tbuckley/cabot-search huggingface dataset:
Patient-Reported Outcomes and Frailty Among Participants in the NHLBI MDS Natural History Study
Authors: Gregory A. Abel, Donnie Hebert, Cecilia Lee, James M. Foran, Steven D. Gore, Wael Saber, Dana Elise Rollison, Eric Padron, Steffanie H. Wilson, Jason Thompson, Myron Waclawiw, Nancy L. DiFronzo, Mikkael A. Sekeres
Journal: Blood (2020)
EBV-EBNA1 constructs an immunosuppressive microenvironment for nasopharyngeal carcinoma by promoting the chemoattraction of Treg cells
Authors: Shaofen Huo, Yunfan Luo, Rui Deng, Xiong Liu, Jie Wang, Lu Wang, Bao Zhang, Fan Wang, Juan Lu, Xiangping Li
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Nasopharyngeal carcinoma (NPC) is primarily caused by the Epstein-Barr virus (EBV) infection in NPC endemic areas. EBNA1 is an EBV-encoded nuclear antigen, which plays a critical role in the maintenance and replication of EBV genome. However, the mechanisms of EBNA1-promoted NPC immune escape are unknown. Regulatory T (Treg) cells are among the key regulators in restraining antitumor responses. However, the mechanisms of accumulation of Treg cells in NPC have not been defined. This study attempted to identify the detailed mechanisms of EBNA1 functions as a tumor accelerator to promote NPC immune escape by enhancing chemoattraction of Treg cells. Methods mRNA profiles were determined by next-generation sequencing in NPC cells. In vitro and in vivo assays were performed to analyze the role of EBNA1 in regulation of recruitment of Treg cells. Colocation and coimmunoprecipitation analyzes were used to identify the SMAD3/c-JUN complex. Chromatin immunoprecipitation assay and dual luciferase reporter assays were designed to demonstrate c-JUN binding to miR-200a promoter and miR-200a targeting to CXCL12 3’Untranslated Regions. The hepatocellular carcinoma models were designed to demonstrate universality of the CXCL12-CXCR4-Treg axis in promoting immune evasion of various tumors. Result A novel molecular mechanism was identified that involves EBV-EBNA1-stimulated chemotactic migration of Treg cells toward NPC microenvironment by upregulation of the transforming growth factor-β1 (TGFβ1)-SMAD3-PI3K-AKT-c-JUN-CXCL12-CXCR4 axis and downregulation of miR-200a. EBV-EBNA1 promotes the chemoattraction of Treg cells by governing the protein–protein interactions of the SMAD3/c-JUN complex in a TGFβ1-dependent manner in vitro and in vivo. TGFβ1 suppresses miR-200a by enhancing the SMAD3/c-JUN complex. miR-200a negatively regulates the CXCL12 chemokine by direct targeting of the CXCL12 3’UTR region. However, CXCL12 acts as the target gene of miR-200a and as an inhibitor of miR-200a transcription, and inhibition of miR-200a by CXCL12 is mediated by c-JUN, which directly binds to the miR-200a promoter and forms a c-JUN-miR-200a-CXCL12-c-JUN feedback loop. In addition, enhanced CXCL12 efficiently attracts CXCR4-positive Treg cells to remodel an immunosuppressive microenvironment. Conclusions EBV-EBNA1 promotes chemotactic migration of Treg cells via the TGFβ1-SMAD3-PI3K-AKT-c-JUN-miR-200a-CXCL12-CXCR4 axis in the NPC microenvironment. These results suggest that EBV-EBNA1 may serve as a potential therapeutic target to reshape the NPC microenvironment.
Abstract 263: Loss of the RNA-binding Protein ZFP36L2 Results in Peri-partum Cardiomyopathy Through Dysregulation of the P53-mTOR Pathway
Authors: Yuki Tatekoshi, Hidemichi Kouzu, Jason S Shapiro, Hsiang-Chun Chang, Adam D Jesus, Paulina J Stanczyk, Issam Ben-Sahra, Perry Blackshear, Hossein Ardehali
Journal: Circulation Research (2020)

Introduction: A loss of function mutation in the mRNA binding protein ZFP36L2 has been associated with congenital heart diseases in humans, although the mechanism remains unclear. Objectives: We sought to elucidate the role of ZFP36L2 in the heart using mice with cardiac-specific ZFP36L2 deletion. Results: Cardiac-specific Zfp36l2 knockout (cs-L2KO) female mice exhibit a dramatic phenotype in which the majority of mice die after repeated pregnancies due to heart failure. We performed RNA-seq in H9c2 cells with ZFP36L2 KD, and found the expression of multiple mTOR pathway genes were altered, including marked repression of Redd1 and Sesn2 . Consistent with the RNA-seq data, the activity of mTORC1 was increased in cs-L2KO mouse hearts and in ZFP36L2 KD H9c2 cells. Loss of TSC2 mitigated mTORC1 hyperactivity in ZFP36L2 KD cells, indicating that ZFP36L2 regulates mTORC1 activity through the TSC2 complex. Overexpression of REDD1 rescued increased mTORC1 activity with ZFP36L2 KD, suggesting that ZFP36L2 regulates mTORC1, in-part through REDD1. Under total amino acid starvation, we observed higher p-S6K T389 levels in ZFP36L2 KD cells, and SESN2 overexpression mitigated p-S6K T389 , indicating loss of ZFP36L2 also regulates mTORC1 through amino acid sensing. p53 is a transcriptional activator of both REDD1 and SESN2, and we found that ZFP36L2 was required to maintain p53 levels by directly destabilizing MDM2 mRNA. Accordingly, administration of Nutlin3, an MDM2 inhibitor, reversed the reduction in p53, REDD1 and SESN2 protein levels, and prevented the increase in S6K phosphorylation in response to ZFP36L2 KD. Next, we treated pregnant mice with rapamycin, and cs-L2KO mice treated with rapamycin displayed significantly improved cardiac function after delivery. Finally, we analyzed human heart samples from patients with peri-partum cardiomyopathy and found ZFP36L2 protein to be significantly decreased and p-S6K T389 levels increased, compared to healthy controls. Conclusions: Our studies demonstrate that ZFP36L2 regulates mTORC1 activity through modifying p53 stability, and that the disruption of this pathway induces peri-partum cardiomyopathy. Inhibition of mTORC1 hyperactivity with rapamycin can be a potential therapy for this disease.
Outcomes of Adult Patients with Acute Lymphoblastic Leukemia Treated with a Modified CALGB 10102 Regimen in a Real World Setting
Authors: Margaux Wooster, Scott Isom, Leslie Renee Ellis, Dianna S. Howard, Megan Manuel, Rupali Bhave, Sarah Dralle, Susan Lyerly, Bayard L. Powell, Timothy S Pardee
Journal: Blood (2017)
Withdrawing Approval of Makena — A Proposal from the FDA Center for Drug Evaluation and Research
Authors: Christina Y. Chang, Christine P. Nguyen, Barbara Wesley, Jia Guo, Laura Lee Johnson, Hylton V. Joffe
Journal: New England Journal of Medicine (2020)

Withdrawing Approval of Makena The FDA’s Center for Drug Evaluation and Research has recommended withdrawing the approval of Makena for the prevention of recurrent preterm birth after a trial faile...
TLR7 and RIG-I dual-adjuvant loaded nanoparticles drive broadened and synergistic responses in dendritic cells in vitro and generate unique cellular immune responses in influenza vaccination
Authors: Randall Toy, M. Cole Keenum, Pallab Pradhan, Katelynn Phang, Patrick Chen, Chinwendu Chukwu, Lily Anh H. Nguyen, Jiaying Liu, Sambhav Jain, Gabrielle Kozlowski, Justin Hosten, Mehul S. Suthar, Krishnendu Roy
Journal: Journal of Controlled Release (2020)
Validity of Quantitative Measurements By the Joint Tissue Examination and Damage Exam (JADE) with Musculoskeletal Ultrasound for the Longitudinal Assessment of Hemophilic Arthropathy
Authors: Akram Mesleh Shayeb, Richard Barnes, Nicolas Gallastegui Crestani, Cris Hanacek, Peter Aguero, Andres Flores, Rebecca Kruse-Jarres, Bruno Steiner, Doris Quon, Cindy Bailey, Annette von Drygalski
Journal: Blood (2020)
Pegcetacoplan Is Superior to Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria Regardless of Prior Transfusion Requirement
Authors: Regis Peffault De Latour, Carlos M. de Castro, Jeffrey Szer, Kensuke Usuki, Peter Hillmen, Morag Griffin, Mohamed Hamdani, Temitayo Ajayi, Hisakazu Nishimori, Ilene C. Weitz
Journal: Blood (2020)
OP0131 Chloroquine myopathy: prevalence and clinical features (preliminary data)
Authors: E Casado, M Larrosa, J Gratacos, J Font, JM Martinez, C Tolosa
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To analyse the prevalence and clinical features of chloroquine myopathy in a cohort of out-patients in a Rheumatology Unit. <h3>Methods</h3> Prospective study of 119 patients (84 female and 35 male), aged 57.8 ± 13.7, taking antimalarials (112 chloroquine, 7 hydroxychloroquine) for more than 6 months. They were evaluated during 2 years. The underlying disease was RA in 69, connective tissue disease in 22, palindromic rheumatism in 14, spondyloarthropathy in 7 and other rheumatic disease in 7. Muscle enzymes were determined in all patients and an electromyography (EMG) was practised in patients with repeated increased determinations. Patients with altered EMG were biopsied. <h3>Results</h3> <i>Laboratory</i>: 18 patients (15%) had a repeated increase of muscle enzymes: LDH in 17 patients, CPK in 5 and aldolase in 1 patient. EMG: practised in 13 patients, showed a muscular involvement in 6. Two patients are pending and 3 were dead before the exam. <i>Muscle biopsy</i>: 6/7 patients had a chloroquine myopathy (optic and electronic microscopy); 1/7 patients had a steroid myopathy. Two patients (RA) with chloroquine myopathy had an associated inflammatory myositis. <i>Clinical features</i>: 6 patients with chloroquine myopathy (5 RA and 1 spondyloarthropathy) represents an accumalated prevalence (2 years) of 5%. The duration of treatment was36 ± 21 months (rest of the group 40 ± 31), with cumulative doses of 203 ± 25 g (rest of the group 305 ± 243 g). All patients presented weakness and had other simultaneous muscle involvement factors (1 cervical myelopathy, 2 hypothyroidism, 3 hypovitaminosis D and 1 prolonged bedrest) at clinical diagnosis. <h3>Conclusion</h3> Toxic chloroquine myopathy is not an excepcional event (accumulated prevalence 5%). When an increase of LDH and/or CPK is present we should to rule out this complication. The presence of other factor with muscle involvement probably makes worse the weakness and gets better its detection.
Computer Vision and Deep Learning Assisted Microchip Electrophoresis for Integrated Anemia and Sickle Cell Disease Screening
Authors: Ran An, Yuncheng Man, Shamreen Iram, Erdem Kucukal, Muhammad Noman Hasan, Ambar Solis-Fuentes, Allison Bode, Ailis Hill, Kevin Cheng, Yuning Huang, Sanjay Ahuja, Jane A. Little, Michael Hinczewski, Umut A. Gurkan
Journal: Blood (2020)
Mosunetuzumab Shows Promising Efficacy in Patients with Multiply Relapsed Follicular Lymphoma: Updated Clinical Experience from a Phase I Dose-Escalation Trial
Authors: Sarit E Assouline, Won Seog Kim, Laurie H. Sehn, Stephen J. Schuster, Chan Yoon Cheah, Loretta J. Nastoupil, Mazyar Shadman, Sung-Soo Yoon, Matthew J Matasar, Catherine Diefenbach, Gareth P. Gregory, Nancy L. Bartlett, Michael C. Wei, Michelle Y. Doral, Shen Yin, Raluca Negricea, Chi-Chung Li, Elicia M. Penuel, Huang Huang, L. Elizabeth Budde
Journal: Blood (2020)
FRI0232 Importance of the radiological studies in the diagnosis of the chronic low back pain
Authors: FP Pérez-Torres, D Ybañez-García, P Pérez-Caballero, M Morales, A Llópis
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Classify the radiological alterations in patients with chronic low back pain (LBP) and to determine their relationship with symptomatology, and value the contribution carried out in the classification by diagnostic groups. <h3>Methods</h3> A longitudinal study of patients that required specialised attendance in the period of time January 95–96 by LBP. All patients were carried a standard radiological study out and the found alterations were classified as alterations of the development and the statics, of the articulate space and of the bony density. Classified the patients in a retrospective way it was determined the contribution of the radiology like confirmed case, probable case, possible case and no case. A statistical study was realised determining absolute and relative frequencies, and χ<sup>2</sup> test with a level of trust of 95%. <h3>Results</h3> Of a total of 472 selected patients, 334 presented alterations of the static (70,8%) and it was a significant relationship between these alterations and all the diagnostic groups for a value of p &lt; 0.0001, except for the groups inflammatory illnesses and alterations for physical agents. Alterations of the articulate space in 362 cases (76,7%), with a significant relationship between these alterations and the spondyloarthropaty (p &lt; 0.001), degenerative modifications and bony illnesses (p &lt; 0.0001). Alterations of the bony density in 361 cases (76,4%), with a significant relationship for all the groups (p &lt; 0.001) except functional dysfunctions and physical agents. The value of the radiology in the classification of patients was useful (p &lt; 0.0001) in the spondyloarthropaty groups and anomalies of the development, it didn't have value (p &lt; 0.0001) in functional dysfunctions and physical agents. Orientation value as possible-probable case (p &lt; 0.0001) in the degenerative modifications groups and bony metabolic illnesses. <h3>Conclusion</h3> 1. Radiological signs predictor of classification are the sclerosis and the ankylosis of sacroiliac joint for the inflammatory illnesses, spondylolysis/spondylolisthesis for anomalies of the development and increase of the discal space for metabolic bony illnesses. 2. The radiology is useful to classify in the inflammatory illnesses and anomalies of the development, it hasn't value in the functional dysfunctions groups and alterations for physical agents, it has an orientation value in degenerative modifications groups and bony illnesses. 3. A 15% of the cases have bony alterations that aren't related with the simptomatology and the diagnosis. <h3>References</h3> Gehweiler JA, Daffner RH. Low back pain: the controversia of radiologic evaluation. AJR 1983;140:109–12 Suarez-Almazor ME, Belseck E, Russell AS, Mackel JV. Use of lumbar radiographs for the early diagnosis of low back pain. J Am Med Assoc. 1997;277:1782–6
Reduction in Transplantation Activity without Impairment in Outcomes in the Covid-19 Era- Data from the Sarah Cannon Blood Cancer Network (SCBCN)
Authors: Minoo Battiwalla, Carlos Bachier, Vikas Bhushan, Michael J. Eckrich, Alireza Eghtedar, Haydar Frangoul, Suman Kambhampati, Shahbaz Malik, Peter A. McSweeney, Jeremy Pantin, Aravind Ramakrishnan, Hana Safah, Paul J Shaughnessy, Betsy Blunk, Tonya Cox, Rocky Billups, Charles F. Lemaistre
Journal: Blood (2020)
Café au lait macules overlying segmental macular hyperpigmentation in a paediatric patient: an early sign for mosaic neurofibromatosis type 1
Authors: J. Zhang, W. Qin, S. Hua, M. Li, Y. Tang, Z. Yao
Journal: British Journal of Dermatology (2020)

The presentation of multiple cafe-au-lait macules (CALMs) in children is a common reason for referral to a dermatologist. Segmental CALMs, a subtype of CALMs, is usually limited to a specific part of the body. Mosaic neurofibromatosis type 1 (NF1; OMIM 162200) is a common congenital disorder associated with segmental CALMs with an incidence of about 1 case/40000 patients, which is lower than the prevalence of patients with germline NF1 mutations1,2 .
Antimullerian Hormone as a Serum Biomarker for Risk of Chemotherapy-Induced Amenorrhea
Authors: Kathryn J Ruddy, Daniel J Schaid, Anthony Batzler, Reena S Cecchini, Ann H Partridge, Aaron Norman, Louis Fehrenbacher, Elizabeth A Stewart, Emanuel Trabuco, Elizabeth Ginsburg, Fergus J Couch, Peter A Fasching, Celine Vachon, Patricia A Ganz
Journal: JNCI Journal of the National Cancer Institute (2020)

Antimullerian hormone (AMH) is a promising biomarker for ovarian reserve. In this study, we assessed AMH before and 1 year after initiation of adjuvant chemotherapy on National Surgical Adjuvant Breast and Bowel Project (NSABP)/NRG Oncology B-47 in female participants aged 42 years and younger (median age = 39 years). At baseline, median AMH was 1.2 ng/mL; 13 (4.7%) values were less than 0.1 ng/mL (the threshold for detectable levels, in the perimenopause and menopause range), and 57 values (20.6%) were less than 0.5 ng/mL. At 1 year, 215 (77.6%) were less than 0.1 ng/mL, and 264 (95.3%) were less than 0.5 ng/mL. Postchemotherapy menses were reported by 46.2% of participants. Multivariable logistic regression found that the odds of having postchemotherapy menses increased with younger age, higher body mass index, and higher prechemotherapy AMH, but not by trastuzumab administration or by the choice of chemotherapy (doxorubicin-cyclophosphamide followed by paclitaxel vs docetaxel-cyclophosphamide). We conclude that higher prechemotherapy AMH predicts a lower risk of chemotherapy-induced amenorrhea and that AMH 1 year after chemotherapy initiation is not informative in this setting because it is likely to be very low.
Splenomegaly in Adolescents and Adults with Sickle Cell Anemia in Tanzania Is Associated with Less Severe Disease
Authors: Neema Budodi Lubuva, Venee N. Tubman, Clara C Chamba, Erius Tebuka, Mbonea Yonazi, Furahini Tluway, Pius Magesa, Lucio Luzzatto, Julie Makani, Magdalena Lyimo
Journal: Blood (2017)
Burden, trends, and risk factors of esophageal cancer in China from 1990 to 2017: an up-to-date overview and comparison with those in Japan and South Korea
Authors: Si Yang, Shuai Lin, Na Li, Yujiao Deng, Meng Wang, Dong Xiang, Grace Xiang, Shuqian Wang, Xianghua Ye, Yi Zheng, Jia Yao, Zhen Zhai, Ying Wu, Jingjing Hu, Huafeng Kang, Zhijun Dai
Journal: Journal of Hematology & Oncology (2020)

Abstract Background The epidemiology of esophageal cancer (EC) can elucidate its causes and risk factors and help develop prevention strategies. We aimed to provide an overview of the burden, trends, and risk factors of EC in China from 1990 to 2017. We also investigated the differences between China, Japan, and South Korea and discussed the possible causes of the disparities. Methods We used the Global Burden of Disease Study 2017 to obtain data on incident cases, deaths, disability-adjusted life-year (DALY) cases, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALY rate of EC in China, Japan, and South Korea from 1990 to 2017. Trend analysis was performed using joinpoint analysis. We measured the associations between ASIR, ASDR, and age-standardized DALY rate and the socio-demographic index (SDI) for 1990–2017. We also analyzed the risk factors associated with EC deaths and DALYs. Results China recorded 234,624 (95% uncertainty intervals: 223,240–246,036) incident cases of and 212,586 (202,673–222,654) deaths from EC in 2017. The ASIR and ASDR declined from 1990 to 2017. Until 2017, the ASIR was 12.23, and ASDR was 11.25 per 100,000 persons. The DALYs were 4,464,980 (4,247,816–4,690,846) with an age-standardized rate of 222.58 per 100,000 persons in 2017. The ASIR, ASDR, and age-standardized DALY rate in China were twice those of Japan and South Korea. These three indicators showed a decreasing trend, whereas SDI increased, in all three countries from 1990 to 2017. Tobacco and alcohol use remained the major risk factors for EC death and DALYs, especially for men in China and women in Japan and South Korea. High body mass index (BMI) and low-fruit diet were the main risk factors for women in China. Conclusions The incident cases and deaths of EC in China, Japan, and South Korea increased from 1990 to 2017, whereas the ASIR, ASDR, and age-standardized DALY rate declined. China had the greatest burden of EC among three countries. SDI and aging along with tobacco use, alcohol use, high BMI, and low-fruit diet were the main risk factors of death and DALYs and should be paid more attention.
Abstract 338: Limited Reduction of Heart Rate Promotes Cardiac Regeneration by Switching the Energy Metabolic Mode in Cardiomyocytes
Authors: Jing Tan, Ming Yang, Haiping Wang, Yandi Wu, Yuanlong Li, Shijie Deng, Tongsheng Huang, Conghui Shen, Xinghui Li, Weibin Cai
Journal: Circulation Research (2020)

Aims: Lack of cardiac regeneration with robust fibrosis response to the acute myocardial injury is the main obstacle to clinical treatment of cardiovascular diseases in humans. Stimulating the proliferation of endogenous cardiomyocytes (CMs) and replacing the scarred tissue with new functional CMs is a potential therapeutic strategy to the patients with heart failure. Heart rate reduction (HRR) is regarded as an effective clinical treatment for myocardial infarction. However, the mechanism of HRR promoting the recovery of cardiac function after injury still remains controversial, and whether there is any endogenous CM proliferation induced by HRR is undefined. Methods and results: The beating of CMs was reduced in vitro and heart rate (HR) of adult mice and different animal models of myocardial injury were modulated by six antiarrhythmic drugs to determine the role of HR in CM proliferation and cardiac repair. RNA-seq, extracellular flux analysis, metabolic flux analysis, and metabonomics were used to study the CM metabolism after HR modulation. We verified that reducing the beating can induce CM proliferation both in vitro and in vivo physiologically, and HRR also promoted cardiac regenerative repair after myocardial injury as well, reversely, increasing HR showed the opposite effect. Mechanistically, HRR reduced energy metabolism requirements and total ATP production of CMs but switched energy metabolic mode that the proportion of ATP production from aerobic glycolysis was increased, while from fatty acid oxidation was decreased. The switching of energy metabolic mode in CMs occurred in synchrony with the changes of glycolytic enzymes activities, these enzymes, including PFKFB3, PKM2, GAPDH, induced G1/S transition for cell cycle re-entry of CMs by upregulating the expression of cyclin D and CDK4/6 and facilitate substrates into the biomass needed to produce a new cell by biosynthesis. This coordinating function of glycolytic enzymes contributed to CM proliferation. Conclusion: Together, these results demonstrate that reduction of heart rate promotes CM proliferation by switching the energy metabolic mode, and highlight the potential therapeutic role of HRR in regenerative medicine.
Follicular Lymphoma in Latin America: Real-World Experience from 763 Patients
Authors: Maria Alejandra Torres Viera, Brady E Beltran, Luis Villela Villela, Denisse A. Castro, Victoria Otero, Lorena Fiad, Camila Peña, Henry Idrobo, Myrna Candelaria, Alana Von Glasenapp, Ivan Perdomo, Maria Virginia Prates, Sally Rose Paredes, Fernando Pérez-Jacobo, Ana Ramirez-Ibarguen, Juan Alejandro Ospina Idarraga, Maria Elena Cabrera, Claudia Gajardo, Macarena Alejandra Roa Salinas, Catalina Díaz, Laura Silva Idárraga, Humberto Martínez Cordero, Melani Otañez, Fabiola Valvert, Efreen Montaño Figueroa, Marcos Di Stefano, Rosio Baena, Juan Antonio Choque, Virginia Abello, Cristaldo Nancy, Guilherme Fleury Perini, Luis E Malpica Castillo, Eduardo Sotomayor, Jorge J. Castillo
Journal: Blood (2020)
Higher Dose of CPX-351 Is Associated with Prolonged Hematologic Recovery: Results from an Interim Safety Analysis of the Randomized, Phase III AMLSG 30-18 Trial
Authors: Verena I Gaidzik, Verena Mayr-Benedikter, Daniela Weber, Anika Schrade, Jürgen Krauter, Juliane S. Walz, Holger Hebart, Beate S. Schultheis, Nadezda Basara, Elisabeth Dietl, Silke Kapp-Schwoerer, Michaela Feuring-Buske, Felicitas Thol, Michael Heuser, Stefan Faderl, Anthony J. Wagner, Maral Saadati, Julia Krzykalla, Axel Benner, Arnold Ganser, Konstanze Döhner, Peter Paschka, Hartmut Döhner
Journal: Blood (2020)