tbuckley/cabot-search huggingface dataset:
RBC-Enhance: A Randomized Pilot Feasibility Trial of Red Cell Transfusion Thresholds in Myelodysplastic Syndromes
Authors: Rena J. Buckstein, Anca Prica, Brian Leber, Nancy Heddle, Karen W.L. Yee, Simon J. Stanworth, David Bowen, Lisa Chodirker, Jennifer Gallagher, Anne Parmentier, Liying Zhang, Alexandre Mamedov, Yulia Lin, Jeannie L Callum
Journal: Blood (2020)
Response to: ‘Correspondence on ‘Gender disparity in authorship of guidelines and recommendations in rheumatology’’ by Stewart<i>et al</i>
Authors: Giovanni Adami, Camilla Benini, Elisabetta Vantaggiato, Denise Rotta, Ombretta Viapiana, Davide Gatti, Maurizio Rossini, Annamaria Iagnocco
Journal: Annals of the Rheumatic Diseases (2020)

We thank Stewart et al for their positive comments on our work and we applaud to their effort in refining and extending our analysis to the senior authorship positions. 1We also read with great interest the paper published by Bagga et al, from the same study group, that explored the gender equality in original clinical works (either funded or not funded by industries). 2In aggregate, an important under-representation of female researchers in the rheumatological field has emerged, regardless of the efforts employed in improving gender equity in the last decade.Indeed, although we found a trend to parity in the last 5 years in the first author position, 3 Stewart et al reported a prevalence of men as senior authors and they previously showed that even clinical research is somewhat dominated by men (although to a lesser extent).We should note that, with our reports, we undoubtedly did not want to convey the message that gender parity has been reached.The academic career path is undeniably uneven and slippery for young women researchers.As an example, we explored the data from the Italian Istituto Nazionale di Statistica, which gather the records regarding the Italian public and private universities.In the last two decades, among students that started their courses in medical school approximately 50%-60% were female.Notwithstanding that, the vast majority of full professors and associate professors of medicine in 2020 are men (1521 vs 277 for full professors and 2159 vs 831 for associate professors).Remarkably, this gender gap in the academic leadership positions seems to be standing even when considering non-professor faculty positions.In 2020, among 4009 non-professor researchers, only 44.6% are women.In summary, our findings and the findings by the group of professor Dalbeth confirmed that the gender gap is still wide open in the academic rheumatology, especially in the leadership positions. 4 5The career advancement is somehow slower for women as compared with men; thus, we strongly endorse the call to action of prioritising gender equity in the academic field.
Development of a Novel MICA/B-Specific CAR As a Pan-Tumor Targeting Strategy for Off-the-Shelf, Cell-Based Cancer Immunotherapy
Authors: Ryan Bjordahl, John Goulding, Mochtar Pribadi, Robert Blum, Chiawei Chang, Yijia Pan, Lucas Ferrari de Andrade, Kai W. Wucherpfennig, Yu-Waye Chu, Hui-yi Chu, Wen-I Yeh, Svetlana Gaidarova, Ellen Liu, Shohreh Sikaroodi, Lauren Fong, Janel Huffman, Tom Lee, Bahram Valamehr
Journal: Blood (2020)
Abstract 448: Strain Rate Dependent Myosin Head Position Changes During Relaxation
Authors: Weikang Ma, Melissa J Bukowski, Alexandra R Matus, Thomas C Irving, Charles S Chung
Journal: Circulation Research (2020)

Impaired cardiac relaxation is present in nearly all cases of heart failure and possibly in up to 25% of the asymptomatic population. Myocardial relaxation is known to be biochemically modified by the calcium reuptake rate, thin filament calcium sensitivity, and crossbridge kinetics. Mechanical regulation of relaxation was thought to be regulated via afterload, but we have recently shown that a lengthening strain was sufficient to modify relaxation. Further, the relaxation rate is actually dependent on the strain rate, a relationship that we termed Mechanical Control of Relaxation. Computational modeling suggests that myosin detachment is a key mechanism underlying Mechanical Control of Regulation, but to date, no experimental evidence for this was available. The objective of this study was to determine if myosin head position changed in response to lengthening strains during relaxation. Intact cardiac trabeculae were mounted within the beamline of the Biophysical Collaborative Access Team (BioCAT) beamline at the Advanced Photon Source at Argonne National Laboratories. The trabeculae were paced and load-clamps were performed during time-resolved imaging of the equatorial axis, which primarily reflects myosin head positioning. Activation (pacing) caused the myosin head localization to shift from the thick filament to near the thin filament (increased I 1,1 /I 1,0 ratio). During stretch, there was a transient decline of the I 1,1 /I 1,0 ratio which recovered until relaxation was complete, when the ratio again reduced indicating myosin returned to the thick filament. These preliminary data suggest that Mechanical Control of Relaxation is caused by perturbations in myosin, but the late-diastolic kinetics suggests that the strain-rate dependent detachment does not lead to immediate deactivation of myosin heads. Modifications of myosin ATPase properties may reveal more specific regulatory targets, which may provide new insight and targets for treating impaired myocardial relaxation.
The Role of Staging Evaluation at Initial Diagnosis of Adult Patients with Clinically Isolated Pulmonary Langerhans Cell Histiocytosis
Authors: Antonious Hazim, Gordon Ruan, Aishwarya Ravindran, Jithma P. Abeykoon, Caleb J Scheckel, Robert Vassallo, Jay Ryu, W. Oliver Tobin, Matthew Koster, Nabila Bennani, Karen Rech, Jason R Young, Mithun Vinod Shah, Gaurav Goyal, Ronald S. Go
Journal: Blood (2020)
Influence and management of conflicts of interest in randomised clinical trials: qualitative interview study
Authors: Lasse Østengaard, Andreas Lundh, Tine Tjørnhøj-Thomsen, Suhayb Abdi, Mustafe H A Gelle, Lesley A Stewart, Isabelle Boutron, Asbjørn Hróbjartsson
Journal: BMJ (2020)

Abstract Objective To characterise and analyse the experiences of trial researchers of if and how conflicts of interest had unduly influenced clinical trials they had worked on, what management strategies they had used to minimise any potential influence, and their experiences and views on conflicts of interest more generally. Design Qualitative interview study. Participants Trial researchers who had participated in at least 10 clinical trials with methodological or statistical expertise. Researchers differed by geographical location, educational background, and experience with different types of funders. Interviewees were identified by searches on Web of Science and snowball sampling. 52 trial researchers were approached by email; 20 agreed to be interviewed. Setting Interviews conducted by telephone, recorded, transcribed verbatim, imported to NVivo 12, and analysed by systematic text condensation. Semistructured interviews focused on financial and non-financial conflicts of interest. Results The interviewees had participated in a median of 37.5 trials and were mainly male physicians who had experience with commercial and non-commercial trial funders. Two predefined themes (influence of conflicts of interest and management strategies) and two additional themes (definition and reporting of conflicts of interest) emerged. Examples of perceived influence of conflicts of interest were: choice of inferior comparator, manipulation of the randomisation process, prematurely stopping the trials, fabrication of data, blocking access to data, and spin (eg, overly favourable interpretation of the results). Examples of strategies to manage conflicts of interest were: disclosure procedures, exclusion of the funder from design and analysis, independent committees, contracts ensuring complete access to the data, and no restriction by the funder on analysis and reporting. Interviewees used different definitions or thresholds for what they considered to be conflicts of interest, and they described different criteria for when to report them. Some interviewees considered non-commercial financial conflicts of interest (eg, funding of trials by governmental health agencies with a political agenda) to be equally or more important than commercial financial conflicts of interest (eg, funding by drug and device companies), but more challenging to report and manage. Conclusion This study described how trial researchers perceive conflicts of interest unduly influencing clinical trials they had worked on, and the management strategies they used to prevent these influences. The results indicated considerable variability in researchers’ understanding of what conflicts of interest are and when they should be reported.
A novel endoscopic submucosal dissection training model using skinned chicken meat with gel
Authors: Sho Suzuki, Hiroshi Kawakami, Tadashi Miike, Yutaro Ishikawa, Tomoya Hirata, Naoki Ichinari, Anna Komura
Journal: Endoscopy (2020)

Gastric endoscopic submucosal dissection (G-ESD) is performed worldwide. However, some trainees are not offered sufficient opportunities to perform G-ESD. Therefore, hands-on seminars using porcine stomachs are actively held, serving as valuable learning opportunities for trainees [1]. However, preparing porcine stomachs is time-consuming and effort-intensive, and leads to problems related to sanitation and pollution. To address these issues, we developed a new G-ESD training model using skinned chicken meat with gel involving the following steps ([Video 1]). (1) An electrode is attached to the chicken meat on the skinless slide ([Fig. 1]). (2) The chicken meat is placed in a 2-L polyethylene terephthalate bottle ([Fig. 1]). (3) Circular marks are made to mimic a virtual tumor region ([Fig. 2]). (4) The first injection solution is made by mixing 40 mL of clear-type polyvinyl alcohol glue with 30 mL of water. The second injection solution is made by dissolving 3 g of borax in 50 mL of warm water and adding 3 g of sodium hydrogen carbonate. These two solutions are injected subcutaneously, and skin lifting is observed, similarly to that of the gastric mucosa ([Fig. 3]). (5) The skin is cut using a knife, and the cut is gradually widened ([Fig. 4, ] [Fig. 5]). The two liquids are mixed and injected under the chicken skin (to mimic the submucosal layer). The greatest advantages of this model are that i) skinned chicken meat can be purchased from any supermarket, ii) there is a low infection risk for hepatitis E virus or other zoonotic infections, and iii) it is a low-cost model ($1.50 – 1.70). Chicken meat preparation is fast, simple, and inexpensive compared with porcine model preparation. Therefore, G-ESD training using this novel model is feasible, efficient, and may be widely available for trainees who do not have the chance to practice G-ESD or attend hands-on seminars.
Abstract 16449: New Onset Heart Failure Due to Effusive Constrictive Pericarditis
Authors: Yousif Al-Saiegh, Philip Williams, Timothy Barry, Elias Impens, Jenna Spears, Sina Manthey
Journal: Circulation (2019)

Introduction: Effusive constrictive pericarditis (ECP) is a rare syndrome characterized by constriction of the heart by the visceral pericardium in the presence of cardiac tamponade caused by fluid...
Abstract 289: Perm1 is a Novel Regulator of Cardiac Energetics and Function
Authors: Shinichi Oka, Amira Sabry, Amanda Horiuchi, Keiko Cawley, Sean O'Very, Maria Zaitsev, Thirupura S Shankar, Jaemin Byun, Chun-yang Huang, Xioayong Xu, Natalia S Torres, Anna Bakhtina, Chris Stubben, Sarah Franklin, Yukio Saijoh, Stavros G Drakos, Junichi Sadoshima, Junco S Warren
Journal: Circulation Research (2020)

Regulation of mitochondrial energetics is key to maintain cardiac function. Perm1 ( P GC-1 and E RR- r egulator, m uscle 1 ) was previously shown to enhance exercise endurance in skeletal muscle through increasing mitochondrial bioenergetics. Despite the significant expression levels of Perm1 in the heart, its role in the healthy and diseased hearts has never been investigated. We found that cardiac Perm1 was downregulated in the mouse failing heart subjected to pressure overload for 4 weeks (24.4 ± 5.9 % of sham operated, p&lt;0.05) and in patients with advanced heart failure (55.2 ± 13.1 % of donors, p&lt;0.05) suggesting a role of Perm1 in cardiac pathology. Phenylephrine (PE)-induced hypertrophy in cardiomyocytes was accompanied by downregulation of Perm1 (55.7 ± 5.7 % of control, p &lt;0.05), and adenovirus-mediated overexpression of Perm1 rescued PE-induced downregulation of estrogen-related receptor alpha (ERRα), a key transcriptional regulator of mitochondrial energetics, and its target gene, Ndufv1 (Complex I), suggesting that downregulation of Perm1 contributes to the development of mitochondrial dysfunction in response to hypertrophic stimuli. Pathway enrichment analysis in cardiomyocytes where Perm1 was knocked-down by siRNA (siPerm1) revealed that the most downregulated pathway was metabolism, while upregulated pathways were mostly related to synthesis and assembly of collagen fibrils (i.e. Col3a1, Col5a1, Col11a1, Lox). Cell stress test using Seahorse XF analyzer showed that basal respiration and ATP production were significantly reduced in siPerm1 cardiomyocytes (40.7 % and 23.6 % of scrambled-siRNA, respectively, both p &lt;0.05). Luciferase reporter gene assay further revealed that Perm1 dose-dependently increased the promoter activity of the ERRα gene and known targets of ERRα, Ndufv1 and Ndufs1 (Complex I). Furthermore, systemic Perm1-knockout mice developed heart failure (3 months old ejection fraction 38.8 %), concurrent with downregulation of proteins involved in oxidative phosphorylation, such as Ndufaf4 and Uqcr11 (-6.14 and -2.39 in fold change, respectively), and increased fibrosis. These results suggest that Perm1 is a novel regulator of cardiac metabolism and function, that enhances energetics and suppresses fibrosis.
Abstract PO-055: Global immune characterization of hepatocellular carcinoma identifies macrophage and T cell subsets related to disease progression
Authors: Guohe Song, Yang Shi, Youpei Lin, Juan Zhang, Shuaixi Yang, Qiang Gao
Journal: Cancer Research (2020)

Abstract Diverse immune cells in the tumor microenvironment form a complex ecosystem, but our knowledge of their heterogeneity and dynamics within hepatocellular carcinoma (HCC) remains poorly understood. We assess the plasticity and phenotypes of immune cells within HCC microenvironment at single-cell level. We performed single-cell RNA sequencing on 41,698 immune cells from 7 pairs of HCC tumors and nontumor liver tissues. We combined bioinformatic analyses, flow cytometry and multiplex immunohistochemistry to assess the heterogeneity of different immune subsets in functional characteristics, transcriptional regulation, phenotypic switching, and interactions. We identified 29 immune subsets of myeloid cells, NK cells, and lymphocytes with unique transcriptomic profiles in HCC. A highly complex immunological network was shaped by immune subsets with diverse characteristics that can transit among different states and mutually engage through intercellular communication. Notably, we identified a subset of M2 macrophage with high expression of CCL18 and transcription factor CREM that was enriched in advanced HCC patients, and potentially participated in tumor progression. We also detected a new subset of activated CD8+ T cells highly expressing XCL1 that correlated with better patient survival, and possibly enhanced anti-tumor response. Meanwhile, distinct transcriptomic signatures, cytotoxic phenotypes and evolution trajectory of effector CD8+ T cells from early-stage to advanced HCC were also identified. Our study presents a comprehensive insight for dissecting the immune microenvironment in HCC and highlights novel macrophage and T cell subsets that could be further exploited in future immunotherapy. Citation Format: Guohe Song, Yang Shi, Youpei Lin, Juan Zhang, Shuaixi Yang, Qiang Gao. Global immune characterization of hepatocellular carcinoma identifies macrophage and T cell subsets related to disease progression [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-055.
Clonal Hematopoiesis Drives Therapy-Related Myeloid Neoplasms Following Autologous Stem Cell Transplantation and Propagates during Disease Evolution
Authors: Johannes Frasez Sørensen, Anni Aggerholm, Marcus H Hansen, Gitte Birk Kerndrup, Lene Hyldahl Ebbesen, Peter Hokland, Anne Stidsholt Roug, Maja Ludvigsen
Journal: Blood (2020)
Validation of a Modified Version of the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)
Authors: Blake T. Langlais, Heidi E. Kosiorek, Gina L. Mazza, Carolyn Mead-Harvey, Richard Butterfield, Jeanne M. Palmer, Ruben Mesa, Amylou C. Dueck
Journal: Blood (2020)
Abstract 325: The Regulation of Endothelial Function Through Hmgcr/mevalonate Pathway Mediated Yap Activity
Authors: Chun Liu, Yu Liu, Christopher Chen, Mo Ameen, Huaxiao Yang, Mengcheng Shen, June Wha Rhee, Ian Y Chen, Nazish Sayed, Joseph C Wu
Journal: Circulation Research (2020)

Background: Cardiovascular diseases (CVD) are the leading cause of death in the United States. Statins, a class of hydroxy-methylglutaryl-coenzyme A reductase (HMGCR) inhibitors, have been proven to be effectively prevent and treat CVD by improving vascular functions independent of their cholesterol-lowering effect. However, the molecular mechanisms by which statins improve cardiovascular functions remain elusive. In this study, we used human induced pluripotent stem cells-derived endothelial cells (hiPSC-ECs) to explore the protective role of statins in the vascular system. Methods and Results: hiPSCs were generated from 3 healthy individuals and differentiated into endothelial cells using two different iPSC clones and two batches (4 biological replicates for each individual). hiPSC-ECs of each individual were treated with simvastatin or a vehicle control. The RNA-sequencing analysis was performed on 12 control and 12 statin-treated hiPSC-ECs. A total number of 2,580 differentially expressed genes (DEGs) were found in simvastatin-treated hiPSC-ECs. Gene enrichment analysis revealed that statin-upregulated DEGs were highly enriched in angiogenesis and anti-inflammation pathways. Interestingly, statin-downregulated DEGs were significantly enriched in epigenetic regulation and nucleosome assembly pathways, suggesting an epigenetic regulatory role of stains in vascular gene expression. To test this hypothesis, we further performed the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) analysis on vehicle or simvastatin treated hiPSC-ECs. Transcription factor (TF) binding motif analyses of ATAC-seq peaks using HOMER revealed that YAP/TEAD binding was the most significantly downregulated TF after statin treatment. Furthermore, we observed that statin can improve endothelial functions (e.g., angiogenesis and nitric oxide production) after the YAP activity was inhibited. The ChIP-seq analysis showed that statin downregulated the expression levels of genes associated with the endothelial-to-mesenchymal transition (EndoMT) by attenuating the binding capacity of YAP. As such, simvastatin effectively rescued diabetic vascular dysfunction mainly through inhibiting EndoMT. Conclusion: We found that statins can improve endothelial functions through attenuating the chromatin accessibility of EndoMT-related genes, a process tightly regulated by the activity of YAP. These findings will provide novel insights into the protective mechanisms of statins in the cardiovascular system beyond their cholesterol-lowering effects.
Identification of Novel Regulatory Pathway for Immunoglobulin Production Provides Rational Treatment for Bortezomib-Resistant Multiple Myeloma Patients
Authors: Alexander Vdovin, Michal Durech, Tomas Jelinek, Tereza Sevcikova, Juli R. Bago, Matous Hrdinka, David Zihala, Renata Snaurova, Hana Sahinbegovic, Tereza Popkova, Ryszard Smolarczyk, Tomasz Cichon, Sebastian Giebel, Roman Hajek, Michal Simicek
Journal: Blood (2020)
Safety and Tolerability of Intra-Venous Ascorbic Acid in Allogeneic Hematopoietic Cell Transplant Recipients: A Matched Historical Control Study
Authors: Gary Simmons, Roy Sabo, Maja Radic, May Aziz, Kelly Hawks, Robyn J Bernard, Ali Jafri, Catherine H Roberts, Ramesh Natarajan, Alpha Fowler, Amir Ahmed Toor
Journal: Blood (2020)
Randomized Phase III Study of Irinotecan Plus Cisplatin Versus Etoposide Plus Cisplatin for Completely Resected High-Grade Neuroendocrine Carcinoma of the Lung: JCOG1205/1206
Authors: Hirotsugu Kenmotsu, Seiji Niho, Masahiro Tsuboi, Masashi Wakabayashi, Genichiro Ishii, Kazuo Nakagawa, Haruko Daga, Hiroshi Tanaka, Haruhiro Saito, Keiju Aokage, Toshiaki Takahashi, Toshi Menju, Takashi Kasai, Ichiro Yoshino, Koichi Minato, Morihito Okada, Junko Eba, Hisao Asamura, Yuichiro Ohe, Shun-ichi Watanabe
Journal: Journal of Clinical Oncology (2020)

PURPOSE To verify the superiority of irinotecan plus cisplatin over etoposide plus cisplatin as postoperative adjuvant chemotherapy for patients with pathologic stage I-IIIA, completely resected, high-grade neuroendocrine carcinoma (HGNEC) of the lung. METHODS This was a randomized, open-label, phase III study on patients with completely resected stage I-IIIA HGNEC of the lung. They were randomly assigned to receive either etoposide (100 mg/m 2 , days 1-3) plus cisplatin (80 mg/m 2 , day 1) or irinotecan (60 mg/m 2 , days 1, 8, 15) plus cisplatin (60 mg/m 2 , day 1) up to four cycles. The primary end point was relapse-free survival (RFS) in the intention-to-treat population. This trial was registered with the Japan Registry of Clinical Trials (jRCTs031180216). RESULTS Between April 2013 and October 2018, 221 patients were enrolled (etoposide plus cisplatin arm, 111 patients; irinotecan plus cisplatin arm, 110 patients). In the second interim analysis, early termination of the trial was recommended because of futility. At a median follow-up of 24.1 months, the 3-year RFS was 65.4% for etoposide plus cisplatin and 69.0% for irinotecan plus cisplatin, with a hazard ratio of 1.076 (95% CI, 0.666 to 1.738; one-sided log-rank P = .619). Grade 3-4 adverse events were more frequent in the etoposide plus cisplatin arm, with febrile neutropenia (20% of 109 patients v 4% of 107 patients) and neutropenia (97% v 36%) being the most common. Meanwhile, grade 3-4 anorexia (6% v 11%) and diarrhea (1% v 8%) were more frequently observed in the irinotecan plus cisplatin arm. CONCLUSION Irinotecan plus cisplatin is not superior to etoposide plus cisplatin for improving RFS in patients with completely resected HGNEC; thus, etoposide plus cisplatin remains the standard treatment.
JMML Fetal Identity Results Either from Retention of a Physiologic Signature or Aberrant Activation of Master Oncofetal Regulators
Authors: Marion Strullu, Aurélie Caye-Eude, Loïc Maillard, Chloé Arfeuille, Elodie Lainey, Florian Piques, Odile Fenneteau, Bruno Cassinat, Fabien Guimiot, Jean-Hugues Dalle, André Baruchel, Christine Chomienne, Dominique Bonnet, Michele Souyri, Hélène Cavé
Journal: Blood (2020)
Poor Prognosis of Multiple Myeloma Predicted By High Levels of Circulating Plasma Cells Is Independent from Other High-Risk Features but Is Modulated By the Achievement of Minimal Residual Disease Negativity
Authors: Luca Bertamini, Mariella Grasso, Mattia D'Agostino, Anna Pascarella, Patrizia Tosi, Federico Monaco, Francesco Pisani, Paola Bertazzoni, Milena Gilestro, Andrea Capra, Piero Galieni, Ombretta Annibali, Vincenzo Pavone, Stefano Molica, Sonia Ronconi, Paola Tacchetti, Pellegrino Musto, Francesca Gay, Mario Boccadoro, Stefania Oliva
Journal: Blood (2020)