tbuckley/cabot-search huggingface dataset:
Abstract 301: Cavin-2 Deletion Attenuates Fibroblast Activation and Cardiac Fibrosis via TGF-β Signaling by Interacting With Hsp90
Authors: Yusuke Higuchi, Takehiro Ogata, Naohiko Nakanishi, Akira Sakamoto, Yumika Tsuji, Shinya Tomita, Satoaki Matoba
Journal: Circulation Research (2020)

Introduction: Heart failure (HF) is a progressive disease associated with high morbidity and mortality. A major cause of HF is the adverse tissue remodeling with interstitial fibrosis. Excessive extracellular matrix (ECM) accumulation is involved in the poor outcome. Transformation to myofibroblasts in resident fibroblasts has an important role for cardiac fibrosis on pressure-overload heart failure. TGF-β signaling is one of the critical pathways in fibroblast activation. Caveolae are major plasma membrane domain defined as 50-100 nm vesicular structures. Caveolins and cavins are known as caveolar-related proteins. TGF-β signaling is tightly connected with caveolae. A previous report shows that induction of Cav-1 expression leads to suppression of TGF-β signaling and an improvement of fibrosis. Although cavin-2/Serum deprivation response protein (SDPR) is also abundant in fibroblasts, the role of cavin-2 in cardiac fibrosis and function remains unknown. Methods and Results: To clarify the role of cavin-2 in cardiac fibroblasts in the pressure-overloaded heart, we performed TAC operation on cavin-2 flox/flox mice and fibroblast-specific cavin-2 knockout (Postin Cre ; SDPR flox/flox ) mice (cavin-2 cKO). Four weeks after TAC, left ventricular fractional shortening (LVFS) was preserved with a significant reduction of cardiac fibrosis in cavin-2 cKO mice. Fibrosis-associated mRNA expression ( Col1a1, Ctgf, Col3 ) and α1 type I collagen deposition were reduced in the hearts of cavin-2-cKO mice after TAC. Transdifferentiation of fibroblasts into activated myofibroblasts is a defining feature of fibrosis. Myofibroblasts express αSMA and secrete ECM proteins via Smad signaling. αSMA-positive cells without showing vascular structure were reduced in cavin-2 cKO after TAC. In mouse embryonic fibroblasts (MEFs), cavin-2 deficiency reduced TGF-β1-induced αSMA production and fibrosis-associated mRNA expression. On the other hand, adenovirus-mediated cavin-2 overexpression significantly increased αSMA production and the fibrosis-associated mRNA expressions. Furthermore, TGF-β1-induced Smad2/3 phosphorylation was attenuated in cavin-2 KO MEFs compared to wild-type (WT) MEFs. A protein-Protein interaction screening using a promiscuous biotin ligase, called BioID, revealed that cavin-2 interacted with Hsp90ab1 and Hsp90b1 which modulate collagen synthesis through regulation of SMA and SMAD pathway. The protein expression level of Hsp90 in cavin-2 KO MEFs significantly decreased compared with that in WT MEFs. Conclusions: Our observations suggest that cavin-2 contributes to the development of cardiac fibrosis through the differentiation from fibroblasts into myofibroblasts via TGF-β/Smad signaling. cavin-2 may be a novel therapeutic target for cardiac fibrosis.
Importance of Flow Cytometry in the Diagnosis of Sezary Syndrome in the State of Rio Grande Do Norte, Brazil
Authors: Maria das Graças Pereira Araujo, Victor lima Soares, Alessandra Suelen Jardim Silva, Gustavo Henrique de Medeiros Oliveira, Lenilton Silva DA Silva Júnior, Hugo Henrique de Freitas Ferreira, Rodrigo Villar Freitas, Taissa Moura Oliveira, Dany GKC Silva, Valéria SF Sales, Rodolfo DA Soares, Hugo Diogenes De Oliveira Paiva, Geraldo Barroso Cavalcanti, Aldair Sousa Paiva
Journal: Blood (2020)
Phase 2 Study of Daratumumab in Combination with Thalidomide and Dexamethasone in Asian Patients with Relapsed/Refractory Myeloma (RRMM) - Interim Analysis of a Trial By the Asian Myeloma Network (AMN)
Authors: Wee-Joo Chng, Cindy Lin, Xinhua Li, Chandramouli Nagarajan, Sung-Soo Yoon, Brian G.M. Durie
Journal: Blood (2020)
Large-Scale Proteomic Analysis of Soluble Compartment in Pediatric Acute Lymphoblastic Leukemia
Authors: Giusy Gentilcore, Sara Deola, Sheanna M Herrera, Che-Ann Lachica, Tayseer Abbas Yousif, Areeg Ahmed, Naima Al Mulla, Ayman Saleh, Tommaso Mina, Patrizia Comoli, Jean-Charles Grivel, Chiara Cugno
Journal: Blood (2020)
AB0185 PROSPECTIVE PROFILE OF URINE METABOLOME IN RHEUMATOID ARTHRITIS
Authors: M. De Oliveira, P. V. Alabarse, M. Farinon, R. Cavalheiro Do Espírito Santo, R. Xavier
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by increased mortality and associated with metabolic disorders. Since the metabolomic profile is known to vary in response to different inflammatory conditions, metabolome analysis could substantially improve diagnosis and prognosis of RA. Objectives: To analyze the urine metabolome profile in RA patients and correlate it with disease activity changes over 12 months Methods: Seventy-nine RA patients, according to ACR/EULAR 2010 classification criteria, between 40 and 70 years old, were recruited and followed for 12 months. Metabolome analysis was performed by Nuclear Magnetic Resonance spectroscopy (NMR), resulting in the identification of 93 metabolites in urine collected at the baseline and after 12 months. Frequency analysis, Pearson Correlation and Multivariate data analysis with orthogonal projections to latent structures (OPLS) method were performed and a statistical significance was considered as p&lt;0.05. Results: The study population was characterized by the majority of women (86.7%), mean age of 56 years old, around 80% with positive anti-CCP or Rheumatoid Factor. During the one year of follow-up, there was no substantial variation in the DAS28 measurement (baseline: 3.8, after 12 months: 4.0). There was no significant correlation between the metabolome pattern and DAS28 score (p&gt;0.05) over time. However, multivariate analysis (OPLS-DA) demonstrated an adequate differentiation of the population with 0.92 of accuracy (Q2: 0.72 and R2: 0.89).There was a significant increase of L-cysteine, choline, L-Phenylalanin, creatine, L-histidine, oxalacetic acid and xanthine, and a decrease of L-threonine, taurine, butyric and gluconic acid (p&lt;0.05) during the follow-up, metabolites that are involved in the skeletal muscle metabolism. Conclusion: The observed biomarkers indicate,as expected, that the RA metabolic profile is associated with inflammation injury and skeletal muscle amino acid metabolism. Correlations with disease activity changes was compromised by the stable disease status during the 12 months. More studies evaluating correlations with skeletal muscle function and mass are underway. Acknowledgments: Disclosure of interest: Marianne Oliveira: None declared, Rafaela Santo: None declared, Mirian Farinon: None declared, Ricardo Xavier Consultant of: Abbvie, Pfizer, Novartis, Janssen, Lilly, Roche Disclosure of Interests: Marianne de Oliveira: None declared, Paulo Vinicius Alabarse: None declared, Mirian Farinon: None declared, Rafaela Cavalheiro do Espírito Santo: None declared, Ricardo Xavier Consultant of: AbbVie, Pfizer, Novartis, Janssen, Eli Lilly, Roche
miR-155 promotes T reg cell development by safeguarding medullary thymic epithelial cell maturation
Authors: Jiayi Dong, Lindsey M. Warner, Ling-Li Lin, Mei-Chi Chen, Ryan M. O'Connell, Li-Fan Lu
Journal: The Journal of Experimental Medicine (2020)

During thymocyte development, medullary thymic epithelial cells (mTECs) provide appropriate instructive cues in the thymic microenvironment for not only negative selection but also the generation of regulatory T (T reg) cells. Here, we identify that miR-155, a microRNA whose expression in T reg cells has previously been shown to be crucial for their development and homeostasis, also contributes to thymic T reg (tT reg) cell differentiation by promoting mTEC maturation. Mechanistically, we show that RANKL stimulation induces expression of miR-155 to safeguard the thymic medulla through targeting multiple known and previously uncharacterized molecules within the TGFβ signaling pathway, which is recognized for its role in restricting the maturation and expansion of mTECs. Our work uncovers a miR-155–TGFβ axis in the thymic medulla to determine mTEC maturity and, consequently, the quantity of tT reg cells and suggests that miR-155 ensures proper tT reg cell development in both cell-intrinsic and -extrinsic manners.
Neighbourhood income and physical distancing during the COVID-19 pandemic in the United States
Authors: Jonathan Jay, Jacob Bor, Elaine O. Nsoesie, Sarah K. Lipson, David K. Jones, Sandro Galea, Julia Raifman
Journal: Nature Human Behaviour (2020)

Physical distancing has been the primary strategy to control COVID-19 in the United States. We used mobility data from a large, anonymized sample of smartphone users to assess the relationship between neighbourhood income and physical distancing during the pandemic. We found a strong gradient between neighbourhood income and physical distancing. Individuals in high-income neighbourhoods increased their days at home substantially more than individuals in low-income neighbourhoods did. Residents of low-income neighbourhoods were more likely to work outside the home, compared to residents in higher-income neighbourhoods, but were not more likely to visit locations such as supermarkets, parks and hospitals. Finally, we found that state orders were only associated with small increases in staying home in low-income neighbourhoods. Our findings indicate that people in lower-income neighbourhoods have faced barriers to physical distancing, particularly needing to work outside the home, and that state physical distancing policies have not mitigated these disparities. Physical distancing during COVID-19 was more difficult for residents of low-income US neighbourhoods. Using smartphone mobility data, Jay et al. find that days at work, not visits to other locations, explain these disparities and that state policies did not correct them.
Reduced-Intensity Induction with Dasatinib Vs. Hypercvad + 2nd Generation TKIs with MRD-Guided Follow-up Therapy Leads to Comparable Rates of MRD-Negative Remission While Reducing Transfusions and Neutropenia in Ph+ ALL
Authors: Jonathan Webster, Hua-Ling Tsai, Eric Gehrie, Tania Jain, Christopher S. Hourigan, William Brian Dalton, Gabrielle T. Prince, Lukasz P. Gondek, Gabriel Ghiaur, Amy E. DeZern, Margaret M. Showel, Ivana Gojo, Douglas E Gladstone, Philip H. Imus, Javier Bolanos-Meade, Leo Luznik, Ephraim J. Fuchs, Christian B. Gocke, Abbas Abbas Ali, Carol Ann Huff, Ivan M. Borrello, Lode J. Swinnen, Nina D. Wagner-Johnston, Richard F. Ambinder, Richard J. Jones, B. Douglas Smith, Mark Levis
Journal: Blood (2020)
Human Placental CD34+-Derived Natural Killer Cells with High Affinity and Cleavage Resistant CD16 (CYNK-101) for ADCC Mediated Cancer Immunotherapy
Authors: Lin Kang, Irene Raitman, Salvatore Rotondo, Joseph Gleason, Shuyang He, Srinivas Somanchi, Valentina Rousseva, Xuan Guo, Hemlata Rana, Andrea DiFiglia, Qian Ye, Tanel Mahlakõiv, William Van Der Touw, Robert Hariri, Xiaokui Zhang
Journal: Blood (2020)
Is patellofemoral pain preventable? A systematic review and meta-analysis of randomised controlled trials
Authors: Adam G Culvenor, Marienke van Middelkoop, Erin M Macri, Kay M Crossley
Journal: British Journal of Sports Medicine (2020)

Objective To evaluate the effectiveness of interventions to reduce the risk of incident patellofemoral pain. Design Systematic review and meta-analysis, with strength of evidence evaluated separately for each intervention type. Data sources MEDLINE, EMBASE, CINAHL, Web of Science and SPORTDiscus. Eligibility criteria for selecting studies Randomised controlled trials evaluating the effectiveness of interventions to reduce patellofemoral pain risk compared with a control/non-exposed group. Results Thirteen trials of mostly military recruits and young athletes analysed six different interventions. There was low certainty evidence from two trials (227 participants) that patellofemoral braces worn during physical activity (compared with no brace) effectively reduced the risk of patellofemoral pain (risk ratio (RR) 0.40, 95% CI 0.22 to 0.73; I 2 =24.0%). There was low certainty evidence from one trial (320 participants) that running technique retraining to (run softer) reduced patellofemoral pain risk (RR 0.21, 95% CI 0.07 to 0.60). There was low certainty evidence from four trials (3364 participants) that multicomponent (strengthening/neuromuscular) exercise programmes did not significantly reduce the risk of patellofemoral pain (RR 0.49, 95% CI 0.18 to 1.36; I 2 =64.9%), although broad CIs may reflect exercise dose variations among studies. There was very low certainty evidence from four trials (2314 participants) that foot orthoses (compared with flat inserts/no orthosis) did not significantly reduce the risk of patellofemoral pain (RR 0.63, 95% CI 0.35 to 1.13; I 2 =0.0%). Static stretching and a running programme that progressed intensity (compared with volume) did not significantly influence patellofemoral pain risk (single studies). Conclusion There is low-level evidence that patellofemoral braces and running technique retraining can reduce the risk of patellofemoral pain by 60%–79%.
Steroid Use, Advanced Stage Disease and ≥3 Lines of Prior Chemotherapy Are Associated with a Higher Risk of Infection Following CD19 CAR T-Cell Therapy for B-NHL: Real World Data from a Large UK Center
Authors: Lorna Neill, Strachan C Mackenzie, Maria A V Marzolini, William Townsend, Kirit M. Ardeshna, Kate Cwynarski, Surjo De, Vanya Gant, Lhara Mure, Sara McElduff, Chantelle Hughes, Karl S Peggs, Claire Roddie, Maeve A O'Reilly
Journal: Blood (2020)
Ibrutinib Induces Durable Remissions in Treatment-Naïve CLL Patients with 17p Deletion/TP53 Mutations: Five Year Follow-up from a Phase 2 Study
Authors: Mariela Sivina, Nitin Jain, Ekaterina Kim, Tapan M. Kadia, Zeev E. Estrov, Maro Ohanian, Michael Andreeff, Mathew Thomas, Philip A. Thompson, Hagop M. Kantarjian, Michael J. Keating, Susan M. O'Brien, William G. Wierda, Alessandra Ferrajoli, Jan A. Burger
Journal: Blood (2020)
Real-World Clinical Outcomes of Patients with Myelofibrosis Treated with Ruxolitinib: Evidence from a Multinational Medical Record Review
Authors: Francesco Passamonti, Florian H. Heidel, Rohan C. Parikh, Derek Tang, Betsy J. Lahue, Jose Alberto Nadal, Keith L. Davis, Mayank Ajmera, Arianna Kee, Pranav Abraham
Journal: Blood (2020)
Sarcoidosis Mimicking Primary Pulmonary Artery Sarcoma
Authors: Abdulrahman Masrani, Demetrios A. Raptis, Barry A. Siegel
Journal: Clinical Nuclear Medicine (2020)

Abstract A 71-year-old man with coronary artery disease, sarcoid uveitis, and recurrent ventricular tachycardia treated with implantable cardioverter-defibrillator presented with increasing dyspnea for several months. Echocardiography showed a large echogenic mass causing severe narrowing of the proximal main pulmonary artery and a resultant gradient of 65 mm Hg. Ventilation-perfusion scintigraphy showed diffusely decreased perfusion of the left lung and an additional mismatched segmental perfusion defect in the left upper lobe. Cardiac MRI could not be performed because of the implantable cardioverter-defibrillator.
Benchmarking definitions of false-positive alerts during computer-aided polyp detection in colonoscopy
Authors: Erik A. Holzwanger, Mohammad Bilal, Jeremy R. Glissen Brown, Shailendra Singh, Aymeric Becq, Kenneth Ernest-Suarez, Tyler M. Berzin
Journal: Endoscopy (2020)

Abstract Background The occurrence of false-positive alerts is an important outcome measure in computer-aided colon polyp detection (CADe) studies. However, there is no consensus definition of a false positive in clinical trials evaluating CADe in colonoscopy. We aimed to study the diagnostic performance of CADe based on different threshold definitions for false-positive alerts. Methods A previously validated CADe system was applied to screening/surveillance colonoscopy videos. Different thresholds for false-positive alerts were defined based on the time an alert box was continuously traced by the system. Primary outcomes were false-positive results and specificity using different threshold definitions of false positive. Results 62 colonoscopies were analyzed. CADe specificity and accuracy were 93.2 % and 97.8 %, respectively, for a threshold definition of ≥ 0.5 seconds, 98.6 % and 99.5 % for a threshold definition of ≥ 1 second, and 99.8 % and 99.9 % for a threshold definition of ≥ 2 seconds. Conclusion Our analysis demonstrated how different threshold definitions of false positive can impact the reported diagnostic performance of CADe for colon polyp detection.
PERSEPT3: A Phase 3 Clinical Trial to Evaluate the Hemostatic Efficacy of Eptacog Beta (Recombinant Human FVIIa) in Perioperative Care in Subjects with Hemophilia Α or B with Inhibitors
Authors: Miguel A. Escobar, Doris Quon, Cindy A. Leissinger, James V Luck, Ahmad Al-Sabbagh, Daniel Bonzo, Ian S Mitchell, W Allan Alexander, Cedric Hermans
Journal: Blood (2020)
Covid-19: Why we still need more women in academia
Authors: Fiona Godlee
Journal: BMJ (2020)

One small but significant impact of the covid pandemic has been its constraining effect on the academic output of women. The first signs of a sex imbalance were seen in the overwhelmingly male line-ups of experts speaking about covid-19 and the poor representation of women on government pandemic advisory panels.12 Meanwhile journals, including The BMJ and our specialty journals, have seen a worrying drop in the proportion of female first authors of research papers. It seems that, while lockdown may have provided men with time and space to boost their academic output, school closures …
Patients with Relapsed/Refractory Marginal Zone Lymphoma in the MAGNIFY Phase IIIb Interim Analysis of Induction R2 Followed By Maintenance
Authors: Morton Coleman, David Jacob Andorsky, Abdulraheem Yacoub, Jason M. Melear, Suzanne R. Fanning, Kathryn S. Kolibaba, Frederick Lansigan, Christopher M. Reynolds, Grzegorz S. Nowakowski, Mecide Gharibo, Erin Ahn, Ju Li, Mathias J. Rummel, Jeff P Sharman
Journal: Blood (2020)
Comprehensive Assessment of Diet Quality and Risk of Precursors of Early-Onset Colorectal Cancer
Authors: Xiaobin Zheng, Jinhee Hur, Long H Nguyen, Jie Liu, Mingyang Song, Kana Wu, Stephanie A Smith-Warner, Shuji Ogino, Walter C Willett, Andrew T Chan, Edward Giovannucci, Yin Cao
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Background The role of poor diet quality in the rising incidence of colorectal cancer (CRC) diagnosed younger than age 50 years has not been explored. Based on molecular features of early-onset CRC, early-onset adenomas are emerging surrogate endpoints. Methods In a prospective cohort study (Nurses’ Health Study II), we evaluated 2 empirical dietary patterns (Western and prudent) and 3 recommendation-based indexes (Dietary Approaches to Stop Hypertension [DASH], Alternative Mediterranean Diet [AMED], and Alternative Healthy Eating Index [AHEI]-2010) with risk of early-onset adenoma overall and by malignant potential (high-risk: ≥1 cm, tubulovillous or villous histology, high-grade dysplasia, or ≥3 adenomas), among 29 474 women with 1 or more lower endoscopy before age 50 years (1991–2011). Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results We documented 1157 early-onset adenomas with 375 at high risk. Western diet was positively associated, whereas prudent diet, DASH, AMED, and AHEI-2010 were inversely associated with risk of early-onset adenoma. The associations were largely confined to high-risk adenomas (the highest vs lowest quintile: Western, OR = 1.67, 95% CI = 1.18 to 2.37; prudent, OR = 0.69, 95% CI = 0.48 to 0.98; DASH, OR = 0.65, 95% CI = 0.45 to 0.93; AMED, OR = 0.55, 95% CI = 0.38 to 0.79; AHEI-2010, OR = 0.71, 95% CI = 0.51 to 1.01; all Ptrend ≤ .03), driven by those identified in the distal colon and rectum (all Ptrend ≤ .04, except AMED: Ptrend = .14). Conclusion Poor diet quality was associated with an increased risk of early-onset distal and rectal adenomas of high malignant potential. These findings provide preliminary but strong support to the role of diet in early-onset CRC.
Multiple myeloma and SARS-CoV-2 infection: clinical characteristics and prognostic factors of inpatient mortality
Authors: Joaquín Martínez-López, María-Victoria Mateos, Cristina Encinas, Anna Sureda, José Ángel Hernández-Rivas, Ana Lopez de la Guía, Diego Conde, Isabel Krsnik, Elena Prieto, Rosalía Riaza Grau, Mercedes Gironella, María Jesús Blanchard, Nerea Caminos, Carlos Fernández de Larrea, María Alicia Senin, Fernando Escalante, José Enrique de la Puerta, Eugenio Giménez, Pilar Martínez-Barranco, Juan José Mateos, Luis Felipe Casado, Joan Bladé, Juan José Lahuerta, Javier de la Cruz, Jesús San-Miguel
Journal: Blood Cancer Journal (2020)

Abstract There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes were compared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admitted at six participating hospitals. Among MM and noncancer patients, median age was 71 years, and 57% of patients were male; 75 and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate–severe in 77 and 89% of patients and critical in 8 and 4%, respectively. Supplemental oxygen was required by 47 and 55% of MM and noncancer patients, respectively, and 21%/9% vs 8%/6% required noninvasive/invasive ventilation. Inpatient mortality was 34 and 23% in MM and noncancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged &gt;65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19.
Biomarker-driven therapies for previously treated squamous non-small-cell lung cancer (Lung-MAP SWOG S1400): a biomarker-driven master protocol
Authors: Mary W Redman, Vassiliki A Papadimitrakopoulou, Katherine Minichiello, Fred R Hirsch, Philip C Mack, Lawrence H Schwartz, Everett Vokes, Suresh Ramalingam, Natasha Leighl, Jeff Bradley, Jieling Miao, James Moon, Louise Highleyman, Crystal Miwa, Michael L LeBlanc, Shakun Malik, Vincent A Miller, Ellen V Sigal, Stacey Adam, David Wholley, Caroline Sigman, Beverly Smolich, Charles D Blanke, Karen Kelly, David R Gandara, Roy S Herbst
Journal: The Lancet Oncology (2020)
CC-486 Reduces Hospitalization and Associated Estimated Costs in Patients with Acute Myeloid Leukemia (AML) in First Remission after Intensive Chemotherapy: Results from the QUAZAR AML-001 Maintenance Trial
Authors: Esther Natalie Oliva, Suman Kambhampati, Albert Oriol, Ignazia La Torre, Barry Skikne, C.L. Beach, Keshava Kumar, Qian Dong, Clara Chen, Sandip Ranjan, Zephirin Kiendrebeogo, Thorsten Braun
Journal: Blood (2020)