tbuckley/cabot-search huggingface dataset:
Fast and accurate medication identification
Authors: Natalia Larios Delgado, Naoto Usuyama, Amanda K. Hall, Rebecca J. Hazen, Max Ma, Siva Sahu, Jessica Lundin
Journal: npj Digital Medicine (2019)

Abstract Much of the AI work in healthcare is focused around disease prediction in clinical settings, which is an important application that has yet to deliver in earnest. However, there are other fundamental aspects like helping patients and care teams interact and communicate in efficient and meaningful ways, which could deliver quadruple-aim improvements. After heart disease and cancer, preventable medical errors are the third leading cause of death in the United States. The largest subset of medical errors is medication error. Providing the right treatment plan for patients includes knowledge about their current medications and drug allergies, an often challenging task. The widespread growth of prescribing and consuming medications has increased the need for applications that support medication reconciliation. We show a deep-learning application that can help reduce avoidable errors with their attendant risk, i.e., correctly identifying prescription medication, which is currently a tedious and error-prone task. We demonstrate prescription-pill identification from mobile images in the NIH NLM Pill Image Recognition Challenge dataset. Our application recognizes the correct pill within the top-5 results at 94% accuracy, which compares favorably to the original competition winner at 83.3% for top-5 under comparable, though not identical configurations. The Institute of Medicine claims that better use of information technology can be an important step in reducing medication errors. Therefore, we believe that a more immediate impact of AI in healthcare will occur with a seamless integration of AI into clinical workflows, readily addressing the quadruple aim of healthcare.
ROLE OF COMPUTED TOMOGRAPHIC CORONARY ANGIOGRAPHY AND CORONARY ARTERY CALCIUM SCORE IN PERIOPERATIVE RISK STRATIFICATION PRIOR TO NONCARDIAC SURGERY: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Anoop Ninan Koshy, Francis Ha, Paul J. Gow, Hui-Chen Han, F.M. Amirul-Islam, Han Lim, Andrew Teh, H.M. Omar Farouque
Journal: Journal of the American College of Cardiology (2019)
ADIPONECTIN, LEFT ATRIAL REMODELING, AND ATRIAL FIBRILLATION: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS
Authors: Kaveh Rezaei Bookani, Mohammad R. Ostovaneh, Bharath Ambale Venkatesh, Shishir Sharma, Matthew Allison, Philip Greenland, Susan Heckbert, Colin O. Wu, David A. Bluemke, Joao Lima
Journal: Journal of the American College of Cardiology (2019)
Abstract 492: Intra Mural Aortic Hematoma: An Unusual Case Presenting With Acute Limb Ischemia
Authors: Nethuja Salagundla, Dylan R Murray, Islam Asm, George H Parker, Anu Salwan
Journal: Circulation Research (2018)

A 50 YO F with PMH of HTN, HLD, DM2, presented with claudication of right lower extremity with cyanotic changes of her toes for past few months, with increasing pain and discoloration. CT Angio showed ulcerated plaque of abdominal aorta and 1.5 cm dissection and stenosis of right common iliac artery. Intervention done with urgent stent placement. Patient returned 5 days later with worsening of pain and cyanosis of right toes with increasing symptoms of heaviness and claudication with about 1-2 blocks. Physical examination suggestive of discoloration of right foot toes, audible pedal pulses on right. Repeat Ct angio showed focal intramural hematoma and dissection within the right common iliac artery just above the stent, with 75% stenosis. Possibly from rupture of ulcer from surgical manipulation. Vascular surgeon and Interventional radiologist, both agreed on stent graft placement based on current guidelines. Patient underwent procedure without complications, pain and cyanosis improved within in next few days. Discussion: Intramural hematoma is currently defined as a hematoma in the medial layer without evidence of an intimal tear, which would otherwise indicate aortic dissection. The exact mechanism of intramural hematoma is unknown, 2 proposed mechanisms are penetrating atheroslerotic lesion or rupture of vasovasorum. Management is based on location; Type A is a surgical emergency, whereas type B is managed medically or by endovascular intervention. It should be noted that penetrating aortic ulcers and intramural hematomas can occur in the distal abdominal aorta and proximal bifurcation, and that these lesions can be managed successfully with endovascular intervention.
BONE MORPHOGENIC PROTEIN-1/TOLLOID-LIKE METALLOPROTEINASE UPREGULATION PROFILE IN HUMAN AND MURINE ISCHEMIC HEART FAILURE
Authors: Estibaliz Castillero, Hirokazu Akashi, Catherine Wang, Marc Najjar, Ruiping Ji, Xianghai Liao, Adriana Mills, Rawan Alhau, Kaitlyn Yong, Joanna Kiperman, Jaise John, Shunichi Homma, Veli Topkara, Koji Takeda, Yoshifumi Naka, Giovanni Ferrari, Paolo Colombo, Christian Schulze, Isaac George
Journal: Journal of the American College of Cardiology (2019)
Abstract 300: MicroRNA-21 Affects Platelets and Their Releasate: A Novel Mechanism for the Anti-Fibrotic Effects of MicroRNA-21 Inhibition
Authors: Temo Barwari, Seda Eminaga, Ruifang Lu, Paul C Armstrong, Christian Schulte, Marc Lynch, Melissa V Chan, Javier Barallobre-Barreiro, Xiaoke Yin, Raimund Pechlaner, Sarah Langley, Mahnaz Sahraei, Marta Fernández-Fuertes, Anna Zampetaki, Peter Santer, Timothy D Warner, Stefan Kiechl, Johann Willeit, Carlos Fernández-Hernando, Yajaira Suárez, Ajay M Shah, Manuel Mayr
Journal: Circulation Research (2018)

Introduction: Fibrosis is a major contributor to cardiac disease. MicroRNA-21 (miR-21) has been implicated as a regulator of fibrosis, with inhibitors of miR-21 currently undergoing clinical trials. We aimed to explore how miR-21 inhibition attenuates fibrosis using a proteomics approach. Methods and Results: As expected, transfection with miR-21 mimics and inhibitors altered the proliferation of murine cardiac fibroblasts. However, proteomic analysis of their conditioned media revealed limited effects on ECM secretion. Similarly, proteomic analysis of hearts from miR-21 null mice showed no major difference in extracellular matrix (ECM) composition. Thus, we searched for additional explanations as to how miR-21 might regulate fibrosis. In the community-based Bruneck study (year 2000 follow-up, n=671), we compared circulating miR-21 with a panel of 229 proteins associated with cardiovascular disease. Several platelet-derived pro-fibrotic factors correlated with plasma miR-21 levels, including the latency-associated peptide of transforming growth factor beta-1 (TGF-β1). This correlation was confirmed by ELISA measurements of active TGF-β1 in plasma (Bruneck 2015 follow-up, n=332). In agreement with this observation in men, systemic inhibition of miR-21 with an antagomiR reduced the platelet release of TGF-β1 in mice. Mechanistically, Wiskott-Aldrich Syndrome protein, a negative regulator of platelet TGF-β1 secretion, was identified as a direct target of miR-21. AntagomiR-21 treatment, however, had no effect on the platelet count or their aggregation response. In contrast, miR-21 null mice had significantly lower platelet counts compared to littermate controls. Conclusions: This study reports a previously unrecognized effect of miR-21 inhibition on platelets. Both genetic deletion of miR-21 and antagomiR treatment affect platelets. The effect of miR-21 inhibition on platelet TGF-β1 release, in particular, may contribute to the anti-fibrotic effects of miR-21 inhibitors.
CO-PREVALENCE AND THE PROGNOSTIC INFLUENCE OF FRAILTY, QUALITY OF LIFE, DEPRESSION, AND COGNITION AMONG OLDER ADULTS UNDERGOING CARDIAC CATHETERIZATION
Authors: Mohammed Al-Hijji, Robert Widmer, Rajiv Gulati, Ryan Lennon, Atta Behfar, Amrit Kanwar, S. Gharacholou, Amir Lerman, Mandeep Singh
Journal: Journal of the American College of Cardiology (2019)
Long-term trajectory of kidney function in autosomal-dominant polycystic kidney disease
Authors: Alan S.L. Yu, Chengli Shen, Douglas P. Landsittel, Jared J. Grantham, Larry T. Cook, Vicente E. Torres, Arlene B. Chapman, Kyongtae Ty Bae, Michal Mrug, Peter C. Harris, Frederic F. Rahbari-Oskoui, Tiange Shi, William M. Bennett
Journal: Kidney International (2019)
CHRONIC TOTAL OCCLUSION PERCUTANEOUS CORONARY INTERVENTIONS IN LATIN AMERICA: CHARACTERISTICS, OUTCOMES AND PREDICTORS OF UNSUCCESSFUL PROCEDURES
Authors: Alexandre Quadros, Joao De Paula, Carlos Campos, Antonio Carlos Botelho, Ricardo Santiago-Trinidad, Marcelo Ribeiro, Pablo Manuel Lamelas, Aníbal Pereira Abelin, Franklin Hanna, Mario Araya, Marcelo Cantarelli, Fabio De Brito, Cleverson Zukowski, Antônio José Muniz, Julia Kurtz Teixeira, Sandra Baradel, Luiz Fernando Ybarra, Pedro Piccaro De Oliveira, Daniel Weillenmann, Karlyse Belli, Lucio Padilla
Journal: Journal of the American College of Cardiology (2019)
INCIDENCE AND PROGNOSIS OF TYPE 1 CARDIORENAL SYNDROMES AMONG PATIENTS WITH ACUTE MYOCARDIAL INFARCTION UNDERGOING PERCUTANEOUS CORONARY INTERVENTION
Authors: Jin Liu, Guoli Sun, Yibo He, Feier Song, Zhaodong Guo, Shiqun Chen, Bowen Liu, Li Lei, Lihao He, Jiyan Chen, Yong Liu, Ning Tan
Journal: Journal of the American College of Cardiology (2019)
Bone mineral density, bone turnover markers, and incident fractures in de novo kidney transplant recipients
Authors: Pieter Evenepoel, Kathleen Claes, Bjorn Meijers, Michaël R. Laurent, Bert Bammens, Maarten Naesens, Ben Sprangers, Hans Pottel, Etienne Cavalier, Dirk Kuypers
Journal: Kidney International (2019)
RECURRENT ACUTE MYOCARDIAL INFARCTION AFTER AN ACUTE MYOCARDIAL INFARCTION
Authors: Grant Henderson, Mouin Abdallah, Michael Johnson, Moses Anabila, Kathleen Kravitz, Jeevanantham Rajeswaran, Venu Menon, Stephen Ellis, A. Lincoff, Eugene Blackstone, Samir Kapadia, Umesh Khot
Journal: Journal of the American College of Cardiology (2019)
ASSESSING THE QUALITY OF REPORTING OF HARMS IN RANDOMIZED CONTROLLED TRIALS PUBLISHED IN HIGH IMPACT CARDIOVASCULAR JOURNALS
Authors: Muhammad Shahzeb Khan, Asim Sheikh, Rohan Kumar Ochani, Noman Lateef, Kaneez Fatima, Safi U. Khan, Rami Doukky, Vincent Figueredo, Richard Krasuski
Journal: Journal of the American College of Cardiology (2019)
APIXABAN DISCONTINUATION PRIOR TO MAJOR SURGERY: RESULTS FROM A PROSPECTIVE SINGLE CENTER STUDY
Authors: Edwin Lam, Luis Eraso, Taki Galanis, Walter Kraft, Geoffrey Ouma, Lynda Thomson, Eugene Viscusi, Douglas Stickle, Jerald Gong, Suzanne Adams, Geno Merli
Journal: Journal of the American College of Cardiology (2019)
Current multifunctional albumin-based nanoplatforms for cancer multi-mode therapy
Authors: Chang Li, Xin Wang, Hang Song, Shuai Deng, Wei Li, Jing Li, Jin Sun
Journal: Asian Journal of Pharmaceutical Sciences (2019)

Albumin has been widely applied for rational design of drug delivery complexes as natural carriers in cancer therapy due to its distinct advantages of biocompatibility, abundance, low toxicity and versatile property. Hence, various types of multifunctional albumin-based nanoplatforms (MAlb-NPs) that adopt multiple imaging and therapeutic techniques have been developed for cancer diagnosis and treatment. Stimuli-responsive release, including reduction-sensitive, pH-responsive, concentration-dependent and photodynamic-triggered, is important to achieve low-toxicity cancer therapy. Several types of imaging techniques can synergistically improve the effectiveness of cancer therapy. Therefore, combinational theranostic is considered to be a prospective strategy to improve treatment efficiency, minimize side effects and reduce drug resistance, which has received tremendous attentions in recent years. In this review, we highlight several stimuli-responsive albumin nanoplatforms for combinational theranostic.
Abstract #2667: What distinguishes a PKC activator like phorbol ester from a PKC functional antagonist like bryostatin 1? Bryologues permit dissection of intermediate patterns of activity
Authors: Noemi Kedei, Gabriella Czifra, Andrea Telek, Matthew Kraft, Anh Truong, Wei Li, Carina Sanchez, Gary Keck, Peter Blumberg
Journal: Cancer Research (2009)

Bryostatin 1, a promising anticancer agent in clinical trials, is a potent PKC activator  in vitro  that paradoxically often antagonizes the effects of the typical PKC activator phorbol 12-myristate 13-acetate (PMA) in cellular systems. Understanding the underlying mechanism(s) responsible for this functional PKC antagonism should afford a new generation of drugs for PKC, a validated therapeutic target. Here, we characterize biological responses to three synthetic bryostatin look-alikes (bryologues 11, 12, and 13 -  JACS  2008, 130, 6660-6661) that differ structurally from bryostatin 1 to only a modest degree. We have examined the behavior of these compounds in multiple biological systems in which PMA induces a response which bryostatin 1 fails to induce and where bryostatin 1 blocks the response to PMA. The responses examined were: 1) cell proliferation and differentiation of U937 human leukemia cells, 2) cell proliferation of K562 human leukemia cells, 3) cell proliferation of LNCaP human prostate cancer cells, 4) apoptosis in LNCaP cells, 5) phosphorylation of PKC delta at position Tyr311 in LNCaP cells, 6) activation of cFos in LNCaP cells, 7) release of arachidonic acid metabolites in CH310T1/2 mouse fibroblasts. We find that the bryologues, like PMA and unlike bryostatin 1, inhibit proliferation of U937 and K562 cells and induce the differentiation (attachment) of U937 cells. On the other hand, in LNCaP cells the three bryologues do not inhibit cell proliferation, unlike PMA, and only partially induce apoptosis. Like PMA, however, they induce tyrosine phosphorylation of PKC delta at position 311, an effect induced very weakly and briefly by bryostatin 1. Finally, the duration of cFos activation by the bryologues in LNCaP cells is intermediate between the transient response to bryostatin 1 and the more sustained response to PMA. In C3H10T1/2 mouse fibroblasts, PMA but not bryostatin 1 induces the rapid release of arachidonic acid metabolites; the bryologues have an effect that is intermediate but closer to that of PMA. We conclude that these bryologues have different extents of phorbol ester or bryostatin 1-like character depending on the cell type and cellular endpoint examined and thus that there are multiple mechanisms responsible for the antagonistic action of bryostatin. The bryologues provide unique tools for now identifying which mechanisms are related to which responses. Finally, these bryologues together with novel derivatives should permit dissection of those structural features linked to their various mechanisms of action.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2667.
FRACTIONAL EXCRETION OF SODIUM AFTER THE TREATMENT OF ACUTE DECOMPENSATED HEART FAILURE PREDICTS THE PROGNOSIS
Authors: Hiroyuki Kono, Takeshi Kitai, Kitae Kim, Atsushi Kobori, Natsuhiko Ehara, Makoto Kinoshita, Shuichiro Kaji, Yutaka Furukawa
Journal: Journal of the American College of Cardiology (2019)
Sickle Human Umbilical Cord Derived Erythroid Progenitor Cells (S-HUDEP2): An Ideal in-Vitro System for Screening Anti-Sickling Compounds for Sickle Cell Disease
Authors: Alicia Chang, So Hyun Park, Ciaran M Lee, Alireza Paikari, Gang Bao, Vivien A Sheehan
Journal: Blood (2018)
Abstract 268: Through the Inhibition of Autophagy Flux miR-221 Plays an Important Role in the Reductions of Hypoxia Reoxygenation Induced Cell Death and Collagen Synthesis in Cardiac Fibroblast
Authors: Yue Zhou, Arthur M Richards, Peipei Wang
Journal: Circulation Research (2018)

Purpose: We have previously reported that miR-221 protects myocytes against H/R-induced injury through the inhibitions of autophagy and apoptosis. It is not known has similar anti-autophagic and anti-apoptotic effects on cardiac fibroblast (cFB) and what role it plays in the regulation of cFB function. Method: Adult rat cFBs were isolated and transfected with miR-221 mimics and mimic control (miR-221 and MC). cFBs were subjected to normoxia (Nor) and H/R conditions. MiR-221 effects were monitored for cell injury (CCK8 and lactate dehydrogenase, LDH), apoptosis (Annexin V and 7-AAD staining), autophagy (LC3 and p62 by Western blot, WB) and collagen synthesis (Sircol). To study autophagy flux, Bafilomycin A1 (Baf) or Rapamycin (Rap) was applied to further inhibit or enhance autophagosome (ATGsome) formation and degradation respectively. Results: miRNA-221 increased cFB viability as indicated by increased CCK8 and reduced LDH release (miR-221 vs. MC) in H/R. This pro-survival effect did not involve apoptosis but reducing autophagy as indicated by unchanged Annexin V staining and reduced LC3-II/I ratio and increased p62 respectively. The protection was blocked by Rap. DMSO, the solvent used for the preparation of Baf and Rap, showed a significant induction of ATGsome formation on its own and override the anti-ATGsome formation effect of miR-221. In the presence of DMSO, miR-221 caused LC3 II accumulation, similar to the effect of Baf. In addition, miR-221 inhibited collagen synthesis as assessed by Sircol measurement. TGF-β, as a positive control, increased collagen synthesis significantly. The regulation of collagen synthesis of miR-221 and TGF-β could be abrogated by Rap and Baf respectively. Under Nor and H/R, the expressions of DDIT4 and Tp53inp1 were significantly downregulated by miR-221. Conclusion: Targeting on DDIT4 and Tp53inp1, miR-221 inhibited autophagy flux by reducing both ATGsome formation and degradation. The inhibition plays an important role in the protection of cFB and regulation of collage synthesis. This study reveals the complexity of cFB functional regulation by miRNA-221, preserving cFB in number without causing additional fibrosis. The unique feature of miR-221 might be an advantage in the treatment of cardiac infarction.
Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis
Authors: Janel O Johnson, Erik P Pioro, Ashley Boehringer, Ruth Chia, Howard Feit, Alan E Renton, Hannah A Pliner, Yevgeniya Abramzon, Giuseppe Marangi, Brett J Winborn, J Raphael Gibbs, Michael A Nalls, Sarah Morgan, Maryam Shoai, John Hardy, Alan Pittman, Richard W Orrell, Andrea Malaspina, Katie C Sidle, Pietro Fratta, Matthew B Harms, Robert H Baloh, Alan Pestronk, Conrad C Weihl, Ekaterina Rogaeva, Lorne Zinman, Vivian E Drory, Giuseppe Borghero, Gabriele Mora, Andrea Calvo, Jeffrey D Rothstein, Carsten Drepper, Michael Sendtner, Andrew B Singleton, J Paul Taylor, Mark R Cookson, Gabriella Restagno, Mario Sabatelli, Robert Bowser, Adriano Chiò, Bryan J Traynor
Journal: Nature Neuroscience (2014)
Predictive role of CT texture analysis in patients with metastatic urothelial cancer treated with PD-1/PD-L1 inhibitors.
Authors: Francesco Alessandrino, Rahul Gujrathi, Amin Nassar, Arwa Alzaghal, Arvind Ravi, Bradley Alexander McGregor, Guru Sonpavde, Atul B. Shinagare
Journal: Journal of Clinical Oncology (2019)

424 Background: Reliable biomarkers to predict response of urothelial cancer to PD-1/PD-L1 inhibitors are still being investigated. Texture analysis represents underlying tumor heterogeneity and may serve as a predictor of response in urothelial cancer. The purpose of this study was to assess predictive ability of CT texture analysis for disease progression in patients with metastatic urothelial cancer treated with PD-1/PD-L1 inhibitor. Methods: In this IRB-approved HIPAA-compliant retrospective study, from total 93 consecutive patients with metastatic urothelial cancer treated with PD-1/PD-L1 inhibitors from 2013-2018, 43 patients with measurable disease per RECIST 1.1 criteria who had contrast-enhanced CT performed within three months after starting treatment were included. Progression-free survival was calculated based on serial follow-up CTs, and 11 patients without progression who did not reach 1 year follow-up were excluded. Texture features of measurable lesions on first follow-up CT were extracted (TexRAD Ltd, Feedback Plc, Cambridge, UK). Stepwise logistic regression analysis to identify patients who had progressive disease (PD) at 12 months was performed and performance assessed using receiver operator curves. Results: Of 32 included patients (24 men, 8 women; median age: 65 years) who had total 80 measurable lesions, 22 progressed by 12 months. On first follow-up CT, the entropy and mean of the lesions were higher (p = 0.04, p = 0.02) for patients with PD by 12 months. Calculated specificity and sensitivity of entropy (AUC = 0.79) were 90%, and 63%; of mean (AUC = 0.81) were 90%, and 50%. A predictive model including mean and entropy yielded 95% sensitivity, 80% specificity, 91% PPV, 89% NPV and 91% accuracy (AUC = 0.863) to identify patients with PD at 12 months. Conclusions: Texture analysis of CT performed within three months after starting PD-1/PD-L1 can help predict patients who progress by 12 months with high accuracy. Further studies investigating the correlation of texture analysis with survival endpoints may help validate the role of texture analysis as a biomarker to predict response to PD1/PD-L1 inhibitors.
STEMI TREATMENT BY CRP REMOVAL PROMISES CLINICAL BENEFIT: FIRST RESULTS OF THE CAMI1 STUDY
Authors: Christoph D. Garlichs, Ahmed Sheriff, Sebastian Kelle, Jan Torzewski, Stephanie Lehrke, Jan Horstkotte, Harald Darius, Christian Pflücke, Franz Heigl, Hüseyin Ince, Steffen Mitzner, Wolfgang Ries
Journal: Journal of the American College of Cardiology (2019)
IL2 AND IL4 GENE POLYMORPHISMS ARE ASSOCIATED WITH LATENT AND CLINICAL RHEUMATIC HEART DISEASE: DATA FROM THE PROVAR STUDY
Authors: Bruno Ramos Nascimento, Júlia P.A. Santos, Andrea Z. Beaton, Luiz Paulo C. Rocha, Cecília H.R. Pinto, Adriana Diamantino, Breno D.F. Rezende, Clara L. Fraga, Letícia Maria M. Rabelo, Craig Sable, Zilda Maria A. Meira, Maria do Carmo Nunes, Walderez Dutra
Journal: Journal of the American College of Cardiology (2019)
Delivery of Bottled Water to Women With Recurrent Urinary Tract Infections: Why in Bulgaria?—Reply
Authors: Thomas M. Hooton, Mariacristina Vecchio, Yair Lotan
Journal: JAMA Internal Medicine (2019)

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COMPREHENSIVE SIMPLIFIED LEFT ATRIAL ASSESSMENT FOR PREDICTING RECURRENCE OF ATRIAL FIBRILLATION FOLLOWING PULMONARY VEIN ISOLATION IN PATIENTS WITH PAROXYSMAL ATRIAL FIBRILLATION
Authors: Fumitaka Soga, Hidekazu Tanaka, Yasuhide Mochizuki, Kentaro Yamashita, Yusuke Tanaka, Ayu Shono, Makiko Suzuki, Sachiko Yoshikawa, Keiko Sumimoto, Nao Shibata, Shun Yokota, Jun Mukai, Makiko Suto, Hiroki Takada, Kumiko Dokuni, Keiko Hatazawa, Eriko Hisamatsu, Kensuke Matsumoto, Koji Fukuzawa, Ken-Ichi Hirata
Journal: Journal of the American College of Cardiology (2019)
A UNIQUE CASE OF VENOTHROMBOEMBOLISM TREATED WITH THE ANGIOVAC SYSTEM
Authors: Matthew T. Finn, Sanjum Sethi, Mehdi Rambod, Matthew Bacchetta, Erika Berman Rosenzweig, Koji Takeda, Ajay Kirtane, Sahil Parikh, Philip Green
Journal: Journal of the American College of Cardiology (2019)