tbuckley/cabot-search huggingface dataset:
Sodium–glucose co‐transporter 2 inhibition in patients hospitalized for acute decompensated heart failure: rationale for and design of the <scp>EMPULSE</scp> trial
Authors: Jasper Tromp, Piotr Ponikowski, Afshin Salsali, Christiane E. Angermann, Jan Biegus, Jon Blatchford, Sean P. Collins, João Pedro Ferreira, Claudia Grauer, Mikhail Kosiborod, Michael E. Nassif, Mitchell A. Psotka, Martina Brueckmann, John R. Teerlink, Adriaan A. Voors
Journal: European Journal of Heart Failure (2021)

Treatment with sodium-glucose co-transporter 2 (SGLT2) inhibitors improves outcomes in patients with chronic heart failure (HF) with reduced ejection fraction. There is limited experience with the in-hospital initiation of SGLT2 inhibitors in patients with acute HF (AHF) with or without diabetes. EMPULSE is designed to assess the clinical benefit and safety of the SGLT2 inhibitor empagliflozin compared with placebo in patients hospitalized with AHF. EMPULSE is a randomized, double-blind, parallel-group, placebo-controlled multinational trial comparing the in-hospital initiation of empagliflozin (10 mg once daily) with placebo. Approximately 500 patients admitted for AHF with dyspnoea, signs of fluid overload, and elevated natriuretic peptides will be randomized 1:1 stratified to HF status (de-novo and decompensated chronic HF) to either empagliflozin or placebo at approximately 165 sites across North America, Europe and Asia. Patients will be enrolled regardless of ejection fraction and diabetes status and will be randomized during hospitalization and after stabilization (between 24 h and 5 days after admission), with treatment continued up to 90 days after initiation. The primary outcome is clinical benefit at 90 days, consisting of a composite of all-cause death, HF events, and ≥5 point change from baseline in Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS), assessed using a 'win-ratio' approach. Secondary outcomes include assessments of safety, change in KCCQ-TSS from baseline to 90 days and change in natriuretic peptides from baseline to 30 days. The EMPULSE trial will evaluate the clinical benefit and safety of empagliflozin in patients hospitalized for AHF.
Trends in the incidence of diagnosed diabetes: a multicountry analysis of aggregate data from 22 million diagnoses in high-income and middle-income settings
Authors: Dianna J Magliano, Lei Chen, Rakibul M Islam, Bendix Carstensen, Edward W Gregg, Meda E Pavkov, Linda J Andes, Ran Balicer, Marta Baviera, Elise Boersma-van Dam, Gillian L Booth, Juliana C N Chan, Yi Xian Chua, Sandrine Fosse-Edorh, Sonsoles Fuentes, Hanne L Gulseth, Romualdas Gurevicius, Kyoung Hwa Ha, Thomas R Hird, György Jermendy, Mykola D Khalangot, Dae Jung Kim, Zoltán Kiss, Victor I Kravchenko, Maya Leventer-Roberts, Chun-Yi Lin, Andrea O Y Luk, Manel Mata-Cases, Didac Mauricio, Gregory A Nichols, Mark M Nielen, Deanette Pang, Sanjoy K Paul, Catherine Pelletier, Santa Pildava, Avi Porath, Stephanie H Read, Maria Carla Roncaglioni, Paz Lopez-Doriga Ruiz, Marina Shestakova, Olga Vikulova, Kang-Ling Wang, Sarah H Wild, Naama Yekutiel, Jonathan E Shaw
Journal: The Lancet Diabetes & Endocrinology (2021)
β-Lapachone induces DNA damage response and radiosensitizes cancer cells dependently on NQO1 expression.
Authors: Se-Hee Son, Seong-Yun Jeong, Sung-Jin Park, Joohee Jung, So Lyoung Yi, Do Young Song, Heon Joo Park, Si Yeol Song, Eun Kyung Choi
Journal: Cancer Research (2008)

2674  β-Lapachone (β-lap) is a novel plant-derived anticancer agent known to be bioactivated by NADP(H): quinone oxidoreductase 1 (NQO1), an enzyme overexpressed in a variety of tumors. Although β-lap is currently in phase II clinical trials as a very promising agent, the accurate mechanism in the cytotoxicity and radiosensitization has not been elucidated. In this study, we show that β-lap induced DNA damage response during apoptosis. Ataxia telangiectasia mutated (ATM) and Chk2 were activated and γ-H2AX was induced by β-lap treatment in cells overexpressing NQO1, but not in cells lacking NQO1. KU55933, a specific inhibitor of ATM compromised the β-lap-induced DNA damage response, suggesting that β-lap-induced DNA damage response is dependent on ATM pathway. Furthermore, β-lap-induced DNA damage response was inhibited by dicumarol, an inhibitor of NQO1, demonstrating that NQO1 is involved in β-lap-induced DNA damage response. β-lap enhanced radiation-induced DNA damage response and cytotoxicity in NQO1-overexpressing cells, but not in cells without NQO1 expression, indicating that NQO1 might play a role for the radiosensitization mediated by β-lap. These results suggest that treatment of β-lap induces DNA damage response in cancer cells dependently on NQO1 expression, and the property of β-lap inducing DNA damage might contribute to radiosensitize cancer cells.
The Costs of Postoperative Delirium
Authors: Mark R. Katlic, Thomas N. Robinson
Journal: JAMA Surgery (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Associations between Blood Lead Levels and Coronary Artery Stenosis Measured Using Coronary Computed Tomography Angiography
Authors: Suwhan Kim, Wonyang Kang, Seunghyeon Cho, Dae-Young Lim, Yeongjae Yoo, Ryoung Jin Park, Byung Chan Lee, Jai-Dong Moon, Won-Ju Park
Journal: Environmental Health Perspectives (2021)
Elevated Urate Levels Do Not Alter Bone Turnover Markers: Randomized Controlled Trial of Inosine Supplementation in Postmenopausal Women
Authors: Nicola Dalbeth, Anne Horne, Borislav Mihov, Angela Stewart, Gregory D. Gamble, Tony R. Merriman, Lisa K. Stamp, Ian R. Reid
Journal: Arthritis & Rheumatology (2021)

Objective Observational studies have consistently demonstrated that serum urate level positively correlates with bone mineral density (BMD). We undertook this study to determine whether moderate hyperuricemia induced by inosine supplements influences bone turnover markers in postmenopausal women over a 6‐month period. Methods One hundred twenty postmenopausal women were recruited for a 6‐month randomized, double‐blind, placebo‐controlled trial. Key exclusion criteria were osteoporosis, previous fragility fracture, bisphosphonate therapy, gout, kidney stones, and a urine pH level of ≤5.0. Participants were randomized in a 1:1 ratio to receive placebo or inosine. The coprimary end points were change in levels of N‐propeptide of type I procollagen (PINP) and change in levels of β‐C‐telopeptide of type I collagen (β‐CTX). Change in BMD, as measured by dual x‐ray absorptiometry, was an exploratory end point. Results Administration of inosine led to a significant increase in serum urate concentration over the study period ( P &lt; 0.0001 for all follow‐up time points). At week 26, the mean change in serum urate concentration was +0.13 mmoles/liter (+2.2 mg/dl) in the inosine group and 0.00 mmoles/liter (0 mg/dl) in the placebo group. There was no difference in PINP or β‐CTX levels between groups over the 6 months. There were no significant changes in bone density between groups over the 6 months. Adverse events and serious adverse events were similar between the 2 groups. Conclusion This clinical trial shows that although inosine supplementation leads to sustained increases in serum urate levels over a 6‐month period, it does not alter markers of bone turnover in postmenopausal women. These findings do not support the concept that urate has direct biologic effects on bone turnover.
Age at Initiation of Cigarette Use in a Nationally Representative Sample of US Youth, 2013-2017
Authors: Adriana Pérez, Roi San N’hpang, Elizabeth Callahan, Meagan Bluestein, Arnold E. Kuk, Baojiang Chen, Cheryl L. Perry, Melissa B. Harrell
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Cigarettes are still a commonly used tobacco product among youth despite recent declines in cigarette use. <h3>Objective</h3> The aim of this study was to prospectively estimate the age of cigarette use initiation among youth (aged 12-17 years) overall, by sex, and by race/ethnicity. <h3>Design, Setting, and Participants</h3> This cohort study used data from waves 1 through 4 of the nationally representative Population Assessment of Tobacco and Health (PATH) study, conducted from September 12, 2013, to January 3, 2018. Two subpopulations of youth were assessed: (1) those nonsusceptible to cigarette use and (2) never users of cigarettes at their first wave of PATH participation. Weighted interval-censoring survival analyses were used to prospectively estimate the age of initiation of cigarette use outcomes. Weighted interval-censoring Cox proportional hazard models were used to estimate differences in the age of initiation by sex and by race/ethnicity. Statistical analyses were performed from October 7, 2019, to May 1, 2020. <h3>Exposures</h3> Differences in the age of initiation by sex and race/ethnicity. <h3>Main Outcomes and Measures</h3> Age of initiation of susceptibility to cigarette use, ever use, past 30-day use, and fairly regular cigarette use overall, by sex, and by race/ethnicity. <h3>Results</h3> A total of 15 776 youth never users and, among them, 11 022 youth who were nonsusceptible to cigarette use, were included in this study (weighted mean [SE] age, 13.5 [0.01] years; 58.6% [SE, 0.46%] non-Hispanic White; and 51.0% [SE, 0.32%] boys) and 15 776 were never users of cigarettes at their first wave of PATH participation (weighted mean [SE] age, 13.7 [0.01] years; 55.0% [SE, 0.29%] non-Hispanic White; and 51.0% [SE, 0.15%] boys). By age 18 years, among those who were nonsusceptible, 46.2% (95% CI, 44.3%-48.2%) became susceptible to cigarette use. Among never users by age 18, 24.3% (95% CI, 20.7%-28.0%) initiated ever cigarette use, 16.4% (95% CI, 14.5%-18.3%) initiated past 30-day cigarette use, and 3.5% (95% CI, 2.3%-4.7%) initiated fairly regular cigarette use. Boys had a higher risk of initiating ever (hazard ratio [HR], 1.21; 95% CI, 1.08-1.36) and past 30-day cigarette use (HR, 1.27; 95% CI, 1.10-1.47) at earlier ages compared with girls. Non-Hispanic White youth had a higher risk of an earlier age of initiation of susceptibility to cigarette use (HR, 0.77; 95% CI, 0.68-0.88), ever use (HR, 0.59; 95% CI, 0.49-0.71), past 30-day use (HR, 0.64; 95% CI, 0.52-0.77), and fairly regular cigarette use (HR, 0.25; 95% CI, 0.14-0.43) compared with non-Hispanic Black youth. <h3>Conclusions and Relevance</h3> The results of this cohort study suggest that, despite current interventions and existing laws, a large number of youth initiated cigarette use before the legal age to purchase tobacco products.
Programmable immune activating electrospun fibers for skin regeneration
Authors: Lu Chen, Liucheng Zhang, Hongbo Zhang, Xiaoming Sun, Dan Liu, Jianming Zhang, Yuguang Zhang, Liying Cheng, Hélder A. Santos, Wenguo Cui
Journal: Bioactive Materials (2021)

Immune cells play a crucial regulatory role in inflammatory phase and proliferative phase during skin healing. How to programmatically activate sequential immune responses is the key for scarless skin regeneration. In this study, an "Inner-Outer" IL-10-loaded electrospun fiber with cascade release behavior was constructed. During the inflammatory phase, the electrospun fiber released a lower concentration of IL-10 within the wound, inhibiting excessive recruitment of inflammatory cells and polarizing macrophages into anti-inflammatory phenotype "M2c" to suppress excessive inflammation response. During the proliferative phase, a higher concentration of IL-10 released by the fiber and the anti-fibrotic cytokines secreted by polarized "M2c" directly acted on dermal fibroblasts to simultaneously inhibit extracellular matrix overdeposition and promote fibroblast migration. The "Inner-Outer" IL-10-loaded electrospun fiber programmatically activated the sequential immune responses during wound healing and led to scarless skin regeneration, which is a promising immunomodulatory biomaterial with great potential for promoting complete tissue regeneration.
An Integrated Systems Biology Approach Identifies the Proteasome as a Critical Host Machinery for ZIKV and DENV Replication
Authors: Guang Song, Emily M. Lee, Jianbo Pan, Miao Xu, Hee-Sool Rho, Yichen Cheng, Nadia Whitt, Shu Yang, Jennifer Kouznetsova, Carleen Klumpp-Thomas, Samuel G. Michael, Cedric Moore, Ki-Jun Yoon, Kimberly M. Christian, Anton Simeonov, Wenwei Huang, Menghang Xia, Ruili Huang, Madhu Lal-Nag, Hengli Tang, Wei Zheng, Jiang Qian, Hongjun Song, Guo-li Ming, Heng Zhu
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract The Zika virus (ZIKV) and dengue virus (DENV) flaviviruses exhibit similar replicative processes but have distinct clinical outcomes. A systematic understanding of virus–host protein–protein interaction networks can reveal cellular pathways critical to viral replication and disease pathogenesis. Here we employed three independent systems biology approaches toward this goal. First, protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and 20,240 human proteins revealed multiple conserved cellular pathways and protein complexes, including proteasome complexes. Second, an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process. Third, high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds, including six proteasome inhibitors that suppress both ZIKV and DENV replication. Integrative analyses of these orthogonal datasets pinpoint proteasomes as critical host machinery for ZIKV/DENV replication. Our study provides multi-omics datasets for further studies of flavivirus–host interactions, disease pathogenesis, and new drug targets.
Abstract 17040: Selective Inhibition of Myocardial NADPH Oxidase with a Dominant-Negative Mutant of p67phox Attenuates Angiotensin II-Induced Cardiac Hypertrophy in Adult Transgenic Mice
Authors: Qiong Zhao, Guiqing Zhao, Chongxu Zhang, Xianyao Xu, Sudhahar Varadarajan, Norifumi Urao, Masuko Fukai, Tohru Fukai, Lei Xiao
Journal: Circulation (2011)

Angiotensin (Ang) II infusion not only induces hypertrophy and fibrosis in mouse heart, but also causes hypertension and inflammation in vivo. Thus, the precise mechanisms of Ang II-induced cardiac...
How the COVID-19 pandemic will change the future of critical care
Authors: Yaseen M. Arabi, Elie Azoulay, Hasan M. Al-Dorzi, Jason Phua, Jorge Salluh, Alexandra Binnie, Carol Hodgson, Derek C. Angus, Maurizio Cecconi, Bin Du, Rob Fowler, Charles D. Gomersall, Peter Horby, Nicole P. Juffermans, Jozef Kesecioglu, Ruth M. Kleinpell, Flavia R. Machado, Greg S. Martin, Geert Meyfroidt, Andrew Rhodes, Kathryn Rowan, Jean-François Timsit, Jean-Louis Vincent, Giuseppe Citerio
Journal: Intensive Care Medicine (2021)
Toll-like receptor 5-mediated signaling enhances liver regeneration in mice
Authors: Wen Zhang, Lei Wang, Xue-Hua Sun, Xian Liu, Yang Xiao, Jie Zhang, Ting Wang, Hui Chen, Yi-Qun Zhan, Miao Yu, Chang-Hui Ge, Chang-Yan Li, Guang-Ming Ren, Rong-Hua Yin, Xiao-Ming Yang
Journal: Military Medical Research (2021)

Abstract Background Toll-like receptor 5 (TLR5)-mediated pathways play critical roles in regulating the hepatic immune response and show hepatoprotective effects in mouse models of hepatic diseases. However, the role of TLR5 in experimental models of liver regeneration has not been reported. This study aimed to investigate the role of TLR5 in partial hepatectomy (PHx)-induced liver regeneration. Methods We performed 2/3 PHx in wild-type (WT) mice, TLR5 knockout mice, or TLR5 agonist CBLB502 treated mice, as a model of liver regeneration. Bacterial flagellin content was measured with ELISA, and hepatic TLR5 expression was determined with quantitative PCR analyses and flow cytometry. To study the effects of TLR5 on hepatocyte proliferation, we analyzed bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) expression with immunohistochemistry (IHC) staining. The effects of TLR5 during the priming phase of liver regeneration were examined with quantitative PCR analyses of immediate early gene mRNA levels, and with Western blotting analysis of hepatic NF-κB and STAT3 activation. Cytokine and growth factor production after PHx were detected with real-time PCR and cytometric bead array (CBA) assays. Oil Red O staining and hepatic lipid concentrations were analyzed to examine the effect of TLR5 on hepatic lipid accumulation after PHx. Results The bacterial flagellin content in the serum and liver increased, and the hepatic TLR5 expression was significantly up-regulated in WT mice after PHx. TLR5-deficient mice exhibited diminished numbers of BrdU- and PCNA-positive cells, suppressed immediate early gene expression, and decreased cytokine and growth factor production. Moreover, PHx-induced hepatic NF-κB and STAT3 activation was inhibited in Tlr5 −/− mice, as compared with WT mice. Consistently, the administration of CBLB502 significantly promoted PHx-mediated hepatocyte proliferation, which was correlated with enhanced production of proinflammatory cytokines and the recruitment of macrophages and neutrophils in the liver. Furthermore, Tlr5 −/− mice displayed significantly lower hepatic lipid concentrations and smaller Oil Red O positive areas than those in control mice after PHx. Conclusion We reveal that TLR5 activation contributes to the initial events of liver regeneration after PHx. Our findings demonstrate that TLR5 signaling positively regulates liver regeneration and suggest the potential of TLR5 agonist to promote liver regeneration.
Targeting the membrane-proximal C2-set domain of CD33 for improved CD33-directed immunotherapy
Authors: Colin D. Godwin, George S. Laszlo, Salvatore Fiorenza, Eliotte E. Garling, Tinh-Doan Phi, Olivia M. Bates, Colin E. Correnti, Benjamin G. Hoffstrom, Margaret C. Lunn, Olivier Humbert, Hans-Peter Kiem, Cameron J. Turtle, Roland B. Walter
Journal: Leukemia (2021)
Re: Maria S. Lindgren, Peter Bue, Nessn Azawi, et al. The DaBlaCa-13 Study: Short-term, Intensive Chemoresection Versus Standard Adjuvant Intravesical Instillations in Non–muscle-invasive Bladder Cancer—A Randomized Controlled Trial. Eur Urol 2020;78:856–62
Authors: Claudia Signorini, Massimo Maffezzini
Journal: European Urology (2021)
Bioresorbable Metals for Biomedical Applications: From Mechanical Components to Electronic Devices
Authors: Hanjun Ryu, Min‐Ho Seo, John A. Rogers
Journal: Advanced Healthcare Materials (2021)

Abstract Bioresorbable metals and metal alloys are of growing interest for myriad uses in temporary biomedical implants. Examples range from structural elements as stents, screws, and scaffolds to electronic components as sensors, electrical stimulators, and programmable fluidics. The associated physical forms span mechanically machined bulk parts to lithographically patterned conductive traces, across a diversity of metals and alloys based on magnesium, zinc, iron, tungsten, and others. The result is a rich set of opportunities in healthcare materials science and engineering. This review article summarizes recent advances in this area, starting with an historical perspective followed by a discussion of materials options, considerations in biocompatibility, and device applications. Highlights are in system level bioresorbable electronic platforms that support functions as diagnostics and therapeutics in the context of specific, temporary clinical needs. A concluding section highlights challenges and emerging research directions.
Sex Differences in Cognitive Decline Among US Adults
Authors: Deborah A. Levine, Alden L. Gross, Emily M. Briceño, Nicholas Tilton, Bruno J. Giordani, Jeremy B. Sussman, Rodney A. Hayward, James F. Burke, Stephanie Hingtgen, Mitchell S. V. Elkind, Jennifer J. Manly, Rebecca F. Gottesman, Darrell J. Gaskin, Stephen Sidney, Ralph L. Sacco, Sarah E. Tom, Clinton B. Wright, Kristine Yaffe, Andrzej T. Galecki
Journal: JAMA Network Open (2021)

Sex differences in dementia risk are unclear, but some studies have found greater risk for women.
Maintenance Treatment With Long-Acting Injectable Antipsychotics for People With Nonaffective Psychoses: A Network Meta-Analysis
Authors: Giovanni Ostuzzi, Federico Bertolini, Cinzia Del Giovane, Federico Tedeschi, Chiara Bovo, Chiara Gastaldon, Michela Nosé, Filippo Ogheri, Davide Papola, Marianna Purgato, Giulia Turrini, Christoph U. Correll, Corrado Barbui
Journal: American Journal of Psychiatry (2021)

Objective: This study compared relapse prevention and acceptability of long-acting injectable (LAI) antipsychotics in the maintenance treatment of adults with nonaffective psychoses. Methods: The authors searched MEDLINE, Embase, PsycINFO, CINAHL, CENTRAL, and online registers for randomized controlled trials published until June 2020. Relative risks and standardized mean differences were pooled using random-effects pairwise and network meta-analysis. The primary outcomes were relapse rate and all-cause discontinuation ("acceptability"). The quality of included studies was rated with the Cochrane Risk of Bias tool, and the certainty of pooled estimates was measured with GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Results: Of 86 eligible trials, 78 (N=11,505) were included in the meta-analysis. Regarding relapse prevention, most of the 12 LAIs included outperformed placebo. The largest point estimates and best rankings of LAIs compared with placebo were found for paliperidone (3-month formulation) and aripiprazole. Moderate to high GRADE certainty for superior relapse prevention compared with placebo was also found for (in descending ranking order) risperidone, pipothiazine, olanzapine, and paliperidone (1-month formulation). In head-to-head comparisons of LAIs, only haloperidol was inferior to aripiprazole, fluphenazine, and paliperidone. For acceptability, most LAIs outperformed placebo, with moderate to high GRADE certainty for (in descending ranking order) zuclopenthixol, aripiprazole, paliperidone (3-month formulation), olanzapine, flupenthixol, fluphenazine, and paliperidone (1-month formulation). In head-to-head comparisons, only LAI aripiprazole had superior acceptability to other LAIs (bromperidol, fluphenazine, paliperidone [1-month formulation], pipothiazine, and risperidone). Conclusions: LAI formulations of paliperidone (3-month formulation), aripiprazole, olanzapine, and paliperidone (1-month formulation) showed the highest effect sizes and certainty of evidence for both relapse prevention and acceptability. Results from this network meta-analysis should inform frontline clinicians and guidelines.
When Gonads Talk to the Heart: Sex Hormones and Cardiac Endocrine Function⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Aldo Clerico, Claudio Passino, Michele Emdin
Journal: Journal of the American College of Cardiology (2011)