tbuckley/cabot-search huggingface dataset:
Detection of p53 mutations in circulating DNA in serum/plasma in lung cancer patients
Authors: Nobutoshi Hagiwara, Leah E. Mechanic, Perwez Hussain, Glenwood E. Trivers, Masao Miyashita, Takashi Tajiri, Koji Sasajima, Elise Bowman, Curtis C. Harris
Journal: Cancer Research (2005)

771  The p53 tumor suppressor gene is mutated in over 50% of all cancers. In addition to the high frequency of the mutation, the characteristic mutation spectrum in p53 is specific for particular cancers and exposures. Therefore, p53 mutation is a good target for investigating cancer. Recently, detection of genetic mutations, such as p53, K-ras, and N-ras, in serum/plasma DNA in cancer patients has been reported as a molecular biomarker. We are testing the hypothesis that specific p53 alterations in serum/plasma DNA are an effective biomarker of disease, exposure, or susceptibility in cancer patients and individuals who are cancer prone. Most previous studies focused on cancer patients and were not quantitative. A highly sensitive assay is necessary due to the low frequency of alterations in serum/plasma DNA. A modified form of the Mutation Load Assay, a highly sensitive, quantitative assay was developed for the detection of p53 mutations in serum/plasma DNA at codon 157, due to the specificity of the 157 mutation for cigarette smoking induced lung cancer, and at codons 248 and 249 due to the frequency of mutations at these positions. The Mutation Load Assay was determined to be highly sensitive. It was demonstrated, using the Mutation Load Assay, that mutations at codon 157(GTC>TTC), 248(CGG>CTG, CAG), and 249(AGG>AGT) were detected in serum DNA from individuals whose primary tumors contained the identical mutations. For these individuals, the mutation frequencies were estimated to be 10-3 - 10-4. After validation of the assay, it was applied to a pilot study of 12 cancer cases, 14 hospital controls, and 16 population controls. DNA was isolated from 600ul of plasma from participants and the p53 copy numbers was determined using real time PCR. The concentration of DNA as determined by estimation of p53 copy number was similar in cases, hospital controls, and population controls. Using 5000 p53 copies per sample, the mutation load assay was performed. In the pilot study, few samples were positive for mutations at codons 248 and 249 and the mutation frequency was low. Ongoing studies are evaluating reproducibility of low levels of detection and the effect of increasing the amount of p53 copies used in the assay.
Cordycepin promotes browning of white adipose tissue through an AMP-activated protein kinase (AMPK)-dependent pathway
Authors: Guihong Qi, Yue Zhou, Xiaopo Zhang, Jiaqi Yu, Xin Li, Xiaoxue Cao, Chongming Wu, Peng Guo
Journal: Acta Pharmaceutica Sinica B (2018)

Obesity is a worldwide epidemic. Promoting browning of white adipose tissue (WAT) contributes to increased energy expenditure and hence counteracts obesity. Here we show that cordycepin (Cpn), a natural derivative of adenosine, increases energy expenditure, inhibits weight gain, improves metabolic profile and glucose tolerance, decreases WAT mass and adipocyte size, and enhances cold tolerance in normal and high-fat diet-fed mice. Cpn markedly increases the surface temperature around the inguinal WAT and turns the inguinal fat browner. Further investigations show that Cpn induces the development of brown-like adipocytes in inguinal and, to a less degree, epididymal WAT depots. Cpn also increases the expression of uncoupling protein 1 (UCP1) and other thermogenic genes in WAT and 3T3-L1 differentiated adipocytes, in which AMP-activated protein kinase (AMPK) plays an important role. Our results provide novel insights into the function of Cpn in regulating energy balance, and suggest a potential utility of Cpn in the treatment of obesity.
Right Atrial Phasic Function in Heart Failure With Preserved and Reduced Ejection Fraction
Authors: Snigdha Jain, Daniel Kuriakose, Ilaina Edelstein, Bilal Ansari, Garrett Oldland, Swetha Gaddam, Khuzaima Javaid, Pritika Manaktala, Jonathan Lee, Rachana Miller, Scott R. Akers, Julio A. Chirinos
Journal: JACC. Cardiovascular imaging (2018)
A phase II study of trastuzumab monotherapy in pretreated patients with non-small cell lung cancers (NSCLCs) harboring HER2 alterations: HOT1303-B trial
Authors: I. Kinoshita, T. Goda, K. Watanabe, M. Maemondo, S. Oizumi, T. Amano, Y. Hatanaka, Y. Matsuno, H. Nishihara, H. Asahina, T. Harada, K. Goto, H. Isobe, M. Nishimura, H. Dosaka-Akita
Journal: Annals of Oncology (2018)
Sequential administration of DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi) induces apoptosis with caspase and reactive oxygen species (ROS)-dependent synergy
Authors: Anchalee Jiemjit, Tamer Fandy, Stephen Baylin, Hetty Carraway, James Herman, Steven Gore
Journal: Cancer Research (2007)

1036  Sequential treatment with DNMTi and HDACi synergize to promote re-expression of transcriptionally silenced genes whose promoters are methylated. This observation has served as a model for several early phase clinical trials in patients with myeloid malignancies and other cancers. Since mechanisms other than gene re-expression may be involved in mediating the clinical efficacy of these drugs, we investigated the effect of sequential treatment of DNMTi and HDACi on apoptosis induction in leukemia cells. Pretreatment of ML-1 or HL-60 with decitabine (DNMTi) for 48 h followed by a variety of HDACi (MS-275, trichostatin A, phenylbutyrate sodium or valproic acid) for 24 h synergistically induced apoptosis (median-effect analysis). Sequential treatment with decitabine followed by HDACi synergistically induced p21WAF1 expression in ML-1 but not HL-60 cells, indicating that p21WAF1 upregulation is not essential for apoptotic synergy. ROS can induce apoptosis in caspase-dependent and independent manners. Sequential administration of decitabine and HDACi led to synergistic generation of ROS. Inhibition of ROS by N-acetyl-L-cysteine (NAC) completely abrogated apoptosis. The pan-caspase inhibitor Z-VAD-FMK also completely inhibited apoptosis after sequential administration of decitabine and HDACi. These data suggest that ROS-induced apoptosis requires caspase activation. While sequential administration of DNMTi and HDACi synergize for both re-expression of methylated genes and apoptosis, a possible relationship between these two molecular synergies requires further investigation.
Association of Youth Triponderal Mass Index vs Body Mass Index With Obesity-Related Outcomes in Adulthood
Authors: Feitong Wu, Marie-Jeanne Buscot, Markus Juonala, Nina Hutri-Kähönen, Jorma S. A. Viikari, Olli T. Raitakari, Costan G. Magnussen
Journal: JAMA Pediatrics (2018)

Debate continues on the limitations of using body mass index (BMI) to assign youth overweight/obesity status. Calculated as weight in kilograms divided by height in meters squared, BMI might not be applicable in youth during periods of rapid growth. Although recent evidence has indicated that triponderal mass index (TMI, calculated as weight in kilograms divided by height in meters cubed) might have better accuracy in estimating youth body fat levels than BMI, its clinical importance in estimating adulthood outcomes has not been examined. Therefore, we assessed whether youth TMI and its combination with BMI or subscapular skin fold thickness (SST), compared with BMI alone, have better utility in estimating adult obesity-related outcomes.
Imaging and serum biomarkers in connective tissue disease–associated interstitial lung diseases: correlation between lung ultrasound B-lines and KL-6 levels
Authors: Yukai Wang, Shaoqi Chen, Zhangzhang Lin, Guangzhou Du, Jianqun Lin, Qisheng Lin, Huang Xiufeng, Guohong Zhang, Daniel E Furst, Luna Gargani, Marco Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2018)

B-Lines are a new sonographic hallmark of connective tissue disease–associated interstitial lung diseases (CTD-ILDs). Promising data have shown that B-lines are associated with high-resolution CT (HRCT), pulmonary function test and some clinical variables, expanding the armamentarium for screening of ILDs.1 Krebs von den Lungen-6 (KL-6) antigen is a mucin-like, high molecular weight glycoprotein expressed on the surface membrane of alveolar epithelial cells Ⅱ and bronchiolar epithelial cells, and increases following cellular injury and/or regeneration.2 Its role in patients with CTD-ILDs has been studied extensively, indicating KL-6 as a useful biomarker of lung fibrosis and severity of the disease.3 To the best of our knowledge, the correlation between B-lines and serum KL-6 levels in CTD-ILDs has not been reported until now.

To investigate the relationship between these two markers, 60 Chinese patients with CTD-ILDs were enrolled. Patients with a history of asthma, chronic …
The Jumbo Man in the Jumbo Mart
Authors: Faith T. Fitzgerald
Journal: Annals of Internal Medicine (2018)

On Being a Doctor16 October 2018The Jumbo Man in the Jumbo MartFaith T. Fitzgerald, MDFaith T. Fitzgerald, MDUniversity of California, Davis, Sacramento, California (F.T.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M18-2352 Audio Reading - “The Jumbo Man in the Jumbo Mart” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "The Jumbo Man in the Jumbo Mart," by F.T. Fitzgerald. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Years ago when I had newly moved to Sacramento, I lived in a house very close to a grocery store called the Jumbo Mart. It really wasn't that big, the selection of items to purchase wasn't that great, and things cost a bit more than at the bigger stores like Safeway or Raley's Bel Air. However, it was very convenient and had more open parking spaces and almost always had far fewer shoppers in the checkout line than these other supermarkets.So, most of the time, I shopped at the Jumbo Mart.One day I was looking for a tube ... Author, Article, and Disclosure InformationAffiliations: University of California, Davis, Sacramento, California (F.T.F.)Corresponding Author: Faith T. Fitzgerald, MD, UC Davis Medical Center, c/o Division of General Medicine, 4150 V Street, Suite 2400, Sacramento, CA 95817; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “The Jumbo Man in the Jumbo Mart” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "The Jumbo Man in the Jumbo Mart," by F.T. Fitzgerald. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 16 October 2018Volume 169, Issue 8Page: 583KeywordsAcromegalyComaCombined antiretroviral therapyIntensive care unitsOintmentsPituitary tumorsSoapsStrokeSurgeryVitamins ePublished: 16 October 2018 Issue Published: 16 October 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A Study of Novel Febrile Neutropenia Risk Factors Related to Bone Marrow or Immune Suppression, Barrier Function, and Bacterial Flora
Authors: Leila Family, Yanli Li, Lie Hong Chen, John H. Page, Zandra K. Klippel, Chun Chao
Journal: Journal of the National Comprehensive Cancer Network (2018)

Background: Previously identified patient-level risk factors for chemotherapy-induced febrile neutropenia (FN) indicate several potential underlying pathogenic mechanisms, including bone marrow suppression, impaired neutrophil function, or disturbances of barrier function. This study evaluated whether additional clinical characteristics related to these pathogenic mechanisms were risk factors for FN. Patients and Methods: The study population included patients diagnosed with non-Hodgkin's lymphoma or breast, lung, colorectal, ovarian, or gastric cancer between 2000 and 2009 at Kaiser Permanente Southern California and treated with myelosuppressive chemotherapy. Those who received prophylactic granulocyte colony-stimulating factor or antibiotics were excluded. Potential risk factors of interest included surgery, radiation therapy, selected dermatologic/mucosal conditions, and use of antibiotics and corticosteroids. All data were collected using electronic medical records. Multivariable Cox models were used to evaluate associations between these factors and risk of FN in the first chemotherapy cycle, and adjusted using propensity score–based functions. Results: A total of 15,971 patients were included. Of these, 4.3% developed FN in the first chemotherapy cycle. Use of corticosteroids was significantly associated with increased risk of FN (adjusted hazard ratio [aHR], 1.53; 95% CI, 1.17–1.98). Selected dermatologic/mucosal conditions and intravenous antibiotic use were marginally associated with increased risk of FN (aHR, 1.40; 95% CI, 0.98–1.93, and 1.35; 95% CI, 0.97–1.87, respectively). Surgery, radiation therapy, and oral antibiotic use were not statistically significantly associated with FN. Conclusions: Dermatologic or mucosal conditions that might affect barrier integrity and use of corticosteroids and intravenous antibiotics prior to chemotherapy may increase risk of FN and should be considered in prophylaxis use and FN prediction modeling.
GW29-e1725 Elevated soluble ST2 level may be associated with cardiac fibrosis in atrial fibrillation
Authors: Tingting Lv, Wenjia Guo, Lun Li, Guobin Miao, Fei She, Rong He, Yuanwei Liu, Haotian Wang, Fulan Liu, Ping Zhang
Journal: Journal of the American College of Cardiology (2018)
Needle-based confocal laser endomicroscopy of pancreatic cystic lesions: a prospective multicenter validation study in patients with definite diagnosis
Authors: Bertrand Napoleon, Maxime Palazzo, Anne-Isabelle Lemaistre, Fabrice Caillol, Laurent Palazzo, Alain Aubert, Louis Buscail, Frédérique Maire, Blandine Mialhe Morellon, Bertrand Pujol, Marc Giovannini
Journal: Endoscopy (2018)

Needle-based confocal laser endomicroscopy (nCLE) enables observation of the inner wall of pancreatic cystic lesions (PCLs) during an endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). This study prospectively evaluated the diagnostic performance of nCLE for large, single, noncommunicating PCLs using surgical histopathology or EUS-FNA cytohistopathology as a reference diagnosis.From April 2013 to March 2016, consecutive patients referred for EUS-FNA of indeterminate PCLs without evidence of malignancy or chronic pancreatitis were prospectively enrolled at five centers. EUS-FNA and nCLE were performed and cystic fluid was aspirated for cytohistopathological and carcinoembryonic antigen (CEA) analysis. The diagnostic performance of nCLE was assessed against the reference standard and compared with that of EUS and CEA. This study was registered on ClinicalTrials.gov (NCT01563133).206 patients underwent nCLE and 78 PCLs (mean size 40 mm, range 20 - 110 mm) had reference diagnoses (53 premalignant and 25 benign PCLs). Post-procedure pancreatitis occurred in 1.3 % of the patients. nCLE was conclusive in 71 of the 78 cases (91 %). The sensitivies and specifities of nCLE for the diagnosis of serous cystadenoma, mucinous PCL, and premalignant PCL were all ≥ 0.95 (with 95 % confidence interval from 0.85 to 1.0). The AUROC was significantly larger for nCLE than for CEA or EUS.nCLE had excellent diagnostic performance that surpassed that of CEA and EUS for the diagnosis of large, single, noncommunicating PCLs. The nCLE procedure should be considered in patients with indeterminate PCLs to ensure a more specific diagnosis.
18F-FDG Uptake in Subcutaneous Fat Preceding Clinical Diagnosis of Human Immunodeficiency Virus–Associated Lipodystrophy
Authors: Michael T. Caton, Nityanand Miskin, Hyewon Hyun
Journal: Clinical Nuclear Medicine (2018)

Abstract A 62-year-old man with human immunodeficiency virus (HIV) on long-standing highly active antiretroviral therapy presented for 18 F-FDG PET/CT evaluation of a pulmonary nodule. The examination showed unusual radiotracer distribution accumulating in the subcutaneous and visceral fat with low cerebral and skeletal muscle uptake. Imaging features were consistent with HIV-associated lipodystrophy, an unsuspected diagnosis that was later confirmed on physical examination. Recognition of HIV-associated lipodystrophy by the nuclear medicine physician is critical as altered biodistribution may affect diagnostic yield or be mistaken for infectious pathology.
James David Pettit
Authors: Caroline Hibbert
Journal: BMJ (2018)

James David Pettit was a highly regarded consultant in anaesthesia and intensive care at Hull and East Yorkshire Hospitals NHS Trust. Born in South Africa and educated at Skinners School in Tunbridge Wells and Haberdashers’ in Monmouth, he moved to the Yorkshire area as an undergraduate and joined the trust as a trainee in 1999. He was …
P3.12-02 Dynamics of DLL3 and ASCL1 Expression in SCLC Over Disease Course
Authors: A. Farago, K. Isse, B. Drapkin, V. Kamesan, M. Kem, L. Saunders, S. Quadri, M. Mino-Kenudson
Journal: Journal of Thoracic Oncology (2018)
Cycling CD4+ T cells in HIV-infected immune nonresponders have mitochondrial dysfunction
Authors: Souheil-Antoine Younes, Aarthi Talla, Susan Pereira Ribeiro, Evgeniya V. Saidakova, Larisa B. Korolevskaya, Konstantin V. Shmagel, Carey L. Shive, Michael L. Freeman, Soumya Panigrahi, Sophia Zweig, Robert Balderas, Leonid Margolis, Daniel C. Douek, Donald D. Anthony, Pushpa Pandiyan, Mark Cameron, Scott F. Sieg, Leonard H. Calabrese, Benigno Rodriguez, Michael M. Lederman
Journal: Journal of Clinical Investigation (2018)

Immune nonresponder (INR) HIV-1–infected subjects are characterized by their inability to reconstitute the CD4+ T cell pool after antiretroviral therapy. This is linked to poor clinical outcome. Mechanisms underlying immune reconstitution failure are poorly understood, although, counterintuitively, INRs often have increased frequencies of circulating CD4+ T cells in the cell cycle. While cycling CD4+ T cells from healthy controls and HIV+ patients with restored CD4+ T cell numbers complete cell division in vitro, cycling CD4+ T cells from INRs do not. Here, we show that cells with the phenotype and transcriptional profile of Tregs were enriched among cycling cells in health and in HIV infection. Yet there were diminished frequencies and numbers of Tregs among cycling CD4+ T cells in INRs, and cycling CD4+ T cells from INR subjects displayed transcriptional profiles associated with the impaired development and maintenance of functional Tregs. Flow cytometric assessment of TGF-β activity confirmed the dysfunction of Tregs in INR subjects. Transcriptional profiling and flow cytometry revealed diminished mitochondrial fitness in Tregs among INRs, and cycling Tregs from INRs had low expression of the mitochondrial biogenesis regulators peroxisome proliferator–activated receptor γ coactivator 1-α (PGC1α) and transcription factor A for mitochondria (TFAM). In vitro exposure to IL-15 allowed cells to complete division, restored the expression of PGC1α and TFAM, and regenerated mitochondrial fitness in the cycling Tregs of INRs. Our data suggest that rescuing mitochondrial function could correct the immune dysfunction characteristic of Tregs in HIV-1–infected subjects who fail to restore CD4+ T cells during antiretroviral therapy.
A Treat to Target Strategy Using Panenteric Capsule Endoscopy in Pediatric Patients With Crohn’s Disease
Authors: Salvatore Oliva, Marina Aloi, Franca Viola, Saverio Mallardo, Fortunata Civitelli, Francesca Maccioni, Cesare Hassan, Paola Papoff, Salvatore Cucchiara, Stanley A. Cohen
Journal: Clinical Gastroenterology and Hepatology (2018)
Abstract 17620: Incremental Values of Biomarkers for Predicting Incident Peripheral Vascular Disease Events in Patients With Established Coronary Artery Diseases
Authors: Yuen Kwun Wong, Chole Y Cheung, Ka Wing Au, Sherry Hong, Chi Ho Lee, Jo Jo S Hai, Kui Kai Lau, Tai Hing Lam, Pak Chung Sham, Aimin Xu, Karen S Lam, Hung Fat Tse
Journal: Circulation (2016)

Background: Conventional clinical risk factors have modest sensitivity and specificity in predicting the occurrence of peripheral vascular disease (PVD). We sought to determine the role of differen...
Primary Hemostatic Disorders and Late Major Bleeding After Transcatheter Aortic Valve Replacement
Authors: Marion Kibler, Benjamin Marchandot, Nathan Messas, Julien Labreuche, Flavien Vincent, Lelia Grunebaum, Viet Anh Hoang, Antje Reydel, Ulun Crimizade, Michel Kindo, Minh Tam Hoang, Floriane Zeyons, Annie Trinh, Hélène Petit-Eisenmann, Fabien De Poli, Pierre Leddet, Alain Duhamel, Laurence Jesel, Mickael Ohana, Sophie Susen, Patrick Ohlmann, Eric Van Belle, Olivier Morel
Journal: Journal of the American College of Cardiology (2018)
Identification of IMDC intermediate-risk subgroups in patients with metastatic clear-cell renal cell carcinoma (ccRCC)
Authors: A. Guida, G. Le Teuff, E. Colomba, G. Baciarello, L. Derosa, Y. Loriot, K. Fizazi, C. Massard, B. Escudier, L. Albiges
Journal: Annals of Oncology (2018)
Antidiabetic Effect of Abextide, a Long‐Acting Exendin‐4 Analogue in Cynomolgus Monkeys
Authors: Gang Niu, Guohao Wang, Joseph Lau, Lixin Lang, Orit Jacobson, Ying Ma, Dale O. Kiesewetter, Shaoliang Zhang, Xiaoyuan Chen
Journal: Advanced Healthcare Materials (2018)

Abextide, synthesized by conjugating an albumin-binding moiety-truncated Evans blue-to glucagon-like peptide 1 receptor (GLP-1R) agonist exendin-4, shows extended drug release and enhanced hypoglycemic effect in diabetic mice. The aim of this study is to evaluate the pharmacodynamics of Abextide in nonhuman primates. Two batches of elderly cynomolgus monkeys with naturally occurring diabetes are used for this study. During the whole experiment period, no abnormalities such as swelling at the injection site, lethargy, or hypoglycemia are observed in all animals. The monkeys in the Abextide group lose appetite after drug administration and then recover over time. In the single dose treatment, at day 1 and day 3 after treatment, decreased plasma glucose level is observed in the Abextide-treated group but not in placebo or Albiglutide-treated group. For monkeys that receive two doses of drug, the blood glucose level in all subjects in Abextide group decreases rapidly upon drug administration and return to a plateau by day 3. A similar pattern of response is seen after the second dose administration. The delayed drug release and hypoglycemic effect of Abextide make it potentially useful as an antidiabetic drug for weekly subcutaneous administration.