tbuckley/cabot-search huggingface dataset:
Downregulation of PLK1 elevates chemosensitivity of various breast cancer cell lines in vitro and in vivo
Authors: B. Spaenkuch, S. Heim, E. Kurunci-Csacsko, C. Lindenau, M. Kaufmann, K. Strebhardt
Journal: Journal of Clinical Oncology (2006)

13169 Background: A central role for polo-like kinases (PLK) in regulating mitosis has been shown in different species. Overexpression of PLK1 is observed in various human tumors, and it is a negative prognostic factor in patients suffering from diverse cancers. In order to reduce side-effects exerted by commonly used anti-neoplastic agents and to enhance chemosensitivity of different breast cancer cell lines, we used phosphorothioate antisense oligonucleotides (ASOs) targeted against PLK1 together with Paclitaxel, Carboplatin and Herceptin. Methods: We used different HER2-positive and -negative breast cancer cell lines (BT-474, MCF-7, MDA-MB-435) to define the role of reduced PLK1 expression for the necessary dose of anti-neoplastic agents. After transfection with PLK1-specific ASOs these agents were added and cell proliferation, cell cycle distribution, and apoptosis were measured. Results: We observed synergistic effects after combination of very low doses of PLK1-specific ASOs with Paclitaxel and Herceptin. Using Carboplatin we could only observe a synergistic effect in MDA-MB-435 cells. Downregulation of PLK1 levels led to an elevated percentage of cells in G2/M. Apoptosis and G2/M arrest were increased after combination of PLK1-specific ASOs with Paclitaxel in MDA-MB-435 cells. In a human Xenograft experiment using MDA-MB-435 cells the combination of PLK1-ASOs with Paclitaxel led to synergistic reduction of tumor growth after three weeks treatment compared to either agent alone. Conclusion: This study suggests that antisense inhibitors against PLK1 at well tolerated doses may be considered as cancer therapeutic agents which elevate chemosensitivity especially against Paclitaxel in very low doses with a significant better outcome than each agent alone. No significant financial relationships to disclose.
TCT-24 Clinical Predictors for Procedural Stroke and Implications for Embolic Protection Device During TAVR: Results From the Multicenter TASK (Transcatheter Aortic valve implantation in-hoSpital stroKe) Study
Authors: Anat Berkovitch, Amit Segev, Alexander Sedaghat, Ariel Finkelstein, Matteo Saccocci, Azeem Latib, Jose de la Torre Hernandez, Lars Sondergaard, Darren Mylotte, Niels van Royen, Azfar Zaman, Jan-malte Sinning, Arie Steinvil, Francesco Maisano, Katia Orvin, Gianmarco Iannopollo, Ole De Backer, Federico Mercanti, Didier Tchetche, Israel Barbash
Journal: Journal of the American College of Cardiology (2019)
Infographic. Running myth: strength training should be high repetition low load to improve running performance
Authors: James L N Alexander, Christian J Barton, Richard W Willy
Journal: British Journal of Sports Medicine (2019)

The important performance benefits of strength training, including heavy resistance, explosive resistance and plyometric training for endurance runners have been well documented in recent systematic reviews.1–5 As such, strength training should be considered an important addition to a well-planned training programme for middle and long distance runners of all levels.

The key benefits runners can obtain from a strength training programme include:

1.  Improved running economy.

2.  Faster time trial performance.

3.  Faster maximal sprint speed.

Strength training interventions lasting 6–20 weeks, added to the training programme of a distance runner with >6 months running experience, have been reported to enhance running economy by 2%–8%.5 Running economy improvements will theoretically enhance endurance running performance by allowing the runner to run at a lower oxygen or energy cost during training and racing.5 These benefits have been reported in runners from a recreational level through …
TCT-102 Impact of Coronary Artery Bypass History in Patients Undergoing Chronic Total Occlusion-Percutaneous Coronary Intervention: Procedural and Clinical Outcomes from the Registry of CrossBoss and Hybrid Procedures in France, the Netherlands, Belgium, and United Kingdom (RECHARGE)
Authors: Simone Budassi, Carlo Zivelonghi, Joseph Dens, Simon Walsh, Paul Knaapen, Alexandre Avran, James Spratt, Pierfrancesco Agostoni
Journal: Journal of the American College of Cardiology (2019)
ImmunoPET, [64Cu]Cu-DOTA-Anti-CD33 PET-CT, Imaging of an AML Xenograft Model
Authors: Sargur Madabushi Srideshikan, Jamison Brooks, Darren Zuro, Bijender Kumar, James Sanchez, Liliana Echavarria Parra, Marvin Orellana, Paresh Vishwasrao, Indu Nair, Junie Chea, Kofi Poku, Nicole Bowles, Aaron Miller, Todd Ebner, Justin Molnar, Joseph Rosenthal, Daniel A. Vallera, Jeffrey Y.C. Wong, Anthony S. Stein, David Colcher, John E. Shively, Paul J. Yazaki, Susanta K. Hui
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Acute myeloid leukemia (AML) is a highly aggressive form of leukemia, which results in poor survival outcomes. Currently, diagnosis and prognosis are based on invasive single-point bone marrow biopsies (iliac crest). There is currently no AML-specific noninvasive imaging method to detect disease, including in extramedullary organs, representing an unmet clinical need. About 85% to 90% of human myeloid leukemia cells express CD33 cell surface receptors, highlighting CD33 as an ideal candidate for AML immunoPET. Experimental Design: We evaluated whether [64Cu]Cu-DOTA-anti-CD33 murine mAb can be used for immunoPET imaging of AML in a preclinical model. MicroCT was adjusted to detect spatial/anatomical details of PET activity. For translational purposes, a humanized anti-CD33 antibody was produced; we confirmed its ability to detect disease and its distribution. We reconfirmed/validated CD33 antibody-specific targeting with an antibody–drug conjugate (ADC) and radioimmunotherapy (RIT). Results: [64Cu]Cu-DOTA-anti-CD33–based PET-CT imaging detected CD33+ AML in mice with high sensitivity (95.65%) and specificity (100%). The CD33+ PET activity was significantly higher in specific skeletal niches [femur (P &amp;lt; 0.00001), tibia (P = 0.0001), humerus (P = 0.0014), and lumber spine (P &amp;lt; 0.00001)] in AML-bearing mice (over nonleukemic control mice). Interestingly, the hybrid PET-CT imaging showed high disease activity in the epiphysis/metaphysis of the femur, indicating regional spatial heterogeneity. Anti-CD33 therapy using newly developed humanized anti-CD33 mAb as an ADC (P = 0.02) and [225Ac]Ac-anti-CD33-RIT (P &amp;lt; 0.00001) significantly reduced disease burden over that of respective controls. Conclusions: We have successfully developed a novel anti-CD33 immunoPET-CT–based noninvasive modality for AML and its spatial distribution, indicating a preferential skeletal niche.
TCT-285 Stent Diameter and Clinical Outcomes After PCI: From the COMBO MASCOT and REMEDEE Collaboration
Authors: Doreen Zeebregts, Puk de Wilde, Vera de Winter, Jaya Chandrasekhar, Deborah Kalkman, Melissa Aquino, Pier Woudstra, Marcel Beijk, Davide Cao, Ridhima Goel, Rishi Chandiramani, Moritz Blum, Anastasios Roumeliotis, Samantha Sartori, Rachel Singleton, Usman Baber, Jan Tijssen, Karel Koch, George Dangas, Antonio Colombo, Robbert de Winter, Roxana Mehran
Journal: Journal of the American College of Cardiology (2019)
IFN-γ enhances cell-mediated cytotoxicity against keratinocytes via JAK2/STAT1 in lichen planus
Authors: Shuai Shao, Lam C. Tsoi, Mrinal K. Sarkar, Xianying Xing, Ke Xue, Ranjitha Uppala, Celine C. Berthier, Chang Zeng, Matthew Patrick, Allison C. Billi, Joseph Fullmer, Maria A. Beamer, Bethany Perez-White, Spiro Getsios, Andrew Schuler, John J. Voorhees, Sung Choi, Paul Harms, J. Michelle Kahlenberg, Johann E. Gudjonsson
Journal: Science Translational Medicine (2019)

IFN-γ enhances keratinocyte death in lichen planus.
Apolipoprotein AI) Promotes Atherosclerosis Regression in Diabetic Mice by Suppressing Myelopoiesis and Plaque Inflammation
Authors: Tessa J. Barrett, Emilie Distel, Andrew J. Murphy, Jiyuan Hu, Michael S. Garshick, Yoscar Ogando, Jianhua Liu, Tomas Vaisar, Jay W. Heinecke, Jeffrey S. Berger, Ira J. Goldberg, Edward A. Fisher
Journal: Circulation (2019)

Despite robust cholesterol lowering, cardiovascular disease risk remains increased in patients with diabetes mellitus. Consistent with this, diabetes mellitus impairs atherosclerosis regression after cholesterol lowering in humans and mice. In mice, this is attributed in part to hyperglycemia-induced monocytosis, which increases monocyte entry into plaques despite cholesterol lowering. In addition, diabetes mellitus skews plaque macrophages toward an atherogenic inflammatory M1 phenotype instead of toward the atherosclerosis-resolving M2 state typical with cholesterol lowering. Functional high-density lipoprotein (HDL), typically low in patients with diabetes mellitus, reduces monocyte precursor proliferation in murine bone marrow and has anti-inflammatory effects on human and murine macrophages. Our study aimed to test whether raising functional HDL levels in diabetic mice prevents monocytosis, reduces the quantity and inflammation of plaque macrophages, and enhances atherosclerosis regression after cholesterol lowering.
TCT-127 Long-Term Clinical Outcomes of Young Acute Myocardial Infarction Patients Underwent Percutaneous Coronary Intervention
Authors: Seung-Woon Rha, Dong Joo Oh, Ahmed Mashaly, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Jinah Cha, Yoonjee Park, Dong Oh Kang, Won Young Jang, Woohyeun Kim, Ja Yeon Choi, Jin Oh Na, Cheol Ung Choi, Chang Gyu Park, Hong Seog Seo
Journal: Journal of the American College of Cardiology (2019)
Abstract 10734: Association Between Fetuin A and Geriatric Sarcopenic Heart Failure: Echocardiographic Survey From Tianliao Old People (TOP) Study
Authors: Wei-Ting Chang, Wei-Chuan Tsai, Chih-Hsing Wu, Yi-Heng Li, Liang-Miin Tsai, Jyh-Hong Chen, Ping-Yen Liu
Journal: Circulation (2013)

Aims: Sarcopenia is an aging condition involving low muscle mass and low muscle function. Fetuin A (FetA), has recently been reported to be as a factor for body composition remodeling. We hypothesi...
TCT-771 Percutaneous Device Closure of Ruptured Sinus of Valsalva: Feasibility of Transthoracic Echocardiography-Assisted Procedure
Authors: Dinkar Bhasin, Arvind Balaji, Sivasubramanian Ramakrishnan, Saurabh Gupta, Shyam Kothari, Anita Saxena, Rakesh Yadav, Vinay Bahl
Journal: Journal of the American College of Cardiology (2019)
Divergent Hypoglycemic Effects of Hepatic-Directed Prandial Insulin: A 6-Month Phase 2b Study in Type 1 Diabetes
Authors: David Klonoff, Bruce Bode, Nathan Cohen, Marc Penn, W. Blair Geho, Douglas B. Muchmore
Journal: Diabetes Care (2019)

OBJECTIVE Hepatic-directed vesicle insulin (HDV) uses a hepatocyte-targeting moiety passively attaching free insulin, improving subcutaneous insulin’s hepatic biodistribution. We assessed HDV-insulin lispro (HDV-L) versus insulin lispro (LIS) in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Insulin Liver Effect (ISLE-1) was a 26-week, phase 2b, multicenter, randomized, double-blind, noninferiority trial. RESULTS Among 176 randomized participants (HDV-L n = 118, LIS n = 58), the difference in change from baseline A1C was 0.09% (95% CI −0.18% to 0.35%), confirming noninferiority (prespecified margin ≤0.4%). Overall, there were no statistically significant differences between treatments for hypoglycemia or insulin dosing. However, baseline A1C modified the treatment group effect (interaction P &amp;lt; 0.001) on clinically apparent hypoglycemia designated by treatment-blinded investigators as severe. Thus, at higher baseline A1C, there was less hypoglycemia and lower insulin dosing with similar A1C outcomes during HDV-L versus LIS, whereas greater risk of hypoglycemia despite similar A1C outcomes and insulin doses was observed with lower baseline A1C. Among poorly controlled participants (A1C ≥8.5%), incidence rates of severe hypoglycemia in the HDV-L and LIS arms were 69 and 97 events/100 person-years, respectively (P = 0.03), whereas with A1C &amp;lt;8.5%, respective rates were 191 and 21 events/100 person-years (P = 0.001). Similar A1C-dependent trends in hypoglycemia were seen with continuous glucose monitoring. Among poorly controlled participants, bolus insulin doses at end point were ∼25% lower with HDV-L (P = 0.02), despite similar A1C outcomes; in better-controlled participants, insulin doses and A1Cs were stable over time in both subgroups. No safety signals were identified. CONCLUSIONS Hepatic biodistribution of HDV-L appears to potentiate insulin effect in T1D, with divergent clinical outcomes in hypoglycemia dependent on baseline A1C.
Effect of Light Flashes vs Sham Therapy During Sleep With Adjunct Cognitive Behavioral Therapy on Sleep Quality Among Adolescents
Authors: Katherine A. Kaplan, Meital Mashash, Rayma Williams, Holly Batchelder, Lolly Starr-Glass, Jamie M. Zeitzer
Journal: JAMA Network Open (2019)

Owing to biological, behavioral, and societal factors, sleep duration in teenagers is often severely truncated, leading to pervasive sleep deprivation.To determine whether a novel intervention, using both light exposure during sleep and cognitive behavioral therapy (CBT), would increase total sleep time in teenagers by enabling them to go to sleep earlier than usual.This double-blind, placebo-controlled, randomized clinical trial, conducted between November 1, 2013, and May 31, 2016, among 102 adolescents enrolled full-time in grades 9 to 12, who expressed difficulty going to bed earlier and waking up early enough, was composed of 2 phases. In phase 1, participants were assigned to receive either 3 weeks of light or sham therapy and were asked to try to go to sleep earlier. In phase 2, participants received 4 brief CBT sessions in addition to a modified light or sham therapy. All analyses were performed on an intent-to-treat basis.Light therapy consisted of receiving a 3-millisecond light flash every 20 seconds during the final 3 hours of sleep (phase 1) or final 2 hours of sleep (phase 2). Sham therapy used an identical device, but delivered 1 minute of light pulses (appearing in 20-second intervals, for a total of 3 pulses) per hour during the final 3 hours of sleep (phase 1) or 2 hours of sleep (phase 2). Light therapy occurred every night during the 4-week intervention. Cognitive behavioral therapy consisted of four 50-minute in-person sessions once per week.Primary outcome measures included diary-based sleep times, momentary ratings of evening sleepiness, and subjective measures of sleepiness and sleep quality.Among the 102 participants (54 female [52.9%]; mean [SD] age, 15.6 [1.1] years), 72 were enrolled in phase 1 and 30 were enrolled in phase 2. Mixed-effects models revealed that light therapy alone was inadequate in changing the timing of sleep. However, compared with sham therapy plus CBT alone, light therapy plus CBT significantly moved sleep onset a mean (SD) of 50.1 (27.5) minutes earlier and increased nightly total sleep time by a mean (SD) of 43.3 (35.0) minutes. Light therapy plus CBT also resulted in a 7-fold greater increase in bedtime compliance than that observed among participants receiving sham plus CBT (mean [SD], 2.21 [3.91] vs 0.29 [0.76]), as well as a mean 0.55-point increase in subjective evening sleepiness as compared with a mean 0.48-point decrease in participants receiving sham plus CBT as measured on a 7-point sleepiness scale.This study found that light exposure during sleep, in combination with a brief, motivation-focused CBT intervention, was able to consistently move bedtimes earlier and increase total sleep time in teenagers. This type of passive light intervention in teenagers may lead to novel therapeutic applications.ClinicalTrials.gov identifier: NCT01406691.
Bubble continuous positive airway pressure for children with high-risk conditions and severe pneumonia in Malawi: an open label, randomised, controlled trial
Authors: Eric D McCollum, Tisungane Mvalo, Michelle Eckerle, Andrew G Smith, Davie Kondowe, Don Makonokaya, Dhananjay Vaidya, Veena Billioux, Alfred Chalira, Norman Lufesi, Innocent Mofolo, Mina Hosseinipour
Journal: The Lancet Respiratory Medicine (2019)

Pneumonia is the leading cause of death among children globally. Most pneumonia deaths in low-income and middle-income countries (LMICs) occur among children with HIV infection or exposure, severe malnutrition, or hypoxaemia despite antibiotics and oxygen. Non-invasive bubble continuous positive airway pressure (bCPAP) is considered a safe ventilation modality that might improve child pneumonia survival. bCPAP outcomes for high-risk African children with severe pneumonia are unknown. Since most child pneumonia hospitalisations in Africa occur in non-tertiary district hospitals without daily physician oversight, we aimed to examine whether bCPAP improves severe pneumonia mortality in such settings.This open-label, randomised, controlled trial was done in the general paediatric ward of Salima District Hospital, Malawi. We enrolled children aged 1-59 months old with WHO-defined severe pneumonia and either HIV infection or exposure, severe malnutrition, or an oxygen saturation of less than 90%. Children were randomly assigned 1:1 to low-flow nasal cannula oxygen or nasal bCPAP. Non-physicians administered care; the primary outcome was hospital survival. Primary analyses were by intention-to-treat and interim and adverse events analyses per protocol. This trial is registered with ClinicalTrials.gov, number NCT02484183, and is closed.We screened 1712 children for eligibility between June 23, 2015, and March 21, 2018. The data safety and monitoring board stopped the trial for futility after 644 of the intended 900 participants were enrolled. 323 children were randomly assigned to oxygen and 321 to bCPAP. 35 (11%) of 323 children who received oxygen died in hospital, as did 53 (17%) of 321 who received bCPAP (relative risk 1·52; 95% CI 1·02-2·27; p=0·036). 13 oxygen and 17 bCPAP patients lacked hospital outcomes and were considered lost to follow-up. Suspected adverse events related to treatment occurred in 11 (3%) of 321 children receiving bCPAP and 1 (<1%) of 323 children receiving oxygen. Four bCPAP and one oxygen group deaths were classified as probable aspiration episodes, one bCPAP death as probable pneumothorax, and six non-death bCPAP events included skin breakdown around the nares.bCPAP treatment in a paediatric ward without daily physician supervision did not reduce hospital mortality among high-risk Malawian children with severe pneumonia, compared with oxygen. The use of bCPAP within certain patient populations and non-intensive care settings might carry risk that was not previously recognised. bCPAP in LMICs needs further evaluation before wider implementation for child pneumonia care.Bill & Melinda Gates Foundation, International AIDS Society, Health Empowering Humanity.
Uptick in Neuroinvasive West Nile
Authors: Bridget Kuehn
Journal: JAMA (2019)

The incidence of neuroinvasive disease linked to West Nile virus (WNV) infections was 25% higher in 2018 (0.51 per 100 000) than the median incidence between 2008 and 2017 (0.41 per 100 000), according to a CDC report.
Incidental Coronary Artery Calcification in Cancer Imaging
Authors: Sarah Cuddy, MBBCh, David L. Payne, BA, David J. Murphy, MBBCh, Ruth M. Dunne, MBBCh, MPH, Raphael Bueno, MD, Ron Blankstein, MD, Marcelo Di Carli, MD, Mandeep R. Mehra, MD, Anju Nohria, MD, John D. Groarke, MBBCh, MPH
Journal: JACC CardioOncology (2019)

Cardiovascular (CV) disease is a leading cause of death among 15 million cancer survivors in the United States today [(1)][1]. Mitigating CV risk in this population should be a priority for both oncologists and cardiologists. Most patients with cancer undergo nongated chest computed tomography (
Measuring the Quality of Diabetes Care
Authors: Dario Giugliano, Maria Ida Maiorino, Katherine Esposito
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
TCT-570 Impact of Modified Composite WIFI Score Including Patient Background and Anatomic Pattern for Predicting Wound Healing on Clinical Outcomes in Chronic Limb-Threatening Ischemia Patients After Endovascular Therapy
Authors: Kenji Makino, Keisuke Hirano, Masahiro Yamawaki, Motoharu Araki, Norihiro Kobayashi, Shinsuke Mori, Yasunari Sakamoto, Masakazu Tsutsumi, Shigemitsu Shirai, Yoshiaki Ito
Journal: Journal of the American College of Cardiology (2019)
Safety and Tolerability of Sustained Lipid-Lowering Therapy
Authors: Maarten J. G. Leening
Journal: JAMA Cardiology (2019)

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 Cardiology 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 Cardiology journal
TCT-580 Prognostic Value of the Index of Microcirculatory Resistance Over Serum Biomarkers in Light Chain Cardiac Amyloidosis
Authors: Joo Myung Lee, Ki Hong Choi, Seung Hun Lee, Soree Kim, Minjung Bak, Kyu Tae Park, Jin-Oh Choi, Eun-Seok Jeon
Journal: Journal of the American College of Cardiology (2019)
Genetic Ablation or Pharmacological Inhibition of PRMT5 Affects Maintenance of Genomic Integrity in Hematopoietic Stem Cells
Authors: Darren Qiancheng Tan, Desmond Wai Loon Chin, Ying Li, Ayako Nakamura-Ishizu, Henry Yang, Toshio Suda
Journal: Blood (2017)