tbuckley/cabot-search huggingface dataset:
EGFR Activates a TAZ-Driven Oncogenic Program in Glioblastoma
Authors: Minling Gao, Yi Fu, Weiqiang Zhou, Gege Gui, Bachuchu Lal, Yunqing Li, Shuli Xia, Hongkai Ji, Charles G. Eberhart, John Laterra, Mingyao Ying
Journal: Cancer Research (2021)

Abstract Hyperactivated EGFR signaling is a driver of various human cancers, including glioblastoma (GBM). Effective EGFR-targeted therapies rely on knowledge of key signaling hubs that transfer and amplify EGFR signaling. Here we focus on the transcription factor TAZ, a potential signaling hub in the EGFR signaling network. TAZ expression was positively associated with EGFR expression in clinical GBM specimens. In patient-derived GBM neurospheres, EGF induced TAZ through EGFR–ERK and EGFR–STAT3 signaling, and the constitutively active EGFRvIII mutation caused EGF-independent hyperactivation of TAZ. Genome-wide analysis showed that the EGFR–TAZ axis activates multiple oncogenic signaling mechanisms, including an EGFR–TAZ–RTK positive feedback loop, as well as upregulating HIF1α and other oncogenic genes. TAZ hyperactivation in GBM stem-like cells induced exogenous mitogen-independent growth and promoted GBM invasion, radioresistance, and tumorigenicity. Screening a panel of brain-penetrating EGFR inhibitors identified osimertinib as the most potent inhibitor of the EGFR–TAZ signaling axis. Systemic osimertinib treatment inhibited the EGFR–TAZ axis and in vivo growth of GBM stem-like cell xenografts. Overall these results show that the therapeutic efficacy of osimertinib relies on effective TAZ inhibition, thus identifying TAZ as a potential biomarker of osimertinib sensitivity. Significance: This study establishes a genome-wide map of EGFR–TAZ signaling in glioblastoma and finds osimertinib effectively inhibits this signaling, justifying its future clinical evaluation to treat glioblastoma and other cancers with EGFR/TAZ hyperactivation.
Wearable Glucose Monitoring and Implantable Drug Delivery Systems for Diabetes Management
Authors: Jinyuan Zhang, Jian Xu, Jongcheon Lim, James K. Nolan, Hyowon Lee, Chi Hwan Lee
Journal: Advanced Healthcare Materials (2021)

Abstract The global cost of diabetes care exceeds $1 trillion each year with more than $327 billion being spent in the United States alone. Despite some of the advances in diabetes care including continuous glucose monitoring systems and insulin pumps, the technology associated with managing diabetes has largely remained unchanged over the past several decades. With the rise of wearable electronics and novel functional materials, the field is well‐poised for the next generation of closed‐loop diabetes care. Wearable glucose sensors implanted within diverse platforms including skin or on‐tooth tattoos, skin‐mounted patches, eyeglasses, contact lenses, fabrics, mouthguards, and pacifiers have enabled noninvasive, unobtrusive, and real‐time analysis of glucose excursions in ambulatory care settings. These wearable glucose sensors can be integrated with implantable drug delivery systems, including an insulin pump, glucose responsive insulin release implant, and islets transplantation, to form self‐regulating closed‐loop systems. This review article encompasses the emerging trends and latest innovations of wearable glucose monitoring and implantable insulin delivery technologies for diabetes management with a focus on their advanced materials and construction. Perspectives on the current unmet challenges of these strategies are also discussed to motivate future technological development toward improved patient care in diabetes management.
Association of imbalance between job workload and functional ability with return to work in ARDS survivors
Authors: Han Su, Ramona O Hopkins, Biren B Kamdar, Susanne May, Victor D Dinglas, Kurt L Johnson, Megan Hosey, Catherine L Hough, Dale M Needham, Hilaire J Thompson
Journal: Thorax (2021)

Inability to return to work (RTW) is common after acute respiratory distress syndrome (ARDS). Mismatch in an individual's job workload and his or her functional ability, termed work ability imbalance, is negatively associated with RTW, but has not been evaluated in ARDS survivors.
Molecular mechanisms of radioactive iodine refractoriness in differentiated thyroid cancer: Impaired sodium iodide symporter (NIS) expression owing to altered signaling pathway activity and intracellular localization of NIS
Authors: Ji Min Oh, Byeong-Cheol Ahn
Journal: Theranostics (2021)

The advanced, metastatic differentiated thyroid cancers (DTCs) have a poor prognosis mainly owing to radioactive iodine (RAI) refractoriness caused by decreased expression of sodium iodide symporter (NIS), diminished targeting of NIS to the cell membrane, or both, thereby decreasing the efficacy of RAI therapy. Genetic aberrations (such as BRAF, RAS, and RET/PTC rearrangements) have been reported to be prominently responsible for the onset, progression, and dedifferentiation of DTCs, mainly through the activation of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Eventually, these alterations result in a lack of NIS and disabling of RAI uptake, leading to the development of resistance to RAI therapy. Over the past decade, promising approaches with various targets have been reported to restore NIS expression and RAI uptake in preclinical studies. In this review, we summarized comprehensive molecular mechanisms underlying the dedifferentiation in RAI-refractory DTCs and reviews strategies for restoring RAI avidity by tackling the mechanisms.
REVERSION OF DNA METHYLATION AT CARDIAC RISK PREDICTOR LOCI DEMONSTRATES THE POTENTIAL OF EPIGENETICS TO GUIDE CHD PREVENTION THERAPY USING DNA FROM BLOOD OR SALIVA
Authors: Robert Philibert, Willem Philibert, Allan Andersen, Kelsey Dawes, Eric Hoffman, Meesha Dogan
Journal: Journal of the American College of Cardiology (2021)
HAND GRIP STRENGTH AND TYPE 2 DIABETES ARE MUTUALLY INDEPENDENT PREDICTORS OF CARDIOVASCULAR EVENTS AND OF MORTALITY IN PATIENTS WITH ESTABLISHED CARDIOVASCULAR DISEASE
Authors: Barbara Larcher, Alexander Vonbank, Arthur Mader, Maximilian Maechler, Lukas Sprenger, Beatrix Mutschlechner, Andreas Leiherer, Daniela Zanolin-Purin, Axel Muendlein, Heinz Drexel, Christoph H. Saely
Journal: Journal of the American College of Cardiology (2021)
Many more people could benefit from blood pressure lowering drugs, say researchers
Authors: Jacqui Wise
Journal: BMJ (2021)

Antihypertensive drug treatment can lower the risk of strokes, heart failure, and heart attacks even in adults with normal blood pressure, a large scale analysis of randomised trials concludes.1

The authors are calling for a change to clinical guidelines so that patients are considered for blood pressure lowering treatment on the basis of their overall cardiovascular risk, irrespective of their blood pressure or whether they have a previous history of cardiovascular disease.

The meta-analysis of pooled individual participant-level data, published in the Lancet , found that each 5 mm Hg reduction in systolic pressure lowered the relative risk of cardiovascular events by about 10%, irrespective of previous diagnoses of cardiovascular disease, and even at normal or high-normal blood pressure values.

The threshold blood pressure levels for starting treatment and the target levels to be achieved by treatment remain controversial. The current …
Abstract 16266: Efficacy and Safety of ICD Use in Peripartum Cardiomyopathy Patients
Authors: Andrew B Hughey, Thomas C Crawford, Nivedita Basu, Madeline K Mahowald, Melinda B Davis
Journal: Circulation (2018)

Introduction: ICDs are used in patients with peripartum cardiomyopathy (PPCM) to prevent sudden cardiac death (SCD), but the long-term ICD-related outcomes in this population are not known. Methods...
CLINICAL FEATURES ASSOCIATED WITH BRIDGING FIBROSIS IN ADOLESCENT PATIENTS WITH FONTAN-ASSOCIATED LIVER DISEASE
Authors: Neil Patel, Sara Khan, Carly Weaver, Cameron Goldbeck, George Yanni, Rohit Kohli, Yuri Genyk, Shengmei Zhou, Nick Shillingford, Patrick Sullivan, Cheryl Takao, Jon Detterich, Paul Kantor, John Cleveland, Cynthia Herrington, Ram Kumar Subramanyan, Vaughn Starnes, Sarah Badran, Juliet Emamaullee
Journal: Journal of the American College of Cardiology (2021)
Genetic and Developmental Contributors to Aortic Stenosis
Authors: Punashi Dutta, Jeanne F. James, Hail Kazik, Joy Lincoln
Journal: Circulation Research (2021)

Aortic stenosis (AS) remains one of the most common forms of valve disease, with significant impact on patient survival. The disease is characterized by left ventricular outflow obstruction and encompasses a series of stenotic lesions starting from the left ventricular outflow tract to the descending aorta. Obstructions may be subvalvar, valvar, or supravalvar and can be present at birth (congenital) or acquired later in life. Bicuspid aortic valve, whereby the aortic valve forms with two instead of three cusps, is the most common cause of AS in younger patients due to primary anatomic narrowing of the valve. In addition, the secondary onset of premature calcification, likely induced by altered hemodynamics, further obstructs left ventricular outflow in bicuspid aortic valve patients. In adults, degenerative AS involves progressive calcification of an anatomically normal, tricuspid aortic valve and is attributed to lifelong exposure to multifactoral risk factors and physiological wear-and-tear that negatively impacts valve structure-function relationships. AS continues to be the most frequent valvular disease that requires intervention, and aortic valve replacement is the standard treatment for patients with severe or symptomatic AS. While the positive impacts of surgical interventions are well documented, the financial burden, the potential need for repeated procedures, and operative risks are substantial. In addition, the clinical management of asymptomatic patients remains controversial. Therefore, there is a critical need to develop alternative approaches to prevent the progression of left ventricular outflow obstruction, especially in valvar lesions. This review summarizes our current understandings of AS cause; beginning with developmental origins of congenital valve disease, and leading into the multifactorial nature of AS in the adult population.
Squaramide‐Based Supramolecular Materials Drive HepG2 Spheroid Differentiation
Authors: Tingxian Liu, Linda van den Berk, Joeri A. J. Wondergem, Ciqing Tong, Markus C. Kwakernaak, Bas ter Braak, Doris Heinrich, Bob van de Water, Roxanne E. Kieltyka
Journal: Advanced Healthcare Materials (2021)

Abstract A major challenge in the use of HepG2 cell culture models for drug toxicity screening is their lack of maturity in 2D culture. 3D culture in Matrigel promotes the formation of spheroids that express liver‐relevant markers, yet they still lack various primary hepatocyte functions. Therefore, alternative matrices where chemical composition and materials properties are controlled to steer maturation of HepG2 spheroids remain desired. Herein, a modular approach is taken based on a fully synthetic and minimalistic supramolecular matrix based on squaramide synthons outfitted with a cell‐adhesive peptide, RGD for 3D HepG2 spheroid culture. Co‐assemblies of RGD‐functionalized squaramide‐based and native monomers resulted in soft and self‐recovering supramolecular hydrogels with a tunable RGD concentration. HepG2 spheroids are self‐assembled and grown (≈150 µm) within the supramolecular hydrogels with high cell viability and differentiation over 21 days of culture. Importantly, significantly higher mRNA and protein expression levels of phase I and II metabolic enzymes, drug transporters, and liver markers are found for the squaramide hydrogels in comparison to Matrigel. Overall, the fully synthetic squaramide hydrogels are proven to be synthetically accessible and effective for HepG2 differentiation showcasing the potential of this supramolecular matrix to rival and replace naturally‐derived materials classically used in high‐throughput toxicity screening.
THE U.S. INITIATIVE TO ELIMINATE RACIAL AND ETHNIC DISPARITIES IN HEALTH; THE IMPACT ON THE OUTCOMES OF STEMI IN NEW JERSEY
Authors: Niharika Bhatia, Deep Vakil, Stavros Zinonos, Nora M. Cosgrove, John B. Kostis, Abel E. Moreyra
Journal: Journal of the American College of Cardiology (2021)
TRENDS AND OUTCOMES OF CARDIOGENIC SHOCK AMONG PATIENTS ADMITTED TO ADVANCED HEART FAILURE CENTERS: ANALYSIS FROM THE NATIONWIDE INPATIENT SAMPLE 2011-2017
Authors: Harsh Mehta, Krishna Prasad Kurpad, Maya Safarova, Mohit Pahuja, Saad Amin, Sumit Sohal, Akshay Goel, Kamal Gupta
Journal: Journal of the American College of Cardiology (2021)
Abstract 9964: Effect of Hyperoxia on Coronary Artery Circulatory Mechanisms Determining Blood Flow Variations
Authors: Tariq Ali Ahmad, Urs Leuenberger, Pradeep Yadav, Ian Gilchrist, Charles Chambers, Abdul Basit, Matthew Muller, Hajduczok Alexander, Lawrence Sinoway
Journal: Circulation (2019)

Introduction: Hyperoxia has been shown to increases vascular resistance and hence decrease flow in healthy coronary arteries through various compensatory mechanisms including nitric oxide pathways....
THE TOTAL AMOUNT OF CRP WITHIN THE FIRST 72 H AFTER STEMI IS CRUCIAL FOR THE OUTCOME
Authors: Ahmed Sheriff, Wolfgang Ries, Jan Torzewski, Christian Pflücke, Harald Darius, Franz Heigl, Hüseyin Ince, Steffen Mitzner, Peter Nordbeck, Christian Butter, Christoph Garlichs
Journal: Journal of the American College of Cardiology (2021)
Abstract P127: Gene-Lifestyle Interactions Detect Novel Blood Pressure Loci
Authors: Oyomoare L Osazuwa-Peters, Karen L Schwander, Yun J Sung, Lisa de las Fuentes, Dabeeru C Rao
Journal: Circulation (2018)

Introduction: Gene-lifestyle interaction effects (GxE more generally) on blood pressure (BP), a promising approach for novel loci discovery, is being actively pursued in the CHARGE Gene-Lifestyle Interactions Working Group using individual lifestyle domains, such as smoking status. Objectives: To explore the potential utility of a “lifestyle index” (aggregating multiple lifestyle domains) for identifying novel BP loci in a GxE context, we performed genome-wide interaction analysis with two lifestyle index variables. Methods: For each of 6,257 subjects (19 – 80 years, 46.9% male) in the Framingham Heart Study SHARe dataset, lifestyle index was defined as the sum of risk scores for four lifestyle factors: smoking status (0 = Never, 1 = Former, 2 = Current), alcohol intake (0 = Moderate, 1 = Never, 2 = Heavy), physical activity (0 = Active, 1= Inactive), and educational level (0=College degree, 1 = Some college, and 2 = No college). We examined GxE for systolic BP using the quantitative index (ranging from 0 to 7) and a binary form of the index (≥ vs &lt; the median), while adjusting for sex, age, and kinship. Promising loci were identified using a 2 df joint test of main and interaction effects at α = 5 x 10 -6 . Results: Sixteen promising single nucleotide polymorphisms (SNPs) representing 8 loci were found when using the quantitative lifestyle index, and 43 SNPs representing 4 loci when using the binary lifestyle index (Table 1), with only one locus common to both indices. Of the 11 unique loci detected, 3 are within 500 kb of known BP loci and 6 are in or near a gene with a known function. Conclusions: We demonstrate that a composite of multiple lifestyle factors can enhance novel discovery.
THE ASSOCIATION OF BODY MASS INDEX AND ANEMIA ON REVASCULARIZATION OUTCOMES IN VERY ELDERLY PATIENTS PRESENTING WITH ACUTE MYOCARDIAL INFARCTION
Authors: Derek Phan, Ara Rostomian, Ming-Sum Lee, Naing Moore, Prakash Mansukhani, Vicken Aharonian, Somjot Brar, Ray Zadegan
Journal: Journal of the American College of Cardiology (2021)
A Systematic Review of the Impact of Surgeon and Hospital Caseload Volume on Oncological and Nononcological Outcomes After Radical Prostatectomy for Nonmetastatic Prostate Cancer
Authors: Thomas Van den Broeck, Daniela Oprea-Lager, Lisa Moris, Mithun Kailavasan, Erik Briers, Philip Cornford, Maria De Santis, Giorgio Gandaglia, Silke Gillessen Sommer, Jeremy P. Grummet, Nikos Grivas, Thomas B.L. Lam, Michael Lardas, Matthew Liew, Malcolm Mason, Shane O’Hanlon, Jakub Pecanka, Guillaume Ploussard, Olivier Rouviere, Ivo G. Schoots, Derya Tilki, Roderick C.N. van den Bergh, Henk van der Poel, Thomas Wiegel, Peter-Paul Willemse, Cathy Y. Yuan, Nicolas Mottet
Journal: European Urology (2021)
BURDEN OF ARRHYTHMIA IN ALCOHOL WITHDRAWAL HOSPITALIZATIONS
Authors: Samarthkumar Thakkar, Harsh Patel, Leela Krishna Teja Boppana, Mohammed Faisaluddin, Ashish Kumar, Aakash Sheth, Betsy Rojas, Toralben Patel, Marmik Patel, Nimit Dalal, Baibhav Bipul, Mohan Rao, Christopher DeSimone, Abhishek Deshmukh
Journal: Journal of the American College of Cardiology (2021)
ANALYZING THE EFFECT OF RENAL FUNCTION IN PATIENTS WITH CHRONIC LIMB ISCHEMIA UNDERGOING ENDOVASCULAR TREATMENT
Authors: Aakash Sheth, Harsh Patel, Kirtenkumar Patel, Samarthkumar Thakkar, Devina Adalja, Krunalkumar Patel, Raj Patel, Fadee Kutom, Toralben Patel, Marmik Patel, Desai Virmitra, Fahria Parisha, Rajkumar Doshi, Sidakpal Panaich
Journal: Journal of the American College of Cardiology (2021)
PREVALENCE AND PREDICTORS OF COVID 19 RELATED BURNOUT AMONG HEALTHCARE WORKERS; FINDINGS FROM BRUCEE LI STUDY
Authors: Mohit Dayal Gupta, Manish Jha, M.P. Girish, Ankit Bansal, Prattay G. Sarkar, Jamal Yusuf, Suresh Kumar, Satish Kumar, Ajeet Jain, Sanjeev Kathuria, Rajni Saijpaul, Rakesh Yadav, Ramakrishnan S, Rajeev Malhotra, Vishal Batra, Saibal Mukhopadhyay, Anubha Gupta, Manu Shetty, Anurag Mishra, Vikas Malhotra, Sandeep Garg
Journal: Journal of the American College of Cardiology (2021)
Improved activity of MC3T3-E1 cells by the exciting piezoelectric BaTiO3/TC4 using low-intensity pulsed ultrasound
Authors: Kunzhan Cai, Yilai Jiao, Quan Quan, Yulin Hao, Jie Liu, Lin Wu
Journal: Bioactive Materials (2021)

Developing bioactive materials for bone implants to enhance bone healing and bone growth has for years been the focus of clinical research. Barium titanate (BT) is an electroactive material that can generate electrical signals in response to applied mechanical forces. In this study, a BT piezoelectric ceramic coating was synthesized on the surface of a TC4 titanium alloy, forming a BT/TC4 material, and low-intensity pulsed ultrasound (LIPUS) was then applied as a mechanical stimulus. The combined effects on the biological responses of MC3T3-E1 cells were investigated. Results of scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray diffraction showed that an uniform nanospheres -shaped BT coating was formed on TC4 substrate. Piezoelectric behaviors were observed using piezoelectric force microscopy with the piezoelectric coefficient d
IMAGING-GUIDED CARDIAC RESYNCHRONIZATION THERAPY: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Babikir Kheiri, Ryle Przybylowicz, Timothy Simpson, Miranda Merrill, Mohammed Osman, Khidir Dalouk, Hind Rahmouni, Eric Stecker, Babak Nazer, Charles Henrikson
Journal: Journal of the American College of Cardiology (2021)
DRUG-COATED BALLOON VERSUS DRUG-ELUTING STENT IN SMALL VESSEL CORONARY ARTERY DISEASE: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Wasawat Vutthikraivit, Pattara Rattanawong, Prapaipan Putthapiban, Pavida Pachariyanon, Genanew Bedanie, Kanak Parmar, Elias Hanna
Journal: Journal of the American College of Cardiology (2021)
IMPACT OF DIASTOLIC INTERVENTRICULAR SEPTAL FLATTENING ON CLINICAL OUTCOME IN PATIENTS WITH SEVERE TRICUSPID REGURGITATION
Authors: Taku Omori, Mika Maeda, Shunsuke Kagawa, Shunsuke Shimada, Goki Uno, Takahiro Shiota
Journal: Journal of the American College of Cardiology (2021)
BURDEN OF MENTAL HEATH DISORDERS AMONG OLDER CHILDREN AND TEENAGERS WITH CONGENITAL HEART DISEASE: A POPULATION-BASED ANALYSIS
Authors: Krishna Kishore Umapathi, Kristie Sparks, Harshitha Dhanpalreddy, Aravind Thavamani, Joshua Murphy, Sawsan Awad
Journal: Journal of the American College of Cardiology (2021)
A CATHETER-BASED ASPIRATION DEBRIDEMENT STRATEGY FOR TRICUSPID ENDOCARDITIS-A FOCUS ON OUTCOMES AND COST-EFFECTIVENESS
Authors: Atul R. Chugh, Anusha Chaturvedi, Manesh Parikshak, Nanette Kelley, Marc Gerdisch, Kathleen Kioussopoulos, Charles Kiell
Journal: Journal of the American College of Cardiology (2021)
Cognitive Function in Adolescents and Young Adults With Youth-Onset Type 1 Versus Type 2 Diabetes: The SEARCH for Diabetes in Youth Study
Authors: Allison L.B. Shapiro, Dana Dabelea, Jeanette M. Stafford, Ralph D’Agostino, Catherine Pihoker, Angela D. Liese, Amy S. Shah, Anna Bellatorre, Jean M. Lawrence, Leora Henkin, Sharon Saydah, Greta Wilkening
Journal: Diabetes Care (2021)

OBJECTIVE Poor cognition has been observed in children and adolescents with youth-onset type 1 (T1D) and type 2 diabetes (T2D) compared with control subjects without diabetes. Differences in cognition between youth-onset T1D and T2D, however, are not known. Thus, using data from SEARCH for Diabetes in Youth, a multicenter, observational cohort study, we tested the association between diabetes type and cognitive function in adolescents and young adults with T1D (n = 1,095) or T2D (n = 285). RESEARCH DESIGN AND METHODS Cognition was assessed via the National Institutes of Health Toolbox Cognition Battery, and age-corrected composite Fluid Cognition scores were used as the primary outcome. Confounder-adjusted linear regression models were run. Model 1 included diabetes type and clinical site. Model 2 additionally included sex, race/ethnicity, waist-to-height ratio, diabetes duration, depressive symptoms, glycemic control, any hypoglycemic episode in the past year, parental education, and household income. Model 3 additionally included the Picture Vocabulary score, a measure of receptive language and crystallized cognition. RESULTS Having T2D was significantly associated with lower fluid cognitive scores before adjustment for confounders (model 1; P &amp;lt; 0.001). This association was attenuated to nonsignificance with the addition of a priori confounders (model 2; P = 0.06) and Picture Vocabulary scores (model 3; P = 0.49). Receptive language, waist-to-height ratio, and depressive symptoms remained significant in the final model (P &amp;lt; 0.01 for all, respectively). CONCLUSIONS These data suggest that while youth with T2D have worse fluid cognition than youth with T1D, these differences are accounted for by differences in crystallized cognition (receptive language), central adiposity, and mental health. These potentially modifiable factors are also independently associated with fluid cognitive health, regardless of diabetes type. Future studies of cognitive health in people with youth-onset diabetes should focus on investigating these significant factors.
TRACE OR LESS VALVULAR REGURGITATION ON TRANSTHORACIC ECHOCARDIOGRAM EXCLUDES NATIVE VALVE INFECTIVE ENDOCARDITIS ON TRANSESOPHAGEAL ECHOCARDIOGRAPHY
Authors: Jamie Elizabeth Diamond, Warren Manning, Jason Matos, Wendy Stead, Lawrence Markson, Jordan Strom
Journal: Journal of the American College of Cardiology (2021)