tbuckley/cabot-search huggingface dataset:
Abstract IA10: Integrated omics analyses identify prognostic biomarkers of oral cavity squamous cell carcinoma in Taiwan
Authors: Kai-Ping Chang, Ting-Wen Chen, Curtis R. Pickering, Jeffrey N. Myers, Yu-Sun Chang
Journal: Clinical Cancer Research (2017)

Abstract To uncover genomic alterations that can be used as molecular markers for oral cavity squamous cell carcinoma (OSCC) in Taiwan, we recruited patients who were ethnically Taiwanese and admitted to Chang Gung Memorial Hospital at Taipei. We performed whole-exome sequencing (WES) of matched tumor/PBMC DNAs from 50 OSCC patients (75-Mbp target region, mean depth = 244 ± 54), and RNA sequencing of matched tumor/adjacent normal tissues from 39 of the 50 patients (mean read count = 38.7 ± 15.2 million). A subset of the identified somatic mutations was validated in 49 tumor tissues using an IonAmpliSeqTM Comprehensive Cancer Panel (CCP; 409 cancer-related genes). In total, our exome sequencing analyses uncovered 33,160 somatic single nucleotide variants (SNVs) and InDels. The targeted approach of CCP enabled us to independently validate 84.91% of the SNVs identified by our whole-exome sequencing. We cross-referenced our data with that of 172 oral cavity cancer samples (OSCC-TCGA) from the Head-Neck Squamous Cell Carcinoma (HNSC) project of TCGA (HNSC-TCGA) and 106 from India (OSCC-India), as annotated in the International Cancer Genome Consortium (ICGC). We found that our patient cohort was characteristic of OSCC with regard to frequently mutated genes, such as CDKN2A, TP53, and NOTCH1. Interestingly, however, our analysis further identified mutations in seven other genes that turned out to be unique, locally prevalent (&amp;gt;10% of patients) alterations. We further used our exome sequencing data to examine copy number alterations in our samples and our findings largely recapitulated the profile found in OSCC-TCGA, which included significantly amplified/deleted regions encompassing genes such as EGFR, FGFR1, FADD, FAT1 and CDKN2A. Comparative analysis of the transcriptomes of tumor and normal tissues allowed us to identify 3,548 genes as being differentially expressed in OSCC-Taiwan; these included 1,220 up-regulated and 2,328 down-regulated genes. Notably, 91.3% of these differentially expressed genes were similarly identified in the OSCC-TCGA data, indicating that the overall expression profile of OSCC is highly similar across ethnic groups. In the meeting, I will report the unique genomic alterations with the potential biomarkers in OSCC, and these findings might introduce a hitherto unknown genetic component of this disease. Citation Format: Kai-Ping Chang, Ting-Wen Chen, Curtis R. Pickering, Jeffrey N. Myers, Yu-Sun Chang. Integrated omics analyses identify prognostic biomarkers of oral cavity squamous cell carcinoma in Taiwan [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr IA10.
Abstract 13902: Comparison of Stent Performance Between ZES and EES
Authors: Shuichi Yoneda
Journal: Circulation (2016)

Introduction: Although drug-eluting stents (DESs) have reduced restenosis, a unique issue beyond restenosis, i.e., impairment of re-endothelialization, which may delay wound healing and cause a relapse of inflammation, leading to neoathroma formation at the stented sites, in addition to lack of neointimal coverage, has arisen. Therefore, overall stent performance should be characterized by the abilities of geometric luminal gain acquisition, neointimal coverage of the stent struts, and stabilization of the underlying inflammatory neoatheroma. Hypothesis: Our hypothesis is that stent performance would be different between 2 second generation DESs, zotarolimus-eluting stent (ZES) and everolimus-eluting stent (EES). Methods: We compared stent performance among ZES, EES and bare metal stent (BMS) using optical coherence tomography (OCT) and coronary angioscope (CA). For 37 stented coronary lesions (EES; 16 lesions, ZES; 10 lesions and BMS; 11 lesions) in 20 patients, we observed stented sites by the OCT at 6-12 months after stent placement and measured neointimal area at the site of minimal lumen area and ratio of uncovered stent strut to the whole struts. Also by the CA, neointimal coverage was observed, and neointimal color was simultaneously observed. From the CA findings, the grades of neointimal coverage and yellow color were classified into 0 to 3. Results: The neointimal area (mm 2 ) was 1.30±1.12 in the EES lesions, 2.74±1.17 in the ZES lesions (P&lt;0.05 vs EES), and 3.76±1.01 in the BMS lesions (P&lt;0.001 vs EES, P=0.07 vs ZES). The OCT-based uncovered ratio was 26.9% in the EES lesions, 2.1% in the ZES lesions (P&lt;0.01 vs EES), and 1.2% in the BMS lesions (P&lt;0.001 vs EES, P=0.9 vs ZES). Stent coverage grade by the CA findings was 0.44±0.53 in the EES lesions, 2.00±1.00 in the ZES lesions (P&lt;0.001 vs EES), and 2.33±0.82 in the BMS lesions (P&lt;0.01 vs EES, P=0.5 vs ZES). The yellow grade was 1.67±0.50 in the EES lesions, 0.29±0.48 in the ZES lesions (P&lt;0.001 vs EES), and 0.17±0.41 in the BMS lesions (P&lt;0.001 vs EES, P=0.7 vs ZES). Conclusions: ZES might be better than BMS in terms of neointimal thickening, and better than EES in terms of neointimal coverage as well as stabilization of inflammatory neoatheroma. ZES may have superior stent performance, compared to EES.
Proteomic and genomic integration identifies kinase and differentiation determinants of kinase inhibitor sensitivity in leukemia cells
Authors: Pedro Casado, Edmund H. Wilkes, Farideh Miraki-Moud, Marym Mohammad Hadi, Ana Rio-Machin, Vinothini Rajeeve, Rebecca Pike, Sameena Iqbal, Santiago Marfa, Nicholas Lea, Steven Best, John Gribben, Jude Fitzgibbon, Pedro R. Cutillas
Journal: Leukemia (2018)

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is an effective treatment for hematologic malignancies.The most frequent cause of post-transplant mortality is disease relapse, the majority of the cases present recurrence of original disease from outgrowth of residual cells having
Migratory CD11b <sup>+</sup> conventional dendritic cells induce T follicular helper cell–dependent antibody responses
Authors: Jayendra Kumar Krishnaswamy, Uthaman Gowthaman, Biyan Zhang, Johan Mattsson, Louis Szeponik, Dong Liu, Renee Wu, Theresa White, Samuele Calabro, Lan Xu, Magalie A. Collet, Marina Yurieva, Samuel Alsén, Per Fogelstrand, Anne Walter, William R. Heath, Scott N. Mueller, Ulf Yrlid, Adam Williams, Stephanie C. Eisenbarth
Journal: Science Immunology (2017)

Conventional DC2s are necessary and sufficient for priming T follicular helper cells.
Abstract 73: Gain-of-function mutant p53 promotes the oncogenic potential of head and neck squamous cell carcinoma cell by targeting forkhead transcription factors FOXO3a and FOXM1
Authors: Noriaki Tanaka, Mei Zhao, Jiexin Zhang, Jing Wang, Ge Zhou, Jeffrey N. Myers
Journal: Clinical Cancer Research (2017)

Abstract Many mutant p53 proteins exert oncogenic gain-of-function (GOF) properties in promoting cancer cell invasive growth and metastasis, but the mechanisms mediating these functions largely remain elusive. We show here that overexpression of the GOF mutant p53 G245D and other GOF p53 mutants enhances invasive cell growth of p53-deficient head and neck squamous cell carcinoma (HNSCC) UM-SCC-1 cells both in vitro 3D culture and in vivo orthotopic tumor mouse model. We demonstrate that the expression of the oncogenic forkhead transcription factor FOXM1 is upregulated by GOF mutant p53s in UM-SCC-1 cells and tumors. Moreover, we show that overexpression of GOF mutant p53 G245D decreases the inhibitory phosphorylation of FOXO3a, a tumor suppressive forkhead transcription factor, leading to its cytoplasmic accumulation. Consistent with the observation that FOXO3a negatively regulates FOXM1 expression, we demonstrate that overexpression FOXO3a decreases GOF mutant p53-mediated FOXM1 expression, whereas downregulation of FOXO3a partially restores decreased FOXM1 expression due to loss of GOF mutant p53. In support of the roles of FOXO3a-FOXM1 signaling axis in mutant p53's GOF signaling, we further show that overexpression of FOXO3a or downregulation of FOXM1 impairs GOF mutant p53-mediated cell invasion, whereas downregulation of FOXO3a, in part, rescues impaired cell invasion due to downregulated GOF mutant p53. Finally, given that AMP-activated protein kinase (AMPK) directly phosphorylates and promotes FOXO3a function, and that our prior demonstration that GOF mutant p53s inhibit AMPK, our current study establishes that GOF mutant p53-AMPK-FOX3a-FOXM1 signaling is one of important mechanisms through which mutant p53s gain oncogenic functions in HNSCCs. Citation Format: Noriaki Tanaka, Mei Zhao, Jiexin Zhang, Jing Wang, Ge Zhou, Jeffrey N. Myers. Gain-of-function mutant p53 promotes the oncogenic potential of head and neck squamous cell carcinoma cell by targeting forkhead transcription factors FOXO3a and FOXM1 [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 73.
Abstract 14531: Activation of NLRP3 Inflammasome Promotes Atrial Fibrillation
Authors: Chunxia Yao, Larry Scott, Xander Wehrens, Dobromir Dobrev, Na Li
Journal: Circulation (2016)

Introduction: Sterile inflammation is frequently observed in patients with atrial fibrillation (AF), the most common cardiac arrhythmia. However, whether inflammation signaling plays a causative ro...
William Brian Andrew Barwell
Authors: James Craggs
Journal: BMJ (2017)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following William Brian Andrew Barwell Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
A Tumor-Activatable Theranostic Nanomedicine Platform for NIR Fluorescence-Guided Surgery and Combinatorial Phototherapy
Authors: Xiaoning Li, Canan Schumann, Hassan A. Albarqi, Christopher J. Lee, Adam W. G. Alani, Shay Bracha, Milan Milovancev, Olena Taratula, Oleh Taratula
Journal: Theranostics (2017)

Fluorescence image-guided surgery combined with intraoperative therapeutic modalities has great potential for intraoperative detection of oncologic targets and eradication of unresectable cancer residues. Therefore, we have developed an activatable theranostic nanoplatform that can be used concurrently for two purposes: (1) tumor delineation with real-time near infrared (NIR) fluorescence signal during surgery, and (2) intraoperative targeted treatment to further eliminate unresected disease sites by non-toxic phototherapy. Methods: The developed nanoplatform is based on a single agent, silicon naphthalocyanine (SiNc), encapsulated in biodegradable PEG-PCL (poly (ethylene glycol)-b-poly(ɛ-caprolactone)) nanoparticles. It is engineered to be non-fluorescent initially via dense SiNc packing within the nanoparticle's hydrophobic core, with NIR fluorescence activation after accumulation at the tumor site. The activatable nanoplatform was evaluated in vitro and in two different murine cancer models, including an ovarian intraperitoneal metastasis-mimicking model. Furthermore, fluorescence image-guided surgery mediated by this nanoplatform was performed on the employed animal models using a Fluobeam® 800 imaging system. Finally, the phototherapeutic efficacy of the developed nanoplatform was demonstrated in vivo. Results: Our in vitro data suggest that the intracellular environment of cancer cells is capable of compromising the integrity of self-assembled nanoparticles and thus causes disruption of the tight dye packing inside the hydrophobic cores and activation of the NIR fluorescence. Animal studies demonstrated accumulation of activatable nanoparticles at the tumor site following systemic administration, as well as release and fluorescence recovery of SiNc from the polymeric carrier. It was also validated that the developed nanoparticles are compatible with the intraoperative imaging system Fluobeam® 800, and nanoparticle-mediated image-guided surgery provides successful resection of cancer tumors. Finally, in vivo studies revealed that combinatorial phototherapy mediated by the nanoparticles could efficiently eradicate chemoresistant ovarian cancer tumors. Conclusion: The revealed properties of the activatable nanoplatform make it highly promising for further application in clinical image-guided surgery and combined phototherapy, facilitating a potential translation to clinical studies.
Efficacy of a type 2 diabetes self-management model with family doctor team support in southern China: a randomised controlled trial
Authors: Xiaoling Sun, Xuhua Tan, Yi Zhu, Weixin Chen, Zhizhao Zhou, Jianghong Liu, Shilan Yu, Wanhua Chen, Yanwen Li, Siming Chen, WenYong Huang, Xiaoyi Wang
Journal: The Lancet (2017)
Abstract 20656: Calibration With Mean Blood Pressure is Essential for Utilization of Brachial Pulse Wave Analysis-Based Ambulatory Central Blood Pressure Monitor for Cardiovascular Patients
Authors: Toshihiro Shoji, Sho Okada, Atsushi nakagomi, Yoshio Kobayashi
Journal: Circulation (2014)

Background:  Central blood pressure (cBP) shows actual pressure load on the heart and proximal large arteries, thus it is deemed to be superior to brachial blood pressure in predicting cardiovascular events.  Recently indirect measurement of cBP was enabled by analysis of arterial pulse wave, resulting in its popular use in the clinical setting. Even Ambulatory central Blood Pressure Monitor (AcBPM) implemented with this program, such as ARC Solver algorithm, is now put into practical use.  There remain several issues regarding indirect measurement of cBP.  There is no consistent agreement on the calibration mode that is indispensable for calculation process. Not all the patient are qualified to interpret the attained data due to lacking of validation in the specific disease population or standardized reference data.   Object:  To determine optimal calibration mode of the AcBPM with ARC Solver algorithm, we compared the accuracy of attained data between two available modes. We also sought to find subpopulation for which this instrument is most suitable.   Method:  For 142 patients who underwent elective coronary angiography in our hospital, we simultaneously measured invasive and noninvasive central blood pressure parameters such as central systolic blood pressure (cSBP), central pulse pressure (cPP), pulsatility. We calibrated the noninvasive data with systolic and diastolic BP(Cal1) or mean and diastolic BP(Cal2). Then we compared the accuracy between two modes. After excluding perturbing factors that can affect data acquisition, we analyzed the same way.   Results:  Cal2 consistently showed better linear correlation in all the parameters (Cal1 vs Cal2: cSBP 0.78 vs 0.81, cPP 0. 64 vs 0.73, Pulsatility 0.51 vs 0.65). Cal2 also showed much less error in the same parameters (Cal1 vs Cal2: 18.8±15.5 vs -4.5±15.5 mmHg, cPP 32.2±16.4 vs 10.6±15.3mmHg, Pulsatility0.30±0.15 vs 0.10±0.14). After excluding perturbing factors, accuracy of these parameters showed little change, whereas additional exclusion of cSBP over 180mmHg further improved its accuracy (-2.0±11.1mmHg).   Conclusions:  Use of Cal2 is essential for clinical application of AcBPM with ARC Solver algorithm.  Extremely high cSBP value should be taken as outlier.
GMC cuts junior doctors’ registration fees
Authors: Abi Rimmer
Journal: BMJ (2017)

The General Medical Council has announced cuts to its registration fees that could save new doctors nearly £1200 over six years.

The GMC said that all doctors who apply for provisional registration from April 2018 will benefit from discounts.

From April the cost of provisional registration will reduce from £90 to £50. The cost of the first full year of registration will be cut from £200 to £150, and the subsequent annual registration fee will reduce from £425 to …
Effect of grass sublingual tablet immunotherapy is similar in children and adults: A Bayesian approach to design pediatric sublingual immunotherapy trials
Authors: Amarjot Kaur, David Skoner, Joseph Ibrahim, Qing Li, Richard F. Lockey, Michael Blaiss, Albrecht Bufe, Jens Strodl Andersen, Giorgio Walter Canonica, Hendrik Nolte
Journal: Journal of Allergy and Clinical Immunology (2017)
Long-term prognosis after childhood convulsive status epilepticus: a prospective cohort study
Authors: Suresh S Pujar, Marina M Martinos, Mario Cortina-Borja, W K Kling Chong, Michelle De Haan, Christopher Gillberg, Brian G Neville, Rod C Scott, Richard F Chin
Journal: The Lancet Child & Adolescent Health (2017)

BackgroundThe prognosis of convulsive status epilepticus (CSE), a common childhood medical neurological emergency, is not well characterised. We aimed to investigate the long-term outcomes in a cohort of participants who previously had CSE.MethodsIn this prospective study, we followed up a population-based childhood CSE cohort from north London, UK (the north London convulsive status epilepticus surveillance study cohort; NLSTEPSS). We collected data from structured clinical neurological assessment, neurocognitive assessment (Wechsler Abbreviated Scale of Intelligence), brain MRI, medical records, and structured interviews with participants and their parents to determine neurological outcomes, with adverse outcome defined as presence of one or more of epilepsy (active or in remission), motor disability, intellectual disability, or statement of special educational needs. We applied multiple imputation to address missing data and performed binary logistic regression analyses on complete-case and imputed datasets to investigate sociodemographic and CSE factors associated with adverse outcomes.FindingsOf 203 survivors (90% of inception cohort), 134 (66%) were assessed at a median follow-up of 8·9 years (IQR 8·2–9·5). The cumulative incidence of epilepsy was 24·7% (95% CI 16·2–35·6), with most (89%) emerging within 18 months after CSE. The cumulative incidence of epilepsy was lower in patients with prolonged febrile seizures (14·3%, 6·3–29·4) and survivors of acute symptomatic CSE (13·3%, 3·7–37·9) than in those of remote symptomatic CSE (45·5%, 21·3–72·0) and unclassified CSE (50·0%, 25·4–74·6). One participant (2·9%, 0·5–14·5) in the prolonged febrile seizures group developed temporal lobe epilepsy with mesial temporal sclerosis. The absence of fever at CSE was the only predictor of incident epilepsy (odds ratio [OR] 7·5, 95% CI 2·25–25·1). Motor and intellectual disability was seen predominantly in participants who had idiopathic and cryptogenic CSE (seven [36·8%, 95% CI 19·1–59·0] and 16 [84·2%, 62·4–94·5] of 19, respectively) and remote symptomatic CSE (33 [62·3%, 48·8–74·1] and 40 [75·5%, 62·4–85·1] of 53), and most of these participants had pre-existing disabilities. Pre-existing epilepsy was the only predictor of intellectual disability (OR 8·0, 95% CI 1·1–59·6). 51·5% (95% CI 43·1–59·8) of those followed up had a statement of special educational needs.InterpretationChildhood CSE is associated with substantial long-term neurological morbidity, but primarily in those who have epilepsy, neurological abnormalities, or both before the episode of CSE. Survivors without neurological abnormalities before CSE have favourable outcomes.FundingBUPA Foundation, The Academy of Medical Sciences, Wellcome Trust, National Institute for Health Research, and Young Epilepsy.
RhoC disrupts tight junction formation and epithelial polarity in inflammatory breast cancer
Authors: Mei Wu, Zhifen Wu, Chia-Jen Liu, Alejandra Ventura, Eileen Whiteman, Ben Margolis, Sofia Merajver
Journal: Cancer Research (2008)

3572  Inflammatory breast cancer (IBC) shows strong expression of E-cadherin. Unlike many other malignant breast cancers with low or null expression of E-cadherin, the mechanism of breast cell transformation into IBC remains poorly understood. Previous studies indicate that overexpression of RhoC GTPase is a specific genetic alteration in IBC tumors and in SUM149, an IBC cell line. We show here that knockdown of RhoC in SUM149 had no effect on the expression levels and the localization of E-cadherin. RhoC silencing, however, induced the formation of functional tight junctions (TJ), as evident by a sharp and continuous ZO-1 staining, correct co-localization of the TJ proteins and ZO-1, high transepithelial resistance, and the appearance of the TJ-like structure under transmission electron microscope. The restoration of TJ in RhoC-knockdown SUM149 cells is dependent on the expression of CRB3, a component in the CRB3/PALS1/PATJ polarity complex, in SUM149. Knockdown of a closely related isoform of RhoC, RhoA, failed to form TJ. Furthermore, knockdown of RhoC in SUM149 restored cell polarity by localizing the CRB3/PALS1/PATJ complex to TJ. In conclusion, RhoC GTPase activity disrupted epithelial polarity and proper formation of TJ to contribute to the epithelial-mesenchymal plasticity of SUM149.
Abstract 11177: No ST-Segment Elevation Resolution in Lead aVR Strongly Predicts In-hospital Adverse Outcomes in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome
Authors: Masami Kosuge, Toshiaki Ebina, Kiyoshi Hibi, Noriaki Iwahashi, Nobuhiko Maejima, Yasushi Matsuzawa, Kazuo Kimura
Journal: Circulation (2016)

Introduction: ST-segment elevation in lead aVR (ST↑aVR) on admission ECG is considered a useful predictor of left main/3-vessel disease (LM/3VD) and poor outcomes in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). However, the prognostic value of the change in ST↑aVR after admission remains unclear. Hypothesis: ST-segment analysis of lead aVR after admission may facilitate risk stratification in NSTE-ACS. Methods: We studied 706 patients with NSTE-ACS undergoing coronary angiography during hospitalization. ECGs were recorded on admission and 6 h after admission. ST↑aVR ≥0.5 mm was considered significant. A reduction of &gt;50% in ST↑aVR between the value on admission and that 6 h later was defined as ST resolution. Patients were classified into the 3 groups according to ECG findings: G-A, no ST↑aVR on admission (n=526); G-B, ST↑aVR on admission with ST resolution (n=114); and G-C, ST↑aVR on admission without ST resolution (n=66). Troponin T (TnT), estimated glomerular filtration rate (eGFR), brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), and summed ST-segment depression (ST↓) were measured on admission. Results: There were no significant differences in sex or coronary risk factors except for diabetes mellitus in the 3 groups. In G-A, G-B, G-C, age was 66±11, 69±11, and 70±11 years; the rates of diabetes mellitus were 29%, 43%, and 55%; Killip ≥2 was 4%, 18%, and 27%; and positive TnT was 27%, 42%, and 53%; the levels of eGFR were 67±24, 61±27, and 54±28 ml/min/1.73 m 2 ; BNP was 148±274, 358±418, and 617±545 pg/ml; hsCRP was 0.414±2.008, 0.655±1.551, and 1.125±2.058 mg/dl; summed ST↓ was 2±2, 7±4, and 11±7 mm; the rates of LM/3VD were 6%, 38%, and 86%; and in-hospital adverse events (death, [re]infarction, or urgent revascularization) were 6%, 17%, and 35%, respectively (all p&lt;0.01). Multivariate analysis showed that as compared with no ST↑aVR , hazard ratios (95% CI) for in-hospital adverse events associated with ST↑aVR with ST resolution and that without ST resolution were 1.60 (0.68-4.38; p=0.25), and 6.11 (2.07-14.9; p&lt;0.001), respectively. Conclusions: No resolution of ST↑aVR, ie., persistent ST↑aVR 6 h after admission, strongly predicts in-hospital adverse outcomes in patients with NSTE-ACS.