tbuckley/cabot-search huggingface dataset:
Safety and Adverse Reactions of CAR T Therapy for the Treatment of Multiple Myeloma: A Systematic Review
Authors: Saad Javed, Tariq Iqtidar Sadiq Syed, Syed Hashim Ali Inam, Syed Maaz Abdullah, Mohammed Musa Najmuddin, Mobeen Zaka Haider, Hejab Fatima, Karun Neupane, Muhammad Khawar Sana, Muhammad Tayyeb, Abdul Jabbar Dar, Muhammad Ali Mirza, Faiz Anwer
Journal: Blood (2020)
IL-33/ST2 induces neutrophil-dependent reactive oxygen species production and mediates gout pain
Authors: Chengyu Yin, Boyu Liu, Yuanyuan Li, Xiaojie Li, Jie Wang, Ruixiang Chen, Yan Tai, Qiyang Shou, Ping Wang, Xiaomei Shao, Yi Liang, Hong Zhou, Wenli Mi, Jianqiao Fang, Boyi Liu
Journal: Theranostics (2020)

Objective: Gout, induced by monosodium urate (MSU) crystal deposition in joint tissues, provokes severe pain and impacts life quality of patients. However, the mechanisms underlying gout pain are still incompletely understood. Methods: We established a mouse gout model by intra-articularly injection of MSU crystals into the ankle joint of wild type and genetic knockout mice. RNA-Sequencing, in vivo molecular imaging, Ca2+ imaging, reactive oxygen species (ROS) generation, neutrophil influx and nocifensive behavioral assays, etc. were used. Results: We found interleukin-33 (IL-33) was among the top up-regulated cytokines in the inflamed ankle. Neutralizing or genetic deletion of IL-33 or its receptor ST2 (suppression of tumorigenicity) significantly ameliorated pain hypersensitivities and inflammation. Mechanistically, IL-33 was largely released from infiltrated macrophages in inflamed ankle upon MSU stimulation. IL-33 promoted neutrophil influx and triggered neutrophil-dependent ROS production via ST2 during gout, which in turn, activated transient receptor potential ankyrin 1 (TRPA1) channel in dorsal root ganglion (DRG) neurons and produced nociception. Further, TRPA1 channel activity was significantly enhanced in DRG neurons that innervate the inflamed ankle via ST2 dependent mechanism, which results in exaggerated nociceptive response to endogenous ROS products during gout. Conclusions: We demonstrated a previous unidentified role of IL-33/ST2 in mediating pain hypersensitivity and inflammation in a mouse gout model through promoting neutrophil-dependent ROS production and TRPA1 channel activation. Targeting IL-33/ST2 may represent a novel therapeutic approach to ameliorate gout pain and inflammation.
SAT0210 Brain magnetic resonance imaging (mri) and proton magnetic resonance spectroscopy (1h-mrs) in systemic lupus erythematosus (sle)
Authors: M Govoni, P Colamussi, N Rizzo, D Santilli, R Ricci, F Trotta
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> We evaluated the usefulness of 1H-MRS in patients with SLE, with or without neurological involvement, in whom single photon emission computed tomography (SPECT) showed cerebral perfusion abnormalities in brain areas with no detectable changes at MRI. <h3>Methods</h3> 9 female SLE patients, with a mean age of 28.7 years (range 14–46) and a mean duration of disease of 2.5 years, underwent cerebral blood flow (CBF) study with 99mTc-SPECT and brain MRI with 1H-MRS analysis. 4 patients complained of headache, 1 patient was being treated for partial epilepsy and 4 patients were asymptomatic and with a negative neurological examination. In brain areas shown to be hypoperfused by SPECT, peak levels of signals from brain metabolites N-acetylaspartic acid (NAA), choline (CHO), and creatine (CRE) were measured on a total of 20 brain voxels (volume = 8 cm<sup>3</sup>) selected on transverse MR images. Values were expressed as NAA/CHO, CHO/CRE and NAA/CRE ratios. Ratios measured in 9 hypoperfused brain areas were compared with those obtained in 11 normoperfused areas. MRI showed a normal appearance in all of the above brain areas. Statistical analysis was performed by means of classical t-test. <h3>Results</h3> NAA/CHO ratio was decreased in 78% of hypoperfused and in 18% of normoperfused brain areas (1.70 ± 0.15 vs 2.55 ± 0.16; p = 0.0017). CHO/CRE ratio was increased in 89% of hypoperfused and in 9% of normoperfused brain areas (1.34 ± 0.08 vs 0.80 ± 0.05; p &lt; 0.0001). No significant differences were detected in NAA/CRE ratios. The comparison of spectroscopic ratios measured both in hypoperfused and normoperfused areas in patients with neurological symptoms with those obtained in asymptomatic patients did not show any significant differences. <h3>Conclusion</h3> In SLE patients, independently from the presence of overt clinical neurological involvement, 1H-MRS is a valuable tool to detect neuronal biochemical changes in brain regions with reduced CBF at SPECT. Although the precise meaning of these abnormalities remains to be determined, their localization in areas with reduced CBF suggests that they could represent an early sign of neuronal injury in SLE patients even in the presence of a normal brain MRI appearance. If proven so, 1H-MRS could be considered a sensitive and accurate measure of neuronal dysfunction in SLE and this would demonstrate that the detection of reduced CBF by SPECT in areas with a normal MRI appearance is not to be regarded as a false positive result.
Effect of Taxane Chemotherapy With or Without Indoximod in Metastatic Breast Cancer
Authors: Veronica Mariotti, Hyo Han, Roohi Ismail-Khan, Shou-Ching Tang, Patrick Dillon, Alberto J. Montero, Andrew Poklepovic, Susan Melin, Nuhad K. Ibrahim, Eugene Kennedy, Nicholas Vahanian, Charles Link, Lucy Tennant, Shelly Schuster, Chris Smith, Oana Danciu, Paul Gilman, Hatem Soliman
Journal: JAMA Oncology (2020)

Indoleamine 2,3-dioxygenase 1 (IDO1) causes tumor immune suppression. The IDO1 pathway inhibitor indoximod combined with a taxane in patients with ERBB2-negative metastatic breast cancer was tested in a prospective clinical trial.To assess clinical outcomes in patients with ERBB2-negative metastatic breast cancer treated with indoximod plus a taxane.This phase 2 double-blinded randomized 1:1 placebo-controlled clinical trial enrolled patients at multiple international centers from August 26, 2013, to January 25, 2016. Eligibility criteria included ERBB2-negative metastatic breast cancer, ability to receive taxane therapy, good performance status, normal organ function, no previous immunotherapy use, and no autoimmune disease. The study was discontinued in June 2017 because of lack of efficacy. Data analysis was performed from February 2019 to April 2020.A taxane (paclitaxel [80 mg/m2] weekly 3 weeks on, 1 week off, or docetaxel [75 mg/m2] every 3 weeks) plus placebo or indoximod (1200 mg) orally twice daily as first-line treatment.The primary end point was progression-free survival (PFS); secondary end points were median overall survival, objective response rate, and toxic effects. A sample size of 154 patients would detect a hazard ratio of 0.64 with 1-sided α = .1 and β = .2 after 95 events. Archival tumor tissue was stained with immunohistochemistry for IDO1 expression as an exploratory analysis.Of 209 patients enrolled, 169 were randomized and 164 were treated (85 in the indoximod arm; 79 in the placebo arm). The median (range) age was 58 (29-85) years; 166 (98.2%) were female, and 135 (79.9%) were White. The objective response rate was 40% and 37%, respectively (indoximod vs placebo) (P = .74). The median (range) follow-up time was 17.4 (0.1-39.4) months. The median PFS was 6.8 months (95% CI, 4.8-8.9) in the indoximod arm and 9.5 months (95% CI, 7.8-11.2) in the placebo arm (hazard ratio, 1.2; 95% CI, 0.8-1.8). Differences between the experimental and placebo arms in median PFS (6.8 vs 9.5 months) and overall survival (19.5 vs 20.6 months) were not statistically significant. Grade 3 or greater treatment-emergent adverse events occurred in 60% of patients in both arms.This randomized clinical trial found that, among patients with ERBB2-negative metastatic breast cancer, addition of indoximod to a taxane did not improve PFS compared with a taxane alone.ClinicalTrials.gov Identifier: NCT01792050.
Employment of Machine Learning Models Yields Highly Accurate Hematological Disease Prediction from Raw Flow Cytometry Matrix Data without the Need for Visualization or Human Intervention
Authors: Martha-Lena Müller, Niroshan Nadarajah, Kapil Jhalani, Inseok Heo, William Wetton, Claudia Haferlach, Torsten Haferlach, Wolfgang Kern
Journal: Blood (2020)
Zanubrutinib in Combination with Venetoclax for Patients with Treatment-Naïve Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma and del(17p): Arm D of the SEQUOIA (BGB-3111-304) Trial
Authors: Constantine S. Tam, Ian W. Flinn, Alessandra Tedeschi, Emmanuelle Ferrant, Jennifer R. Brown, Tadeusz Robak, Paolo Ghia, Sowmya B. Kuwahara, Jason C. Paik, Lei Hua, Aileen Cohen, Jane Huang, Peter Hillmen
Journal: Blood (2020)
Results of the PROPINE randomized controlled study suggest tapering of prednisone treatment for relapses of steroid sensitive nephrotic syndrome is not necessary in children
Authors: Antonio Gargiulo, Laura Massella, Barbara Ruggiero, Lucilla Ravà, Marta Ciofi degli Atti, Marco Materassi, Francesca Lugani, Elisa Benetti, William Morello, Daniela Molino, Francesca Mattozzi, Marco Pennesi, Silvio Maringhini, Andrea Pasini, Bruno Gianoglio, Carmine Pecoraro, Giovanni Montini, Luisa Murer, Gian Marco Ghiggeri, Paola Romagnani, Marina Vivarelli, Francesco Emma
Journal: Kidney International (2020)
ENESTop 5-Year Update: Durability of Treatment-Free Remission Following Second-Line Nilotinib and Exploratory Analysis of Molecular Response Regain after Nilotinib Re-Initiation in Patients with Chronic Myeloid Leukemia
Authors: Francois-Xavier Mahon, Nelma D Clementino, Mikhail Fominykh, Jeffrey H. Lipton, Anna G. Turkina, Beatriz Moiraghi, Franck E Nicolini, Naoto Takahashi, Tomasz Sacha, Dong-Wook Kim, Rafik Fellague-Chebra, Ranjan Tiwari, Catherine Bouard, Timothy P. Hughes
Journal: Blood (2020)
Deliberating the Diagnostic Dilemma of Heart Failure With Preserved Ejection Fraction
Authors: Jennifer E. Ho, Margaret M. Redfield, Gregory D. Lewis, Walter J. Paulus, Carolyn S.P. Lam
Journal: Circulation (2020)

There is a lack of consensus on how we define heart failure with preserved ejection fraction (HFpEF), with wide variation in diagnostic criteria across society guidelines. This lack of uniformity in disease definition stems in part from an incomplete understanding of disease pathobiology, phenotypic heterogeneity, and natural history. We review current knowledge gaps and existing diagnostic tools and algorithms. We present a simple approach to implement these tools within the constraints of the current knowledge base, addressing separately (1) hospitalized individuals with rest congestion, where diagnosis is more straightforward; and (2) individuals with exercise intolerance, where diagnosis is more complex. Here, a potential role for advanced or provocative testing, including evaluation of hemodynamic responses to exercise is considered. More importantly, we propose focus areas for future studies to develop accurate and feasible diagnostic tools for HFpEF, including animal models that recapitulate human HFpEF, and human studies that both address a fundamental understanding of HFpEF pathobiology, and new diagnostic approaches and tools, as well. In sum, there is an urgent need to more accurately define the syndrome of HFpEF to inform diagnosis, patient selection for clinical trials, and, ultimately, future therapeutic approaches.
An unusual case of acquired facial pigmentation
Authors: Patrick Bryan, Antonia Lloyd-Lavery
Journal: BMJ (2020)

A woman in her 70s presented to the dermatology clinic with a two year history of blue-grey hyperpigmentation on her face, which symmetrically involved her forehead, eyelids, cheeks, nose, and perioral skin (fig 1). Similar blue-grey discoloration was noted on her gingiva (fig 2).



Fig 1 
Marked discoloration to the eyebrows, forehead, cheeks, and perioral skin





Fig 2 
Blue-grey discoloration also involving the gingiva



The patient had had rosacea since her late teens, for which she had been taking oral minocycline intermittently for more than 20 years. Three months before this presentation she was advised to stop the minocycline because it was …
Alan John McLintic
Authors: Leyla Sanai
Journal: BMJ (2020)

Alan John McLintic was the kind of man who never wanted for social or professional invitations. Drily witty, as at ease talking about medicine, philosophy, literature, ethics, music, rugby, sport, wine, or politics, he was a bon viveur who never took himself too seriously, despite his win in the genetic lottery for talent and charm.

A registrar in cardiology before switching to anaesthetics, he was conscientious, clever, and compassionate, loved by medical and nursing staff alike, and deeply appreciated by patients. If asked to produce a presentation for …
Abstract 241: Retinoic Acid Promotes Metabolic Maturation of Human Embryonic Stem Cell-derived Cardiomyocytes
Authors: Shumei Miao, Xing Fang, Xiaoxiao Wang, Lingqun Ye, Jingsi Yang, Xuan Ni, Dandan Zhao, Hongchun Wu, Xinglong Han, Miao Yu, Lei Li, Zhenya Shen, Wei Lei, Zhen-Ao Zhao, Shijun Hu
Journal: Circulation Research (2020)

Cardiomyocytes differentiated from human embryonic stem cells (hESCs) represent a promising cell source for heart repair, disease modeling and drug testing. However, improving the differentiation efficiency and maturation of hESC-derived cardiomyocytes (hESC-CMs) is still a major concern. Retinoic acid (RA) signaling plays multiple roles in heart development, and studies on RA can provide clues for understanding cardiomyocyte differentiation and maturation. In this study, we studied the roles of RA during cardiomyocyte differentiation and maturation, systematically. After adding RA at different stages of cardiomyocyte differentiation, we compared the efficiency of differentiation by quantitative real-time PCR and flow cytometry. We found that RA treatment at the lateral mesoderm stage (days 2-4) significantly improved cardiomyocyte differentiation, as evidenced by the upregulation of TNNT2, NKX2.5 and MYH6 on day 10 of differentiation. In addition, flow cytometry showed that the proportion of differentiated cardiomyocytes in the RA-treated group was significantly higher than that in control group. Furthermore, RA was added at different time intervals after purification to induce cardiomyocyte maturation. Our results demonstrated that RA treatment on days 15-20 increased cardiomyocyte area, sarcomere length, multinucleation and mitochondrial copy number, and promoted RNA splicing switch. Importantly, RA-treated cardiomyocytes showed decreased glycolysis and enhanced mitochondrial oxidative phosphorylation, with the increased utilization of fatty acid and exogenous pyruvate but not glutamine. In conclusion, our data indicated that RA treatment at an early time window (days 2-4) promotes the efficiency of cardiomyocyte differentiation and that RA treatment post beating (days 15-20) promotes cardiomyocyte metabolic maturation. The biphasic effects of RA provide new insights for improving cardiomyocyte differentiation and quality.
Classification and Quantification of Oncogenic Ikaros Isoforms in B Cell Precursor Acute Lymphoblastic Leukemia By RNA-Seq
Authors: Guangsi Zhang, Cao Panxiang, Fang Wang, Xue Chen, Yang Zhang, Mingyu Wang, Xiaoli Ma, Jiaqi Chen, Daijing Nie, Hongxing Liu
Journal: Blood (2020)
Glofitamab Step-up Dosing Induces High Response Rates in Patients with Hard-to-Treat Refractory or Relapsed Non-Hodgkin Lymphoma
Authors: Martin Hutchings, Carmelo Carlo-Stella, Emmanuel Bachy, Fritz C. Offner, Franck Morschhauser, Michael Crump, Gloria Iacoboni, Anna Sureda Balari, Joaquin Martinez-Lopez, Linda Lundberg, Mark Dixon, David Perez Callejo, James Relf, David Carlile, Emily Piccione, Kathryn Humphrey, Michael Dickinson
Journal: Blood (2020)
Pre-Menopausal Breast Fat Density Might Predict MACE During 10 Years of Follow-Up
Authors: Celestino Sardu, Gianluca Gatta, Gorizio Pieretti, Luigi Viola, Cosimo Sacra, Graziella Di Grezia, Lanfranco Musto, Salvatore Minelli, Daniele La Forgia, Mariangela Capodieci, Alessandro Galiano, Angela Vestito, Angela De Lisio, Pia Clara Pafundi, Ferdinando Carlo Sasso, Salvatore Cappabianca, Gianfranco Nicoletti, Giuseppe Paolisso, Raffaele Marfella
Journal: JACC. Cardiovascular imaging (2020)
Extracellular vesicle-shuttled miRNAs: a critical appraisal of their potential as nano-diagnostics and nano-therapeutics in type 2 diabetes mellitus and its cardiovascular complications
Authors: Francesco Prattichizzo, Giulia Matacchione, Angelica Giuliani, Jacopo Sabbatinelli, Fabiola Olivieri, Paola de Candia, Valeria De Nigris, Antonio Ceriello
Journal: Theranostics (2020)

Type 2 diabetes mellitus (T2DM) is a complex multifactorial disease causing the development of a large range of cardiovascular (CV) complications.Lifestyle changes and pharmacological therapies only partially halt T2DM progression, and existing drugs are unable to completely suppress the increased CV risk of T2DM patients.Extracellular vesicles (EV)s are membrane-coated nanoparticles released by virtually all living cells and are emerging as novel mediators of T2DM and its CV complications.As a matter of fact, several preclinical models suggest a key involvement of EVs in the initiation and/or progression of insulin resistance, β-cell dysfunction, diabetic dyslipidaemia, atherosclerosis, and other T2DM complications.In addition, preliminary findings also suggest that EV-associated molecular cargo, and in particular the miRNA repertoire, may provide with useful diagnostic and/or prognostic information for the management of T2DM.Here, we review the latest findings showing that EV biology is altered during the entire trajectory of T2DM, i.e. from diagnosis to development of CV complications.We also critically highlight the potential of this emerging research field, by describing both preclinical and clinical observations, and the limitations that must be overcome to translate the preclinical findings into the development of EV-based nano-diagnostic and/or nano-therapeutic tools.Finally, we summarize how two lifestyle changes known to prevent or limit T2DM, i.e. diet and exercise, affect EV number and composition, with a focus on the possible role of EVs contained in food in shaping metabolic responses, a promising approach still in its infancy.
FGM: nearly 3000 girls are paraded in Kenya as pandemic hinders control efforts
Authors: Owen Dyer
Journal: BMJ (2020)

About 2800 girls from southwestern Kenya’s Kuria community who recently underwent female genital mutilation (FGM) have been paraded through town centres in recent weeks, as local traditional leaders make the most of reduced police vigilance during the covid-19 pandemic.

The girls, aged about 12, are showered with gifts from market crowds as they march in tinselled blankets, carrying balloons to signify their recent ordeal. The processions are accompanied by groups of machete wielding men, who warn the police and local anti-FGM activists not to intervene.

The Kuria people’s “Esaro” initiation ceremonies begin in late September with the circumcision of boys, and girls generally follow, sometimes disguised as boys to trick the police. At least 80 Kuria girls from Migori who fled home to escape FGM are being sheltered in the Taranganya girls’ secondary …
Efficacy and Safety of Ravulizumab in Older Patients Aged &amp;gt;65 Years with Paroxysmal Nocturnal Hemoglobinuria in the 301 and 302 Phase 3 Extension Studies
Authors: Regis Peffault De Latour, Jeffrey Szer, Austin Kulasekararaj, Jin Seok Kim, Caroline I. Piatek, Alexander D. Kulagin, Anita Hill, Jimmy Wang, Ji Yu, Masayo Ogawa, Hubert Schrezenmeier, Jong Wook Lee
Journal: Blood (2020)
Abstract 283: Western Diet Induces Diastolic Dysfunction Linked to Impaired Cardiac Lipid Storage Dynamics That Predate Systolic Dysfunction
Authors: E Douglas K Lewandowski, Andrew N Carley, E Douglas D Lewandowski
Journal: Circulation Research (2020)

Western diet (WD), containing high fat and high refined sugar, is associated with increased risk of cardiovascular disease. However, mechanisms linking WD to cardiomyopathy are far from understood. We hypothesize that WD induces cardiac dysfunction by dysregulation of cardiac lipid dynamics. Adult C57BL/6J mice were fed with either standard chow (CON, fat 4.5 %, sucrose 0%) or western diet (WD, fat 45%, sucrose 21%). At 20 weeks, WD mice exhibited higher body mass, reduced glucose tolerance, and increased isovolumetric relaxation time (IVRT), with no systolic dysfunction vs. CON. However, at 24 weeks, WD caused both systolic and diastolic dysfunction with decreases in left ventricular ejection fraction (66±2% CON vs. 54±2 WD, P &lt;0.05) and fractional shortening (35±2% CON vs. 27±1 WD), with elevated IVRT and E/E’ ratio vs CON. Real time, dynamic-mode 13 C NMR and endpoint LC/MS of isolated perfused hearts supplied 13 C palmitate and 13 C oleate, with unlabeled glucose and lactate, revealed elevated TG content (28% increase vs. CON) with reduced TG turnover in WD hearts (35% decrease vs. CON), concurrent with early diastolic dysfunction at 20 weeks and preceding systolic dysfunction at 24 weeks. WD induced lower content of the TG lipase, ATGL (48% vs. CON), with no change in the TG synthase, DGAT1, suggesting elevated cardiac TG and lower TG turnover are due to reduced TG hydrolysis and not TAG synthesis. Impaired lipid storage dynamics can cause increased generation of potentially lipotoxic acyl intermediates, leading to cardiac dysfunction. The mitochondrial long chain fatty acid transporter, CPT1b was reduced (50%), with no change in the lesser, co-expressed CPT1a isoform in WD hearts. Despite reduced CPT1b in WD hearts, contributions from LCFAs to acetyl CoA production in the citric acid cycle were unchanged, suggesting that the WD provided sufficient LCFAs for mitochondrial oxidation and that the reduced CPT1b was not limiting. In conclusion, western diet expands the TG pool but impairs fat storage dynamics via low ATGL, leading to early diastolic dysfunction and eventual systolic dysfunction. Nutrient overload from WD leads to impaired cardiac lipid dynamics with early diastolic dysfunction that is distinguished from HFpEF due to later systolic dysfunction.
DAC-Based Conditioning Regimen Versus Standard Conditioning Regimen for Myelodysplastic Syndrome
Authors: Yintian Zhang, Min Dai, Ya Gao, Ying Xu, Weiru Li, Xiaoyin Bu, Jinman Zhong, Shengchun Cai, Fen Huang, Zhiping Fan, Baohong Ping
Journal: Blood (2020)
Safety and Efficacy of Ex Vivo Expanded Healthy Donor-Derived Double Negative T Cells for the Treatment of AML Relapsed after Allogeneic Stem Cell Transplantation: A First in-Human Phase I/IIa Clinical Trial
Authors: Tang Baolin, Jongbok Lee, Siqi Cheng, Wen Yao, Dongyao Wang, Meijuan Tu, Zhiqiang Xiang, Liangquan Geng, Mingxia Wang, Ping Qiang, Pingping Teng, Guangyu Sun, Tianzhong Pan, Huilan Liu, Liming Yang, Zimin Sun, Li Zhang, Xiaoyu Zhu
Journal: Blood (2020)
Investigating the Quality of Life of Patients with Acute Leukemia, with a Focus on Age and Patient-Reported Experience
Authors: Zack Pemberton-Whiteley, Samantha Nier, Jan Geissler, Sophie Wintrich, Bregje Verhoeven, Rita I O Christensen, Sam Salek, Esther Natalie Oliva, Tatyana Ionova, Jennie Bradley, Anne Rosemary Tate
Journal: Blood (2020)