tbuckley/cabot-search huggingface dataset:
Prospective clinical study of circulating tumor cells for colorectal cancer screening.
Authors: Wen-Sy Tsai, Ashish Nimgaonkar, Oscar Segurado, Ying Chang, Ben Hsieh, Hung-Jen Shao, Jen-chia Wu, Jr-Ming Lai, Mana Javey, Drew Watson, Rui Mei
Journal: Journal of Clinical Oncology (2018)

556 Background: Colorectal cancer (CRC) is among the most preventable cancers when precancerous lesions are detected at an early stage. Current screening methods for CRC require bowel prep or stool-based testing that are inconvenient, resulting in low compliance. Stool based tests have limited sensitivity for the detection of precancerous lesions. We have conducted a prospective clinical study over a period of &gt; 3 years to assess a novel assay to detect and enumerate circulating tumor cells (CTCs) in a blood sample for early CRC detection. Methods: A single-center, IRB-approved, prospective and blinded clinical study was conducted in 620 subjects including 438 with adenoma, polyps or stage I-IV CRC and 182 healthy controls. For each subject, 2mL peripheral whole blood collected through a routine blood draw was processed using the CellMax biomimetic platform (CMx). The CMx test is a proprietary microfluidic biochip that minimizes non-specific binding and accurately enumerates CTCs. A multivariate analysis was performed to assess the clinical performance characteristics of the CMx test. Results: Disease status was evaluated by a standard clinical protocol which included colonoscopy and biopsy results. Probability of CRC risk was assessed by an age-adjusted regression model which correlated CTCs to clinical status. The CMx test’s overall accuracy was 88% for all stages of colorectal illness, including precancerous lesions. Conclusions: The study has demonstrated high accuracy for the detection of CRC using a novel CTC assay. It is the first study to show high sensitivity in the detection of precancerous colorectal lesions. The simple blood draw required can be easily integrated into a patient’s routine physical, increasing test compliance.[Table: see text]
Hyperactive ryanodine receptors in human heart failure and ischaemic cardiomyopathy reside outside of couplons
Authors: Eef Dries, Demetrio J Santiago, Guillaume Gilbert, Ilse Lenaerts, Bert Vandenberk, Chandan K Nagaraju, Daniel M Johnson, Patricia Holemans, H Llewelyn Roderick, Niall Macquaide, Piet Claus, Karin R Sipido
Journal: Cardiovascular Research (2018)

In ventricular myocytes from humans and large mammals, the transverse and axial tubular system (TATS) network is less extensive than in rodents with consequently a greater proportion of ryanodine receptors (RyRs) not coupled to this membrane system. TATS remodelling in heart failure (HF) and after myocardial infarction (MI) increases the fraction of non-coupled RyRs. Here we investigate whether this remodelling alters the activity of coupled and non-coupled RyR sub-populations through changes in local signalling. We study myocytes from patients with end-stage HF, compared with non-failing (non-HF), and myocytes from pigs with MI and reduced left ventricular (LV) function, compared with sham intervention (SHAM). Single LV myocytes for functional studies were isolated according to standard protocols. Immunofluorescent staining visualized organization of TATS and RyRs. Ca2+ was measured by confocal imaging (fluo-4 as indicator) and using whole-cell patch-clamp (37°C). Spontaneous Ca2+ release events, Ca2+ sparks, as a readout for RyR activity were recorded during a 15 s period following conditioning stimulation at 2 Hz. Sparks were assigned to cell regions categorized as coupled or non-coupled sites according to a previously developed method. Human HF myocytes had more non-coupled sites and these had more spontaneous activity than in non-HF. Hyperactivity of these non-coupled RyRs was reduced by Ca2+/calmodulin-dependent kinase II (CaMKII) inhibition. Myocytes from MI pigs had similar changes compared with SHAM controls as seen in human HF myocytes. As well as by CaMKII inhibition, in MI, the increased activity of non-coupled sites was inhibited by mitochondrial reactive oxygen species (mito-ROS) scavenging. Under adrenergic stimulation, Ca2+ waves were more frequent and originated at non-coupled sites, generating larger Na+/Ca2+ exchange currents in MI than in SHAM. Inhibition of CaMKII or mito-ROS scavenging reduced spontaneous Ca2+ waves, and improved excitation–contraction coupling. In HF and after MI, RyR microdomain re-organization enhances spontaneous Ca2+ release at non-coupled sites in a manner dependent on CaMKII activation and mito-ROS production. This specific modulation generates a substrate for arrhythmia that appears to be responsive to selective pharmacologic modulation.
Use of Complementary and Alternative Medicine in Older Adults With Diabetes
Authors: Taeho Greg Rhee, Sarah M. Westberg, Ila M. Harris
Journal: Diabetes Care (2018)

Older adults with diabetes are at high risk for having multiple chronic conditions and diabetes complications and often take multiple medications concomitantly. Studies have shown that many Americans are using complementary and alternative medicine (CAM) to either improve or manage their health (1,2). Individuals have diverse purposes for using CAM, from treating specific conditions, such as back and neck pain (e.g., acupuncture and chiropractic), to improving general health and wellness (e.g., meditation and tai chi). Since relatively little is known about the prevalence and patterns of CAM use in older adults with diabetes, we investigated this topic to guide integrated, patient-centered health care use for this population.

We used data from the 2012 National Health Interview Survey (NHIS), which is an annual cross-sectional in-person interview survey demonstrating health care trends among noninstitutionalized civilians in the U.S. (3). The NHIS collects comprehensive CAM-related information every 5 years. The sample included adults aged 65 or older who reported having …
Mitotic Exit Dysfunction through the Deregulation of APC/C Characterizes Cisplatin-Resistant State in Epithelial Ovarian Cancer
Authors: Anil Belur Nagaraj, Olga Kovalenko, Rita Avelar, Peronne Joseph, Annalyn Brown, Arshia Surti, Sandra Mantilla, Analisa DiFeo
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Acquired resistance to cisplatin is a major barrier to success in treatment of various cancers, and understanding mitotic mechanisms unique to cisplatin-resistant cancer cells can provide the basis for developing novel mitotic targeted therapies aimed at eradicating these cells. Experimental Design: Using cisplatin-resistant models derived from primary patient epithelial ovarian cancer (EOC) cells, we have explored the status of mitotic exit mechanisms in cisplatin-resistant cells. Results: We have uncovered an unexpected role of long-term cisplatin treatment in inducing mitotic exit vulnerability characterized by increased spindle checkpoint activity and functional dependency on Polo-like kinase 1 (PLK1) for mitotic exit in the presence of anaphase promoting complex/cyclosome (APC/C) dysfunction in a cisplatin-resistant state. Accordingly, PLK1 inhibition decreased the survival of cisplatin-resistant cells in vitro and in vivo and exacerbated spindle checkpoint response in these cells. APC/CCDC20 inhibition increased sensitivity to pharmacologic PLK1 inhibition, further confirming the existence of APC/C dysfunction in cisplatin-resistant cells. In addition, we uncovered that resistance to volasertib, PLK1 inhibitor, is due to maintenance of cells with low PLK1 expression. Accordingly, stable PLK1 downregulation in cisplatin-resistant cells induced tolerance to volasertib. Conclusions: We provide the first evidence of APC/C dysfunction in cisplatin-resistant state, suggesting that understanding APC/C functions in cisplatin-resistant state could provide a basis for developing novel mitotic exit–based therapies to eradicate cisplatin-resistant cancer cells. Our results also show that PLK1 downregulation could underlie emergence of resistance to PLK1-targeted therapies in cancers. Clin Cancer Res; 24(18); 4588–601. ©2018 AACR.
Age-related differences in gene expression in colorectal cancer (CRC).
Authors: Raphael M Byrne, Rebecca Ruhl, Christian Lanciault, Sudarshan Anand, Abhinav Nellore, Vassiliki Liana Tsikitis
Journal: Journal of Clinical Oncology (2018)

654 Background: Colorectal cancer (CRC) in young patients is increasing in incidence and is associated with worse outcomes than CRC in older patients. While distinct molecular subtypes of CRC have been recently characterized, it is unclear whether there are molecular differences between the tumors of young and old patients. We sought to identify differences in gene expression of CRC between these two groups. Our discovery analysis identified a gene signature of several differentially expressed RNAs, from which we validated PEG10. The PEG10 gene on chromosome 7q21.3 has been implicated in liver, gallbladder, thyroid, and blood cancers, and is thought to play a role in cancer cell survival and regulation of apoptosis. In hepatocellular carcinoma, increased PEG10 expression has been associated with younger patient age. Methods: RNA sequencing data was obtained from The Cancer Genome Atlas (TCGA) and analyzed for differences in gene expression between patients ≤ 45 years old and those ≥ 65 years old. The identified differentially expressed genes were then validated with qPCR using human CRC tissue from patients ≤ 45 years old and those ≥ 65 years old. Results: RNA sequencing data from patients ≤ 45 years old (n = 29) and patients ≥ 65 years old (n = 299) identified seven genes with increased expression in younger patients: ZNF334 (log 2 [fold change] = 2.30), DSC3 (1.78), PEG10 (1.67), CACNA1I (1.54), PKIA (1.33), MAP9 (1.27), and EPHX3 (1.17) (p &lt; 0.07). Validation with qPCR for PEG10 was most promising, and was performed on both young (n = 10, mean age = 39) and old patient samples ( n= 8, mean age = 72). Two cancers (20%) in the young group received radiation treatment and five (50%) received chemotherapy. One cancer (12.5%) in the old group received radiation and two (25%) received chemotherapy. PEG10 had increased expression in the young group with log 2 [fold change] = 3.16 (p &lt; 0.02). Conclusions: We have identified a potentially unique gene expression signature for CRC in young patients, which includes PEG10. Functional analysis of PEG10 and other genes is underway using in vitro cell culture, archived human tumor tissue, and mouse tumor models.
Abstract 17084: Timing of Onset of Pyrexia and Cardiac Arrest Outcomes by Duration of Targeted Temperature Management
Authors: Anne V Grossestreuer, Benjamin S Abella, Douglas J Wiebe, Michael W Donnino, David F Gaieski
Journal: Circulation (2016)

Introduction: Post-arrest pyrexia (≥38°C) has been associated with poor outcomes in recent clinical studies. Optimal duration and degree of targeted temperature management (TTM) remain unclear. It ...
230P Experience with the implant of vascular access devices by medical oncologists in a non-surgical setting
Authors: A. Revuelta, D. Rodríguez Rubí, L. Fáez, M.D.P. Solís, S. Fernández Arrojo, C. Iglesias Gómez, D. Gómez, J. del Río Fernández, A. Castillo Trujillo, E. Esteban González
Journal: Journal of Thoracic Oncology (2018)
Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells
Authors: Quirin Hammer, Timo Rückert, Eva Maria Borst, Josefine Dunst, André Haubner, Pawel Durek, Frederik Heinrich, Gilles Gasparoni, Marina Babic, Adriana Tomic, Gabriella Pietra, Mikalai Nienen, Igor Wolfgang Blau, Jörg Hofmann, Il-Kang Na, Immo Prinz, Christian Koenecke, Philipp Hemmati, Nina Babel, Renate Arnold, Jörn Walter, Kevin Thurley, Mir-Farzin Mashreghi, Martin Messerle, Chiara Romagnani
Journal: Nature Immunology (2018)
172P Safety and efficacy phase 2 study of nab-paclitaxel maintenance treatment after nab-paclitaxel plus carboplatin in stage IIIB/IV non-small cell lung cancer
Authors: A. Nakao, J. Uchino, N. Nagata, K. Takayama, K. Watanabe, M. Fujita
Journal: Journal of Thoracic Oncology (2018)
Chronic obstructive pulmonary disease in China: a nationwide prevalence study
Authors: Liwen Fang, Pei Gao, Heling Bao, Xun Tang, Baohua Wang, Yajing Feng, Shu Cong, Juan Juan, Jing Fan, Ke Lu, Ning Wang, Yonghua Hu, Linhong Wang
Journal: The Lancet Respiratory Medicine (2018)
Abstract 12719: Heart Failure Self-Care Associated With Brain Injury in Executive Control Regions
Authors: Sarah E Choi, Bhaswati Roy, Rajesh Kumar, Gregg C Fonarow, Mary A Woo
Journal: Circulation (2016)

Heart failure (HF) patients often have poor self-care (SC) management that is linked to increased morbidity and mortality and decreased quality of life. While inadequate SC is known to be strongly related to cognitive/executive decision-making ability, associations between HF SC and brain injury to regions that control executive function (pre-frontal cortices) has not been reported. Methods: To assess the relationships between HF SC and brain injury in the pre-frontal cortices, diffusion tensor imaging (DTI) was performed in 10 HF (age, 56.8±8.1 years; 8 male; body-mass-index, 25.4±4.1 kg/m2; left ventricular ejection fraction, 26.4±11.9%; New York Heart Association functional class II/III 94/6%), using a 3.0-Tesla magnetic resonance imaging scanner, and self-care was measured with the validated Self-Care of Heart Failure Inventory (SCHFI) questionnaire. Mean diffusivity (MD) maps were calculated, normalized to a common space, and smoothed. The region-of-interest (ROI) analyses were performed on the smoothed MD maps by placing left and right prefrontal ROIs. Both left and right prefrontal cortex values were correlated with SCHFI scores (maintenance and confidence subscales) in HF subjects using partial correlation procedures (covariates, age, and gender). Results: Continuous data variables were normally distributed (Shapiro-Wilks Test of Normality). Mean SCHFI maintenance score was 74.66±11.24 and SCHFI confidence score was 70.07±16.80. Correlation of MD values with SCHFI Confidence at left prefrontal cortex: r= -0.941, p&lt; 0.001; right prefrontal cortex: r= -0.858, p= 0.006. Correlation of MD values with SCHFI Maintenance at left prefrontal cortex: r= -0.602, p= 0.115/not significant; right prefrontal cortex: r= -0.854, p= 0.007. Conclusions: With exception of the left prefrontal cortex and SCHFI Maintenance, there were very strong negative correlations between SCHFI subscales (Confidence and Maintenance) and MD values of the pre-frontal cortices. These findings provide evidence that brain injury in cognitive brain regions have strong associations with HF SC. Further research is needed to determine if interventions which support neurogenesis or neuroprotection of these brain regions can positively impact SC in persons with HF.
Pattern of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in primary and metastatic epithelial ovarian cancer (EOC).
Authors: Soizick Jeanne Lynette Mesnage, Aurelie Auguste, Catherine Genestie, Ariane Dunant, Erwann Pain, Francoise Drusch, Sebastien Gouy, Philippe Morice, Enrica Bentivegna, Catherine Lhomme, Patricia Pautier, Judith Michels, Audrey Le Formal, Bianca Cheaib, Julien Adam, Alexandra Leary
Journal: Journal of Clinical Oncology (2017)

64 Background: Tumour immune response plays a critical role in progression and prognosis of EOC, however patterns of TILs and PD-L1 expression in primary and metastatic disease remain poorly described. Methods: Patients treated with neoadjuvant chemotherapy (NACT) for advanced EOC, between 2002-2014, and available sequential tumours (pre-NACT, post-NACT, or relapse) were retrospectively identified. Stromal TILs (sTILs) were evaluated according to the International TILs Working Group 2014 (Salgado 2015) on whole sections, and scored as a percentage of stromal area. Immune cell PD-L1 expression was evaluated by immunohistochemistry (E1L3N clone, Cell Signaling) in a smaller number of tumours. Cutoffs for analysis were: high sTILs ≥50%, PD-L1 positivity ≥5% membranous staining. Results: Among a total of 236 tumour samples from 150 patients (110 pre-NACT, 111 post-NACT, and 15 relapse tumours) median sTILs levels was significantly higher in metastatic tumours ( n=151) compared with primary tumours ( n=85) (median 30, IQR 10-50 vs. 15, IQR 5-30, p=0.0004). Among diagnostic samples, median sTILs level was 20 (IQR 10-45, n=85) in metastatic tumours compared with 10 (IQR 5-20, n =25) in primary tumours ( p=0064). Similarly in post-NACT samples, median sTILs level was 40 (IQR 15-60, n=51) in metastatic tumours compared with 20 (IQR 6.25-30, n=60) in primary tumours ( p=0026). Among relapse samples median sTILs level was 30 (IQR 10-50, n=15). Among all available samples ( n=97) PD-L1 positivity was detected in 33% (9/30) of primary and 50% (34/68) of metastatic tumours (Fisher’s exact test OR 2.3, 95%CI 0.94-5.4, p =0.08). Conclusions: In patients with EOC there is increased lymphocytic infiltration in both synchronous metastatic disease at diagnosis, and metachronous metastatic disease at relapse, compared with the primary tumour. This suggests increased immunogenicity as disease progresses. Furthermore, there is a trend towards upregulation of the PD-L1 immune checkpoint with disease progression.
Legumain, an asparaginyl endopeptidase, mediates the effect of M2 macrophages on attenuating renal interstitial fibrosis in obstructive nephropathy
Authors: Dekun Wang, Min Xiong, Chuan'ai Chen, Lingfang Du, Ze Liu, Yuzhi Shi, Mianzhi Zhang, Junbo Gong, Xiangrong Song, Rong Xiang, Ergang Liu, Xiaoyue Tan
Journal: Kidney International (2018)
Modified CLIP score with albumin-bilirubin grade in relation to prognostic value in HBV-related hepatocellular carcinoma patients treated with transcatheter arterial chemoembolization therapy.
Authors: Xiu-Rong Cai, Zhan-Hong Chen, Qu Lin, Min Dong, Xiao-kun Ma, Jie Chen, Jing-yun Wen, Xiang-yuan Wu
Journal: Journal of Clinical Oncology (2018)

480 Background: Child-Pugh grade is widely used to assess hepatic function reserve, but it is relatively subjective for assessment of hepatic encephalopathy. A newly developed scoring system combining albumin and bilirubin, called ALBI grade, aims to assess liver function objectively. In prognosis prediction of hepatocellular carcinoma (HCC), The Cancer of the Liver Italian Program (CLIP) score is commonly used in clinical practice and includes Child-Pugh evaluation. We substituted ALBI grade for Child-Pugh grade to establish ALBI-CLIP system and conducted this study to validate the prognostic value of ALBI -CLIP in HBV-related HCC patients after TACE therapy. Methods: We retrospectively analyzed HBV-related HCC patients who received TACE therapy. Baseline data were collected and evaluated. Child-Pugh grade and ALBI grade were integrated into CLIP and ALBI-CLIP systems, respectively. Univariate and multivariate analyses were conducted to identify independent prognostic factors for overall survival. Comparisons of receiver operating characteristic (ROC) curves and likelihood ratio test (LRT) were used to compare the value of ALBI-CLIP, CLIP and TNM staging systems in predicting survival. Results: A total of 207 patients were included. 153 (73.9%) and 54 (26.1%) patients were classified as Child-Pugh grade A and B, respectively. But according to ALBI grade, 57 (27.5%), 136 (65.7%) and 14 (6.8%) of them were correspondingly divided into Grade 1, 2 and 3. Comparisons of ROC curves showed that ALBI-CLIP and CLIP had similar areas under the curve, both of which were larger than that of TNM system in predicting 3-month, 6-month, 1-year and 2-year survival. LRT indicated that both ALBI-CLIP and CLIP had larger χ 2 values and smaller values of Akaike information criterion (AIC), compared with TNM system (χ 2 = 29.771, 29.479, 9.105; AIC = 858.215, 858.069, 879.410 for ALBI-CLIP, CLIP and TNM, respectively). Conclusions: Our current study suggested that modified CLIP score with albumin-bilirubin grade retained prognostic value in HBV-related HCC treated with TACE therapy.
Development and validation of a prognostic score to predict tuberculosis mortality
Authors: Duc T. Nguyen, Edward A. Graviss
Journal: Journal of Infection (2018)

To develop and validate a simple prognostic scoring system to predict the mortality risk during treatment in tuberculosis patients.Using data from the CDC's Tuberculosis Genotyping Information Management System of TB patients in Texas reported from 01/2010 to 12/2016, age ≥ 15 years and having an outcome as "completed" or "died", we developed and validated a prognostic mortality scoring system-based logistic regression beta-coefficients.The developmental and validation cohorts consisted of 3378 and 3377 patients, respectively. The score used 9 demographic and clinical characteristics, which are usually available at the patient's initial visits to a healthcare facility. Prognostic scores were categorized into three groups that predicted mortality: low-risk (<15 points), medium-risk (15-18 points), and high-risk (>18 points). The model had excellent discrimination and calibration with an area under the receiver operating characteristic curve of 0.82 and 0.80, and a non-significant Hosmer-Lemeshow test P = 0.514 and P = 0.613 in the developmental and validation cohorts, respectively.Our validated TB prognostic scoring system, which used demographic and clinical characteristics available at the patient's initial visits, can be a practical tool for health care providers to identify TB patients with high mortality risk so that appropriate treatment, medical supports and follow-up resources could be appropriately allocated.
Updating NHS technologies: a WhatsApp-like system would improve communication
Authors: Iona E F McKechnie
Journal: BMJ (2018)

As a “young person” I am unsurprised at the high number of physicians using WhatsApp to communicate in the healthcare setting.1 Many, if not the majority, of other businesses around the world use WhatsApp or similar programmes to communicate with each other instantly. But they will not be as concerned with information governance and confidentiality as …
Abstract P140: Association Between Physical Activity and Oxidative Stress Biomarkers in Generally Healthy Women: The Nurses’ Health Study
Authors: Tianying Wu, Shuman Yang, Majken Jensen, Eric Rimm, Walter Willett
Journal: Circulation (2016)

Background: The associations between physical activity and oxidative stress biomarkers are still controversial, and few large human studies have comprehensively investigated the relationship between physical activity and oxidative stress biomarkers. The purpose of this study was to examine the association between physical activity and oxidative stress biomarkers in a large sample of women by measuring biomarkers of both oxidation and antioxidant defense. Methods: We conducted a cross-sectional study among 1,144 generally healthy women ages 43-70 years, who were included in a prospective nested case-control study of coronary heart disease in the Nurses’ Health Study. Fluorescent oxidation products (FlOPs) are oxidation markers reflecting global oxidation burden. Antioxidant defense was quantified by the activities of three major antioxidant enzymes in erythrocyte (superoxide dismutase [SOD], glutathione peroxidase [GPx] and catalase [CAT]). Self-reported physical activity was estimated in metabolic equivalents per week. The associations of physical activity with the levels of FlOPs and the activities of SOD, GPx, CAT were analyzed with linear regression models. Results: Physical activity was not associated with FlOP levels, or GPx and CAT activities after adjusting for covariates (all Ptrend &gt; 0.15). Higher levels of physical activity were associated with decreased SOD activity (Ptrend &lt; 0.01). We then conducted subgroup analysis of participants with and without any vigorous physical activity. Greater levels of physical activity were associated with lower SOD activity among participants with any vigorous physical activity (Ptrend = 0.02). Conclusions: Greater physical activity was associated with lower SOD activity, but not with higher plasma FlOPs in generally healthy women.