tbuckley/cabot-search huggingface dataset:
TIMP3 expression associates with prognosis in colorectal cancer and its novel arylsulfonamide inducer, MPT0B390, inhibits tumor growth, metastasis and angiogenesis
Authors: Han-Li Huang, Yi-Min Liu, Ting-Yi Sung, Tsui-Chin Huang, Ya-Wen Cheng, Jing-Ping Liou, Shiow-Lin Pan
Journal: Theranostics (2019)

Tissue inhibitors of metalloproteinase 3 (TIMP3) are a major endogenous inhibitor of matrix metalloproteinase (MMPs) that inhibit tumor growth, invasion, metastasis and angiogenesis.In this study, we found that TIMP3 expression is associated with positive prognosis of colorectal cancer (CRC) clinicopathologically.Therefore, we developed a series of arylsulfonamide derivatives as TIMP3 inducers in order to define potential colorectal cancer therapeutic agent.Among these, MPT0B390 was selected for anti-tumor, anti-metastasis, and anti-angiogenesis property determination.Methods: The relationship between TIMP3 expression and clinical pathological features in colorectal patients and cell lines were determined by immunohistochemistry, bioinformatics analysis and western blotting.The anti-tumor function was validated by using MTT, apoptosis pathway detection and in vivo xenograft model for tumor growth inhibition determination.The anti-metastatic function was validated using a transwell migration assay, and using in vivo lung metastasis and liver metastasis models.The mechanism of MPT0B390-induced TIMP3 expression was further tested using qPCR and Chromatin IP assay.The anti-angiogenesis function was examined by using transwell migration assay, and in vivo Matrigel plug assay.Results: After screening candidate compounds, we identified MPT0B390 as an effective inducer of TIMP3.We showed that MPT0B390 induces TIMP3 expression significantly and inhibits CRC cell growth in vitro and in vivo.By inducing TIMP3 expression, MPT0B390 can also exert its anti-metastasis effect to inhibit CRC cell migration and invasion and downregulates migration markers such as uPA, uPAR, and c-Met.Subsequent Chromatin immunoprecipitation assay revealed that MPT0B390 can significantly inhibit EZH2 expression as well as its binding to TIMP3 promoter region to regulate TIMP3 induction.In addition to the anti-tumor and anti-metastasis capability, MPT0B390 can also induce TIMP3 expression in endothelial cells to inhibit tumor angiogenesis. Conclusion:These data suggest the potential therapeutic applications of the TIMP3 inducer, MPT0B390, for colorectal cancer treatment.
TCT-67 Predictors and Outcomes After Stent Failure Is Treated With Either CABG or PCI: An Individual Patient-Data Pooled Analysis From 32,880 Patients
Authors: Zhaoyang Chen, Akiko Maehara, Aaron Crowley, Gary Mintz, Pieter Smits, Roxana Mehran, Patrick Serruys, Gregg Stone
Journal: Journal of the American College of Cardiology (2019)
TCT-51 IVUS Predictors of Stent Expansion in Severely Calcified Lesions
Authors: Mingyou Zhang, Mitsuaki Matsumura, Eisuke Usui, Masahiko Noguchi, Tatsuhiro Fujimura, Khady Fall, Tamim Nazif, Sahil A. Parikh, Leroy Rabbani, Manish Parikh, Ajay Jayant Kirtane, Martin Leon, Gregg Stone, Jeffrey W. Moses, Dimitrios Karmpaliotis, Ziad Ali, Gary Mintz, Akiko Maehara
Journal: Journal of the American College of Cardiology (2019)
Revisiting NTRKs as an emerging oncogene in hematological malignancies
Authors: Sunil K. Joshi, Monika A. Davare, Brian J. Druker, Cristina E. Tognon
Journal: Leukemia (2019)

Abstract NTRK fusions are dominant oncogenic drivers found in rare solid tumors. These fusions have also been identified in more common cancers, such as lung and colorectal carcinomas, albeit at low frequencies. Patients harboring these fusions demonstrate significant clinical response to inhibitors such as entrectinib and larotrectinib. Although current trials have focused entirely on solid tumors, there is evidence supporting the use of these drugs for patients with leukemia. To assess the broader applicability for Trk inhibitors in hematological malignancies, this review describes the current state of knowledge about alterations in the NTRK family in these disorders. We present these findings in relation to the discovery and therapeutic targeting of BCR–ABL1 in chronic myeloid leukemia. The advent of deep sequencing technologies has shown that NTRK fusions and somatic mutations are present in a variety of hematologic malignancies. Efficacy of Trk inhibitors has been demonstrated in NTRK-fusion positive human leukemia cell lines and patient-derived xenograft studies, highlighting the potential clinical utility of these inhibitors for a subset of leukemia patients.
Abstract 16609: Characterization of Neurodevelopmental Defects Associated With a Mouse Model of Hypoplastic Left Heart Syndrome
Authors: George C Gabriel, Nathan Salamacha, William T Reynolds, Tuantuan Tan, Xiaoqin Liu, Hisato Yagi, Abha Bais, Ashok Panigrahy, Dennis Simon, Yijen Wu, Cecilia W Lo
Journal: Circulation (2018)

Introduction: Hypoplastic left heart syndrome (HLHS), a congenital heart defect involving left-sided heart structures, is associated with poor neurodevelopmental outcome, with &gt;30% experiencing neurodevelopmental impairment. A mouse model of HLHS showed brain abnormalities, suggesting a shared genetic etiology for brain and cardiac defects in HLHS. Hypothesis: Mutations in Sap130 and Pcdha9 causing HLHS in mice may individually or together cause brain abnormalities and neurobehavioral deficits. Methods and Results: Confocal histopathology and MR imaging was used to analyze the brain in mutant mice that were double Sap130/Pcdha9 homozygous, single Pcdha9 or Sap130 homozygous, or with forebrain targeted Emx1-Cre deletion of a floxed Sap130 allele . Sap130/Pcdha9 and Sap130 mutants exhibited overlapping phenotypes with microcephaly, thin cortex, and defects in the olfactory bulb, cerebellum, corpus callosum, and hippocampus, structures commonly affected in HLHS. RNAseq of Sap130/Pcdha9 mutant brain showed dysregulation of genes mediating learning and memory, long-term potentiation, motor coordination, feeding-processes often affected in HLHS. In the Emx1-Cre forebrain deleted Sap130 mice, forebrain hypoplasia was associated with cortical thinning and hippocampal dysplasia (Fig1 A,B). DTI connectome analysis showed global reduction in neuronal connections. Homozygous Pcdha9 mutant mice, which are adult viable, showed only hippocampal dysplasia, but connectome analysis also showed global reduction in neuronal connections (Fig1 C,D). In line with this, behavioral tests showed deficits in spatial memory acquisition and cued fear conditioning (Fig1 E,F). Conclusions: We showed HLHS associated Pchda9 and Sap130 mutations, individually or together, can cause brain defects with reduced neuronal connections and neurobehavioral deficits. These defects can occur independent of the cardiac lesion, indicating they are not of hemodynamic origin.
Tissue adhesive hyaluronic acid hydrogels for sutureless stem cell delivery and regeneration of corneal epithelium and stroma
Authors: Laura Koivusalo, Maija Kauppila, Sumanta Samanta, Vijay Singh Parihar, Tanja Ilmarinen, Susanna Miettinen, Oommen P. Oommen, Heli Skottman
Journal: Biomaterials (2019)

Regeneration of a severely damaged cornea necessitates the delivery of both epithelium-renewing limbal epithelial stem cells (LESCs) and stroma-repairing cells, such as human adipose-derived stem cells (hASCs). Currently, limited strategies exist for the delivery of these therapeutic cells with tissue-like cellular organization. With the added risks related to suturing of corneal implants, there is a pressing need to develop new tissue adhesive biomaterials for corneal regeneration. To address these issues, we grafted dopamine moieties into hydrazone-crosslinked hyaluronic acid (HA-DOPA) hydrogels to impart tissue adhesive properties and facilitate covalent surface modification of the gels with basement membrane proteins or peptides. We achieved tissue-like cellular compartmentalization in the implants by encapsulating hASCs inside the hydrogels, with subsequent conjugation of thiolated collagen IV or laminin peptides and LESC seeding on the hydrogel surface. The encapsulated hASCs in HA-DOPA gels exhibited good proliferation and cell elongation, while the LESCs expressed typical limbal epithelial progenitor markers. Importantly, the compartmentalized HA-DOPA implants displayed excellent tissue adhesion upon implantation in a porcine corneal organ culture model. These results encourage sutureless implantation of functional stem cells as the next generation of corneal regeneration.
Results from the U.S. Life after Stopping TKIs (LAST) Study
Authors: Ehab Atallah, Charles A. Schiffer, Jerald P. Radich, Kevin Weinfurt, Mei-Jie Zhang, Vamsi Kota, Javier Pinilla-Ibarz, Joseph O. Moore, Richard A. Larson, Vivian Oehler, Michael J. Mauro, Michael W. Deininger, James E. Thompson, Neil P. Shah, Martha Wadleigh, Ellen K Ritchie, Richard T Silver, Jorge E. Cortes, Arielle Baim, Mary M. Horowitz, Kathryn Flynn
Journal: Blood (2017)
Targeting Foam Cell Formation in Atherosclerosis: Therapeutic Potential of Natural Products
Authors: Dongdong Wang, Yang Yang, Yingnan Lei, Nikolay T. Tzvetkov, Xingde Liu, Andy Wai Kan Yeung, Suowen Xu, Atanas G. Atanasov
Journal: Pharmacological Reviews (2019)

Foam cell formation and further accumulation in the subendothelial space of the vascular wall is a hallmark of atherosclerotic lesions. Targeting foam cell formation in the atherosclerotic lesions can be a promising approach to treat and prevent atherosclerosis. The formation of foam cells is determined by the balanced effects of three major interrelated biologic processes, including lipid uptake, cholesterol esterification, and cholesterol efflux. Natural products are a promising source for new lead structures. Multiple natural products and pharmaceutical agents can inhibit foam cell formation and thus exhibit antiatherosclerotic capacity by suppressing lipid uptake, cholesterol esterification, and/or promoting cholesterol ester hydrolysis and cholesterol efflux. This review summarizes recent findings on these three biologic processes and natural products with demonstrated potential to target such processes. Discussed also are potential future directions for studying the mechanisms of foam cell formation and the development of foam cell-targeted therapeutic strategies.
TCT-547 Sham-Controlled Trials of Invasive Cardiovascular Interventions: A Systematic Review and Meta-Analysis
Authors: Lucas Lauder, Sean Scholz, Sebastian Ewen, William Wijns, Patrick Serruys, Elazer Edelman, Davide Capodanno, Bruno da Costa, Peter Juni, Felix Mahfoud
Journal: Journal of the American College of Cardiology (2019)
The Role of Humidity in Associations of High Temperature with Mortality: A Multicountry, Multicity Study
Authors: Ben Armstrong, Francesco Sera, Ana Maria Vicedo-Cabrera, Rosana Abrutzky, Daniel Oudin Åström, Michelle L. Bell, Bing-Yu Chen, Micheline de Sousa Zanotti Stagliorio Coelho, Patricia Matus Correa, Tran Ngoc Dang, Magali Hurtado Diaz, Do Van Dung, Bertil Forsberg, Patrick Goodman, Yue-Liang Leon Guo, Yuming Guo, Masahiro Hashizume, Yasushi Honda, Ene Indermitte, Carmen Íñiguez, Haidong Kan, Ho Kim, Jan Kyselý, Eric Lavigne, Paola Michelozzi, Hans Orru, Nicolás Valdés Ortega, Mathilde Pascal, Martina S. Ragettli, Paulo Hilario Nascimento Saldiva, Joel Schwartz, Matteo Scortichini, Xerxes Seposo, Aurelio Tobias, Shilu Tong, Aleš Urban, César De la Cruz Valencia, Antonella Zanobetti, Ariana Zeka, Antonio Gasparrini
Journal: Environmental Health Perspectives (2019)

Background: There is strong experimental evidence that physiologic stress from high temperatures is greater if humidity is higher. However, heat indices developed to allow for this have not consistently predicted mortality better than dry-bulb temperature. Objectives: We aimed to clarify the potential contribution of humidity an addition to temperature in predicting daily mortality in summer by using a large multicountry dataset. Methods: In 445 cities in 24 countries, we fit a time-series regression model for summer mortality with a distributed lag nonlinear model (DLNM) for temperature (up to lag 3) and supplemented this with a range of terms for relative humidity (RH) and its interaction with temperature. City-specific associations were summarized using meta-analytic techniques. Results: Adding a linear term for RH to the temperature term improved fit slightly, with an increase of 23% in RH (the 99th percentile anomaly) associated with a 1.1% [95% confidence interval (CI): 0.8, 1.3] decrease in mortality. Allowing curvature in the RH term or adding terms for interaction of RH with temperature did not improve the model fit. The humidity-related decreased risk was made up of a positive coefficient at lag 0 outweighed by negative coefficients at lags of 1–3 d. Key results were broadly robust to small model changes and replacing RH with absolute measures of humidity. Replacing temperature with apparent temperature, a metric combining humidity and temperature, reduced goodness of fit slightly. Discussion: The absence of a positive association of humidity with mortality in summer in this large multinational study is counter to expectations from physiologic studies, though consistent with previous epidemiologic studies finding little evidence for improved prediction by heat indices. The result that there was a small negative average association of humidity with mortality should be interpreted cautiously; the lag structure has unclear interpretation and suggests the need for future work to clarify. https://doi.org/10.1289/EHP5430
Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer: a multicentre, randomised, open-label, phase 2 trial
Authors: Antoinette R Tan, Gail S Wright, Anu R Thummala, Michael A Danso, Lazar Popovic, Timothy J Pluard, Hyo S Han, Željko Vojnović, Nikola Vasev, Ling Ma, Donald A Richards, Sharon T Wilks, Dušan Milenković, Zhao Yang, Joyce M Antal, Shannon R Morris, Joyce O'Shaughnessy
Journal: The Lancet Oncology (2019)
TCT-403 Dual Antithrombotic Therapy Is Safe and Effective in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: Updated Systematic Review and Meta-Analysis
Authors: Shahrukh Bakar, Mahvash Shere, Dennis Ko, Janet Martin, Pallav Garg
Journal: Journal of the American College of Cardiology (2019)
Invasive Pneumococcal Disease—Not Evenly Shared by All Children
Authors: Stephen I. Pelton, Rotem Lapidot, Inci Yildirim
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Quantitative Results of a National Intervention to Prevent Hospital-Acquired Catheter-Associated Urinary Tract Infection
Authors: Jennifer Meddings, Milisa Manojlovich, Jessica M. Ameling, Russell N. Olmsted, Andrew J. Rolle, M. Todd Greene, David Ratz, Ashley Snyder, Sanjay Saint
Journal: Annals of Internal Medicine (2019)

Background: Many hospitals struggle to prevent catheter-associated urinary tract infection (CAUTI). Objective: To evaluate the effect of a multimodal initiative on CAUTI in hospitals with high burden of health care–associated infection (HAI). Design: Prospective, national, nonrandomized, clustered, externally facilitated, pre–post observational quality improvement initiative, for 3 cohorts active between November 2016 and May 2018. Setting: Acute care, long-term acute care, and critical access hospitals, including intensive care and non–intensive care wards. Participants: Target hospitals had a high burden of Clostridioides difficile infection plus central line–associated bloodstream infection, CAUTI, or hospital-onset methicillin-resistant Staphylococcus aureus bloodstream infection, defined as cumulative attributable differences above the first tertile in the Targeted Assessment for Prevention (TAP) strategy. Some additional nonrecruited hospitals also joined. Intervention: Multimodal intervention, including Practice Change Assessment tool to identify infection prevention and control (IPC) and HAI prevention gaps; Web-based, on-demand modules involving onboarding, foundational IPC practices, HAI-specific 2-tiered approach to prioritize and implement interventions, and TAP resources; monthly webinars; state partner–led in-person meetings; and feedback. State partners made site visits to at least 50% of their enrolled hospitals, to support self-assessments and coach. Measurements: Rates of CAUTI and urinary catheter device utilization ratio. Results: Of 387 participating hospitals from 23 states and the District of Columbia, 361 provided CAUTI data. Over the study period, the unadjusted CAUTI rate was low and relatively stable, decreasing slightly from 1.12 to 1.04 CAUTIs per 1000 catheter-days. Catheter utilization decreased from 21.46 to 19.83 catheter-days per 100 patient-days from the pre- to the postintervention period. Limitations: The intervention period was brief, with no assessment of fidelity. Baseline CAUTI rates were low. Patient characteristics were not assessed. Conclusion: This multimodal intervention yielded no substantial improvements in CAUTI or urinary catheter utilization. Primary Funding Source: Centers for Disease Control and Prevention.
Healing Physicians
Authors: Lisa J. Merlo
Journal: JAMA (2016)

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-48 Bioresorbable Scaffold Versus Metallic Drug-Eluting Stent in Patients at High Risk of Restenosis (COMPARE-ABSORB trial): Very Late Device Thrombosis While on Extended DAPT
Authors: Robert-Jan Van Geuns, Chun-Chin Chang, Bernard Chevalier, Tommaso Gori, Emanuele Barbato, Giuseppe Tarantini, Stephan Achenbach, Dariusz Dudek, Javier Escaned, Mohamed Abdel-Wahab, Giovanni Esposito, Jan Tijssen, Marie-Claude Morice, Yoshinobu Onuma, Pieter Smits
Journal: Journal of the American College of Cardiology (2019)
TCT-571 Glasgow Prognostic Score Predicts the Clinical Outcomes in Critical Limb Ischemia With Tissue Loss After Endovascular Treatment
Authors: Kenji Makino, Keisuke Hirano, Shinsuke Mori, Masahiro Yamawaki, Motoharu Araki, Norihiro Kobayashi, Yasunari Sakamoto, Masakazu Tsutsumi, Shigemitsu Shirai, Yohsuke Honda
Journal: Journal of the American College of Cardiology (2019)
TCT-15 Prognostic Impact of Healed Coronary Plaque in Nonculprit Segments Assessed by Optical Coherence Tomography
Authors: Eisuke Usui, Gary Mintz, Tetsumin Lee, Mitsuaki Matsumura, Masahiro Hoshino, Yoshihisa Kanaji, Tomoyo Sugiyama, Taishi Yonetsu, Tsunekazu Kakuta, Akiko Maehara
Journal: Journal of the American College of Cardiology (2019)
TCT-250 Prevalence and Predictors of Coronary Artery Perforation During Percutaneous Coronary Interventions: Data From the ORPKI National Registry in Poland
Authors: Michal Wegiel, Tomasz Rakowski, Zbigniew Siudak, Krzysztof Plens, Artur Dziewierz, Ralf Birkemeyer, Pawel Kleczynski, Tomasz Tokarek, Lukasz Rzeszutko, Dariusz Dudek
Journal: Journal of the American College of Cardiology (2019)
Practice of spirometry among physicians caring for children with asthma in Portugal – The EspiroPed survey
Authors: C. Constant, J. Cosme, R.M. Fernandes, P. Fonte, J.A. Fonseca, C. Alves, T. Bandeira
Journal: Pulmonology (2019)

Aims:  to evaluate and compare current knowledge and practice in spirometry(SPR) prescription and interpretation among 4 physician groups caring for children/adolescents with asthma in Portugal: pediatricians(Ped), pulmonologists(Pn), allergy and immunology doctors(AI) and general practitioners(GP).   Methods:  Electronic survey sent to members of the 4 national societies. Only completed surveys from doctors following asthmatic children/adolescents were considered. Survey items addressed knowledge, accessibility, practices, interpretation and limitations regarding SPR. Survey Monkey® platform was used, with modified Dillman9s technique and anonymized data. Descriptive and comparative analysis was done (χ2 test). A local ethics committee gave approval.   Results:  Data from 423 doctors (89Ped, 40Pn, 30AI and 364GP) was analysed; 4% referred training in Pediatric Respiratory Medicine. 30%Ped, 90%Pn, 93%AI and 19%GP knew about SPR ATS/ERS guidelines (p 60%Pn and >85%Ped/AI/GP.   Conclusions:  Ped/GP report less familiarity with SPR in asthmatic children than Pn/AI. Acknowledging these gaps will allow implementation of specific SPR dissemination strategies adjusted to each specialty.