twin is presumably increased, cardiac puncture offers a possible, if unpalatable, alternative to the stark choice of either abortion of a normal fetus or acceptance of a handicapped infant.Twins occur in at least 1% of term pregnancies, and are more liable to miscarriage and premature birth.When an at- risk pregnancy is suspected to be multiple both genetic counselling and amniocentesis should be left to the experts.
AB1165 MEDICATION ADHERENCE DATA IN A RANDOMIZED TRIAL: LARGE CHALLENGES TO COME FROM RAW DATA TO A WORKABLE AND RELIABLE DATASET
Authors: L. Hartman, E. Alessandri, R. Bos, D. Opris-Belinski, M. R. Kok, H. Griep-Wentink, R. Klaasen, C. Allaart, G. Bruyn, H. Raterman, M. Voshaar, N. Gomes, R. Pinto, T. Klausch, W. Lems, M. Boers
Journal: Annals of the Rheumatic Diseases (2020)

Background: Medication adherence in the GLORIA trial, among elderly patients with rheumatoid arthritis, is measured with caps that register openings of the medication bottle. At each study visit, one or two medication bottles with cap (kits) are dispensed, each containing 90 capsules. Multiple steps are needed to come to a workable dataset to describe adherence. Objectives: To describe the steps that are needed to come from raw data to a workable dataset to analyze adherence data that are recorded by electronic caps. Methods: The medication bottle contains a cap with the ability to register cap openings. The raw dataset from the caps consist of an excel file with one opening event per row, recorded as date and time. One cap yields approximately 90 rows. First, the kit numbers were matched to the corresponding patient numbers, that are recorded in another excel file. Instances where two kits were dispensed were recorded with two kit numbers in one cell and need to be copied to two cells with one kit number. Second, the VLOOKUP function was used to combine dates and kit numbers. One row now contains all openings from one kit. Then, the number of days between first opening and each next opening date was calculated. A range of 90 days was made to calculate how many times the bottle was opened on each day of the 90-days period. The results were color-coded to visualize instances of zero, one or ≥two openings on a day. Results: The colored calendar matrix (Figure 1) can now be used to categorize adherence patterns. Conclusion: A monitoring cap seems a simple instrument to measure adherence. However, multiple steps and a lot of time are needed to come to a workable dataset for the study of adherence patterns. Acknowledgments: The GLORIA project is funded by the European Union’s Horizon 2020 research and innovation programme under the topic ‟Personalizing Health and Care’’, grant agreement No 634886. Disclosure of Interests: Linda Hartman: None declared, Elisa Alessandri: None declared, Reinhard Bos: None declared, Daniela Opris-Belinski Speakers bureau: as declared, Marc R Kok Grant/research support from: BMS and Novartis, Consultant of: Novartis and Galapagos, Hanneke Griep-Wentink: None declared, Ruth Klaasen: None declared, Cornelia Allaart: None declared, George Bruyn: None declared, Hennie Raterman Grant/research support from: UCB, Consultant of: Abbvie, Amgen, Bristol-Myers Sqibb, Cellgene and Sanofi Genzyme, Marieke Voshaar Grant/research support from: part of phd research, Speakers bureau: conducting a workshop (Pfizer), Nuno Gomes: None declared, Rui Pinto: None declared, Thomas Klausch: None declared, WIllem Lems Grant/research support from: Pfizer, Consultant of: Lilly, Pfizer, Maarten Boers: None declared
3D Bioprinting of Oxygenated Cell‐Laden Gelatin Methacryloyl Constructs
Authors: Ahmet Erdem, Mohammad Ali Darabi, Rohollah Nasiri, Sivakoti Sangabathuni, Yavuz Nuri Ertas, Halima Alem, Vahid Hosseini, Amir Shamloo, Ali S. Nasr, Samad Ahadian, Mehmet R. Dokmeci, Ali Khademhosseini, Nureddin Ashammakhi
Journal: Advanced Healthcare Materials (2020)

Abstract Cell survival during the early stages of transplantation and before new blood vessels formation is a major challenge in translational applications of 3D bioprinted tissues. Supplementing oxygen (O 2 ) to transplanted cells via an O 2 generating source such as calcium peroxide (CPO) is an attractive approach to ensure cell viability. Calcium peroxide also produces calcium hydroxide that reduces the viscosity of bioinks, which is a limiting factor for bioprinting. Therefore, adapting this solution into 3D bioprinting is of significant importance. In this study, a gelatin methacryloyl (GelMA) bioink that is optimized in terms of pH and viscosity is developed. The improved rheological properties lead to the production of a robust bioink suitable for 3D bioprinting and controlled O 2 release. In addition, O 2 release, bioprinting conditions, and mechanical performance of hydrogels having different CPO concentrations are characterized. As a proof of concept study, fibroblasts and cardiomyocytes are bioprinted using CPO containing GelMA bioink. Viability and metabolic activity of printed cells are checked after 7 days of culture under hypoxic condition. The results show that the addition of CPO improves the metabolic activity and viability of cells in bioprinted constructs under hypoxic condition.
The Establishment of the Nordic Cardio-Oncology Society
Authors: Agneta Månsson Broberg, Suvi Tuohinen, Tanja Skytta, Jürgen Geisler, þórdís Jóna Hrafnkelsdóttir, Agnes Smáradóttir, Kirsten Melgaard Nielsen, Birgitte V. Offersen, Marianne Jarfelt, Geeta Gulati
Journal: JACC CardioOncology (2020)

Cardio-oncology is a relatively new, albeit quickly expanding field. The efficacy of modern cancer therapy has increased the number of long-term cancer survivors. However, the long-term survival for cancer patients may in some cases be limited by cardiovascular toxicities secondary to necessary
Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses
Authors: Jun Siong Low, Yagmur Farsakoglu, Maria Carolina Amezcua Vesely, Esen Sefik, Joseph B. Kelly, Christian C.D. Harman, Ruaidhri Jackson, Justin A. Shyer, Xiaodong Jiang, Linda S. Cauley, Richard A. Flavell, Susan M. Kaech
Journal: The Journal of Experimental Medicine (2020)

CD8+ tissue-resident memory T cells (TRM cells) are poised at the portals of infection and provide long-term protective immunity. Despite their critical roles, the precise mechanics governing TRM cell reactivation in situ are unknown. Using a TCR-transgenic Nur77-GFP reporter to distinguish "antigen-specific" from "bystander" reactivation, we demonstrate that lung CD8+ TRM cells are reactivated more quickly, yet less efficiently, than their counterparts in the draining LNs (TLN cells). Global profiling of reactivated memory T cells revealed tissue-defined and temporally regulated recall response programs. Unlike the reactivation of CD8+ TLN cells, which is strictly dependent on CD11c+XCR1+ APCs, numerous antigen-presenting partners, both hematopoietic and non-hematopoietic, were sufficient to reactivate lung CD8+ TRM cells, but the quality of TRM cell functional responses depended on the identity of the APCs. Together, this work uncovers fundamental differences in the activation kinetics, mechanics, and effector responses between CD8+ memory T cells in peripheral vs. lymphoid organs, revealing a novel tissue-specific paradigm for the reactivation of memory CD8+ T cells.