tbuckley/cabot-search huggingface dataset:
Progressive Cortical Thinning in Patients With Focal Epilepsy
Authors: Marian Galovic, Victor Q. H. van Dooren, Tjardo S. Postma, Sjoerd B. Vos, Lorenzo Caciagli, Giuseppe Borzì, Juana Cueva Rosillo, Khue Anh Vuong, Jane de Tisi, Parashkev Nachev, John S. Duncan, Matthias J. Koepp
Journal: JAMA Neurology (2019)

It is controversial whether epilepsy is a static or progressive disease. Evidence of progressive gray matter loss in epilepsy would support early diagnosis, rapid treatment, and early referral for surgical interventions.To demonstrate progressive cortical thinning in patients with focal epilepsy distinct from cortical thinning associated with normal aging.A case-control neuroimaging study was conducted from August 3, 2004, to January 26, 2016, among 190 patients with focal epilepsy at a tertiary epilepsy referral center (epilepsy data) and 3 independent comparison cohorts matched for age and sex (healthy volunteer data; n = 141).Two or more high-resolution T1-weighted magnetic resonance imaging scans at least 6 months apart (mean [SD] interval, 2.5 [1.6] years).Global and vertexwise rate of progressive cortical thinning.A total of 190 people with focal epilepsy (99 women and 91 men; mean [SD] age, 36 [11] years; 396 magnetic resonance imaging scans) were compared with 141 healthy volunteers (76 women and 65 men; mean [SD] age, 35 [17] years; 282 magnetic resonance imaging scans). Widespread highly significant progressive cortical thinning exceeding normal aging effects, mainly involving the bilateral temporal lobes, medial parietal and occipital cortices, pericentral gyri, and opercula, was seen in 146 individuals with epilepsy (76.8%; 95% CI, 58%-95%). The mean (SD) annualized rate of global cortical thinning in patients with epilepsy was twice the rate of age-associated thinning observed in healthy volunteers (0.024 [0.061] vs 0.011 [0.029] mm/y; P = .01). Progression was most pronounced in adults older than 55 years and during the first 5 years after the onset of seizures. Areas of accelerated cortical thinning were detected in patients with early onset of epilepsy and in patients with hippocampal sclerosis. Accelerated thinning was not associated with seizure frequency, history of generalized seizures, or antiepileptic drug load and did not differ between patients with or without ongoing seizures. Progressive atrophy in temporal (n = 101) and frontal (n = 28) lobe epilepsy was most pronounced ipsilaterally to the epileptic focus but also affected a widespread area extending beyond the focus and commonly affected the contralateral hemisphere. For patients with temporal lobe epilepsy, accelerated cortical thinning was observed within areas structurally connected with the ipsilateral hippocampus.Widespread progressive cortical thinning exceeding that seen with normal aging may occur in patients with focal epilepsy. These findings appear to highlight the need to develop epilepsy disease-modifying treatments to disrupt or slow ongoing atrophy. Longitudinal cortical thickness measurements may have the potential to serve as biomarkers for such studies.
Engineered nanoparticles for imaging and drug delivery in colorectal cancer
Authors: Eluri Pavitra, Begum Dariya, Gowru Srivani, Sung-Min Kang, Afroz Alam, Putty-Reddy Sudhir, Mohammad Amjad Kamal, Ganji Seeta Rama Raju, Young-Kyu Han, Bhaskar Venkata Kameswara Subrahmanya Lakkakula, Ganji Purnachandra Nagaraju, Yun Suk Huh
Journal: Seminars in Cancer Biology (2019)
Abstract 858: Oncogenic EGFR mutations as genomic biomarkers for cetuximab and panitumumab response in colorectal adenocarcinoma
Authors: Nayoung Kim, Jeonghee Cho
Journal: Cancer Research (2019)

Abstract Somatic mutations of Epidermal Growth Factor Receptor (EGFR) occur in ~3% of colorectal cancer patients. Here, through systematic functional screening of 21 recurrent EGFR mutations selected from public datasets, we show that 11 colon cancer-derived EGFR mutants; G63R, E114K, R165Q, R222C, S492R, P596L, K708R, E709K, G719S, G724S and L858R, are oncogenic, and able to transform cells in a ligand-independent manner. We demonstrate that cellular transformation by these mutants requires receptor dimerization. Importantly, the EGF-induced and constitutive oncogenic potential of these EGFR mutants are inhibited by cetuximab or panitumumab in vivo and in vitro. Taken together, we propose that a subset of EGFR mutations can serve as genomic predictors for response to anti-EGFR antibodies and that metastatic CRC patients with such mutations may benefit from these drugs as part of the first-line therapy. Citation Format: Nayoung Kim, Jeonghee Cho. Oncogenic EGFR mutations as genomic biomarkers for cetuximab and panitumumab response in colorectal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 858.
Abstract 16209: Clusterin-Nanoliposome Complex Attenuates Human Arteriole Endothelial Dysfunction Induced by AL Amyloid Light Chain Proteins
Authors: Daniel A Franco, Seth Truran, Volkmar Weissig, Camelia Burciu, Anthony Maltagliati, Shishir Murarka, Parameswaran Hari, Raymond Q Migrino
Journal: Circulation (2012)

Endothelial dysfunction is an early pathology in AL amyloidosis involving misfolded light chain protein (LC) toxicity. Clusterin (Clu) is a chaperone protein that stabilizes misfolded proteins. Con...
Abstract 14547: Strain Relaxation Index Predicts Heart Failure and Atrial Fibrillation Over a 10 Year Follow-Up Period: The Multi-Ethnic Study of Atherosclerosis
Authors: Bharath Ambale Venkatesh, Anderson Armstrong, Chia-Ying Liu, Sirisha Donekal, Kihei Yoneyama, Colin Wu, Antoinette S Gomes, Gregory W Hundley, David A Bluemke, Joao A Lima
Journal: Circulation (2012)

INTRODUCTION A novel strain relaxation index (SRI) is introduced to assess diastolic function by cardiac magnetic resonance (CMR), using myocardial deformation during LV relaxation. We investigate ...
Conflicts of Interest in Dermatology Patient Advocacy Organizations
Authors: Marc Boutin
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Abstract 11610: Communication in Pediatric Cardiac Intensive Care Unit Family Meetings May Benefit From Better Coordination of Team Members to Meet Family Needs
Authors: Jennifer Walter, Theodore Schall, Aaron Dewitt, Robert Arnold, Chris Feudtner
Journal: Circulation (2018)

Introduction: Parents of children in the pediatric cardiac intensive care unit (CICU) report inadequate communication and a lack of empathy during conversations with their clinicians. Objectives: I...
Abstract 510: Selective and potent CDK8 inhibitors enhance NK cell activity and promote tumor surveillance
Authors: Marco H. Hofmann, Rajeswaran Mani, Harald Engelhardt, Maria A. Impagnatiello, Sebastian Carotta, Marc A. Kerenyi, Seila Lorenzo-Herrero, Jark Boettcher, Dirk Scharn, Heribert Arnhof, Andreas Zoephel, Renate Schnitzer, Thomas Gerstberger, Girish Rajgolikar, Swagata Goswami, Sumithira Vasu, Peter Ettmayer, Segundo R. Gonzalez, Mark Pearson, Darryl B. McConnell, Norbert Kraut, Natarajan Muthusamy, Juergen Moll
Journal: Cancer Research (2019)

Abstract Natural killer (NK) cells play a pivotal role in controlling cancer. Activation of NK cells is tightly regulated by multiple extracellular receptors and internal signaling nodes. The production of perforin and granzyme B, key NK cytolytic molecules, is regulated by the suppressive signaling intermediate Cyclin Dependent Kinase 8 (CDK8) through phosphorylation and inhibition of STAT1S727. We identified highly potent and selective CDK8 inhibitors, including BI-9811 and BI-1347, that we previously reported as valuable probe compounds (Hofmann M.H. et al., AACR Annual Meeting 2017, Abstract 4630). CDK8 inhibition promoted activation of NK cells but had no direct cytotoxic activity on the majority of cancer cell lines tested. Single agent treatment with the CDK8 inhibitor BI-1347 increased the survival of mice bearing melanoma and breast cancer allografts. In addition to this, treatment with BI-1347 resulted in enhanced NK-cell mediated lysis of myeloid leukaemia and lymphoma cells. We evaluated whether increased efficacy could be observed upon activation of both the innate and the adaptive immune system by combining the CDK8 inhibitor with a SMAC mimetic. SMAC mimetic treatment enhanced T-cell activity and increased NK cell number in the murine EMT6 breast cancer model. Increased survival upon combination treatment was dependent on a pulsatile schedule of the CDK8 inhibitor BI-1347, which permitted activation of NK cells but avoided a hypo-responsive steady state. These results demonstrate that CDK8 inhibitors could be used either as a single agent in hematological cancers or be combined with modulators of the adaptive immune system to inhibit the growth of solid tumors. Citation Format: Marco H. Hofmann, Rajeswaran Mani, Harald Engelhardt, Maria A. Impagnatiello, Sebastian Carotta, Marc A. Kerenyi, Seila Lorenzo-Herrero, Jark Boettcher, Dirk Scharn, Heribert Arnhof, Andreas Zoephel, Renate Schnitzer, Thomas Gerstberger, Girish Rajgolikar, Swagata Goswami, Sumithira Vasu, Peter Ettmayer, Segundo R. Gonzalez, Mark Pearson, Darryl B. McConnell, Norbert Kraut, Natarajan Muthusamy, Juergen Moll. Selective and potent CDK8 inhibitors enhance NK cell activity and promote tumor surveillance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 510.
A comparison of the utilization and efficacy of palliative chemotherapy for the treatment of locally advanced or metastatic gastroesophageal carcinoma: a retrospective single-center analysis
Authors: R. Baumgartner, H. Taghizadeh, G. Jomrich, S. Schoppmann, M. Preusser, A. Ilhan-Mutlu
Journal: Annals of Oncology (2019)
A video decision aid to improve acute myeloid leukemia patients’ illness understanding: Results of a pilot trial.
Authors: Thomas William LeBlanc, Susan C. Locke, Kris Herring, Debra M. Davis, Jesse D Troy, Karen E. Steinhauser, Kathryn I. Pollak, Peter A. Ubel
Journal: Journal of Clinical Oncology (2019)

7040 Background: Many acute myeloid leukemia (AML) patients harbor misunderstandings about their illness, overestimating both their likelihood of cure and risks of intensive therapies. Decision aids (DA) can improve illness understanding and reduce decisional conflict, but are not routinely used in AML. Methods: We developed an AML DA with input from patients, caregivers, clinicians, and laypersons, via the International Patient Decision Aids Standards (IPDAS) process. It includes 10 short animated videos with voiceovers, covering AML basics, etiology, outcomes, treatment paradigms, and risks/benefits of various treatment approaches. We enrolled 20 patients in a pilot feasibility and efficacy trial, with pre/post survey assessments of AML knowledge via an 18-item questionnaire, decisional conflict (Decisional Conflict Scale; DCS), anxiety (State Trait Anxiety Inventory, Short Form; STAI-6), and measures of DA usability and satisfaction. Results: Participants were a mean of 62.4 years old, 12 (60%) were male, 17 (85%) white, and 15 (75%) had newly-diagnosed disease. Mean time since AML diagnosis was 145 days (median 31; range 2-1092). 16 (80%) exhibited high-school-level understanding of medical terms per the REALM-SF, and participants on average exhibited moderate numeracy (mean score of 4.1 on the Subjective Numeracy Scale). All participants completed the study, exceeding our pre-determined feasibility threshold. AML knowledge scores generally improved, from a mean of 11.8 correct items on pre-test, to 15.2 on post-test assessment (p &lt; 0.0001), with 80% of participants achieving improved scores. Struggles remained regarding patients’ understanding of the role that genetic tests play in AML care. There was no increase in anxiety after watching the videos, but decisional conflict was significantly reduced, from a mean of 28.5 at baseline to 22 in the post-test (p = .019). Participants reported high satisfaction and usability scores for the DA. Conclusions: Our AML decision aid exhibits favorable performance characteristics, with high satisfaction and usability, a marked increase in patient knowledge, and reduced decisional conflict. Further testing is warranted in a randomized trial. Clinical trial information: NCT03442452.
Pharmacotherapy in bronchiolitis at discharge from emergency departments within the Pediatric Emergency Research Networks: a retrospective analysis
Authors: Alisha Jamal, Yaron Finkelstein, Nathan Kuppermann, Stephen B Freedman, Todd A Florin, Franz E Babl, Stuart R Dalziel, Roger Zemek, Amy C Plint, Dale W Steele, David Schnadower, David W Johnson, Derek Stephens, Anupam Kharbanda, Damian Roland, Mark D Lyttle, Charles G Macias, Ricardo M Fernandes, Javier Benito, Suzanne Schuh
Journal: The Lancet Child & Adolescent Health (2019)
Abstract 4437: Effects of atypical protein Kinase c inhibitor (DNDA) on lung cancer proliferation and migration by PKC-ι/FAK ubiquination through the Cbl-b pathway
Authors: Raja Reddy Bommareddy, Rekha Patel, Mildred Acevedo Duncan
Journal: Cancer Research (2019)

Abstract Lung cancer is the second most common cancer and it is the leading cause of cancer death in both men and women. PKC isozymes play an important role in the development and progression of many cancers by regulating the cell cycle, survival, apoptosis, cell motility and malignant transformation. Our focus is to study the role of atypical PKCs (aPKC) in cell proliferation and migration in lung cancer cell lines. We used a novel non-specific inhibitor of aPKC namely DNDA (3,4-amino-2,7napthalenedisulfonic acid). Our hypothesis is that DNDA inhibits cell proliferation and migration of lung cancer cells. Our data from cell viability and flow cytometry showed significant reduction in cell proliferation and induction of apoptosis with DNDA (10µM) in A549 and H1299 lung cancer cells. Additionally, DNDA showed no toxic effect on BEAS-2B normal lung cells. Elevated levels of Focal Adhesion kinase (FAK) are implicated in the progression of cancer and plays a vital role in the invasion and migration of cancer cells. Western blot results showed that the phosphorylation of PKC-ι and phosphorylation of FAK were decreased in A549 lung cancer cells upon DNDA treatment. Moreover, there was no significant reduction in phosphorylation of FAK in H1299 lung cancer cells upon treatment with DNDA. Immunoprecipitation (IP) data revealed an association of PKC-ι with FAK and FAK with Cbl-b. Ubitest results suggests that PKC-ι regulates the cleavage of FAK through its ubiquination by cbl-b and thus inhibits the migration of A549 lung cancer cells which was evident from scratch assay. Our data indicates that DNDA might inhibit the migration of A549 lung cancer cells by PKC-ι/FAK ubiquination via Cbl-b. Citation Format: Raja Reddy Bommareddy, Rekha Patel, Mildred Acevedo Duncan. Effects of atypical protein Kinase c inhibitor (DNDA) on lung cancer proliferation and migration by PKC-ι/FAK ubiquination through the Cbl-b pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4437.
Studies Evaluating Statin Adherence and Outcome Should Adjust for Smoking Persistence and Antiplatelet Treatment Discontinuation
Authors: Pierre-Vladimir Ennezat, Raphaëlle-Ashley Guerbaai, Sylvestre Maréchaux
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
Abstract 156: Visfatin induces LOX expression and promotes tumor metastasis through the Src/Akt signaling pathway in human chondrosarcoma cells
Authors: Cheng-Chieh Yu, Chih-Yang Lin, Chih-Hsin Tang
Journal: Cancer Research (2019)

Abstract Chondrosarcoma, a common primary bone malignancy that affects the joints and bones, is associated with metastases in the lung, especially in cases of high-grade chondrosarcoma. The protein lysyl oxidase (LOX) can contribute to tumor growth and metastasis, while the adipokine visfatin is pro-angiogenic and facilitates tumorigenesis as well as metastasis. However, it is unclear as to whether any association exists between visfatin and LOX expression in human chondrosarcoma metastasis. We have discovered that visfatin induces the migration, invasion and increased expression of LOX mRNA and protein in human chondrosarcoma cell lines (JJ012 and SW1353). Pretreatment of these cell lines with Src and Akt inhibitors, or transfecting them with small interfering RNAs (siRNAs), inhibited visfatin-induced chondrosarcoma metastasis and LOX expression. Thus, visfatin promotes chondrosarcoma metastasis by inducing LOX expression via the Src/Akt signaling pathway in the JJ012 cell line. microRNA analysis revealed that visfatin-induced Src/Akt signaling is responsible for downregulating mature miR-26b-5p, which targets the 3' untranslated region (3`UTR) of LOX but does not affect primary and precursor miR-26b-5p expression. This downregulation of miR-26b-5p expression by visfatin was dose-dependent. Pretreatment with Src and Akt inhibitors or transfection with siRNA reversed miR-26b-5p expression. The migration and invasion ability of JJ012 cells was reduced when they were transfected with the miR-26b-5p mimic. In summary, our data demonstrate that visfatin induces LOX expression and promotes chondrosarcoma cell migration and invasion through the Src/Akt signaling pathway, by inhibiting miR-26b-5p. Citation Format: Cheng-Chieh Yu, Chih-Yang Lin, Chih-Hsin Tang. Visfatin induces LOX expression and promotes tumor metastasis through the Src/Akt signaling pathway in human chondrosarcoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 156.
Synthetic analogs of the marine natural product hemiasterlin: Optimization and discovery of E7974, a novel and potent antitumor agent
Authors: James J. Kowalczyk, Shawn E. R. Schiller, Mark Spyvee, Hu Yang, Boris M. Seletsky, Christina J. Shaffer, Veronique Marceau, Ye Yao, Galina Kuznetsov, Karen Tendyke, Diana Liu, Cheryl Rowell, Bruce A. Littlefield, Edward M. Suh
Journal: Cancer Research (2005)

1213  A series of 13 anthrapyrazole (AP) compounds that were analogs of piroxantrone and losoxantrone were synthesized. Three-dimensional quantitative structure-activity analyses (3D-QSAR) were carried out on the AP compounds using comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) in order to determine the factors affecting the cell growth inhibitory (CHO, DZR, K562 and K/VP.5 cells), DNA binding (ΔTm) and inhibition of DNA topoisomerase II decatenation catalytic activity. Conformational analysis of all analogs was first performed with the CONFORT module implemented in SYBYL to identify the global minimum energy conformation. The most active compound, AP10, was then used as the template molecule. Steric and electrostatic fields were determined in CoMFA and three additional fields (hydrophobic, hydrogen donor and hydrogen acceptor) were determined in CoMSIA. Both CoMFA and CoMSIA analysis of the biological properties yielded statistically significant models upon partial least squares analysis. The information obtained from CoMFA and CoMSIA 3D-contour maps is to be used to predict the activity of new anthrapyrazoles with increased activity. Support: CIHR and a Canada Research Chair in Drug Development
Abstract P010: Serum Vitamin D and Risk of Heart Failure: Prospective Results From the Moli-sani Study
Authors: Simona Costanzo, Amalia De Curtis, Augusto Di Castelnuovo, Mariarosaria Persichillo, Maria B Donati, Giovanni de Gaetano, Licia Iacoviello
Journal: Circulation (2016)

Introduction: Vitamin D deficiency has been associated with the progression of heart failure (HF) and Vitamin D supplementation may have protective effects in patients with HF. However, little is known on the predictive value of circulating Vitamin D levels on HF risk. Hypothesis: Low serum Vitamin D levels are associated with incident HF in a large prospective cohort of Italian adults. Methods: We analyzed 18,689 (48.4% men, age ≥35 years) HF-free individuals randomly recruited from the general population of the Moli-sani study, for whom complete data on HF and serum Vitamin D were available. Vitamin D was measured on serum by an immunoassay in the central laboratory of European BiomarCaRE project (Abbott Architect 25-OH Vitamin D, Wiesbaden, Germany). The cohort was followed up for a median of 4.2 years (80,849 person-years). Baseline serum Vitamin D was categorized in deficient/insufficient, hypovitaminosis, and normal (Table). Incident cases of HF were identified by linkage with the regional archive of hospital discharges. Hazard ratios (HRs) were calculated using Cox-proportional hazard models. Results: Subjects with normal, hypo or insufficient levels of Vitamin D were 12.2%, 79.6% and 8.2%, respectively. We identified 412 incident cases of HF. The incidence of HF was 1.1%, 2.2% and 3.9%, respectively in subjects with normal, hypo and insufficient levels of Vitamin D. After a multivariable analysis, considering a large panel of potential covariates, individuals with deficient/insufficient levels of serum Vitamin D showed a higher risk of developing HF (HR: 1.78, 95% CI: 1.07-2.97) than those with normal levels. Further adjustment for C-Reactive Protein did not modify the association (Table). Conclusions: Deficiency of Vitamin D is associated with a significantly higher risk of HF in a general adult population. This association was not explained by an inflammatory marker such as C-Reactive Protein.