tbuckley/cabot-search huggingface dataset:
Abstract 17341: Deep Sequencing Analysis of Myocardial and Circulating microRNA Profiles in Patients with Advanced Heart Failure and Controls
Authors: Kemal M Akat, D'Vesharronne Moore, Miguel Brown, Pavel Morozov, Christina Wu, Hirokazu Akashi, Thomas Tuschl, P. Christian Schulze
Journal: Circulation (2012)

Background: MicroRNA (miRNA) profiles in patients with heart failure (HF) show considerable differences compared to normal cardiac profiles. Recently, several cardiac-specific miRNAs have been desc...
The clinical impact of performing routine next generation sequencing (NGS) in gastrointestinal stromal tumors (GIST).
Authors: Ciara Marie Kelly, Timothy Geoffrey Bowler, Sandra P. D'Angelo, Mark Andrew Dickson, Mrinal M. Gounder, Mary Louise Keohan, Taylor Vonya, Sam S. Yoon, Samuel Singer, Ronald P. DeMatteo, Cristina R. Antonescu, Ahmet Zehir, Marc Ladanyi, David B. Solit, Ping Chi, William D. Tap
Journal: Journal of Clinical Oncology (2017)

11010 Background: The majority of GISTs harbor activating mutations in KIT or PDGFRα but the clinical relevance of other genomic alterations is unknown. We sought to determine the clinical impact of performing routine NGS and to describe the molecular landscape in GIST. Methods: From April 2014 to August 2016, 177 patients (pts) consented to an IRB-approved protocol. Tumor and matched normal samples were prospectively analyzed in a CLIA-compliant laboratory, with MSK-IMPACT, a NGS assay of up to 468 cancer-associated genes. Results: 191 samples were analyzed. NGS was most often performed in the setting of advanced disease (n = 108 (57%)). The primary tumor was most commonly tested (n = 120 (63%)). NGS guided clinical management in 79% (n = 150) of cases [matched therapy (MT) offered, n = 120/150 (80%); MT not offered, n = 24/150 (16%)]. In 25/41 cases (61%) where NGS did not influence management, treatment was not indicated because the GISTs were low risk. Most samples had ≤ 3 mutations (muts) (range: 0-17). Actionable muts were identified in 155/191 samples (81%). These included muts in KIT, PDGFRα and BRAF [oncoKB stratification: level 1 (84%), 2A (13%), 2B (2%), 3A(1%)]. 33/177 pts did not have a KIT/ PDGFRα mut [SDH deficiency, n = 15 (45%), NF1, n = 10 (30%), BRAF, n = 1(3%), NF1&amp;BRAF, n = 1 (3%)]. 5pts had quadruple wild type GIST. Most GISTs had at least one genetic alteration in a non-driver allele (74%, n = 141/191)[frequently mutated genes in KIT exon 11 driven i) primary tumors include TP53, MAX, MLL2, SETD2, PIK3CA, TSC1; and ii) metastatic tumors include RB1, SETD2, PTEN, ANKRD11, TP53, TSC1]. CDKN2A deletion was the most common copy number alteration identified in KIT driven GIST and occurred most often in metastatic samples (with and without co-occurring, secondary KIT muts) and those with high mitotic rate. Conclusions: NGS of GIST informs clinical management in the majority of pts through the identification of muts in canonical driver genes. NGS also identifies a high prevalence of tumor-specific genetic alterations in non-canonical driver genes. These genes function in multiple pathways including intracellular signaling, chromatin remodeling, proteasomal degradation and cell cycle regulation.
Clinical outcome and risk factors for failure in late acute prosthetic joint infections treated with debridement and implant retention
Authors: Marjan Wouthuyzen-Bakker, Marine Sebillotte, Jose Lomas, Adrian Taylor, Eva Benavent Palomares, Oscar Murillo, Javad Parvizi, Noam Shohat, Javier Cobo Reinoso, Rosa Escudero Sánchez, Marta Fernandez-Sampedro, Eric Senneville, Kaisa Huotari, José Maria Barbero, Joaquín Garcia-Cañete, Jaime Lora-Tamayo, Matteo Carlo Ferrari, Danguole Vaznaisiene, Erlangga Yusuf, Craig Aboltins, Rihard Trebse, Mauro José Salles, Natividad Benito, Andrea Vila, Maria Dolores Del Toro, Tobias Siegfried Kramer, Sabine Petersdorf, Vicens Diaz-Brito, Zeliha Kocak Tufan, Marisa Sanchez, Cédric Arvieux, Alex Soriano
Journal: Journal of Infection (2018)
Abstract 3083: Ameliorative effect of ethanolic extract of <i>Annona muricata</i> against sodium arsenite-induced hepatotoxicty in Wistar rats
Authors: Adenike M. Adegboyega
Journal: Cancer Research (2018)

Abstract Ingestion of arsenic in drinking water causes cancer at multiple tissues and there is no cure. Cancer has become a great monster to human race, as it places a significant emotional and economic burden on families and governments all over the world. Research is therefore directed at chemoprevention using medicinal herbs for the management of arsenicosis. In this study, we evaluated the in vitro antioxidant and protection offered by Annona muricata L. (AM) against sodium arsenite induced hepatotoxicity in rats. Antioxidant and radical scavenging activities of AM were compared to vitamin C and butylated hydroxytoluene (BHT). Proximate and phytochemical analyses were also carried out. Hepatoprotective study was investigated with six groups of rats that received distilled water (Control), 5.0 mg/kg bwt of NaAsO2, 250 mg/kg bwt AM, 500 mg/kg bwt AM, NaAsO2 plus 250 mg/kg AM, NaAsO2 and 500 mg/kg AM. The NaAsO2 was given once on days 7, 14 and 21, while AM was administered orally daily for 21 days. Serum transaminases and alkaline phosphatase activities were determined and liver histopathology carried out. AM contained 2.00% ash, 1.94% crude fat, 25.65% crude fibre, 2.88% protein and 58.62% carbohydrate. Phytochemical analysis indicated the presence of alkaloids, flavonoids and cardiac glycosides. The reducing power and metal chelating ability was in the order Vit C &amp;gt; BHT &amp;gt; AM, while for DPPH scavenging ability AM &amp;gt; Vit C &amp;gt; BHT. The NaAsO2 significantly (p &amp;lt; 0.05) increased the liver function enzymes relative to control. However, AM treatment markedly reduced the marker enzymes and restores the severe vaculation of hepatocytes in the NaAsO2 group to near normal. Our findings suggest that AM may constitute a remedy against arsenic induced hepatic injuries. Citation Format: Adenike M. Adegboyega. Ameliorative effect of ethanolic extract of Annona muricata against sodium arsenite-induced hepatotoxicty in Wistar rats [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3083.
Pathological Response and Survival in Triple-Negative Breast Cancer Following Neoadjuvant Carboplatin plus Docetaxel
Authors: Priyanka Sharma, Sara López-Tarruella, José Angel García-Saenz, Qamar J. Khan, Henry L. Gómez, Aleix Prat, Fernando Moreno, Yolanda Jerez-Gilarranz, Agustí Barnadas, Antoni C. Picornell, María del Monte-Millán, Milagros González-Rivera, Tatiana Massarrah, Beatriz Pelaez-Lorenzo, María Isabel Palomero, Ricardo González del Val, Javier Cortés, Hugo Fuentes-Rivera, Denisse Bretel Morales, Iván Márquez-Rodas, Charles M. Perou, Carolyn Lehn, Yen Y. Wang, Jennifer R. Klemp, Joshua V. Mammen, Jamie L. Wagner, Amanda L. Amin, Anne P. O’Dea, Jaimie Heldstab, Roy A. Jensen, Bruce F. Kimler, Andrew K. Godwin, Miguel Martín
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Prognostic value of pathologic complete response (pCR) and extent of pathologic response attained with anthracycline-free platinum plus taxane neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) is unknown. We report recurrence-free survival (RFS) and overall survival (OS) according to degree of pathologic response in patients treated with carboplatin plus docetaxel NAC. Patients and Methods: One-hundred and ninety patients with stage I–III TNBC were treated with neoadjuvant carboplatin (AUC6) plus docetaxel (75 mg/m2) every 21 days × 6 cycles. pCR (no evidence of invasive tumor in breast and axilla) and Residual cancer burden (RCB) were evaluated. Patients were followed for recurrence and survival. Extent of pathologic response was associated with RFS and OS using the Kaplan–Meier method. Results: Median age was 51 years, and 52% were node-positive. pCR and RCB I rates were 55% and 13%, respectively. Five percent of pCR patients, 0% of RCB I patients, and 58% of RCB II/III patients received adjuvant anthracyclines. Three-year RFS and OS were 79% and 87%, respectively. Three-year RFS was 90% in patients with pCR and 66% in those without pCR [HR = 0.30; 95% confidence interval (CI), 0.14–0.62; P = 0.0001]. Three-year OS was 94% in patients with pCR and 79% in those without pCR (HR = 0.25; 95% CI, 0.10–0.63; P = 0.001). Patients with RCB I demonstrated 3-year RFS (93%) and OS (100%) similar to those with pCR. On multivariable analysis, higher tumor stage, node positivity, and RCB II/III were associated with worse RFS. Conclusions: Neoadjuvant carboplatin plus docetaxel yields encouraging efficacy in TNBC. Patients achieving pCR or RCB I with this regimen demonstrate excellent 3-year RFS and OS without adjuvant anthracycline.
Late Arterial Responses (6 and 12 Months) After 32P β-Emitting Stent Placement
Authors: AndrewFarb, SwetaShroff, MichaelJohn, WilliamSweet, RenuVirmani
Journal: Circulation (2001)

pick;5248p1-foo;0;;clb/clb>Background—Three-month studies of stent-delivered brachytherapy in the rabbit model show reduced neointimal growth. However, intimal healing is delayed, raising the possibility that intimal inhibition is merely delayed rather than prevented. The purpose of this study was to explore the long-term histological changes after placement of β-emitting radioactive stents in normal rabbit iliac arteries. Methods and Results—Three-millimeter β-emitting 32P stents (6, 24, and 48 μCi) were placed in normal rabbit iliac arteries with nonradioactive stents as controls. Animals were euthanatized at 6 and 12 months, and histological assessment, morphometry, and analysis of endothelialization were performed. Morphometric measurements demonstrated a >50% reduction in intimal growth and percent lumen stenosis within 24- and 48-μCi stents versus control nonradioactive stents at both 6 and 12 months. However, the 24- and 48-μCi stents also showed delayed healing of the intimal surface, characterize...
Abstract 4290: Mad1 promotes tumor progression through destabilization of p53
Authors: Jun Wan, Beth A. Weaver
Journal: Cancer Research (2018)

Abstract Mitotic arrest deficient 1 (Mad1) plays a well-characterized role in the mitotic checkpoint. However, interphase roles of Mad1 that do not impact mitotic checkpoint function are still largely uncharacterized. We have found that upregulation of Mad1, which is common in human breast cancer, results in decreased protein stability of the tumor suppressor p53 in multiple cell types. To gain mechanistic insight into this process, we first determined whether increasing expression of Mad1 alters its localization. Upregulated Mad1 localizes to puncta within interphase nuclei in both breast cancer tissue and cultured cells. We found that upregulated Mad1 localizes to ProMyelocytic Leukemia Nuclear Bodies (PML NBs), which have been implicated in the stabilization of p53. Immunoprecipitation results indicate that Mad1 and PML interact and that the C-terminal domain (CTD) of Mad1 and the N-terminal domain of PML are required for this interaction. Within the CTD of Mad1, the SUMO-Interacting Motif (SIM) is critical for the localization of Mad1 to PML NBs. MDM2 is an E3 ubiquitin ligase that targets p53 for degradation. In response to DNA damage, PML sequesters Mdm2 to the nucleolus, which stabilizes p53. In cells with elevated levels of Mad1, Mad1 interrupts the interaction between PML and MDM2. Mad1, rather than MDM2, is sequestered to the nucleolus after DNA damage, and Mad1 displaces MDM2 from PML. The displaced MDM2 is no longer sequestered in the nucleolus, freeing it to ubiquitinate p53, resulting in p53 destabilization. Upregulation of Mad1 promotes the growth of orthotopic mammary tumors. Mammary tumors with upregulated Mad1 show decreased levels of p53 and its downstream effector p21. Our results show that, in addition to causing a low rate of chromosome missegregation, Mad1 upregulation has an unexpected interphase role in promoting tumor formation and progression by destabilizing p53. Thus, Mad1 upregulation promotes tumors in through at least two distinct pathways. Citation Format: Jun Wan, Beth A. Weaver. Mad1 promotes tumor progression through destabilization of p53 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4290.
Abstract P216: Relationships of Nativity and Length of Residence in the U.S. with Favorable Cardiovascular Health Among Hispanics/Latinos of Diverse Backgrounds: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Kiarri N Kershaw, Rebeca Espinoza Giacinto, Franklyn Gonzalez, Carmen R Isasi, Hugo Salgado, Jeremiah Stamler, Gregory A Talavera, Wassim Tarraf, Linda Van Horn, Donghong Wu, Martha Daviglus
Journal: Circulation (2016)

Objectives: Little is known about the relationship of acculturation and favorable cardiovascular (CV) health (i.e., low CV risk) in the Hispanic/Latino population. Methods: Age-adjusted prevalences (weighted for sampling probability and non-response) are reported. Logistic regression was used to examine associations of acculturation (measured using nativity and length of residence: &lt;10 years, ≥10 years, and US-born) with low CV risk (not currently smoking; no diabetes; untreated total cholesterol &lt;200mg/dL; untreated blood pressure &lt;120/&lt;80; body mass index &lt;25 kg/m 2 ; and no major ECG abnormalities) in 15,047 HCHS/SOL participants (52.4% women) of Central American, South American, Cuban, Dominican, Mexican, Puerto Rican background, and Hispanic/Latino men and women identifying as other or &gt;1 background group. We also tested whether these associations varied by Hispanic/Latino background. Results: Among women, age-adjusted low CV risk prevalence was highest for those living in the US &lt; 10 years (15.4%) and similar for those living in the US ≥ 10 years (9.4%) and born in the US (9.2%). Low CV risk prevalence in was lower in men, but patterns were similar by acculturation (&lt;10 years: 4.5%; ≥ 10 years: 5.6%; US-born: 6.0%). In multivariable-adjusted models (Table), women living in the US&lt;10 years were more likely to be low CV risk than US-born women; these associations did not vary by Hispanic/Latino background (P for interaction=0.72). Findings varied significantly in men (P for interaction &lt;0.001), but there was no strong patterning in low CV risk prevalence by length of residence for most groups. Conclusions: These findings highlight the role that acculturation plays in shaping cardiovascular health in Hispanics/Latinos.
Doctor who failed two patients while working at showjumping events is struck off
Authors: Clare Dyer
Journal: BMJ (2018)

A doctor who kept working as the medical officer at showjumping events despite having lost his licence to practise has been struck off the UK medical register.

A medical practitioners tribunal also found that Alexandros Charitou, who worked regularly for British Eventing, had fallen below the standard expected of a competent practitioner in his treatment of two riders who fell off their horses.

In one case he told a woman with severe back pain to go home and consult her GP the next day, diagnosing muscle spasms. She was driven away by her husband and went to the Royal Surrey County Hospital, where a scan revealed …
Abstract 1291: Master regulator analysis of paragangliomas carrying SDH, VHL, or MAML3 genetic alterations
Authors: John A. Smestad, Louis J. Maher
Journal: Cancer Research (2018)

Abstract Background: Succinate dehydrogenase (SDH) loss and mastermind-like 3 (MAML3) translocation are two clinically important genetic alterations that occur in subtypes of human paraganglioma and pheochromocytoma (PPGL) neuroendocrine tumors that correlate with increased rates of metastasis. Although hypotheses exist for how global activation of pseudohypoxia and epigenomic hypermethylation are driven via dioxygenase poisoning in the context of SDH loss, it remains unclear how these defects drive tumorigenesis. Additionally, MAML3 translocation has recently been identified as a genetic alteration in PGL and is poorly understood. We hypothesize that a key to understanding the tumorigenic basis for these genetic alterations is the deconvolution of the gene expression profiles in these tumors and identification of the transcription factors responsible for the observed transcriptional changes. Methods: In the present work, we leverage publicly-available human tumor gene expression profiling experiments (N=179) to reconstruct a PPGL tumor-specific transcriptional network. Inferred network structure was subsequently validated by examining the frequency of known transcription factor DNA-binding motifs in the inferred regulons. We subsequently use the inferred transcriptional networks and known gene expression signatures for specific PPGL subtypes to perform a master regulator analysis nominating specific transcription factors that may control observed oncogenic patterns of gene expression. The findings of the master regulator analysis were confirmed by duplication of the analysis on a second PPGL-specific inferred transcriptional network (N=188 specimens). Results: A small number of master regulator transcription factors are likely drivers of the observed subtype-specific gene expression patterns in SDH loss- and MAML3 translocation-positive PPGL. Unexpectedly, hypoxia-inducible transcription factors were not identified as master regulators in SDH-loss tumors. Additionally, analysis of the MAML3 translocation subtype master regulators revealed that a single transcription factor, IRX4, may control 37% of the deferentially expressed genes in this highly malignant tumor subtype. Conclusions: These observations from unbiased analyses suggest a basis for future development of targeted therapies for specific PPGL molecular subtypes. Citation Format: John A. Smestad, Louis J. Maher. Master regulator analysis of paragangliomas carrying SDH, VHL, or MAML3 genetic alterations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1291.
Abstract 3545: Identifying the effects of lung cancer exosomes on non-tumorigenic human bronchial epithelial cells
Authors: Hana Kubo, Sean E. Humphrey, Sarunya Kitdumrongthum, Feng Tian, Sarah Allen, Andrea L. Kasinski
Journal: Cancer Research (2018)

Abstract Lung cancer is the leading cause of death from cancer in most industrialized countries and many lung cancer patients remain undiagnosed until the development of locally advanced or metastatic lung cancer. Despite extensive research, universal biomarkers for the early diagnosis of lung cancer remain elusive, and therapies for treating lung cancer patients remain ineffective and unfocused. This makes the identification of new diagnostic biomarkers and therapeutic targets for the treatment of lung cancer a critical need for patients. Exosomes, nanovesicles secreted by a variety of cell types, are known to transfer bioactive molecules such as proteins and nucleic acids that induce physiological changes in recipient cells. Exosomes secreted by cancer cells have been shown to promote tumor initiation, progression, and metastasis in various cancer types, but have been understudied in lung cancer. Our study aims to identify the effects lung cancer secreted exosomes may have on non-cancerous cells of the tumor microenvironment by assessing their tumorigenic effects on normal lung epithelial cells. To that end, we treated normal lung epithelial cells with exosomes derived from a panel of human non-small lung cancer cell lines. Treated cells acquired the ability to invade and migrate. As a proxy for metastasis, cancer exosomes are also being assayed for their ability to permeabilize a monolayer of normal lung epithelial cells. Further assessing the molecules within cancer exosomes critical for promoting these oncogenic behaviors in non-tumorigenic cells could lead to the discovery of potential diagnostic biomarkers and therapeutic targets for inhibiting tumor growth in affected patients. Citation Format: Hana Kubo, Sean E. Humphrey, Sarunya Kitdumrongthum, Feng Tian, Sarah Allen, Andrea L. Kasinski. Identifying the effects of lung cancer exosomes on non-tumorigenic human bronchial epithelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3545.
Abstract 15932: Telomere Length and Autophagy Modulate Cardiac Progenitor Cell Fate
Authors: Collin Matsumoto, Jacqueline Emathinger, Pearl Quijada, Aimee B Levinson, Minyoung Shin, Nathalie Nguyen, Mark Sussman, Nirmala Hariharan
Journal: Circulation (2016)

Several cell intrinsic changes occurring with age lead to exhaustion of the stem cell pool. Delineating the role of age-associated factors such as telomere shortening is critical to enhance the reg...
Radiological diagnosis of interstitial lung disease: is it all about pattern recognition?
Authors: Simon L.F. Walsh, Martin Kolb
Journal: European Respiratory Journal (2018)

<b>Radiological diagnosis of ILD is pattern-based and linked to underlying histology. The future of radiological diagnosis in ILD may be the identification of disease behaviour-based radiological phenotypes that predict disease outcome.</b>http://ow.ly/Dg0Q30l4Rh8
Abstract 15714: Electrical versus Anatomic Left Ventricular Hypertrophy Associated With Sudden Death
Authors: Kumar Narayanan, Navid Darouian, Audrey Uy-Evanado, Carmen Teodorescu, Kyndaron Reinier, Harpriya Chugh, Karen Gunson, Jonathan Jui, Sumeet S Chugh
Journal: Circulation (2015)

Introduction: We have previously reported that electrocardiographic (ECG) left ventricular hypertrophy (LVH) can occur in the absence of increased LV mass (echocardiographic LVH), and conveys unique risk of sudden cardiac arrest (SCA). We further characterized this adverse “electrical remodeling” by comparing SCA cases with isolated electrical vs. isolated anatomic LVH. Hypothesis: Cases with electrical versus anatomic LVH have distinct clinical profiles Methods: Adult SCA cases were prospectively ascertained from multiple sources in a Northwestern US metro area (population approx. 1 million). Clinical/demographic information was obtained from medical records. ECGs, prior and unrelated to SCA were reviewed in blinded fashion to detect ECG-LVH (Sokolow-Lyon criteria). LV mass, obtained from echocardiograms was used to identify echo-LVH (LV Mass Index &gt; 134 g/m2 men; 110 g/m2 women). Cases with isolated ECG-LVH versus isolated echo-LVH were compared to identify distinctive characteristics. Patients who had LVH by both tests and those without LVH by either test were excluded. Results: Among 323 SCA cases (2002-14; 69.0 ± 13.5 yrs; 66.9% male) with adequate information available, echo-LVH was present in 134 (41.5%) cases and ECG-LVH in 58 (18.0%) cases. After elimination of cases with LVH by both modalities, 103 (31.9%) cases had isolated echo-LVH while 27 (8.3%) had isolated ECG-LVH. Compared to cases with isolated ECG-LVH, isolated echo-LVH cases had lower LV ejection fraction (45.2 ± 16.9 vs. 53.0 ± 14.8%; p=0.03), were more likely to be current smokers (30.8 vs. 8.7%; p=0.06), obese (41.7 vs. 25.9%; p=0.12) and African-American (19.4 vs 7.4%; p=0.15). There were no significant differences between the two groups for systemic hypertension (78.6 vs. 88.9%; p=0.23), age, sex, diabetes, renal disease, coronary artery disease or prior myocardial infarction. Prescription of anti-hypertensive medications including ACE inhibitors, angiotensin receptor blockers and beta blockers were equally likely in both groups. Conclusions: Patients with electrical vs. anatomic LVH appear to have distinct clinical profiles. These findings can serve as a foundation for further investigation of genetic and acquired mechanisms of electrical LVH leading to sudden death.