tbuckley/cabot-search huggingface dataset:
The mitochondrial peptidase, neurolysin, regulates respiratory chain supercomplex formation and is necessary for AML viability
Authors: Sara Mirali, Aaron Botham, Veronique Voisin, Changjiang Xu, Jonathan St-Germain, David Sharon, Fieke W. Hoff, Yihua Qiu, Rose Hurren, Marcela Gronda, Yulia Jitkova, Boaz Nachmias, Neil MacLean, Xiaoming Wang, Andrea Arruda, Mark D. Minden, Terzah M. Horton, Steven M. Kornblau, Steven M. Chan, Gary D. Bader, Brian Raught, Aaron D. Schimmer
Journal: Science Translational Medicine (2020)

Neurolysin (NLN) is a zinc metallopeptidase whose mitochondrial function is unclear. We found that NLN was overexpressed in almost half of patients with acute myeloid leukemia (AML), and inhibition of NLN was selectively cytotoxic to AML cells and stem cells while sparing normal hematopoietic cells. Mechanistically, NLN interacted with the mitochondrial respiratory chain. Genetic and chemical inhibition of NLN impaired oxidative metabolism and disrupted the formation of respiratory chain supercomplexes (RCS). Furthermore, NLN interacted with the known RCS regulator, LETM1, and inhibition of NLN disrupted LETM1 complex formation. RCS were increased in patients with AML and positively correlated with NLN expression. These findings demonstrate that inhibiting RCS formation selectively targets AML cells and stem cells and highlights the therapeutic potential of pharmacologically targeting NLN in AML.
Kidney tissue hypoxia dictates T cell–mediated injury in murine lupus nephritis
Authors: Ping-Min Chen, Parker C. Wilson, Justin A. Shyer, Margaret Veselits, Holly R. Steach, Can Cui, Gilbert Moeckel, Marcus R. Clark, Joe Craft
Journal: Science Translational Medicine (2020)

HIF-1 dictates effector function of infiltrating T cells in lupus, causing tissue damage that can be abrogated by its blockade in murine models.
Effects of Rivaroxaban on Thrombotic Events in Heart Failure Patients With Coronary Disease and Sinus Rhythm
Authors: Barry H. Greenberg, Stefan D. Anker, William M. Byra, John G. Cleland, Min Fu, Mihai Gheorghiade, Carolyn S. Lam, Mandeep R. Mehra, James D. Neaton, Christopher C. Nessel, Theodore E. Spiro, Dirk J. van Veldhuisen, Faiez Zannad
Journal: Circulation (2018)
Ultrasmall gold nanoparticles in cancer diagnosis and therapy
Authors: Miao Fan, Yu Han, Shutao Gao, Hongyu Yan, Lingzhi Cao, Zhenhua Li, Xing-Jie Liang, Jinchao Zhang
Journal: Theranostics (2020)

Due to their lower systemic toxicity, faster kidney clearance and higher tumor accumulation, ultrasmall gold nanoparticles (less than 10 nm in diameter) have been proved to be promising in biomedical applications. However, their potential applications in cancer imaging and treatment have not been reviewed yet. This review summarizes the efforts to develop systems based on ultrasmall gold nanoparticles for use in cancer diagnosis and therapy. First, we describe the methods for controlling the size and surface functionalization of ultrasmall gold nanoparticles. Second, we review the research on ultrasmall gold nanoparticles in cancer imaging and treatment. Specifically, we focus on the applications of ultrasmall gold nanoparticles in tumor visualization and bioimaging in different fields such as magnetic resonance imaging, photoacoustic imaging, fluorescence imaging, and X-ray scatter imaging. We also highlight the applications of ultrasmall gold nanoparticles in tumor chemotherapy, radiotherapy, photodynamic therapy and gene therapy.
Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity
Authors: Dylan J. Richards, Yang Li, Charles M. Kerr, Jenny Yao, Gyda C. Beeson, Robert C. Coyle, Xun Chen, Jia Jia, Brooke Damon, Robert Wilson, E. Starr Hazard, Gary Hardiman, Donald R. Menick, Craig C. Beeson, Hai Yao, Tong Ye, Ying Mei
Journal: Nature Biomedical Engineering (2020)
A hundred days into the coronavirus disease (COVID-19) pandemic
Authors: Ines Steffens
Journal: Eurosurveillance (2020)

Preview this article: A hundred days into the coronavirus disease (COVID-19) pandemic, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/25/14/eurosurv-25-14-1-1.gif
Microrobots: A Needle‐Type Microrobot for Targeted Drug Delivery by Affixing to a Microtissue (Adv. Healthcare Mater. 7/2020)
Authors: Seungmin Lee, Jin‐young Kim, Junyoung Kim, Ali Kafash Hoshiar, Jongeon Park, Sunkey Lee, Jonghyun Kim, Salvador Pané, Bradley J. Nelson, Hongsoo Choi
Journal: Advanced Healthcare Materials (2020)

In article number 1901697 by Hongsoo Choi and co-workers, a drug-loaded micro-robot can be attached to a target micro-tissue by swimming in a corkscrew motion with magnetic torque under a rotating magnetic field. The needle-type micro-robot has the potential to improve targeted drug delivery to a micro-tissue in vitro in physiological fluid environments.
Pan-cancer analysis of advanced patient tumors reveals interactions between therapy and genomic landscapes
Authors: Erin Pleasance, Emma Titmuss, Laura Williamson, Harwood Kwan, Luka Culibrk, Eric Y. Zhao, Katherine Dixon, Kevin Fan, Reanne Bowlby, Martin R. Jones, Yaoqing Shen, Jasleen K. Grewal, Jahanshah Ashkani, Kathleen Wee, Cameron J. Grisdale, My Linh Thibodeau, Zoltan Bozoky, Hillary Pearson, Elisa Majounie, Tariq Vira, Reva Shenwai, Karen L. Mungall, Eric Chuah, Anna Davies, Mya Warren, Caralyn Reisle, Melika Bonakdar, Gregory A. Taylor, Veronika Csizmok, Simon K. Chan, Zusheng Zong, Steve Bilobram, Amir Muhammadzadeh, Darryl D’Souza, Richard D. Corbett, Daniel MacMillan, Marcus Carreira, Caleb Choo, Dustin Bleile, Sara Sadeghi, Wei Zhang, Tina Wong, Dean Cheng, Scott D. Brown, Robert A. Holt, Richard A. Moore, Andrew J. Mungall, Yongjun Zhao, Jessica Nelson, Alexandra Fok, Yussanne Ma, Michael K. C. Lee, Jean-Michel Lavoie, Shehara Mendis, Joanna M. Karasinska, Balvir Deol, Ana Fisic, David F. Schaeffer, Stephen Yip, Kasmintan Schrader, Dean A. Regier, Deirdre Weymann, Stephen Chia, Karen Gelmon, Anna Tinker, Sophie Sun, Howard Lim, Daniel J. Renouf, Janessa Laskin, Steven J. M. Jones, Marco A. Marra
Journal: Nature Cancer (2020)
The Hi's and Lo's of Cytarabine in Acute Myeloid Leukemia
Authors: Justin M. Watts, Terrence Bradley
Journal: Clinical Cancer Research (2020)

Cytarabine is the backbone of AML therapy, but the dose used during induction has remained controversial. Using an intermediate dose of cytarabine, compared with conventional dose, was shown to improve disease-free and overall survival in adult patients in China up to age 55, particularly in patients with intermediate cytogenetic risk.See related article by Wei et al., p. 3154.
circPRRC2A promotes angiogenesis and metastasis through epithelial-mesenchymal transition and upregulates TRPM3 in renal cell carcinoma
Authors: Wei Li, Feng-Qiang Yang, Chen-Min Sun, Jian-Hua Huang, Hai-Min Zhang, Xue Li, Guang-Chun Wang, Ning Zhang, Jian-Ping Che, Wen-Tao Zhang, Yang Yan, Xu-Dong Yao, Bo Peng, Jun-Hua Zheng, Min Liu
Journal: Theranostics (2020)

Background: Circular RNAs (circRNAs) have been identified as essential regulators in a plethora of cancers. Nonetheless, the mechanistic functions of circRNAs in Renal Cell Carcinoma (RCC) remain largely unknown. Methods: In this study, we aimed to identify novel circRNAs that regulate RCC epithelial-mesenchymal transition (EMT), and to subsequently determine their regulatory mechanisms and clinical significance. Results: circPRRC2A was identified by circRNA microarray and validated by qRT-PCR. The role of circPRRC2A in RCC metastasis was evaluated both in vitro and in vivo. We found that increased expression of circPRRC2A is positively associated with advanced clinical stage and worse survivorship in RCC patients. Mechanistically, our results indicate that circPRRC2A prevents the degradation of TRPM3, a tissue-specific oncogene, mRNA by sponging miR-514a-5p and miR-6776-5p. Moreover, circPRRC2A promotes tumor EMT and aggressiveness in patients with RCC. Conclusions: These findings infer the exciting possibility that circPRRC2A may be exploited as a therapeutic and prognostic target for RCC patients.
Biohorology and biomarkers of aging: Current state-of-the-art, challenges and opportunities
Authors: Fedor Galkin, Polina Mamoshina, Alex Aliper, João Pedro de Magalhães, Vadim N. Gladyshev, Alex Zhavoronkov
Journal: Ageing Research Reviews (2020)

The aging process results in multiple traceable footprints, which can be quantified and used to estimate an organism's age. Examples of such aging biomarkers include epigenetic changes, telomere attrition, and alterations in gene expression and metabolite concentrations. More than a dozen aging clocks use molecular features to predict an organism's age, each of them utilizing different data types and training procedures. Here, we offer a detailed comparison of existing mouse and human aging clocks, discuss their technological limitations and the underlying machine learning algorithms. We also discuss promising future directions of research in biohorology - the science of measuring the passage of time in living systems. Overall, we expect deep learning, deep neural networks and generative approaches to be the next power tools in this timely and actively developing field.
Trends in Mechanical Support Use as a Bridge to Adult Heart Transplant Under New Allocation Rules
Authors: Thomas C. Hanff, Michael O. Harhay, Stephen E. Kimmel, Maria Molina, Jeremy A. Mazurek, Lee R. Goldberg, Edo Y. Birati
Journal: JAMA Cardiology (2020)

This study investigates trends in mechanical support use after implementation of the Organ Procurement and Transplantation Network’s new heart transplant allocation rules.
Clinical Characteristics of Patients Who Died of Coronavirus Disease 2019 in China
Authors: Jianfeng Xie, Zhaohui Tong, Xiangdong Guan, Bin Du, Haibo Qiu
Journal: JAMA Network Open (2020)

Another interesting finding of this case series is that hypertension was the most common chronic comorbidity among patients who died.A previous 2020 case series 1 also reported a higher rate of hypertension among patients with COVID-19 who were admitted to intensive care units than among patients with COVID-19 who were not admitted to intensive care units.However, hypertension usually is not an independent risk factor associated with mortality in patients with sepsis. 5According to a study from earlier this year, 6 severe acute respiratory syndrome coronavirus 2 infects the lungs through the angiotensin-converting enzyme II receptor.Further research is needed to find the mechanism of COVID-19.In addition, clinical studies are also needed to confirm whether angiotensin-converting enzyme inhibitors and angiotensin receptor blockers could be beneficial for patients with COVID-19.Our study has some limitations.One limitation is that our data were from patients who died during late January 2020, and they may not be representative of later cases of COVID-19.This case series found that delayed intubation was common in the early stage of the COVID-19 epidemic in Wuhan.Potential reasons for the delay include lack of invasive mechanical ventilators and lack of specific clinical training for respiratory support.
Endothelial to mesenchymal transition contributes to nicotine-induced atherosclerosis
Authors: Wei Qin, Longyin Zhang, Zhange Li, Dan Xiao, Yue Zhang, Haiying Zhang, Justine Nyakango Mokembo, Seth Mikaye Monayo, Nabanit Kumar Jha, Philipp Kopylov, Dmitri Shchekochikhin, Yong Zhang
Journal: Theranostics (2020)

Rationale: Nicotine exposure via cigarette smoking is strongly associated with atherosclerosis.However, the underlying mechanisms remain poorly understood.The current study aimed to identify whether endothelial to mesenchymal transition (EndMT) contributes to nicotine-induced atherosclerosis.Methods: ApoE -/-mice were administered nicotine in their drinking water for 12 weeks.The effects of nicotine on EndMT were determined by immunostaining on aortic root and RNA analysis in aortic intima.In vitro nicotine-treated cell model was established on human aortic endothelial cells (HAECs).The effects of nicotine on the expression of EndMT-related markers, ERK1/2 and Snail were quantified by real-time PCR, western blot and immunofluorescent staining.Results: Nicotine treatment resulted in larger atherosclerotic plaques in ApoE -/-mice.The vascular endothelial cells from nicotine-treated mice showed mesenchymal phenotype, indicating EndMT.Moreover, nicotine-induced EndMT process was accompanied by cytoskeleton reorganization and impaired barrier function.The α7 nicotine acetylcholine receptor (α7nAChR) was highly expressed in HAECs and its antagonist could effectively relieve nicotine-induced EndMT and atherosclerotic lesions in mice.Further experiments revealed that ERK1/2 signaling was activated by nicotine, which led to the upregulation of Snail.Blocking ERK1/2 with inhibitor or silencing Snail by small interfering RNA efficiently preserved endothelial phenotype upon nicotine stimulation. Conclusion:Our study provides evidence that EndMT contributes to the pro-atherosclerotic property of nicotine.Nicotine induces EndMT through α7nAChR-ERK1/2-Snail signaling in endothelial cells.EndMT may be a therapeutic target for smoking-related endothelial dysfunction and cardiovascular disease.
Tumor mutational load predicts time to first treatment in chronic lymphocytic leukemia (<scp>CLL</scp>) and monoclonal B‐cell lymphocytosis beyond the <scp>CLL</scp> international prognostic index
Authors: Geffen Kleinstern, Daniel R. O'Brien, Xing Li, Shulan Tian, Brian F. Kabat, Kari G. Rabe, Aaron D. Norman, Huihuang Yan, Celine M. Vachon, Nicholas J. Boddicker, Timothy G. Call, Sameer A. Parikh, Laura Bruins, Cecilia Bonolo de Campos, Jose F. Leis, Tait D. Shanafelt, Wei Ding, James R. Cerhan, Neil E. Kay, Susan L. Slager, Esteban Braggio
Journal: American Journal of Hematology (2020)

Next-generation sequencing identified about 60 genes recurrently mutated in chronic lymphocytic leukemia (CLL). We examined the additive prognostic value of the total number of recurrently mutated CLL genes (i.e., tumor mutational load [TML]) or the individually mutated genes beyond the CLL international prognostic index (CLL-IPI) in newly diagnosed CLL and high-count monoclonal B-cell lymphocytosis (HC MBL). We sequenced 59 genes among 557 individuals (112 HC MBL/445 CLL) in a multi-stage design, to estimate hazard ratios (HR) and 95% confidence intervals (CI) for time-to-first treatment (TTT), adjusted for CLL-IPI and sex. TML was associated with shorter TTT in the discovery and validation cohorts, with a combined estimate of continuous HR = 1.27 (CI:1.17-1.39, P = 2.6 × 10-8 ; c-statistic = 0.76). When stratified by CLL-IPI, the association of TML with TTT was stronger and validated within low/intermediate risk (combined HR = 1.54, CI:1.37-1.72, P = 7.0 × 10-14 ). Overall, 80% of low/intermediate CLL-IPI cases with two or more mutated genes progressed to require therapy within 5 years, compared to 24% among those without mutations. TML was also associated with shorter TTT in the HC MBL cohort (HR = 1.53, CI:1.12-2.07, P = .007; c-statistic = 0.71). TML is a strong prognostic factor for TTT independent of CLL-IPI, especially among low/intermediate CLL-IPI risk, and a better predictor than any single gene. Mutational screening at early stages may improve risk stratification and better predict TTT.
Abstract 10025: Human Umbilical Cord Stem Cells Increase Heart Contractility and Decrease Fibrosis in Congenital Cardiomyopathy
Authors: Robert Henning, Ernesto Jimenez
Journal: Circulation (2015)

Introduction: We have established that human umbilical cord blood stem cells ( hUCSC ) decrease inflammation and infarct size in acute myocardial infarctions in rats. We hypothesized that hUCSC can limit the progressive LV fibrosis and LV failure that occurs in TO2 hamsters, a model of congenital cardiomyopathy due to sarcoglycan deficiency. Methods: 22 TO2 1 month old hamsters were treated with intramyocardial ( IM ) hUCBC, 4х 10 6 ,in Isolyte®, and 23 TO2 1 month old hamsters were treated with IM Isolyte. 16 1 month old F1B hamsters served as controls and received IM Isolyte. No hamster was given immunosuppressive treatment. Echocardiograms were performed on all hamsters prior to and monthly after treatment for 6 months. Heart tissues were stained with hematoxylin and eosin, Masson’s Trichrome and human nuclear antibody. Results: In the F1B hamsters, LV fractional shortening ( FS ) and ejection fractions ( EF ) did not significantly decrease over 6 months. In contrast, in Isolyte treated TO2 hamsters, FS decreased from 56.2±1.0% to 19.7±3.2% and EF decreased from 89.5±1.4% to 41.9 ±5.9% at 6 months (both p &lt; 0.001). The FS and EF in hUCSC treated TO2 hamsters also progressively decreased over 6 months but changes were more gradual, especially during first month after hUCSC when FS was 52.0±1.5% and EF was 89.5±1.4%, which was not significantly different from the F1B hamsters. In the hUCSC treated hamsters, the FS and EF were 20-30% greater than FS and EF in Isolyte TO2 hamsters at 3 and 5 months (p &lt; 0.01). Injection of hUCBC in a subset of Isolyte treated TO2s at 4 months increased LV EF at age 5 months to 57.5±2.3% compared with a EF of 41.6±3.1% (p&lt; 0.01) in Isolyte treated TO2s. In Isolyte treated TO2s at 6-7 months, fibrosis involved 30.0±5.0% of LV and 35.0±5.0% of LV septum. In contrast, in hUCSC treated hamsters, fibrosis involved only 16.5± 2.3% of LV and 16.3±1.8% of septum (p&lt; 0.05). The average number of blood vessels per myocardial microscopic field in hUCSC treated hearts was 53.5 ± 0.8 versus 46.2 ± 3.0 in Isolyte treated TO2 hearts (p &lt; 0.05). Conclusion: hUCSC, given as a single intramyocardial injection, can limit fibrosis and increase heart contractility over the short term in TO2 hamsters with congenital cardiomyopathy.
Clonal Hematopoiesis of Indeterminate Potential (CHIP) in Patients with Coronary Artery Disease and in Centenarians. Further Clues Linking Chip with Cardiovascular Risk
Authors: Luca Bertamini, Claudia Sala, Nicola Martinelli, Cristina Papayannidis, Cristina Giuliani, Giovanni Malerba, Paolo Garagnani, Oliviero Olivieri, Giovanni Martinelli, Claudio Franceschi, Domenico Girelli
Journal: Blood (2017)
Patient-Reported Cognitive Impairment Among Women With Early Breast Cancer Randomly Assigned to Endocrine Therapy Alone Versus Chemoendocrine Therapy: Results From TAILORx
Authors: Lynne I. Wagner, Robert J. Gray, Joseph A. Sparano, Timothy J. Whelan, Sofia F. Garcia, Betina Yanez, Amye J. Tevaarwerk, Ruth C. Carlos, Kathy S. Albain, John A. Olson, Matthew P. Goetz, Kathleen I. Pritchard, Daniel F. Hayes, Charles E. Geyer, E. Claire Dees, Worta J. McCaskill-Stevens, Lori M. Minasian, George W. Sledge, David Cella
Journal: Journal of Clinical Oncology (2020)

PURPOSE Cancer-related cognitive impairment (CRCI) is common during adjuvant chemotherapy and may persist. TAILORx provided a novel opportunity to prospectively assess patient-reported cognitive impairment among women with early breast cancer who were randomly assigned to chemoendocrine therapy (CT+E) versus endocrine therapy alone (E), allowing us to quantify the unique contribution of chemotherapy to CRCI. METHODS Women with a 21-gene recurrence score of 11 to 25 enrolled in TAILORX were randomly assigned to CT+E or E. Cognitive impairment was assessed among a subgroup of 552 evaluable women using the 37-item Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) questionnaire, administered at baseline, 3, 6, 12, 24, and 36 months. The FACT-Cog included the 20-item Perceived Cognitive Impairment (PCI) scale, our primary end point. Clinically meaningful changes were defined a priori and linear regression was used to model PCI scores on baseline PCI, treatment, and other factors. RESULTS FACT-Cog PCI scores were significantly lower, indicating more impairment, at 3, 6, 12, 24, and 36 months compared with baseline for both groups. The magnitude of PCI change scores was greater for CT+E than E at 3 months, the prespecified primary trial end point, and at 6 months, but not at 12, 24, and 36 months. Tests of an interaction between menopausal status and treatment were nonsignificant. CONCLUSION Adjuvant CT+E is associated with significantly greater CRCI compared with E at 3 and 6 months. These differences abated over time, with no significant differences observed at 12 months and beyond. These findings indicate that chemotherapy produces early, but not sustained, cognitive impairment relative to E, providing reassurance to patients and clinicians in whom adjuvant chemotherapy is indicated to reduce recurrence risk.
Role of apolipoprotein E in electronegative low-density lipoprotein-induced mitochondrial dysfunction in cardiomyocytes
Authors: Wei-Yu Chen, Yun-Fang Chen, Hua-Cheng Chan, Ching-Hu Chung, Hsien-Yu Peng, Yu-Cheng Ho, Chu-Huang Chen, Kuan-Cheng Chang, Chih-Hsin Tang, An-Sheng Lee
Journal: Metabolism (2020)
Amygdala-Midbrain Connections Modulate Appetitive and Aversive Learning
Authors: Elizabeth E. Steinberg, Felicity Gore, Boris D. Heifets, Madison D. Taylor, Zane C. Norville, Kevin T. Beier, Csaba Földy, Talia N. Lerner, Liqun Luo, Karl Deisseroth, Robert C. Malenka
Journal: Neuron (2020)
Proton pump inhibitors and the risk of gallbladder cancer: a hospital-based case–control study
Authors: Jianping Xiong, Yaqin Wang, Guang Chen, Long Jin
Journal: Gut (2020)

We read with great interest the article by Chuang et al 1 confirming proton pump inhibitor (PPI) use is associated with increased risk of cholecystitis.1 PPIs are a potent class of agents used to suppress gastric acid secretion and are among the most commonly prescribed medications globally.2 Presently, PPIs are routinely recommended for several GI disorders, including GORD, and as prophylaxis against peptic ulcer disease and GI bleeding in susceptible populations, such as individuals on dual antiplatelet therapy for secondary prevention of cardiovascular disease.3–5 In view of the large population of patients receiving PPI therapy, in many cases long-term therapy, ensuring the safety of PPI therapy is of considerable public health importance.6 Recently, PPIs have been reported to be associated with cholecystitis and might possibly be carcinogenic.1 However, no research has been conducted to investigate the association of PPIs with gallbladder cancer (GBC). Herein, a hospital-based case–control study was carried out in China to explore the association between PPIs and GBC risk.

A hospital-based case–control study was performed by enrolling 3030 …
Engineering peptide-targeted liposomal nanoparticles optimized for improved selectivity for HER2-positive breast cancer cells to achieve enhanced in vivo efficacy
Authors: Baksun Kim, Jaeho Shin, Junmin Wu, David T. Omstead, Tanyel Kiziltepe, Laurie E. Littlepage, Basar Bilgicer
Journal: Journal of Controlled Release (2020)