tbuckley/cabot-search huggingface dataset:
Abstract 16885: Exposure to Heavy Metals Increases Cardiovascular Risk by Elevation of Serum Lipid Levels- a National Health and Nutrition Examination Survey Based Study
Authors: Olajide A Buhari, Adebayo C Atanda, Fitsumberhan Medhane, Robert T Faillace
Journal: Circulation (2018)

Introduction: Heavy metals, defined as metals with densities higher than 5g/cm3, can interact with various physiological processes in the body with cardiovascular consequences. We sought to gain a better understanding of the relationship between serum levels of heavy metals and serum total and LDL-cholesterol. Hypothesis: Serum total and LDL-cholesterol may be related to serum levels of heavy metals. Methods: a Cross-sectional survey using the NHANES 2009-2012 database. Age, Gender, were considered as covariates. Serum total cholesterol (TC; normal &lt;200 mg/dl) and LDL cholesterol (LDL-C; normal &lt; 100 mg/dl) were related to levels of lead, cadmium, and mercury. Results: We divided subjects into three tertiles, T1, T2 and T3 based on levels of heavy metals. The exposure for heavy metals was significantly different across all age groups and gender (P&lt;0.0001) therefore we adjusted for these variables. There was a significant difference in the level of LDL-C and TC from the first to the third tertile for lead with progressively increasing values (P &lt;0.0001). After adjusting for age and sex, the odds of having a higher TC was higher in T3 for lead when compared with T1 (OR 1.567,95CI1.376-1.786), the odds were also higher in T3 for mercury (OR 1.730,95CI 1.512-1.981) and cadmium (OR 1.412, 95CI1.184-1.700). Concerning LDL-C, the odds of having a higher LDL was more in T3 for lead when compared to T1( OR 1.225, 95CI 0.835-1.739), also the odds of having a higher LDL-C was higher in T2 for mercury (OR 1.233, 95CI 1.004-1.515). Compared to the reference group, the odds of having a higher TC level was statistically significant (p &lt; 0.01) in T3 for all the metals studied, and the odds of having a higher LDL cholesterol was more in the second tertile for mercury (p &lt; 0.01). Conclusions: Our study demonstrates increasing serum levels of heavy metals are significantly associated with increasing TC and LDL-C. This, in turn, may be associated with cardiovascular consequences in populations exposed to heavy metals such as areas with natural disaster water crises raising the consideration of screening for heavy metals as a risk for hyperlipidemia and cardiovascular disease.
Outcomes of Contact Tracing in San Francisco, California—Test and Trace During Shelter-in-Place
Authors: Darpun D. Sachdev, Hannah K. Brosnan, Michael J. A. Reid, Michelle Kirian, Stephanie E. Cohen, Trang Q. Nguyen, Susan Scheer
Journal: JAMA Internal Medicine (2020)

Regardless of Age, Obesity and Hypertension Increase Risks With COVID-19Older age has consistently been associated with higher mortality in patients with coronavirus disease 2019 (COVID-19). 1,2nfortunately, as shown by Cunningham et al 3 in this issue of JAMA Internal Medicine, COVID-19 does not spare young people.Using a national all-payer hospital database, the investigators identified 3222 nonpregnant adults aged 18 to 34 years who were admitted to US hospitals for COVID-19.Morbidity was substantial: 21% required intensive care, and 2.7% died.Mortality was higher among those who had obesity, hypertension, and male sex, as has been noted in general adult populations.Combined with what we know about the greater risk of older persons, what does this study tell us about COVID-19 and young adults?First, while young adults are much less likely than older persons to become seriously ill, if they reach the point of hospitalization, their risks are substantial.Second, obesity, hypertension, and male sex put patients of all ages at greater risk.As obesity and hypertension are preventable and treatable conditions, reducing the risk of serious COVID 19 illness should be added to the already long list of reasons to increase medical and public health efforts in young adults to promote healthful diets and increased exercise.Finally, the article by Cunningham et al 3 establishes that COVID-19 is a life-threatening disease in people of all ages and that social distancing, facial coverings, and other approaches to prevent transmission are as important in young adults as in older persons.
Melanocortin 1 receptor attenuates early brain injury following subarachnoid hemorrhage by controlling mitochondrial metabolism <i>via</i> AMPK/SIRT1/PGC-1α pathway in rats
Authors: Weilin Xu, Jun Yan, Umut Ocak, Cameron Lenahan, Anwen Shao, Jiping Tang, Jianmin Zhang, John H. Zhang
Journal: Theranostics (2020)

Mitochondria-mediated oxidative stress and apoptosis contribute greatly to early brain injury (EBI) following subarachnoid hemorrhage (SAH). This study hypothesized that activation of melanocortin 1 receptor (MC1R), using BMS-470539, attenuates EBI by controlling mitochondrial metabolism after SAH. Methods: We utilized BMS-470539, MSG-606, selisistat, and PGC-1α to verify the neuroprotective effects of MC1R. We evaluated short- and long-term neurobehavior after SAH. Western blotting, immunofluorescence, and Golgi staining techniques were performed to assess changes in protein levels. Results: The results of western blotting suggested that the expression of SIRT1 and PGC-1α were increased, reaching their peaks at 24 h following SAH. Moreover, BMS-470539 treatment notably attenuated neurological deficits, and also reduced long-term spatial learning and memory impairments caused by SAH. The underlying neuroprotective mechanisms of the BMS-470539/MC1R system were mediated through the suppression of oxidative stress, apoptosis, and mitochondrial fission by increasing the levels of SIRT1, PGC-1α, UCP2, SOD, GPx, Bcl-2, cyto-Drp1, and ATP, while decreasing the levels of cleaved caspase-3, Bax, mito-Drp1, ROS, GSH/GSSG, and NADPH/NADP+ ratios. The neuroprotective effects of the BMS-470539/MC1R system were significantly abolished by MSG-606, selisistat, and PGC-1α siRNA. Conclusions: The activation of MC1R with BMS-470539 significantly attenuated EBI after SAH by suppressing the oxidative stress, apoptosis, and mitochondrial fission through the AMPK/SIRT1/PGC-1α signaling pathway.
Risk of Gvhd and Survival in Patients with Acute Leukemia Who Were Bridged to Allogeneic Stem Cell Transplantation (alloSCT) with Venetoclax- Based Therapy
Authors: Akash Mukherjee, Denái R. Milton, Elias Jabbour, Naval Daver, Alison Gulbis, Celina Ledesma, Marina Konopleva, Courtney D. DiNardo, Farhad Ravandi, Tapan M. Kadia, Gheath Alatrash, Amin M. Alousi, May Daher, David Marin, Amanda L. Olson, Betul Oran, Partow Kebriaei, Neeraj Saini, Samer A. Srour, Uday R. Popat, Jin S. Im, Rohtesh Mehta, Gabriela Rondon, Hagop M. Kantarjian, Richard E. Champlin, Issa F. Khouri
Journal: Blood (2020)
Cannabinoid receptor type 2 promotes kidney fibrosis through orchestrating β-catenin signaling
Authors: Shan Zhou, Qinyu Wu, Xu Lin, Xian Ling, Jinhua Miao, Xi Liu, Chengxiao Hu, Yunfang Zhang, Nan Jia, Fan Fan Hou, Youhua Liu, Lili Zhou
Journal: Kidney International (2020)

The endocannabinoid system has multiple effects. Through interacting with cannabinoid receptor type 1 and type 2, this system can greatly affect disease progression. Previously, we showed that activated cannabinoid receptor type 2 (CB2) mediated kidney fibrosis. However, the underlying mechanisms remain underdetermined. Here, we report that CB2 was upregulated predominantly in kidney tubular epithelial cells in unilateral urinary obstruction and ischemia-reperfusion injury models in mice, and in patients with a variety of kidney diseases. CB2 expression was closely correlated with the progression of kidney fibrosis and accompanied by the activation of β-catenin. Furthermore, CB2 induced the formation of a β-arrestin 1/Src/β-catenin complex, which further triggered the nuclear translocation of β-catenin and caused fibrotic injury. Incubation with XL-001, an inverse agonist to CB2, or knockdown of β-arrestin 1 inhibited CB2-triggered activation of β-catenin and fibrotic injury. Notably, CB2 potentiated Wnt1-induced β-arrestin 1/β-catenin activation and augmented the pathogenesis of kidney fibrosis in mice with unilateral ischemia-reperfusion injury or folic acid-induced nephropathy. Knockdown of β-arrestin 1 inhibited the CB2 agonist AM1241-induced β-catenin activation and kidney fibrosis. By promoter sequence analysis, putative transcription factor binding sites for T-cell factor/lymphoid enhancer factor were found in the promoter regions of the CB2 gene regardless of the species. Overexpression of β-catenin induced the binding of T-cell factor/lymphoid enhancer factor-1 to these sites, promoted the expression of CB2, β-arrestin 1, and the proto-oncogene Src, and triggered their accumulation. Thus, the CB2/β-catenin pathway appears to create a reciprocal activation feedback loop that plays a central role in the pathogenesis of kidney fibrosis.
Superiority of Thiotepa-Containing Conditioning Regimens in Patients with Primary Diffuse Large B-Cell Lymphoma (DLBCL) of the Central Nervous System (CNS) Undergoing Autologous Hematopoietic Cell Transplantation (autoHCT)
Authors: Trent Wang, Michael Scordo, Kwang Woo Ahn, Stella Chen, Mohamed A. Kharfan-Dabaja, Alex F. Herrera, Mehdi Hamadani, Craig S. Sauter
Journal: Blood (2020)
Assessment of Hematologic and Coagulation Parameters As Predictive Value in COVID-19 with Unfavourable Evolution
Authors: Viola Maria Popov, Lelia Iliescu, Marius Ioan Balea, Daniela Georgeta Georgescu, Mihaela Andreescu, Horia Bumbea, Meilin Omer, Marius Lucian Aurel Balea, Catalina Parvu, Andra Bogdana Grigorie, Mihaela Popescu, Oana Patrinoiu, Ana Rus, Daniela Gologanu, Valentin Nedelcu, Geanina Ofiteru, Claudia Despan, Mihaela Niculae Badoiu, Adriana Badea, Oana Constantin, Lidia Felicia Mihai, Andreea Calen, Silvia Ion, Gabriel Adrian Popescu, Adriana Hristea, Bogdan Mastalier, Bogdan Diaconescu
Journal: Blood (2020)
Protein Energy Malnutrition Significantly Increases Mortality and Adverse Outcomes in Acute Myelogenous Leukemia (AML) Patients with Neutropenic Fever: Findings of a Nationwide Inpatient Sample Analysis
Authors: Binav Baral, Hafeez Shaka, Trilok Shrivastava, Shristi Upadhyay Banskota, Andres E Mendez-Hernandez, Maryam Zia
Journal: Blood (2020)
Mechanisms of vascular dysfunction in the interleukin-10–deficient murine model of preeclampsia indicate nitric oxide dysregulation
Authors: Hajrunisa Cubro, Karl A. Nath, Sonja Suvakov, Oscar Garcia-Valencia, Santosh Parashuram, Wendy M. White, Tracey L. Weissgerber, Meryl C. Nath, Natasa M. Milic, Fernando Sontag, Livius V. d’Uscio, Yi Zhu, James L. Kirkland, Tamar Tchkonia, Mariam P. Alexander, Reade A. Quinton, Zvonimir S. Katusic, Joseph P. Grande, Vesna D. Garovic
Journal: Kidney International (2020)
Engineered iPSC-Derived NK Cells Expressing Recombinant CD64 for Enhanced ADCC
Authors: Kate Dixon, Robert Hullsiek, Kristin Snyder, Zachary Davis, Melissa Khaw, Tom Lee, Hui-Yi Chu, Ramzey Abujarour, Jason Dinella, Paul Rogers, Ryan Bjordahl, Jeffrey S. Miller, Bahram Valamehr, Jianming Wu, Bruce Walcheck
Journal: Blood (2020)
Abstract 464: Dynamic Regulation of the Epidermal Growth Factor Receptor Protein Interactome via β1-adrenergic Receptor-mediated Transactivation in Cardiomyocytes
Authors: Jeanette Einspahr
Journal: Circulation Research (2020)

Heart Failure (HF) is a chronic, progressive condition wherein the heart cannot perfuse adequate amounts of blood and oxygen to meet the demands of metabolizing tissues. Gold standard HF therapeutics currently consist of a small repertoire of neurohormone modulators that still result in ~50% mortality within 5 years. Our ongoing goal is to develop new signaling modalities as refined HF therapeutics. We have shown that β1-adrenergic receptor (β1AR) stimulation rapidly induces epidermal growth factor receptor (EGFR)-dependent protein signaling responses in various regions of cardiomyocytes (CM). We hypothesize that differences in the subcellular localization and protein interactomes of EGFR following differential ligand stimulation modulate CM functions in distinct manners. To test this, we infected neonatal rat ventricular myocytes (NRVM) with adenoviruses encoding HA-β1AR and Flag-EGFR, stimulated them with vehicle, isoproterenol or EGF for 5 min and performed mass spectroscopy analysis of the Flag-EGFR immunoprecipitates. While hundreds of protein interactions were identified, one of the highly enriched subcellular groups belonged to mitochondrial proteins, for which there is no information regarding the role of EGFR in their regulation in CM. Via fractionation and digestion analyses, we have confirmed EGFR localization to the outer mitochondrial membrane in CM and have begun to assess the impact of EGFR on mitochondrial function. Transmission electron microcopy analysis of mitochondrial morphology show that CM-specific EGFR knockdown (CM-EGFR-KD) increases mitochondrial circularity and mitochondria/area without changes in other parameters including perimeter or cristae density, suggesting altered bioenergetic potential. Indeed, extracellular flux (Seahorse) analysis of CM-EGFR-KD versus control CM revealed that CM-EGFR-KD increased maximal and reserve capacities and a trend toward increased ATP production. Elucidating the mechanism(s) of EGFR localization to and association with proteins at CM mitochondria, as well as its impact on mitochondrial function normally or in response to catecholamine stimulation will provide insight into the potential utility of targeting mitochondrial EGFR to improve HF outcomes.
Current and future cancer staging after neoadjuvant treatment for solid tumors
Authors: David R. Byrd, James D. Brierley, Thomas P. Baker, Daniel C. Sullivan, Donna M. Gress
Journal: CA A Cancer Journal for Clinicians (2020)

Abstract Until recently, cancer registries have only collected cancer clinical stage at diagnosis, before any therapy, and pathological stage after surgical resection, provided no treatment has been given before the surgery, but they have not collected stage data after neoadjuvant therapy (NAT). Because NAT is increasingly being used to treat a variety of tumors, it has become important to make the distinction between both the clinical and the pathological assessment without NAT and the assessment after NAT to avoid any misunderstanding of the significance of the clinical and pathological findings. It also is important that cancer registries collect data after NAT to assess response and effectiveness of this treatment approach on a population basis. The prefix y is used to denote stage after NAT. Currently, cancer registries of the American College of Surgeons' Commission on Cancer only partially collect y stage data, and data on the clinical response to NAT ( yc or posttherapy clinical information) are not collected or recorded in a standardized fashion. In addition to NAT, nonoperative management after radiation and chemotherapy is being used with increasing frequency in rectal cancer and may be expanded to other treatment sites. Using examples from breast, rectal, and esophageal cancers, the pathological and imaging changes seen after NAT are reviewed to demonstrate appropriate staging.
위 및 식도 정맥류 출혈시 경내경정맥 간내문맥간정맥 단락술의 치료효과
Authors: 김영탁, 권혁만, 김대현, 금민수, 권영오, 김성국, 최용환, 정준모, 김용주 ( Young Tak Kim), Hyek Man kwen, Dae Hyun Kim, Min Su Kum, Young Oh Kwen, Sung kook kim, Yong Hwan Choi, Joon Mo Chung, Yong Joo kim
Journal: Clinical and Molecular Hepatology (1996)

Background/Aims:Transjugular intrahepatic portosystemic shunt(TIPS) is a promising method of treatment for gastric and esophageall variceal bleeding. Immediate technical and short-term clinical results have been reportn!. This study is performed to evaluate long-term outcome after TIPS in patients who underwent the pracedure for variceal bleeding. Methods:Forty patients who underwent TIPS hetween August 1991 and February 199S were followed up by clinical examination, upper gastrointestina! Endoscopy and Duplex sonogrphy. Results:The mean portohepatic pressure gradient prior to TIPS was 30.1+ 8.7cmH ancl dropped to 16.6+ 6.7cmH2O after shunt(p<0.001). The cumulative survival rate was 67.5% at 6 months. 57.4% at 1 year, 37.1% at 2 years and 26.8% at 3 years.  Survival after TIPS was inversely related to Child-Pugh class. The incidence of recurrent variceal bleeding was 25%. The causes of death were hepatic failure(53.6 %), recurrent variceal bleeding(28.6'%), sepsis(7.1 %) and unknown causes(10.7'%). Conelueien:TIPS is an effective method for treatment of variceal bleeding in unsuccessful cases by other treatments including endoscopic therapy and the most important prognostic factor is preprocedual hepatic resenre(Child-Pugh class), TIPS by itself is not defioite therapy, but in combination with careful follow-up surveillance and percutaneous shunt revision is very effective therapeutic strategy. TIPS is particularly valuable in tlreating patients with variceal bleeding hefor liver transplantation and in treating patients with poor liver function.
Post-Traumatic Stress Disorder (PTSD) Symptoms in Patients with Acute Myeloid Leukemia (AML)
Authors: Hermioni L. Amonoo, Areej El-Jawahri, Thomas W. LeBlanc, Alison R. Kavanaugh, Jason A. Webb, Lara Traeger, Annemarie D. Jagielo, Dagny M. Vaughn, Madeleine Elyze, Regina M. Longley, Amir T. Fathi, Gabriela S. Hobbs, Andrew M. Brunner, Nina R. O'Connor, Selina M. Luger, Jillian Gustin, Bhavana Bhatnagar, Nora K. Horick
Journal: Blood (2020)
Unmet Needs in AL Amyloidosis: Outcomes in the Modern Era Among the Highest Risk, Newly Diagnosed AL Amyloidosis Patients
Authors: Angela Dispenzieri, Shaji K. Kumar, Francis K. Buadi, Martha Q. Lacy, David Dingli, Yi L. Hwa, Amie Fonder, Miriam A. Hobbs, Suzanne R. Hayman, Taxiarchis Kourelis, Rahma M Warsame, Eli Muchtar, Nelson Leung, Prashant Kapoor, Martha Grogan, Yi Lin, Ronald S. Go, Wilson I Gonsalves, Mustaqeem A. Siddiqui, Robert A. Kyle, John A. Lust, S. Vincent Rajkumar, Morie A Gertz
Journal: Blood (2020)
Bioinformatics Analysis of Differently Expressed Mirnas in CD5 Positive Relapsed and Refractory Diffuse Large B-Cell Lymphoma and Their Potential Theoretical and Clinical Investigations
Authors: Qian Zhang, Chao Xue, Xin Wang, Kang Lu, Xueling Ge, Xiao Lv, Lingyan Zhang, Hongzhi Xu, Yujie Jiang
Journal: Blood (2020)
Adoptive Cord Blood T Regulatory Cell Therapy Leads to Resolution of Inflammation and Decreased Proteinuria in Lupus Nephritis
Authors: Mi-Ae Lyu, Joseph D. Khoury, Meixian Huang, Mitsutaka Nishimoto, Ke Zeng, Li Li, Hongbing Ma, Tara Sadeghi, Simrit Parmar
Journal: Blood (2020)
Salvage Therapy with Low-Dose Ruxolitinib Led to a Significant Improvement in Bronchiolitis Obliterans Syndrome in Patients with cGvHD after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: He Huang, Yanmin Zhao, Guifang Ouyang, Jimin Shi, Yi Luo, Yamin Tan, Jian Yu, Huarui Fu, Xiaoyu Lai, Lizhen Liu
Journal: Blood (2020)
Routine Use of Gemtuzumab Ozogamicin in 7+3-Based Inductions for All "Non-Adverse" Risk AML
Authors: Gavin Hui, Abdullah Ladha, Edna Cheung, Caroline Berube, Steven Coutre, Jason Gotlib, Michaela Liedtke, Tian Y Zhang, Lori S. Muffly, Gabriel N. Mannis
Journal: Blood (2020)
Venetoclax Therapy for Relapsed and Treatment Refractory AML: Clinical Outcomes and Molecular Predictors
Authors: Maximilian Stahl, Kamal Menghrajani, Andriy Derkach, Alexander Chan, Wenbin Xiao, Jacob L Glass, Amber C. King, Anthony Daniyan, Christopher Famulare, Bernadette M. Cuello, Omar Abdel-Wahab, Ross L. Levine, Aaron D Viny, Eytan M. Stein, Mikhail Roshal, Martin S. Tallman, Aaron D Goldberg
Journal: Blood (2020)
Ibrutinib Plus Fludarabine, Cyclophosphamide, and Rituximab As the Treatment for Chronic Lymphocytic Leukemia/ Small Lymphocytic Leukemia: A Single-Center Real World Study
Authors: Huayuan Zhu, Hui Shen, Yilian Yang, Chong-Yang Ding, Yeqin Sha, Hongling Mi, Jingyan Qiu, Ruize Chen, Yujie Wu, Chun Qiao, Li Wang, Lei Fan, Wei Xu, Jianyong Li
Journal: Blood (2020)
Safety, Pharmacokinetics and Activity of CA-4948, an IRAK4 Inhibitor, for Treatment of Patients with Relapsed or Refractory Hematologic Malignancies: Results from the Phase 1 Study
Authors: Grzegorz S. Nowakowski, Lori A. Leslie, Anas Younes, Allison C. Rosenthal, Matthew A. Lunning, Krish Patel, Daniel J. Landsburg, Elizabeth Martinez, Reinhard von Roemeling, Christopher Lieberman, Han W. Tun
Journal: Blood (2020)
Use of multiple period, cluster randomised, crossover trial designs for comparative effectiveness research
Authors: Karla Hemming, Monica Taljaard, Charles Weijer, Andrew B Forbes
Journal: BMJ (2020)

Many treatments are adopted into clinical practice without a solid evidence base and might be used heterogeneously across settings. Rigorous randomised controlled trials are therefore needed to inform decisions about the comparative effectiveness of treatments in common use. The mainstay of comparative effectiveness research is pragmatic trial design, which emphasises broad eligibility criteria, simple logistics, routinely collected outcome data, and cost efficient designs. Although treatment differences at the individual level might be small, they can become important when aggregated across large populations. To detect these small differences, very large trials are often required. In multiple period, cluster randomised, crossover trials, the study design randomises clusters (eg, hospitals) to exposure to different interventions in a randomly determined order, and is an attractive design for comparative effectiveness research. The trial design can be highly statistically efficient, compared with other competing designs, and can have many logistical advantages. Several prominent examples of this trial design have been published recently, yet practical guidance is lacking on how best to design these trials to ensure that they provide robust evidence. Some considerations include how to determine the frequency and number of crossovers, the importance of a time balanced design, how to determine the required sample size, and how to analyse appropriately. The justification for using this design (over a design randomising on the level of individual patients) also raises ethical concerns when used to evaluate individual level interventions without the prospective informed consent of individual participants. In this article, we outline the key methodological and ethical requirements needed for the robust design of multiple period, cluster randomised, crossover trials.
Reduced-Intensity Chemotherapy with Mini-Hyper-CVD Plus Inotuzumab Ozogamicin, with or without Blinatumomab, in Older Adults with Newly Diagnosed Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia: Results from a Phase II Study
Authors: Nicholas J. Short, Hagop M. Kantarjian, Farhad Ravandi, Xuelin Huang, Nitin Jain, Tapan M. Kadia, Joseph D. Khoury, Jeffrey L. Jorgensen, Sa A Wang, Yesid Alvarado, Jan A. Burger, Naval Daver, Gautam Borthakur, Courtney D. DiNardo, Marina Konopleva, Naveen Pemmaraju, Guillermo Garcia-Manero, William G. Wierda, Steven M. Kornblau, Jovitta Jacob, Meagan Rostykus, Monica Kwari, Caitlin R. Rausch, Christopher Loiselle, Anna Milton, Juan Rivera, Rebecca Garris, Susan M. O'Brien, Elias Jabbour
Journal: Blood (2020)