tbuckley/cabot-search huggingface dataset:
Covid-19: “There is no alternative,” says Johnson, announcing new restrictions for England
Authors: Zosia Kmietowicz
Journal: BMJ (2020)

There is no alternative," says Johnson, announcing new restrictions for England Zosia KmietowiczNew national measures to try to stem the rising number of cases of covid-19 in England will come into force on 5 November, as the government conceded that the surge in cases and hospital admissions now threatened to breach NHS capacity.
Effect of Nintedanib on Lung Function in Patients With Systemic Sclerosis−Associated Interstitial Lung Disease: Further Analyses of a Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Toby M. Maher, Maureen D. Mayes, Michael Kreuter, Elizabeth R. Volkmann, Martin Aringer, Ivan Castellvi, Maurizio Cutolo, Christian Stock, Nils Schoof, Margarida Alves, Ganesh Raghu
Journal: Arthritis & Rheumatology (2020)

Objective In the SENSCIS trial in subjects with systemic sclerosis–associated interstitial lung disease (SSc‐ILD), nintedanib reduced the rate of decline in forced vital capacity (FVC) over 52 weeks by 44% versus placebo. This study was undertaken to investigate the effects of nintedanib on categorical changes in FVC and other measures of ILD progression. Methods In post hoc analyses, we assessed the proportions of subjects with categorical changes in FVC % predicted at week 52 and the time to absolute decline in FVC of ≥5% predicted or death and absolute decline in FVC of ≥10% predicted or death. Results A total of 288 subjects received nintedanib and 288 subjects received placebo. At week 52, in subjects treated with nintedanib and placebo, respectively, 55.7% and 66.3% had any decline in FVC % predicted, 13.6% and 20.1% had a decline in FVC of &gt;5% to ≤10% predicted, and 3.5% and 5.2% had a decline in FVC of &gt;10% to ≤15% predicted; 34.5% and 43.8% had a decrease in FVC of ≥3.3% predicted (proposed minimal clinically important difference [MCID] for worsening of FVC), while 23.0% and 14.9% had an increase in FVC of ≥3.0% predicted (proposed MCID for improvement in FVC). Over 52 weeks, the hazard ratio (HR) for an absolute decline in FVC of ≥5% predicted or death with nintedanib versus placebo was 0.83 (95% confidence interval [95% CI] 0.66−1.06) ( P = 0.14), and the HR for an absolute decline in FVC of ≥10% predicted was 0.64 (95% CI 0.43−0.95) ( P = 0.029). Conclusion These results suggest that nintedanib has a clinically relevant benefit on the progression of SSc‐ILD.
Abstract 216: Natural History of Kawasaki Disease with Medium-sized Coronary Aneurysm: Long-term Follow-up in a Tertiary Medical Center
Authors: Pei-Yuan Wu, Li-Chuan Sun, Ming-Tai Lin, Chun-An Chen, Shuenn-Nan Chiu, Chun-Wei Lu, Jou-Kou Wang, Mei-Hwan Wu
Journal: Circulation (2015)

Objectives: Patients with coronary artery aneurysms are at risk for thrombotic and stenotic complications later in their lives. The longitudinal changes of medium-sized coronary aneurysms caused by Kawasaki disease (KD) and their long-term outcome are still unclear in Taiwan. Methods: We retrospectively reviewed medical records of KD patients with medium-sized coronary aneurysms (4-8mm). The longitudinal change of coronary diameters were re-evaluated by domestic coronary z score calculator. The coronary artery diametes were transformed to standard deviation units from the mean (Z-score) normalized for body surface area. We also look for the potential risk factors for the persistence of coronary lesions. Results: Between 1983 and 2012, 56 KD patients suffered from medium aneurysms. The male to female ratio was 41:15. The mean age of disease onset was 2.13 years old, and 39.3% (22 of 56) was diagnosed at below 1 year old. The mean follow up duration was 8.2 years. No death occurred in this group of patient, and only one patient with persistent coronary aneurysm and stenosis/calcification had clinical evidence of myocardial ischemia. However, coronary aneurysms persisted in 24 (42.8%) patients and were associated with stenosis in 8 patients (14.3%), and calcification in 4 patients (7.1%). The coronary aneurysm persistence-free survival rates at 6 months, and 1, 2, 5 years after KD onset were 81%, 69%, 52%, 43%, respectively. Chi-square analysis revealed KD patients with history of ever deterioration of coronary Z score were significantly associated with the persistence of coronary aneurysms ( P = 0.0125). However, the initial aneurysm Z score (+4.43 vs +4.49), male gender or IVIG use were not risk factors to the persistence of coronary aneurysms. Conclusion: The prognosis of Kawasaki disease patient who developed medium size coronary aneurysm was good. However, those with ever deterioration of coronary Z scores were high risk group to have persistent coronary aneurysms. Specific therapies to promote vascular health in these patients should be advocated.
Collagenase IV and clusterin-modified polycaprolactone-polyethylene glycol nanoparticles for penetrating dense tumor tissues
Authors: Hao-Yan Huang, Li-Qing Chen, Wei Sun, Huan-Huan Du, Shunli Dong, Atef Mohammed Qasem Ahmed, Dingyun Cao, Jing-Hao Cui, Yi Zhang, Qing-Ri Cao
Journal: Theranostics (2020)

Purpose: Novel collagenase IV (ColIV) and clusterin (CLU)-modified polycaprolactone-polyethylene glycol (PCL-PEG) nanoparticles that load doxorubicin (DOX) were designed and fully evaluated in vitro and in vivo. Methods: PCL-PEG-ColIV was synthesized by linking PCL-PEG and ColIV through a carbodiimide method. DOX-loaded nanoparticles (DOX-PCL-PEG-ColIV) were self-assembly prepared, followed by noncovalently adsorbing CLU on the DOX-PCL-PEG-ColIV surface to obtain DOX-PCL-PEG-ColIV /CLU nanoparticles, which can penetrate through the tumor extracellular matrix (ECM) and inhibit phagocytosis by macrophage. The physicochemical properties of nanoparticles were characterized. The cellular uptake and antiphagocytosis ability of nanoparticles in MCF-7 tumor cells and RAW264.7 cells were investigated. The penetration ability of nanoparticles was individually evaluated in the two-dimensional (2D) and three-dimensional (3D) ECM models. The tissue distribution and antitumor effect of nanoparticles were evaluated in MCF-7 cell-bearing nude mice. Results: Compared with DOX-PCL-PEG-COOH nanoparticles, DOX-PCL-PEG-ColIV/CLU nanoparticles could effectively overcome the phagocytosis by RAW264.7 and showed excellent cellular uptake in MCF-7 cells. In addition, they showed remarkable penetration ability through the 2D and 3D ECM models. DOX-PCL-PEG-ColIV/CLU nanoparticles significantly reduced the drug distribution in the liver and spleen and enhanced the drug accumulation in tumor tissue compared with DOX-PCL-PEG-COOH or DOX-PCL-PEG-ColIV nanoparticles. DOX-PCL-PEG-ColIV/CLU nanoparticles showed remarkable antitumor effect but did not cause severe pathological damages in the main tissues, including the heart, liver, spleen, lung, and kidney. Conclusion: Novel ColIV and CLU-modified PCL-PEG nanoparticles showed excellent cellular uptake, ECM penetration, antiphagocytosis, and antitumor effects both in vitro and in vivo.
Personalized Targeted Radioimmunotherapy with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] in Patients with Active Relapsed or Refractory Acute Myeloid Leukemia Results in Successful Donor Hematopoietic Cells Engraftment with the Timing of Engraftment Not Related to the Radiation Dose Delivered
Authors: Boglarka Gyurkocza, Rajneesh Nath, Hannah Choe, Stuart Seropian, Patrick J. Stiff, Sunil Abhyankar, Edward Agura, Mark Litzow, Benjamin K. Tomlinson, George L. Chen, Parameswaran Hari, Johnnie Orozco, Zaid S. Al-Kadhimi, Camille Abboud, Koen Van Besien, Mitchell Sabloff, Margarida Magalhaes Magalhaes-Silverman, James M. Foran, Michael W. Schuster, Partow Kebriaei, Moshe Y. Levy, Hillard M Lazarus, Sergio A. Giralt, Qing Liang, Mark S. Berger, Vijay Reddy, John M. Pagel
Journal: Blood (2020)
Analysis of the Global Methylation Profile of Accelerated and Blast Phase Myeloproliferative Neoplasms and Its Association with Response to Decitabine-Based Therapy
Authors: Raajit K. Rampal, Qin Yang, Richard P. Koche, Erin McGovern, Christopher Famulare, Rona Singer Weinberg, John Mascarenhas, Ross L. Levine, Ronald Hoffman, Maria E. Figueroa
Journal: Blood (2020)
Abstract PO-133: Breast tumors maintain a reservoir of subclonal diversity during primary expansion
Authors: Darlan Conterno Minussi, Michael Nicholson, Hanghui Ye, Alexander Davis, Kaile Wang, Emi Sei, Haowei Du, Mashiat Rabbani, Cheng Peng, Min Hu, Shanshan Bai, Thomas McDonald, Aislyn Schalck, Anna Casasent, Angelica Barrera, Hui Chen, Bora Lim, Banu Arun, Funda Meric-Bernstam, Franziska Michor, Nicholas Navin
Journal: Cancer Research (2020)

Abstract Our knowledge of copy number evolution during the expansion of primary breast tumors is limited. To investigate this process, we developed a single-cell, single-molecule DNA sequencing method and performed copy number analysis of 13,808 single cells from six triple-negative breast cancers (TNBCs) and two breast cancer cell lines. Our data shows that breast tumors and cell lines are comprised of a large milieu (17-26) of subclones that are organized into a few (4-8) major superclones. Phylogenetic analysis and mathematical modeling show that copy number evolution was ongoing during the expansion of the primary tumor, after the initial punctuated burst of genomic instability. By expanding single daughter cells in culture, we show that cancer cells re-diversify their genomes and do not retain isogenic properties. These data elucidate modes of evolution and show that TNBCs maintain a vast reservoir of subclonal copy number diversity during the expansion of the primary tumor mass. Citation Format: Darlan Conterno Minussi, Michael Nicholson, Hanghui Ye, Alexander Davis, Kaile Wang, Emi Sei, Haowei Du, Mashiat Rabbani, Cheng Peng, Min Hu, Shanshan Bai, Thomas McDonald, Aislyn Schalck, Anna Casasent, Angelica Barrera, Hui Chen, Bora Lim, Banu Arun, Funda Meric-Bernstam, Franziska Michor, Nicholas Navin. Breast tumors maintain a reservoir of subclonal diversity during primary expansion [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-133.
Abstract 306: Loss of a Disintegrin and Metalloproteinase-15 Impairs Fibroblast Activation Following Myocardial Infarction Resulting in Ventricular Rupture
Authors: Michael J Chute, Mengcheng Shen, Sayantan Jana, Wang Wang, Zamaneh Kassiri
Journal: Circulation Research (2020)

Background: Myocardial infarction (MI) occurs when blood flow to a region of the myocardium is interrupted. Over time, the damaged myocardium is replaced with scar tissue through activation of an inflammatory phase, followed by a reparative and a maturation phase. A disintegrin and metalloproteinase-15 (ADAM15) is a membrane-bound enzyme that is expressed in inflammatory cells and the heart, and its expression in the heart is increased following myocardial infarction. However, its function in heart disease has not yet been explored. We hypothesized that ADAM15 deficiency will impede the inflammatory response post-MI, which could reduce inflammation but also hinder scar formation causing adverse remodeling of the surviving myocardium. Methods: MI was induced in adult male wildtype (WT) and ADAM15-deficient ( Adam15 -/- ) mice by permanent ligation of the left anterior descending artery. LV structure, systolic and diastolic functions were assessed by echocardiography. Hearts were excised at 3-days or 1 week post-MI, processed for histological and molecular analyses. Fibrillar collagen organization was assessed by Second Harmonic Generation. Cardiac fibroblasts (cFBs) were isolated from WT or Adam15 -/- hearts, and subjected to ischemia (hypoxia + nutrient deletion) in vitro . Results: Adam15 -/- mice exhibited significantly compromised survival post-MI, mainly due to LV rupture. Cardiac contractility was reduced in Adam15 -/- compared to WT-MI mice. Collagen fibers in the scar tissue were distorted and scarce in Adam15 -/- MI hearts, associated with reduced levels of a major cross-linking enzyme, lysyl oxidase. In vitro, Adam15 -/- cFBs showed impaired myofibroblast transformation under ischemic conditions, suggesting attenuated fibroblast activation. Conclusion: Adam15 -deficiency impairs the wound healing process post-MI, leading to deleterious remodelling and LV rupture.
Orvacabtagene Autoleucel (orva-cel; JCARH125): A Fully Human BCMA-Targeted Second-Generation CAR T Cell Product Characterized By a Predominant Central Memory Phenotype with High in Vitro and In Vivo Proliferative Potential and Sustained In Vivo Persistence
Authors: Lucrezia Colonna, Garnet Navarro, Todd Devries, Valeria Beckett, Anthony Amsberry, Aditya Radhakrishnan, Julia Piasecki, Mark Heipel, Yan Li, Uma Kavita, Melissa G Works, Mirna Mujacic
Journal: Blood (2020)
Splenic Marginal Zone Lymphoma: French Registries Population-Based Treatment and Survival Analyses (2002-2014)
Authors: Marc Maynadie, Sophie Gauthier, Morgane Mounier, Côme Bommier, Sebastien Orazio, Hélène Rachou, Alain Monnereau, Xavier Troussard, Catherine Thieblemont
Journal: Blood (2020)
FRI0166 HIGH FREQUENCY OF KIDNEY STONES AND/OR NEPHROCALCINOSIS IN PRIMARY SJOGREN’S SYNDROME MIGHT ACCELERATE CHRONIC RENAL DYSFUNCTION DUE TO TUBULOINTERSTITIAL DISEASE
Authors: Y. Fujisawa, Y. Suzuki, T. Zoshima, S. Hara, K. Ito, I. Mizushima, H. Fujii, M. Kawano
Journal: Annals of the Rheumatic Diseases (2020)

Background: The renal involvement of primary Sjögren’s syndrome (pSS) is characterized by distal renal tubular acidosis (RTA), tubulointerstitial nephritis (TIN), and/or glomerulonephritis [1,2]. Kidney stones and nephrocalcinosis are presumably caused by subclinical distal tubular acidosis, but its clinical significance has not been clarified. Objectives: This study aimed to clarify the frequency and clinical features of patients with pSS with kidney stones and/or nephrocalcinosis. Methods: We examined 59 patients with anti SS-A/Ro positive pSS who underwent abdominal computed tomography and/or ultrasound between 1998 and 2019 at Kanazawa University Hospital. We identified 2 groups of patients with primary Sjögren’s syndrome: 1) patients with kidney stones and/or nephrocalcinosis (group A: n=19) and 2) those without kidney stones and/or nephrocalcinosis (group B: n=40), and retrospectively analyzed their clinical features. Results: Kidney stones and/or nephrocalcinosis were confirmed in 19 of 59 (32%) patients with pSS. The patients comprised 4 males and 55 females with an average age of 60 years (range, 30 to 83 years) and mean observation period of 96 months (range 1 to 336 months). Estimated glomerular filtration rate (eGFR) at the time of diagnostic imaging (group A vs group B: 71.5 ml/min/1.73 m 2 vs 82.8 ml/min/1.73 m 2 ; p=0.37) and eGFR at last follow up (group A vs group B: 59.3 ml/min/1.73 m 2 vs 74.7 ml/min/1.73 m 2 ;p=0.03) of group A were lower than those of group B and urinary β2-microgloblin (group A vs group B: 7222 μg/mL vs 437 μg/mL; p=0.01) and urinary N-acetyl-β-D-glucosaminidase (group A vs group B: 5.8 U/L vs 3.9 U/L; p=0.22) of group A were higher than those of group B, while serum electrolytes (sodium, potassium, chloride, calcium, phosphorus), fractional excretion of calcium (group A vs group B: 1.2% vs1.5%; p=0.916), ESSDAI (group A vs group B: 7.6 vs 4.3; p=0.069), and eGFR decrease rate were not significantly different. Conclusion: 32% patients with anti SS-A/Ro positive pSS had kidney stones and/or nephrocalcinosis in our cohort and their presence might accelerate chronic renal dysfunction due to tubulointerstitial disease (subclinical RTA or TIN). References: [1]Jain A et al. Renal involvement in primary Sjogren’s syndrome: a prospective cohort study. Rheumatol Int 2018; 38: 2251-62. [2]Jasiek M et al. A multicentre study of 95 biopsy-proven cases of renal disease in primary Sjögren’s syndrome. Rheumatology 2017; 56: 362-70. Acknowledgments: We thank Mr. John Gelblum for critical reading of the manuscript. Disclosure of Interests: None declared
Extensive Characterization of the Hemostatic Derangement Occurring in COVID-19 Patients Admitted to the Bergamo Hospital
Authors: Patricia Gomez-Rosas, Marina Marchetti, Eleonora Sanga, Sara Gamba, Cristina Verzeroli, Laura Russo, Francesco Restuccia, Andrea D'Alessio, Ezio Bonanomi, Marco Rizzi, Stefano Fagiuoli, Luca Lorini, Anna Falanga
Journal: Blood (2020)
Highly Efficient Gene Editing of Human Hematopoietic Stem Cells to Treat X-Linked Sideroblastic Anemia
Authors: Riguo Fang, Yingchi Zhang, Pengfei Yuan, Huihui Yang, Lingling Yu, Yongjian Zhang, Jia Shi, Guangzhen Ji, Jingliao Zhang, Wei Qi, Xiaofan Zhu, Dong Wei, Tao Cheng
Journal: Blood (2020)
Dose- and Schedule-Dependent Immunomodulatory Effects of the Novel Celmod Agent CC-92480 in Patients with Relapsed/Refractory Multiple Myeloma
Authors: Lilly Wong, Manisha Lamba, María Dolores Jiménez Nuñez, Daniel Bauer, Paul G. Richardson, Nizar J. Bahlis, Annette J. Vangsted, Karthik Ramasamy, Suzanne Trudel, Joaquín Martínez-Lopez, María-Victoria Mateos, Paula Rodriguez-Otero, Sagar Lonial, Rakesh Popat, Albert Oriol, Chatchada Karanes, Robert Z. Orlowski, Jesus G. Berdeja, Michael Pourdehnad, Daniel W. Pierce
Journal: Blood (2020)
Administration of Cells Engineered to Secrete Fviii-mcoET3 in Prenatal Sheep Recipients Results in Sustained Curative Fviii Plasma Levels for 3 Years after Birth, without Immune or Toxicity-Related Adverse Events
Authors: Martin Rodriguez, Brady Trevisan, Sunil George, Ritu M Ramamurthy, Andrew Rabah, Jordan E Shields, Denise Schwahn, Jorge Figueroa, Diane Meares, John Owen, Michael Gautreaux, Anthony Atala, Christopher B Doering, H. Trent Spencer, Christopher D Porada, M. Graca Almeida-Porada
Journal: Blood (2020)
Clonal Hematopoiesis in Patients Receiving Immune Checkpoint Inhibitor Therapy
Authors: Abhay Singh, Nuria Mencia-Trinchant, Elizabeth A. Griffiths, Matthew Gravina, Rutaba Tajammal, Mark G. Faber, Annmarie Nowak, Marc S. Ernstoff, LunBiao Yan, Megan M. Herr, Duane C. Hassane, Monica L. Guzman, Eunice S. Wang, Amanda Przespolewski, Swapna Thota
Journal: Blood (2020)
Outcomes of Pediatric Patients with JMML Following Unrelated Donor Transplant: The Impact of Donor KIR Gene Content and KIR Ligand Matching
Authors: Hemalatha G Rangarajan, Marcelo De Souza Pereira, Ruta Brazauskas, Michael R Verneris, Andrew St. Martin, Stephen R. Spellman, Dean Anthony Lee
Journal: Blood (2020)
Pre-Treatment Health-Related Quality of Life Parameters May Have Prognostic Impact in Elderly Patients with Mantle Cell Lymphoma. the Nordic Lymphoma Group MCL4 (LENA-BERIT) Experience
Authors: Åsa Lindberg, Christian Winther Eskelund, Alexandra Albertsson-Lindblad, Arne Kolstad, Anna Laurell, Riikka Räty, Kirsten Grønbæk, Christian H. Geisler, Mats Jerkeman
Journal: Blood (2020)
Comparison of Long‐Term Clinical Outcomes Between Spontaneous and Therapy‐Induced HBsAg Seroclearance
Authors: Jonggi Choi, Sun Yoo, Young‐Suk Lim
Journal: Hepatology (2020)

Background and Aims HBsAg seroclearance is considered a realistic goal in patients with chronic hepatitis B (CHB), known as “functional cure.” However, it remains elusive whether nucleos(t)ide analogue (NUC)‐induced HBsAg seroclearance, compared with spontaneous HBsAg seroclearance, differs in its association with favorable long‐term clinical outcomes. Approach and Results A total of 1,972 CHB patients with confirmed HBsAg seroclearance at least two consecutive times, 6 months apart, were retrospectively analyzed. Risks of HCC development and composite clinical events, including HCC, liver‐related death, and liver transplantation, were compared between spontaneous and NUC‐induced HBsAg seroclearance. Of 1,972 patients, mean patient age was 53.7 years, and 64.4% were men. Cirrhosis was present in 297 (15.1%) patients. HBsAg seroclearance was achieved spontaneously in 1,624 (82.4%) patients and by NUC treatment in 348 (17.6%). HCC developed in 49 patients, with an annual incidence of 0.38 of 100 person‐years (PY) during a median follow‐up of 5.6 years. With 336 propensity‐score–matched pairs, risks of HCC ( P = 0.52) and clinical events ( P = 0.14) were not significantly different between NUC‐induced and spontaneous HBsAg seroclearance. By multivariable analysis, NUC‐induced HBsAg seroclearance, compared with spontaneous HBsAg seroclearance, was not associated with the significantly higher risk of HCC (adjusted HR [AHR], 1.49; P = 0.26) and clinical events (AHR, 1.78; P = 0.06). Conclusions Risks of HCC and clinical events were not significantly different between spontaneous and NUC‐induced HBsAg seroclearance. Nonetheless, annual risk of HCC exceeds the recommended cutoff for HCC surveillance even after HBsAg seroclearance, suggesting that continued HCC surveillance is required.
Sex-Based Disparities in Outcome in Childhood Acute Lymphoblastic Leukemia (ALL): A Children's Oncology Group (COG) Report
Authors: Sumit Gupta, David T. Teachey, Meenakshi Devidas, Zhiguo Chen, Kimberly P. Dunsmore, Eric C Larsen, Kelly Maloney, Leonard A. Mattano, Stuart S. Winter, Andrew J Carroll, Nyla A Heerema, Michael J Borowitz, Brent L Wood, William L. Carroll, Naomi J Winick, Elizabeth A. Raetz, Mignon L. Loh, Stephen P. Hunger
Journal: Blood (2020)