tbuckley/cabot-search huggingface dataset:
Oncocardiology—Past, Present, and Future
Authors: Edward T. H. Yeh, Hui-Ming Chang
Journal: JAMA Cardiology (2016)

Oncocardiology is a medical discipline that focuses on the identification, prevention, and treatment of cardiovascular complications related to cancer therapy. This discipline has gained interest from the cardiology community in recent years because of a remarkable increase in the number of cancer survivors and the proliferation of new cancer therapies causing cardiovascular complications, such as hypertension, heart failure, vascular complications, and cardiac arrhythmia. In this review, we provide historical perspectives, highlight new discoveries, and speculate on the opportunity created by merging the research interests and clinical practices of cardiology and oncology.The old paradigm of anthracycline cardiotoxic effects is replaced by new insights that anthracycline targets topoisomerase II β to cause DNA double-strand breaks and a profound change in the transcriptome leading to the generation of reactive oxygen species and the development of mitochondriopathy. Prevention of anthracycline cardiotoxic effects should be based on inhibiting or degrading topoisomerase II β. New challenges were posed by the introduction of trastuzumab and tyrosine kinase inhibitors that revolutionized cancer therapy. The on-target cardiotoxic effects of trastuzumab were owing to a prosurvival benefit of Her2 that binds to neuregulin, whereas the off-target effect of multitargeted tyrosine kinase inhibitors may be mediated by disruption of the vascular endothelial growth factor signaling pathway or the stress-induced angiogenesis. Sensitive imaging techniques, such as global strain, and biomarkers have allowed for early detection of cardiotoxic effects. Early treatment with heart failure medications may be beneficial in preventing the development of late cardiotoxic effects.Close collaboration between cardiologists and oncologists is required to meet the demand of an increasing number of cancer survivors. New insights based on mechanistic studies or genetic discoveries will pave the way for better prevention, diagnosis, and treatment of cancer therapy-induced cardiovascular complications.
Rictor has a pivotal role in maintaining quiescence as well as stemness of leukemia stem cells in MLL-driven leukemia
Authors: Y Fang, Y Yang, C Hua, S Xu, M Zhou, H Guo, N Wang, X Zhao, L Huang, F Yu, H Cheng, M L Wang, L Meng, T Cheng, W Yuan, D Ma, J Zhou
Journal: Leukemia (2016)
P0474 : Characterisation of the immune profiles of chronic hepatitis B patients following NUC discontinuation by cyTOF mass cytometry
Authors: L. Rivino, M. Van Den Berg, N. Le Bert, S. Koh, U.S. Gill, N.K. Hansi, G.R. Foster, A. Bertoletti, P.T. Kennedy
Journal: Journal of Hepatology (2015)
Фактори ризику розвитку стеатозу печінки в дітей
Authors: Yu.M. Stepanov, N.Yu. Zavhorodnia, O.Yu. Lukianenko, V.B. Yagmur, I.Yu. Skyrda, O.P. Petishko
Journal: GASTROENTEROLOGY (2016)

Неалкогольна жирова хвороба печінки є найбільш частою причиною захворювань печінки в дітей у всьому світі. Мета: визначити фактори ризику стеатозу печінки в дітей. Методи дослідження. Під нашим спостереженням були 32 дитини з розладами шлунково-кишкового тракту. Визначення наявності й ступеня стеатозу печінки проводили з використанням апарата FibroScan® 502 touch із визначенням контрольованого параметра ультразвукового затухання (CAP). За показниками CAP діти були розподілені на 2 групи: 1-ша група (основна) — 13 дітей із стеатозом (40,6 %), 2-га група (контрольна) — 19 дітей без стеатозу (59,4 %). Для визначення факторів ризику ми проаналізували історію життя й захворювання, дані об’єктивного клінічного й лабораторного обстеження хворих. Результати. Аналіз вікового розподілу показав, що в основній групі переважають діти віком понад 10 років (відносний ризик (RR) 3,3; відношення шансів (OR) 4,0; р = 0,1). Ожиріння було виявлене у 12 (92,3 %) дітей у групі хворих із стеатозом і в 9 (47 %) дітей, які не мали стеатозу. Збільшення окружності талії понад 95-й перцентиль спостерігалося у 12 (92,3 %) дітей в основній групі і 8 (42,1 %) дітей контрольної групи (RR 7,2; OR 16,5; р &lt; 0,05). Було встановлено, що наявність пубертатного гіпоталамічного синдрому пов’язана з ризиком розвитку стеатозу печінки в дітей (RR 30,6; OR 4,8; р &lt; 0,05). Обговорення. Як провідний фактор ризику розвитку стеатозу печінки в дітей слід розглядати абдомінальний тип ожиріння в поєднанні із захворюваннями ендокринної системи, а саме гіпоталамічним синдромом.
Medullary carcinoma of the breast: Ten year clinical experience of the Kuwait Cancer Control Centre
Authors: S. Samir, M. S. Fayaz, M. M. Motawy, S. Abuzallouf, T. George, M. M. Abdelhady, A. Bedair
Journal: Journal of Clinical Oncology (2008)

22188 Background: Medullary carcinomas of the breast account for fewer than 7% of all invasive breast cancers. Some investigators include medullary carcinomas in the favourable histologic subtype, despite its aggressive histologic appearance. However, others fail to confirm its favourable prognosis. Methods: This was a retrospective analysis of sixty-one (61) cases of breast cancer cases diagnosed with Medullary Carcinoma, presenting to the Kuwait Cancer Control Centre between 1995 and 2005. Results: Median survival time was 122 months and the seven year disease free survival was 82%. Overall survival rate was not assessed as no cases died during the study period. No cases were metastatic from the start and only eight cases developed metastases, local recurrence or contralateral breast primary. 68.8% of the cases were Stage I or IIA (i.e. no lymph node affection). Conclusions: There is no overt favourable prognosis of medullary carcinoma when compared to invasive ductal carcinoma. Prognosis is more related to stage than histologic subtyping. The majority of cases were negative estrogen and progesterone receptor status and node negative. No significant financial relationships to disclose.
Prediction Of CR On Reinduction In Patients With Newly Diagnosed Acute Myeloid Leukemia Given Intensive Induction Regimens: A Report From SWOG and Cleveland Clinic
Authors: Megan Othus, Mukherjee Sudipto, Mikkael A. Sekeres, John Godwin, Jeanne E. Anderson, Stephen Petersdorf, Frederick R. Appelbaum, Harry P Erba, Elihu H. Estey
Journal: Blood (2013)
Progressive MS Alliance Industry Forum: Maximizing Collective Impact To Enable Drug Development
Authors: P. Zaratin, G. Comi, T. Coetzee, K. Ramsey, K. Smith, A. Thompson, M. Panzara
Journal: Trends in Pharmacological Sciences (2016)

The Progressive MS Alliance Industry Forum describes a new approach to address barriers to developing treatments for progressive multiple sclerosis (MS). This innovative model promises to facilitate robust collaboration between industry, academia, and patient organizations and accelerate research towards the overarching goal of developing safe and effective treatments for progressive MS.
Modification of platinum sensitivity by KEAP1/NRF2 signals in non-small cell lung cancer
Authors: Yijun Tian, Kongming Wu, Qian Liu, Na Han, Li Zhang, Qian Chu, Yuan Chen
Journal: Journal of Hematology & Oncology (2016)

The objective of this study was to evaluate the effect of platinum-based drugs on nuclear-factor erythroid2 like 2 (NRF2) signaling in non-small cell lung cancer cell lines with or without Kelch-like ECH-associated protein 1 (KEAP1) mutations and to determine the role of NRF2 and KEAP1 on platinum-based drug treatment. We used real-time PCR to assess relative mRNA expression and used western blotting and immunofluorescence assays to assess protein expression. Small interfering RNA and shuttle plasmids were used to modulate the expression of NRF2, wild-type KEAP1, and mutant KEAP1. Drug sensitivity to platinum-based drugs was evaluated with Cell Count Kit-8. We found that platinum-based therapies modified the NRF2 signaling pathway differently in KEAP1-mutated non-small cell lung cancer (NSCLC) cell lines compared with wild-type KEAP1 cell lines. The reactive degree of NRF2 signaling also varies between nedaplatin and cisplatin. The modification of NRF2 or KEAP1 expression in NSCLC cell lines disrupted downstream gene expression and cell sensitivity to platinum-based drugs. Finally, gene expression data retrieved from The Cancer Genome Atlas (TCGA) consortium indicated that KEAP1 mutation significantly affects NRF2 signaling activity in patients with NSCLC. Our findings suggest that NRF2 signaling plays an indispensable role in NSCLC cell sensitivity to platinum-based treatments and provides a rationale for using NRF2 as a specific biomarker for predicting which patients will be most likely to benefit from platinum-based treatment.
How long is now? The multiple timescales of language processing
Authors: Christopher J. Honey, Janice Chen, Kathrin Müsch, Uri Hasson
Journal: Behavioral and Brain Sciences (2016)

Abstract Christiansen &amp; Chater (C&amp;C) envision language function as a hierarchical chain of transformations, enabling rapid, continuous processing of input. Their notion of a “Now-or-Never” bottleneck may be elaborated by recognizing that timescales become longer at successive levels of the sensory processing hierarchy – that is, the window of “Now” expands. We propose that a hierarchical “process memory” is intrinsic to language processing.
The Consult Guys - Fact or Fiction: O<sub>2</sub>for Myocardial Infarction?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2016)

Web Exclusives16 August 2016The Consult Guys - Fact or Fiction: O2 for Myocardial Infarction?FREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDSearch for more papers by this author and Howard H. Weitz, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W16-0008 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Consult Guys bring a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations.For more videos from and information on The Consult Guys, visit www.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Janssen, Portola; Consultancies: Bristol-Myers Squibb, Janssen. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 16 August 2016Volume 165, Issue 4Page: CG1KeywordsDisclosureMuscular dystrophiesMyocardial infarctionResearch grantsResearch reporting guidelines ePublished: 16 August 2016 Issue Published: 16 August 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.Loading ...
Ranibizumab Treatment for Pigment Epithelial Detachment Secondary to Neovascular Age-Related Macular Degeneration
Authors: David Sarraf, Nikolas J.S. London, Rahul N. Khurana, Pravin U. Dugel, Shamika Gune, Lauren Hill, Lisa Tuomi
Journal: Ophthalmology (2016)

To analyze the effect of baseline presence and height of pigment epithelial detachments (PEDs) on visual and anatomic outcomes at 24 months in patients with neovascular age-related macular degeneration (AMD) treated with ranibizumab.Post hoc analysis of HARBOR, a 24-month, phase III, randomized, multicenter, double-masked, active treatment-controlled study (clinicaltrials.gov identifier, NCT00891735).One thousand ninety-seven patients with neovascular AMD.Intravitreal ranibizumab 0.5 mg or 2.0 mg monthly or pro re nata (PRN) after 3 monthly loading doses.We evaluated the effect of presence and height of baseline PED on several outcomes at 24 months, including best-corrected visual acuity (BCVA), change in PED height, resolution of PED, and number of injections in the PRN arms. Development of macular atrophy at month 24 by presence or absence of PED was evaluated.Five hundred ninety-eight (54.5%) patients showed PED at baseline. In the ranibizumab 0.5-mg PRN group, mean numbers of injections were similar for patients with PED present or absent at baseline (14.0 vs. 12.5). Mean BCVA gains from baseline to 24 months were seen in all treatment groups and were comparable in patients with or without PED at baseline treated with ranibizumab 0.5 mg monthly (PED present at baseline, +9.0 letters; PED absent at baseline, +11.3 letters), 0.5 mg PRN (present, +8.4; absent, +7.9), 2.0 mg monthly (present, +7.1; absent, +11.1), or 2.0 mg PRN (present, +7.2; absent, +8.8). When analyzed by baseline PED height, mean BCVA gains were demonstrated and comparable in all treatment groups at 24 months except for patients treated with ranibizumab 2.0 mg monthly in the extra-large group (PEDs ≥352 μm; mean BCVA change, -0.8 letters). At 24 months, 53.2% (0.5 mg monthly), 44.5% (0.5 mg PRN), 70.4% (2.0 mg monthly), and 57.3% (2.0 mg PRN) of patients showed complete resolution of PED.Ranibizumab 0.5 mg given monthly or PRN effectively treated PEDs in patients with neovascular AMD, and significant vision gains resulted regardless of PED status and height at baseline. In this analysis, there was no additional vision benefit with a higher dose of ranibizumab (2.0 mg).
Abstract POSTER-BIOL-1348: No association between PARK2 and BRCA1-associated gynecologic cancers
Authors: Christine Walsh, Hoorig Nassanian, Hasmik Agadjanian, Carl Miller, Sandra Orsulic, Beth Karlan
Journal: Clinical Cancer Research (2015)

Abstract Purpose of study: We sought to identify genomic modifiers of gynecologic cancer penetrance in BRCA1 185delAG mutation carriers. In a pilot study using the Illumina 610K Quad chip to perform a whole genome analysis of 592,532 single nucleotide polymorphisms (SNP), we found significant SNP genotype differences in the PARK2 gene between BRCA1 185delAG mutation carriers who developed gynecologic cancer (cases) compared to those who did not (controls). These SNPS created a haplotype structure that was present at four-times higher frequency in cases than controls (37% vs. 9%, p=0.0009). We hypothesized that PARK2, which has been shown to be mutated in other cancers and to have a tumor suppressive function, plays a role in the biology of BRCA1-associated gynecologic cancer development. Experimental Procedures: To validate a PARK2 risk haplotype in an independent dataset, we isolated germline DNA from 85 BRCA1 185delAG mutation carriers and used TaqMan SNP Genotyping to genotype seven SNPs in PARK2. To determine whether a correlation exits between the PARK2 risk haplotype and PARK2 expression levels in tissue, we quantified PARK2 expression in normal ovaries and ovarian cancer tissue using quantitative real-time PCR (qPCR). To determine the rate of PARK2 mutations in 17 BRCA1-associated ovarian cancers, we used a touchdown PCR protocol to amplify and sequence each PARK2 exon. To identify exon deletions and duplications in the PARK2 gene, we utilized the multiplex ligation-dependent probe amplification (MLPA) technique. Summary of Data: In an independent dataset of 85 BRCA1 185delAG mutation carriers, we found the PARK2 risk haplotype to be present in 35 (17%) of cases. The risk haplotype was present in a higher proportion of cancer cases than benign controls (6/12 or 50% vs. 29/73 or 8%), but this was not significant (p=0.54). We did not find a difference in PARK2 ovarian tissue expression levels in patients with and without the PARK2 risk haplotype. We sequenced the PARK2 gene and performed MPLA analysis from tumor DNA of 17 ovarian cancers from BRCA1 185delAG mutation carriers, but did not identify any deleterious PARK2 mutations or exon deletions and duplications. Conclusions: We did not validate a PARK2 risk haplotype as a modifier of gynecologic cancer penetrance in BRCA1 185delAG mutation carriers. We did not find evidence for PARK2 inactivation in BRCA1-associated gynecologic tumors. Citation Format: Christine Walsh, Hoorig Nassanian, Hasmik Agadjanian, Carl Miller, Sandra Orsulic, Beth Karlan. No association between PARK2 and BRCA1-associated gynecologic cancers [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1348.
Abstract 1955: IKKϵ maintains MEK activation and suppresses non-canonical NF-κB signaling in triple-negative breast cancer
Authors: Carrie House, Valentina Grajales, Helmae Wubneh, Danielle Kimble, Marianne Kim, Christina Annunziata
Journal: Cancer Research (2015)

Abstract Metastatic breast cancer carries a poor prognosis despite the success of newly targeted therapies. Treatment options remain especially limited for the subtype of triple negative breast cancer (TNBC). Several signaling pathways, including NF-κB, are altered in TNBC, and the complexity of this disease implies multifaceted pathway interactions and compensatory signaling. We hypothesized that a subset of TNBCs expresses IKKϵ to promote a specific NF-κB signaling program that can enhance metastatic potential. Our data suggest that IKKϵ supports MEK activation and suppresses non-canonical signaling by the p52 NF-κB transcription factor. We found that NF-κB p52 expression is inversely proportional to activated MEK. We further demonstrate that IKKϵ and MEK cooperate to support viability and invasion potential under adherent conditions, whereas the p52 transcription factor supports viability under non-adherent conditions, underscoring the contrasting roles of these proteins. This study illustrates the diverse roles of NF-κB signaling components in TNBC, and highlights the adaptability of NF-κB in maintaining cancer cell survival under different microenvironments. A better understanding of the diversity of NF-κB signaling may ultimately improve the development of novel therapeutic regimens for TNBC. Citation Format: Carrie House, Valentina Grajales, Helmae Wubneh, Danielle Kimble, Marianne Kim, Christina Annunziata. IKKϵ maintains MEK activation and suppresses non-canonical NF-κB signaling in triple-negative breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1955. doi:10.1158/1538-7445.AM2015-1955
Abstract 18838: The Impacts of Burst Exercise Compared to Sustained Exercise on the Cardiometabolic Status and Exercise Behavior of Newly Diagnosed Type 2 Diabetic Patients
Authors: Avinash Pandey, Paul Poirier
Journal: Circulation (2015)

Introduction: Physical activity is an integral part of type 2 diabetes (NIDDM) rehabilitation. Historically, NIDDM rehabilitation has employed low intensity, sustained exercise. Recent studies have demonstrated cardiometabolic benefits of high intensity burst exercise in healthy volunteers. The impacts of burst exercise in NIDDM have yet to be assessed. This study compared the impacts of burst and sustained exercises on cardiometabolic factors including: BMI, exercise adherence, cardiopulmonary fitness, HbA1C and lipid profiles in newly diagnosed NIDDM. Hypothesis: High-intensity burst physical activity may yield greater cardiometabolic benefits than low intensity, sustained exercise. Methods: This was a single center, single blind randomized trial. 76 patients, within three months of diagnosis of NIDDM, were recruited. Patients were randomized to a control group prescribed 30 minutes of exercise five days a week at 65% of target heart rate or an intervention group prescribed ten minutes of exercise three times a day, five days a week at 85% of target heart rate. All patients underwent routine blood tests, stress tests and logged exercise duration and frequency in logbooks. Patients were excluded from the study if they had evidence for diabetic end organ damage or cardiovascular disease, or took medications which would impact the cardiometabolic parameters assessed in this study. Results: Of 225 patients screened, 76 patients were recruited for the study with an average age of 67; 70% were male. No significant differences in demographics were noted between groups. Patients prescribed the burst regimen exercised 27% more than the control (p&lt;0.01). Burst exercise patients also showed a 2.3 fold greater improvement in HbA1c (p&lt;0.01). The intervention group also improved more in their lipid profile, BMI and cardiopulmonary fitness (as measured by stress testing). Linear regression analysis revealed greater improvements in both HbA1C and BMI with burst exercise than with sustained exercise, for the same duration of exercise. Conclusions: The burst exercise regimen significantly improved the cardiometabolic and fitness status of newly diagnosed NIDDM. This regimen may represent a simple and effective way to improve diabetes rehabilitation.
Increasing airway obstruction from 8 to 18 years in extremely preterm/low-birthweight survivors born in the surfactant era
Authors: Lex W Doyle, Anne-Marie Adams, Colin Robertson, Sarath Ranganathan, Noni M Davis, Katherine J Lee, Jeanie L Cheong
Journal: Thorax (2016)

<h3>Background</h3> The evolution of airway obstruction into late adolescence of extremely preterm (gestational age &lt;28 weeks) or extremely low-birthweight (birth weight &lt;1000 g) survivors in the era after surfactant was introduced is unclear. <h3>Objective</h3> To compare changes in spirometry from 8 to 18 years of age of a geographical cohort of preterm survivors with normal birth weight controls, and to determine higher risk groups within the preterm cohort. <h3>Methods</h3> Of 297 extremely preterm/low-birthweight survivors born in 1991–1992 in the state of Victoria, Australia, 81% and 70% had spirometry at 8 and 18 years of age, respectively. Corresponding rates among 260 normal birth weight controls were 80% and 58%, respectively. Data were analysed using linear mixed models. <h3>Results</h3> The preterm group had substantial impairments in airflow at both ages compared with controls (eg, mean differences in z-score for FEV<sub>1</sub>; 8 years −1.02, 95% CI −1.21 to −0.82; 18 years −0.92, 95% CI −1.14 to −0.71). The preterm group had a greater increase in small airway obstruction between 8 and 18 years compared with controls. Within the preterm group, those who had bronchopulmonary dysplasia in the newborn period and those who were smokers at 18 years had airway obstruction that increased over time compared with those who did not. <h3>Conclusions</h3> Preterm survivors born in the surfactant era had significant impairments in airflow through childhood into late adolescence that increased over time compared with controls. At-risk preterm participants include those who had bronchopulmonary dysplasia, and smokers at 18 years.
Nature, Nurture, and Cancer Risks: Genetic and Nutritional Contributions to Cancer
Authors: Evropi Theodoratou, Maria Timofeeva, Xue Li, Xiangrui Meng, John P.A. Ioannidis
Journal: Annual Review of Nutrition (2017)

It is speculated that genetic variants are associated with differential responses to nutrients (known as gene–diet interactions) and that these variations may be linked to different cancer risks. In this review, we critically evaluate the evidence across 314 meta-analyses of observational studies and randomized controlled trials of dietary risk factors and the five most common cancers (breast, lung, prostate, colorectal, and stomach). We also critically evaluate the evidence across 13 meta-analyses of observational studies of gene–diet interactions for the same cancers. Convincing evidence for association was found only for the intake of alcohol and whole grains in relation to colorectal cancer risk. Three nutrient associations had highly suggestive evidence and another 15 associations had suggestive evidence. Among the examined gene–diet interactions, only one had moderately strong evidence.